Background/Objectives: While antibiotic prophylaxis is crucial for preventing infections, its impact on the development of antibiotic-resistant infections and clinical outcomes remains underexplored. We aimed to systematically assess the impact of medical and surgical antibiotic prophylaxis (SAP) on the development of antibiotic-resistant infections, clinical outcomes, and costs. Methods: A systematic review and meta-analysis of the effect of antibiotic prophylaxis on antibiotic-resistant infections, mortality, length of hospital stay, and/or costs was conducted in hemato-oncological or surgical patient populations. Pooled estimates of the relative risk (RR) or weighted mean difference (WMD) were derived using random-effect meta-analysis. Results: Of 10,409 screened studies, 109 (30%) comprising 131,519 patients were included. In 55 hemato-oncological studies, prophylaxis significantly reduced Gram-negative infections (RR: 0.51; 95% CI: 0.45 to 0.59) without an effect on mortality (RR = 1.01; 95% CI: 0.89 to 1.15), while the risk of developing an infection resistant to prophylactic antibiotics during hospitalization was doubled (RR: 2.05; 95% CI: 1.88 to 2.23). The length of hospitalization was reduced by 1.85 days. Among 54 surgical studies, SAP lowered surgical-site infections (RR: 0.58; 95% CI: 0.49 to 0.69). Extending prophylaxis beyond the recommended duration did not improve infection rates (RR: 1.10; 95% CI: 0.98 to 1.24). No association was demonstrated between prophylaxis adjusted by colonization status and the development of resistant infections. Conclusion: Though proven beneficial, our results highlight the critical need for targeted antibiotic stewardship programs (ASPs) in both settings. A meticulous risk assessment balancing the benefits of preventing life-threatening infections against the risk of driving antimicrobial resistance, and a tailored ASP, is urgently needed for hemato-oncological patients.

Received: 06 October 2023 Accepted: 11 October 2023 Article published online: 09 January 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

Received: 06 October 2023 Accepted: 11 October 2023 Article published online: 09 January 2024 © 2024. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany

The pathophysiology of COVID-19 associated thrombosis seems to be multifactorial, involving interplay between cellular and plasmatic elements of the hemostasis. We hypothesized that COVID-19 is accompanied by platelet apoptosis with subsequent alteration of the coagulation system. We investigated depolarization of mitochondrial inner transmembrane potential (ΔΨm), cytosolic calcium (Ca ²⁺ ) concentration, and phosphatidylserine (PS) externalization by flow cytometry. Platelets from intensive care unit (ICU) COVID-19 patients (n=21) showed higher ΔΨm depolarization, cytosolic Ca ²⁺ concentration and PS externalization, compared to healthy controls (n=18) and COVID-19 non-ICU patients (n=4). Moreover significant higher cytosolic Ca ²⁺ concentration and PS was observed compared to septic ICU control group (ICU control). In ICU control group (n=5; ICU non-COVID-19) cytosolic Ca ²⁺ concentration and PS externalization was comparable to healthy control, with an increase ΔΨm depolarization. Sera from ICU COVID-19 13 patients induced significant increase in apoptosis markers (ΔΨm depolarization, cytosolic Ca ²⁺ concentration and PS externalization). compared to healthy volunteer and septic ICU control. Interestingly, immunoglobulin G (IgG) fractions from COVID-19 patients induced an Fc gamma receptor IIA dependent platelet apoptosis (ΔΨm depolarization, cytosolic Ca ²⁺ concentration and PS externalization). Enhanced PS externalization in platelets from ICU COVID-19 patients was associated with increased sequential organ failure assessment (SOFA) score (r=0.5635) and DDimer (r=0.4473). Most importantly, patients with thrombosis had significantly higher PS externalization compared to those without. The strong correlations between apoptosis markers and increased D-Dimer levels as well as the incidence of thrombosis may indicate that antibody-mediated platelet apoptosis potentially contributes to sustained increased thromboembolic risk in ICU COVID-19 patients. Key points: Severe COVID-19 is associated with increased antibody-mediated platelet apoptosis. Platelet apoptosis in severe COVID-19 is correlated with D-Dimer and higher incidence of thromboembolisms.

Background: Tumor immunogenicity is a concept for modeling the susceptibility of tumors to immune checkpoint inhibitors (ICIs) and other immunotherapies. Single biomarkers, such as tumor mutation burden (TMB) or PDL1 expression, have been shown to correlate with ICI outcomes but are poor predictors of overall and progression-free survival (OS, PFS). Complex machine learning models that integrate multiple biomarkers have shown improved predictions but often lack clear a priori interpretability. In this study, we developed a coherent Multi-Omics Tumor Immunogenicity score (MOTIscore) that combines immunogenicity biomarkers derived from genomic and transcriptomic data and demonstrated its generalizability across multiple cancer types. Methods: Several immunogenicity biomarkers, including TMB, neoantigen burden, T-cell receptor repertoire, PDL1 expression, B2M expression, and variants in pathways of ICI response and resistance, were integrated using a weighted sum scoring scheme. The weights were determined using statistical tests in a large melanoma ICI cohort. We compared the MOTIscore with a machine learning (ML) model trained using the same biomarkers and evaluated the model using melanoma, gastric cancer, and pan-cancer datasets. Results: MOTIscore achieved results similar to those of the ML model in predicting ICI in melanoma and gastric cancer, with both outperforming TMB. Gastric cancer and melanoma patients with high MOTIscores had a significantly extended overall and progression-free survival. Gene set enrichment analysis revealed the enrichment of immune-related pathways in patients with high MOTIscores. Differential expression analysis between patients with high and low immunogenicity identified highly expressed C-X-C motif chemokine ligands as important characteristics associated with successful ICI therapy and significantly improved PFS. MOTIscores varied widely across cancers treated in the molecular tumor board at our hospital and showed distinct distributions between non-immunogenic and immunogenic cancer types. Conclusions: MOTIscore demonstrated improved ICI outcome predictions compared to single-omics biomarkers. Patients with higher tumor immunogenicity also show significantly improved OS and PFS in melanoma and gastric cancer. The results demonstrate the potential use of the MOTIscore to prioritize ICI in personalized cancer treatment. However, ICI outcomes and survival should be investigated in prospective studies, and additional cancer types and larger patient cohorts are needed.

Aberrant cellular signaling underlies cancer development and progression. Identifying alterations in these pathways yields critical insights for personalized oncology. Clinically, assessing the activation status of signaling proteins complements genetic and histopathological analyses, improving therapeutic evaluation and accuracy. In this study, we employed the high-throughput Western blot system DigiWest for the characterization of gastrointestinal tumors, both retrospectively and in a proof-of-concept direct clinical application. Retrospective analyses of pancreatic and colorectal carcinomas ( n = 20) compared with matched normal tissues revealed distinct protein expression and activation patterns differentiating tumor subtypes and defining clinically relevant subgroups. By resolving individualized, treatment-relevant signaling signatures we demonstrate the feasibility of molecular-level personalization in samples with high clinical heterogeneity. In the clinical proof-of-concept, single core needle biopsies from 14 patients with gastrointestinal tumors who underwent Molecular Tumor Board presentation were analyzed. The resulting proteomic profiles uncovered patient-specific, targetable pathway activation patterns and showed concordance with mutational data and therapy recommendations. Collectively, these findings establish DigiWest as a valuable, robust complementary tool to sequencing-based approaches for personalized diagnostics and treatment evaluation in precision oncology.