Is pathological response an adequate surrogate marker for survival in neoadjuvant therapy with immune checkpoint inhibitors?

Pathological response (PR) is an oncological outcome measure that indicates the therapeutic response to neoadjuvant therapy. In clinical trials involving neoadjuvant or perioperative interventions, overall survival and disease/event-free survival are typically the primary outcome measures. Although some evidence suggests that pathological complete response (pCR) can serve as a surrogate marker for the primary endpoint in prospective trials, it remains uncertain whether pCR is a true surrogate marker for patients with cancer undergoing curative resection across all solid tumours.

A peptide mimic of SOCS1 modulates equine peripheral immune cells and ocular effector functions : implications for recurrent uveitis.

Introduction: Recurrent uveitis (RU), an autoimmune disease, is a leading cause of ocular detriment in humans and horses. Equine and human RU share many similarities including spontaneous disease and aberrant cytokine signaling. Reduced levels of SOCS1, a critical regulator of cytokine signaling, is associated with several autoimmune diseases.

Deletion of metal transporter Zip14 reduces major histocompatibility complex II expression in murine small intestinal epithelial cells.

Documented worldwide, impaired immunity is a cardinal signature resulting from loss of dietary zinc, an essential micronutrient. A steady supply of zinc to meet cellular requirements is regulated by an array of zinc transporters. Deletion of the transporter Zip14 (Slc39a14) in mice produced intestinal inflammation.

Current and emerging treatment options for BRAFV600-mutant melanoma.

Introduction: BRAF mutations are the most common driver mutation in cutaneous melanoma, present in 40% of cases. Rationally designed BRAF targeted therapy (TT) has been developed in response to this, and alongside immune checkpoint inhibitors (ICI), forms the backbone of systemic therapy options for BRAF-mutant melanoma. Various therapeutic approaches have been studied in the neoadjuvant, adjuvant and advanced settings, and there is a wealth of information to guide clinicians managing these patients.

Tracking Nongenetic Evolution from Primary to Metastatic ccRCC: TRACERx Renal.

Using joint genomic-transcriptomic analysis of 243 samples, we reveal recurrent patterns of nongenetic evolution in ccRCC not exclusively governed by genetic factors, including T-cell depletion, tumor T-cell receptor coevolution, potential cGAS-STING repression, and increased cell proliferation. These patterns can aid clinical management and guide novel treatment approaches.

Tracking non-genetic evolution from primary to metastatic ccRCC: TRACERx Renal.

While the key aspects of genetic evolution and their clinical implications in clear cell renal-cell carcinoma (ccRCC) are well-documented, how genetic features co-evolve with the phenotype and tumor microenvironment (TME) remains elusive. Here, through joint genomic-transcriptomic analysis of 243 samples from 79 patients recruited to the TRACERx Renal study, we identify pervasive non-genetic intratumor heterogeneity, with over 40% not attributable to genetic alterations. By integrating tumor transcriptomes and phylogenetic structures, we observe convergent evolution to specific phenotypic traits, including cell proliferation, metabolic reprogramming and overexpression of putative cGAS-STING repressors amid high aneuploidy.

An Agent-Based Model of Metabolic Signaling Oscillations in Biofilms.

Microbes of nearly every species can form biofilms, communities of cells bound together by a self-produced matrix. It is not understood how variation at the cellular level impacts putatively beneficial, colony-level behaviors, such as cell-to-cell signaling. Here we investigate this problem with an agent-based computational model of metabolically driven electrochemical signaling in biofilms.

Avelumab + axitinib versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma: final analysis of the phase III JAVELIN Renal 101 trial.

Background: In the phase III JAVELIN Renal 101 trial (NCT02684006), first-line treatment with avelumab + axitinib resulted in significantly longer progression-free survival (PFS) and a higher objective response rate (ORR) versus sunitinib in patients with advanced renal cell carcinoma (aRCC). We report the final analysis, including the primary analysis of overall survival (OS).

Patients And Methods: Patients with untreated aRCC (any prognostic risk score) were enrolled.

Cleavage of Cartilage Oligomeric Matrix Protein (COMP) by ADAMTS4 generates a neoepitope associated with osteoarthritis and other forms of degenerative joint disease.

Osteoarthritis (OA) is a highly prevalent joint disease, affecting millions of people worldwide and characterized by degradation of articular cartilage, subchondral bone remodeling and low-grade inflammation, leading to pain, stiffness and disability. Cartilage Oligomeric Matrix Protein (COMP) is a major structural component of cartilage and its degradation has been proposed as a marker of OA severity/progression. Several proteases cleave COMP in vitro, however, it is unclear which of these COMPase activities is prevalent in an osteoarthritic joint.

Commercial influences on patient and public involvement: a renewed call for research and action.

Patient and public involvement is increasingly advocated in health policy, research and practice. Patients and people with lived experience, carers and the general public should have a say in how policy is generated, how services are delivered and how research is conducted. Through this perspective article, we hope to stimulate discussion and debate around industry influence in patient and public involvement, specifically pertaining to patient organizations, which often play a key role in patient and public involvement activities.

Long-term outcomes among patients who respond within the first year to nivolumab plus ipilimumab or nivolumab monotherapy: A pooled analysis in 935 patients.

Purpose: To investigate the predictive value of RECIST response within 3, 6, or 12 months on long-term survival, and explore differences between nivolumab+ipilimumab and nivolumab monotherapy, we analyzed pooled 5-year data of 935 responder and non-responder patients at various time points after treatment initiation in CheckMate 069, 066, and 067 studies.

Patients And Methods: Treatment-naive advanced melanoma patients received nivolumab+ipilimumab or nivolumab monotherapy. To decrease immortal time bias, 3-, 6-, or 12-month overall survival (OS) and progression-free survival (PFS) landmark analyses were performed.

Economic, cultural, and social inequalities in potentially inappropriate medication: A nationwide survey- and register-based study in Denmark.

Background: Potentially inappropriate medication (PIM) is associated with negative health outcomes and can serve as an indicator of treatment quality. Previous studies have identified social inequality in treatment but often relied on narrow understandings of social position or failed to account for mediation by differential disease risk among social groups. Understanding how social position influences PIM exposure is crucial for improving the targeting of treatment quality and addressing health disparities.

Adapting the design of the ongoing RAMPART trial in response to external evidence: An example for trials which take many years to run and report.

Clinical trials to establish the efficacy of new agents in the adjuvant cancer setting typically take many years to complete. During that time, external factors can impact recruitment and reporting plans. An example is a new standard of care becoming available during the recruitment period.

High-resolution multimodal profiling of human epileptic brain activity via explanted depth electrodes.

The availability and integration of electrophysiological and molecular data from the living brain is critical in understanding and diagnosing complex human disease. Intracranial stereo electroencephalography (SEEG) electrodes used for identifying the seizure focus in patients with epilepsy could enable the integration of such multimodal data. Here, we report multimodal profiling of epileptic brain activity via explanted depth electrodes (MoPEDE), a method that recovers extensive protein-coding transcripts, including cell type markers, DNA methylation, and short variant profiles from explanted SEEG electrodes matched with electrophysiological and radiological data allowing for high-resolution reconstructions of brain structure and function.

Longitudinal stability of molecular endotypes of knee osteoarthritis patients.

Objective: To assess the longitudinal stability of biomarker-based molecular endotypes of knee osteoarthritis (KOA) participants from APPROACH and to evaluate the consistency of findings in an independent KOA population.

Methods: Nineteen biomarkers were measured longitudinally in 295 KOA participants from the APPROACH cohort. K-means clustering was used to identify the structural damage, inflammation, and low tissue turnover endotypes at the six-, 12-, and 24-month follow-ups.

Fishy business in Seattle: Salmon mislabeling fraud in sushi restaurants vs grocery stores.

Salmon is the most commonly consumed finfish in the United States of America (USA), and the mislabeling of salmon is a widespread problem. Washington State is a global supplier of wild-caught Pacific salmon and local salmon mislabeling results in substantial economic, ecological, and cultural impacts. Previous studies in Washington State identified high levels of mislabeled salmon in both markets and restaurants, resulting in local legislation being passed that requires proper labeling of salmon products, including identifying it as wild-caught or farm-raised.

Usage of the Anemia Control Model Is Associated with Reduced Hospitalization Risk in Hemodialysis.

Introduction: The management of anemia in chronic kidney disease (CKD-An) presents significant challenges for nephrologists due to variable responsiveness to erythropoietin-stimulating agents (ESAs), hemoglobin (Hb) cycling, and multiple clinical factors affecting erythropoiesis. The Anemia Control Model (ACM) is a decision support system designed to personalize anemia treatment, which has shown improvements in achieving Hb targets, reducing ESA doses, and maintaining Hb stability. This study aimed to evaluate the association between ACM-guided anemia management with hospitalizations and survival in a large cohort of hemodialysis patients.

Non-Optical, Label-free Electrical Capacitance Imaging of Microorganisms.

Unlabelled: Many fundamental insights into microbiology have come from imaging, which is typically synonymous with optical techniques. However, the sample preparation needed for many optical microscopy methods such as labeling, fixing, or genetic modification, limits the range of species and environments we can investigate. Here we demonstrate the use of electrical capacitance measurements as a non-optical method for imaging live microbial samples.

Dual Immune Checkpoint Inhibition in Melanoma and PD-L1 Expression: The Jury Is Still Out.

This comment discusses the use of PD-L1 as a biomarker to guide treatment decisions for metastatic melanoma.

Factors Influencing Outcomes and Survival in Anal Cancer.

Background: We aim to ascertain prognostic factors in the current management of anal cancer within this study.

Methods: We reviewed the management and outcomes of anal cancer cases over a seven-year period, inclusive (2016-2023). The primary objectives were to assess the demographic characteristics, clinical presentation, and outcomes of all anal cancer patients within our institution.