Unsupervised deep learning of electrocardiograms enables scalable human disease profiling.

The 12-lead electrocardiogram (ECG) is inexpensive and widely available. Whether conditions across the human disease landscape can be detected using the ECG is unclear. We developed a deep learning denoising autoencoder and systematically evaluated associations between ECG encodings and ~1,600 Phecode-based diseases in three datasets separate from model development, and meta-analyzed the results.

Comprehensive analysis of targetable mutations and tumor microenvironment in urachal cancer.

Urachal cancer, a rare malignancy, generally presents in the clinical setting with advanced stages of disease. Systemic treatment with chemotherapy is generally utilized in this setting. However, there remains a paucity of data on the effectiveness of immune checkpoint inhibitors or targeted therapies for urachal cancer.

Identification of cardiac wall motion abnormalities in diverse populations by deep learning of the electrocardiogram.

Cardiac wall motion abnormalities (WMA) are strong predictors of mortality, but current screening methods using Q waves from electrocardiograms (ECGs) have limited accuracy and vary across racial and ethnic groups. This study aimed to identify novel ECG features using deep learning to enhance WMA detection, referencing echocardiography as the gold standard. We collected ECG and echocardiogram data from 35,210 patients in California and labeled WMA using unstructured language parsing of echocardiographic reports.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Multiple Myeloma Previously Treated With Lenalidomide and an Anti-CD38 Monoclonal Antibody.

Background: This analysis explored real-world characteristics, treatment patterns and clinical outcomes in patients with relapsed or refractory multiple myeloma (RRMM) previously treated with lenalidomide and an anti-CD38 monoclonal antibody (mAb) and requiring subsequent treatment.

Materials And Methods: The PREAMBLE and Connect MM prospective registries of patients with multiple myeloma (MM), and the US nationwide Flatiron Health electronic health record-derived de-identified database were analysed. MM-specific treatment patterns (prior/index therapies) and outcomes (progression-free survival [PFS]/overall survival [OS]) were assessed.

Axial spondyloarthritis.

Axial spondyloarthritis manifests as a chronic inflammatory disease primarily affecting the sacroiliac joints and spine. Although chronic back pain and spinal stiffness are typical initial symptoms, peripheral (ie, enthesitis, arthritis, and dactylitis) and extra-musculoskeletal (ie, uveitis, inflammatory bowel disease, and psoriasis) manifestations are also common. Timely and accurate diagnosis is challenging and relies on identifying a clinical pattern with a combination of clinical, laboratory (HLA-B27 positivity), and imaging findings (eg, structural damage on pelvic radiographs and bone marrow oedema on MRI of the sacroiliac joints).

Efficacy, safety, and target engagement of dazukibart, an IFNβ specific monoclonal antibody, in adults with dermatomyositis: a multicentre, double-blind, randomised, placebo-controlled, phase 2 trial.

Background: Dermatomyositis is a chronic autoimmune disease with distinctive cutaneous eruptions and muscle weakness, and the pathophysiology is characterised by type I interferon (IFN) dysregulation. This study aims to assess the efficacy, safety, and target engagement of dazukibart, a potent, selective, humanised IgG1 neutralising monoclonal antibody directed against IFNβ, in adults with moderate-to-severe dermatomyositis.

Methods: This multicentre, double-blind, randomised, placebo-controlled, phase 2 trial was conducted at 25 university-based hospitals and outpatient sites in Germany, Hungary, Poland, Spain, and the USA.

Induced pluripotent stem-cell-derived CD19-directed chimeric antigen receptor natural killer cells in B-cell lymphoma: a phase 1, first-in-human trial.

Background: FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab.

Constitutive surface expression of the thromboxane A2 receptor is Pim kinase-dependent.

Background: The thromboxane A2 receptor (TPαR) plays an important role in the amplification of platelet responses during thrombosis. Receptor activity is regulated by internalization and receptor desensitization. The mechanism by which constitutive surface expression of the TPαR is regulated is unknown.

AZD2693, a PNPLA3 antisense oligonucleotide, for the treatment of MASH in 148M homozygous participants: two randomized phase I trials.

Background & Aims: A common genetic variant (rs738409) encoding isoleucine to methionine at position 148 in the PNPLA3 protein is a determinant of hepatic steatosis, inflammation, fibrosis, cirrhosis, and liver-related mortality. AZD2693 is a liver-targeted antisense oligonucleotide against PNPLA3 mRNA. We evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics in single ascending dose (SAD) and multiple ascending dose (MAD) studies.

Procalcitonin-guided duration of antibiotic treatment in children hospitalised with confirmed or suspected bacterial infection in the UK (BATCH): a pragmatic, multicentre, open-label, two-arm, individually randomised, controlled trial.

Background: Procalcitonin is a rapid response biomarker specific for bacterial infection, which is not routinely used in the UK National Health Service. We aimed to assess whether using a procalcitonin-guided algorithm would safely reduce the duration of antibiotic therapy compared with usual care, in which C-reactive protein is the commonly used biomarker.

Methods: The BATCH trial was a pragmatic, multicentre, open-label, parallel, two-arm, individually randomised, controlled trial conducted in 15 hospitals in England and Wales.

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.

Transarterial chemoembolisation combined with lenvatinib plus pembrolizumab versus dual placebo for unresectable, non-metastatic hepatocellular carcinoma (LEAP-012): a multicentre, randomised, double-blind, phase 3 study.

Background: Transarterial chemoembolisation (TACE) is standard care for unresectable, non-metastatic hepatocellular carcinoma. We aimed to evaluate the addition of lenvatinib and pembrolizumab to TACE versus dual placebo plus TACE in patients with unresectable, non-metastatic hepatocellular carcinoma.

Methods: In this multicentre, randomised, double-blind, phase 3 study (LEAP-012), patients were recruited from 137 global sites in 33 countries or regions.

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.

Nivolumab combination therapies in patients with advanced gastric and gastroesophageal junction cancer: the phase II FRACTION gastric cancer study.

Background: Nivolumab-based therapies are efficacious with acceptable safety in patients with gastric cancer (GC) and gastroesophageal junction cancer (GEJC). Novel nivolumab-based combination immunotherapies may offer enhanced efficacy in these indications. FRACTION-GC was a signal-seeking, randomized, open-label, phase II adaptive-design trial assessing efficacy and safety of nivolumab in combination with ipilimumab [cytotoxic T lymphocyte antigen-4 (CTLA-4) antibody], relatlimab (lymphocyte-activation gene 3 antibody), or IDO1i (BMS986205, an indoleamine-2,3-dioxygenase-1 inhibitor) in patients with unresectable, advanced/metastatic GC/GEJC.

Clinical Outcomes With Immune Checkpoint Inhibitors in Patients With FGFR2/3, MTAP or ERBB2 Genomic Alterations in Advanced Urothelial Carcinoma.

Background: FGFR2/3, MTAP and ERBB2 genomic alterations have treatment targets in advanced urothelial carcinoma (aUC). These alterations may affect tumor microenvironment and outcomes with immune checkpoint inhibitors (ICIs) in aUC.

Patients And Methods: We identified patients with available genomic data in our multi-institution cohort of patients with aUC treated with ICI.

Classification of α-thalassemia data using machine learning models.

Background: Around 7% of the global population has congenital hemoglobin disorders, with over 300,000 new cases of α-thalassemia annually. Diagnosis is costly and inaccurate in low-income regions, often relying on complete blood count (CBC) tests. This study employs machine learning (ML) to classify α-thalassemia traits based on gender and CBC, exploring the effects of grouping silent- and non-carriers.

Phase-specific changes in hip joint loading during gait following sacroiliac joint fusion: Findings from a finite element analysis.

Background: Low back pain affects over 80 % of adults, with sacroiliac joint dysfunction accounting for 15-30 % of these cases. Sacroiliac fusion is a surgical procedure for refractory joint pain. While the biomechanics of the joint and its fusion relative to the spinal column are well-known, the hip-spine relationship post-fusion remains unclear.

A Phase 2b, multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of intravenous prasinezumab in early-stage Parkinson's disease (PADOVA): Rationale, design, and baseline data.

Introduction: Prasinezumab was shown to potentially delay motor progression in individuals with early-stage Parkinson's disease (PD) who were either treatment-naïve or on monoamine oxidase type B inhibitor (MAO-Bi) therapy in the PASADENA study. We report the rationale, design, and baseline patient characteristics of the PADOVA study, designed to evaluate prasinezumab in an early-stage PD population receiving standard-of-care (SOC) symptomatic medications.

Methods: PADOVA (NCT04777331) is a Phase 2b, multicenter, randomized, double-blind, placebo-controlled, parallel-group study, in which individuals with early-stage PD on SOC stable symptomatic monotherapy (levodopa or MAO-Bi) receive intravenous prasinezumab 1500 mg every 4 weeks.

Accelerative Effects of Transcutaneous Electrical Acustimulation on Postoperative Recovery After Thoracolumbar Vertebral Fracture Associated With Suppressed Sympathetic Activity and Interleukin-6.

Objectives: Gastrointestinal (GI) disturbance is a frequent complication in patients with thoracolumbar vertebral fracture (TVF). Transcutaneous electrical acustimulation (TEA) has been reported to effectively accelerate postoperative GI function recovery after abdominal surgery. This study aimed to investigate the effects of TEA on postoperative recovery and the associated mechanisms.

The Society of Thoracic Surgeons (STS) Clinical Practice Guideline on Surgical Management of Oligometastatic Non-small Cell Lung Cancer.

Background: The use of local consolidative therapy (LCT) in patients with oligometastatic non-small cell lung cancer (NSCLC) is rapidly evolving, with a preponderance of data supporting the benefits of such therapeutic approaches incorporating pulmonary resection for appropriately selected candidates. However, practices vary widely institutionally and regionally, and evidence-based guidelines are lacking.

Methods: The Society of Thoracic Surgeons assembled a panel of thoracic surgical oncologists to evaluate and synthesize the available evidence regarding the role of pulmonary resection as LCT.

Variations in Revascularization Strategies for Chronic Limb-Threatening Ischemia: A Nationwide Analysis of Medicare Beneficiaries.

Background: Recent data support both surgical-first and endovascular-first revascularization approaches for chronic limb-threatening ischemia (CLTI), but hospital-based practices are poorly described.

Objectives: This aim of this study was to characterize contemporary variations and outcomes associated with each strategy among U.S.

Evaporation Kinetics and Final Particle Morphology of Multicomponent Salt Solution Droplets.

In both nature and industry, aerosol droplets contain complex mixtures of solutes, which in many cases include multiple inorganic components. Understanding the drying kinetics of these droplets and the impact on resultant particle morphology is essential for a variety of applications including improving inhalable drugs, mitigating disease transmission, and developing more accurate climate models. However, the previous literature has only focused on the relationship between drying kinetics and particle morphology for aerosol droplets containing a single nonvolatile component.

Optimising fatigue, abdominal pain and faecal incontinence in people with inflammatory bowel disease (IBD-BOOST Optimise): feasibility study of a checklist and algorithm for initial nurse-led management.

Objective: Many people with inflammatory bowel disease (IBD) experience fatigue, pain and faecal incontinence that some feel are inadequately addressed. It is unknown how many have potentially reversible medical issues underlying these symptoms.

Methods: We conducted a study testing the feasibility of a patient-reported symptom checklist and nurse-administered management algorithm ('Optimise') to manage common medical causes of IBD-related fatigue, pain and faecal incontinence.