BMC Medicine

BACKGROUND: Lenvatinib is widely used in treatment of unresectable hepatocellular carcinoma (uHCC), but the benefit of its combination with immunotherapy needs to be verified. This study evaluated the efficacy and safety of tislelizumab plus lenvatinib in systemic treatment-naïve patients with uHCC. METHODS: In this multicenter, single-arm, phase 2 study, systemic treatment-naïve patients with uHCC received tislelizumab 200 mg every three weeks plus lenvatinib (bodyweight ≥ 60 kg: 12 mg; < 60 kg: 8 mg; once daily)...

BACKGROUND: Little is known about the safety and efficacy of discontinuing antiplatelet therapy via LMWH bridging therapy in elderly patients with coronary stents implanted for > 12 months undergoing non-cardiac surgery. This randomized trial was designed to compare the clinical benefits and risks of antiplatelet drug discontinuation via LMWH bridging therapy. METHODS: Patients were randomized 1:1 to receive subcutaneous injections of either dalteparin sodium or placebo...

BACKGROUND: The molecular pathways linking short and long sleep duration with incident diabetes mellitus (iDM) and incident coronary heart disease (iCHD) are not known. We aimed to identify circulating protein patterns associated with sleep duration and test their impact on incident cardiometabolic disease. METHODS: We assessed sleep duration and measured 78 plasma proteins among 3336 participants aged 46-68 years, free from DM and CHD at baseline, and identified cases of iDM and iCHD using national registers...

BACKGROUND: The stalling global progress in malaria control highlights the need for novel tools for malaria elimination, including transmission-blocking vaccines. Transmission-blocking vaccines aim to induce human antibodies that block parasite development in the mosquito and mosquitoes becoming infectious. The Pfs48/45 protein is a leading Plasmodium falciparum transmission-blocking vaccine candidate. The R0.6C fusion protein, consisting of Pfs48/45 domain 3 (6C) and the N-terminal region of P...

BACKGROUND: Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression. METHODS: Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022...

BACKGROUND: The co-administration of drugs known to interact greatly impacts morbidity, mortality, and health economics. This study aims to examine the drug-drug interaction (DDI) phenomenon with a large-scale longitudinal analysis of age and gender differences found in drug administration data from three distinct healthcare systems. METHODS: This study analyzes drug administrations from population-wide electronic health records in Blumenau (Brazil; 133 K individuals), Catalonia (Spain; 5...

BACKGROUND: The prevalence of depression among people with chronic pain remains unclear due to the heterogeneity of study samples and definitions of depression. We aimed to identify sources of variation in the prevalence of depression among people with chronic pain and generate clinical prediction models to estimate the probability of depression among individuals with chronic pain. METHODS: Participants were from the UK Biobank. The primary outcome was a "lifetime" history of depression...

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases. METHODS: In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled...

BACKGROUND: Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare. This information could improve strategies for detection...

BACKGROUND: Tobacco smoking affects women's fertility and is associated with substantial risks of adverse pregnancy outcomes. This study explored trends by socioeconomic position in patterns of smoking, use of non-combustible nicotine products, and quitting activity among women of reproductive age in England. METHODS: Data come from a nationally representative monthly cross-sectional survey. Between October 2013 and October 2023, 197,266 adults (≥ 18 years) were surveyed, of whom 44,052 were women of reproductive age (18-45 years)...

BACKGROUND: The metabolic benefits of bariatric surgery that contribute to the alleviation of metabolic dysfunction-associated steatotic liver disease (MASLD) have been reported. However, the processes and mechanisms underlying the contribution of lipid metabolic reprogramming after bariatric surgery to attenuating MASLD remain elusive. METHODS: A case-control study was designed to evaluate the impact of three of the most common adipokines (Nrg4, leptin, and adiponectin) on hepatic steatosis in the early recovery phase following sleeve gastrectomy (SG)...

BACKGROUND: Defining healthcare facility catchment areas is a key step in predicting future healthcare demand in epidemic settings. Forecasts of hospitalisations can be informed by leading indicators measured at the community level. However, this relies on the definition of so-called catchment areas or the geographies whose populations make up the patients admitted to a given hospital, which are often not well-defined. Little work has been done to quantify the impact of hospital catchment area definitions on healthcare demand forecasting...

BACKGROUND: Long covid (post covid-19 condition) is a complex condition with diverse manifestations, uncertain prognosis and wide variation in current approaches to management. There have been calls for formal quality standards to reduce a so-called "postcode lottery" of care. The original aim of this study-to examine the nature of quality in long covid care and reduce unwarranted variation in services-evolved to focus on examining the reasons why standardizing care was so challenging in this condition...

BACKGROUND: Lung health is increasingly recognized as an essential factor in mental health. However, prospective evidence on lung function with incident depression remains to be determined. The study aimed to examine the prospective association between impaired lung function and incident depression and the underlying biological mechanisms. METHODS: This prospective cohort study comprised 280,032 non-depressed individuals with valid lung function measurements from the UK Biobank...

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer...

BACKGROUND: The COVID-19 pandemic resulted in major inequalities in infection and disease burden between areas of varying socioeconomic deprivation in many countries, including England. Areas of higher deprivation tend to have a different population structure-generally younger-which can increase viral transmission due to higher contact rates in school-going children and working-age adults. Higher deprivation is also associated with a higher presence of chronic comorbidities, which were convincingly demonstrated to be risk factors for severe COVID-19 disease...

BACKGROUND: To study the shared genetic structure between autoimmune diseases and B-cell acute lymphoblastic leukemia (B-ALL) and identify the shared risk loci and genes and genetic mechanisms involved. METHODS: Based on large-scale genome-wide association study (GWAS) summary-level data sets, we observed genetic overlaps between autoimmune diseases and B-ALL, and cross-trait pleiotropic analysis was performed to detect shared pleiotropic loci and genes. A series of functional annotation and tissue-specific analysis were performed to determine the influence of pleiotropic genes...

BACKGROUND: Chronic low back pain (CLBP) is a significant problem affecting millions of people worldwide. Three widely implemented psychological techniques used for CLBP management are cognitive therapy (CT), mindfulness meditation (MM), and behavioral activation (BA). This study aimed to evaluate the relative immediate (pre- to post-treatment) and longer term (pre-treatment to 3- and 6-month follow-ups) effects of group, videoconference-delivered CT, BA, and MM for CLBP. METHODS: This is a secondary analysis of a three-arm, randomized clinical trial comparing the effects of three active treatments-CT, BA, and MM-with no inert control condition...

BACKGROUND: Colorectal cancer (CRC) lacks established biomarkers or molecular targets for predicting or enhancing radiation response. Phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 2 (PREX2) exhibits intricate implications in tumorigenesis and progression. Nevertheless, the precise role and underlying mechanisms of PREX2 in CRC radioresistance remain unclear. METHODS: RNA-seq was employed to identify differentially expressed genes between radioresistant CRC cell lines and their parental counterparts...

BACKGROUND: Prediction of lymph node metastasis (LNM) is critical for individualized management of papillary thyroid carcinoma (PTC) patients to avoid unnecessary overtreatment as well as undesired under-treatment. Artificial intelligence (AI) trained by thyroid ultrasound (US) may improve prediction performance. METHODS: From September 2017 to December 2018, patients with suspicious PTC from the first medical center of the Chinese PLA general hospital were retrospectively enrolled to pre-train the multi-scale, multi-frame, and dual-direction deep learning (MMD-DL) model...