Diffusion capacity and static hyperinflation as markers of disease progression predict 3-year mortality in COPD: Results from COSYCONET.

Background And Objective: Chronic obstructive pulmonary disease (COPD) exhibits diverse patterns of disease progression, due to underlying disease activity. We hypothesized that changes in static hyperinflation or KCO % predicted would reveal subgroups with disease progression unidentified by preestablished markers (FEV, SGRQ, exacerbation history) and associated with unique baseline biomarker profiles. We explored 18-month measures of disease progression associated with 18-54-month mortality, including changes in hyperinflation parameters and transfer factor, in a large German COPD cohort.

Cabozantinib Plus Nivolumab in Adult Patients with Advanced or Metastatic Renal Cell Carcinoma: A Retrospective, Non-Interventional Study in a Real-World Cohort/GUARDIANS Project.

Introduction: Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients.

Methods: Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria.

Myopia and Other Refractive Error and Their Relationships to Glaucoma Screening.

Prcis: A large disk, a large parapapillary delta zone and a long axial length may be used as screening criteria to detect glaucomatous optic neuropathy in highly myopic eyes.

Purpose: To describe aspects for screening of glaucomatous optic neuropathy in dependence of refractive error, under special consideration of high myopia.

Methods/results: Studies on the anatomy of the myopic optic nerve head and results of investigations on the relationship between glaucomatous optic neuropathy and axial myopia were included.

The temporal mismatch across listening sides affects cortical auditory evoked responses in normal hearing listeners and cochlear implant users with contralateral acoustic hearing.

Combining a cochlear implant with contralateral acoustic hearing typically enhances speech understanding, although this improvement varies among CI users and can lead to an interference effect. This variability may be associated with the effectiveness of the integration between electric and acoustic stimulation, which might be affected by the temporal mismatch between the two listening sides. Finding methods to compensate for the temporal mismatch might contribute to the optimal adjustment of bimodal devices and to improve hearing in CI users with contralateral acoustic hearing.

Management of complications of chimeric antigen receptor T-cell therapy: a report by the European Society of Blood and Marrow Transplantation.

Chimeric antigen receptor (CAR) T cells are in standard clinical use to treat relapsed or refractory hematologic malignancies, such as non-Hodgkin lymphoma, multiple myeloma and acute lymphoblastic leukemia. Owing to the rapidly progressing field of CAR T-cell therapy and the lack of generally accepted treatment guidelines, we hypothesized significant differences between European centers in prevention, diagnosis and management of short- and long-term complications. To capture the current CAR T-cell management among European Society for Blood and Marrow Transplantation (EBMT) centers and to determine the medical need and specific areas for future clinical research the EBMT Transplant Complications Working Party performed a survey among 227 EBMT CAR T-cell centers.

Risk-adjusted Screening for Prostate Cancer-Defining the Low-risk Group by Data from the PROBASE Trial.

Background: Risk-adjusted screening for prostate cancer (PCa) aims to reduce harms by less frequent retesting, especially in men at a low risk of PCa. Definitions of low risk are based mainly on studies in men starting screening at age 55-60 yr.

Objective: To identify men at age 45 yr with a low risk of PCa.

LRBA, a BEACH protein mutated in human immune deficiency, is widely expressed in epithelia, exocrine and endocrine glands, and neurons.

Mutations in LRBA, a BEACH domain protein, cause severe immune deficiency in humans. LRBA is expressed in many tissues and organs according to biochemical analysis, but little is known about its cellular and subcellular localization, and its deficiency phenotype outside the immune system. By LacZ histochemistry of Lrba gene-trap mice, we performed a comprehensive survey of LRBA expression in numerous tissues, detecting it in many if not all epithelia, in exocrine and endocrine cells, and in subpopulations of neurons.

Amplification Is Frequent in Solid Tumors and Predicts Enfortumab Vedotin Response in Metastatic Urothelial Cancer.

Purpose: The anti-NECTIN4 antibody-drug conjugate enfortumab vedotin (EV) is approved for patients with metastatic urothelial cancer (mUC). However, durable benefit is only achieved in a small, yet uncharacterized patient subset. is located on chromosome 1q23.

Variability in Receptive Language Development Following Bilateral Cochlear Implantation.

Objectives: The primary aim was to investigate the variability in language development in children aged 5-7.5 years after bilateral cochlear implantation (CI) up to the age of 2 years, and any impact of the age at implantation and additional noncognitive or anatomical disorders at implantation.

Design: Data of 84 congenitally deaf children that had received simultaneous bilateral CI at the age of ≤ 24 months were included in this retrospective study.

Auditory capacity of the better-hearing ear in asymmetric hearing loss.

Purpose: Our aim was to investigate the course of the hearing capacity of the better-hearing ear in single-sided deafness (SSD) and asymmetric hearing loss (AHL) over time, in a multicenter study.

Methods: We included 2086 pure-tone audiograms from 323 patients with SSD and AHL from four hospitals and 156 private practice otorhinolaryngologists. We collected: age, gender, etiology, duration of deafness, treatment with CI, number and monosyllabic speech recognition, numerical rating scale (NRS) of tinnitus intensity, and the tinnitus questionnaire according to Goebel and Hiller.

Efficacy and quality of life for FOLFOX/bevacizumab +/- irinotecan in first-line metastatic colorectal cancer-final results of the AIO CHARTA trial.

Background: FOLFOXIRI plus bevacizumab has demonstrated benefits for metastatic colorectal cancer (mCRC) patients. However, challenges arise in its clinical implementation due to expected side effects and a lack of stratification criteria.

Methods: The AIO "CHARTA" trial randomised mCRC patients into clinical Group 1 (potentially resectable), 2 (unresectable/risk of rapid progression), or 3 (asymptomatic).

Multiparametric Magnetic Resonance Imaging in Prostate Cancer Screening at the Age of 45 Years: Results from the First Screening Round of the PROBASE Trial.

Background: Magnetic resonance imaging (MRI) has been suggested as a tool for guiding biopsy recommendations in prostate cancer (PC) screening.

Objective: To determine the performance of multiparametric MRI (mpMRI) in young men at age 45 yr who participated in a PC screening trial (PROBASE) on the basis of baseline prostate-specific antigen (PSA).

Design, Setting, And Participants: Participants with confirmed PSA ≥3 ng/ml were offered mpMRI followed by MRI/transrectal ultrasound fusion biopsy (FBx) with targeted and systematic cores.

Digital Rectal Examination Is Not a Useful Screening Test for Prostate Cancer.

Background: Annual digital rectal examination (DRE) is recommended as a stand-alone screening test for prostate cancer (PCa) in Germany for 45+ yr olds. DRE diagnostic performance in men as young as 45 yr old has not been proved by a screening trial.

Objective: To determine DRE diagnostic performance in a screening trial.

Skeletal muscle fibers produce B-cell stimulatory factors in chronic myositis.

Introduction: We aimed to identify B-cell-mediated immunomechanisms in inclusion body myositis (IBM) and polymyositis (PM) as part of the complex pathophysiology.

Materials And Methods: Human primary myotube cultures were derived from orthopedic surgery. Diagnostic biopsy specimens from patients with IBM (n=9) and PM (n=9) were analyzed for markers of B cell activation (BAFF and APRIL) and for chemokines that control the recruitment of B cells (CXCL-12 and CXCL-13).

Alpha-1 Antitrypsin Augmentation and the Liver Phenotype of Adults With Alpha-1 Antitrypsin Deficiency (Genotype Pi∗ZZ).

Background & Aims: α1-Antitrypsin (AAT) is a major protease inhibitor produced by hepatocytes. The most relevant AAT mutation giving rise to AAT deficiency (AATD), the 'Pi∗Z' variant, causes harmful AAT protein accumulation in the liver, shortage of AAT in the systemic circulation, and thereby predisposes to liver and lung injury. Although intravenous AAT augmentation constitutes an established treatment of AATD-associated lung disease, its impact on the liver is unknown.

Janus kinase-inhibition modulates hepatitis E virus infection.

Hepatitis E virus (HEV) usually causes a self-limiting disease, but especially immunocompromised individuals are at risk to develop a chronic and severe course of infection. Janus kinase (JAK) inhibitors (JAKi) are a novel drug class for the treatment of autoimmune inflammatory rheumatic disease (AIRD). As JAKs play a key role in innate immunity, viral infections and reactivations are frequently reported during JAKi treatment in AIRD patients.

Enfortumab Vedotin in Metastatic Urothelial Carcinoma: Survival and Safety in a European Multicenter Real-world Patient Cohort.

Background: Treatment options for patients with urothelial cancer (UC) refractory to platinum and immunotherapy are limited and survival is short. Enfortumab vedotin (EV) is a monoclonal anti-NECTIN4 antibody conjugated to monomethyl auristatin. It was recently approved because of superior survival in comparison to standard-of-care (SOC) chemotherapy.

Design and implementation of ParkinsonAKTIV: an interventional study to evaluate the effectiveness of a novel online platform to guide quickcard-based treatment decisions.

Introduction: Patients with Parkinson's Disease (PD) require an all-encompassing and individualized care including pharmacological as well as non-pharmacological treatment approaches, such as physical therapy, occupational therapy and speech and swallowing therapy. ParkinsonAKTIV is an innovative, multidisciplinary, and comprehensive approach to guide this non-pharmacological PD treatment in northwestern Germany. Its online communication platform called JamesAKTIV has been developed to enhance and standardize PD healthcare professionals' communication.

A Ubiquitous Chromatin Opening Element and DNA Demethylation Facilitate Doxycycline-Controlled Expression during Differentiation and in Transgenic Mice.

Synthetic expression cassettes provide the ability to control transgene expression in experimental animal models through external triggers, enabling the study of gene function and the modulation of endogenous regulatory networks in vivo. The performance of synthetic expression cassettes in transgenic animals critically depends on the regulatory properties of the respective chromosomal integration sites, which are affected by the remodeling of the chromatin structure during development. The epigenetic status may affect the transcriptional activity of the synthetic cassettes and even lead to transcriptional silencing, depending on the chromosomal sites and the tissue.

Equal access to outreach mental health care? Exploring how the place of residence influences the use of intensive home treatment in a rural catchment area in Germany.

Background: Internationally, intensive psychiatric home treatment has been increasingly implemented as a community-based alternative to inpatient admission. Since 2018, the so-called Inpatient Equivalent Home Treatment (IEHT; German: "Stationsäquivalente Behandlung", short: "StäB") has been introduced as a particularly intensive form of home treatment that provides at least one daily treatment contact in the service users' (SU) home environment. Prior research shows that this can be challenging in rural catchment areas.

Do Not Go Gentle into That Deaf Night: A Holistic Perspective on Cochlear Implant Use as Part of Healthy Aging.

Research suggests that cochlear implant (CI) use in elderly people improves speech perception and health-related quality of life (HRQOL). CI provision could also prevent dementia and other comorbidities and support healthy aging. The aim of this study was (1) to prospectively investigate potential changes in HRQOL and speech perception and (2) to identify clinical action points to improve CI treatment.

Signal strength of STING activation determines cytokine plasticity and cell death in human monocytes.

The cyclic GMP-AMP synthase (cGAS)/stimulator of interferon genes (STING) pathway is a cytosolic sensor of microbial and host-derived DNA and plays a key role in innate immunity. Activation of STING by cyclic dinucleotide (CDN) ligands in human monocytes induces a type I interferon response and production of pro-inflammatory cytokines associated with the induction of massive cell death. In this study we have re-evaluated the effect of signal strength of STING activation on the cytokine plasticity of human monocytes.

Poor timing and failure of source control are risk factors for mortality in critically ill patients with secondary peritonitis.

Purpose: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control.

Methods: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (< 2 h), 'urgent' (2-6 h), and 'delayed' (> 6 h).

Adherence to a risk-adapted screening strategy for prostate cancer: First results of the PROBASE trial.

PROBASE is a population-based, randomized trial of 46 495 German men recruited at age 45 to compare effects of risk-adapted prostate cancer (PCa) screening starting either immediately at age 45, or at a deferred age of 50 years. Based on prostate-specific antigen (PSA) levels, men are classified into risk groups with different screening intervals: low-risk (<1.5 ng/ml, 5-yearly screening), intermediate-risk (1.

Cross-species transcriptome analysis for early detection and specific therapeutic targeting of human lupus nephritis.

Objectives: Patients with lupus nephritis (LN) are in urgent need for early diagnosis and therapeutic interventions targeting aberrant molecular pathways enriched in affected kidneys.

Methods: We used mRNA-sequencing in effector (spleen) and target (kidneys, brain) tissues from lupus and control mice at sequential time points, and in the blood from 367 individuals (261 systemic lupus erythematosus (SLE) patients and 106 healthy individuals). Comparative cross-tissue and cross-species analyses were performed.