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        "titulo" => "Registro informatizado de la telangiectasia hemorr&#225;gica hereditaria &#40;Registro RiHHTa&#41; en Espa&#241;a&#58; objetivos&#44; m&#233;todos y resultados preliminares"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hereditary hemorrhagic telangiectasia &#40;HHT&#41;&#44; or Osler-Weber-Rendu disease&#44; is a systemic disease with autosomal dominant inheritance&#46; The disease&#39;s worldwide incidence rate is 1&#47;5000&#8211;8000 and is categorized among rare diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">1&#8211;4</span></a> More than 800 mutations in more than 5 genes have been reported&#44; but the considerable majority of them are located in the genes that encode for endoglin &#40;<span class="elsevierStyleItalic">ENG</span>&#41; or activin &#40;<span class="elsevierStyleItalic">ACVRL1</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> Both proteins form part of the transforming growth factor&#946; family&#44; which intervenes in the vascular signaling pathways&#44; influencing the regulation of angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">6</span></a> Abnormalities in these proteins therefore give rise to abnormal and excessive vascular growth&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite being a genetic disease&#44; the diagnosis of HHT is clinical and performed according to the Cura&#231;ao Criteria &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a> Telangiectasia is the characteristic lesion of HHT and consists of the substitution of the normal capillary bed by an aberrant direct connection between the arteriole and venule&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Telangiectasias can be found in the skin and mucous membranes&#44; especially in the nasal mucosa&#44; causing recurrent epistaxis&#44; which is the main symptom of this disease&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Given that HHT is a systemic disease&#44; vascular involvement can occur in any organ&#44; although it mostly affects the lungs and liver&#46; This involvement occurs both at the microvasculature level &#40;in the form of telangiectasia&#41; and as arteriovenous fistulas or aneurysms in larger vessels&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">5&#44;7&#44;9</span></a> The recommendation is to perform a screening for these potential vascular malformations for their early detection and management according to scientific evidence&#44; as well as an appropriate follow-up of these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">10&#44;11</span></a> Although there is no curative treatment&#44; there are drugs with positive results in various aspects of the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#8211;14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The systemic nature of HHT&#44; its low prevalence and considerable clinical variability makes for a complex understanding of the disease&#44; especially in uncommon situations&#46; This aspect is common in the field of rare diseases&#44; where it is difficult to accumulate sufficient experience on the natural course of a disease and these patients&#8217; prognosis&#46; The preparation of registries helps overcome these difficulties&#44; representing a priority in the management of rare diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15&#44;16</span></a> The use of quality registries also helps reach a consensus on diagnostic&#8211;therapeutic measures&#44; reflect on the patient management in standard clinical practice&#44; offer evidence for preparing clinical guidelines and generate hypotheses for developing clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">16&#8211;19</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">We present the development of the first and only HHT registry in Spain&#44; the Computerized Registry of Hereditary Hemorrhagic Telangiectasia &#40;RiHHTa&#41;&#44; the clinical characteristics and the relevant diagnostic aspects of the first patients added to the registry&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design of the RiHHTa registry</span><p id="par0035" class="elsevierStylePara elsevierViewall">The RiHHTa is a multicenter&#44; prospective and observational registry&#44; developed within the Rare Diseases Workgroup of the Spanish Society of Internal Medicine&#46; RiHHTa has an online design&#44; accessible from <a id="intr0010" class="elsevierStyleInterRef" href="https://rihhta.healthincode.com/">https&#58;&#47;&#47;RiHHTa&#46;healthincode&#46;com</a> with individual access for each researcher and available in Spanish and English &#40;with the possibility for further internationalization&#41;&#46; The registry&#39;s main objectives are to improve the management of patients with HHT&#44; to contribute to the dissemination and understanding of the disease and to reach a consensus among its members on diagnosis-therapeutic measures &#40;as a form of networking&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The creation of RiHHTa counted on the nonremunerated collaboration of the genetic studies company Health in Code &#40;A Coru&#241;a&#44; Spain&#41;&#44; which has broad experience in cardiomyopathy registries&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">20&#44;21</span></a> The registry also enables the creation of personalized reports for each patient&#44; which prove useful for the healthcare tasks of the participating researchers&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patient and variables</span><p id="par0045" class="elsevierStylePara elsevierViewall">The included patients are those with a clinical diagnosis according to the Cura&#231;ao Criteria<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a> or with a genetic diagnosis&#44; who have signed the informed consent document for entering their data into the RiHHTa registry&#46; The registry is organized by families&#44; and the variables are divided into 5 large sections&#58; demographic&#44; clinical&#44; additional examination&#44; treatment and outcome data&#46; The severity of the epistaxis is quantified using the Epistaxis Severity Score&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> The assessment of the passage of contrast using echocardiography to detect pulmonary arteriovenous fistulas was conducted according to the Barzilai et al&#46; classification in 4 grades&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> For the study of gastrointestinal tract involvement&#44; the recommendations were followed for practicing the technique for those patients with anemia disproportionate to the degree of epistaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The entry of the patients&#8217; personal data included in the registry and the treatment and communication of that data were performed according to the provisions of the law on the protection of personal data&#46; To safeguard the identity of the included patients&#44; the RiHHTa registry generated an encrypted identifier for each patient&#46; The design and operation of the RiHHTa registry was approved by the Ethics Committee of the University Hospital of Bellvitge &#40;Barcelona&#44; Spain&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">The results are expressed using absolute and relative frequencies for the qualitative variables&#46; For the quantitative variables&#44; we employed the mean&#44; standard deviation and range&#46; The descriptive analysis was performed for the entire sample&#46; The comparison between the groups of the distribution of the categorical variables was performed using the chi-squared test&#46; The comparison of the distribution of the quantitative variables that did not follow a normal distribution was performed using Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#59; otherwise&#44; we employed the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; The differences were considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46; The statistical analysis was performed using the SPSS program version 18&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">The RiHHTa registry was launched on the 6th of June 2016&#46; Since then and up to December 2017&#44; data from 152 patients from 104 families were entered&#46; From these patients&#44; there has been sufficient data to analyze a total of 141 patients from 92 families&#46; All patients were white except for 2 who were Hispanic and Asian&#46; The mean age was 51&#46;2 years&#44; and 91 &#40;64&#46;5&#37;&#41; were women&#46; The patients&#8217; comorbidities are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; It is worth noting that 8 &#40;5&#46;7&#37;&#41; patients had atrial fibrillation&#44; 2 of whom underwent atrial appendage closure due to a contraindication for anticoagulation&#46; Almost a third &#40;27&#46;7&#37;&#41; of the patients underwent some previous surgery&#44; and 17 &#40;12&#46;1&#37;&#41; patients had a family history of cancer&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The onset of HHT was in the form of recurrent epistaxis in 130 &#40;92&#46;2&#37;&#41; patients and brain abscesses in 11 &#40;7&#46;8&#37;&#41; patients&#46; These abscesses were due to previously undiagnosed pulmonary arteriovenous fistulas in 3 &#40;2&#46;1&#37;&#41; patients and to various causes in the rest &#40;5&#46;7&#37;&#41;&#46; Virtually all patients &#40;97&#46;2&#37;&#41; presented recurrent epistaxis&#44; which required emergency care for 50 &#40;35&#46;5&#37;&#41; patients and the transfusion of packed red blood cells for 31 &#40;22&#37;&#41; patients&#46; Mucocutaneous telangiectasias&#44; which were present in 126 &#40;89&#46;4&#37;&#41; patients&#44; were mostly located in the lips&#44; tongue and fleshy part of the fingers&#46; Almost all those affected &#40;89&#46;4&#37;&#41; had a family history of HHT&#44; and most &#40;63&#46;8&#37;&#41; had visceral involvement&#46; According to the Cura&#231;ao Criteria&#44; 122 &#40;86&#46;5&#37;&#41; patients met 3 or more criteria&#44; which constituted a definitive diagnosis&#46; However&#44; the mean age at diagnosis was 42&#46;1 years&#46; The clinical characteristics of the patients in terms of HHT are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">In terms of the screening tests&#44; the passage of contrast in the transthoracic echocardiography &#40;TTE&#41; was not detected or was grade 1 in 59 &#40;41&#46;8&#37;&#41; patients&#46; However&#44; chest CT angiography was performed on 36 of these patients&#44; and pulmonary arteriovenous fistulas were detected in only 7 of these patients&#46; Six of the patients only had 1 fistula&#44; and none were susceptible to embolization&#46; Pulmonary arteriovenous fistulas were detected in 36 &#40;45&#46;5&#37;&#41; of the 79 patients studied using lung CT angiography&#44; with a mean of 2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7 &#40;1&#8211;14&#41; pulmonary arteriovenous fistulas per patient&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Hepatic involvement was observed in 43 &#40;67&#46;2&#37;&#41; of the 64 patients who were studied&#46; These patients presented a tendency toward higher concentrations of cholestatic enzymes&#44; with significantly higher bilirubin levels than those with no hepatic involvement&#46; Telangiectasias and arteriovenous and arterioportal fistulas were more common in the liver&#46; When the patients underwent abdominal CT angiography&#44; other extrahepatic vascular disorders were detected in 14 &#40;10&#37;&#41; patients&#44; mostly pancreatic&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A genetic study was conducted on 64 &#40;45&#46;4&#37;&#41; patients&#44; observing a mutation in the <span class="elsevierStyleItalic">ENG</span> and <span class="elsevierStyleItalic">ACVRL1</span> genes in 20 &#40;31&#46;2&#37;&#41; and 44 &#40;68&#46;8&#37;&#41; patients&#44; respectively&#46; The considerable majority &#40;64&#46;7&#37;&#41; of those who presented <span class="elsevierStyleItalic">ENG</span> mutations showed lung involvement&#46; Virtually all &#40;95&#46;6&#37;&#41; of those who presented an <span class="elsevierStyleItalic">ACVRL1</span> mutation had hepatic involvement&#46; The 2 &#40;1&#46;4&#37;&#41; patients who met only 1 Cura&#231;ao criterion and 5 of the 17 &#40;12&#46;1&#37;&#41; patients who met only 2 criteria underwent a genetic study with a mutation in the <span class="elsevierStyleItalic">ACVRL1</span> gene&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Brain involvement was detected in only 3 &#40;3&#46;9&#37;&#41; of the patients studied&#44; with no clinical repercussion in any of them&#46; Gastrointestinal losses were suspected in 36 patients&#44; 20 &#40;55&#46;5&#37;&#41; of whom presented telangiectasias in the gastrointestinal tract&#44; predominantly &#40;95&#37;&#41; in upper gastrointestinal tract&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the results of all the additional examinations&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The RiHHTa registry reveals the need to optimize the early diagnosis of patients with HHT&#44; which presents age-dependent symptoms&#44; with a progressive development of signs and symptoms from childhood to the fourth decade of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">3&#44;24</span></a> However&#44; the mean age at diagnosis in the RiHHTa registry was 42 years in an adult population with a mean age of 51 years&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The recurrence and severity of epistaxis is the factor that most affects these patients&#8217; quality of life&#44; as well as the need to visit the emergency department and for blood transfusions&#44; as occurred in 35&#46;5&#37; and 22&#37; of the patients included in the RiHHTa registry&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">25&#44;26</span></a> Detecting patients with recurrent epistaxis and a family history of this condition should alert clinicians as to potential HHT and is an opportunity to optimize the early diagnosis of HHT&#46; These two facts&#44; along with a simple examination of the hands and oral cavity to detect mucocutaneous telangiectasias&#44; which are present in 89&#46;4&#37; of the patients in the RiHHTa registry&#44; define a definitive diagnosis of HHT &#40;according to the Cura&#231;ao criteria&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Rare disease registries help us understand the infrequent situations of a disease&#44; which are difficult to recognize at a single center&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15&#8211;17</span></a> Thus&#44; in the RiHHTa registry&#44; at least 20 &#40;14&#46;2&#37;&#41; patients had an indication for anticoagulation &#40;10 for heart disease and 10 for venous thromboembolism &#91;VTE&#93;&#41;&#46; HHT by itself does not represent an absolute contraindication for anticoagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> A study using online interviews found that 38&#37; of 150 patients who reported having undergone anticoagulation showed no worsening of their typical epistaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> However&#44; for those patients with atrial fibrillation and a contraindication for anticoagulation&#44; the recommendation is to perform left atrial appendage closure&#44; as was conducted in 2 cases in the RiHHTa registry&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Moreover&#44; iron-deficiency anemia has been related to a compensatory increase in factor <span class="elsevierStyleSmallCaps">viii</span> and to an increased risk of VTE in patients with HHT&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">29&#44;30</span></a> In fact&#44; the 7&#37; rate of VTE in the registry is greater than the expected incidence rate in a population with a mean age between 50 and 59 years&#44; which would be 1&#47;1000&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> The RiHHTa registry could provide future information on anticoagulation tolerance in patients with HHT in standard clinical practice&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Hepatic involvement was the most common visceral manifestation&#44; which is consistent with the increased prevalence of mutations in the <span class="elsevierStyleItalic">ACVRL1</span> gene&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> Mutations in the <span class="elsevierStyleItalic">ACVRL1</span> gene define type 2 HHT&#44; with a greater prevalence of hepatic involvement&#44; as occurred with 95&#37; of the patients with mutations in this gene who were included in the RiHHTa&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> The most common form of hepatic involvement has been telangiectasias&#44; which are usually asymptomatic&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">32&#44;33</span></a> The 3 types of involvement identified through abdominal CT angiography involve different follow-ups and complications&#46; Thus&#44; arteriovenous and portal-venous fistulas can cause signs and symptoms of heart failure with a high cardiac index&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">32&#44;33</span></a> However&#44; this parameter was reported in the registry in only half of the 16 patients with this involvement&#46; Abdominal CT angiography also helps detect arterioportal fistulas that can cause portal hypertension&#44; which should be searched for during the follow-up&#46; Abnormal laboratory hepatic function values have been related to an increased risk of clinically significant hepatic impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a> In fact&#44; patients with hepatic impairment in RiHHTa showed a higher elevation of cholestatic parameters than those who did not have this impairment&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Contrast TTE is the test of choice for screening pulmonary arteriovenous fistulas&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> Which are more common in patients with <span class="elsevierStyleItalic">ENG</span> gene mutations&#44; which define type 1 HHT&#44; as occurred in 64&#37; of the patients included in the RiHHTa who presented mutations in this gene&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> In a study conducted with 95 patients&#44; the 24 patients with no passage of contrast and the 34 patients with grade 1 &#40;according to the Barzilai classification&#41; presented no arteriovenous fistulas in the chest CT angiography&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">23&#44;35</span></a> However&#44; an unnecessary chest CT angiography was performed for 36 of the 59 patients with grade 0 or 1 in the RiHHTa registry&#46; Proper screening of the disease&#39;s manifestations needs to be conducted to reduce its complications&#46; In this respect&#44; 3 patients began with brain abscesses as the initial symptom&#46; The prior detection of pulmonary arteriovenous fistulas would have permitted antibiotic prophylaxis against risk conditions and assessment of their embolization&#44; thereby reducing the risk of this complication&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> In fact&#44; brain abscesses&#44; which were present in 7 &#40;5&#37;&#41; patients in the RiHHTa registry&#44; are a common and preventable complication in individuals with HHT and occur 30 times more often in these patients than in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">36</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Brain malformations have a different behavior&#44; because they are present from birth&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">3</span></a> However&#44; given the low prevalence and therapeutic difficulties&#44; there is no high-grade evidence or recommendations for screening these malformations in asymptomatic adult patients with HHT&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">11&#44;37&#44;38</span></a> However&#44; 77 &#40;54&#46;6&#37;&#41; patients in the RiHHTa registry underwent a study for cerebral arteriovenous malformations&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Gastrointestinal tract involvement is the last manifestation and starts in the 5th or 6th decade of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">39&#44;40</span></a> Its study is recommended for patients with anemia disproportionate to the degree of epistaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> This is due to the fact that although 80&#37; of the patients with HHT present telangiectasias in the gastrointestinal tract&#44; only 25&#8211;30&#37; develop symptomatic gastrointestinal involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">41&#44;42</span></a> The predominance of gastroduodenal involvement observed in the RiHHTa registry has been scarcely published and supports the recommendation for starting the screening with esophagogastroduodenoscopy&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">39&#44;41&#44;42</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion&#44; the RiHHTa registry represents an initiative for the coordinated study among its members&#44; which provides information on uncommon conditions and helps identify areas of improvement in the management of patients with HHT&#46; We detected improper use of chest CT angiography and observed the usefulness of abdominal CT angiography in defining subtypes of hepatic vascular involvement and detecting extrahepatic involvement&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Authorship</span><p id="par0130" class="elsevierStylePara elsevierViewall">Concept and design of the manuscript&#46; Antoni Riera-Mestre&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Data collection&#58; Antoni Riera-Mestre&#44; Jos&#233; Mar&#237;a Mora Luj&#225;n&#44; Rosario Sanchez Mart&#237;nez&#44; Miguel Angel Torralba Cabeza&#44; Jos&#233; Luis Patier de la Pe&#241;a&#44; Mar&#237;a Coloma Juyol Rodrigo&#44; Daniel Lopez Wolf&#44; Ana Ojeda Sosa&#44; Lorenzo Monserrat&#44; M&#243;nica L&#243;pez Rodr&#237;guez&#59; and the researchers of the RiHHTa registry of the Rare Diseases Workgroup of the Spanish Society of Internal Medicine&#44; listed in <a class="elsevierStyleCrossRef" href="#sec0050">Appendix 1</a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; Antoni Riera-Mestre&#44; Jos&#233; Mar&#237;a Mora Luj&#225;n&#44; Miguel Angel Torralba Cabeza&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Drafting&#44; review and approval of the submitted manuscript&#58; Antoni Riera-Mestre&#44; Jos&#233; Mar&#237;a Mora Luj&#225;n&#44; Rosario Sanchez Mart&#237;nez&#44; Miguel Angel Torralba Cabeza&#44; Jos&#233; Luis Patier de la Pe&#241;a&#44; Mar&#237;a Coloma Juyol Rodrigo&#44; Daniel Lopez Wolf&#44; Ana Ojeda Sosa&#44; Lorenzo Monserrat&#44; M&#243;nica L&#243;pez Rodr&#237;guez&#59; and the researchers of the RiHHTa registry of the Rare Diseases Workgroup of the Spanish Society of Internal Medicine&#44; listed in <a class="elsevierStyleCrossRef" href="#sec0050">Appendix 1</a>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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    "fechaRecibido" => "2018-06-02"
    "fechaAceptado" => "2018-07-26"
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          "clase" => "keyword"
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            0 => "Hemorrhagic hereditary telangiectasia"
            1 => "Rare diseases"
            2 => "RiHHTa registry"
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            0 => "Telangiectasia hemorr&#225;gica hereditaria"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hereditary hemorrhagic telangiectasia &#40;HHT&#41; is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">After development a multicentric Spanish national registry&#44; called RiHHTa&#44; main clinical manifestations and diagnostic procedures of the first patients introduced are described&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">141 patients were included&#44; of which 91 &#40;64&#46;5&#37;&#41; were women&#46; The mean age at diagnosis was 42 years&#46; Mutations in the <span class="elsevierStyleItalic">ACVRL1</span> gene predominated over the <span class="elsevierStyleItalic">ENG</span> gene&#46; The initial symptom was recurrent epistaxis in 130 &#40;92&#46;2&#37;&#41; patients and in three &#40;2&#46;1&#37;&#41;&#44; brain abscess&#46; Pulmonary arteriovenous &#40;AV&#41; fistula were detected in 36 &#40;45&#37;&#41; of the 79 patients who underwent thoracic CT angiography&#46; The contrast echocardiography detected very few bubbles &#40;grade I&#41; or none&#44; in 36 &#40;45&#37;&#41; of these 79 affected patients&#46; In 43 &#40;67&#46;2&#37;&#41; of the 64 patients with an abdominal CT angiography&#44; hepatic vascular malformations were detected&#44; mostly telangiectasias&#44; AV and arterio-portal fistula&#44; and extrahepatic in 14 &#40;10&#37;&#41; subjects&#46; More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3&#46;9&#37; of them&#46; The upper part of the intestinal tube was the most &#40;95&#37;&#41; affected region&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The RiHHTa registry allows improving the management of patients with HHT&#46; An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La telangiectasia hemorr&#225;gica hereditaria &#40;HHT&#44; por sus siglas en ingl&#233;s&#41; es una enfermedad minoritaria con herencia autos&#243;mica dominante que provoca una afectaci&#243;n vascular sist&#233;mica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Tras la elaboraci&#243;n de un registro nacional espa&#241;ol multic&#233;ntrico&#44; denominado RiHHTa&#44; se describen las principales manifestaciones cl&#237;nicas y procedimientos diagn&#243;sticos de los primeros pacientes introducidos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se han introducido datos de 141 pacientes&#44; de los que 91 &#40;64&#44;5&#37;&#41; eran mujeres&#46; La edad media al diagn&#243;stico fue de 42 a&#241;os&#46; Las mutaciones en el gen <span class="elsevierStyleItalic">ACVRL1</span> predominaron sobre el gen <span class="elsevierStyleItalic">ENG</span>&#46; El s&#237;ntoma inicial fue la epistaxis recurrente en 130 &#40;92&#44;2&#37;&#41; pacientes y en 3 &#40;2&#44;1&#37;&#41;&#44; el absceso cerebral&#46; Se detectaron f&#237;stulas arteriovenosas &#40;AV&#41; pulmonares en 36 &#40;45&#37;&#41; de los 79 pacientes a los que se les practic&#243; una angio-TC tor&#225;cica&#46; En 36 &#40;45&#37;&#41; de estos 79 afectados no se hab&#237;a detectado paso de contraste en la ecocardiograf&#237;a o este era grado 1&#46; En 43 &#40;67&#44;2&#37;&#41; de los 64 pacientes con una angio-TC abdominal se detectaron malformaciones vasculares hep&#225;ticas&#44; mayoritariamente telangiectasias&#44; f&#237;stulas AV y arterio-portales&#44; y extrahep&#225;ticas en 14 &#40;10&#37;&#41; sujetos&#46; Se realiz&#243; cribado de malformaci&#243;n AV cerebral a m&#225;s de la mitad de los pacientes&#44; detect&#225;ndose en un 3&#44;9&#37;&#46; La parte del tubo digestivo m&#225;s afectada fue la superior &#40;95&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El Registro RiHHTa permite identificar puntos de mejora en el manejo de los pacientes con HHT&#46; Se ha detectado un uso inadecuado de la angio-TC tor&#225;cica y la utilidad de la angio-TC abdominal para definir los subtipos de afectaci&#243;n vascular hep&#225;tica y detectar afectaci&#243;n vascular extrahep&#225;tica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The names of the RiHHTa Registry researchers are listed in <a class="elsevierStyleCrossRef" href="#sec0050">Appendix 1</a>&#46;</p>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Riera-Mestre A&#44; Mora Luj&#225;n JM&#44; Sanchez Mart&#237;nez R&#44; Torralba Cabeza MA&#44; Patier de la Pe&#241;a JL&#44; Juyol Rodrigo MC&#44; et al&#46; Registro informatizado de la telangiectasia hemorr&#225;gica hereditaria &#40;Registro RiHHTa&#41; en Espa&#241;a&#58; objetivos&#44; m&#233;todos y resultados preliminares&#46; Rev Clin Esp&#46; 2018&#59;218&#58;468&#8211;476&#46;</p>"
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            "apendice" => "<p id="par0160" class="elsevierStylePara elsevierViewall">Coordinator of the RiHHTa registry&#58; A&#46; Riera-Mestre&#46; C&#46; Alonso Cotoner&#44; M&#46; Beneyto Florido&#44; A&#46; Fern&#225;ndez&#44; R&#46; Gil S&#225;nchez&#44; J&#46;S&#46; Garc&#237;a Morillo&#44; J&#46;F&#46; G&#243;mez Cerezo&#44; V&#46; G&#243;mez del Olmo&#44; P&#46; Iglesias&#44; M&#46;C&#46; Juyol Rodrigo&#44; N&#46; Lopez Osle&#44; M&#46; L&#243;pez Rodr&#237;guez&#44; D&#46; L&#243;pez Wolf&#44; M&#46;C&#46; Moreno de la Santa Garc&#237;a&#44; A&#46; Ojeda Sosa&#44; J&#46;L&#46; Patier de la Pe&#241;a&#44; M&#46;L&#46; Perez Garcia&#44; A&#46; Riera-Mestre&#44; R&#46; S&#225;nchez Mart&#237;nez&#44; M&#46;A&#46; Torralba Cabeza&#44; R&#46; Zarrabeitia Puente&#46;</p>"
            "etiqueta" => "Appendix 1"
            "titulo" => "Members of the RiHHTa Registry of the Rare Diseases Workgroup of the Spanish Society of Internal Medicine"
            "identificador" => "sec0050"
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        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Shovlin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The HHT is defined as definitive &#40;for patients who meet 3 or more criteria&#41;&#44; probable &#40;those who meet 2 criteria&#41; and unlikely &#40;if 1 or none criteria are met&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; GI&#44; gastrointestinal&#59; HHT&#44; hereditary hemorrhagic telangiectasia&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epistaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Spontaneous and recurrent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multiple&#44; in characteristic sites&#58; lips&#44; oral cavity&#44; fingers&#44; nasal fossae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Visceral lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Gastrointestinal telangiectasia&#44; pulmonary&#44; hepatic&#44; brain and spinal arteriovenous malformations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">First-degree family member with HHT according to these criteria&nbsp;\t\t\t\t\t\t\n
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BMI&#44; body mass index&#59; DVT&#44; deep vein thrombosis&#59; PE&#44; pulmonary embolism&#59; VTE&#44; venous thromboembolism&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Clinical characteristics</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sex&#44; no&#46; of females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">91 &#40;64&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean age&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;2 &#40;13&#8211;89&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean weight&#44; kg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;6 &#40;45&#8211;162&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean height&#44; cm &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">165&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;2 &#40;147&#8211;189&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span> &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;8 &#40;16&#46;6&#8211;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;10&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Comorbidities</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tobacco use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18 &#40;12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exsmoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;9&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alcoholism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;5&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Arterial hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;19&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 &#40;15&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;18&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atrial fibrillation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;5&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mechanical valvular prosthesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic lung disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;8&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ischemic cerebrovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Brain abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Surgical antecedent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39 &#40;27&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Family history of cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;12&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>History of VTE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DVT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ESS&#44; Epistaxis Severity Score&#59; PRBC&#44; packed red blood cells&#46;</p>"
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Initial symptom</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Epistaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130 &#40;92&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Brain abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;2&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;5&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean age at diagnosis&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;5 &#40;7&#8211;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Cura&#231;ao criteria</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;12&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45 &#40;31&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77 &#40;54&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Recurrent epistaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">137 &#40;97&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean ESS &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5 &#40;0&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Emergency department care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 &#40;35&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73 &#40;51&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Transfusion of PRBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31 &#40;22&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cutaneous-mucosal telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">126 &#40;89&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Digital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74 &#40;52&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lingual&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">91 &#40;64&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Labial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95 &#40;67&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35 &#40;24&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Conjunctival&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;6&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;30&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Visceral lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90 &#40;63&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">126 &#40;89&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of hereditary hemorrhagic telangiectasia&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AF&#44; alkaline phosphatase&#59; ALT&#44; alanine aminotransferase&#59; AST&#44; aspartate aminotransferase&#59; AV&#44; arteriovenous&#59; GGT&#44; gamma glutamyl transpeptidase&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Blood analysis &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">SD&#59; range&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hemoglobin&#44; g&#47;dL</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4 &#40;5&#46;6&#8211;18&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Leukocytes</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">9</span></span><span class="elsevierStyleItalic">&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1 &#40;2&#46;2&#8211;24&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Platelets</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">9</span></span><span class="elsevierStyleItalic">&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">265&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>88&#46;4 &#40;124&#8211;669&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">INR</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;02<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12 &#40;0&#46;7&#8211;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Creatinine&#44; &#956;mol&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;2 &#40;47&#46;7&#8211;150&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Glomerular filtration rate&#44; mL&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4 &#40;50&#46;8&#8211;150&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ferritin&#44; mg&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>149&#46;4 &#40;3&#8211;1137&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">TSAT&#44; &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;0 &#40;2&#8211;44&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Transthoracic echography &#40;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">N</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">86&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bubble study grade</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33 &#40;38&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;30&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20 &#40;23&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;5&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;2&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mean ejection fraction &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">67&#41;&#44; &#37;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4 &#40;40&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mean systolic pulmonary arterial pressure &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">32&#41;&#44; mm Hg</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;42 &#40;16&#8211;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mean Cardiac output &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">23&#41;&#44; bpm</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#59; &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9 &#40;2&#46;6&#8211;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cardiac index &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">17&#41;&#44; bpm&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#59; range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;1&#46;7&#8211;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#62;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Genetic mutation &#40;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">N</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">64&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ENG</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20 &#40;31&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pulmonary involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;17 &#40;64&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatic involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;14 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ACVRL1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44 &#40;68&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pulmonary involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#47;26 &#40;30&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatic involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#47;23 &#40;95&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Visceral involvement</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pulmonary AV fistulae &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">79&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;54&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36 &#40;45&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mean number of AV fistulas<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7 &#40;1&#8211;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hepatic involvement &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">64&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;32&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ALT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AST&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AP&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GGT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Bilirubin&#44; mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;67&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ALT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AST&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AP&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>96&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GGT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>91&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Bilirubin&#44; mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Type of involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AV fistulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Portal-venous fistulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Arterioportal fistulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Focal nodular hyperplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Regenerative nodular hyperplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Other intraabdominal involvement</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pancreatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cerebral AV malformation &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">77&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74 &#40;96&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;3&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Gastrointestinal tract involvement &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">20&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mean age&#44; years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;9 &#40;44&#8211;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mean age at diagnosis&#44; years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;0 &#40;27&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Type of involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Gastroduodenal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Gastro-duodenum-colon&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Additional examinations&#46;</p>"
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
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            0 => array:3 [
              "identificador" => "bib0215"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Hereditary hemorrhagic telangiectasia"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;E&#46; Guttmacher"
                            1 => "D&#46;A&#46; Marchuk"
                            2 => "R&#46;I&#46; White Jr&#46;"
                          ]
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                    0 => array:2 [
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                      "Revista" => array:6 [
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                        "volumen" => "333"
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                        "link" => array:1 [
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                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
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                ]
              ]
            ]
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              "identificador" => "bib0220"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary hemorrhagic telangiectasia &#40;HHT&#41;&#58; a population-based study of prevalence and mortality in Danish HHT patients"
                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:3 [
                            0 => "A&#46;D&#46; Kjeldsen"
                            1 => "P&#46; Vase"
                            2 => "A&#46; Green"
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                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
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                            "web" => "Medline"
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                        ]
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              "identificador" => "bib0225"
              "etiqueta" => "3"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary haemorrhagic telangiectasia &#40;Osler-Weber-Rendu syndrome&#41;&#58; a view from the 21st century"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;E&#46; Begbie"
                            1 => "G&#46;M&#46; Wallace"
                            2 => "C&#46;L&#46; Shovlin"
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                        ]
                      ]
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                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Postgrad Med J"
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                        "volumen" => "79"
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                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12566546"
                            "web" => "Medline"
                          ]
                        ]
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                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0230"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Telangiectasia hemorr&#225;gica hereditaria&#46; Available from&#58; <a id="intr0015" class="elsevierStyleInterRef" href="http://www.orpha.net/">www&#46;orpha&#46;net</a> &#91;accessed 1&#46;06&#46;18&#93;&#46;"
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            4 => array:3 [
              "identificador" => "bib0235"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Hereditary hemorrhagic telangiectasia&#58; genetics and molecular diagnostics in a new era"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46; McDonald"
                            1 => "W&#46; Wooderchak-Donahue"
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Original article
Computerized registry of patients with hemorrhagic hereditary telangiectasia (RiHHTa registry) in Spain: Objectives, methods, and preliminary results
Registro informatizado de la telangiectasia hemorrágica hereditaria (Registro RiHHTa) en España: objetivos, métodos y resultados preliminares
A. Riera-Mestrea,b,c,
Corresponding author
ariera@bellvitgehospital.cat

Corresponding author.
, J.M. Mora Lujána,c, R. Sanchez Martínezc,d, M.A. Torralba Cabezac,e, J.L. Patier de la Peñac,f, M.C. Juyol Rodrigoc,g, D. Lopez Wolfc,h, A. Ojeda Sosac,i, L. Monserratc,j, M. López Rodríguezc,k, on behalf of the Researchers of the RiHHTa Registry ◊
a Unidad de Telangiectasia Hemorrágica Hereditaria, Servicio de Medicina Interna, Hospital Universitari de Bellvitge-IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
b Facultad de Medicina y Ciencias de la Salud, Universitat de Barcelona, Barcelona, Spain
c Grupo de Trabajo en Enfermedades Minoritarias, Sociedad Española de Medicina Interna, Spain
d Servicio de Medicina Interna, Hospital General Universitario de Alicante, Alicante, Spain
e Servicio de Medicina Interna, Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain
f Servicio de Medicina Interna, Hospital Universitario Ramón y Cajal, Madrid, Spain
g Servicio de Medicina Interna, Hospital Universitario Miguel Servet, Zaragoza, Spain
h Servicio de Medicina Interna, Hospital Universitario Fundación Alcorcón, Alcorcón, Madrid, Spain
i Servicio de Medicina Interna, Hospital Insular Universitario de Gran Canaria, Las Palmas de Gran Canaria, Las Palmas, Spain
j Health in Code, A Coruña, Spain
k Servicio de Medicina Interna, Hospital Central de la Cruz Roja, Madrid, Spain
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Members of the RiHHTa Registry of the Working Group on Minority Diseases of the Spanish Society of Internal Medicine
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        "titulo" => "Registro informatizado de la telangiectasia hemorr&#225;gica hereditaria &#40;Registro RiHHTa&#41; en Espa&#241;a&#58; objetivos&#44; m&#233;todos y resultados preliminares"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Background</span><p id="par0005" class="elsevierStylePara elsevierViewall">Hereditary hemorrhagic telangiectasia &#40;HHT&#41;&#44; or Osler-Weber-Rendu disease&#44; is a systemic disease with autosomal dominant inheritance&#46; The disease&#39;s worldwide incidence rate is 1&#47;5000&#8211;8000 and is categorized among rare diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">1&#8211;4</span></a> More than 800 mutations in more than 5 genes have been reported&#44; but the considerable majority of them are located in the genes that encode for endoglin &#40;<span class="elsevierStyleItalic">ENG</span>&#41; or activin &#40;<span class="elsevierStyleItalic">ACVRL1</span>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> Both proteins form part of the transforming growth factor&#946; family&#44; which intervenes in the vascular signaling pathways&#44; influencing the regulation of angiogenesis&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">6</span></a> Abnormalities in these proteins therefore give rise to abnormal and excessive vascular growth&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Despite being a genetic disease&#44; the diagnosis of HHT is clinical and performed according to the Cura&#231;ao Criteria &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a> Telangiectasia is the characteristic lesion of HHT and consists of the substitution of the normal capillary bed by an aberrant direct connection between the arteriole and venule&#46;<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">8</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0015" class="elsevierStylePara elsevierViewall">Telangiectasias can be found in the skin and mucous membranes&#44; especially in the nasal mucosa&#44; causing recurrent epistaxis&#44; which is the main symptom of this disease&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Given that HHT is a systemic disease&#44; vascular involvement can occur in any organ&#44; although it mostly affects the lungs and liver&#46; This involvement occurs both at the microvasculature level &#40;in the form of telangiectasia&#41; and as arteriovenous fistulas or aneurysms in larger vessels&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">5&#44;7&#44;9</span></a> The recommendation is to perform a screening for these potential vascular malformations for their early detection and management according to scientific evidence&#44; as well as an appropriate follow-up of these patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">10&#44;11</span></a> Although there is no curative treatment&#44; there are drugs with positive results in various aspects of the disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0270"><span class="elsevierStyleSup">12&#8211;14</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The systemic nature of HHT&#44; its low prevalence and considerable clinical variability makes for a complex understanding of the disease&#44; especially in uncommon situations&#46; This aspect is common in the field of rare diseases&#44; where it is difficult to accumulate sufficient experience on the natural course of a disease and these patients&#8217; prognosis&#46; The preparation of registries helps overcome these difficulties&#44; representing a priority in the management of rare diseases&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15&#44;16</span></a> The use of quality registries also helps reach a consensus on diagnostic&#8211;therapeutic measures&#44; reflect on the patient management in standard clinical practice&#44; offer evidence for preparing clinical guidelines and generate hypotheses for developing clinical trials&#46;<a class="elsevierStyleCrossRefs" href="#bib0290"><span class="elsevierStyleSup">16&#8211;19</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">We present the development of the first and only HHT registry in Spain&#44; the Computerized Registry of Hereditary Hemorrhagic Telangiectasia &#40;RiHHTa&#41;&#44; the clinical characteristics and the relevant diagnostic aspects of the first patients added to the registry&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Design of the RiHHTa registry</span><p id="par0035" class="elsevierStylePara elsevierViewall">The RiHHTa is a multicenter&#44; prospective and observational registry&#44; developed within the Rare Diseases Workgroup of the Spanish Society of Internal Medicine&#46; RiHHTa has an online design&#44; accessible from <a id="intr0010" class="elsevierStyleInterRef" href="https://rihhta.healthincode.com/">https&#58;&#47;&#47;RiHHTa&#46;healthincode&#46;com</a> with individual access for each researcher and available in Spanish and English &#40;with the possibility for further internationalization&#41;&#46; The registry&#39;s main objectives are to improve the management of patients with HHT&#44; to contribute to the dissemination and understanding of the disease and to reach a consensus among its members on diagnosis-therapeutic measures &#40;as a form of networking&#41;&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">The creation of RiHHTa counted on the nonremunerated collaboration of the genetic studies company Health in Code &#40;A Coru&#241;a&#44; Spain&#41;&#44; which has broad experience in cardiomyopathy registries&#46;<a class="elsevierStyleCrossRefs" href="#bib0310"><span class="elsevierStyleSup">20&#44;21</span></a> The registry also enables the creation of personalized reports for each patient&#44; which prove useful for the healthcare tasks of the participating researchers&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patient and variables</span><p id="par0045" class="elsevierStylePara elsevierViewall">The included patients are those with a clinical diagnosis according to the Cura&#231;ao Criteria<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a> or with a genetic diagnosis&#44; who have signed the informed consent document for entering their data into the RiHHTa registry&#46; The registry is organized by families&#44; and the variables are divided into 5 large sections&#58; demographic&#44; clinical&#44; additional examination&#44; treatment and outcome data&#46; The severity of the epistaxis is quantified using the Epistaxis Severity Score&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">22</span></a> The assessment of the passage of contrast using echocardiography to detect pulmonary arteriovenous fistulas was conducted according to the Barzilai et al&#46; classification in 4 grades&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">23</span></a> For the study of gastrointestinal tract involvement&#44; the recommendations were followed for practicing the technique for those patients with anemia disproportionate to the degree of epistaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">The entry of the patients&#8217; personal data included in the registry and the treatment and communication of that data were performed according to the provisions of the law on the protection of personal data&#46; To safeguard the identity of the included patients&#44; the RiHHTa registry generated an encrypted identifier for each patient&#46; The design and operation of the RiHHTa registry was approved by the Ethics Committee of the University Hospital of Bellvitge &#40;Barcelona&#44; Spain&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">The results are expressed using absolute and relative frequencies for the qualitative variables&#46; For the quantitative variables&#44; we employed the mean&#44; standard deviation and range&#46; The descriptive analysis was performed for the entire sample&#46; The comparison between the groups of the distribution of the categorical variables was performed using the chi-squared test&#46; The comparison of the distribution of the quantitative variables that did not follow a normal distribution was performed using Student&#39;s <span class="elsevierStyleItalic">t</span>-test&#59; otherwise&#44; we employed the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test&#46; The differences were considered statistically significant when <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46; The statistical analysis was performed using the SPSS program version 18&#46;0 &#40;SPSS Inc&#46;&#44; Chicago&#44; IL&#44; USA&#41;&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">The RiHHTa registry was launched on the 6th of June 2016&#46; Since then and up to December 2017&#44; data from 152 patients from 104 families were entered&#46; From these patients&#44; there has been sufficient data to analyze a total of 141 patients from 92 families&#46; All patients were white except for 2 who were Hispanic and Asian&#46; The mean age was 51&#46;2 years&#44; and 91 &#40;64&#46;5&#37;&#41; were women&#46; The patients&#8217; comorbidities are shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; It is worth noting that 8 &#40;5&#46;7&#37;&#41; patients had atrial fibrillation&#44; 2 of whom underwent atrial appendage closure due to a contraindication for anticoagulation&#46; Almost a third &#40;27&#46;7&#37;&#41; of the patients underwent some previous surgery&#44; and 17 &#40;12&#46;1&#37;&#41; patients had a family history of cancer&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The onset of HHT was in the form of recurrent epistaxis in 130 &#40;92&#46;2&#37;&#41; patients and brain abscesses in 11 &#40;7&#46;8&#37;&#41; patients&#46; These abscesses were due to previously undiagnosed pulmonary arteriovenous fistulas in 3 &#40;2&#46;1&#37;&#41; patients and to various causes in the rest &#40;5&#46;7&#37;&#41;&#46; Virtually all patients &#40;97&#46;2&#37;&#41; presented recurrent epistaxis&#44; which required emergency care for 50 &#40;35&#46;5&#37;&#41; patients and the transfusion of packed red blood cells for 31 &#40;22&#37;&#41; patients&#46; Mucocutaneous telangiectasias&#44; which were present in 126 &#40;89&#46;4&#37;&#41; patients&#44; were mostly located in the lips&#44; tongue and fleshy part of the fingers&#46; Almost all those affected &#40;89&#46;4&#37;&#41; had a family history of HHT&#44; and most &#40;63&#46;8&#37;&#41; had visceral involvement&#46; According to the Cura&#231;ao Criteria&#44; 122 &#40;86&#46;5&#37;&#41; patients met 3 or more criteria&#44; which constituted a definitive diagnosis&#46; However&#44; the mean age at diagnosis was 42&#46;1 years&#46; The clinical characteristics of the patients in terms of HHT are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">In terms of the screening tests&#44; the passage of contrast in the transthoracic echocardiography &#40;TTE&#41; was not detected or was grade 1 in 59 &#40;41&#46;8&#37;&#41; patients&#46; However&#44; chest CT angiography was performed on 36 of these patients&#44; and pulmonary arteriovenous fistulas were detected in only 7 of these patients&#46; Six of the patients only had 1 fistula&#44; and none were susceptible to embolization&#46; Pulmonary arteriovenous fistulas were detected in 36 &#40;45&#46;5&#37;&#41; of the 79 patients studied using lung CT angiography&#44; with a mean of 2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7 &#40;1&#8211;14&#41; pulmonary arteriovenous fistulas per patient&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">Hepatic involvement was observed in 43 &#40;67&#46;2&#37;&#41; of the 64 patients who were studied&#46; These patients presented a tendency toward higher concentrations of cholestatic enzymes&#44; with significantly higher bilirubin levels than those with no hepatic involvement&#46; Telangiectasias and arteriovenous and arterioportal fistulas were more common in the liver&#46; When the patients underwent abdominal CT angiography&#44; other extrahepatic vascular disorders were detected in 14 &#40;10&#37;&#41; patients&#44; mostly pancreatic&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">A genetic study was conducted on 64 &#40;45&#46;4&#37;&#41; patients&#44; observing a mutation in the <span class="elsevierStyleItalic">ENG</span> and <span class="elsevierStyleItalic">ACVRL1</span> genes in 20 &#40;31&#46;2&#37;&#41; and 44 &#40;68&#46;8&#37;&#41; patients&#44; respectively&#46; The considerable majority &#40;64&#46;7&#37;&#41; of those who presented <span class="elsevierStyleItalic">ENG</span> mutations showed lung involvement&#46; Virtually all &#40;95&#46;6&#37;&#41; of those who presented an <span class="elsevierStyleItalic">ACVRL1</span> mutation had hepatic involvement&#46; The 2 &#40;1&#46;4&#37;&#41; patients who met only 1 Cura&#231;ao criterion and 5 of the 17 &#40;12&#46;1&#37;&#41; patients who met only 2 criteria underwent a genetic study with a mutation in the <span class="elsevierStyleItalic">ACVRL1</span> gene&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Brain involvement was detected in only 3 &#40;3&#46;9&#37;&#41; of the patients studied&#44; with no clinical repercussion in any of them&#46; Gastrointestinal losses were suspected in 36 patients&#44; 20 &#40;55&#46;5&#37;&#41; of whom presented telangiectasias in the gastrointestinal tract&#44; predominantly &#40;95&#37;&#41; in upper gastrointestinal tract&#46; <a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a> shows the results of all the additional examinations&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0090" class="elsevierStylePara elsevierViewall">The RiHHTa registry reveals the need to optimize the early diagnosis of patients with HHT&#44; which presents age-dependent symptoms&#44; with a progressive development of signs and symptoms from childhood to the fourth decade of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">3&#44;24</span></a> However&#44; the mean age at diagnosis in the RiHHTa registry was 42 years in an adult population with a mean age of 51 years&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The recurrence and severity of epistaxis is the factor that most affects these patients&#8217; quality of life&#44; as well as the need to visit the emergency department and for blood transfusions&#44; as occurred in 35&#46;5&#37; and 22&#37; of the patients included in the RiHHTa registry&#44; respectively&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">25&#44;26</span></a> Detecting patients with recurrent epistaxis and a family history of this condition should alert clinicians as to potential HHT and is an opportunity to optimize the early diagnosis of HHT&#46; These two facts&#44; along with a simple examination of the hands and oral cavity to detect mucocutaneous telangiectasias&#44; which are present in 89&#46;4&#37; of the patients in the RiHHTa registry&#44; define a definitive diagnosis of HHT &#40;according to the Cura&#231;ao criteria&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">Rare disease registries help us understand the infrequent situations of a disease&#44; which are difficult to recognize at a single center&#46;<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">15&#8211;17</span></a> Thus&#44; in the RiHHTa registry&#44; at least 20 &#40;14&#46;2&#37;&#41; patients had an indication for anticoagulation &#40;10 for heart disease and 10 for venous thromboembolism &#91;VTE&#93;&#41;&#46; HHT by itself does not represent an absolute contraindication for anticoagulation&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> A study using online interviews found that 38&#37; of 150 patients who reported having undergone anticoagulation showed no worsening of their typical epistaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">27</span></a> However&#44; for those patients with atrial fibrillation and a contraindication for anticoagulation&#44; the recommendation is to perform left atrial appendage closure&#44; as was conducted in 2 cases in the RiHHTa registry&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">28</span></a> Moreover&#44; iron-deficiency anemia has been related to a compensatory increase in factor <span class="elsevierStyleSmallCaps">viii</span> and to an increased risk of VTE in patients with HHT&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">29&#44;30</span></a> In fact&#44; the 7&#37; rate of VTE in the registry is greater than the expected incidence rate in a population with a mean age between 50 and 59 years&#44; which would be 1&#47;1000&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">31</span></a> The RiHHTa registry could provide future information on anticoagulation tolerance in patients with HHT in standard clinical practice&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">Hepatic involvement was the most common visceral manifestation&#44; which is consistent with the increased prevalence of mutations in the <span class="elsevierStyleItalic">ACVRL1</span> gene&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> Mutations in the <span class="elsevierStyleItalic">ACVRL1</span> gene define type 2 HHT&#44; with a greater prevalence of hepatic involvement&#44; as occurred with 95&#37; of the patients with mutations in this gene who were included in the RiHHTa&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> The most common form of hepatic involvement has been telangiectasias&#44; which are usually asymptomatic&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">32&#44;33</span></a> The 3 types of involvement identified through abdominal CT angiography involve different follow-ups and complications&#46; Thus&#44; arteriovenous and portal-venous fistulas can cause signs and symptoms of heart failure with a high cardiac index&#46;<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">32&#44;33</span></a> However&#44; this parameter was reported in the registry in only half of the 16 patients with this involvement&#46; Abdominal CT angiography also helps detect arterioportal fistulas that can cause portal hypertension&#44; which should be searched for during the follow-up&#46; Abnormal laboratory hepatic function values have been related to an increased risk of clinically significant hepatic impairment&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">34</span></a> In fact&#44; patients with hepatic impairment in RiHHTa showed a higher elevation of cholestatic parameters than those who did not have this impairment&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Contrast TTE is the test of choice for screening pulmonary arteriovenous fistulas&#44;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> Which are more common in patients with <span class="elsevierStyleItalic">ENG</span> gene mutations&#44; which define type 1 HHT&#44; as occurred in 64&#37; of the patients included in the RiHHTa who presented mutations in this gene&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">5</span></a> In a study conducted with 95 patients&#44; the 24 patients with no passage of contrast and the 34 patients with grade 1 &#40;according to the Barzilai classification&#41; presented no arteriovenous fistulas in the chest CT angiography&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">23&#44;35</span></a> However&#44; an unnecessary chest CT angiography was performed for 36 of the 59 patients with grade 0 or 1 in the RiHHTa registry&#46; Proper screening of the disease&#39;s manifestations needs to be conducted to reduce its complications&#46; In this respect&#44; 3 patients began with brain abscesses as the initial symptom&#46; The prior detection of pulmonary arteriovenous fistulas would have permitted antibiotic prophylaxis against risk conditions and assessment of their embolization&#44; thereby reducing the risk of this complication&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> In fact&#44; brain abscesses&#44; which were present in 7 &#40;5&#37;&#41; patients in the RiHHTa registry&#44; are a common and preventable complication in individuals with HHT and occur 30 times more often in these patients than in the general population&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">36</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Brain malformations have a different behavior&#44; because they are present from birth&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">3</span></a> However&#44; given the low prevalence and therapeutic difficulties&#44; there is no high-grade evidence or recommendations for screening these malformations in asymptomatic adult patients with HHT&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">11&#44;37&#44;38</span></a> However&#44; 77 &#40;54&#46;6&#37;&#41; patients in the RiHHTa registry underwent a study for cerebral arteriovenous malformations&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Gastrointestinal tract involvement is the last manifestation and starts in the 5th or 6th decade of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">39&#44;40</span></a> Its study is recommended for patients with anemia disproportionate to the degree of epistaxis&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">11</span></a> This is due to the fact that although 80&#37; of the patients with HHT present telangiectasias in the gastrointestinal tract&#44; only 25&#8211;30&#37; develop symptomatic gastrointestinal involvement&#46;<a class="elsevierStyleCrossRefs" href="#bib0415"><span class="elsevierStyleSup">41&#44;42</span></a> The predominance of gastroduodenal involvement observed in the RiHHTa registry has been scarcely published and supports the recommendation for starting the screening with esophagogastroduodenoscopy&#46;<a class="elsevierStyleCrossRefs" href="#bib0405"><span class="elsevierStyleSup">39&#44;41&#44;42</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In conclusion&#44; the RiHHTa registry represents an initiative for the coordinated study among its members&#44; which provides information on uncommon conditions and helps identify areas of improvement in the management of patients with HHT&#46; We detected improper use of chest CT angiography and observed the usefulness of abdominal CT angiography in defining subtypes of hepatic vascular involvement and detecting extrahepatic involvement&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Authorship</span><p id="par0130" class="elsevierStylePara elsevierViewall">Concept and design of the manuscript&#46; Antoni Riera-Mestre&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Data collection&#58; Antoni Riera-Mestre&#44; Jos&#233; Mar&#237;a Mora Luj&#225;n&#44; Rosario Sanchez Mart&#237;nez&#44; Miguel Angel Torralba Cabeza&#44; Jos&#233; Luis Patier de la Pe&#241;a&#44; Mar&#237;a Coloma Juyol Rodrigo&#44; Daniel Lopez Wolf&#44; Ana Ojeda Sosa&#44; Lorenzo Monserrat&#44; M&#243;nica L&#243;pez Rodr&#237;guez&#59; and the researchers of the RiHHTa registry of the Rare Diseases Workgroup of the Spanish Society of Internal Medicine&#44; listed in <a class="elsevierStyleCrossRef" href="#sec0050">Appendix 1</a>&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Data analysis and interpretation&#58; Antoni Riera-Mestre&#44; Jos&#233; Mar&#237;a Mora Luj&#225;n&#44; Miguel Angel Torralba Cabeza&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Drafting&#44; review and approval of the submitted manuscript&#58; Antoni Riera-Mestre&#44; Jos&#233; Mar&#237;a Mora Luj&#225;n&#44; Rosario Sanchez Mart&#237;nez&#44; Miguel Angel Torralba Cabeza&#44; Jos&#233; Luis Patier de la Pe&#241;a&#44; Mar&#237;a Coloma Juyol Rodrigo&#44; Daniel Lopez Wolf&#44; Ana Ojeda Sosa&#44; Lorenzo Monserrat&#44; M&#243;nica L&#243;pez Rodr&#237;guez&#59; and the researchers of the RiHHTa registry of the Rare Diseases Workgroup of the Spanish Society of Internal Medicine&#44; listed in <a class="elsevierStyleCrossRef" href="#sec0050">Appendix 1</a>&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Hereditary hemorrhagic telangiectasia &#40;HHT&#41; is a rare disease with autosomal dominant inheritance that causes systemic vascular affectation&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">After development a multicentric Spanish national registry&#44; called RiHHTa&#44; main clinical manifestations and diagnostic procedures of the first patients introduced are described&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">141 patients were included&#44; of which 91 &#40;64&#46;5&#37;&#41; were women&#46; The mean age at diagnosis was 42 years&#46; Mutations in the <span class="elsevierStyleItalic">ACVRL1</span> gene predominated over the <span class="elsevierStyleItalic">ENG</span> gene&#46; The initial symptom was recurrent epistaxis in 130 &#40;92&#46;2&#37;&#41; patients and in three &#40;2&#46;1&#37;&#41;&#44; brain abscess&#46; Pulmonary arteriovenous &#40;AV&#41; fistula were detected in 36 &#40;45&#37;&#41; of the 79 patients who underwent thoracic CT angiography&#46; The contrast echocardiography detected very few bubbles &#40;grade I&#41; or none&#44; in 36 &#40;45&#37;&#41; of these 79 affected patients&#46; In 43 &#40;67&#46;2&#37;&#41; of the 64 patients with an abdominal CT angiography&#44; hepatic vascular malformations were detected&#44; mostly telangiectasias&#44; AV and arterio-portal fistula&#44; and extrahepatic in 14 &#40;10&#37;&#41; subjects&#46; More than half of the patients were screened for the presence of brain arteriovenous malformations which was found in 3&#46;9&#37; of them&#46; The upper part of the intestinal tube was the most &#40;95&#37;&#41; affected region&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The RiHHTa registry allows improving the management of patients with HHT&#46; An inadequate use of thoracic CT angiography and the usefulness of abdominal CT angiography has been detected in order to define subtypes of hepatic vascular involvement and detect extrahepatic vascular involvement&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La telangiectasia hemorr&#225;gica hereditaria &#40;HHT&#44; por sus siglas en ingl&#233;s&#41; es una enfermedad minoritaria con herencia autos&#243;mica dominante que provoca una afectaci&#243;n vascular sist&#233;mica&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Tras la elaboraci&#243;n de un registro nacional espa&#241;ol multic&#233;ntrico&#44; denominado RiHHTa&#44; se describen las principales manifestaciones cl&#237;nicas y procedimientos diagn&#243;sticos de los primeros pacientes introducidos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se han introducido datos de 141 pacientes&#44; de los que 91 &#40;64&#44;5&#37;&#41; eran mujeres&#46; La edad media al diagn&#243;stico fue de 42 a&#241;os&#46; Las mutaciones en el gen <span class="elsevierStyleItalic">ACVRL1</span> predominaron sobre el gen <span class="elsevierStyleItalic">ENG</span>&#46; El s&#237;ntoma inicial fue la epistaxis recurrente en 130 &#40;92&#44;2&#37;&#41; pacientes y en 3 &#40;2&#44;1&#37;&#41;&#44; el absceso cerebral&#46; Se detectaron f&#237;stulas arteriovenosas &#40;AV&#41; pulmonares en 36 &#40;45&#37;&#41; de los 79 pacientes a los que se les practic&#243; una angio-TC tor&#225;cica&#46; En 36 &#40;45&#37;&#41; de estos 79 afectados no se hab&#237;a detectado paso de contraste en la ecocardiograf&#237;a o este era grado 1&#46; En 43 &#40;67&#44;2&#37;&#41; de los 64 pacientes con una angio-TC abdominal se detectaron malformaciones vasculares hep&#225;ticas&#44; mayoritariamente telangiectasias&#44; f&#237;stulas AV y arterio-portales&#44; y extrahep&#225;ticas en 14 &#40;10&#37;&#41; sujetos&#46; Se realiz&#243; cribado de malformaci&#243;n AV cerebral a m&#225;s de la mitad de los pacientes&#44; detect&#225;ndose en un 3&#44;9&#37;&#46; La parte del tubo digestivo m&#225;s afectada fue la superior &#40;95&#37;&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El Registro RiHHTa permite identificar puntos de mejora en el manejo de los pacientes con HHT&#46; Se ha detectado un uso inadecuado de la angio-TC tor&#225;cica y la utilidad de la angio-TC abdominal para definir los subtipos de afectaci&#243;n vascular hep&#225;tica y detectar afectaci&#243;n vascular extrahep&#225;tica&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">The names of the RiHHTa Registry researchers are listed in <a class="elsevierStyleCrossRef" href="#sec0050">Appendix 1</a>&#46;</p>"
        "identificador" => "fn0005"
      ]
      1 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Please cite this article as&#58; Riera-Mestre A&#44; Mora Luj&#225;n JM&#44; Sanchez Mart&#237;nez R&#44; Torralba Cabeza MA&#44; Patier de la Pe&#241;a JL&#44; Juyol Rodrigo MC&#44; et al&#46; Registro informatizado de la telangiectasia hemorr&#225;gica hereditaria &#40;Registro RiHHTa&#41; en Espa&#241;a&#58; objetivos&#44; m&#233;todos y resultados preliminares&#46; Rev Clin Esp&#46; 2018&#59;218&#58;468&#8211;476&#46;</p>"
      ]
    ]
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            "apendice" => "<p id="par0160" class="elsevierStylePara elsevierViewall">Coordinator of the RiHHTa registry&#58; A&#46; Riera-Mestre&#46; C&#46; Alonso Cotoner&#44; M&#46; Beneyto Florido&#44; A&#46; Fern&#225;ndez&#44; R&#46; Gil S&#225;nchez&#44; J&#46;S&#46; Garc&#237;a Morillo&#44; J&#46;F&#46; G&#243;mez Cerezo&#44; V&#46; G&#243;mez del Olmo&#44; P&#46; Iglesias&#44; M&#46;C&#46; Juyol Rodrigo&#44; N&#46; Lopez Osle&#44; M&#46; L&#243;pez Rodr&#237;guez&#44; D&#46; L&#243;pez Wolf&#44; M&#46;C&#46; Moreno de la Santa Garc&#237;a&#44; A&#46; Ojeda Sosa&#44; J&#46;L&#46; Patier de la Pe&#241;a&#44; M&#46;L&#46; Perez Garcia&#44; A&#46; Riera-Mestre&#44; R&#46; S&#225;nchez Mart&#237;nez&#44; M&#46;A&#46; Torralba Cabeza&#44; R&#46; Zarrabeitia Puente&#46;</p>"
            "etiqueta" => "Appendix 1"
            "titulo" => "Members of the RiHHTa Registry of the Rare Diseases Workgroup of the Spanish Society of Internal Medicine"
            "identificador" => "sec0050"
          ]
        ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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        "fuente" => "<span class="elsevierStyleItalic">Source</span>&#58; Shovlin et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">7</span></a>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">The HHT is defined as definitive &#40;for patients who meet 3 or more criteria&#41;&#44; probable &#40;those who meet 2 criteria&#41; and unlikely &#40;if 1 or none criteria are met&#41;&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; GI&#44; gastrointestinal&#59; HHT&#44; hereditary hemorrhagic telangiectasia&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Description&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Epistaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Spontaneous and recurrent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Multiple&#44; in characteristic sites&#58; lips&#44; oral cavity&#44; fingers&#44; nasal fossae&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Visceral lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Gastrointestinal telangiectasia&#44; pulmonary&#44; hepatic&#44; brain and spinal arteriovenous malformations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">First-degree family member with HHT according to these criteria&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Cura&#231;ao criteria&#46;</p>"
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; BMI&#44; body mass index&#59; DVT&#44; deep vein thrombosis&#59; PE&#44; pulmonary embolism&#59; VTE&#44; venous thromboembolism&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Clinical characteristics</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sex&#44; no&#46; of females&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">91 &#40;64&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean age&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">51&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;2 &#40;13&#8211;89&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean weight&#44; kg &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>17&#46;6 &#40;45&#8211;162&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean height&#44; cm &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">165&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;2 &#40;147&#8211;189&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean BMI&#44; kg&#47;m<span class="elsevierStyleSup">2</span> &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>5&#46;8 &#40;16&#46;6&#8211;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BMI<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg&#47;m<span class="elsevierStyleSup">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;10&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Comorbidities</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tobacco use&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18 &#40;12&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exsmoker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;9&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Alcoholism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;5&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Arterial hypertension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27 &#40;19&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Diabetes mellitus&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Dyslipidemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22 &#40;15&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Heart disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;18&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Atrial fibrillation&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;5&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mechanical valvular prosthesis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronic lung disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;8&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ischemic cerebrovascular disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Brain abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Surgical antecedent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">39 &#40;27&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Osteoporosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Family history of cancer&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;12&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>History of VTE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;7&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>DVT&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;4&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PE&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; ESS&#44; Epistaxis Severity Score&#59; PRBC&#44; packed red blood cells&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Initial symptom</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Epistaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">130 &#40;92&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Brain abscess&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;2&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;5&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean age at diagnosis&#44; years &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;5 &#40;7&#8211;81&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Cura&#231;ao criteria</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;1&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;12&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">45 &#40;31&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77 &#40;54&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Recurrent epistaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">137 &#40;97&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mean ESS &#40;SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5 &#40;0&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Emergency department care&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">50 &#40;35&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anemia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">73 &#40;51&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Transfusion of PRBC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31 &#40;22&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cutaneous-mucosal telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">126 &#40;89&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Digital&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74 &#40;52&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Lingual&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">91 &#40;64&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Labial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">95 &#40;67&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Oral&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35 &#40;24&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Conjunctival&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;6&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Other locations&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;30&#46;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Visceral lesions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">90 &#40;63&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Family history&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">126 &#40;89&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Clinical characteristics of hereditary hemorrhagic telangiectasia&#46;</p>"
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          "leyenda" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Abbreviations&#58; AF&#44; alkaline phosphatase&#59; ALT&#44; alanine aminotransferase&#59; AST&#44; aspartate aminotransferase&#59; AV&#44; arteriovenous&#59; GGT&#44; gamma glutamyl transpeptidase&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Number of patients&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">141&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Blood analysis &#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">SD&#59; range&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hemoglobin&#44; g&#47;dL</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;4 &#40;5&#46;6&#8211;18&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Leukocytes</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">9</span></span><span class="elsevierStyleItalic">&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1 &#40;2&#46;2&#8211;24&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Platelets</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#215;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">10</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">9</span></span><span class="elsevierStyleItalic">&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">265&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>88&#46;4 &#40;124&#8211;669&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">INR</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;02<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12 &#40;0&#46;7&#8211;1&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Creatinine&#44; &#956;mol&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;2 &#40;47&#46;7&#8211;150&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Glomerular filtration rate&#44; mL&#47;min&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">93&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>18&#46;4 &#40;50&#46;8&#8211;150&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Ferritin&#44; mg&#47;l</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">87&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>149&#46;4 &#40;3&#8211;1137&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">TSAT&#44; &#37;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">19&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;0 &#40;2&#8211;44&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Transthoracic echography &#40;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">N</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">86&#41;</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Bubble study grade</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33 &#40;38&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26 &#40;30&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20 &#40;23&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;5&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;2&#46;3&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mean ejection fraction &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">67&#41;&#44; &#37;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">63&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;4 &#40;40&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Mean systolic pulmonary arterial pressure &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">32&#41;&#44; mm Hg</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">31&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;42 &#40;16&#8211;66&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">mean Cardiac output &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">23&#41;&#44; bpm</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#59; &#40;range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9 &#40;2&#46;6&#8211;11&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cardiac index &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">17&#41;&#44; bpm&#47;m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">&#40;mean</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#177;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">SD&#59; range&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2 &#40;1&#46;7&#8211;6&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>&#62;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Genetic mutation &#40;</span><span class="elsevierStyleItalic"><span class="elsevierStyleBold">N</span></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleBold">64&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ENG</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20 &#40;31&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pulmonary involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&#47;17 &#40;64&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatic involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#47;14 &#40;50&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">ACVRL1</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">44 &#40;68&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pulmonary involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#47;26 &#40;30&#46;7&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hepatic involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">22&#47;23 &#40;95&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleBold">Visceral involvement</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Pulmonary AV fistulae &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">79&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;54&#46;4&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">36 &#40;45&#46;6&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mean number of AV fistulas<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7 &#40;1&#8211;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Hepatic involvement &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">64&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;32&#46;8&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ALT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AST&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AP&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>19&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GGT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">33&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>37&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Bilirubin&#44; mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;21<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">43 &#40;67&#46;2&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>ALT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>11&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AST&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AP&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">113&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>96&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>GGT&#44; U&#47;l&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">70&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>91&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Bilirubin&#44; mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;5<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Type of involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>telangiectasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>AV fistulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Portal-venous fistulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Arterioportal fistulas&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Focal nodular hyperplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Regenerative nodular hyperplasia&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Other intraabdominal involvement</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;10&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pancreatic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;5&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Cerebral AV malformation &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">77&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">74 &#40;96&#46;1&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;3&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Gastrointestinal tract involvement &#40;N</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#61;</span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">20&#41;</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mean age&#44; years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">61&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;9 &#40;44&#8211;83&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Mean age at diagnosis&#44; years<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD &#40;range&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">53&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;0 &#40;27&#8211;80&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Type of involvement&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Gastroduodenal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&nbsp;\t\t\t\t\t\t\n
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Article information
ISSN: 22548874
Original language: English
DOI:10.1016/j.rceng.2018.07.001
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