No abstract

In the coronavirus disease 2019 (COVID‐19) pandemic, organ transplant recipients are considered to be at high risk for an unfavorable outcome. However, in particular the role of immunosuppression in patients infected with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) remains undetermined. Here, we present a 62‐year‐old male COVID‐19 patient with recent heart transplantation who developed only mild symptoms, but had prolonged virus shedding, and summarize the available data on COVID‐19 in cardiac allograft recipients. Initially the patient presented with a transient episode of fever and sore throat but no other symptoms, in particular no cough or dyspnea at rest. After diagnosis, immunosuppression was continued unchanged. On day 7, his temperature increased again with concurrent mild rise of C‐reactive protein, IL‐6, and pro‐B‐type natriuretic peptide levels. Hydroxychloroquine was started and continued for 7 days. While the patient no longer had clinical symptoms 20 days after initial presentation, virus culture of throat swabs on days 18 and 21 confirmed active virus replication and SARS‐CoV‐2 PCR remained positive on day 35 with copy numbers similar to the onset of infection. In conclusion, the immunosuppression regimen in transplant recipients with mild COVID‐19‐associated symptoms may be continued unchanged. However, it may contribute to delayed virus polymerase chain reaction conversion and thus possible prolonged infectivity.

Background: Anaplastic thyroid carcinoma (ATC) and metastatic poorly differentiated thyroid carcinomas (PDTCs) are rare aggressive malignancies with poor overall survival (OS) despite extensive multimodal therapy. These tumors are highly proliferative, with frequently increased tumor mutational burden (TMB) compared with differentiated thyroid carcinomas, and elevated programmed death ligand 1 (PD-L1) levels. These tumor properties implicate responsiveness to antiangiogenic and antiproliferative multikinase inhibitors such as lenvatinib, and immune checkpoint inhibitors such as pembrolizumab. Patients and Methods: In a retrospective study, we analyzed six patients with metastatic ATC and two patients with PDTC, who received a combination therapy of lenvatinib and pembrolizumab. Lenvatinib was started at 14-24 mg daily and combined with pembrolizumab at a fixed dose of 200 mg every three weeks. Maximum treatment duration with this combination was 40 months, and 3 of 6 ATC patients are still on therapy. Patient tumors were characterized by whole-exome sequencing and PD-L1 expression levels (tumor proportion score [TPS] 1-90%). Results: Best overall response (BOR) within ATCs was 66% complete remissions (4/6 CR), 16% stable disease (1/6 SD), and 16% progressive disease (1/6 PD). BOR within PDTCs was partial remission (PR 2/2). The median progression-free survival was 17.75 months for all patients, and 16.5 months for ATCs, with treatment durations ranging from 1 to 40 months (1, 4, 11, 15, 19, 25, 27, and 40 months). Grade III/IV toxicities developed in 4 of 8 patients, requiring dose reduction/discontinuation of lenvatinib. The median OS was 18.5 months, with three ATC patients being still alive without relapse (40, 27, and 19 months) despite metastatic disease at the time of treatment initiation (UICC and stage IVC). All patients with longterm (>2 years) or complete responses (CRs) had either increased TMB or a PD-L1 TPS >50%.

A team of experts from the fields of gynaecology and obstetrics, diabetology, internal medicine, paediatrics and midwifery from Germany, Austria and Switzerland produced a new version of the existing S3 guideline on gestational diabetes. It replaces the recommendations of the German Association for Gynaecology and Obstetrics and the German Diabetes Association on the diagnosis and treatment of gestational diabetes from 2011 and is valid for the three German-speaking countries. The primary aim of the guideline is to improve and standardise the prevention, screening, diagnosis, treatment and follow-up of gestational diabetes through evidence-based recommendations for the outpatient and inpatient area. A large number of new studies and data published in the last few years required a comprehensive revision of the 2011 guideline. The new aspects include early screening of pregnant women with a high risk for diabetes or gestational diabetes, the validity of two-stage screening in the third trimester by means of the 50-g challenge test, as specified in the maternity guidelines, use of metformin instead of or in addition to insulin in gestational diabetes, and birth planning with GDM and/or macrosomia. The recommendations are based on the evidence from the literature, which was selected through a systematic external literature search. All recommendations had to pass through a consensus process. The present text corresponds to the practice guideline on gestational diabetes, which is an action-oriented short version of the evidence-based S3 guideline that can be viewed on the internet.

Sunitinib has modest activity in advanced refractory ACC, which compares favorably with other targeted treatments in these patients. Sunitinib serum levels might have been profoundly reduced by mitotane induced cytochrome P450-3A4 activity attenuating its antitumor activity and adverse effects. Together these findings suggest that sunitinib deserves further investigation in mitotane-naïve ACC patients.