Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial.

Background: Locally advanced cervical cancer is treated with chemoradiotherapy (standard of care), but many patients still relapse and die from metastatic disease. We investigated chemoradiotherapy with or without induction chemotherapy to determine whether induction chemotherapy improves both progression-free survival and overall survival.

Methods: The INTERLACE trial was a multicentre, randomised phase 3 trial done at 32 medical centres in Brazil, India, Italy, Mexico, and the UK.

Vaccines against mpox: MVA-BN and LC16m8.

Introduction: Global outbreaks involving mpox clade IIb began in mid-2022. Today, clade IIb and clade I outbreaks continue. Reliable mpox vaccines can prevent serious mpox disease and death.

Preclinical efficacy and pharmacokinetics of an RNA-encoded T cell-engaging bispecific antibody targeting human claudin 6.

We present the preclinical pharmacology of BNT142, a lipid nanoparticle (LNP)-formulated RNA (RNA-LNP) encoding a T cell-engaging bispecific antibody that monovalently binds the T cell marker CD3 and bivalently binds claudin 6 (CLDN6), an oncofetal antigen that is absent from normal adult tissue but expressed on various solid tumors. Upon BNT142 RNA-LNP delivery in cell culture, mice, and cynomolgus monkeys, RNA is translated, followed by self-assembly into and secretion of the functional bispecific antibody RiboMab02.1.

The Use of Methylene Blue in Conjunction With Hydroxocobalamin and Multiple Pressors to Treat Severe Vasoplegia in a Patient Due to Calcium Channel Blocker Toxicity: A Case Report.

Vasoplegia, the demonstration of persistently low systemic vascular resistance (SVR) and resistant hypotension in the presence of a normal cardiac index despite aggressive resuscitation attempts, is a serious clinical diagnosis that requires prompt treatment to prevent patient morbidity and mortality. Currently, treatment of vasoplegia involves treatment with vasopressors such as vasopressin, norepinephrine, and hydroxocobalamin. However, some evidence suggests that in addition to this treatment regimen, the addition of methylene blue may result in a reduction in overall norepinephrine equivalent vasopressor requirements, increased mean arterial pressure, and an improved clinical course.

Defining Transcriptomic Heterogeneity between Left and Right Ventricle-Derived Cardiac Fibroblasts.

Cardiac fibrosis is a key aspect of heart failure, leading to reduced ventricular compliance and impaired electrical conduction in the myocardium. Various pathophysiologic conditions can lead to fibrosis in the left ventricle (LV) and/or right ventricle (RV). Despite growing evidence to support the transcriptomic heterogeneity of cardiac fibroblasts (CFs) in healthy and diseased states, there have been no direct comparisons of CFs in the LV and RV.

The Development of Fat Embolism Syndrome (FES) and Multiple Small Pulmonary Emboli Following Open Reduction Internal Fixation (ORIF) of a Left Femur Fracture: A Case Report.

Fat embolism syndrome (FES) is a rare but potentially life-threatening complication that can occur following orthopedic procedures, such as long bone fracture repairs. FES is caused by the release of fat globules into the bloodstream, leading to the obstruction of blood vessels and subsequent tissue damage. Pulmonary embolism (PE), a condition in which a blood clot travels to the lungs, is another potential complication of orthopedic procedures due to the mobilization of blood clots during surgery.

Is cardioplegia system pressure the optimal measure of coronary perfusion during antegrade cardioplegia delivery? A critical review of pressure measurements for optimal antegrade delivery.

Antegrade cardioplegia is routinely given during cardiac surgery. The delivery of antegrade cardioplegia from the cardiopulmonary bypass machine has many variables. Many perfusionists rely exclusively on cardioplegia system pressure to ensure safe antegrade delivery.

Co-Expression of an IL-15 Superagonist Facilitates Self-Enrichment of GD-Targeted CAR-NK Cells and Mediates Potent Cell Killing in the Absence of IL-2.

In contrast to T lymphocytes, natural killer (NK) cells do not require prior sensitization but are rapidly activated upon encountering virally infected or neoplastic cells. In addition, NK cells can be safely applied in an allogeneic setting, making them important effector cells for the development of off-the-shelf therapeutics for adoptive cancer immunotherapy. To further enhance their therapeutic potential, here, we engineered continuously expanding NK-92 cells as a clinically relevant model to express a humanized second-generation chimeric antigen receptor (CAR) with a composite CD28-CD3ζ signaling domain (hu14.

Use of novel artificial intelligence computer-assisted detection (AI-CAD) for screening mammography: an analysis of 17,884 consecutive two-view full-field digital mammography screening exams.

Background: Novel artificial intelligence computer-assisted detection (AI-CAD) systems based on deep learning (DL) promise to support screen reading.

Purpose: To test a DL-AI-CAD system compared to human reading on consecutive screening mammograms.

Material And Methods: In this retrospective study, 17,884 consecutive anonymized screening mammograms, double-read from January to November 2018, were processed by the DL-AI-CAD system.

Genotyping and population characteristics of the China Kadoorie Biobank.

The China Kadoorie Biobank (CKB) is a population-based prospective cohort of >512,000 adults recruited from 2004 to 2008 from 10 geographically diverse regions across China. Detailed data from questionnaires and physical measurements were collected at baseline, with additional measurements at three resurveys involving ∼5% of surviving participants. Analyses of genome-wide genotyping, for >100,000 participants using custom-designed Axiom arrays, reveal extensive relatedness, recent consanguinity, and signatures reflecting large-scale population movements from recent Chinese history.

Benefit-risk assessment of vaccines.

Benefit-risk assessment (BRA) is critical for decision-making throughout the vaccine life cycle. It requires scientific assessment of evidence to make an informed judgment on whether the vaccine has a favourable benefit-risk profile i.e.

Prevalence and clinical characteristics of non-malignant CT detected incidental findings in the SUMMIT lung cancer screening cohort.

Background: Pulmonary and extrapulmonary incidental findings are frequently identified on CT scans performed for lung cancer screening. Uncertainty regarding their clinical significance and how and when such findings should be reported back to clinicians and participants persists. We examined the prevalence of non-malignant incidental findings within a lung cancer screening cohort and investigated the morbidity and relevant risk factors associated with incidental findings.

Considerations for unblinding individual study participants during vaccine trials.

Premature unblinding of individual participants is rarely reported in publications, but such unblinding can disrupt vaccine trials by causing worry and drop-out of other participants or "pseudo unblinding," in which participants or investigators over-interpret certain symptoms as being related to receiving an investigational product. This review summarizes appropriate reasons for unblinding in vaccine trials. Regulatory guidance could be improved by distinguishing guidance for vaccine trials from drug trials, with the recognition that unblinding individual participants in vaccine studies is rarely needed for management of adverse events following immunization.

Long-term ambient air pollution exposure and cardio-respiratory disease in China: findings from a prospective cohort study.

Background: Existing evidence on long-term ambient air pollution (AAP) exposure and risk of cardio-respiratory diseases in China is mainly on mortality, and based on area average concentrations from fixed-site monitors for individual exposures. Substantial uncertainty persists, therefore, about the shape and strength of the relationship when assessed using more personalised individual exposure data. We aimed to examine the relationships between AAP exposure and risk of cardio-respiratory diseases using predicted local levels of AAP.

High-sensitive troponin T and N-terminal pro-B-type natriuretic peptide independently predict survival and cardiac-related events in adults with congenital heart disease.

Aims: High-sensitive troponin T (hs-TnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and C-reactive protein (CRP) are established prognostic biomarkers for cardiovascular (CV) morbidity and mortality and frequently used in symptomatic and/or hospitalized adults with congenital heart disease (ACHD). Their prognostic value in clinically stable ACHD has not yet been well established. This study investigates the predictive value of hs-TnT, NT-proBNP, and CRP for survival and CV events in stable ACHD.

Heterogeneity in the diagnosis and prognosis of ischemic stroke subtypes: 9-year follow-up of 22,000 cases in Chinese adults.

Background: Reliable classification of ischemic stroke (IS) etiological subtypes is required in research and clinical practice, but the predictive properties of these subtypes in population studies with incomplete investigations are poorly understood.

Aims: To compare the prognosis of etiologically classified IS subtypes and use machine learning (ML) to classify incompletely investigated IS cases.

Methods: In a 9-year follow-up of a prospective study of 512,726 Chinese adults, 22,216 incident IS cases, confirmed by clinical adjudication of medical records, were assigned subtypes using a modified Causative Classification System for Ischemic Stroke (CCS) (large artery atherosclerosis (LAA), small artery occlusion (SAO), cardioaortic embolism (CE), or undetermined etiology) and classified by CCS as "evident," "probable," or "possible" IS cases.

[Image-guided biopsy of the prostate gland].

The recommendations on carrying out a multiparametric magnetic resonance imaging (mpMRI) for the primary diagnostics and during active surveillance of prostate cancer, include as a consequence an image-guided sampling from conspicuous areas. In doing so, the information on the localization provided by mpMRI is used for a targeted biopsy of the area suspected of being a tumor. The targeted sampling is mainly performed under sonographic control and after fusion of MRI and ultrasound but can also be (mostly in special cases) carried out directly in the MRI scanner.

Tomosynthesis with synthesised two-dimensional mammography yields higher cancer detection compared to digital mammography alone, also in dense breasts and in younger women: A systematic review and meta-analysis.

Objectives: This systematic review and meta-analysis focuses on breast cancer screening performance outcomes stratified into breast density, age, and reading procedure using 'digital breast tomosynthesis (DBT) with synthesised two-dimensional mammography (s2D)' compared to 'digital mammography (DM) alone'.

Methods: Studies comparing 'DBT with s2D' and 'DM' were searched in PubMed and Cochrane library. Pooled risk ratios (RR) using fixed or random effects models (F-/REM) for cancer detection rates (CDR), recall rates, interval cancer rates (ICR), biopsy rates, and positive predictive values (PPV) 1-3 were calculated.

Association between involuntary smoking and risk of cervical cancer in Chinese female never smokers: A prospective cohort study.

Involuntary smoking was a major public health problem for women in China. Previous studies mainly focused on secondhand smoke (SHS), which referred to direct exposure to smoke from burning cigarettes. Little evidence existed about the relationship between thirdhand smoke (THS), the residual tobacco smoke remaining in the environment after tobacco had been smoked, and cervical cancer.

Low-risk Lifestyle and Health Factors and Risk of Mortality and Vascular Complications in Chinese Patients With Diabetes.

Background: There is an evidence gap about whether a low-risk lifestyle is as important as achieving blood pressure (BP) and random blood glucose (RBG) control.

Objectives: To explore the long-term impacts and relative importance of low-risk lifestyle and health factors on the risk of all-cause and cancer mortality and macrovascular and microvascular complications among patients with diabetes.

Methods: This study included 26,004 diabetes patients in the China Kadoorie Biobank.

The hospitalization burden of all-cause pneumonia in China: A population-based study, 2009-2017.

Background: Pneumonia represents a public health problem of substantial health and economic burden. However, the evidence on the burden of adult pneumonia is limited in China.

Methods: The China Kadoorie Biobank recruited 512,725 participants aged 30-79 years from five urban and five rural areas during 2004-2008.