Leptomeningeal metastatic disease: new frontiers and future directions.

Leptomeningeal metastatic disease (LMD), encompassing entities of 'meningeal carcinomatosis', neoplastic meningitis' and 'leukaemic/lymphomatous meningitis', arises secondary to the metastatic dissemination of cancer cells from extracranial and certain intracranial malignancies into the leptomeninges and cerebrospinal fluid. The clinical burden of LMD has been increasing secondary to more sensitive diagnostics, aggressive local therapies for discrete brain metastases, and improved management of extracranial disease with targeted and immunotherapeutic agents, resulting in improved survival. However, owing to drug delivery challenges and the unique microenvironment of LMD, novel therapies against systemic disease have not yet translated into improved outcomes for these patients.

Biomarker-Guided Antibiotic Duration for Hospitalized Patients With Suspected Sepsis: The ADAPT-Sepsis Randomized Clinical Trial.

Importance: For hospitalized critically ill adults with suspected sepsis, procalcitonin (PCT) and C-reactive protein (CRP) monitoring protocols can guide the duration of antibiotic therapy, but the evidence of the effect and safety of these protocols remains uncertain.

Objective: To determine whether decisions based on assessment of CRP or PCT safely results in a reduction in the duration of antibiotic therapy.

Design, Setting, And Participants: A multicenter, intervention-concealed randomized clinical trial, involving 2760 adults (≥18 years), in 41 UK National Health Service (NHS) intensive care units, requiring critical care within 24 hours of initiating intravenous antibiotics for suspected sepsis and likely to continue antibiotics for at least 72 hours.

Factors Influencing Nerinetide Effect on Infarct Volume in Patients Without Alteplase in the Randomized ESCAPE-NA1 Trial.

Background: In the ESCAPE-NA1 trial (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischemic Stroke), treatment with nerinetide was associated with a smaller infarct volume among patients who did not receive intravenous alteplase. We assessed the effect of nerinetide on the surrogate imaging outcome of final infarct volume in patients who did not receive intravenous alteplase and explored predictors of outcome and modifiers of nerinetide's effect on infarct volume.

Methods: ESCAPE-NA1 was a multicenter, randomized trial in which patients with acute stroke with a baseline Alberta Stroke Program Early CT Score >4, undergoing endovascular thrombectomy, were randomized to receive intravenous nerinetide or placebo.

Prioritising domains of glucocorticoid therapy to measure in trials: Results from a modified delphi exercise from the OMERACT glucocorticoid impact working group.

Introduction: There is no consensus amongst patients and healthcare professionals about how to measure important adverse effects of glucocorticoids (GCs) that includes the patient's perspective. The OMERACT GC Impact working group sought to identify the domains of greatest importance to both patients and healthcare professionals for use in a proposed core outcome set.

Methods: Patients and healthcare professionals participated in a Delphi consensus exercise to rate the importance of previously identified candidate domains.

"It's put a routine and regimen in my life" - Participant experiences with a programme of community walking and home-based circuit training for intermittent claudication.

Introduction: The WALKSTRONG trial includes a programme of community walking and home-based circuit training which has been developed for people with intermittent claudication (IC). The aim of the present study was to determine the acceptability of the programme for those who took part, by gleaning their opinions and experiences.

Methods: All participants eligible for the WALKSTRONG trial were approached regarding completing a semi-structured interview, selected from three groups: A) programme completers, B) programme withdrawers and C) programme decliners.

Cost-effectiveness of a Low-cost Educational Messaging and Prescription-fill Reminder Intervention to Improve Medication Adherence Among Individuals With Intellectual and Developmental Disability and Hypertension.

Background: Adults with intellectual and developmental disabilities (IDDs) have a similar prevalence of hypertension as the general population, but a higher rate of medication nonadherence at 50% compared with the average of 30%.

Objectives: To assess the cost-effectiveness of educational messaging and prescription-fill reminders to adults with IDD and hypertension and their helpers among Medicaid members in a randomized control trial.

Research Design: The authors calculated net cost savings by subtracting per-participant intervention costs from differences in spending between preintervention/postintervention cases versus controls.

Real-world experience of galcanezumab in the prevention of migraine in Spain: a systematic literature review.

Introduction: In the context of migraine preventive therapy, new therapeutic modalities such as monoclonal antibodies targeting the calcitonin gene-related peptide receptor (CGRP) or ligand offer potential advantages over traditional preventive treatments.

Methods: This systematic literature review gathered recent real-world evidence from Spain on the use of galcanezumab, a CGRP-targeting treatment, in migraine patients. The review included observational studies in English or Spanish, published from August 2020 to August 2023, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and Cochrane guidelines.

Effects of Pancreatic Fistula After Minimally Invasive and Open Pancreatoduodenectomy.

Importance: Postoperative pancreatic fistulas (POPF) are the biggest contributor to surgical morbidity and mortality after pancreatoduodenectomy. The impact of POPF could be influenced by the surgical approach.

Objective: To assess the clinical impact of POPF in patients undergoing minimally invasive pancreatoduodenectomy (MIPD) and open pancreatoduodenectomy (OPD).

Integrating Out-of-Pocket Costs Into Shared Decision-Making for Heart Failure With Reduced Ejection Fraction: A Stepped-Wedge Trial (POCKET-COST-HF).

Background: Guideline-directed medical therapy for heart failure (HF) with reduced ejection fraction can entail high out-of-pocket (OOP) costs, prompting concerns about financial toxicity and access. OOP costs are generally unavailable during encounters. This trial assessed the impact of providing patient-specific OOP costs to patients and clinicians.

Design of an international, phase IV, open-label study of simoctocog alfa in women/girls with hemophilia A undergoing surgery (NuDIMENSION).

Background: Although hemophilia A mainly affects males, carriers (defined as females with hemophilia A, as well as symptomatic or asymptomatic hemophilia A carriers) are at risk of excessive bleeding, particularly during trauma or during surgical procedures. Clinical trials have focused on male patients with severe disease, and data for females are limited. Improved, evidence-based treatment guidelines for management of hemophilia A carriers are required.

COVID-19 clinical phenotypes in vaccinated and nonvaccinated solid organ transplant recipients: a multicenter validation study.

Clinical phenotypes of COVID-19, associated with mortality risk, have been identified in the general population. The present study assesses their applicability in solid organ transplant recipients (SOTR) hospital-admitted by COVID-19. In a cohort of 488 SOTR, nonvaccinated (n = 394) and vaccinated (n = 94) against SARS-CoV-2, we evaluated 16 demographic, clinical, analytical, and radiological variables to identify the clinical phenotypes A, B, and C.

Real-world efficacy of the dabrafenib-trametinib (D-T) combination in BRAF V600E-mutated metastatic non-small cell lung cancer (NSCLC): Results from the IFCT-2004 BLaDE cohort.

Background: BRAF V600E mutations occur in 2-5 % of advanced non-small cell lung cancer (NSCLC) patients. The dabrafenib-trametinib (D-T) combination was associated with improved and durable OS in patients in phase II. This study (IFCT-2004 BLaDE study) reported the efficacy of D-T combination in a large retrospective French real-world multicenter cohort of patients with advanced BRAF V600E-mutated NSCLC.

Efficacy of Computer-Aided Three-Dimensional Ultrasound Guidance for Neuraxial Anesthesia in Adult Patients: A Systematic Review and Meta-Analysis.

Artificial intelligence for ultrasound scanning in regional anesthesia is a rapidly developing interdisciplinary field. This study aimed to evaluate the efficacy of computer-aided three-dimensional ultrasound (C-aided US) guidance for neuraxial anesthesia in adult patients. We searched all randomized controlled trials (RCTs) of adult patients who required neuraxial anesthesia in the MEDLINE, CENTRAL, Embase, International Clinical Trials Registry Platform (ICTRP), and ClinicalTrials.

Cost-effectiveness of C-reactive protein point of care testing for safely reducing antibiotic consumption for acute exacerbations of chronic obstructive pulmonary disease as part of the multicentre, parallel-arm, open, individually randomised, controlled PACE trial.

Objectives: Many patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care do not benefit from antibiotics. Excessive use wastes resources, promotes antimicrobial resistance and can harm patients.

Design: We conducted a within-trial economic evaluation, using a UK National Health Service perspective, as part of the multicentre, parallel-arm, open, individually randomised, controlled PACE trial.

Impact of personalized response-directed surgery and adjuvant therapy on survival after neoadjuvant immunotherapy in stage III melanoma: Comparison of 3-year data from PRADO and OpACIN-neo.

Background: Pathologic response following neoadjuvant immune checkpoint blockade (ICB) in stage III melanoma serves as a surrogate marker for long-term outcomes. This may support more personalized, response-directed treatment strategies.

Methods: The OpACIN-neo and PRADO trials were phase 2 studies evaluating neoadjuvant treatment with ipilimumab and nivolumab in stage III melanoma.

Ravulizumab and Efgartigimod in Myasthenia Gravis: A Real-World Study.

Background And Objectives: Biologics that target pathogenic antibodies (Abs) and their effector functions such as the complement inhibitor ravulizumab and the neonatal Fc receptor agonist efgartigimod have recently been approved for the treatment of acetylcholine receptor (AChR)-Ab-positive myasthenia gravis (MG), but comparative studies are lacking.

Methods: In a prospective, exploratory real-world study, we assessed clinical efficacy, safety, and biological effects of ravulizumab and efgartigimod treatment initiation. Myasthenia Gravis-Activities of Daily Living and Quantitative Myasthenia Gravis scores were used as clinical endpoints.

Twice-Yearly Lenacapavir for HIV Prevention in Men and Gender-Diverse Persons.

Background: Twice-yearly subcutaneous lenacapavir has been shown to be efficacious for prevention of HIV infection in cisgender women. The efficacy of lenacapavir for preexposure prophylaxis (PrEP) in cisgender men, transgender women, transgender men, and gender-nonbinary persons is unclear.

Methods: In this phase 3, double-blind, randomized, active-controlled trial, we randomly assigned participants in a 2:1 ratio to receive subcutaneous lenacapavir every 26 weeks or daily oral emtricitabine-tenofovir disoproxil fumarate (F/TDF).