Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life. METHODS: We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations). RESULTS: The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash. CONCLUSIONS: Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).

Arterial Spin-Labeling MR Imaging in the Detection of Intracranial Arteriovenous Malformations in Patients with Hereditary Hemorrhagic Telangiectasia.

BACKGROUND AND PURPOSE: Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that causes vascular malformations in a variety of organs and tissues, including brain AVMs. Because brain AVMs have the potential to cause disabling or fatal intracranial hemorrhage, detection of these lesions before rupture is the goal of screening MR imaging/MRA examinations in patients with HHT. Prior studies have demonstrated superior sensitivity for HHT-related brain AVMs by using postcontrast MR imaging sequences as compared with MRA alone. We now present data regarding the incremental benefit of including arterial spin-labeling (ASL) perfusion sequences as part of MR imaging/MRA screening in patients with this condition. MATERIALS AND METHODS: We retrospectively analyzed 831 patients at the UCSF Hereditary Hemorrhagic Telangiectasia Center of Excellence. Of these, 42 patients had complete MR imaging/MRA, ASL perfusion scans, and criterion-standard DSA data. Two neuroradiologists reviewed imaging studies and a third provided adjudication when needed. RESULTS: Eight patients had no brain AVMs detected on DSA. The remaining 34 patients had 57 brain AVMs on DSA. Of the 57 identified AVMs, 51 (89.5%) were detected on ASL and 43 (75.4%) were detected on conventional MR imaging/MRA sequences (P = .049), with 8 lesions detected on ASL perfusion but not on conventional MR imaging. CONCLUSIONS: ASL provides increased sensitivity for brain AVMs in patients with HHT. Inclusion of ASL should be considered as part of comprehensive MR imaging/MRA screening protocols for institutions taking care of patients with HHT.

Exploring effects of atmospheric conditions in hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis, telangiectasias, and visceral arteriovenous malformations. Individuals with HHT often identify low humidity and temperature as detrimental to epistaxis severity. We set out to assess the relationship between humidity and temperature on epistaxis severity in patients with HHT. METHODS: Retrospective cross-sectional study at an academic hospital with an HHT center between July 1, 2014 and January 1, 2022. The primary outcome of this study was ESS. Pearson correlation analyses and multiple linear regression analyses were performed to test the association between weather variables and epistaxis severity scre (ESS). Results were reported as coefficient and 95% confidence interval (CI). RESULTS: Four hundred twenty-nine patients were included in the analysis. Through a Pearson correlation analysis, neither humidity (regression coefficient = -0.01; 95% CI, -0.006 to 0.003; p = 0.50), daily low temperature (regression coefficient = 0.01; 95% CI, -0.011 to 0.016; p = 0.72), or daily high temperature (regression coefficient = 0.01; 95% CI, -0.004 to 0.013; p = 0.32) were significantly correlated with ESS. In a multiple linear regression analysis, adjusting for both daily low temperature and humidity, medications taken, demographics, and genotype, neither daily low temperature (regression coefficient = -0.02; 95% CI, -0.04 to 0.01; p = 0.14) nor humidity (regression coefficient = 0.01; 95% CI, -0.01 to 0.01; p = 0.64) were significantly associated with ESS. CONCLUSION: We have shown in a large clinical sample that neither humidity nor temperature were strongly correlated with HHT patient epistaxis severity.

Identifying racial disparities in hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant disorder characterized by recurrent epistaxis (nose bleeds), mucosal telangiectasias (spider veins), and arteriovenous malformations. Although HHT affects all racial groups, few studies have explored racial disparities among patients with HHT. METHODS: We performed a retrospective chart review of HHT patients who were seen at a single academic center between July 1, 2014 and January 1, 2022. The primary outcomes of this study were the Epistaxis Severity Score (ESS) and the presence of pulmonary, cerebral, gastrointestinal, spinal, and hepatic arteriovenous malformations (AVMs). We analyzed racial differences using t-tests and analysis of variance (ANOVA) for continuous variables, and chi-squared tests for categorical variables. We then performed multivariable linear and logistic regressions on outcomes. RESULTS: Our review identified 35 Asian, 6 Black or African American, 72 Hispanic or Latino, and 244 White or Caucasian patients who met the inclusion criteria. Through an analysis of variance model, race/ethnicity was not significantly associated with ESS. Two univariable logistic regression models between race and both pulmonary and brain AVMs showed that race was associated with the incidence of pulmonary AVMs (p<0.01), with Asian patients at a 2.3-fold increased risk of pulmonary AVMs compared with White patients (p=0.03). Race was also associated with the incidence of cerebral AVMs (p<0.01) with Hispanic or Latino patients at a 4.8-fold increased risk compared with White patients (p<0.01). CONCLUSION: Patients who identified as Asian may have higher rates of pulmonary AVMs while patients identifying as Hispanic or Latino may have more cerebral AVMs. The correlations may be important for identifying risk factors in certain patient populations.

Large thrombosed portomesenteric venous aneurysm treated with pharmacomechanical thrombolysis combined with TIPS placement.

BACKGROUND: Aneurysms are rare anomalies of the portomesenteric venous system. Thrombotic complications of these lesions can lead to mesenteric venous ischemia and bowel infarction, potentially requiring surgical intervention. Herein we describe a case of mesenteric ischemia due to a large thrombosed portomesenteric aneurysm treated with endovascular techniques. CASE PRESENTATION: A 37-year-old previously healthy male who presented with abdominal pain to his local emergency department was found to have a thrombosed 12.0 × 5.1 cm portomesenteric venous aneurysm with evidence of mesenteric ischemia on CT. When conservative management with anticoagulation failed, transhepatic pharmacomechanical thrombolysis was initially performed. This was followed by TIPS placement with additional trans-TIPS thrombectomy to improve sluggish portal outflow and prevent re-thrombosis. The patient's symptoms and imaging findings of ischemia resolved after endovascular therapy. No surgical intervention was required, and the patient was discharged on enoxaparin before being transitioned to apixaban. The TIPS remained patent at 2-year follow-up, with no change in the size of the aneurysm or re-thrombosis noted. The patient's synthetic liver function was preserved with no evidence of hepatic encephalopathy during the follow-up period. CONCLUSIONS: Endovascular therapies may be used to manage thrombotic complications of portomesenteric venous aneurysms, obviating the need for surgical intervention in selected patients.

Synergy in IR-Hybrid CT/C-arm in the setting of critical trauma.

Access to multi-detector computed tomography (MDCT) scanning for interventional procedures can prove to be logistically challenging as resources are often in different areas within the hospital. At some institutions, interventional radiology suites have moved to the operating room, separate from the diagnostic radiology department. At these institutions, complex interventional procedures requiring both fluoroscopy and MDCT may pose logistical challenges, especially as they pertain to timely patient transfers. Hybrid CT/fluoroscopy suite provides rapid, reliable MDCT assessment of trauma patients before and after emergent surgery, as well as access to the entire spectrum of emergent image-guided interventions in the same suite.

Hereditary Hemorrhagic Telangiectasia: The Convergence of Genotype, Phenotype, and Imaging in Modern Diagnosis and Management of a Multisystem Disease.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease that manifests as vascular malformations in the brain, lung, liver, gastrointestinal tract, nasal mucosa, and skin. Diagnosis and management of HHT is guided in large part by imaging studies, making it a condition with which the radiology community needs familiarity. Proper screening and care lead to improved morbidity and mortality in patients with HHT. International guidelines were recently updated and form the basis for a detailed discussion of the role of imaging and image-guided therapy in HHT. © RSNA, 2021 Online supplemental material is available for this article.

An international, multicenter study of intravenous bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-Bleed study.

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.

Calcium Stimulation Test for Insulinoma Localization in an End-stage Renal Disease Patient on Diazoxide.

Insulinomas are rare, and even rarer in patients with end-stage renal disease (ESRD). Clear criteria for the biochemical diagnosis of insulinomas in patients with renal failure have not been established, and hypoglycemia is often attributed to the renal disease itself, frequently leading to a delay in diagnosis. We describe a case of a patient who presented with asymptomatic recurrent hypoglycemia during hemodialysis. Disease progression and biochemical testing strongly suggested an insulinoma. Computed tomography (CT) of the abdomen and pelvis, 111In-pentetreotide scintigraphy and endoscopic ultrasound did not localize a pancreatic tumor. A calcium stimulation test was performed while the patient was taking diazoxide due to severe hypoglycemia with fasting for a couple of hours without treatment. The test showed a marked increase in insulin after calcium infusion in the dorsal pancreatic artery, localizing the tumor to the body and tail of the gland. Exploratory surgery easily identified a tumor at the body of the pancreas and pathology confirmed an insulin-secreting pancreatic neuroendocrine tumor. On follow-up, there was resolution of the hypoglycemia. We review the challenges of diagnosing an insulinoma in ESRD and describe a successful intra-arterial calcium stimulation test done in an ESRD patient while continuing diazoxide.

The Role of Liver Imaging in Hereditary Hemorrhagic Telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by spontaneous epistaxis, telangiectasia, and visceral vascular malformations. Hepatic vascular malformations are common, though a minority are symptomatic. Symptoms are dependent on the severity and exact type of shunting caused by the hepatic malformation: Arteriosystemic shunting leads to manifestations of high output cardiac failure, and arterioportal shunting leads to portal hypertension. Radiologic imaging, including ultrasound, computed tomography (CT), and magnetic resonance imaging (MRI), is an important tool for assessing liver involvement. Doppler ultrasonography is the first-line screening modality for HHT-related liver disease, and it has a standardized scale. Imaging can determine whether shunting is principally to the hepatic vein or the portal vein, which can be a key determinant of patients' symptoms. Liver-related complications can be detected, including manifestations of portal hypertension, focal liver masses as well as ischemic cholangiopathy. Ultrasound and MRI also have the ability to quantify blood flow through the liver, which in the future may be used to determine prognosis and direct antiangiogenic therapy.

Second International Guidelines for the Diagnosis and Management of Hereditary Hemorrhagic Telangiectasia.

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.

Gallbladder Cryoablation for Chronic Cholecystitis in High-Risk Surgical Patients: 1-Year Clinical Experience with Imaging Follow-up.

PURPOSE: To assess the short-term safety and efficacy of gallbladder cryoablation in high-risk patients. MATERIALS AND METHODS: A single-center, retrospective review of clinical and imaging follow-up from patients who were referred for gallbladder cryoablation between August 2018 and July 2019 was performed. All patients had serious pre-procedural comorbidities and were unacceptable surgical candidates (mean age, 52.5 years; mean American Society of Anesthesiologists score, 3.67). Primary efficacy measures included technical success, absence of symptoms after cholecystostomy tube removal, and imaging evidence of cystic duct obstruction and gallbladder involution. The primary safety measure was the absence of Society of Interventional Radiology moderate or greater adverse events. RESULTS: Technical success was 86%, with 1 of 7 patients unable to undergo cryoablation because of adhesions preventing hydrodissection of the colon away from the gallbladder. Mean duration of clinical follow-up after discharge was 278 days (range, 59-498 days). Abdominal pain was absent in all patients after ablation. Cholecystostomy tubes were removed immediately after ablation (n = 5) or on post-procedure day 11 (n = 1). Computed tomography or magnetic resonance imaging was obtained at 1-3 months (n = 6), 4-6 months (n = 4), and 6-12 months (n = 5) after the procedure and demonstrated gallbladder involution in 5 of 6 patients. One patient had asymptomatic distention of the gallbladder on follow-up imaging. Hepatobiliary iminodiacetic acid scans were completed in 5 of 6 patients 1 month after ablation and demonstrated cystic duct occlusion in all 5 patients. One moderate adverse event (infection) and 1 life-threatening adverse event (hemorrhage) occurred. CONCLUSIONS: Gallbladder cryoablation might be a viable treatment option for high-risk patients with gallbladder disease and warrants further investigation.

Angiopoietin-2 predicts morbidity in adults with Fontan physiology.

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM.

First in-Human Gallbladder Cryoablation in a Patient with Acute Calculous Cholecystitis Initially Treated with a Cholecystostomy Tube.

A 71-year-old poor surgical candidate with acute calculous cholecystitis was initially managed with cholecystostomy tube drainage for 28 days. He subsequently underwent gallbladder cryoablation under moderate sedation with 3 cryoprobes and 2 separate 10-8-10 freeze-thaw cycles targeting the gallbladder neck/body and fundus followed by cholecystostomy tube removal. He was discharged 1 day after ablation. Magnetic resonance and hepatobiliary iminodiacetic acid scan 1 month postablation demonstrated a thick-walled, distended gallbladder and no filling of the cystic duct. Magnetic resonance 3 months postablation demonstrated retraction of the gallbladder wall with luminal collapse. The patient denied any pain after discharge and is asymptomatic 3 months after ablation.