Background The role of sex hormone-binding globulin (SHBG) levels in clinical risk stratification and intervention for coronary heart disease (CHD) remains uncertain. We aimed to examine whether circulating levels of SHBG are predictive of CHD risk in men and women. Methods We investigated the association between SHBG and the risk of incident CHD in 128 322 men and 135 103 women free of CHD at baseline in the prospective United Kingdom Biobank (UKB) cohort. The unconfounded associations were estimated using Mendelian randomization (MR) analysis. We further conducted a meta-analysis to integrate currently available prospective evidence. CHD events included nonfatal and fatal myocardial infarction and coronary revascularization. Results In the UKB, during a median of 11.7 follow-up years, 10 405 men and 4512 women developed CHD. Serum levels of SHBG were monotonically associated with a decreased risk of CHD in both men (adjusted hazard ratio [HR] per log nmol/L increase in SHBG: 0.88 [0.83–0.94]) and women (HR: 0.89 [0.83–0.96]). MR-based analyses suggested causality and a dose-response relationship of SHBG with CHD risk. A cumulative meta-analysis including 216 417 men and 138 282 women from 11 studies showed that higher levels of SHBG were prospectively associated with decreased CHD risk in men comparing the highest with the lowest quartile: pooled relative risk (RR) 0.81 (0.74–0.89) and women (pooled RR: 0.86 [0.78–0.94]). Conclusions Higher circulating SHBG levels were directly and independently predictive of lower CHD risk in both men and women. The utility of SHBG for CHD risk stratification and prediction warrants further study.

Background To inform policy and implementation that can enhance prevention and improve tuberculosis (TB) care cascade outcomes, this review aimed to summarize the impact of various interventions on care cascade outcomes for active TB. Methods and findings In this systematic review and meta-analysis, we retrieved English articles with comparator arms (like randomized controlled trials (RCTs) and before and after intervention studies) that evaluated TB interventions published from January 1970 to September 30, 2022, from Embase, CINAHL, PubMed, and the Cochrane library. Commentaries, qualitative studies, conference abstracts, studies without standard of care comparator arms, and studies that did not report quantitative results for TB care cascade outcomes were excluded. Data from studies with similar comparator arms were pooled in a random effects model, and outcomes were reported as odds ratio (OR) with 95% confidence interval (CI) and number of studies (k). The quality of evidence was appraised using GRADE, and the study was registered on PROSPERO (CRD42018103331). Of 21,548 deduplicated studies, 144 eligible studies were included. Of 144 studies, 128 were from low/middle-income countries, 84 were RCTs, and 25 integrated TB and HIV care. Counselling and education was significantly associated with testing (OR = 8.82, 95% CI:1.71 to 45.43; I2 = 99.9%, k = 7), diagnosis (OR = 1.44, 95% CI:1.08 to 1.92; I2 = 97.6%, k = 9), linkage to care (OR = 3.10, 95% CI = 1.97 to 4.86; I2 = 0%, k = 1), cure (OR = 2.08, 95% CI:1.11 to 3.88; I2 = 76.7%, k = 4), treatment completion (OR = 1.48, 95% CI: 1.07 to 2.03; I2 = 73.1%, k = 8), and treatment success (OR = 3.24, 95% CI: 1.88 to 5.55; I2 = 75.9%, k = 5) outcomes compared to standard-of-care. Incentives, multisector collaborations, and community-based interventions were associated with at least three TB care cascade outcomes; digital interventions and mixed interventions were associated with an increased likelihood of two cascade outcomes each. These findings remained salient when studies were limited to RCTs only. Also, our study does not cover the entire care cascade as we did not measure gaps in pre-testing, pretreatment, and post-treatment outcomes (like loss to follow-up and TB recurrence). Conclusions Among TB interventions, education and counseling, incentives, community-based interventions, and mixed interventions were associated with multiple active TB care cascade outcomes. However, cost-effectiveness and local-setting contexts should be considered when choosing such strategies due to their high heterogeneity.

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Introduction Accurately assessing axillary lymph node (ALN) status in breast cancer is vital for clinical decision making and prognosis. The purpose of this study was to evaluate the predictive value of sentinel lymph node (SLN) mapped by multidetector-row computed tomography lymphography (MDCT-LG) for ALN metastasis in breast cancer patients. Methods 112 patients with breast cancer who underwent preoperative MDCT-LG examination were included in the study. Long-axis diameter, short-axis diameter, ratio of long-/short-axis and cortical thickness were measured. Logistic regression analysis was performed to evaluate independent predictors associated with ALN metastasis. The prediction of ALN metastasis was determined with related variables of SLN using receiver operating characteristic (ROC) curve analysis. Results Among the 112 cases, 35 (30.8%) cases had ALN metastasis. The cortical thickness in metastatic ALN group was significantly thicker than that in non-metastatic ALN group (4.0 ± 1.2 mm vs. 2.4 ± 0.7 mm, P < 0.001). Multi-logistic regression analysis indicated that cortical thickness of > 3.3 mm (OR 24.53, 95% CI 6.58–91.48, P < 0.001) had higher risk for ALN metastasis. The best sensitivity, specificity, negative predictive value(NPV) and AUC of MDCT-LG for ALN metastasis prediction based on the single variable of cortical thickness were 76.2%, 88.5%, 90.2% and 0.872 (95% CI 0.773–0.939, P < 0.001), respectively. Conclusion ALN status can be predicted using the imaging features of SLN which was mapped on MDCT-LG in breast cancer patients. Besides, it may be helpful to select true negative lymph nodes in patients with early breast cancer, and SLN biopsy can be avoided in clinically and radiographically negative axilla.

Background The sex‐specific associations between birth weight and the risk of chronic kidney disease (CKD) later in life remain controversial. This study aimed to examine the shape of the relationship between birth weight and the risk of CKD in men and women. Methods A total of 277,252 participants free of CKD at baseline from the United Kingdom Biobank (UKB) prospective cohort were included in the analysis. Cox proportional hazard regression model was used to estimate the association between birth weight and the risk of incident CKD with adjustment for potential confounders. Results During a median follow‐up of 11.9 years, we identified 13,030 (4.7%) CKD cases. Compared with normal birth weight (2.5–4.0 kg), low birth weight (LBW, <2.5 kg) was associated with an 11% higher risk of CKD in men (adjusted hazard ratio [HR]: 1.11 [95% CI 1.01–1.21]) and a 27% higher risk of CKD in women (HR: 1.27 [1.19–1.36]) (p for interaction = 0.02). High birth weight (HBW, >4.0 kg) was associated with an 11% lower risk of CKD (HR: 0.89 [0.83–0.95]) in men but not in women (HR: 0.96 [0.89–1.04]) (p for interaction = 0.13). Furthermore, the LBW‐CKD association was stronger in obese (HR: 1.28 [1.18–1.39]) than in nonobese participants (HR: 1.16 [1.09–1.24], p for interaction = 0.03). Conclusions We found an L‐shaped relationship between birth weight and the risk of CKD in women but a linear shape in men. The LBW‐CKD association was mitigated to some extent by maintaining healthy body weight in adulthood. Our findings support the notion that the CKD risk should be managed from a lifecycle perspective.

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