AA Amyloidosis: A Contemporary View.

Purpose Of Review: Amyloid A (AA) amyloidosis is an organ- or life-threatening complication of chronic inflammatory disorders. Here, we review the epidemiology, causes, pathogenesis, clinical features, and diagnostic and therapeutic strategies of AA amyloidosis.

Recent Findings: The incidence of AA amyloidosis has declined due to better treatment of the underlying diseases.

Clinical outcomes with metformin use in diabetic patients with compensated cirrhosis: a systematic review and meta-analysis.

Background: Previous studies have demonstrated a beneficial effect of metformin in patients with cirrhosis, but no improvement in liver histology.

Aim: To investigate the impact of metformin on mortality and hepatic decompensation in people with diabetes with compensated cirrhosis.

Methods: Medline, Embase and Cochrane databases were searched from inception to February 2023 for studies reporting results regarding the impact of metformin on all-cause mortality and hepatic decompensation in people with diabetes with compensated cirrhosis.

Enhanced medullary and extramedullary granulopoiesis sustain the inflammatory response in lupus nephritis.

Objectives: In SLE, deregulation of haematopoiesis is characterised by inflammatory priming and myeloid skewing of haematopoietic stem and progenitor cells (HSPCs). We sought to investigate the role of extramedullary haematopoiesis (EMH) as a key player for tissue injury in systemic autoimmune disorders.

Methods: Transcriptomic analysis of bone marrow (BM)-derived HSPCs from patients with SLE and NZBW/F1 lupus-prone mice was performed in combination with DNA methylation profile.

Nonalcoholic Fatty Liver Disease (NAFLD) and Cardiovascular Risk: Is Imaging Helpful?

Nonalcoholic Fatty Liver Disease (NAFLD) is proving to be a globally prevalent condition. Moreover, NAFLD may be an independent risk factor associated with higher cardiovascular (CVD) morbidity and mortality. Further studies are needed to assess whether NAFLD needs to be included in the atherosclerotic risk score algorithms or whether patients with NAFLD need to be screened early on to assess their CVD risk especially since imaging such as positron emission tomography can be used to assess both NAFLD and CV disease at the same time.

Glomerulonephritis and inflammatory bowel disease: A tale of gut-kidney axis dysfunction.

The incidence and prevalence of Inflammatory Bowel Disease (IBD) has increased over the past decades, imposing a growing socioeconomic burden on healthcare systems globally. Most of the morbidity and mortality related to IBD is typically attributed to gut inflammation and its complications; yet the disease is characterized by various extraintestinal manifestations that can be severe. Glomerulonephritis (GN) is of particular interest since a significant proportion of patients evolve into end-stage kidney disease, requiring kidney replacement therapy and associated with high morbidity and mortality.

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.

Molecular Taxonomy of Systemic Lupus Erythematosus Through Data-Driven Patient Stratification: Molecular Endotypes and Cluster-Tailored Drugs.

Objectives: Treatment of Systemic Lupus Erythematosus (SLE) is characterized by a largely empirical approach and relative paucity of novel compound development. We sought to stratify SLE patients based on their molecular phenotype and identify putative therapeutic compounds for each molecular fingerprint.

Methods: By the use of whole blood RNA-seq data from 120 SLE patients, and in a data-driven, clinically unbiased manner, we established modules of commonly regulated genes (molecular endotypes) and re-stratified patients through hierarchical clustering.

Gene Expression as a Guide to the Development of Novel Therapies in Primary Glomerular Diseases.

Despite improvements in understanding the pathogenic mechanisms of primary glomerular diseases, therapy still remains nonspecific. We sought to identify novel therapies targeting kidney-intrinsic injury of distinct primary glomerulonephritides through computational systems biology approaches. We defined the unique transcriptional landscape within kidneys from patients with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and thin basement membrane nephropathy (TBMN).