University Hospital Leipzig

The safety and efficacy of peripartum transfusion support depends on a comprehensive risk analysis, the provision of substantiated criteria for ordering blood products, and surveillance of outcomes over time. We aimed to determine bleeding frequencies and volumes of blood loss, associated patient risk factors, and the effectiveness of our transfusion support scheme. Birth records of 12,255 pregnant women who gave birth at our hospital were screened for haemorrhage volumes, mode of delivery, bleeding aetiology, accompanying risk factors as well as outcome. Transfusion related data was extracted from the electronic blood product database. A total of 204 (1.6 %) women who gave birth within the 5-year study period received at least one RBC transfusion within 48 h after delivery. Differences in haemorrhage volumes in all women compared to those receiving RBC transfusion confirmed an increased probability of RBC transfusion with larger haemorrhage volumes. Uterus atony bleeding (UAB) was the most common cause associated with transfusions. Six risk factors for RBC transfusion among transfused patients were identified that showed a probability of >10 %: Adherent placenta (31.4 %), preterm rupture of membranes (PROM) (25.5 %), age over 35 (25.0 %), a previous caesarean section (19.6 %), gestational diabetes mellitus (15.2 %), and a twin pregnancy (11.8 %). An overall crossmatch-to-transfusion (C/T) ratio of 2.75:1 was reached and no patient with major haemorrhage-related morbidity or mortality was recorded. Evaluation of peripartum haemorrhage and associated RBC transfusion using the described methodology revealed RBC transfusions in 1.6 % of all women who gave birth within the study period. The described blood ordering scheme demonstrates a safe and efficient utilisation of blood products.

To provide recommendations for the most appropriate endovascular intervention of femoropopliteal (FP) arterial disease based on plaque characterization. A panel of 22 physicians from multiple disciplines participated in a modified Delphi consensus, leveraging the RAND/UCLA Appropriateness Method. Panelists engaged in 2 rounds of voting, following a literature review, with an in-person discussion prior to the second round of voting. A rigorous statistical approach was used to analyze the points of agreement and disagreement. Consensus-based recommendations on the most appropriate endovascular approaches for treating patients with FP lesions, stratified by lesion morphology, were generated. Overall, 490 individual items were included in the voting, 458 (93%) of which achieved consensus and 32 (7%) were nonconsensus items, based on a priori criteria under the following categories: (a) recommendations on method for determining plaque morphology, (b) preferred endovascular devices for vessel preparation and definitive treatment stratified by (i) plaque morphology and (ii) Tosaka classification of in-stent restenosis, and (c) vessel preparation device safety-related considerations. This international, multidisciplinary consensus provides evidence- and expert-informed recommendations for vessel preparation and definitive treatment of FP arterial disease, tailored to plaque morphology. These consensus recommendations aim to support clinical decision making and promote best interventional practices by serving as an expert opinion supplement to existing guideline-based care pathways.

IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder in which IgG4+ B cells and T cells interact to drive chronic organ inflammation. Patients with multiorgan involvement may become refractory to standard therapy, resulting in progressive organ damage and risk of organ failure. Here, we report a patient with treatment-refractory multiorgan IgG4-RD treated with CD19-directed chimeric antigen receptor (CAR) T cells and describe the clinical and immunologic effects over more than 12 months of follow-up. A 60-year-old man with IgG4-RD involving the pancreas, hepatobiliary tract, and lungs, who was refractory to long-term immunosuppression, received autologous CD19-directed CAR T cells. Disease course was monitored longitudinally and multimodal immune profiling was performed on peripheral blood. CAR T cell therapy was well tolerated, with only grade 1 cytokine release syndrome, no neurotoxicity, and transient cytopenias without infections. Treatment induced B-cell aplasia lasting 6 months, while serum IgG4 levels normalized by month 8 and remained within the reference range thereafter. FAPI (fibroblast activation protein inhibitor) PET/CT demonstrated regression of fibroinflammatory activity, accompanied by improved lung function and quality of life. Immunosuppressive therapy was completely discontinued without disease flares for more than 12 months. B cell reconstitution consisted predominantly of naïve and transitional subsets. This was paralleled by a decline in T follicular helper cells and CD4+ cytotoxic T cells and attenuation of fibro-inflammatory and B cell-mediated signaling networks on interactome analyses. In this treatment-refractory case of multiorgan IgG4-RD, CD19-directed CAR T cell therapy induced durable, treatment-free remission with normalization of serum IgG4 and improvement across multiple clinical endpoints. Multimodal immune profiling indicates that CAR T cells can reset the B cell compartment and dampen pathogenic T cell and stromal interactions, supporting prospective evaluation of CAR T cell therapy in IgG4-RD.

Handheld ultrasound (HHUS) devices are increasingly used in clinical practice due to their portability and cost-effectiveness. However, HHUS image quality remains variable, and a standardized expert-based evaluation protocol is lacking. This study compares the image quality of B-mode recordings of five HHUS models with a high-end reference system (HEUS) using a blinded assessment to identify differences, covariates, offering a standardized evaluation framework.In this blinded, multi-center study, video sequences of the liver, pancreas, and sigmoid colon were recorded in ten volunteers using 5 HHUS devices - Vscan Air, Butterfly iQ+, Philips Lumify, Clarius C3, and Clarius C3 HD3 - and one HEUS (GE Logiq E10). Twenty-two physicians with many years of abdominal ultrasound experience rated blinded clips for 5 image quality parameters.The HEUS consistently received the highest ratings. Image quality differed significantly between HHUS devices. Clarius systems showed the smallest deviation from the reference, followed by Vscan Air and Philips Lumify. All image parameters significantly correlated with the overall impression, without a single dominant factor. The patients' BMI had no relevant influence. Examiner experience was less impactful than device familiarity and personal preference.The image quality of HEUS remained superior to all tested HHUS devices. Further subdivision of image quality aspects did not provide additional information. Furthermore, we could not identify significant covariates in our setup. These findings could justify simplified setups with reduced questionnaires and requirements for examiners.

Chromophobe renal cell carcinoma (ChRCC) is characterized by the accumulation of abnormal mitochondria, a high rate of mitochondrial DNA (mtDNA) mutations, and altered oxidative metabolism. There are no existing circulating biomarkers to distinguish metastatic ChRCC from clear cell renal cell carcinoma (ccRCC). High-throughput plasma proteomic profiling using the SomaScan platform was performed in 18 ChRCC (including 16 metastatic ChRCC) and 197 metastatic ccRCC patients. Data were harmonized to generate a unified 7K-protein matrix. Differential expression analysis was performed using limma (version 3.62.2). Of 7272 quantified human plasma proteins, 209 were differentially expressed between ChRCC and ccRCC. Upregulated proteins in ChRCC included essential β-oxidation enzymes such as ECH1 (enoyl-CoA hydratase 1) and ECI1 (enoyl-CoA delta-isomerase 1), suggesting increased long-chain fatty acid degradation. Creatine and energy-buffering pathways were also represented, with increased CKMT1A (Creatine Kinase, Mitochondrial 1A) in ChRCC. KIM-1 (Kidney Injury Molecule-1) and leptin were lower in ChRCC, consistent with the known upregulation of these proteins in ccRCC. Pathway enrichment analyses revealed an overrepresentation of mitochondrial protein degradation, fatty acid β-oxidation, and respiratory electron transport in ChRCC, suggesting that ChRCC sheds a unique mitochondrial signature into the peripheral circulation. A bootstrap-based LASSO logistic regression restricted to upregulated mitochondrial proteins in ChRCC vs. ccRCC consistently selected ECI1 and CKMT1A. The LASSO model achieved an AUROC of 0.964. Compared to ccRCC, the plasma proteome of metastatic ChRCC is dominated by mitochondrial metabolic enzymes, revealing a systemic metabolic phenotype strikingly aligned with the known histologic accumulation of abnormal mitochondria in ChRCC cells.

Standard of care for non-metastatic colon cancer is surgery followed by stage-guided adjuvant therapy and/or structured follow-up. Upfront surgery in resectable colon cancer is irrespective of local T/N stage, whereas adjuvant systemic therapy is recommended according to pathological staging. The role of neoadjuvant chemotherapy remains unclear. Whereas perioperative systemic therapy in colon cancer seems to be safe and may lead to pathologic downstaging, evidence on improved survival and quality of life remains scarce. The PROTECTOR / FIRE‑10 trial aims to generate evidence that perioperative systemic therapy improves survival without compromising quality of life in locally advanced, mismatch-repair proficient colon cancer patients. Open-label, randomized, controlled, multicenter, phase III study with two parallel arms. Patients with locally advanced colon or upper rectal cancer staged cT3-4 and/or cN+ are randomized in a 2:1 fashion (favoring preoperative therapy) to investigate the efficacy, patient reported quality of life, and safety of preoperative therapy followed by surgery (Arm A) versus direct surgery followed by non-study specific stage-guided adjuvant therapy (Arm B). Stratification during randomization will be performed according to the following parameters: Fit for mFOLFOXIRI vs. mFOLFOX/CAPOX vs. 80%-mFOLFOX/CAPOX, ECOG 0 vs. ECOG 1-2, and left-sided primary vs. right-sided primary tumor. Only patients with confirmed mismatch-repair proficient and/or microsatellite stable tumor can be included. Preoperative treatment in Arm A is performed for a maximum of 6 biweekly cycles of FOLFOX/FOLFOXIRI or for a maximum of 4 triweekly cycles CAPOX (i.e., appr. 12 weeks). Patients in both arms should undergo quality-controlled surgery of the primary tumor, performed as complete mesocolic excision. Patients will be followed up with regard to relapse, survival and if applicable subsequent anti-cancer treatments until death or for at least 5 years after randomization, whichever date is earlier. The PROTECTOR / FIRE‑10 trial compares preoperative systemic therapy to upfront surgery (with stage-guided adjuvant therapy) in patients with locally advanced colon cancer. This study is registered with clinicaltrials.gov (NCT06899477) and EudraCT (2023-508076-11-00).

The teaching of elementary skin lesions and the ABCDE rule are central components of undergraduate medical education in dermatology. This content is typically taught using photographs, moulages, or patient examples. Independent practice under supervision, however, is often difficult to implement in everyday clinical work. Standardized patients (SPs) equipped with moulages offer an opportunity to link technical content with communication skills. Using temporary, two-dimensional transfer tattoos or three-dimensional moulages, a wide range of common skin and nail changes can be realistically depicted on standardized patients and integrated into medical student teaching. Questionnaire-based evaluations and the results of a clinical, practical exam (Objective Structured Clinical Examination, OSCE) were used to assess the benefit and compare the required level of complexity. Eighty-six medical students in Leipzig participated in a voluntary small-group dermatology examination course to improve lesion description and skin cancer screening skills. Two-dimensional transfer tattoos specifically highlighted often-overlooked skin areas and supported training in conveying clinical findings. A total of 83.7 % of students reported a benefit from using two-dimensional tattoos. In the OSCE exam, no significant difference was observed between two- and three-dimensional depictions (p = 0.082; mean scores 22.54 vs. 23.28). Transfer tattoos provide a simple and effective means of creating realistic dermatology teaching and examination scenarios. Two-dimensional tattoos are not inferior to more complex three-dimensional moulages when used with standardized patients in an examination context.

Rapid adjustments are a key component of effective radiative forcing, influencing both short- and long-term climate responses and prediction uncertainty. Volcanic eruptions act as “natural laboratories” for studying these adjustments, providing insights into the atmospheric and surface mechanisms that occur in response to sudden stratospheric aerosol perturbations.To disentangle these responses from internal variability and anthropogenic trends, we adopt a stepwise approach, analysing six model and observational datasets that capture rapid adjustments to imposed negative shortwave forcing. These include idealized reduced-solar-constant datasets (abrupt-solm4p from CFMIP), idealized stratospheric aerosol layer simulations with non-absorbing and absorbing aerosols (provided by Moritz Günther), and fixed as well as fully coupled sea surface temperatures. Furthermore, the volc-pinatubo-full simulations from VolMIP, CMIP6 historical simulations, ERA5 reanalysis, and CLARA satellite observations were analysed.Across these datasets, we identify characteristic adjustment patterns of radiative fluxes, temperature, circulation, and cloud properties on timescales of months to a year after peak forcing. In volcanic eruptions, stratospheric temperature and dynamical adjustments play a key role and are often closely coupled to tropospheric responses. Comparing idealized solar and aerosol forcing with realistic Pinatubo simulations and observations allows us to assess the extent to which simplified experiments capture essential adjustment patterns typical for volcanic eruptions.Results reveal consistent vertical and regional adjustment fingerprints across datasets, while also highlighting model limitations. For example, due to low stratospheric resolution and simplified QBO parametrizations, models fail to reproduce the full stratospheric temperature response observed in ERA5, whereas observations are more strongly influenced by internal variability than ensemble-mean model results.These findings demonstrate the value of volcanic eruptions as a useful tool for constraining rapid adjustments to shortwave forcing and for improving their representation in climate models.

Receiving a diagnosis of a vision-threatening eye condition is a psychologically salient event for many patients. Across ophthalmology, fear, uncertainty, and emotional distress are commonly observed at the time of diagnosis, often before substantial functional vision loss occurs. Although depression and anxiety are well documented in chronic eye disease, diagnosis-linked distress remains inconsistently recognised and is rarely addressed systematically within routine ophthalmic care. This article introduces post-visual diagnosis distress (PVDD) as a descriptive, nondiagnostic framework to characterise the predictable, loss-related emotional responses that may arise following the diagnosis of a vision-threatening or irreversible eye condition. PVDD is not proposed as a psychiatric disorder, but as a clinically meaningful construct that helps legitimise patient experience, supports empathetic communication, and facilitates timely recognition and appropriate signposting when distress is significant. Drawing on evidence from age-related macular degeneration, glaucoma, and other chronic eye diseases, and informed by multidisciplinary perspectives spanning ophthalmology, psychiatry, counselling, patient advocacy, and public health, the article argues that recognising PVDD may improve patient engagement, quality of life, and psychological outcomes.