Reduced-intensity, risk factor–stratified immunosuppression for acquired hemophilia A: single-center observational study

Immunosuppressive therapy (IST) is administered to patients with acquired hemophilia A (AHA) to eradicate autoantibodies against coagulation factor VIII (FVIII). Data from registries previously demonstrated that IST is often complicated by adverse events, in particular infections. This pilot study was set out to assess the feasibility of reduced-intensity, risk factor-stratified IST. We followed a single-center consecutive cohort of twenty-five patients with AHA receiving IST according to a new institutional treatment standard. Based on results from a previous study, GTH-AH 01/2020, patients were stratified into 'poor risk' (FVIII < 1 IU/dl or inhibitor ≥ 20 Bethesda units (BU)/ml) or 'good risk' (FVIII ≥ 1 IU/dl and inhibitor < 20 BU/ml). Outcomes were compared between the current cohort and the GTH registry as a historic control (n = 102). Baseline characteristics of the cohort were not different from the historic control. Partial remission, defined as FVIII recovered to > 50 IU/dl, was achieved by 68% of patients after a median time of 112 days, which was lower and significantly later than in the historic control (hazard ratio: 1.8, 95% confidence interval 1.2-2.8). Complete remission, overall survival, and frequency of fatal infections were not different. Grade 3 and 4 infections were more frequent. The impact of risk factors that was observed in the historic cohort was no longer apparent, as partial and complete remission and overall survival were similar in 'good risk' and 'poor risk' patients. In conclusion, reduced-intensity, risk factor-stratified IST is feasible in AHA but did not decrease the risk of infections and mortality in this cohort

Essaysammlung zu mentaler Gesundheit

Liebe Leserin, lieber Leser, das folgende Buch enthält Aufsätze von Studierenden, die im Rahmen eines Seminars zu psychischer Gesundheit und Resilienz von Medizinstudierenden entstanden sind. Um die Mühe und die gelungenen Aufsätze zu würdigen, haben wir entschieden einige der Ausätze im Rahmen dieses Sammelbandes zu veröffentlichen. Vorausschicken möchte ich jedoch den Hinweis, dass es sich um Seminararbeiten handelt, die zwar informativ und für einige sicherlich interessant zu lesen sind, jedoch nicht an den wissenschaftlichen Standard eines Reviewartikels heranreichen können oder wollen. Die Studierenden wurden dazu angehalten Primärliteratur zu verwenden und nach wissenschaftlichen Standards zu zitieren, es konnte jedoch nicht ausführlich überprüft werden, inwiefern dieser Maßstab umgesetzt wurde. Es bleibt Ihnen als Leserin oder Leser selbst überlassen die Informationen selbst zu prüfen und kritisch zu hinterfragen, wenn Sie wissenschaftlich damit arbeiten möchten. In jedem Fall wünschen wir viel Freude bei der Lektüre und gute Inspirationen! Dr. med. Michael Alexander Pelzl Nürnberg, 6. November 202

Long-Term Outcomes after Vaccine-Induced Thrombotic Thrombocytopenia

Vaccine-induced thrombotic thrombocytopenia (VITT), or thrombosis with thrombocytopenia syndrome (TTS), is a rare but serious complication of adenovirus-based vaccines against severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Observation of long-term outcomes is important to guide treatment of affected patients. This single-center consecutive cohort study included all patients diagnosed based on (1) vaccination 4 to 21 days before symptom onset, (2) signs or symptoms of venous or arterial thrombosis, (3) thrombocytopenia < 150/nL, (4) positive anti-platelet factor 4 (PF4) antibody, and (5) elevated D-Dimer > 4 times the upper limit of normal. Nine patients were enrolled. Acute management consisted of parenteral anticoagulants, corticosteroids, intravenous immunoglobulin (IVIG), and/or eculizumab. Eculizumab was successfully used in two patients with recurrent thromboembolic events after IVIG. Direct oral anticoagulants were given after hospital discharge. Median follow-up duration was 300 days (range 153 to 380). All patients survived the acute phase of the disease and were discharged from hospital. One patient died from long-term neurological sequelae of cerebral venous sinus thrombosis 335 days after diagnosis. Eight out of nine patients were alive at last follow-up, and seven had fully recovered. Anti-PF4 antibodies remained detectable for at least 12 weeks after diagnosis, and D-Dimer remained elevated in some patients despite oral anticoagulation. No recurrent thromboembolic events, other signs of VITT relapse, or bleeding complications occurred after discharge. In conclusion, VITT appears to be a highly prothrombotic condition. IVIG is not always successful, and eculizumab may be considered a rescue agent. Long-term management with direct oral anticoagulants appears to be safe and effective

While p73 is essential, p63 is completely dispensable for the development of the central nervous system

The ancient p53 paralogs p63 and p73 regulate specific tissue formation, cell survival and cell death via their TA and ΔN isoforms. Targeted disruption of the p73 locus leads to severe defects in the development of the central nervous system (CNS), and p73 has recently been shown to be an essential regulator of neural stem cell maintenance and differentiation in both embryonal and adult neurogenesis. In contrast, global p63−/− mice lack skin and limbs. Moreover, p63 is detectable in embryonic cortex. It has previously been proposed to also play critical pro-death and pro-survival roles in neural precursors of the developing sympathetic and central nervous system, respectively, based on experimental overexpression and siRNA-mediated knockdown of p63