Protocol for perfusing human axillary lymph nodes ex vivo to study structure and function in real time.

Lymph nodes regulate immunity and maintain fluid balance in health and disease. Here, we present a protocol that uses normothermic perfusion to sustain patient-derived lymph nodes ex vivo for up to 24 h to study their structure and function. We describe steps for setting up both thermoregulatory and perfusion circuits, cannulating human lymph nodes, and perfusion.

Pembrolizumab in Patients With Advanced Clear Cell Gynecological Cancer: A Phase 2 Nonrandomized Clinical Trial.

Importance: Advanced clear cell gynecological cancers (CCGCs) have a poor prognosis, with response rates to second-line chemotherapy less than 8%. Preliminary clinical activity with programmed cell death 1 protein (PD-1) inhibitors reported in CCGC merits further investigation.

Objective: To assess the clinical benefit of pembrolizumab in patients with previously treated advanced CCGC.

Selinexor plus ruxolitinib in JAK inhibitor treatment-naïve myelofibrosis: SENTRY Phase 3 study design.

Selinexor is an investigational, selective oral XPO1 inhibitor that may inhibit myelofibrosis (MF)-relevant JAK/STAT and non-JAK/STAT pathways with potential synergy with ruxolitinib. SENTRY (XPORT-MF-034; NCT04562389) is a Phase 1/3 study evaluating safety and efficacy of selinexor plus ruxolitinib for treatment of patients with JAK inhibitor (JAKi) treatment-naïve MF. The Phase 1 open label portion of the study included a 3 + 3 dose escalation and dose expansion, with no dose limiting toxicities observed.

Dilated cardiomyopathy in the young: a patient-scientist informed review of unmet needs.

Dilated cardiomyopathy (DCM) is a leading cause of heart failure and the most common indication for a heart transplant. Guidelines are regularly based on studies of adults and applied to the young. Children and adolescents diagnosed with DCM face different lifestyle challenges from individuals diagnosed in adulthood that include medical trauma and are influenced by maturity levels and confidence with advocacy to adults.

Autism spectrum disorder common variants associated with regional lobe volume variations at birth: cross-sectional study in 273 European term neonates in developing human connectome project.

Increasing lines of evidence suggest cerebral overgrowth in autism spectrum disorder (ASD) children in early life, but few studies have examined the effect of ASD common genetic variants on brain volumes in a general paediatric population. This study examined the association between ASD polygenic risk score (PRS) and volumes of the frontal, temporal, parietal, occipital, fronto-temporal and parieto-occipital lobes in 273 term-born infants of European ancestry in the developing Human Connectome Project. ASD PRS was positively associated with frontal (β = 0.

Evidence for regional anesthesia in preventing chronic postsurgical pain.

Chronic postsurgical pain (CPSP) is a common adverse outcome following surgical procedures. Despite ongoing research, the risk factors and effective strategies for mitigating CPSP remain uncertain. Regional anesthesia is a potentially beneficial yet debated intervention for mitigating the risk of CPSP.

Extended Risankizumab Treatment in Patients With Crohn's Disease Who Did Not Achieve Clinical Response to Induction Treatment.

Background & Aims: The efficacy and safety of extended treatment with risankizumab (RZB), an anti-interleukin-23 p19 monoclonal antibody, were evaluated in patients with moderate to severe Crohn's disease (CD) who did not achieve clinical response to 12 weeks (W) RZB induction treatment ('initial nonresponders').

Methods: Initial nonresponders to intravenous (IV) RZB induction (600 mg or 1200 mg at W0, W4, and W8) were rerandomized 1:1:1 to receive extended blinded RZB treatment (1200 mg IV at W12, W16, and W20, or subcutaneous [SC] 180 mg or 360 mg at W12 and W20). Patients with clinical response to SC RZB at W24 ('delayed responders') continued their dose in FORTIFY.

Considerations for Anthropometry Specific to People with Disproportionate Short Stature.

In the clinical care of people with disproportionate short stature, healthcare practitioners need to accurately collect anthropometric measurements over time, including height, weight, head circumference, and lengths of affected limb and body segments. Accurate anthropometric measurements are important for diagnostic evaluation, tracking growth, measuring response to pharmacologic therapies or surgeries, and monitoring for potential complications. However, for this clinical population, anthropometric measurements may need to be adjusted or modified to accommodate characteristics such as body disproportions, joint contractures, long bone deformities, spinal deformities, or muscle hypotonia.

Combination therapy as a new standard of care in diabetic and non-diabetic chronic kidney disease.

Unlabelled: Combination therapy, involving the use of multiple medications together, is becoming a new standard of care for chronic kidney disease (CKD). For people with CKD, combination therapy offers the promise of preventing kidney failure and reducing the risk of heart problems. This approach is appealing because different drugs target distinct mechanisms involved in CKD progression.

Multimodality Therapy Including Pleurectomy/Decortication in Pleural Mesothelioma: Long-Term Outcomes in 152 Consecutive Patients A Retrospective Cohort Study.

Objective: Evaluate the long-term outcomes of pleurectomy decortication, systemic chemotherapy and prophylactic radiotherapy in pleural mesothelioma (PM).

Summary Background Data: There is no known cure for PM and cytoreductive surgery remains controversial.

Methods: Retrospective analysis of a cohort of patients treated consecutively between October 2004 and October 2019.

Implementation of prehospital point-of-care ultrasound using a novel continuous feedback approach in a UK helicopter emergency medical service.

Background: There has been increased use of prehospital point-of-care ultrasound (PoCUS) by helicopter emergency medical services (HEMS) in recent years. Lack of governance structure and evidence of benefit have been described as major barriers to its implementation. This paper describes a novel approach to implementation of prehospital PoCUS and clinical governance framework in a UK HEMS.

"The NET effect": Neutrophil extracellular traps-a potential key component of the dysregulated host immune response in sepsis.

Neutrophils release neutrophil extracellular traps (NETs) as part of a healthy host immune response. NETs physically trap and kill pathogens as well as activating and facilitating crosstalk between immune cells and complement. Excessive or inadequately resolved NETs are implicated in the underlying pathophysiology of sepsis and other inflammatory diseases, including amplification of the inflammatory response and inducing thrombotic complications.

Multiple states clustering analysis (MSCA), an unsupervised approach to multiple time-to-event electronic health records applied to multimorbidity associated with myocardial infarction.

Multimorbidity is characterized by the accrual of two or more long-term conditions (LTCs) in an individual. This state of health is increasingly prevalent and poses public health challenges. Adapting approaches to effectively analyse electronic health records is needed to better understand multimorbidity.

Autism common variants associated with white matter alterations at birth: cross-sectional fixel-based analyses of 221 European term-born neonates from the developing human connectome project.

Increasing lines of evidence suggest white matter (WM) structural changes associated with autism can be detected in the first year of life. Despite the condition having high heritability, the relationship between autism common genetic variants and WM changes during this period remains unclear. By employing advanced regional and whole-brain fixel-based analysis, the current study investigated the association between autism polygenic scores (PS) and WM microscopic fibre density and macrostructural morphology in 221 term-born infants of European ancestry from the developing Human Connectome Project.

An international survey of diffusion and perfusion magnetic resonance imaging implementation in the head and neck.

Objective: The goal of this international survey was to understand how diffusion (DWI) and perfusion imaging (PWI) are being applied to clinical head and neck imaging.

Methods And Materials: An online questionnaire focusing on acquisition, clinical indications, analysis, and reporting of qualitative DWI (QlDWI), quantitative DWI (QnDWI) and dynamic contrast-enhanced PWI (DCE-PWI) in the head and neck was circulated to members of the American Society of Head and Neck Radiology (ASHNR) and European Society of Head and Neck Radiology (ESHNR) over a 3-month period. Descriptive statistics and group comparisons were calculated with SPSS® v27.

Determinants of 5-year survival in patients with advanced NSCLC with PD-L1≥50% treated with first-line pembrolizumab outside of clinical trials: results from the Pembro-real 5Y global registry.

Background: Pembrolizumab monotherapy is an established front-line treatment for advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS)≥50%. However, real-world data on its long-term efficacy remains sparse.

Methods: This study assessed 5-year outcomes of first-line pembrolizumab monotherapy in a large, multicenter, real-world cohort of patients with advanced NSCLC and PD-L1 TPS≥50%, referred to as Pembro-real 5Y.

PLACE: Multicenter Study for Right Ventricular Failure on Mechanical Cardiocirculatory Supports.

Isolated acute right ventricular failure (aRVF) is associated with poor prognosis in different scenarios. In severe conditions, temporary mechanical cardiocirculatory support (tMCS) is required. PLACE is an international, retrospective, multicenter registry including 17 centers that investigated patients affected by isolated aRVF and treated with various types of tMCS from January 2000 to December 2020.

Increased NFAT and NFκB signalling contribute to the hyperinflammatory phenotype in response to Aspergillus fumigatus in a mouse model of cystic fibrosis.

Aspergillus fumigatus (Af) is a major mould pathogen found ubiquitously in the air. It commonly infects the airways of people with cystic fibrosis (CF) leading to Aspergillus bronchitis or allergic bronchopulmonary aspergillosis. Resident alveolar macrophages and recruited neutrophils are important first lines of defence for clearance of Af in the lung.

Switching from Dupilumab to Abrocitinib in Patients With Moderate-to-Severe Atopic Dermatitis: A Post Hoc Analysis of Efficacy After Treatment With Dupilumab in JADE DARE.

Introduction: Primary results of the JADE DARE trial (NCT04345367) demonstrated that abrocitinib was superior to dupilumab in reducing the signs and symptoms of moderate-to-severe atopic dermatitis (AD). This post hoc analysis evaluated the efficacy and safety of abrocitinib in patients with moderate-to-severe AD who were responders or nonresponders to dupilumab using various definitions of response.

Methods: Data included dupilumab-treated patients from JADE DARE who switched to abrocitinib 200 mg when enrolled in the ongoing JADE EXTEND trial (NCT03422822).

Long-Term Results of Treatment of Aortoiliac Occlusive Disease With the Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) Technique: A UK Multicenter Study.

Objective: This updated UK multicenter study aims to report long-term results following use of the Covered Endovascular Reconstruction of the Aortic Bifurcation (CERAB) technique for treating aortoiliac occlusive disease (AIOD) in patients with chronic limb-threatening ischemia (CLTI) or intermittent claudication (IC).

Methods: A retrospective analysis was conducted including 85 patients who underwent CERAB between November 1, 2012, and March 31, 2020, till March 2024. Anatomical data were assessed using pre-operative imaging.