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ABSTRACT: Hereditary hemorrhagic telangiectasia (HHT) is the second-most common inherited bleeding disorder (BD) worldwide and remains without approved therapies. HHT causes serious mucosal bleeding resulting in severe iron-deficiency anemia, major psychosocial complications, and visceral arteriovenous malformations in the brain, lung, and liver, which can cause life-threatening hemorrhagic complications. No study has examined the relative morbidity of HHT and von Willebrand disease (VWD), which is the most common inherited BD in women. We performed an observational cohort study of women with HHT or VWD, comparing a representative sample of 100 randomly selected women with HHT to 100 randomly selected age-matched women with VWD. In HHT vs VWD, recurrent epistaxis and gastrointestinal bleeding were more likely (odds ratio [OR], 32.73 [95% confidence interval, 13.81-71.80]; P < .0001 and 5.69 [2.59-12.89]; P < .0001) and heavy menstrual bleeding was less likely (OR, 0.32 [0.18-0.57]; P < .0001). Iron-deficiency anemia was significantly more likely, and the lowest hemoglobin was significantly lower in HHT than in VWD. The odds of iron infusion dependence, requirement for red cell transfusion, and hemostatic surgical procedures were significantly higher-17-fold, threefold, and eightfold higher, respectively-and hospital admissions to manage disease complications were both â¼14 times more frequent in women with HHT vs those with VWD. In conclusion, much higher disease-related morbidity, mortality, and health care use were observed in women with HHT vs VWD, providing evidence that HHT may be the most clinically significant inherited BD in women. Given the vast gap in research funding for HHT compared with both hemophilia (a disease primarily of men) and VWD, these findings have significant implications for gender equity in hematology.
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Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/terapia , Femenino , Persona de Mediana Edad , Adulto , Enfermedades de von Willebrand/complicaciones , Enfermedades de von Willebrand/epidemiología , Epistaxis/etiología , Anemia Ferropénica/etiología , Anciano , Estudios de CohortesRESUMEN
Clobazam is a 1,5-benzodiazepine frequently used as an adjunctive agent for refractory seizures and status epilepticus. Clobazam undergoes metabolism to an active metabolite norclobazam which is subsequently hydroxylated by CYP2C19, a cytochrome with several pharmacogenetic variants. Patients with poor metabolizer phenotypes may have elevated norclobazam levels and subsequent adverse effects. We present a case of an Asian American male receiving clobazam at a standard therapeutic dose for seizure disorder who became comatose secondary to significantly elevated norclobazam concentrations. Genetic testing revealed the patient was a poor CYP2C19 metabolizer, accounting for the impaired clearance. Clinicians should be aware of the patient populations at risk for these genetic polymorphisms and adjust initial doses based on package labeling or consider therapeutic drug monitoring to avoid adverse effects.
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INTRODUCTION: Data describing safety and tolerability of anticoagulation and antiplatelet therapy in hereditary hemorrhagic telangiectasia (HHT), the second-most-common inherited bleeding disorder, is limited. METHODS: We performed a scoping review, searching MEDLINE and EMBASE from inception to March 2023 for eligible studies reporting detailed clinical data describing antithrombotic use in HHT. Data extracted included study design, patient population, and characteristics and outcomes of antithrombotic therapy. RESULTS: Of 625 unique manuscripts identified through database search, 77 were included: 64 case reports/case series describing 65 patients and 13 cohort studies. Data were extracted on a total of 466 patients with HHT, covering 587 episodes of antithrombotic therapy. The most common reasons for antithrombotic therapy were venous thromboembolism (VTE) (44.6 %), atrial arrhythmias (17.8 %) and stroke (10.5 %). anticoagulation was used in in 356 episodes (61.9 %), antiplatelet therapy in 140 episodes (24.3 %), and both together in 50 episodes (8.7 %). Complications of therapy included worsened HHT-associated bleeding (primarily epistaxis and gastrointestinal bleeding) in 198 antithrombotic treatment episodes (38.9 %) and premature antithrombotic therapy discontinuation in 142 episodes (28.9 %). Bleeding-directed therapy (local ablative therapy and systemic therapies) were employed to address worsening bleeding in 14.6 % of episodes. No specific complications of therapy were reported in 322 total antithrombotic events (58.4 %). Rates of bleeding (8.3 % to 80 %), therapy discontinuation (14.3 % to 57.1 %), and other complications ranged considerably from study to study. CONCLUSION: Current publications vary widely on the outcomes and tolerability of antithrombotics in HHT, but confirm the clinical challenge of adequate antithrombotic therapy in this population. More formal studies are needed to better guide optimal antithrombotic use in HHT.
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Telangiectasia Hemorrágica Hereditaria , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Fibrinolíticos/uso terapéutico , Epistaxis/epidemiología , Epistaxis/etiología , Epistaxis/terapia , Anticoagulantes/uso terapéuticoRESUMEN
BACKGROUND: Antithrombotic therapy (anticoagulation and antiplatelet therapy) is frequently needed in patients with hereditary hemorrhagic telangiectasia (HHT); however, data describing and guiding its use are very limited. OBJECTIVES: To investigate the safety, tolerability, and effectiveness of antithrombotic therapy in HHT in a cohort large enough to compare agents, evaluate for baseline predictors of premature discontinuation, and evaluate hematologic support requirements and healthcare utilization before and after antithrombitc therapy initiation. METHODS: We performed a multicenter observational cohort study characterizing the outcomes of antithrombic therapy in adults with HHT. RESULTS: A total of 119 patients with HHT with 187 discrete antithrombotic therapy episodes were included. Of these, 59 patients (50%) dose-reduced and/or prematurely discontinued therapy (including 52 patients [44%] who discontinued) due to worsened bleeding complications. Initiation at reduced dose intensity had a similar premature discontinuation rate (49%) as initiation at standard dose intensity (43%). In a multivariable logistic model, a history of gastrointestinal bleeding was associated with 3.25-fold odds of discontinuation (p = .001). Hemoglobin was significantly lower (10.8 g/dL vs 12.2 g/dL, p < .001), and the need for hematologic support (intravenous iron and/or red blood cell transfusion) was significantly higher (29 patients vs 12 patients, p = .004) in the 3 months after antithrombotic therapy initiation vs the 3 months before; emergency department visits and hospital admissions due to bleeding also increased. The rates of dose-reduction and/or premature discontinuation were similar regardless of the anticoagulant class (warfarin, 46%; heparin-based, 48%; direct oral anticoagulants, 44%) or with multiple simultaneous agents (44%) but were slightly lower with single-agent antiplatelet therapy (37%). Thromboembolism despite receiving antithrombotic therapy was common (18 patients, 15%) with varying outcomes. CONCLUSION: Antithrombotic therapy is challenging in HHT, resulting in objectively higher morbidity and health care utilization from worsened bleeding. Discontinuation rates approached 50% regardless of the dose intensity at initiation or type of antithrombotic agent used and were higher in patients with a gastrointestinal bleeding history.
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Telangiectasia Hemorrágica Hereditaria , Adulto , Humanos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/diagnóstico , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/efectos adversos , Fibrinolíticos/uso terapéutico , Anticoagulantes/efectos adversos , Hemorragia Gastrointestinal/inducido químicamenteRESUMEN
BACKGROUND: Without aggressive treatment, pulmonary arterial hypertension (PAH) has a 5-year mortality of approximately 40%. A patient's response to vasodilators at diagnosis impacts the therapeutic options and prognosis. We hypothesized that analyzing perfusion images acquired before and during vasodilation could identify characteristic differences between PAH and control subjects. METHODS: We studied 5 controls and 4 subjects with PAH using HRCT and 13NN PET imaging of pulmonary perfusion and ventilation. The total spatial heterogeneity of perfusion (CV2Qtotal) and its components in the vertical (CV2Qvgrad) and cranio-caudal (CV2Qzgrad) directions, and the residual heterogeneity (CV2Qr), were assessed at baseline and while breathing oxygen and nitric oxide (O2 + iNO). The length scale spectrum of CV2Qr was determined from 10 to 110 mm, and the response of regional perfusion to O2 + iNO was calculated as the mean of absolute differences. Vertical gradients in perfusion (Qvgrad) were derived from perfusion images, and ventilation-perfusion distributions from images of 13NN washout kinetics. RESULTS: O2 + iNO significantly enhanced perfusion distribution differences between PAH and controls, allowing differentiation of PAH subjects from controls. During O2 + iNO, CV2Qvgrad was significantly higher in controls than in PAH (0.08 (0.055-0.10) vs. 6.7 × 10-3 (2 × 10-4-0.02), p < 0.001) with a considerable gap between groups. Qvgrad and CV2Qtotal showed smaller differences: - 7.3 vs. - 2.5, p = 0.002, and 0.12 vs. 0.06, p = 0.01. CV2Qvgrad had the largest effect size among the primary parameters during O2 + iNO. CV2Qr, and its length scale spectrum were similar in PAH and controls. Ventilation-perfusion distributions showed a trend towards a difference between PAH and controls at baseline, but it was not statistically significant. CONCLUSIONS: Perfusion imaging during O2 + iNO showed a significant difference in the heterogeneity associated with the vertical gradient in perfusion, distinguishing in this small cohort study PAH subjects from controls.
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Hipertensión Arterial Pulmonar , Humanos , Voluntarios Sanos , Óxido Nítrico , Estudios de Cohortes , Hipertensión Pulmonar Primaria Familiar , Imagen de Perfusión , Biomarcadores , OxígenoRESUMEN
Macitentan is an oral endothelin receptor antagonist for the management of pulmonary arterial hypertension (PAH). The OPsumit® USers Registry (OPUS) and the OPsumit® Historical USers cohort (OrPHeUS) medical chart review provide real-world data for patients newly initiating macitentan. This study aims to describe the characteristics, safety profile, and clinical outcomes of PAH patients newly treated with macitentan in the combined OPUS/OrPHeUS data set. OPUS was a prospective, multicenter, long-term, observational drug registry from April 2014 to June 2020. OrPHeUS was a retrospective, US, multicenter chart review: observation period October 2013 to March 2017. All analyses were descriptive. At registry closure in June 2020, the combined population consisted of 5654 patients, of whom 81.9% were diagnosed with PAH. For these 4626 patients, median duration of macitentan exposure observed was 14.5 (Q1 = 5.2, Q3 = 29.0) months; idiopathic PAH (54.8%) was the most common form of PAH; macitentan was initiated as monotherapy (37.9%), or as part of double (48.0%) or triple therapy (14.1%); discontinuation due to nonhepatic/hepatic adverse events occurred in 17.1%/0.3% of patients; 9.9% of patients experienced ≥1 hepatic adverse events; Kaplan-Meier estimates showed that at 1 year 59.9% (95% confidence interval: 58.3, 61.5) of patients were free from hospitalization and survival was 90.4% (89.3, 91.3). This analysis of real-world data from the combined OPUS and OrPHeUS populations demonstrated that macitentan is well tolerated in a large, diverse population of PAH patients, with overall and hepatic safety profiles consistent with previous macitentan clinical trials.
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BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). METHODS: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. RESULTS: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. CONCLUSIONS: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.
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Tratamiento Farmacológico de COVID-19 , Hospitalización , Óxido Nítrico/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Respiración/efectos de los fármacos , Administración por Inhalación , COVID-19/complicaciones , COVID-19/virología , Relación Dosis-Respuesta a Droga , Humanos , Óxido Nítrico/farmacología , Óxido Nítrico/uso terapéutico , Neumonía Viral/complicacionesRESUMEN
RATIONALE: Pulmonary Arterial Hypertension (PAH), a rare complication of HHT is associated with poor outcome. There are no trials to date that have investigated whether pulmonary vasodilator therapy improves hemodynamics or survival in this disease. OBJECTIVE: To determine whether pulmonary vasodilator therapy improves survival, exercise capacity, or hemodynamics in HHT patients with pre-capillary PH. METHODS: We performed a before-and-after observational study on a multicenter cohort of subjects with HHT-PAH who received intravenous prostanoid therapy. We then conducted a systematic review, searching Medline and EMBASE through December 2019. Studies that enrolled HHT-PAH subjects and reported treatment outcomes were selected. PROSPERO #158179. RESULTS: Twenty-one articles were selected. Studies were before-and-after observational studies, case reports, and case series. Among all subjects with HHT-PAH, both mPAP (65 ± 19 pre-treatment vs 51 ± 16 mmHg post-treatment p = 0.04) and PVR (12 ± 6 pre-treatment vs 8 ± 4 WU post-treatment p = 0.01) improved with treatment. The mPAP improved with either oral (57 ± 17 pre-treatment versus 44 ± 13 mmHg post-treatment, p = 0.03) or intravenous (80 ± 15 pre-treatment versus 64 ± 16 mmHg post-treatment, p = 0.017) therapy. PVR also improved with either oral (10 ± 4 pre-treatment versus 6 ± 3 WU post-treatment, p = 0.004) or intravenous (17 ± 5 pre-treatment versus 10 ± 4 WU post-treatment, p = 0.04) therapy. Survival among HHT-PAH patients who received oral or intravenous therapy was not different (p = 0.2). Unadjusted survival among HHT-PAH patients was longer than that of IPAH patients (p = 0.008). There was no difference in side effects among HHT-PAH patient who received oral or intravenous therapy (p = 0.1). CONCLUSION: Pulmonary vasodilator therapy is effective in improving hemodynamics of subjects with HHT-PAH and was not associated with increased risk of side effects.
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Hipertensión Pulmonar , Hipertensión Arterial Pulmonar , Telangiectasia Hemorrágica Hereditaria , Hipertensión Pulmonar Primaria Familiar , Hemodinámica , Humanos , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/etiología , Estudios Multicéntricos como Asunto , Estudios Observacionales como Asunto , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológicoRESUMEN
INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare genetic disease with prevalence of approximately 1 in 5000-10,000. We evaluated the prevalence and association of cerebrovascular and cardiovascular comorbidities in HHT patients using national database. METHODS: Retrospective observational study was performed using National Inpatient Sampling (NIS) database for the year 2014. HHT patients and comorbidities were identified using ICD-9 codes. Univariate and multivariate analyses were performed using SAS. RESULTS: Prevalence of HHT was 0.0119% with predominance in White population. Mean age of HHT patients was 59 years. Increased proportion of HHT patients had hypertension (46.8% vs 42%), anemia (28.9% vs 15.1%), chronic pulmonary disease (24.8% vs 16.4%), congestive heart failure (15.7% vs 7.5%), liver disease (7.9% vs 2.8%), migraine (4.5% vs 1.5%), and cerebrovascular malformations (0.8% vs 0.03%), whereas chronic kidney disease (12.7% vs 12.2%), headaches (1.3% vs 1.1%), seizures (0.7% vs 0.9%), transient ischemic attacks (1.06% vs 1.03%), ischemic (1.2% vs 1.0%), and hemorrhagic (0.5% vs 0.3%) strokes were similar to those without HHT. Multivariable model shows increase in cerebrovascular malformations (OR 11.04, CI 2.49-22.26, p < 0.0001), migraine (OR 3.23, CI 2.30-4.52, p < 0.0001), chronic blood loss anemia (OR 6.83, CI 5.36-8.71, p < 0.0001), congestive heart failure (OR 1.55, CI 1.26-1.91, p < 0.0001), chronic pulmonary disease (OR 1.30, CI 1.09-1.56, p = 0.0038), and hepatic disease (OR 2.63, CI 2.01-3.45, p < 0.0001) in HHT patients as compared to non-HHT patients. CONCLUSION: There is a need for a large prospective registry of HHT patients that can corroborate these associations and burden of cerebrovascular and cardiovascular diseases.
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Enfermedades Cardiovasculares , Sistema Cardiovascular , Telangiectasia Hemorrágica Hereditaria , Enfermedades Cardiovasculares/epidemiología , Costo de Enfermedad , Humanos , Persona de Mediana Edad , Prevalencia , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/epidemiologíaAsunto(s)
Angiografía por Tomografía Computarizada , Hipertensión Pulmonar/diagnóstico por imagen , Arteria Pulmonar , Embolia Pulmonar/diagnóstico por imagen , Sarcoma/diagnóstico , Neoplasias Vasculares/diagnóstico , Anciano , Enfermedad Crónica , Diagnóstico Diferencial , Femenino , Humanos , Hipertensión Pulmonar/complicaciones , Hipertensión Pulmonar/patología , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/patología , Embolia Pulmonar/etiología , Embolia Pulmonar/patología , Sarcoma/patología , Neoplasias Vasculares/patologíaRESUMEN
Hereditary hemorrhagic telangiectasia (HHT, Osler-Weber-Rendu disease) is a rare multisystem vascular disorder causing chronic gastrointestinal bleeding, epistaxis, and severe anemia. Bevacizumab, an anti-vascular endothelial growth factor antibody, may be effective to treat bleeding in HHT. This international, multicenter, retrospective study evaluated the use of systemic bevacizumab to treat HHT-associated bleeding and anemia at 12 HHT treatment centers. Hemoglobin, epistaxis severity score, red cell units transfused, and intravenous iron infusions before and after treatment were evaluated using paired means testing and mixed-effects linear models. 238 HHT patients received bevacizumab for a median of 12 (range, 1-96) months. Compared with pretreatment, bevacizumab increased mean hemoglobin by 3.2 g/dL (95% CI, 2.9-3.5 g/dL) [mean hemoglobin 8.6 (8.5, 8.8) g/dL versus 11.8 (11.5, 12.1) g/dL, p<0.0001)] and decreased the epistaxis severity score (ESS) by 3.4 (3.2-3.7) points [mean ESS 6.8 (6.6-7.1) versus 3.4 (3.2-3.7), P<0.0001] during the first year of treatment. Compared with 6 months pretreatment, RBC units transfused decreased by 82% [median of 6.0 (IQR 0.0-13.0) units versus 0 (IQR, 0.0-1.0) units, P<0.0001] and iron infusions decreased by 70% [median of 6.0 (1.0-18.0) infusions versus 1.0 (0.0-4.0) infusions, P<0.0001] during the first 6 months of bevacizumab treatment. Outcomes were similar regardless of underlying pathogenic mutation. Following initial induction infusions, continuous/scheduled bevacizumab maintenance achieved higher hemoglobin and lower ESS than intermittent/as needed maintenance but with more drug exposure. Bevacizumab was well tolerated: hypertension, fatigue, and proteinuria were the most common adverse events. Venous thromboembolism occurred in 2% of patients. In conclusion, systemic bevacizumab was safe and effective to manage chronic bleeding and anemia in HHT.
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Telangiectasia Hemorrágica Hereditaria , Administración Intravenosa , Bevacizumab/uso terapéutico , Hemorragia/tratamiento farmacológico , Humanos , Estudios Retrospectivos , Telangiectasia Hemorrágica Hereditaria/complicaciones , Telangiectasia Hemorrágica Hereditaria/tratamiento farmacológicoRESUMEN
To describe the frequency with which pulmonary capillary wedge pressure measurements, obtained during right heart catheterization, are falsely elevated and to educate operators on techniques to improve accuracy of pulmonary capillary wedge pressure reporting. Failure to completely occlude pulmonary artery branch vessels during balloon inflation can lead to falsely elevated, "incomplete" pulmonary capillary wedge pressures. Balloon deflation prior to catheter retraction may result in catheter advancement into smaller branch vessels, yielding an inadvertent but more accurate alternative pulmonary capillary wedge pressure. We hypothesized that this phenomenon can be identified on retrospective review of right heart catheterization tracings, which occurs commonly and goes unrecognized by operators. We conducted a retrospective study of patients undergoing right heart catheterization or right heart catheterization and left heart catheterization with computer-generated pulmonary capillary wedge pressure ≥20 from January 2015 to June 2017. Alternative pulmonary capillary wedge pressures were defined as a pulmonary capillary wedge pressure trace during balloon deflation ≥3 mmHg lower than the reported pulmonary capillary wedge pressure. Inter-rater reliability of tracing reviewers was also evaluated. Results showed that, of the 182 tracings reviewed, an alternative pulmonary capillary wedge pressure was identified in 26 or 14.3% of cases. Eleven of these alternative pulmonary capillary wedge pressures were ≤15 mmHg with a calculated pulmonary vascular resistance ≥3 Wood units in 10 patients, re-classifying the etiology of pulmonary hypertension from post-capillary to pre-capillary in 38.5% of cases. For the eight patients for whom left heart catheterization data were available, left ventricular end-diastolic pressure aligned with the alternative pulmonary capillary wedge pressure. In conclusion, inadvertently obtained, but likely more accurate, alternative pulmonary capillary wedge pressures were identified in almost 15% of procedures reviewed from a busy academic institution. As wedge pressures often drive diagnosis and treatment decisions for patients with cardiac and pulmonary pathology, operators should be attuned to balloon deflation as a time when alternative pulmonary capillary wedge pressures may be identified as they are likely more reflective of left ventricular end-diastolic pressure. Additional tools to ensure accuracy of pulmonary capillary wedge pressure reporting are reviewed.
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DESCRIPTION: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.
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Telangiectasia Hemorrágica Hereditaria/diagnóstico , Telangiectasia Hemorrágica Hereditaria/terapia , Anemia/etiología , Anemia/terapia , Malformaciones Arteriovenosas/etiología , Malformaciones Arteriovenosas/terapia , Niño , Epistaxis/etiología , Epistaxis/terapia , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/terapia , Enfermedades Genéticas Congénitas/etiología , Enfermedades Genéticas Congénitas/terapia , Humanos , Hígado/irrigación sanguínea , Telangiectasia Hemorrágica Hereditaria/complicacionesAsunto(s)
COVID-19/complicaciones , COVID-19/diagnóstico por imagen , Hipoxia/complicaciones , Hipoxia/diagnóstico por imagen , COVID-19/patología , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Humanos , Hipoxia/patología , Pulmón/irrigación sanguínea , Pulmón/diagnóstico por imagen , Pulmón/patología , Imagen de Perfusión , Imagen Radiográfica por Emisión de Doble Fotón , SARS-CoV-2 , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Hepatic involvement in hereditary hemorrhagic telangiectasia (HHT) is common and can be associated with severe clinical consequences, including portal hypertension, cardiac failure, and encephalopathy. However, there are no reliable clinical predictors of hepatic involvement and its associated complications, limiting appropriate identification of these patients. In this work, we define the utility of serum ammonia and liver biochemical tests (LFTs) in predicting hepatic HHT involvement and its complications. METHODS: We performed a retrospective study examining a well-characterized cohort of patients with HHT. Clinical characteristics, laboratory tests, liver imaging, transthoracic echocardiography assessment of right ventricular systolic pressure (RVSP), and history of other HHT-related outcomes were assessed. Patients were followed for the development of encephalopathy. RESULTS: Of 45 patients with definite HHT, 18 (40%) had elevated ammonia levels. An elevated ammonia associated with the presence of hepatic arteriovenous malformations (AVMs) on imaging (P < 0.03) and when combined with elevated liver tests increased the sensitivity for hepatic AVMs by 18% (55% for LFTs vs 73% for LFTs plus ammonia). Furthermore, an elevated serum ammonia in patients with HHT associated with an elevated RVSP (>35 mm Hg), providing an 80% sensitivity and 71% specificity for predicting the presence of pulmonary hypertension. In contrast, there was no association with an elevated serum ammonia and encephalopathy over a total of 859 months of follow-up. DISCUSSION: Elevated ammonia in a cohort of patients with HHT was associated with the presence of hepatic AVMs and elevated RVSP, but no other complications of HHT, including encephalopathy.
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Malformaciones Arteriovenosas/sangre , Hiperamonemia/sangre , Hepatopatías/sangre , Hipertensión Arterial Pulmonar/sangre , Telangiectasia Hemorrágica Hereditaria/sangre , Adulto , Anciano , Anciano de 80 o más Años , Alanina Transaminasa/sangre , Fosfatasa Alcalina/sangre , Amoníaco/sangre , Malformaciones Arteriovenosas/diagnóstico por imagen , Malformaciones Arteriovenosas/etiología , Aspartato Aminotransferasas/sangre , Estudios de Cohortes , Ecocardiografía , Femenino , Humanos , Hiperamonemia/etiología , Hepatopatías/diagnóstico por imagen , Hepatopatías/etiología , Masculino , Persona de Mediana Edad , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Hipertensión Arterial Pulmonar/etiología , Estudios Retrospectivos , Sensibilidad y Especificidad , Telangiectasia Hemorrágica Hereditaria/complicaciones , Adulto JovenRESUMEN
Pulmonary embolism (PE) is a life-threatening condition and a leading cause of morbidity and mortality. There have been many advances in the field of PE in the last few years, requiring a careful assessment of their impact on patient care. However, variations in recommendations by different clinical guidelines, as well as lack of robust clinical trials, make clinical decisions challenging. The Pulmonary Embolism Response Team Consortium is an international association created to advance the diagnosis, treatment, and outcomes of patients with PE. In this consensus practice document, we provide a comprehensive review of the diagnosis, treatment, and follow-up of acute PE, including both clinical data and consensus opinion to provide guidance for clinicians caring for these patients.
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Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Enfermedad Aguda , Consenso , Estudios de Seguimiento , Humanos , Embolia Pulmonar/diagnóstico por imagen , Medición de RiesgoAsunto(s)
Ejercicio Físico/fisiología , Imagen de Perfusión/métodos , Tomografía de Emisión de Positrones/métodos , Hipertensión Arterial Pulmonar/diagnóstico por imagen , Hipertensión Arterial Pulmonar/fisiopatología , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
The original version of the article unfortunately contained an error in conflict of interest. This erratum is published with the correct conflict of interest.