University Hospital Ulm

To assess the discriminatory ability of vertebra-specific volumetric bone mineral density (vBMD), finite element analysis-derived fracture load (FEA-derived FL), and texture analysis (TA) features for incidental vertebral fractures, and to compare performance between thoracic and lumbar levels. We retrospectively reviewed baseline and follow-up thoracolumbar CT scans from 420 patients and identified 11 patients with incidental vertebral fractures contributing to 20 fractured vertebrae (7 females; mean age 65.5years). For each fractured vertebra, three level-matched control vertebrae from patients without fractures were selected, yielding 58 controls across 29 control patients (total 78 vertebrae). Parameters evaluated include vBMD, FEA-derived FL, and TA features (24 total). Discriminatory ability was assessed using area under the curve (AUC) values. vBMD, FEA-derived FL, and 4 of 24 TA features showed group-wise differences between fractured and control vertebrae groups. AUCs were 0.76 [95% CI 0.55-0.90] (vBMD) and 0.73 [95% CI 0.52-0.90] (FEA-derived FL); selected texture features ranged 0.70-0.72. Region-stratified AUC point estimates were higher in the lumbar than in the thoracic vertebrae, but the 95% CIs were wide/overlapping; comparisons are descriptive. vBMD had the numerically largest AUC point estimate for discriminating fractured from control vertebrae; FEA-derived FL was similar, and selected texture features showed modest discrimination with comparable point estimates across lumbar and thoracic levels, generating the hypothesis of less region dependence. Regional comparisons are descriptive. Findings are exploratory and intended to prioritize candidate measures for validation and future multivariable modeling before any clinical application.

The Bacillus Calmette-Guérin (BCG) vaccine protects infants from severe tuberculosis by eliciting cellular immune responses, particularly through the activation of CD8+ cytotoxic T lymphocytes. Given that hypoxia is a defining feature of the pulmonary microenvironment during Mycobacterium tuberculosis infection, especially within granulomatous lesions, we investigated how limited oxygen availability influences the expansion and effector functions of BCG-induced cytotoxic T cells. Mycobacteria-specific short-term T-cell lines were generated and restimulated with BCG-infected macrophages under normoxic and hypoxic conditions. To analyze the immune response, Boolean gating was applied to flow cytometry data to compare the frequencies of cytotoxic T-cell subsets within BCG-responsive CD8+ T-cell population. Under normoxia, BCG-responsive CD8+ T cells exhibited elevated expression of perforin, granulysin, and granzyme B, with a significant enrichment of polycytotoxic cells co-expressing all three molecules. Hypoxia differentially modulated these markers: perforin expression remained unchanged, granulysin was substantially increased, whereas granzyme B declined, resulting in a net reduction of polycytotoxic T cells. These findings demonstrate that oxygen availability shapes the functional profile of vaccine-induced cytotoxic T cells. Considering the hypoxic nature of inflamed and infected lung tissue, our results highlight the importance of evaluating vaccine efficacy in physiologically relevant microenvironments and may inform strategies to enhance polycytotoxic T-cell responses for improved tuberculosis protection.

Neurological recovery following spinal cord injury (SCI) is commonly studied through changes in high-level descriptors of injury severity, such as the American Spinal Injury Association Impairment Scale (AIS) grade, or total upper and/or lower extremity motor scores. More recently, the analysis of segmental motor scores has attracted interest as it provides a more detailed understanding of the exact location and extent of changes occurring during recovery. We propose to augment the analysis of segmental motor recovery with a qualitative descriptor of local motor score patterns, which is defined for all upper and lower extremity myotomes below the neurological level of injury (NLI) and based on a categorization of the changes along the rostrocaudal motor score sequence. Our hypothesis is that recovery of segmental motor scores depends on the residual function as described by the newly proposed descriptors of local motor score patterns. Using data of 1385 patients from the European Multicenter Study about SCI, we analyze differences in recovery at approximately 6 months after injury between local motor score patterns and find an increased probability of full motor recovery for myotomes associated with increased motor scores in the caudal direction. We further use an aggregated descriptor of motor score patterns focusing on increases of motor scores in the caudal direction as an alternative or complementary feature to the AIS grade in prediction models for segmental motor scores at recovery. We observe equivalent predictive performance as measured by the root mean square error between actual and predicted motor scores below the NLI for models using the same set of features and additionally either the AIS grade (median = 0.79) or local pattern (median = 0.80). This is noteworthy as the definition of local motor score patterns requires only the examination of the 10 key muscles of the International Standards for Neurological Classification of SCI on each side of the body, while the AIS grade can only be reliably determined if extensive sensory testing is performed in addition. These results indicate the potential benefits of considering information inherent to the rostrocaudal sequence of motor scores for a better understanding of motor recovery. Furthermore, it supports the development and use of abbreviated sensorimotor examinations specifically in the early phase after SCI.

The updated version of the German S3 guideline for bladder cancer introduces several changes in the areas of diagnostics, perioperative systemic therapy, and rehabilitation, as well as psycho-oncological and palliative care for bladder cancer patients. In urinary diagnostics, the Paris system, including aquality algorithm, has been introduced to improve the comparability of cytological findings. Imaging diagnostics now recommends multiparametric magnetic resonance imaging (MRI) with Vesical Imaging-Reporting and Data System (VI-RADS) reporting as an alternative or complement to computed tomography (CT) scans. CT urography remains the gold standard for the upper urinary tract, while intravenous pyelography (IVP) is no longer recommended. In perioperative systemic therapy, the importance of multidisciplinary case conferences for muscle-invasive bladder cancer (MIBC) is emphasized to enable as many patients as possible to receive perioperative systemic therapy. Rehabilitation now follows quality criteria (multiprofessional teams, long-term concepts) and includes an expanded assessment of physical and psychological burdens. Particularly relevant is the treatment of sexual dysfunction in women after cystectomy. In psycho-oncology and palliative medicine, early integration of the S3 guidelines is required, including advanced care planning (ACP) starting from the diagnosis of advanced tumors. These changes aim for higher diagnostic accuracy, better treatment planning, and holistic patient care.

The presence of traumatic brain injury (TBI) is a critical determinant of post-traumatic mortality and morbidity. Not only is TBI one of the leading causes of death among severely injured patients, but it also substantially impacts long-term outcomes following severe trauma. Neurocritical care has a profound effect on outcomes following brain injury; nevertheless, its application in preclinical studies remains infrequent. This review therefore discusses strategies to improve the translational relevance of experimental TBI research, including the integration of neurocritical care principles in animal models. The review further addresses the impact of observation periods after injury and the selection of appropriate animal models (large vs. small animal models). In addition, commonly used injury induction methods-including controlled cortical impact (CCI), fluid percussion injury (FPI), weight-drop models, and blast injury paradigms-are discussed in terms of their reproducibility and clinical relevance. Finally, the review explores whether age, comorbidities, and sex influence TBI outcomes-and, if so, how these variables should be incorporated into experimental designs to improve translational fidelity.

Autoantibodies can predict clinical type 1 diabetes, impacting early diagnosis, prevention, and management. While integrating antibody testing into routine practice is debated globally, ethical considerations are often overlooked. This paper explores these ethical concerns through qualitative analysis based on a literature review.A PubMed literature search provided the foundation for a qualitative ethical analysis. Arguments regarding type 1 diabetes screening were extracted from 92 eligible articles and categorized using Beauchamp and Childress's four ethical principles. A thematic and principle-oriented ethical analysis was conducted.Key ethical concerns include decision-making for children, risk determination, screening timepoints, psychological aspects, DKA rates, treatment options, and monetary and personnel aspects. Addressing these issues ensures general population screening aligns with autonomy, beneficence, nonmaleficence, and justice.Conclusions;General population antibody screening for type 1 diabetes presents ethical challenges requiring careful consideration. While early detection offers benefits, risks such as psychological distress, stigmatization, and resource diversion must be taken into consideration. Further research should assess feasibility, including human resource demands, parental and child anxiety, optimal screening timepoints, development of educational material, children's involvement in screening, and expanding options for prevention, including teplizumab approval in the EU. What is Known: • Autoantibodies can identify individuals at risk for Type 1 Diabetes before symptom onset, and population screening is increasingly discussed as a strategy to reduce complications such as diabetic ketoacidosis at diagnosis. What is New: • This study provides a structured ethical analysis of general population antibody screening for Type 1 Diabetes using the four-principle framework of Beauchamp and Childress (autonomy, beneficence, nonmaleficence, justice) • It identifies key ethical domains, including decision-making for children, psychological impact, screening timing, resource allocation, and emerging preventive options such as Teplizumab, that should guide future implementation and research on population screening programs.

Cytoplasmic TDP-43 pathology is a pathological sign of ALS/ALS-FTD and a converging disease event across different genotypes, phenotypes and CNS areas. To understand this process and target it therapeutically, we need to define which cell types are affected and which cell-type specific effects make them particularly vulnerable. We coupled flow-cytometry nuclear sorting and sequencing with single-nucleus multi-omic ATAC-seq and RNA-seq and spatial transcriptomics to define the transcriptional cell type of affected neurons in the post-mortem ALS/ALS-FTD motor cortex (30 ALS, 20 ALS-FTD & 32 control samples). Here, we show that mainly excitatory cortical neurons are affected by TDP-43 pathology and define the cell types that are affected the most: intratelencephalic L2-L3-LINC00507-FREM3, L3-L5-RORB-LNX2, L3-L5-RORB-ADGRL4 & L6-THEMIS-LINC00343 neurons and extratelencephalic L5-FEZF2-NTNG1 neurons. Transcriptional aberrations by TDP-43 pathology, like cryptic exon inclusion, are cell-type specific and affect distinct gene sets in each cell type, highlighting the need to address TDP-43 pathology in a cell-type specific manner.

Traumatic brain injury (TBI) is a complex condition in which multiple pathophysiological mechanisms influence the course of the disease. After the initial mechanical impact, neuroinflammatory reactions of glial cells along with infiltrating peripheral immune cells determine the overall clinical outcome. However, these secondary processes and their molecular determinants promoting either beneficial or detrimental consequences are not well-defined. Here, we show that TBI-mediated NF-κB activation in astrocytes impairs their homeostatic functions, amplifies the post-traumatic neuroimmune response and disturbs the multicellular CNS scar development in a male mouse model of TBI. Our results further demonstrate a specific deficit in the formation of the glial limitans border and establish that paracrine signaling pathways induced by NF-κB-activated astrocytes can prevent a beneficial restoration of the CNS integrity after TBI. These findings enhance our understanding on the NF-κB-mediated post-traumatic pathophysiology and provide information on future targeted therapies to improve TBI outcome.

Intra-articular steroid injections (IASI) and knee arthroscopies are occasionally performed after total knee arthroplasty (TKA) in patients with persistent pain, inflammation, or mechanical symptoms. Prior studies have raised concern regarding a potential increased risk of periprosthetic joint infection (PJI) following such procedures. Comparative data on infection rates across these post-TKA interventions remain limited. This study evaluates and compares the incidence of PJI in patients who underwent IASI, knee arthroscopy, or both following primary TKA. A retrospective cohort study was conducted using patients who received primary TKA between January 2017 and January 2023. PJI was defined according to the 2018 Musculoskeletal Infection Society (MSIS) criteria. Infection rates were compared using Fisher’s exact test. The control group was propensity score matched on a 5:1 ratio independently for IASI and knee arthroscopy based on age, sex, ASA score, Charlson comorbidity index, and surgical date. 362 patients (372 knees) met inclusion criteria for the treatment groups: 173 received steroid injection only (group 1), 142 underwent arthroscopy only (group 2), and 57 received both (group 3). When comparing all treatment groups (1.34%) to the matched control group of 1850 patients (0.97%), there was no significant difference between infection rates (p = 0.5708) at a minimum 2 year follow up. The infection rate in group 1 was 1.73%, in group 2 was 0.70%, and in group 3 was 1.75%. Two of the 3 infections in group 1 occurred within 30 days of IASI. The 6 month PJI rate in the 230 knees receiving IASI (group 1 and 3) was 0.87%. The fact that two infections occurred within 30 days of IASI suggests a slightly increased risk of infection after IASI. However, reported PJI rates within 6 months of IASI and Arthroscopy are very low and both are considered reasonable treatment options in selected patients.