Run-in periods and treatment outcomes in asthma trials: A narrative review.

Background: The run-in period is an important element of randomized controlled trials, and is often used in respiratory disease trials. The design of the run-in period can greatly impact results and data interpretation, and as such should be designed carefully.

Methods: In this review, we describe the design of run-in periods across six phase 3A trials of triple therapy in asthma, and discuss how differences in run-in period design (specifically the duration, treatment, and reporting of run-in results) may have the potential to alter the interpretation of study outcomes.

Proposal for a uniform protocol and checklist for cadaveric courses for surgeons with special interest in open abdominal wall reconstruction.

Purpose: Over the last decade, there has been a rapid rise in the development and refinement of abdominal wall repair (AWR) techniques. Numerous cadaveric AWR training courses have been set up with the goal of helping practicing surgeons learn and incorporate them into their surgical repertoire. Some maybe excellent but their quality and consistency are unknown.

STK19 drives transcription-coupled repair by stimulating repair complex stability, RNA Pol II ubiquitylation, and TFIIH recruitment.

Transcription-coupled nucleotide excision repair (TC-NER) efficiently eliminates DNA damage that impedes gene transcription by RNA polymerase II (RNA Pol II). TC-NER is initiated by the recognition of lesion-stalled RNA Pol II by CSB, which recruits the CRL4 ubiquitin ligase and UVSSA. RNA Pol II ubiquitylation at RPB1-K1268 by CRL4 serves as a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment.

Cytosolic nucleic acid sensors and interferon beta-1 activation drive radiation-induced anti-tumour immune effects in human pancreatic cancer cells.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related deaths worldwide with limited treatment options due to extensive radiation and chemotherapy resistance. Monotherapy with immune checkpoint blockade showed no survival benefit. A combination of immunomodulation and radiotherapy may offer new treatment strategies, as demonstrated for non-small cell lung cancer.

Socioeconomic inequalities in patients undergoing abdominal wall reconstruction in the North-West of England, UK: a three-centre retrospective cohort study.

Purpose: Patients from deprived areas are more likely to experience longer waiting times for elective surgery, be multimorbid, and have inferior outcomes from elective and emergency surgery. This study aims to investigate how surgical outcomes vary by deprivation for patients undergoing elective abdominal wall reconstruction.

Methods: A three-centre retrospective cohort study was conducted across three hospitals in North-West England, including patients with complex ventral hernias undergoing abdominal wall reconstruction between 2013 and 2021.

CLosure of Abdominal MidlineS Survey (CLAMSS): A national survey investigating current practice in the closure of abdominal midline incisions in UK surgical practice.

Aim: Incisional herniation (IH) is a frequent complication following midline abdominal closure with significant associated morbidity. Randomized controlled trials have demonstrated that the small bites technique (SBT) and prophylactic mesh augmentation (PMA) may reduce IH compared to mass closure techniques, but data are lacking on their implementation in contemporary surgical practice. This survey aimed to evaluate the use of the SBT and PMA and to identify factors associated with their adoption.

FIP200 Phosphorylation Regulates Late Steps in Mitophagy.

Mitophagy is a specific type of autophagy responsible for the selective elimination of dysfunctional or superfluous mitochondria, ensuring the maintenance of mitochondrial quality control. The initiation of mitophagy is coordinated by the ULK1 kinase complex, which engages mitophagy receptors via its FIP200 subunit. Whether FIP200 performs additional functions in the subsequent later phases of mitophagy beyond this initial step and how its regulation occurs, remains unclear.

Characterization of Moderate and Severe Asthma Exacerbations in the CAPTAIN Study.

Background: Limited data exist on the relative impact of moderate and severe exacerbations on asthma control and impairment.

Objective: To explore data from the CAPTAIN trial to evaluate the relationship between first moderate or severe exacerbation and changes in lung function, symptoms, physical activity limitation scores, and short-acting β-agonist (SABA) usage to determine the clinical relevance of moderate events.

Methods: CAPTAIN was a phase IIIA 24- to 52-week, multicenter, international, randomized controlled trial evaluating efficacy and safety of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) versus FF/VI in patients with uncontrolled asthma on inhaled corticosteroid/long-acting β-agonist.

Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized.

Spatial transcriptomic analysis reveals local effects of intratumoral fusobacterial infection on DNA damage and immune signaling in rectal cancer.

Mucinous colorectal cancer (CRC) is a common histological subtype of colorectal adenocarcinoma, associated with a poor response to chemoradiotherapy. The commensal facultative anaerobes fusobacteria, have been associated with poor prognosis specifically in mesenchymal CRC. Interestingly, fusobacterial infection is especially prevalent in mucinous CRC.

The interplay between autophagy and cGAS-STING signaling and its implications for cancer.

Autophagy is an intracellular process that targets various cargos for degradation, including members of the cGAS-STING signaling cascade. cGAS-STING senses cytosolic double-stranded DNA and triggers an innate immune response through type I interferons. Emerging evidence suggests that autophagy plays a crucial role in regulating and fine-tuning cGAS-STING signaling.

Development and validation of a claims-based algorithm to identify moderate exacerbations in patients with asthma treated in the US.

Introduction: Definitions of moderate asthma exacerbation have been inconsistent, making their economic burden difficult to assess. An algorithm to accurately identify moderate exacerbations from claims data is needed.

Methods: A retrospective cohort study of Reliant Medical Group patients aged ≥18 years, with ≥1 prescription claim for inhaled corticosteroid/long-acting β-agonist, and ≥1 medical claim with a diagnosis code for asthma was conducted.

Preoperative parameters (signalment, digital radiography, urinalysis, urine microbiological culture) and novel algorithm improve prediction of canine urocystolith composition.

Objective: To determine the accuracy of 4 preoperative parameters (signalment, urinalysis, urine microbiological culture, and digital radiography) in predicting urocystolith composition, compare accuracy between evaluators of varying clinical experience and a mobile application, and propose a novel algorithm to improve accuracy.

Animals: 175 client-owned dogs with quantitative analyses of urocystoliths between January 1, 2012, and July 31, 2020.

Methods: Prospective experimental study.

Electro-antibacterial therapy (EAT) to enhance intracellular bacteria clearance in pancreatic cancer cells.

Intratumoral bacteria have been implicated in driving tumor progression, yet effective treatments to modulate the tumor microbiome remain limited. In this study, we investigate the use of electroporation in combination with metronidazole to enhance the clearance of intracellular Fusobacterium nucleatum within pancreatic cancer cells. We explore various parameters, including electric field strength, pulse width, and pulse number to assess the permeability of pancreatic cancer cells infected with F.

Delphi consensus statement for understanding and managing the subcostal hernia: subcostal hernias collaborative report (scholar study).

Introduction: Subcostal hernias are categorized as L1 based on the European Hernia Society (EHS) classification and frequently involve M1, M2, and L2 sites. These are common after hepatopancreatic and biliary surgeries. The literature on subcostal hernias mostly comprises of retrospective reviews of small heterogenous cohorts, unsurprisingly leading to no consensus or guidelines.

Baseline Characteristics and ICS/LAMA/LABA Response in Asthma: Analyses From the CAPTAIN Study.

Background: Findings from CAPTAIN (NCT02924688) suggest that treatment response to fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) differs according to baseline type 2 inflammation markers in patients with moderate to severe asthma. Understanding how other patient physiologic and clinical characteristics affect response to inhaled therapies may guide physicians toward a personalized approach for asthma management.

Objective: To investigate, using CAPTAIN data, the predictive value of key demographic and baseline physiologic variables in patients with asthma (lung function, bronchodilator reversibility, age, age at asthma onset) on response to addition of the long-acting muscarinic antagonist UMEC to inhaled corticosteroid/long-acting β-agonist combination FF/VI, or doubling the FF dose.

Older patients and dialysis shared decision-making. Insights from an ethnographic discourse analysis of interviews and clinical interactions.

Objective: To describe and analyse the perspectives and communication practices of kidney clinicians and older patients (aged 60 +) during collaborative education and decision-making about dialysis.

Methods: This qualitative study drew on pluralistic data sources and analytical approaches investigating elicited semi-structured interviews (n = 31) with doctors (n = 8), nurses (n = 8) and patients (n = 15), combined with ethnographic observations, written artefacts and audio-recorded naturally-occurring interactions (n = 23, education sessions n = 4; consultations n = 19) in a tertiary Australian kidney outpatient clinic. Data were analysed for themes and linguistic discourse features.

Implementing the time-to-event continual reassessment method in the presence of partial orders in a phase I head and neck cancer trial.

Background: In this article we describe the methodology of the time-to-event continual reassessment method in the presence of partial orders (PO-TITE-CRM) and the process of implementing this trial design into a phase I trial in head and neck cancer called ADePT-DDR. The ADePT-DDR trial aims to find the maximum tolerated dose of an ATR inhibitor given in conjunction with radiotherapy in patients with head and neck squamous cell carcinoma.

Methods: The PO-TITE-CRM is a phase I trial design that builds upon the time-to-event continual reassessment method (TITE-CRM) to allow for the presence of partial ordering of doses.

Shared decision making in chronic kidney disease: a qualitative study of the impact of communication practices on treatment decisions for older patients.

Background: Effective interpersonal communication is critical for shared decision-making (SDM). Previous SDM communication training in nephrology has lacked context-specific evidence from ethnographic analysis of SDM interactions with older patients considering treatment options of end stage kidney disease (ESKD). This study explores communication strategies in SDM discussions in nephrology, specifically focusing on older patients considering dialysis as kidney replacement therapy (KRT).