Olaparib as treatment for platinum-sensitive relapsed ovarian cancer by BRCA mutation and homologous recombination deficiency: Phase 2 LIGHT study final overall survival analysis.

Background: LIGHT (oLaparib In HRD-Grouped Tumor types; NCT02983799) prospectively evaluated olaparib treatment in patients with platinum-sensitive relapsed ovarian cancer (PSROC) assigned to cohorts by known BRCA mutation (BRCAm) and homologous recombination deficiency (HRD) status: germline BRCAm (gBRCAm), somatic BRCAm (sBRCAm), HRD-positive non-BRCAm, and HRD-negative. At the primary analysis, olaparib treatment demonstrated activity across all cohorts, with greatest efficacy in terms of objective response rate and progression-free survival observed in the g/sBRCAm cohorts. The authors report final overall survival (OS).

PREVENT and Pooled Cohort Equations in Mortality Risk Prediction: National Health and Nutrition Examination Survey.

Background: The Predicting Risk of CVD Events (PREVENT) equations were developed to address limitations of the Pooled Cohort Equations (PCEs) in predicting atherosclerotic cardiovascular disease (ASCVD) risk. The comparative effectiveness of the PREVENT equations versus the PCEs in predicting mortality risk remains unknown.

Objectives: The purpose of this study was to compare the risk discrimination value of the PREVENT equations with the PCEs for predicting mortality.

The potential role of tumor deposits in the prognosis and TNM staging for colorectal cancer.

Background: Tumor deposits (TDs) can impact proper staging of cancer, which is crucial for discussing prognosis and determining the appropriate treatment plan. Our study aimed to correlate how TDs influence prognosis of resected colorectal cancer (CRC) and how to optimize tumor-node-metastasis (TNM) staging with respect to TDs for clinical decision-making.

Methods: A retrospective analysis was performed on 611 patients with CRC treated in Jiangsu Cancer Hospital from January 1, 2010 to December 31, 2020 among whom 197 had TDs.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

GestaltGAN: synthetic photorealistic portraits of individuals with rare genetic disorders.

The facial gestalt (overall facial morphology) is a characteristic clinical feature in many genetic disorders that is often essential for suspecting and establishing a specific diagnosis. Therefore, publishing images of individuals affected by pathogenic variants in disease-associated genes has been an important part of scientific communication. Furthermore, medical imaging data is also crucial for teaching and training deep-learning models such as GestaltMatcher.

Initial Decline in Glomerular Filtration Rate With Finerenone in HFmrEF/HFpEF: A Prespecified Analysis of FINEARTS-HF.

Background: An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF).

Objectives: The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone.

Methods: In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo.

Navigating Children's Risky Play: A Comparative Analysis of Saudi Mothers and Fathers.

Despite documented benefits for development, children are engaging in considerably fewer risky play activities. Research on parent gender and children's risky play is inconsistent. Gender and cultural context shape how individuals perceive and tolerate children's risky play.

The Impact of Contemporary Glucagon-like Peptide-1 Receptor Agonists on the Onset, Severity, and Conversion to Arthroplasty in Hip and Knee Osteoarthritis.

Background: The growing popularity of glucagon-like peptide-1 receptor agonists (GLP-1-RAs) for weight loss could significantly impact joint preservation and arthroplasty. While this will in part be driven by the association between obesity, osteoarthritis (OA), and total joint arthroplasty (TJA), recent evidence also indicates that GLP-1-RAs may have direct joint-protective, anti-inflammatory effects.

Purpose: To evaluate the association between GLP-1-RA use and the onset and progression of hip and knee OA in an obese population.

Targeting mitophagy in neurodegenerative diseases.

Mitochondrial dysfunction is a hallmark of idiopathic neurodegenerative diseases, including Parkinson disease, amyotrophic lateral sclerosis, Alzheimer disease and Huntington disease. Familial forms of Parkinson disease and amyotrophic lateral sclerosis are often characterized by mutations in genes associated with mitophagy deficits. Therefore, enhancing the mitophagy pathway may represent a novel therapeutic approach to targeting an underlying pathogenic cause of neurodegenerative diseases, with the potential to deliver neuroprotection and disease modification, which is an important unmet need.

Healthcare burden of narcolepsy in Japan: A retrospective analysis of health insurance claims from the Japan Medical Data Center.

Background: Narcolepsy is a chronic disorder that requires lifelong management; however, few studies have evaluated disease burden of narcolepsy. We estimated the healthcare burden of narcolepsy in Japan using data from the Japan Medical Data Center health insurance claims database.

Methods: This was a retrospective analysis of clinical burden, healthcare resource utilization, and costs among incident narcolepsy cases and matched controls identified between January 1, 2014 and December 31, 2019.

Prevention of liver cancer in the era of next-generation antivirals and obesity epidemic.

Preventive interventions are expected to substantially improve the prognosis of patients with primary liver cancer, predominantly hepatocellular carcinoma (HCC) and cholangiocarcinoma. HCC prevention is challenging in the face of the evolving etiological landscape, particularly the sharp increase in obesity-associated metabolic disorders, including metabolic dysfunction-associated steatotic liver disease (MASLD). Next-generation anti-HCV and HBV drugs have substantially reduced, but not eliminated, the risk of HCC and have given way to new challenges in identifying at-risk patients.

Buparlisib and Paclitaxel in Patients with Head and Neck Squamous Cell Carcinoma: Immunogenomic Biomarkers of Efficacy from the BERIL-1 Study.

Background: BERIL-1 was a randomized phase 2 study that studied paclitaxel with either buparlisib, a pan-class I PIK3 inhibitor, or placebo in patients with recurrent or metastatic (R/M) head and neck squamous cell cancer (HNSCC). Considering the therapeutic paradigm shift with immune checkpoint inhibitors (ICIs) now approved in the first-line setting, we present an updated immunogenomic analysis of patients enrolled in BERIL-1, including patients with immune-infiltrated tumors.

Objective: The objective of this study was to identify biomarkers predictive of treatment efficacy in the context of the post-ICI therapeutic landscape.

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.

Ultrasensitive ctDNA detection for preoperative disease stratification in early-stage lung adenocarcinoma.

Circulating tumor DNA (ctDNA) detection can predict clinical risk in early-stage tumors. However, clinical applications are constrained by the sensitivity of clinically validated ctDNA detection approaches. NeXT Personal is a whole-genome-based, tumor-informed platform that has been analytically validated for ultrasensitive ctDNA detection at 1-3 ppm of ctDNA with 99.

Retinal vascular fingerprints predict incident stroke: findings from the UK Biobank cohort study.

Objective: To investigate the associations between a comprehensive set of retinal vascular parameters and incident stroke to unveil new associations and explore its predictive power for stroke risk.

Methods: Retinal vascular parameters were extracted from the UK Biobank fundus images using the Retina-based Microvascular Health Assessment System. We used Cox regression analysis, adjusted for traditional risk factors, to examine the associations, with false discovery rate adjustment for multiple comparisons.

Occult collision tumor of the gastroesophageal junction comprising adenocarcinomas with distinct molecular profiles.

Collision tumors, characterized by the coexistence of two unique neoplasms in close approximation, are rare and pose diagnostic challenges. This is particularly true when the unique neoplasms are of the same histologic type. Here we report such a case where comprehensive tumor profiling by next generation sequencing (NGS) as well as immunohistochemistry revealed two independent adenocarcinomas comprising what was initially diagnosed as a single adenocarcinoma of the gastroesophageal (GEJ) junction.

Management of a Muskellunge Fish Bite to the Thumb With Subsequent Flexor Tendon Laceration.

Despite frequent occurrences, especially throughout the Appalachian region, fish bite injuries remain largely underreported. Muskellunge anglers are at a particularly heightened risk due to the fish's large mouth and notably sharp teeth. We present a case of a male who sustained an injury to the right volar thumb following a muskellunge bite.

Early Change in C-Reactive Protein and Venous Thromboembolism in Patients Treated With Immune Checkpoint Inhibitors.

Background: Patients with cancer treated with immune-checkpoint inhibitors (ICIs) have a substantial risk of venous thromboembolism (VTE). The association between ICI-induced inflammation and hypercoagulability is unclear, and no biomarkers currently exist to stratify VTE risk.

Objectives: The authors sought to determine the association between the early changes in C-reactive protein (CRP) after ICI initiation and the risk of VTE.

Radiomics signature for dynamic monitoring of tumor inflamed microenvironment and immunotherapy response prediction.

Background: The efficacy of immune checkpoint inhibitors (ICIs) depends on the tumor immune microenvironment (TIME), with a preference for a T cell-inflamed TIME. However, challenges in tissue-based assessments via biopsies have triggered the exploration of non-invasive alternatives, such as radiomics, to comprehensively evaluate TIME across diverse cancers. To address these challenges, we develop an ICI response signature by integrating radiomics with T cell-inflamed gene-expression profiles.

Asian Thoracic Oncology Research Group expert consensus statement on the peri-operative management of non-small cell lung cancer.

The peri-operative management of non-small cell lung cancer (NSCLC) in earlier stage disease has seen significant advances in recent years with the incorporation of immune checkpoint inhibitors and targeted therapy. However, many unanswered questions and challenges remain, including the application of clinical trial data to routine clinical practice. Recognising the unique demographic profile of Asian patients with NSCLC and heterogeneous healthcare systems, the Asian Thoracic Oncology Research Group (ATORG) convened a consensus meeting in Singapore on 26 April 2024 to discuss relevant issues spanning diagnostic testing to post-neoadjuvant treatment considerations and future directions.

Durvalumab with or without bevacizumab with transarterial chemoembolisation in hepatocellular carcinoma (EMERALD-1): a multiregional, randomised, double-blind, placebo-controlled, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard of care for patients with unresectable hepatocellular carcinoma that is amenable to embolisation; however, median progression-free survival is still approximately 7 months. We aimed to assess whether adding durvalumab, with or without bevacizumab, might improve progression-free survival.

Methods: In this multiregional, randomised, double-blind, placebo-controlled, phase 3 study (EMERALD-1), adults aged 18 years or older with unresectable hepatocellular carcinoma amenable to embolisation, an Eastern Cooperative Oncology Group performance status of 0 or 1 at enrolment, and at least one measurable intrahepatic lesion per modified Response Evaluation Criteria in Solid Tumours (RECIST) were enrolled at 157 medical sites including research centres and general and specialist hospitals in 18 countries.

Cemiplimab in recurrent cervical cancer: Final analysis of overall survival in the phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial.

Aim: Cemiplimab has demonstrated significantly longer survival than physician's choice of chemotherapy in patients with recurrent cervical cancer after first-line platinum-containing chemotherapy. We report the final survival analysis from the phase III randomized study (EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9).

Methods: Cemiplimab (n = 304) or chemotherapy (n = 304) were administered every 3 weeks.