Balloon pulmonary angioplasty (BPA) is an emerging treatment for patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH).We report on a prospective series of 56 consecutive patients who underwent 266 BPA interventions (median, five per patient) at two German institutions. All patients underwent a comprehensive diagnostic work-up including right heart catheterisation at baseline and 24 weeks after their last intervention.BPA resulted in improvements in WHO functional class, 6 min walk distance (mean change, +33 m), right ventricular function and haemodynamics, including a decline in mean pulmonary artery pressure by 18% and in pulmonary vascular resistance by 26%. Procedure-related adverse events occurred in 9.4% of the interventions. The most common complications were related to pulmonary vascular injury and consecutive pulmonary bleeding. Most of these events were asymptomatic and self-limiting, but one patient died from pulmonary bleeding, resulting in a mortality rate of 1.8%.BPA resulted in haemodynamic and clinical improvements but was also associated with a considerable number of complications, including one fatal pulmonary bleeding. As the effects of BPA on survival are unknown, randomised controlled outcome trials comparing BPA with approved medical therapies in patients with inoperable CTEPH are required to allow for appropriate risk-benefit assessments.

Summary Background Programmed cell death protein‐1‐targeted immunotherapy has shown promising results in phase II studies of hepatocellular carcinoma. Aim To evaluate safety and efficacy of nivolumab and pembrolizumab in an international, multicentre, real‐world cohort of patients with advanced hepatocellular carcinoma. Methods Sixty‐five patients treated with nivolumab (n = 34) or pembrolizumab (n = 31) between July 10, 2015 and December 31, 2018 (data cut‐off) across six centres in Austria and Germany were retrospectively analysed. Results Child‐Pugh class A/B/C was 32 (49%)/28 (43%)/5 (8%). Immunotherapy was used as systemic first‐/second‐/third‐/fourth‐line treatment in 9 (14%)/27 (42%)/26 (40%)/3 (5%) patients. Fifty‐four patients had at least one follow‐up imaging and were, therefore, available for radiological response assessment. The overall response and disease control rates were 12% and 49% respectively. Of 52 evaluable patients, four (8%) had hyperprogressive disease. Median time to progression was 5.5 (95% CI, 3.5‐7.4) months, median progression‐free survival was 4.6 (95% CI, 3.0‐6.2) months, and median overall survival was 11.0 (95% CI, 8.2‐13.8) months. Most common adverse events were infections (n = 7), rash (n = 6), pruritus (n = 3), fatigue (n = 3), diarrhoea (n = 3) and hepatitis (n = 3). Efficacy and safety results were comparable between Child‐Pugh A and B patients; however, median overall survival (OS) was shorter in Child‐Pugh B patients (16.7 vs 8.6 months; P = 0.065). There was no difference in terms of efficacy and adverse events between patients who received immunotherapy as first‐/second‐line and third‐/fourth‐line respectively. Conclusions Programmed cell death protein‐1‐targeted immunotherapy with nivolumab or pembrolizumab showed promising efficacy and safety in patients with advanced hepatocellular carcinoma, including subjects with Child‐Pugh stage B and patients with intensive pretreatment.

Background The coronavirus disease 2019 (COVID-19) pandemic led to far-reaching restrictions of social and professional life, affecting societies all over the world. To contain the virus, medical schools had to restructure their curriculum by switching to online learning. However, only few medical schools had implemented such novel learning concepts. We aimed to evaluate students’ attitudes to online learning to provide a broad scientific basis to guide future development of medical education. Methods Overall, 3286 medical students from 12 different countries participated in this cross-sectional, web-based study investigating various aspects of online learning in medical education. On a 7-point Likert scale, participants rated the online learning situation during the pandemic at their medical schools, technical and social aspects, and the current and future role of online learning in medical education. Results The majority of medical schools managed the rapid switch to online learning (78%) and most students were satisfied with the quantity (67%) and quality (62%) of the courses. Online learning provided greater flexibility (84%) and led to unchanged or even higher attendance of courses (70%). Possible downsides included motivational problems (42%), insufficient possibilities for interaction with fellow students (67%) and thus the risk of social isolation (64%). The vast majority felt comfortable using the software solutions (80%). Most were convinced that medical education lags behind current capabilities regarding online learning (78%) and estimated the proportion of online learning before the pandemic at only 14%. In order to improve the current curriculum, they wish for a more balanced ratio with at least 40% of online teaching compared to on-site teaching. Conclusion This study demonstrates the positive attitude of medical students towards online learning. Furthermore, it reveals a considerable discrepancy between what students demand and what the curriculum offers. Thus, the COVID-19 pandemic might be the long-awaited catalyst for a new “online era” in medical education.

This paper reviews the (predominantly grey) literature on impacts of highly pathogenic avian influenza (HPAI) strain H5N1 and control responses on the livestock sector and associated industries in developing countries. The authors distinguish between impacts that arise directly through HPAI-related morbidity and mortality, those that are a consequence of public intervention to control or eradicate HPAI, and impacts that are mediated through market reactions. The paper further considers how these impacts propagate up-and downstream through related supply and distribution networks, how short-term reactions are followed by longer-term adjustments, how impacts include direct cost elements and foregone income, and why losses to the poultry sector will, at least to some extent, be 'passed on' on the one hand, for example through compensation, and, on the other hand, be compensated for by gains in other livestock subsectors. Differences in methodology applied in the reviewed reports result in a lack of comparability of estimates for HPAI 'costs/impacts' across countries and even within countries and are compounded by information deficits. Despite these shortcomings, the literature permits some significant conclusions to be drawn on the relative importance of direct and indirect impacts and on their distribution across different types of poultry producers. The paper ends by outlining directions of future research that combine epidemiology and economics to provide a framework for disease control decisionmaking.

A 55-year-old, previously healthy man was admitted to another hospital with deep-venous thrombosis in both legs and massive pulmonary embolism verified by chest computed tomography (CT). He presented with severe dyspnea and hypotension refractory to inotropes. Fibrinolytic therapy with recombinant tissue plasminogen activator was initiated, but the patient further deteriorated and required cardiopulmonary resuscitation for a period of 30 minutes. After return of spontaneous circulation, he remained in cardiogenic shock despite the use of inotropes and vasopressors, which is why our hospital was contacted.Our mobile extracorporeal membrane oxygenation (ECMO) team was dispatched and the patient received veno-arterial ECMO support with a 24 French venous cannula inserted via the right femoral vein and advanced into the right atrium and a 17 French arterial cannula inserted into the right femoral artery and advanced into the right iliacal artery. With an ECMO blood flow of 4.5 L/min, hemodynamics stabilized and the patient was transported to Hannover Medical School. Here, the patient was mechanically ventilated with an inspiratory oxygen fraction of 1.0 and the arterial PO 2 measured in blood obtained from the right radial artery was >400 mm Hg. The mean systemic blood pressure was 90 mm Hg, but the arterial pressure curves were almost nonpulsatile, and echocardiography showed little contractions of both the right and the left ventricle.Another CT scan performed approximately 14 hours after fibrinolysis showed persistent subtotal thromboembolic occlusion of the pulmonary vascular bed. In addition, there was an extensive filling defect in the ventral aspects of the ascending aorta (Figure 1). The left atrium, the left ventricle, and the aortic bulb were void of contrast material, whereas the aortic arch and the descending aorta were well contrasted (Figures 2 and 3).These images demonstrated the so-called ECMO watershed, where well-contrasted blood coming from the ECMO circuit met low-contrasted blood coming from the left ventricle. The patient with his subtotally occluded pulmonary vascular bed and near complete loss of cardiac contractility had almost complete blood supply from the ECMO and very little regular blood flow. The ECMO device took up most of the contrast media, whereas only a small amount passed the pulmonary vascular bed. Hence, the aorta was filled mostly retrograde. Most of the aorta, including all 3 supraaortic vessels, received well-contrasted and well-oxygenated blood from the ECMO whereas the aortic bulb with the coronary arteries received noncontrasted blood coming from the left ventricle (Figures 2 and 3).In patients receiving veno-arterial ECMO support, the term watershed describes the phenomenon that blood coming from the ECMO flows in the opposite direction than blood coming from the left ventricle.1,2 The level where these 2 blood streams meet (ie, the watershed) depends on the relative pressures and flows in both systems. The oxygen content of the blood coming from the left ventricle is un...

Background: To analyze demography, clinical signs, and survival of intensive care patients diagnosed with nonocclusive mesenteric ischemia (NOMI) and to evaluate the effect of a local intra-arterial prostaglandin therapy. Methods: Retrospective observational study screening 455 intensive care patients with acute arterial mesenteric perfusion disorder in a tertiary care hospital within the past 8 years. Lastly, 32 patients with NOMI were enrolled, of which 11 received local intra-arterial prostaglandin therapy. The diagnosis of NOMI was based on the clinical presentation and established biphasic computed tomography criteria. Clinical and biochemical data were obtained 24 hours before, at the time, and 24 hours after diagnosis. Results: Patients were 60.5 (49.3-73) years old and had multiple comorbidities. Most of them were diagnosed with septic shock requiring high doses of norepinephrine (NE: 0.382 [0.249-0.627] μg/kg/min). The Sequential Organ Failure Assessment (SOFA) score was 18 (16-20). A decrease in oxygenation (Pao2/Fio2), pH, and bicarbonate and an increase in international normalized ratio, lactate, bilirubin, leucocyte count, and NE dose were early indicators of NOMI. Median SOFA score significantly increased in the last 24 hours before diagnosis of NOMI (16 vs 18, P < .0001). Overall, 28-day mortality was 75% (81% nonintervention vs 64% intervention cohort; P = .579). Median SOFA scores 24 hours after intervention increased by +5% in the nonintervention group and decreased by 5.5% in the intervention group ( P = .0059). Conclusions: Our data suggest that NOMI is a detrimental disease associated with progressive organ failure and a high mortality. Local intra-arterial prostaglandin application might hold promise as a rescue treatment strategy. These data encourage future randomized controlled trials are desirable.

Background & Aims Portal vein tumour thrombosis (PVTT) has a significant impact on the prognosis of patients with hepatocellular carcinoma (HCC). The degree of PVTT varies from sub‐/segmental invasion to complete occlusion of the main trunk. Aim of this study was to evaluate whether the degree of PVTT correlates with prognosis. Methods A total of 1317 patients with HCC treated at our tertiary referral centre between January 2005 and December 2016 were included. PVTT was diagnosed by contrast‐enhanced computed tomography or magnetic resonance imaging. The extent of PVTT was documented according to the Liver Cancer Study Group of Japan classification: Vp0 = no PVTT, Vp1 = segmental portal vein invasion, Vp2 = right anterior/posterior portal vein, Vp3 = right/left portal vein and Vp4 = main trunk. Median overall survival (OS) was calculated for each group. Results Portal vein tumour thrombosis was present in 484 (36.8%) patients. Median OS without PVTT was 35.7 months, significantly longer than in patients with PVTT (7.2 months, P < 0.001). The patients with PVTT were subclassified as follows: 103 Vp1, 87 Vp2, 143 Vp3 and 151 Vp4. The corresponding median OS yielded 14.6, 9.4, 5.8 and 4.8 months for Vp1‐Vp4, respectively (P < 0.001). Conclusions Portal vein tumour thrombosis in patients with HCC is associated with a dismal prognosis. The results indicate an association between the extent of PVTT and OS. However, the extent of PVTT is not that decisive, as even minor PVTT leads to a very poor prognosis. Therefore, meticulous evaluation of cross‐sectional imaging is crucial for the clinical management of patients with HCC.

Background Chemosaturation with percutaneous hepatic perfusion (CS-PHP; Hepatic CHEMOSAT® Delivery System; Delcath Systems Inc, USA) is a novel interventional procedure, which delivers high doses of melphalan directly to the liver in patients with liver tumors while limiting systemic toxicity through hemofiltration of the hepatic venous blood. We have previously shown promising efficacy for patients with ocular melanoma (OM) and cholangiocarcinoma (CCA) within our single-center and multi-center experiences. The aim of this study was to analyze the safety and efficacy of CS-PHP after 141 treatments at Hannover Medical School, Germany. Methods Overall response rates (ORR) were assessed according to Response Evaluation Criteria In Solid Tumors (RECIST1.1). Median Overall survival (mOS), median progression-free survival (mPFS), and median hepatic PFS (mhPFS) were analyzed using the Kaplan–Meier estimation. Results Overall, 60 patients were treated with CS-PHP in the salvage setting from October 2014 until January 2019 at Hannover Medical School with a total of 141 procedures. Half of the patients were patients with hepatic metastases of ocular melanoma (OM) (n = 30), 14 patients had CCA (23.3%), 6 patients had hepatocellular carcinoma (10%), and 10 patients were treated for other secondary liver malignancies (16.7%). In total, ORR and disease stabilization rate were 33.3% and 70.3% (n = 25), respectively. ORR was highest for patients with OM (42.3%), followed by patients with CCA (30.8%). Independent response-associated factors were normal levels of lactate dehydrogenase (odds ratio (OR) 13.7; p = 0.015) and diagnosis with OM (OR 9.3; p = 0.028). Overall, mOS was 9 months, mPFS was 4 months, and mhPFS was 5 months. Patients with OM had the longest mOS, mPFS, and mhPFS with 12, 6, and 6 months, respectively. Adverse events included most frequently significant, but transient, hematologic toxicities (80% of grade 3/4 thrombopenia), less frequently hepatic injury up to liver failure (3.3%) and cardiovascular events including two cases of ischemic insults (5%). Conclusion Salvage treatment with CS-PHP is safe and effective particularly in patients OM and CCA. Careful attention should be paid to possible, serious hepatic, and cardiovascular complications.