Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observe comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identifies distinct non-small cell lung cancer-like (NSCLC-like, KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles.

Efficacy and Safety of Thrombolysis for Pediatric Venous Thromboembolism: A Systematic Review and Meta-analysis.

We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation versus anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in five population, intervention, comparison, outcomes (PICO) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals), and absolute effects per 1,000 patients.

American Society of Hematology/International Society on Thrombosis and Haemostasis 2024 updated guidelines for treatment of venous thromboembolism in pediatric patients.

Background: The American Society of Hematology (ASH) guidelines on treatment of pediatric venous thromboembolism (VTE) were published in 2018. In the last 6 years, there has been a 10-fold increase in the number of children involved in VTE treatment trials.

Objective: The ASH Committee on Quality and Guidelines agreed to update the pediatric guidelines in conjunction with the International Society on Thrombosis and Haemostasis (ISTH).

2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis.

Objective: The objective is to provide evidence-based and expert guidance for the screening, treatment, and management of lupus nephritis.

Methods: The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations.

2024 American College of Rheumatology (ACR) Guideline for the Screening, Treatment, and Management of Lupus Nephritis.

Objective: The objective is to provide evidence-based and expert guidance for the screening, treatment, and management of lupus nephritis.

Methods: The Core Team developed clinical questions for screening, treatment, and management of lupus nephritis using the PICO format (population, intervention, comparator, and outcome). Systematic literature reviews were completed for each PICO question, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was used to assess the quality of evidence and to formulate recommendations.

Risk of bias assessment tools often addressed items not related to risk of bias and used numerical scores.

Objectives: We aimed to determine whether the existing risk of bias assessment tools addressed constructs other than risk of bias or internal validity and whether they used numerical scores to express quality, which is discouraged and may be a misleading approach.

Methods: We searched Ovid MEDLINE and Embase to identify quality appraisal tools across all disciplines in human health research. Tools designed specifically to evaluate reporting quality were excluded.

Establishing Meaningful Patient-Centered Outcomes with Relevance for Patients with Polycystic Kidney Disease: Patient, Caregiver, and Researcher Priorities for Research in Polycystic Kidney Disease.

Key Points: Participants are less concerned about mortality than they are about kidney health. Psychological effect emerged as the most important theme regarding the effects of polycystic kidney disease on patients.

Background: Patient involvement in research can help to ensure that the evidence generated aligns with their needs and priorities.

Analysis of terminated pulmonary hypertension clinical trials. What are we doing wrong?

Despite significant interest in the diagnosis and treatment of pulmonary hypertension (PH) over the past two decades, there have been no notable advancements in reducing mortality. One contributing factor to this lack of progress is the insufficient number of well-designed and conducted trials. We aimed to evaluate factors associated with termination of PH clinical trials, to serve as a reference when designing future trials.