Consistent FFP2-masking as part of reducing viral respiratory infections on medical wards for allogeneic hematopoietic stem cell transplantation.

Patients undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT) are highly susceptible to infections. The consequent use of masks on wards for allo-HSCT has been controversial in the past decades and was not common before the COVID-19 pandemic. We retrospectively compared incidence and outcomes of viral respiratory infections during allo-HSCT on our specialized ward between 01/2018 and 09/2020 to the era of FFP2 masking between 10/2020 and 10/2022 covering similar seasons of the year. Each group consisted of 150 matched patients. The usage of FFP2 masks reduced the incidence of viral respiratory infections from 22.1 to 2.1% (p < 0.005). This reduced the time on ward from a median of 26 days to 23.5 days (p = 0.002). It also resulted in less use of CT-scans (p = 0.003) and bronchoalveolar lavage procedures (p = 0.057). Median time to proof of infection was 21 days after admission in both groups. No difference was detected in progression free survival, hospital survival or non-relapse mortality (p = 0.78). Our retrospective results indicate that FFP2 masks worn by patients and hospital staff may help to significantly reduce the incidence of viral respiratory infections, including COVID-19, shorten the in-hospital time, and reduce costs without affecting survival.

[Proposal for participation in intensive care and emergency medicine studies for patients unable to give informed consent (Cologne Model)]. / Vorschlag für ein Verfahren zur Teilnahme an intensiv- und notfallmedizinischen Studien bei nichteinwilligungsfähigen Patient*innen (Kölner Modell).

When conducting clinical trials in intensive care and emergency medicine, physicians, ethics committees, and legal experts have differing views regarding the inclusion of patients who are incapable of giving consent. These different views on the participation of patients who are not capable of giving consent also complicate how clinical trials are prepared and conducted. Based on the results of a literature search, a consensus model (Cologne Model) was developed by physicians performing clinical research, ethics committees, and lawyers in order to provide patients, those scientifically responsible for the study, ethics committees, and probate (guardianship) judges with a maximum of patient safety and legal certainty, while simultaneously enabling scientific research.

[Recurrent SARS-CoV-2 infections in immunodeficiency]. / Rezidivierende SARS-CoV-2-Infektionen bei Immundefizienz.

A patient with immunodeficiency due to a B-cell lymphoma has repeatedly been tested positive for SARS-CoV­2 during the ongoing SARS-CoV­2 pandemic and has twice received in-hospital treatment. Chronic and recurrent SARS-CoV­2 infections are a threat to the individual health of immunodeficient patients. Only few therapeutic options are available especially due to emerging virus variants with immune escape mechanisms. The medical care of immunodeficient patients with SARS-CoV­2 infections is a great challenge to the treating physician in the ongoing pandemic.

Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies.

The BCL2 inhibitor venetoclax has been approved to treat different hematological malignancies. Because there is no common genetic alteration causing resistance to venetoclax in chronic lymphocytic leukemia (CLL) and B-cell lymphoma, we asked if epigenetic events might be involved in venetoclax resistance. Therefore, we employed whole-exome sequencing, methylated DNA immunoprecipitation sequencing, and genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 screening to investigate venetoclax resistance in aggressive lymphoma and high-risk CLL patients. We identified a regulatory CpG island within the PUMA promoter that is methylated upon venetoclax treatment, mediating PUMA downregulation on transcript and protein level. PUMA expression and sensitivity toward venetoclax can be restored by inhibition of methyltransferases. We can demonstrate that loss of PUMA results in metabolic reprogramming with higher oxidative phosphorylation and adenosine triphosphate production, resembling the metabolic phenotype that is seen upon venetoclax resistance. Although PUMA loss is specific for acquired venetoclax resistance but not for acquired MCL1 resistance and is not seen in CLL patients after chemotherapy-resistance, BAX is essential for sensitivity toward both venetoclax and MCL1 inhibition. As we found loss of BAX in Richter's syndrome patients after venetoclax failure, we defined BAX-mediated apoptosis to be critical for drug resistance but not for disease progression of CLL into aggressive diffuse large B-cell lymphoma in vivo. A compound screen revealed TRAIL-mediated apoptosis as a target to overcome BAX deficiency. Furthermore, antibody or CAR T cells eliminated venetoclax resistant lymphoma cells, paving a clinically applicable way to overcome venetoclax resistance.

[Economics and management of CAR T- cell therapy : Status quo and future perspectives]. / Ökonomie und Management bei der CAR-T-Zell-Therapie : Status quo und Ausblick.

BACKGROUND: Virtually no other topic has attracted more attention in oncology in recent years than chimeric antigen receptor (CAR) T­cell therapy (CAR T). On the one hand it opens up completely new treatment options for cancer patients, while on the other it generates treatment costs exceeding € 300,000 per treatment. OBJECTIVES: The aim of this work is to analyze the economic, procedural and organizational challenges of CAR T­cell therapy from the perspective of the service provider, the cost-bearer and the pharmaceutical manufacturer. MATERIAL AND METHODS: The current German diagnosis-related-group (G-DRG) catalog, the G­DRG tariff, of the German Federal Joint Committee (G-BA) guidelines and G­DRG coding principles were used to evaluate the reimbursement and remuneration system in Germany. Practical experiences of medical sites were integrated in the analysis. RESULTS: The findings demonstrate great economic challenges especially from the perspective of a CAR T site. Increasing certification and qualification efforts lead to financial pressure. Insufficient reimbursement and inadequate cost-covering for CAR T treatment result in budget restrictions for hospitals. CONCLUSION: High drug costs as well as enormous personnel and infrastructural requirements demand transparent and sufficient reimbursement for hospitals. Interaction between hospital and pharmaceutical manufacturer in the CAR T process might enable new means of cooperation.