Ocrelizumab dose selection for treatment of pediatric relapsing-remitting multiple sclerosis: results of the OPERETTA I study.

Background: The presented study identified the appropriate ocrelizumab dosing regimen for patients with pediatric-onset multiple sclerosis (POMS).

Methods: Patients with POMS aged 10-17 years were enrolled into cohort 1 (body weight [BW] < 40 kg, ocrelizumab 300 mg) and cohort 2 (BW ≥ 40 kg, ocrelizumab 600 mg) during a 24-week dose-exploration period (DEP), followed by an optional ocrelizumab (given every 24 weeks) extension period.

Primary Endpoints: pharmacokinetics, pharmacodynamics (CD19 B-cell count); secondary endpoint: safety; exploratory endpoints: MRI activity, protocol-defined relapses, Expanded Disability Status Scale (EDSS) score change.

Predicting Alzheimer's disease subtypes and understanding their molecular characteristics in living patients with transcriptomic trajectory profiling.

Introduction: Deciphering the diverse molecular mechanisms in living Alzheimer's disease (AD) patients is a big challenge but is pivotal for disease prognosis and precision medicine development.

Methods: Utilizing an optimal transport approach, we conducted graph-based mapping of transcriptomic profiles to transfer AD subtype labels from ROSMAP monocyte samples to ADNI and ANMerge peripheral blood mononuclear cells. Subsequently, differential expression followed by comparative pathway and diffusion pseudotime analysis were applied to each cohort to infer the progression trajectories.

Current landscape and future prospects of interleukin-2 receptor (IL-2R) agonists in cancer immunotherapy.

Immune checkpoint blockade (ICB) has significantly improved the survival for many patients with advanced malignancy. However, fewer than 50% of patients benefit from ICB, highlighting the need for more effective immunotherapy options. High-dose interleukin-2 (HD IL-2) immunotherapy, which is approved for patients with metastatic melanoma and renal cell carcinoma, stimulates CD8 T cells and NK cells and can generate durable responses in a subset of patients.

Identifying cognitive test scores associated with early tau burden in Alzheimer's disease.

Introduction: This study aimed to identify cognitive tests that optimally relate to tau positron emission tomography (PET) signal in the inferior temporal cortex (ITC), a neocortical region associated with early tau accumulation in Alzheimer's disease (AD).

Methods: We analyzed cross-sectional data from the harvard aging brain study (HABS) (= 128) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study (= 393). We used elastic net regression to identify the most robust cognitive correlates of tau PET signal in the ITC.

CD137 agonism enhances anti-PD1 induced activation of expanded CD8 T cell clones in a neoadjuvant pancreatic cancer clinical trial.

Successful pancreatic ductal adenocarcinoma (PDAC) immunotherapy requires therapeutic combinations that induce quality T cells. Tumor microenvironment (TME) analysis following therapeutic interventions can identify response mechanisms, informing design of effective combinations. We provide a reference single-cell dataset from tumor-infiltrating leukocytes (TILs) from a human neoadjuvant clinical trial comparing the granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting allogeneic PDAC vaccine GVAX alone, in combination with anti-PD1 or with both anti-PD1 and CD137 agonist.

Reversal of inflammatory reprogramming by vasodilator agents in pulmonary hypertension.

Background: Pulmonary arterial hypertension (PAH) is a deadly disease without effective non-invasive diagnostic and prognostic testing. It remains unclear whether vasodilators reverse inflammatory activation, a part of PAH pathogenesis. Single-cell profiling of inflammatory cells in blood could clarify these PAH mechanisms.

Real-World Outcomes in Patients with Advanced Penile Squamous Cell Carcinoma Receiving Immune Checkpoint Inhibitors: A Single Institution Experience.

Introduction: Advanced penile squamous cell carcinoma (pSCC) is a rare and aggressive malignancy with a poor prognosis and an unmet need for biomarkers. We performed a retrospective evaluation of real-world efficacy, safety outcomes, and baseline inflammatory biomarkers in patients with advanced pSCC treated with immune checkpoint inhibitors (ICIs).

Methods: We performed a retrospective review of patients with advanced pSCC who received ICIs from 2012 to 2023 at the Winship Cancer Institute of Emory University in Atlanta, GA.

Patient-reported outcome measures for life participation in patients with chronic kidney disease: a systematic review.

Background: The symptoms, comorbidities and treatment burden associated with chronic kidney disease (CKD) can be debilitating and limit life participation in patients with CKD not requiring kidney replacement therapy (KRT). The aim of this study was to identify the characteristics, content and psychometric properties of patient-reported outcome measures (PROMs) used to assess life participation in patients with CKD.

Methods: We searched MEDLINE, Embase, PsycINFO and CINAHL from database inception to February 2023 for all studies that reported life participation in patients with CKD (stages 1-5 not requiring kidney replacement therapy).

Patterns of incident Burkitt lymphoma during the HIV epidemic among the Black African and White population in South Africa.

Background: Burkitt lymphoma (BL) may be HIV-associated but data on BL trends in South Africa (SA), where HIV is highly prevalent, are scarce. We compared BL incidence trends over 36 years among Black African and White individuals.

Methods: We included histologically diagnosed BL from the National Cancer Registry in SA between 1986-2021.

Randomized clinical trial of a digital integrative medicine intervention among patients undergoing active cancer treatment.

Exercise and mindfulness-based interventions have growing evidence for managing fatigue and comorbid symptoms; however, packaging them in a cohesive digital way for patients undergoing cancer treatment has not been evaluated. We conducted a randomized controlled trial to assess the impact of a 12 week digital integrative medicine program, Integrative Medicine at Home (IM@Home), versus enhanced usual care on fatigue severity (primary outcome), comorbid symptoms and acute healthcare utilization (secondary outcomes), in 200 patients with solid tumors experiencing fatigue during treatment. Fatigue severity decreased more in IM@Home than in the control (1.

Awakening not associated with an increased rate of cortisol secretion.

Cortisol is released upon activation of the hypothalamic-pituitary-adrenal axis, varies across the day, possesses an underlying diurnal rhythm and is responsive to stressors. The endogenous circadian peak of cortisol occurs in the morning, and increases in cortisol observed post-awakening have been named the cortisol awakening response (CAR) based on the belief that the act of waking up stimulates cortisol secretion. However, objective evidence that awakening induces cortisol secretion is limited.

The effect of a brief intervention video on gambling advertising resistance: Results of a randomized, on-line experimental study.

Background And Aims: Gambling advertising is nowadays prevalent in multiple jurisdictions and can take multiple forms, such as TV adverts and social media promotions. However, few independently designed interventions for gambling advertising have been empirically tested. We aimed to measure the effectiveness of an inoculative intervention video for gambling advertising, which was developed based on previous interventions for alcohol and tobacco, and which used input from academics and experts by experience.

Look-alike modelling in violence-related research: A missing data approach.

Violence has been analysed in silo due to difficulties in accessing data and concerns for the safety of those exposed. While there is some literature on violence and its associations using individual datasets, analyses using combined sources of data are very limited. Ideally data from the same individuals would enable linkage and a longitudinal understanding of experiences of violence and their (health) impacts and consequences.

Electronic Patient-Reported Outcome System Implementation in Outpatient Cardiovascular Care: A Randomized Clinical Trial.

Importance: The integration of patient-reported outcome (PRO) assessments in cardiovascular care has encountered considerable obstacles despite their established clinical relevance.

Objective: To assess the impact of a physician- and patient-friendly electronic PRO (ePRO) monitoring system on the quality of cardiovascular care in clinical practice.

Design, Setting, And Participants: This open-label, multicenter, pilot randomized clinical trial was phase 2 of a multiphase study that was conducted from October 2022 to October 2023 and focused on the implementation and evaluation of an ePRO monitoring system in outpatient clinics in Japan.

Prognostic significance of immune reconstitution following CD19 CAR T-cell therapy for relapsed/refractory B-cell lymphoma.

Immune deficits after CD19 chimeric antigen receptor (CAR) T-cell therapy can be long-lasting, predisposing patients to infections and non-relapse mortality. In B-cell non-Hodgkin lymphoma (B-NHL), the prognostic impact of immune reconstitution (IR) remains ill-defined, and detailed cross-product comparisons have not been performed to date. In this retrospective observational study, we longitudinally characterized lymphocyte subsets and immunoglobulin levels in 105 B-NHL patients to assess patterns of immune recovery arising after CD19 CAR-T.

Impact of alternative diagnostic labels for melanoma in situ on management choices and psychological outcomes: protocol for an online randomised study.

Introduction: A diagnosis of melanoma in situ presents negligible risk to a person's lifespan or physical well-being, but existing terminology makes it difficult for patients to distinguish these from higher risk invasive melanomas. This study aims to explore whether using an alternative label for melanoma in situ may influence patients' management choices and anxiety levels.

Methods And Analysis: This study is a between-subjects randomised online experiment, using hypothetical scenarios.

Modified Delphi expert elicitation of the clinical and economic burden of obstructive hypertrophic cardiomyopathy in England and Northern Ireland.

Objective: To estimate the resource use of patients with obstructive hypertrophic cardiomyopathy (HCM), stratified by New York Heart Association (NYHA) class, in the English and Northern Irish healthcare systems via expert elicitation.

Design: Modified Delphi framework methodology.

Setting: UK HCM secondary care centres (n=24).

Echocardiographic phenotypes of diabetic myocardial disorder: evolution over 15 months follow-up in the ARISE-HF trial.

Background: Diabetic myocardial disorder (DbMD, evidenced by abnormal echocardiography or cardiac biomarkers) is a form of stage B heart failure (SBHF) at high risk for progression to overt HF. SBHF is defined by abnormal LV morphology and function and/or abnormal cardiac biomarker concentrations.

Objective: To compare the evolution of four DbMD groups based on biomarkers alone, systolic and diastolic dysfunction alone, or their combination.

Using group model building to frame the commercial determinants of dietary behaviour in adolescence - findings from online system mapping workshops with adolescents, policymakers and public health practitioners in the Southwest of England.

Background: In England, 23% of children aged 11 start their teenage years living with obesity. An adolescent living with obesity is five times more likely to live with obesity in adult life. There is limited research and policy incorporating adolescents' views on how they experience the commercial determinants of dietary behaviour and obesity, which misses an opportunity to improve services and policies that aim to influence the prevalence of childhood obesity.

Dietary-Lifestyle Patterns and Colorectal Cancer Risk: Global Cancer Update Programme (CUP Global) Systematic Literature Review.

Background: While healthy dietary and lifestyle factors have been individually linked to lower colorectal cancer (CRC) risks, recommendations for whole diet-lifestyle patterns remained unestablished due to limited studies and inconsistent pattern definitions.

Objective: This updated review synthesized literature on dietary-lifestyle patterns and CRC risk/mortality.

Methods: PubMed and Embase were searched through 31 March 2023 for randomized controlled trials and prospective cohort studies examining adulthood dietary patterns combined with modifiable lifestyle factors such as adiposity, smoking, alcohol consumption, physical activity, and/or others.

Investigating eating architecture and the impact of the precision of recorded eating time: a cross-sectional study.

Background: The precision of recorded eating times directly affects the estimation of eating architecture i.e. size, timing, and frequency of eating.

Frailism: a scoping review exploring discrimination against people living with frailty.

People living with frailty can experience discrimination, but unlike the characteristics of age and disability, frailty is not protected by law. Frailty is a clinical syndrome associated with ageing in which health deficits increase a person's vulnerability to illness, disability, and death. This scoping review, conducted by a team of methodologists, clinicians, lawyers, and patients, aimed to investigate the extent of discrimination against people living with frailty described in health-care literature.

Ramadan intermittent fasting for patients with gastrointestinal and hepatobiliary diseases: practical guidance for health-care professionals.

Ramadan intermittent fasting can pose challenges and risks for some groups of patients. Based on a narrative literature review and our clinical expertise, we provide practical guidance for clinicians managing patients with gastrointestinal and hepatobiliary conditions who wish to fast during Ramadan. Following the established International Diabetes Federation and Diabetes and Ramadan International Alliance risk stratification framework, we categorised patients' risk as low or moderate, high, or very high.

"It's OK for Me to Cry": Client and Therapist Perspectives on Change Processes in SPEAKS Therapy for Anorexia Nervosa.

Introduction And Aims: Existing therapies for Anorexia Nervosa (AN) have limited effectiveness, necessitating the development of novel therapies and interventions. Hypothesizing and targeting clear mechanisms of change within treatment offer potential opportunities to improve them. The SPEAKS program aimed to develop, trial, and evaluate a therapy which targets key emotional and social factors known to be relevant in the development and maintenance of AN.

PARADIGM-PV: a randomized, multicenter phase 4 study to assess the efficacy and safety of ropeginterferon alfa-2b in patients with low- or high-risk polycythemia vera.

Polycythemia vera (PV) is characterized by clonal hematopoietic stem or progenitor cells with constitutively active somatic mutation(s) in the Janus kinase 2 gene. Phlebotomy (Phl) and aspirin are often used alone for low-risk PV patients. However, data from the Low-PV study demonstrated that Phl and aspirin may not be adequate for patients.