Hannover Medical School

The European Paediatric Surgeons' Association (EUPSA) and the European Reference Network for Rare Inherited and Congenital Anomalies (ERNICA) conducted a survey to assess the current surgical management and care practices for esophageal atresia (EA) in order to assess changes over the past decade.An online survey consisting of 56 questions was administered to EUPSA members and ERNICA representatives between March and September 2025. The questionnaire covered seven domains: center structure, preoperative assessment, surgical management of esophageal atresia and tracheoesophageal fistula (EA-TEF) patients and long-gap EA, postoperative care, long-term follow-up, and the management of complications. Results were compared to practices reported in a previous EUPSA Network Office survey in 2013.There were a total of 202 respondents from 41 countries with 60% from European Union countries. Compared with previous surveys, the routine use of preoperative bronchoscopy and the use of trans-anastomotic tubes were found to be significantly more common (both p < 0.001). A marked increase in preference for thoracoscopic techniques for EA-TEF was observed (p < 0.001). The routine use of chest drains, elective paralysis, and contrast studies prior to feeding initiation also rose significantly over the decade (p ≤ 0.004). Yet for many areas of care, there remains variation between surgeons, and structured long-term follow-up arrangements are not universal.The findings demonstrate increased standardization and suggest increased adherence to recommendations in the management of EA-TEF. However, significant variation persists in long-term follow-up, transition-to-adult-care programs, and structured quality-of-life assessment, highlighting areas for future harmonization across European centers.

Repeated mild traumatic brain injuries (rmTBIs) pose a high risk of developing chronic traumatic encephalopathy (CTE). Since this neurodegenerative disease is diagnosed only post-mortem, new biomarkers for early detection are needed. Although age at injury and biological sex are important factors in many brain pathologies, little is known about their relevance to rmTBI-induced CTE-like consequences. Hence, this study explored how biological sex and age at the time of impact affect progression and changes in biomarker candidates after experimental rmTBI. Rats of both sexes, aged 7weeks (adolescent) or 14weeks (adult), were subjected to three mTBIs at 5-day intervals. Neurological, behavioral and cognitive impairments, as well as changes in potential plasma and brain biomarkers, were assessed up to 12weeks post-injury. The generalized estimating equation model was used to compare sexes and age groups. RmTBI induced ongoing neurological impairment. While no depressive-like behavior was observed, long-term, age-specific changes in anxiety were observed after rmTBI. A short-term increase in plasma p-tau was found after rmTBI only in male and adolescent rats. Plasma neuron-specific enolase (NSE) levels were elevated in adolescent animals at both 2weeks and 12weeks post-rmTBI. An increase in brain neurofibrillary tangles (NFT) was detected 12-weeks after rmTBI. Correlation analyses suggested NSE as a prospective biomarker for anhedonia-like behavior, and brain NFT as an indicator of neurological impairment. We found that behavioral outcomes and biomarker changes following rmTBI in rats were both age- and sex-dependent. This information will help in developing translatable diagnostics to guide CTE treatment in clinical settings.

Retroviruses are immunosuppressive, and there is evidence that a highly conserved immunosuppressive domain (isu domain) in their transmembrane envelope protein contributes to this activity. Studies have shown that inactivated retroviruses, their purified transmembrane envelope proteins, and synthetic peptides corresponding to the isu domain inhibit mitogen-triggered proliferation of peripheral blood mononuclear cells (PBMCs) and modulate their cytokine and gene expression. This has been demonstrated for human immunodeficiency virus type 1 (HIV-1), as well as for beta- and gammaretroviruses and for both exogenous and endogenous retroviruses, including syncytins. In the case of HIV-1, homopolymers of its isu peptide stimulated an increased release of IL-10, IL-6, and other cytokines from human PBMCs. Up-regulated genes included IL-6, IL-8, and IL-10, as well as MMP-1, TREM-1, and IL-1β. In vivo, in a mouse tumor model, tumor cells that were unable to induce tumors in immunocompetent animals gained the ability to do so when expressing the transmembrane envelope protein or the isu domain of various retroviruses on their surface. Here, we demonstrate that the transmembrane envelope protein p15E of PERV can modulate cytokine expression in human PBMCs. Human 293 cells were transfected with four constructs that express a portion of p15E, including the isu domain, and were cultured in the presence of a selection medium containing hygromycin. The p15E-expressing cells were co-cultured with human PBMCs, leading to the release of IL-6 and IL-10 protein and the modulation of multiple cytokines and other markers, including IL-6, IL-10, IFN-α, TNF-α, MMP1, and SEPP1. Similar, but more pronounced, effects were observed when PERV-producing 293 and pig cells were used in parallel; both expressed higher levels of p15E. Additionally, p15E expression reduced MHC class I expression, and preliminary data indicate that p15E expression could have a protective effect against cellular cytotoxicity. This finding underscores the need for further research to elucidate the dynamics of p15E expression and its immunosuppressive activity. It also contributes to the understanding of the immunosuppressive properties of pathogenic retroviruses. Furthermore, expressing the immunosuppressive p15E of PERV on the surface of a pig xenotransplant may reduce the need for pharmaceutical immunosuppressants.

BackgroundChimeric antigen receptor (CAR) T-cell therapy has transformed the treatment of refractory hematological malignancies but is frequently complicated by immune effector cell-associated neurotoxicity syndrome (ICANS). Early clinical recognition remains challenging, as the commonly used Immune Effector Cell-Associated Encephalopathy (ICE) score lacks sensitivity for subtle deficits.MethodsIn this prospective bicentric study, 100 patients treated with CAR T-cells at Hannover Medical School and Charité - Universitätsmedizin Berlin underwent systematic neurological assessments using both ICE and the newly developed Berlin-Hannover ICANS Severity Assessment (BHISA). Examinations were performed at baseline prior to CAR T-cell infusion, on day 6–7 (±1 day) post-infusion, and during ICANS episodes. Data on the clinical course, other toxicities, comorbidities, CAR T-cell products, and ICANS treatment were collected.ResultsThirty-seven patients (37%) developed ICANS, which was associated with preceding cytokine release syndrome and specific CAR T-cell products. While ICE scores clustered at maximum values both at baseline and follow-up, BHISA showed a broader distribution and higher sensitivity to subtle changes. Correlation analyses confirmed agreement between ICE and BHISA, but BHISA captured early cognitive decline more reliably. Receiver operating characteristic analyses demonstrated comparable diagnostic accuracy (BHISA: AUC = 0.783, ICE: AUC = 0,777), with consistently higher sensitivity of BHISA at matched specificity. (Specificity target = 0.7, BHISA sensitivity = 0.743, ICE sensitivity = 0.571; Specificity target = 0.8, BHISA sensitivity = 0.629, ICE sensitivity = 0.571).ConclusionBHISA may provide a more sensitive and more differentiated screening tool for ICANS than ICE by incorporating additional cognitive and motor domains, while remaining easy to use. This may enable earlier and more nuanced detection of CAR T related neurotoxicity, potentially improving patient monitoring across a heterogeneous population.

Anorexia nervosa (AN) is a severe psychiatric disorder displaying an altered gut microbiome. Faecal microbiome transplantation (FMT) has emerged as a powerful research tool and potential treatment option in AN due to the microbiome-gut-brain axis. Current studies are limited and reveal variable FMT protocols. This leads to heterogeneous outcomes and complicates drawing definitive conclusions from existing literature. This review aims to compile and assess the different protocols and develop recommendations on ideal donors, handling of faeces, recipients, duration/frequency of FMT, and measuring transfer success for future FMT studies regarding AN. We systematically screened three databases (Pubmed, Embase, Web of Science), identifying 13 studies, including two human case reports, one human study protocol, and 10 animal studies. While all studies demonstrated microbial alterations in the recipients, not all animal studies successfully induced an AN/underweight phenotype, suggesting that precise coordination of study protocol components to allow further refinement is essential. Researchers should prioritise clear, comprehensive, and transparent documentation to ensure the interpretability and reproducibility of FMT procedures. Detailed reporting will enable more meaningful comparisons across studies, deepen our understanding of the microbiome's role in AN, and help identify methodological factors that influence outcomes. Ultimately, completeness of documentation in FMT studies in AN has substantial potential to support future clinical applications and improve patient care.

Growing evidence suggests major outcome and risk factor disparities between men and women undergoing cardiovascular surgery. Thus, sex-specific approaches are increasingly being adopted in cardiovascular medicine. However, data on sex-specific outcomes and risk stratification in complex thoracoabdominal aortic repair remain limited. We present a retrospective single-center analysis of 311 consecutive patients, including 99 women (31.8%), who underwent open surgical thoracoabdominal aortic repair between 2000 and 2024. Propensity score matching was performed prior to a comparative analysis of intraoperative parameters, postoperative outcome, and complications, as well as short- and long-term mortality between female and male patients. In the initial study population, men had a significantly higher BMI (26.3 vs. 23.1 kg/m2, p < 0.001) and greater prevalence of coronary artery disease (37.7% vs. 21.2%, p = 0.004) and hyperlipidemia (27.8% vs. 12.1%, p = 0.002) compared to women. Postoperatively, wound infections were more frequent in women in the unmatched cohort (12.1% vs. 4.3%, p = 0.01), but no sex-related differences in mortality, ICU length of stay, or long-term survival were observed after propensity score matching. Multivariate regression revealed highly distinct predictors of early mortality in each sex: prior cardiac surgery and urgency in men versus hypertension, chronic kidney disease, coronary artery disease, and older age at the time of operation in women. Overall outcomes and survival following thoracoabdominal aortic repair were comparable between men and women. However, underlying risk factors for early mortality differed fundamentally between sexes. These findings underscore the importance of a sex-specific preoperative risk assessment in the surgical decision-making process prior to open thoracoabdominal aortic repair.

NPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in FLT3-ITD, DNMT3A, IDH1/IDH2, and TET2 genes, was applied to a training cohort of NPM1-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the NPM1-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.

Large language models (LLMs) have the potential to scale assessment in medical education, but their psychometric equivalence to expert-written items and the detectability of their origin remain uncertain. In a preregistered, single-center, blinded observational, within-subject comparison, we evaluated 24 GPT-4o-generated versus 24 human-authored topic-matched multiple-choice questions (MCQs) across radiation oncology, radiology, and nuclear medicine. Medical students (n = 82) and physicians (n = 46) completed an identical 48-item formative mock examination, with item origin masked. Item difficulty (human: mean 0.65 [SD 0.22] vs LLM: 0.67 [0.20]) and discrimination (0.27 [0.12] vs 0.29 [0.12]) did not differ significantly; participants did not identify item origin above chance (0.50). Expert ratings of appropriateness and didactic quality showed low interrater agreement (ICC = 0.07-0.18). In this expert-reviewed, human-in-the-loop workflow, the item difficulty and discriminatory power of MCQs generated with GPT-4o did not differ significantly from those of expert-authored items, and were not reliably recognized as AI-generated by examinees. These findings delineate a feasible pathway for responsibly scaling formative assessment content in imaging-focused medical education, while underscoring the need for explicit educational policies regarding oversight, transparency, and fairness.