BMC Medicine最新文献

Background: Associations of anxiety disorder and depression with coronary artery disease (CAD) are heterogeneous between populations. This study investigated how genetic susceptibility to CAD alters these associations with incident CAD, comparing and combining anxiety disorder and depression.

Methods: This is a prospective cohort study using UK Biobank. Diagnoses of anxiety disorder and depression were ascertained through linked hospital admission data. Incident CAD was ascertained through hospital admission and death certificate data after baseline. CAD polygenic risk score (PRS_CAD) was obtained from CARDIoGRAMplus4 and categorised into low, intermediate, and high. Cox proportional hazard models were used to examine associations between anxiety disorder and depression and CAD.

Results: Both anxiety disorder (HR 2.31, 95% CI 1.92-2.78) and depression (HR 2.15, 95% CI 1.90-2.24) were associated with CAD after adjusting for sociodemographic confounders. There was an addictive interaction between depression and PRS_CAD (RERI 0.97, 95% CI 0.12-1.81) such that the association between depression and CAD was strongest among those with a high PRS_CAD whilst there was no such evidence for anxiety disorder. Anxiety disorder only (HR 1.68, 95% 1.16-2.44), depression only (HR 2.13, 95% CI 1.72-2.64), and concomitant anxiety disorder and depression (HR 3.85, 95% CI 2.48-5.98) were associated with CAD even among people with a low PRS_CAD. Adjusting for potential mediators attenuated all these associations across PRS categories.

Conclusions: CAD genetic susceptibility might partly contribute to the clustering of depression and CAD but does not provide a full explanation, nor does it explain the association between anxiety disorder and CAD. Therefore, other mechanisms should be explored.

Background: Gastric intestinal metaplasia (GIM) represents an important precancerous lesion in intestinal-type gastric cancer, triggered by persistent Helicobacter pylori (H. pylori) infection. In a previous study, we unveiled SlyD as a novel virulence factor of H. pylori, establishing its role in GIM induction through TPT1. However, the underlying mechanism remains undetermined.

Methods: Gastric epithelial cells were stimulated with H. pylori 26695, a SlyD inactivated mutant (ΔSlyD), and purified HpSlyD protein, respectively. Real-time qPCR and western blot were subsequently used to assess the expression levels of hnRNPK, TPT1, OCT1, and GIM markers. RNA sequencing was employed to identify differentially expressed genes associated with H. pylori SlyD infection. Protein stability was evaluated using cycloheximide. Molecular interactions were investigated through co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. Additionally, molecular docking was utilized to predict TPT1 inhibitors. Immunohistochemistry staining was conducted to validate hnRNPK, TPT1, OCT1, and CDX2 expression in gastric tissue samples from both human and Mongolian gerbils.

Results: H. pylori SlyD upregulates TPT1 and induces the expression of GIM markers through hnRNPK. The interaction between hnRNPK and TPT1 enhances TPT1 protein stability, with H. pylori SlyD intensifying this association. TPT1 promotes the expression of GIM markers mediated via OCT1, which binds to CDX2 promoter region, thereby modulating its transcriptional activity. Dihydroartemisinin has the potential to target TPT1, inhibiting the H. pylori SlyD-induced expression of GIM markers.

Conclusions: In vitro and in vivo experiments verified that H. pylori SlyD enhances TPT1 stability through hnRNPK, leading to OCT1-mediated transcriptional activation of CDX2 and the initiation of the GIM process. Our study offers novel perspectives on the pathogenesis of H. pylori-related gastric precancerous conditions.

Background: Postpartum maternal depression and socioeconomic factors are established risk factors for the mental health of offspring. It has been consistently unclear as to whether female or male offspring are more vulnerable to the effects of postpartum maternal depression at different stages of the child's life course. To determine whether the characteristics of postpartum maternal depression with a history of prenatal depression influence sex differences in offspring internalizing symptoms across childhood and adolescence, socioeconomic factors should be considered.

Methods: We systematically searched PubMed, Embase, PsycINFO, CNKI, and SinoMed databases from inception to November 28, 2023, and selected longitudinal cohort studies that quantified sex differences in internalizing symptoms of children and adolescents. Pooled standardized mean differences (SMDs) were calculated using random-effects models. ROBINS-E tool was used to rate the quality of evidence.

Results: Twenty-eight studies were eligible between 1997 and 2023, including 24,022 mother-child dyads. Sex-difference trajectories of offspring internalizing symptoms were identified after exposure to postpartum maternal depression, ranging from a lack of significant sex differences in childhood to a higher prevalence observed among girls than boys in adolescence (SMD, 0.25, 95% CI, 0.13-0.38). Economic income and maternal education affected the associations between the magnitude and concurrent recurrence of postpartum depression and significant sex differences in adolescent internalizing symptoms, respectively. After adjusting for socioeconomic factors, early nonconcurrent recurrence of postpartum depression was associated with greater odds of internalizing symptoms among adolescent girls than among boys (β = 0.03, 95% CI, 0.01-0.06); however, there was no statistical significance after adjusting for prenatal depression.

Conclusions: Socioeconomic factors differentially impacted the association between postpartum maternal depression and significant sex differences in adolescent internalizing symptoms. Independent of socioeconomic factors and prenatal depression, postpartum maternal depression was not associated with significant sex differences in adolescent internalizing symptoms. Therefore, the significant sex effects of postpartum maternal depression are more likely due to complex interactions between maternal depression and the intrauterine and postpartum environments that shape offspring sex-difference trajectories, with consequences occurring for later internalizing symptoms in adolescence.

Trial registration: PROSPERO, CRD42022301445.

Background: Nervous system toxicity (NST) is a frequent and serious adverse event (AE) associated with blinatumomab, the first bispecific antibody drug targeting CD19 and CD3. Real-world data are needed to better understand the incidence and characteristics of NST in clinical practice.

Methods: Data were obtained from the FDA Adverse Event Reporting System (FAERS). The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence interval progressive neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were utilized for data mining.

Results: A total of 5,962 blinatumomab-related cases were analyzed. NSTs were more frequent in males (44.01%) and younger individuals (18-45 years, 28.39%), with a higher prevalence in the USA (77.99%). Forty-three signals of NST were identified, of which neurotoxicity, neurological symptoms, agnosia, intention tremor, and immune effector cell-associated neurotoxicity syndrome had the highest ROR values. Concomitant use of medication for age, musculoskeletal system, genitourinary system, and sexual hormones were independent risk factors for NST, and age was an independent protective factor for fatal NST. The median time to onset (TTO) for neurological events was 3 days (range, 1 ~ 21). The highest fatality rate for neurological events was observed for increased intracranial pressure disorders, which also had the highest co-occurrence rate with cytokine release syndrome (CRS).

Conclusions: Age is an independent protective factor for fatal NST, and CRS leads to a higher fatality rate for NST patients treated with blinatumomab. Thorough medication evaluation should be conducted before administering blinatumomab, especially for high-risk patients with preexisting neurological conditions.

Background: In this study, we evaluated the potential of a network approach to electromyography and electroencephalography recordings to detect covert command-following in healthy participants. The motivation underlying this study was the development of a diagnostic tool that can be applied in common clinical settings to detect awareness in patients that are unable to convey explicit motor or verbal responses, such as patients that suffer from disorders of consciousness (DoC).

Methods: We examined the brain and muscle response during movement and imagined movement of simple motor tasks, as well as during resting state. Brain-muscle networks were obtained using non-negative matrix factorization (NMF) of the coherence spectra for all the channel pairs. For the 15/38 participants who showed motor imagery, as indexed by common spatial filters and linear discriminant analysis, we contrasted the configuration of the networks during imagined movement and resting state at the group level, and subject-level classifiers were implemented using as features the weights of the NMF together with trial-wise power modulations and heart response to classify resting state from motor imagery.

Results: Kinesthetic motor imagery produced decreases in the mu-beta band compared to resting state, and a small correlation was found between mu-beta power and the kinesthetic imagery scores of the Movement Imagery Questionnaire-Revised Second version. The full-feature classifiers successfully distinguished between motor imagery and resting state for all participants, and brain-muscle functional networks did not contribute to the overall classification. Nevertheless, heart activity and cortical power were crucial to detect when a participant was mentally rehearsing a movement.

Conclusions: Our work highlights the importance of combining EEG and peripheral measurements to detect command-following, which could be important for improving the detection of covert responses consistent with volition in unresponsive patients.

Background: Since its emergence in 2019, COVID-19 has continued to pose significant threats to both the physical and mental health of the global population, as well as to healthcare systems worldwide (Raman et al., Eur Heart J 43:1157-1172, 2022). Emerging evidence indicates that COVID-19 may lead to post-acute COVID-19 syndrome (PACS) with cardiovascular implications, potentially driven by factors such as ACE2 interaction with viruses, systemic inflammation, and endothelial dysfunction. However, there remains a limited amount of research on the cardiovascular manifestations of PACS, which may delay the development of optimal treatment strategies for affected patients. Therefore, it is crucial to investigate the prevalence of cardiovascular sequelae in COVID-19 patients and to determine whether COVID-19 infection acts as an independent risk factor for these outcomes.

Methods: This meta-analysis adhered to PRISMA guidelines and was registered in PROSPERO (CRD42024524290). A systematic search of PubMed, Embase, and the Cochrane Library was conducted up to March 17, 2024. The primary outcomes included hypertension, palpitations, and chest pain, with pooled effect estimate reported as proportions and odds ratios (ORs) with 95% confidence intervals (CIs). Sensitivity and subgroup analysis were performed to assess the robustness of the results and to identify sources of heterogeneity.

Results: A total of 37 studies, encompassing 2,965,467 patients, were included in the analysis. Pooled results from case-control studies revealed that, compared to the control group, the ORs of chest pain in the COVID-19 group was 4.0 (95% CI: 1.6, 10.0). The ORs for palpitation and hypertension were 3.4 (95% CI: 1.1, 10.2) and 1.7 (95% CI: 1.6, 1.8), respectively. The proportions of PACS patients experiencing chest pain, palpitation, and hypertension as sequelae were 22% (95% CI: 14%, 33%), 18% (95% CI: 13%, 24%), and 19% (95% CI: 12%, 31%), respectively.

Conclusions: Our findings indicate that 15% of COVID-19 patients experience cardiovascular sequelae. Furthermore, COVID-19 infection significantly increases the likelihood of developing these sequelae compared to uninfected individuals. Future research should prioritize investigating the underlying pathological mechanisms and developing targeted preventive and management strategies.

Trial registration: CRD42024524290.

Background: High systolic blood pressure (HSBP) can cause adverse cardiovascular events and is therefore associated with a heavy global disease burden. However, this disease burden is poorly understood in youth and young adults. We aimed to explore this population to better understand the evolving trends in HSBP-related disease burden, which is crucial for effectively controlling and mitigating harmful effects.

Methods: This systematic analysis used data from the 2021 Global Burden of Disease Study, spanning 1990-2021. Participants were aged 15-39 years from 204 countries/territories. We analysed HSBP-related disease burden by region, sex, age, and temporal trends. The primary outcomes were disability-adjusted life years (DALYs), mortality rates, and estimated annual percentage change.

Results: Globally, the number of HSBP-related deaths among youth and young adults has increased by 36.11% (95% uncertainty interval [95% UI], 20.96-52.37%), whereas the number of DALYs has increased by 37.68% (95% UI, 22.69-53.65%); however, global mortality and DALY rates have remained relatively stable. In 2021, the mortality and DALY rates were 4.29 (95% UI, 3.29-5.28) and 263.37 (95% UI, 201.40-324.46) per 100,000 population, respectively. The overall HSBP-related burden was higher in males than in females, with increasing and decreasing trends for males and females, respectively. Regionally, significant improvements in HSBP-related burden were observed in most high-sociodemographic index (SDI) regions, including high-income Asia Pacific (deaths: percentage change, - 72.65%; DALYs: percentage change, - 69.30%) and Western Europe (deaths: percentage change, - 72.89%; DALYs: percentage change, - 67.48%). In contrast, middle-SDI regions had the highest number of deaths and DALYs in 2021, whereas low-middle-SDI regions had the highest mortality and DALY rates. Furthermore, low-SDI regions experienced the largest increase in the number of deaths and DALYs. The HSBP-related burden increased with age; in addition, the proportion of deaths or DALYs due to ischaemic heart disease and stroke increased with age, reaching > 75% for those > 25 years of age.

Conclusions: The increase in global HSBP-related burden among youth and young adults indicates that current preventative efforts are insufficient. Therefore, targeted measures are needed to counter the trends in HSBP-related diseases and reduce disparities across regions and sexes.

Background: Long-COVID is defined as the persistency or development of new symptoms 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Common persistent symptoms are fatigue, sleep disturbances, post-exertional malaise (PEM), pain, and cognitive problems. Long-COVID is estimated to be present in about 65 million people. We aimed to explore clinical and biological factors that might contribute to Long-COVID.

Methods: Prospective longitudinal cohort study including patients infected with SARS-CoV-2 between March 2020 and March 2022. Patients were assessed between 4 and 12 months after infection at the COVID follow-up clinic at UZ Leuven. We performed a comprehensive clinical assessment (including questionnaires and the 6-min walking test) and biological measures (global DNA methylation, telomere length, mitochondrial DNA copy number, inflammatory cytokines, and serological markers such as C-reactive protein, D-dimer, troponin T).

Results: Of the 358 participants, 328 were hospitalised, of which 130 had severe symptoms requiring intensive care admission; 30 patients were ambulatory referrals. Based on their clinical presentation, we could identify 6 main clusters. One-hundred and twenty-seven patients (35.4%) belonged to at least one cluster. The bigger cluster included PEM, fatigue, sleep disturbances, and pain (n = 57). Troponin T and telomere shortening were the two main markers predicting Long-COVID and PEM-fatigue symptoms.

Conclusions: Long-COVID is not just one entity. Different clinical presentations can be identified. Cardiac involvement (as measured by troponin T levels) and telomere shortening might be a relevant risk factor for developing PEM-fatigue symptoms and deserve further exploring.

Background: Urgent care centers (UCCs) are a growing segment of healthcare with high rates of inappropriate antibiotic use. MeMed BV® (MMBV) is a blood test that differentiates bacterial from viral infections. Between April 2022 and March 2023, we introduced MMBV into routine care at ten UCCs. The primary objective was to assess MMBV's impact on antibiotic use; the secondary objective was to assess whether MMBV aided in patient management.

Methods: A pragmatic prospective cohort study. Physicians who ordered MMBV reported electronically (in real-time) whether they intended to prescribe antibiotics before ordering the test and upon UCC discharge whether MMBV aided in patient management. Hospitalizations were recorded for 7 days post-UCC discharge.

Results: During implementation, 3920 MMBV tests were ordered for adults (age ≥ 18) by 144 physicians. The study cohort had 59% female patients and the median age was 42 years (IQR 31-58). For the primary objective, 3262 cases were included. MMBV indicated 629/3262 (19.3%) cases of potentially unwarranted antibiotics, of which physicians avoided prescriptions in 397/629 (63.1%). MMBV indicated 405/3262 (12.4%) cases of potentially missed bacterial infections. Physicians prescribed antibiotics to 283/405 (69.9%). MMBV adherence was associated with fewer hospitalizations (7.8% vs. 30.3%, p < 0.001). For the secondary objective, 2901 cases were included. Physicians reported MMBV aided patient management in 2494/2901 (86.0%) cases and contributed to avoiding emergency department referrals in 595/2901 (20.5%).

Conclusions: Implementing MMBV aided urgent care center physicians in their clinical decision-making and may have contributed to appropriate antibiotic use, better resource utilization, and patient management.

Background: Antenatal steroid (ANS) therapy is given to women at risk of preterm delivery to accelerate fetal lung maturation. However, the benefit of ANS therapy is variable and how maternal and fetal factors contribute to this observed variability is unknown. We aimed to test the degree of concordance in preterm lung function, and correlate this with genomic, transcriptomic, and pharmacokinetic variables in preterm dizygotic twin ovine fetuses.

Methods: Thirty-one date-mated ewes carrying twin fetuses at 123 ± 1 days' gestation received maternal intramuscular injections of either (i) 1 × 0.25 mg/kg betamethasone phosphate and acetate (CS1, n = 11 twin pairs) or (ii) 2 × 0.25 mg/kg betamethasone phosphate and acetate, 24 h apart (CS2, n = 10 twin pairs) or (iii) 2 × saline, 24 h apart (negative control, n = 10 twin pairs). Fetuses were surgically delivered 24 h after their final treatment and ventilated for 30 min.

Results: ANS-exposed female fetuses had lower arterial partial pressure of carbon dioxide (PaCO₂) values than male fetuses (76.5 ± 38.0 vs. 97.2 ± 42.5 mmHg), although the observed difference was not statistically significant (p = 0.1). Only 52% of ANS-treated twins were concordant for lung maturation responses. There was no difference in fetal lung tissue or plasma steroid concentrations within or between twin pairs. Genomic analysis identified 13 single-nucleotide polymorphisms (SNPs) statistically associated with ANS-responsiveness, including in the proto-oncogene MET and the transcription activator STAT1.

Conclusions: Twin fetal responses and ANS tissue levels were comparable with those from singleton fetuses in earlier studies. Twin ovine fetuses thus benefit from ANS in a similar manner to singleton fetuses, and a larger dose of betamethasone is not required. Assuming no difference in input from the placental or maternal compartments, fetal lung responses to ANS therapy in dizygotic twin preterm lambs are dependent on the fetus itself. These data suggest a potential heritable role in determining ANS responsiveness.