BACKGROUND: Uncertainty remains about the long-term effects of air pollutants (AP) on multiple diseases, especially subtypes of cardiovascular disease (CVD). We aimed to assess the individual and joint associations of fine particulate matter (PM2.5), along with its chemical components, nitrogen dioxide (NO2) and ozone (O3), with risks of 32 health conditions.
METHODS: A total of 17,566 participants in Sichuan Province, China, were included in 2018 and followed until 2022, with an average follow-up period of 4.2 years. The concentrations of AP were measured using a machine-learning approach. The Cox proportional hazards model and quantile g-computation were applied to assess the associations between AP and CVD.
RESULTS: Per interquartile range (IQR) increase in PM2.5 mass, NO2, O3, nitrate, ammonium, organic matter (OM), black carbon (BC), chloride, and sulfate were significantly associated with increased risks of various conditions, with hazard ratios (HRs) ranging from 1.06 to 2.48. Exposure to multiple air pollutants was associated with total cardiovascular disease (HR 1.75, 95% confidence intervals (CIs) 1.62-1.89), hypertensive diseases (1.49, 1.38-1.62), cardiac arrests (1.52, 1.30-1.77), arrhythmia (1.76, 1.44-2.15), cerebrovascular diseases (1.86, 1.65-2.10), stroke (1.77, 1.54-2.03), ischemic stroke (1.85, 1.61-2.12), atherosclerosis (1.77, 1.57-1.99), diseases of veins, lymphatic vessels, and lymph nodes (1.32, 1.15-1.51), pneumonia (1.37, 1.16-1.61), inflammatory bowel diseases (1.34, 1.16-1.55), liver diseases (1.59, 1.43-1.77), type 2 diabetes (1.48, 1.26-1.73), lipoprotein metabolism disorders (2.20, 1.96-2.47), purine metabolism disorders (1.61, 1.38-1.88), anemia (1.29, 1.15-1.45), sleep disorders (1.54, 1.33-1.78), renal failure (1.44, 1.21-1.72), kidney stone (1.27, 1.13-1.43), osteoarthritis (2.18, 2.00-2.39), osteoporosis (1.36, 1.14-1.61). OM had max weights for joint effects of AP on many conditions.
CONCLUSIONS: Long-term exposure to increased levels of multiple air pollutants was associated with risks of multiple health conditions. OM accounted for substantial weight for these increased risks, suggesting it may play an important role in these associations.

BACKGROUND: The prognosis, recurrence rates, and secondary prevention strategies varied significantly among different subtypes of acute ischemic stroke (AIS). Machine learning (ML) techniques can uncover intricate, non-linear relationships within medical data, enabling the identification of factors associated with etiological classification. However, there is currently a lack of research utilizing ML algorithms for predicting AIS etiology.
OBJECTIVE: We aimed to use interpretable ML algorithms to develop AIS etiology prediction models, identify critical factors in etiology classification, and enhance existing clinical categorization.
METHODS: This study involved patients with the Third China National Stroke Registry (CNSR-III). Nine models, which included Natural Gradient Boosting (NGBoost), Categorical Boosting (CatBoost), Extreme Gradient Boosting (XGBoost), Random Forest (RF), Light Gradient Boosting Machine (LGBM), Gradient Boosting Decision Tree (GBDT), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), and logistic regression (LR), were employed to predict large artery atherosclerosis (LAA), small vessel occlusion (SVO), and cardioembolism (CE) using an 80:20 randomly split training and test set. We designed an SFS-XGB with 10-fold cross-validation for feature selection. The primary evaluation metrics for the models included the area under the receiver operating characteristic curve (AUC) for discrimination and the Brier score (or calibration plots) for calibration.
RESULTS: A total of 5,213 patients were included, comprising 2,471 (47.4%) with LAA, 2,153 (41.3%) with SVO, and 589 (11.3%) with CE. In both LAA and SVO models, the AUC values of the ML models were significantly higher than that of the LR model (P < 0.001). The optimal model for predicting SVO (AUC [RF model] = 0.932) outperformed the optimal LAA model (AUC [NGB model] = 0.917) and the optimal CE model (AUC [LGBM model] = 0.846). Each model displayed relatively satisfactory calibration. Further analysis showed that the optimal CE model could identify potential CE patients in the undetermined etiology (SUE) group, accounting for 1,900 out of 4,156 (45.7%).
CONCLUSIONS: The ML algorithm effectively classified patients with LAA, SVO, and CE, demonstrating superior classification performance compared to the LR model. The optimal ML model can identify potential CE patients among SUE patients. These newly identified predictive factors may complement the existing etiological classification system, enabling clinicians to promptly categorize stroke patients\' etiology and initiate optimal strategies for secondary prevention.

OBJECTIVE: Community-acquired pneumonia (CAP) is a common respiratory disease that frequently requires hospitalisation, and is a significant cause of death worldwide. This study aimed to evaluate the usefulness of alpha-1-antichymotrypsin (AACT) as a diagnostic and prognostic biomarker of CAP.
METHODS: We conducted a multicentre prospective cohort study in patients hospitalised with CAP. Plasma AACT levels were measured using a quantitative enzyme-linked immunosorbent assay. Receiver-operating characteristic (ROC) curves and Cox proportional hazards regression were used to assess the association between plasma AACT levels and CAP diagnosis and prognosis.
RESULTS: A total of 274 patients with CAP were enrolled in the study. AACT levels were elevated in patients with CAP, especially those with severe CAP and non-survivors. The area under the curve (AUC) of AACT and CRP for diagnosing CAP was 0.755 and 0.843. Cox regression showed that CURB-65 and AACT levels were independent predictors of 30-day mortality. ROC curves showed that plasma AACT levels had the highest accuracy for predicting acute respiratory distress syndrome (ARDS), with an AUC of 0.862. Combining AACT with Pneumonia Severity Index and CURB-65 significantly improved their predictive accuracy for predicting 30-day mortality.
CONCLUSIONS: Plasma AACT levels are elevated in patients with CAP, but plasma AACT level is inferior to the C-reactive protein level for diagnosing CAP. The AACT level can reliably predict the occurrence of ARDS and 30-day mortality in patients with CAP.

The neuropathology of mood disorders, including the diagnostic transition from major depressive disorder (MDD) to bipolar disorder (BD), is poorly understood. This study investigated resting-state electroencephalography (EEG) activity in patients with MDD and those whose diagnosis changed from MDD to BD. Among sixty-eight enrolled patients with MDD, the diagnosis of 17 patients converted to BD during the study period. We applied machine learning techniques to differentiate the two groups using sensor- and source-level EEG features. At the sensor level, patients with BD showed higher theta band power at the AF3 channel and low-alpha band power at the FC5 channel compared to patients with MDD. At the source level, patients with BD showed higher theta band activity in the right anterior cingulate and low-alpha band activity in the left parahippocampal gyrus. These four EEG features were selected for discriminating between BD and MDD with the best classification performance showing an accuracy of 80.88%, a sensitivity of 76.47%, and a specificity of 82.35%. Our findings revealed distinct theta and low-alpha band activities in patients with BD and MDD. These differences could potentially serve as candidate neuromarkers for the diagnosis and diagnostic transition between the two distinct mood disorders.

UNASSIGNED: The clinical and public health relevance of widespread testing for asymptomatic Chlamydia trachomatis (chlamydia) infections is under debate. To address uncertainties in screening programs, we estimate reproductive tract complication risks following asymptomatic and symptomatic chlamydia infections in a long-term prospective cohort.
UNASSIGNED: A cohort of 5704 reproductive-age women recruited from a chlamydia screening study was followed for up to 14 years. Chlamydia positivity was determined using screening polymerase chain reaction test results, self-reported diagnoses (with/without symptoms), and chlamydia Immunoglobulin G antibodies. Outcome data (pregnancies, pelvic inflammatory disease (PID), ectopic pregnancy, and tubal factor infertility) were collected through self-completed questionnaires. Cox regression calculated adjusted hazard ratios (aHR) with confidence intervals (CI) to compare outcomes between time-updated chlamydia groups since sexual debut.
UNASSIGNED: During 104,612 person-years, 2103 (36.9%) women were chlamydia-positive and 3692 women (64.7%) had been pregnant at least once. Risks for PID, ectopic pregnancy and tubal factor infertility were 1.62 (95% CI 1.20-2.17), 1.84 (95% CI 1.14-2.95) and 2.75 (95% CI 1.53-4.94), compared to chlamydia-negatives. aHRs for PID after symptomatic and asymptomatic infections were 2.29 (95% CI 1.62-3.25) and 1.06 (95% CI 0.66-1.69), respectively. Incidence of PID, ectopic pregnancy and tubal factor infertility after symptomatic chlamydia infection remained low with rates per 1000 person-years of 5.8, 1.9, and 1.8, respectively.
UNASSIGNED: We found a significantly higher risk of PID, ectopic pregnancy and tubal factor infertility in chlamydia-positive women compared to chlamydia-negative women, although the overall incidence rates of complications remained low. Symptomatic, but not asymptomatic, chlamydia infections were associated with PID risk, suggesting the largest disease burden of complications is in this group.
UNASSIGNED: The Netherlands Organisation for Health Research and Development (ZonMW Netherlands) and Research Funding from the Ministry of Health, Welfare and Sports.

OBJECTIVE: Erythritol, a sugar alcohol (polyol), has recently been linked to the risks of major adverse cardiovascular events. We investigated whether plasma erythritol and other polyols (mannitol/sorbitol) were associated with the risk of incident coronary heart disease (CHD).
METHODS: This prospective nested case-control study included 762 incident cases of CHD and 762 controls from the Nurses\' Health Study. Plasma concentrations of polyols were measured at baseline (1989-90 or 2000-02). Associations of erythritol with cardiometabolic risk factors were also analyzed in the Women\'s Lifestyle Validation Study (n=728; blood collected in 2010-12).
RESULTS: Higher erythritol levels were related to more adverse cardiometabolic risk factor status. The relative risk (RR) for CHD per 1-SD increment was 1.15 [95% CI: 1.04, 1.28] for erythritol and 1.16 [1.05, 1.28] for mannitol/sorbitol, after adjusting for diet quality, lifestyles, and adiposity. Compared with women in the lowest quartile, those in the highest quartile (Q4) of erythritol had a RR 1.55 [1.13, 2.14] for CHD. The RR in Q4 of erythritol was 1.61 [1.15, 2.24; p=0.006] when hypertension and dyslipidemia were further added to the model; the RR was 1.21 [0.86, 1.70] after adjustment for diabetes. For mannitol/sorbitol, the RR in the Q4 was 1.42 [1.05, 1.91; p=0.022] for CHD in the multivariable-adjusted model including diabetes.
CONCLUSIONS: Higher plasma erythritol and mannitol/sorbitol were related to elevated risks of CHD even after adjustment for diet, lifestyles, adiposity, and other risk factors. The unfavorable association of mannitol/sorbitol, but not erythritol, with CHD risk remained significant independently of diabetes/hyperglycemia.
The present study shows unfavorable associations of circulating erythritol and mannitol/sorbitol with long-term coronary heart disease (CHD) risk even after adjustments for overall diet quality, lifestyle factors, and several other traditional CHD risk factors among women at usual risk. In contrast to mannitol/sorbitol, the association between high erythritol levels and increased CHD risk was no longer significant upon additional inclusion of diabetes in the multivariable-adjusted model. Our findings from the two independent study populations of women without prior CHD suggest endogenous and exogenous erythritol levels are related to unfavorable cardiometabolic risk factor status.

UNASSIGNED: Intracorporeal anastomosis (IA) is becoming increasingly popular and replacing extracorporeal anastomosis (EA) for reconstruction in laparoscopic and robotic surgery for right-sided colon cancer (LSRCC). Intracorporeal overlap anastomosis (IOA) is the most widely used IA technique. This study aimed to examine the safety of IOA by investigating its short-term results during the implementation phase.
UNASSIGNED: This multicenter prospective cohort study was conducted by the Kanagawa Yokohama Colorectal Cancer (KYCC) Study Group. Patients with stage 1-3 colon cancer who planned to undergo LSRCC with IOA reconstruction were eligible. The incidence of anastomotic leakage (AL) of Clavien-Dindo (C-D) grade ≥3 was evaluated as the primary endpoint, and other surgical outcomes and postoperative complications of C-D grades ≥2 were the secondary endpoints.
UNASSIGNED: A total of 127 patients were enrolled, of whom 120 were finally analyzed. The incidence of C-D grade ≥2 complications was 8.3%. The incidence of C-D grade ≥3 AL was 0.8%. This trend was lower than that reported in previous randomized controlled trials (RCTs) and acceptable. Additionally, 1.7% of the patients developed abdominal abscesses, and no cases of anastomotic stenosis were observed. The median operative time was 257 min, and the reconstruction procedure required 32 min. Stapler closure of the enterotomy and facility experience of more than 30 cases were associated with a shorter reconstruction time during IOA.
UNASSIGNED: IOA is feasible and can be safely performed during the implementation phase in patients undergoing LSRCC.

BACKGROUND: There is no consensus on the cause and effect of systemic chronic inflammation (SCI) regarding chronic obstructive pulmonary disease (COPD). The impact of second-hand smoke (SHS) on COPD has reached inconsistent conclusions.
METHODS: The China Kadoorie Biobank cohort was followed up from the 2004-08 baseline survey to 31 December 2018. Among the selected 445,523 participants in the final analysis, Cox and linear regressions were performed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of tobacco exposure with COPD risk and baseline levels of log-transformed inflammatory factors [βs (95% CIs)], respectively.
RESULTS: Participants were followed up for a median of 12.1 years and 11,825 incident COPD events were documented. Ever-smokers were associated with a higher risk of COPD than non-smokers with non-weekly SHS exposure. A younger age to start smoking, a greater amount of daily tobacco consumption, and deeper inhalation were associated with increased risk of COPD and correlated with elevated levels of plasma high-sensitivity C-reactive protein (hs-CRP, all Ptrend < 0.001) even two years before COPD onset. Among former smokers, COPD risk declined with longer smoking cessation (Ptrend < 0.001) and those quitting smoking for over ten years presented no difference in COPD risk and hs-CRP level from non-smokers [HR (95% CI) = 1.05 (0.89, 1.25), β (95% CI) = 0.17 (- 0.09, 0.43)]. Among non-smokers, weekly SHS exposure was associated with a slightly higher COPD risk [HR (95% CI) = 1.06 (1.01, 1.12)].
CONCLUSIONS: Incremental exposure to tobacco smoke was related to elevated SCI level before COPD onset, then an increase in COPD susceptibility. Quitting smoking as early as possible is suggested as a practical approach to reducing COPD risk in smokers. Given the high prevalence of both COPD and SHS exposure, the risk associated with SHS exposure deserves attention.

BACKGROUND: The current evidence regarding the association between long-term exposure to ozone (O3) and hypertension incidence is limited and inconclusive, particularly at low O3 concentrations. Therefore, our research aims to investigate the potential link between long-term O3 exposure and hypertension in a region with low pollution levels.
METHODS: From 2010 to 2012, we conducted a cohort prospective study by recruiting nearly 10,000 attendees through multistage cluster random sampling in Guizhou Province, China. These individuals were followed up from 2016 to 2020, and 5563 cases were finally included in the analysis. We employed a high-resolution model with both temporal and spatial accuracy to estimate the maximum daily 8-h average O3 and utilized annual average O3 concentrations for three exposure periods (2009_10, 2007_10, 2005_10) as the exposure indicator. Time-dependent covariates Cox regression model was exerted to estimate the hazard ratios (HRs) of hypertension incidence. Generalized linear model was employed to assess the association between O3 and systolic, diastolic, pulse, and mean arterial pressure. The dose-response curve was explored using a restricted cubic spline function.
RESULTS: 1213 hypertension incidents occurred during 39,001.80 person-years, with an incidence density of 31.10/1000 Person Years (PYs). The average O3 concentrations during the three exposure periods were 66.76 μg/m3, 67.85 μg/m3, and 67.21 μg/m3, respectively. Per 1 μg/m3 increase in O3 exposure was associated with 11 % increase in the incidence of hypertension in the single-pollution model, and the association was more pronounced in Han, urban, and higher altitude areas. SBP, PP, and MAP were increased by 0.619 (95 % CI, 0.361-0.877) mm Hg, 0.477 (95 % CI, 0.275-0.679) mm Hg, 0.301 (95 % CI, 0.127-0.475) mm Hg, respectively. Furthermore, we observed a nonlinear exposure-response relationship between O3 and hypertension incidence.
CONCLUSIONS: Long-term exposure to low-level O3 exposure is associated with an increased risk of hypertension.

BACKGROUND: The health statuses of closely connected individuals are interdependent. Little is known about mortality risk associated with partner\'s cancer diagnosis and cause-specific mortality risk associated with partner\'s death.
METHODS: Relative risks for all-cause and cause-specific mortality following a partner\'s cancer diagnosis or death compared to the period when the partner is cancer-free and alive were investigated in the population-based prospective cohort study that enrolled 140,420 people at the age between 40-69 in 1990-1994.
RESULTS: 55,050 participants (27,665 men and 27,385 women) who were identified as married couples were followed-up for 1,073,746.1 (518,368.5 in men and 555,377.6 in women) person-years, during which 9,816 deaths (7,217 in men and 2,599 in women) were observed. After a partner\'s cancer diagnosis, the mortality rate ratio (MRR) of all-cause mortality was not increased among both men and women, while an increase of externally-caused MRR was observed. The suicide MRR significantly increased among men (MRR = 2.90 [95% CI, 1.70-4.93]) and it persisted for more than 5 years. After a partner\'s death, the MRRs of all-cause, cardiovascular disease (CVD), respiratory disease (RD), and externally-caused mortality significantly increased only among men. Stratified analysis by smoking status among men showed significantly increased MRRs of CVD and RD mortality among former/current smokers, but not among never-smokers.
CONCLUSIONS: Partner\'s cancer diagnosis did not increase all-cause mortality risk, but increased externally-caused mortality risk, especially suicide among men. The impact of partner\'s death on mortality risk differed by the mortality causes and sex, and smoking affected some of cause-specific mortality risk.