Endoplasmic reticulum stress as a driver and therapeutic target for kidney disease.

The endoplasmic reticulum (ER) has crucial roles in metabolically active cells, including protein translation, protein folding and quality control, lipid biosynthesis, and calcium homeostasis. Adverse metabolic conditions or pathogenic genetic variants that cause misfolding and accumulation of proteins within the ER of kidney cells initiate an injurious process known as ER stress that contributes to kidney disease and its cardiovascular complications. Initiation of ER stress activates the unfolded protein response (UPR), a cellular defence mechanism that functions to restore ER homeostasis.

Peri-extubation settings in preterm neonates: a systematic review and meta-analysis.

Objective: To systematically review: 1) peri-extubation settings; and 2) association between peri-extubation settings and outcomes in preterm neonates.

Study Design: In this systematic review, studies were eligible if they reported patient-data on peri-extubation settings (objective 1) and/or evaluated peri-extubation levels in relation to clinical outcomes (objective 2). Data were meta-analyzed when appropriate using random-effects model.

Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer.

In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer.

A Phase Ib/II Study of the JAK1 Inhibitor, Itacitinib, plus -Paclitaxel and Gemcitabine in Advanced Solid Tumors.

Lessons Learned: Itacitinib in combination with -paclitaxel plus gemcitabine demonstrated an acceptable safety profile with clinical activity in patients with advanced solid tumors including pancreatic cancer.The results support future studies of itacitinib as a component of combination regimens with other immunologic and targeted small molecule anticancer agents.

Background: Cytokine-mediated signaling via JAK/STAT is central to tumor growth, survival, and systemic inflammation, which is associated with cancer cachexia, particularly in pancreatic cancer.

Randomized, Double-Blind, Phase II Study of Ruxolitinib or Placebo in Combination With Capecitabine in Patients With Metastatic Pancreatic Cancer for Whom Therapy With Gemcitabine Has Failed.

Purpose: Patients with advanced pancreatic adenocarcinoma have a poor prognosis and limited second-line treatment options. Evidence suggests a role for the Janus kinase (JAK)/signal transducer and activator of transcription pathway in the pathogenesis and clinical course of pancreatic cancer.

Patients And Methods: In this double-blind, phase II study, patients with metastatic pancreatic cancer who had experienced treatment failure with gemcitabine were randomly assigned 1:1 to the JAK1/JAK2 inhibitor ruxolitinib (15 mg twice daily) plus capecitabine (1,000 mg/m(2) twice daily) or placebo plus capecitabine.

Venous thromboembolism in patients with diffuse large B-cell lymphoma.

We conducted a retrospective record review to determine the frequency of venous thromboembolism (VTE) in patients with diffuse large B-cell lymphoma (DLBCL). All records from 1990 to 2001 of patients with the diagnosis of DLBCL at a tertiary care hospital were reviewed. Those with transformation from low-grade lymphoma, central nervous system lymphoma, HIV-related lymphoma or with incomplete records were excluded.