Identifying genetic differences between bipolar disorder and major depression through multiple genome-wide association analyses.

Background: Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

Aims: We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Impact of sex hormones on pheochromocytomas, paragangliomas, and gastroenteropancreatic neuroendocrine tumors.

Objective: The effects of sex hormones remain largely unexplored in pheochromocytomas and paragangliomas (PPGLs) and gastroenteropancreatic neuroendocrine tumors (GEP-NETs).

Methods: We evaluated the effects of estradiol, progesterone, Dehydroepiandrosterone sulfate (DHEAS), and testosterone on human patient-derived PPGL/GEP-NET primary culture cell viability (n = 38/n = 12), performed next-generation sequencing and immunohistochemical hormone receptor analysis in patient-derived PPGL tumor tissues (n = 36).

Results: In PPGLs, estradiol and progesterone (1 µm) demonstrated overall significant antitumor effects with the strongest efficacy in PPGLs with NF1 (cluster 2) pathogenic variants.

A Critical Appraisal of the Application of Frailty and Sarcopenia in the Spinal Oncology Population.

Study Design: Systematic review and clinimetric analysis.

Objectives: Frailty and sarcopenia predict worse surgical outcomes among spinal degenerative and deformity-related populations; this association is less clear in the context of spinal oncology. Here, we sought to identify frailty and sarcopenia tools applied in spinal oncology and appraise their clinimetric properties.

Validation of a hypomorphic variant in CDK13 as the cause of CHDFIDD with autosomal recessive inheritance through determination of an episignature.

Autosomal dominant CDK13-related disease is characterized by congenital heart defects, dysmorphic facial features, and intellectual developmental disorder (CHDFIDD). Heterozygous pathogenic variants, particularly missense variants in the kinase domain, have previously been described as disease causing. Using the determination of a methylation pattern and comparison with an established episignature, we reveal the first hypomorphic variant in the kinase domain of CDK13, leading to a never before described autosomal recessive form of CHDFIDD in a boy with characteristic features.

Weather-Related Factors and Patient-Reported Outcomes (PROs) in Cancer Patients: Results from the ExPRO Study.

Objective: The ExPRO (External factors influencing patient reported outcomes of patients with malignant diseases) study explored associations between QoL data and environmental factors on the day of questionnaire completion: mean temperature, sunshine hours, season, and lunar phase.

Methods: We undertook a cross-sectional analysis of baseline data in the prospective cohort study at two cancer centers in eastern Germany. From December 2020 to December 2021, cancer patients completed the EORTC QLQ-C30 questionnaire upon admission.

Prospective Multicenter Evaluation of the MDS "Suggestive of PSP" Diagnostic Criteria.

Background: The recent Movement Disorders Society (MDS)-progressive supranuclear palsy (PSP) diagnostic criteria conceptualized three clinical diagnostic certainty levels: "suggestive of PSP" for sensitive early diagnosis based on subtle clinical signs, "possible PSP" balancing sensitivity and specificity, and "probable PSP" highly specific for PSP pathology.

Objective: The aim of this study was to prospectively validate the criteria against long-term clinical follow-up and characterize the diagnostic certainty increase over time.

Methods: Patients with "possible PSP" or "suggestive of PSP" diagnosis and clinical follow-up were recruited in two German multicenter longitudinal observational studies (ProPSP and DescribePSP).

Predictive Potential of ECMO Blood Flow for Hemolysis and Outcome of Patients with Severe ARDS.

Treatment with veno-venous extracorporeal membrane oxygenation (VV ECMO) has become a frequently considered rescue therapy in patients with severe acute respiratory distress syndrome (ARDS). Hemolysis is a common complication in patients treated with ECMO. Currently, it is unclear whether increased ECMO blood flow (Q̇) contributes to mortality and might be associated with increased hemolysis.

First Experiences with Fusion of PET-CT and MRI Datasets for Navigation-Assisted Percutaneous Biopsies for Primary and Metastatic Bone Tumors.

The aim of this study was to compare the technique of navigation-assisted biopsy based on fused PET and MRI datasets to CT-guided biopsies in terms of the duration of the procedure, radiation dose, complication rate, and accuracy of the biopsy, particularly in anatomically complex regions. Between 2019 and 2022, retrospectively collected data included all navigated biopsies and CT-guided biopsies of suspected primary bone tumors or solitary metastases. Navigation was based on preoperative CT, PET-CT/-MRI, and MRI datasets, and tumor biopsies were performed using intraoperative 3D imaging combined with a navigation system.

Translational and clinical comparison of whole genome and transcriptome to panel sequencing in precision oncology.

Precision oncology offers new cancer treatment options, yet sequencing methods vary in type and scope. In this study, we compared whole-exome/whole-genome (WES/WGS) and transcriptome sequencing (TS) with broad panel sequencing by resequencing the same tumor DNA and RNA as well as normal tissue DNA for germline assessment, from 20 patients with rare or advanced tumors, who were originally sequenced by WES/WGS ± TS within the DKFZ/NCT/DKTK MASTER program from 2015 to 2020. Molecular analyses resulted in a median number of 2.

The Transcription Factor SOX18 Inhibitor Small Molecule 4 Is a Potential Treatment of Cancer-Induced Lymphatic Metastasis and Lymphangiosarcoma.

Background: Malignant tumors release growth factors, promoting lymphangiogenesis in primary tumors and draining sentinel lymph nodes, ultimately facilitating lymph node metastasis. As a malignant lymphatic tumor entity, lymphangiosarcomas are characterized by low survival rates and limited treatment options. The transcription factor SOX18 plays a crucial role in both lymphatic endothelial cell differentiation and cancer-induced lymphangiogenesis.

Determinants of perceived patient benefit in a longitudinal cohort study of patients with psoriasis and atopic dermatitis.

The Dermatology Life Quality Index (DLQI) should be used to assess treatment success in psoriasis (PSO). However, the DLQI does not assess the importance and achievement of treatment goals. The Patient Benefit Index (PBI) is a questionnaire that takes both into account.

Neutrophil Extracellular Traps (NETs) as a Potential Target for Anti-Aging: Role of Therapeutic Apheresis.

Neutrophil extracellular traps (NETs) are large structures composed of chromatin, histones and granule-derived proteins released extracellularly by neutrophils. They are generally considered to be a part of the antimicrobial defense strategy, preventing the dissemination of pathogens. However, overproduction of NETs or their ineffective clearance can drive various pathologies, many of which are associated with advanced age and involve uncontrolled inflammation, oxidative, cardiovascular and neurodegenerative stress as underlying mechanisms.

Development of a pandemic-related core set of quality indicators for quality and patient safety in University Hospitals in Germany.

Background: The COVID-19 pandemic entailed a global health crisis, significantly affecting medical service delivery in Germany as well as elsewhere. While intensive care capacities were overloaded by COVID cases, not only elective cases but also non-COVID cases requiring urgent treatment unexpectedly decreased, potentially leading to a deterioration in health outcomes. However, these developments were only uncovered retrospectively.

Contribution of individual phospholipase A enzymes to the cleavage of oxidized phospholipids in human blood plasma.

Phospholipids containing oxidized esterified PUFA residues (OxPLs) are increasingly recognized for multiple biological activities and causative involvement in disease pathogenesis. Pharmacokinetics of these compounds in blood plasma is essentially not studied. Human plasma contains both genuine phospholipases A (PAF-AH (also called Lp-PLA) and sPLA) and multifunctional enzymes capable of removing sn-2 residues in native and oxidized PLs (LCAT, PRDX6).

Introducing the forearm fracture index to define the diametaphyseal junction zone through clinical evaluation in a cohort of 366 diametaphyseal radius fractures.

Background: Unstable diametaphyseal radius fractures (DMRFs) can be prone to complications, and treatment strategies are heterogeneous. Studies are difficult to interpret as definitions of the diametaphyseal junction zone (DMJZ) are impractical for clinical use, imprecise, or prone to error.

Methods: We introduce the forearm fracture index (FFI) to define DMRFs in radiographs and ultrasound.

Differentiation Between Pellucid-Like Keratoconus and Pellucid Marginal Degeneration Using Swept-Source Optical Coherence Tomography.

Purpose: The distinction between pellucid-like keratoconus (PLK) and pellucid marginal corneal degeneration (PMD) based on tomographic examinations is difficult. In this study, corneal tomographic and biomechanical parameters, after classifying PMD and PLK using swept-source optical coherence tomography, were analyzed.

Methods: Diagnoses of PLK and PMD were made using SS-OCT imaging, two groups were formed: PLK (n = 30) and PMD (n = 10).

Global Challenges in the Access of Endovascular Treatment for Acute Ischemic Stroke (Global MT Access).

Background: Mechanical thrombectomy (MT) is the standard of care for eligible acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) since 2015.

Aim: Our aim was to determine the key challenges for MT implementation and access worldwide.

Methods: We conducted an international online survey consisting of 37 questions, distributed through the World Stroke Organization network, and as invited by co-authors between December 2022 and March 2023.

Vestibular Hypofunction in Patients with Presbycusis: A Cross-Sectional Study.

Vestibular Hypofunction (VH) and hearing loss can affect quality of life and lead to disability, especially in the elderly. Studies investigating presbycusis and vestibular function in the aging population have been conducted separately, but few have examined the combination of both conditions in older patients, with inconsistent results that may be due to small sample sizes or heterogeneity in the methods used to assess vestibular function. We aimed to characterize the occurrence of VH in patients with presbycusis using the video head impulse test (vHIT), which is a specific and reliable assessment tool for VH.

Developmental beta-cell death orchestrates the islet's inflammatory milieu by regulating immune system crosstalk.

While pancreatic beta-cell proliferation has been extensively studied, the role of cell death during islet development remains incompletely understood. Using a genetic model of caspase inhibition in beta cells coupled with mathematical modeling, we here discover an onset of beta-cell death in juvenile zebrafish, which regulates beta-cell mass. Histologically, this beta-cell death is underestimated due to phagocytosis by resident macrophages.

Generalized, sublethal damage-based mathematical approach for improved modeling of clonogenic survival curve flattening upon hyperthermia, radiotherapy, and beyond.

Mathematical modeling can offer valuable insights into the behavior of biological systems upon treatment. Different mathematical models (empirical, semi-empirical, and mechanistic) have been designed to predict the efficacy of either hyperthermia (HT), radiotherapy (RT), or their combination. However, mathematical approaches capable of modeling cell survival from shared general principles for both mono-treatments alone and their co-application are rare.

Finding predictive factors of exercise adherence in randomized controlled trials on low back pain: an individual data re-analysis using machine learning techniques.

Objective: To identify predictors of adherence in supervised and self-administered exercise interventions for individuals with low back pain.

Design: Cohort study.

Setting: Rehabilitation.

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

Simulator training in focus assessed transthoracic echocardiography (FATE) for undergraduate medical students: results from the FateSim randomized controlled trial.

Introduction: Ultrasound is important in heart diagnostics, yet implementing effective cardiac ultrasound requires training. While current strategies incorporate digital learning and ultrasound simulators, the effectiveness of these simulators for learning remains uncertain. This study evaluates the effectiveness of simulator-based versus human-based training in Focused Assessed with Transthoracic Echocardiography (FATE).