Ecologically sustainable benchmarking of AI models for histopathology.

Deep learning (DL) holds great promise to improve medical diagnostics, including pathology. Current DL research mainly focuses on performance. DL implementation potentially leads to environmental consequences but approaches for assessment of both performance and carbon footprint are missing.

Remission induction therapies and long-term outcomes in granulomatosis with polyangiitis and microscopic polyangiitis: real-world data from a European cohort.

To explore disease characteristics, renal involvement and induction treatment strategies over the last decades and evaluate relapse rates and renal outcomes in ANCA-associated vasculitides (AAV). We retrospectively analyzed remission, relapse rates and the occurrence of the composite endpoint (comprising death and renal failure) in newly diagnosed AAV cases in four tertial referral centers in Germany and Switzerland diagnosed between 1999 and 2022. Hazard ratios were computed by Cox proportional hazard and Kaplan-Meier curves were plotted to compare therapeutic strategies after propensity-matching.

Laboratory measurement of autoantibodies to Annexin A1: Review and measurements in health and COVID-19.

Annexin A1, a protein released by neutrophils, is a potent regulator of inflammation in the intact form, but loses this activity when cleaved. The presence of autoantibodies to this protein can impact its function. An immunoassay, developed to measure autoantibodies to Annexin A1 in plasma or serum, has been developed and performances are reported.

Serum uromodulin associates with kidney function and outcome in a cohort of hospitalised COVID-19 patients.

This study investigates the prevalence and evaluates the prognostic implications of acute kidney injury (AKI) in COVID-19 patients, with a novel emphasis on the evaluation of serum uromodulin (sUmod) as a potential kidney-specific biomarker. A cohort of hospitalised COVID-19 patients (n = 378) was examined for AKI using standard criteria. In addition to traditional urinary biomarkers, sUmod levels were analysed.

Breast Cancer Stem Cells Upregulate IRF6 in Stromal Fibroblasts to Induce Stromagenesis.

The microenvironment of a cancer stem cell (CSC) niche is often found in coexistence with cancer-associated fibroblasts (CAFs). Here, we show the first in-depth analysis of the interaction between primary triple-negative breast cancer stem cells (BCSCs) with fibroblasts. Using 2D co-culture models with specific seeding ratios, we identified stromal fibroblast aggregation at the BCSC cluster periphery, and, on closer observation, the aggregated fibroblasts was found to encircle BCSC clusters in nematic organization.

Cellular metabolism changes in atherosclerosis and the impact of comorbidities.

Cell activation and nutrient dysregulation are common consequences of atherosclerosis and its preceding risk factors, such as hypertension, dyslipidemia, and diabetes. These diseases may also impact cellular metabolism and consequently cell function, and the other way around, altered cellular metabolism can impact disease development and progression through altered cell function. Understanding the contribution of altered cellular metabolism to atherosclerosis and how cellular metabolism may be altered by co-morbidities and atherosclerosis risk factors could support the development of novel strategies to lower the risk of CVD.

Distinct pulmonary patterns in ANCA-associated vasculitides: insights from a retrospective single center cohort study.

ANCA-associated vasculitides (AAV) comprise granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis. All forms may involve different organ systems, yet kidney and lung involvement are common and fatal in many cases. Here, we aimed to determine the predictive value of pulmonary disease manifestation and individual CT findings in AAV patients.

DNA-binding protein-A: a multitool in tubular epithelial cells.

Acute kidney injury is still associated with high morbidity and mortality. Reichardt et al. investigated DNA-binding protein-A (Ybx3) in acute kidney injury induced by ischemia-reperfusion injury and found that mice lacking Ybx3 have altered mitochondrial function and increased antioxidant activity, making them more resistant to ischemia-reperfusion injury-acute kidney injury.

Coronary Microvascular Dysfunction in Acute Cholestasis-Induced Liver Injury.

Background: Previous studies have shown cardiac abnormalities in acute liver injury, suggesting a potential role in the associated high mortality.

Methods: We designed an experimental study exploring the short-term effects of acute cholestasis-induced liver injury on cardiac function and structure in a rodent bile duct ligation (BDL) model to elucidate the potential interplay. Thirty-seven male rats were subjected to BDL surgery ( = 28) or served as sham-operated ( = 9) controls.

A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy.

Atacicept is a first-in-class, dual anti-B-cell Activation Factor-A Proliferation-Inducing Ligand fusion protein in clinical evaluation for treatment of IgA nephropathy. To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b clinical trial ORIGIN enrolled 116 individuals with biopsy-proven IgA nephropathy. Participants were randomized to atacicept 150, 75, or 25 mg versus placebo once weekly for up to 36 weeks.

An Open-label Phase 2 Study of Eneboparatide, a Novel PTH Receptor 1 Agonist, in Hypoparathyroidism.

Context: Hypoparathyroidism is a rare disorder characterized by a deficiency in PTH resulting in hypocalcemia, hyperphosphatemia, and hypercalciuria. Eneboparatide is an investigational peptide agonist of the PTH1 receptor for the treatment of chronic hypoparathyroidism (HP).

Objective: To evaluate the efficacy, safety, and tolerability of eneboparatide in HP patients.

Deep learning applications for kidney histology analysis.

Purpose Of Review: Nephropathology is increasingly incorporating computational methods to enhance research and diagnostic accuracy. The widespread adoption of digital pathology, coupled with advancements in deep learning, will likely transform our pathology practices. Here, we discuss basic concepts of deep learning, recent applications in nephropathology, current challenges in implementation and future perspectives.

The spectrum of thrombotic microangiopathy related to monoclonal gammopathy.

Background: Recent studies showed a high prevalence of monoclonal gammopathy (MG) in patients with thrombotic microangiopathy (TMA) aged over 50 years and suggested that complement dysregulation is pivotal for the disease to develop. Here, we studied this premise in seven patients with TMA and coexisting MG.

Methods: Patients with TMA on kidney biopsy and/or peripheral blood were recruited from the prospective COMPETE cohort (NCT04745195) and Limburg Renal Registry.

Multiomic profiling of transplant glomerulopathy reveals a novel T-cell dominant subclass.

Kidney transplant (KTx) biopsies showing transplant glomerulopathy (TG) (glomerular basement membrane double contours (cg) > 0) and microvascular inflammation (MVI) in the absence of C4d staining and donor-specific antibodies (DSAs) do not fulfill the criteria for chronic active antibody-mediated rejection (CA-AMR) diagnosis and do not fit into any other Banff category. To investigate this, we initiated a multicenter intercontinental study encompassing 36 cases, comparing the immunomic and transcriptomic profiles of 14 KTx biopsies classified as cg+MVI DSA/C4d with 22 classified as CA-AMR DSA/C4d through novel transcriptomic analysis using the NanoString Banff-Human Organ Transplant (B-HOT) panel and subsequent orthogonal subset analysis using two innovative 5-marker multiplex immunofluorescent panels. Nineteen genes were differentially expressed between the two study groups.

Non-canonical Hedgehog signaling mediates profibrotic hematopoiesis-stroma crosstalk in myeloproliferative neoplasms.

The role of hematopoietic Hedgehog signaling in myeloproliferative neoplasms (MPNs) remains incompletely understood despite data suggesting that Hedgehog (Hh) pathway inhibitors have therapeutic activity in patients. We aim to systematically interrogate the role of canonical vs. non-canonical Hh signaling in MPNs.

Copeptin, Natriuretic Peptides, and Cardiovascular Outcomes in Patients With CKD: The German Chronic Kidney Disease (GCKD) Study.

Rationale & Objective: Copeptin and Midrange pro-atrial natriuretic peptide (MR-pro-ANP) are associated with outcomes independently of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) in patients with heart failure (HF). The value of these markers in patients with chronic kidney disease (CKD) has not been studied.

Study Design: Prospective cohort study.

Mechanisms of kidney fibrosis and routes towards therapy.

Kidney fibrosis is the final common pathway of virtually all chronic kidney diseases (CKDs) and is therefore considered to be a promising therapeutic target for these conditions. However, despite great progress in recent years, no targeted antifibrotic therapies for the kidney have been approved, likely because the complex mechanisms that initiate and drive fibrosis are not yet completely understood. Recent single-cell genomic approaches have allowed novel insights into kidney fibrosis mechanisms in mouse and human, particularly the heterogeneity and differentiation processes of myofibroblasts, the role of injured epithelial cells and immune cells, and their crosstalk mechanisms.