Nevin Manimala

Medicine (Baltimore). 2026 Jun 12;105(24):e49163. doi: 10.1097/MD.0000000000049163.

ABSTRACT

This ecological study was based on secondary, population-level data from the Global Burden of Disease 2021 study. We systematically assessed the burden of Guillain-Barré syndrome (GBS) from 1990 to 2021 at global, regional, and national levels, and projected trends through 2041. Temporal trends were evaluated using joinpoint regression to calculate the average annual percentage change. Future trends up to 2041 were projected using autoregressive integrated moving average models. In 2021, the global number of prevalent GBS cases reached 471,850, with an age-standardized prevalence rate of 5.91 per 100,000, a 229% increase since 1990 (average annual percentage change: 3.34). Substantial regional disparities were observed, and frontier analysis indicated an inverse correlation between the sociodemographic index (SDI) and age-standardized rates. The disease burden was higher in males than in females, with peak prevalence occurring among children aged 5 to 9 years. The coronavirus disease 2019 pandemic was temporally associated with a marked increase in GBS burden in 2021, coinciding with a shift in the burden toward low-SDI regions. Projections suggest that the age-standardized prevalence rate will continue to rise through 2041, disproportionately affecting resource-limited areas. The global burden of GBS increased markedly from 1990 to 2021, with a notable rise after 2019 that was temporally associated with the coronavirus disease 2019 pandemic. Addressing this growing burden will warrant targeted interventions, strengthened surveillance, and equitable allocation of resources, particularly in low-SDI populations.

PMID:42299592 | DOI:10.1097/MD.0000000000049163

Medicine (Baltimore). 2026 Jun 12;105(24):e49203. doi: 10.1097/MD.0000000000049203.

ABSTRACT

Erectile dysfunction (ED) is a prevalent health condition with significant psychosocial impacts, yet the causal role of age at first sexual intercourse (AFS) remains unclear. This study investigated the causal effect of AFS on the risk of ED using Mendelian randomization (MR) and Bayesian methods. Five traditional 2-sample MR analyses and 5 Bayesian MR analyses were performed using genome-wide association studies summary statistics from European populations. Sensitivity analyses included MR Egger regression, MR-pleiotropy residual sum and outlier, and Cochran Q-test. In mixed-sex cohorts (Groups 1 and 2), inverse variance weighted results demonstrated significant protective effects: odds ratio (OR) = 0.626, θ = -0.469, P = 2.73 × 10-6 for Group 1 and OR = 0.617, θ = -0.483, P = 3.56 × 10-5 for Group 2. The analyses for male-specific cohorts (Groups 3-10) showed weaker but consistent effects. For Group 3, OR = 0.643, θ = -0.442, P = .010. For Group 4, some instrumental variables associated with confounders were removed. The result became statistically insignificant: OR = 0.680, θ = -0.385, P = .064. For Group 5, the instrument selection criteria were relaxed and significance was retained: OR = 0.695, θ = -0.364, P = .016. For Groups 6 to 10, Bayesian MR was used to strengthen the inferences. In particular, for Group 8, which has a strongly informed prior, a posterior mean θ = -0.358 and a 95% credible interval (-0.575, -0.136) were obtained. This study provides evidence supporting a causal protective effect of later AFS on ED risk. While traditional MR analyses in male-specific cohorts yielded suggestive results, Bayesian MR analyses, which allow for the integration of prior evidence, provided more precise estimates and strengthened the causal inference. These findings may inform future sexual health policies. Strengths include the use of male-specific cohorts and Bayesian enhancement for weak instruments. Limitations include reliance on European-ancestry data and inability to stratify ED subtypes.

PMID:42299590 | DOI:10.1097/MD.0000000000049203

Medicine (Baltimore). 2026 Jun 12;105(24):e49213. doi: 10.1097/MD.0000000000049213.

ABSTRACT

Patients with end-stage renal disease (ESRD) who are on maintenance hemodialysis (HD) often experience chronic, low-level inflammation, which is closely linked to complications such as anemia, poor nutritional status, and cardiovascular issues. The purpose of this study was to assess the average level of the systemic immune-inflammation index (SII) among individuals receiving regular HD due to ESRD and to explore the clinical and laboratory variables associated with ongoing inflammatory conditions, as indicated by the SII. This descriptive cross-sectional study involved 116 patients diagnosed with ESRD who were receiving maintenance HD. Blood samples were collected and tested for complete blood count, serum albumin, lipid profile (including cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol, and triglycerides), and high-sensitivity C-reactive protein (hs-CRP). Several inflammatory markers were derived from the complete blood count results, including the neutrophil-to-lymphocyte ratio, SII, systemic inflammation response index, and pan-immune-inflammation value. Among the 116 HD patients included in the analysis, the median SII was 498.22 (363.85-749.52). Elevated hs-CRP levels (≥3 mg/L) were observed in 35.34% of patients and were associated with clinical and laboratory characteristics such as gender, body mass index, hemoglobin, triglycerides, albumin, HDL-C, and inflammatory indices such as SII, neutrophil-to-lymphocyte ratio, systemic inflammation response index, and pan-immune-inflammation value (P < .05). hs-CRP showed a moderate positive correlation with SII (r = 0.32, P < .001) and an association with anemia, hypoalbuminemia, and dyslipidemia. Receiver operating characteristic analysis demonstrated that SII had the highest area under the curve (0.673), and the combination of high SII and low albumin significantly increased the odds of elevated hs-CRP (OR = 6.50, 95% confidence interval: 1.73-24.39, P < .05). The median SII in HD patients was 498.22, and it showed a moderate correlation with hs-CRP. The high-inflammation group (hs-CRP ≥ 3 mg/L) showed a statistically significant association with hemoglobin, albumin, triglycerides, and HDL-C (P < .05). The combination of SII and albumin improved the identification of patients at high inflammatory risk. These findings suggest that SII and the SII-albumin combination may serve as practical surrogate markers of systemic inflammation in routine dialysis care.

PMID:42299587 | DOI:10.1097/MD.0000000000049213

Medicine (Baltimore). 2026 Jun 12;105(24):e48840. doi: 10.1097/MD.0000000000048840.

ABSTRACT

This study used a two-sample Mendelian randomization (MR) method to explore the potential causal relationship between air quality, cholelithiasis, and its related risk factor, blood lipids. This study used MR in European and East Asian groups, utilizing publicly available genome-wide association study data. The main method was inverse-variance weighting, with additional quality checks including weighted median, MR-Egger, simple, and weighted models. The Cochran Q test assessed heterogeneity. MR-Egger regression and MR-PRESSO checked for gene pleiotropy, with sensitivity tests using leave-one-out analysis. No statistically significant association was observed between air pollution and cholelithiasis in both European and East Asian populations for all pollutants analyzed, including PM2.5 (European: P = .745, East Asian: P = .209), PM2.5 to 10 (European: P = .737), PM10 (European: P = .258, East Asian: P = .977), nitrogen dioxide (European: P = .986, East Asian: P = .893), and nitrogen oxides (European: P = .902, East Asian: P = .843). However, significant correlations between air pollution and blood lipids were identified. In European populations, PM2.5 was significantly correlated with triglycerides (β = 0.428, odds ratio = 1.534, 95% confidence interval = 1.058-2.225; P = .024). In East Asian populations, PM2.5 showed a significant association with low-density lipoprotein (LDL) cholesterol (β = 0.050, odds ratio = 1.051, 95% confidence interval = 1.006-1.098; P = .026). Importantly, no evidence of heterogeneity or pleiotropy was detected in these associations, bolstering the credibility of our findings. Our study found no clear causal link between air pollution and cholelithiasis. However, we observed significant correlations between PM2.5 and triglycerides in Europeans, and between PM2.5 and LDL cholesterol in East Asians. These results suggest that PM2.5 might affect triglyceride and LDL cholesterol metabolism differently in various populations, potentially raising the risk of cholelithiasis indirectly.

PMID:42299586 | DOI:10.1097/MD.0000000000048840

Medicine (Baltimore). 2026 Jun 12;105(24):e49298. doi: 10.1097/MD.0000000000049298.

ABSTRACT

This study aimed to explore the diagnostic value of combining serologic indexes with the Gleason score (GS) in identifying prostate cancer bone metastasis. We included 108 patients diagnosed with prostate cancer at the Third Hospital of Mianyang from December 2019 to December 2021. Clinical data were collected, and patients were divided into 2 groups: 44 cases with prostate cancer bone metastasis and 64 cases without bone metastasis. We compared age, serum total prostate-specific antigen (TPSA), free prostate-specific antigen (FPSA), fibrinogen (FIB), alkaline phosphatase (ALP), serum albumin (ALB), and GS between the 2 groups. Logistic regression analysis was used to assess the correlation between serologic indexes and prostate cancer bone metastasis. The diagnostic value of combining multiple indexes versus single indexes was evaluated using receiver operating characteristic curves. The serum TPSA, FPSA, FIB, ALP and GS levels of patients in the prostate cancer bone metastasis group were higher than those of patients in the prostate cancer without bone metastasis group, while the ALB level in the bone metastasis group was lower than that in the non-bone metastasis group. The differences in each index were statistically significant when compared between the 2 groups (P < .05). The univariate logistic analysis revealed that TPSA (OR:0.984, P < .001), FPSA (OR:0.899, P < .001), ALP (OR:0.986, P < .05), and GS (OR:0.569, P < .05) were positively correlated with prostate cancer bone metastasis. Multivariate analysis showed that ALP (OR = 0.991, P < .05) was an independent risk factor for bone metastasis in prostate cancer after adjusting for Age, ALB, and FIB. The area under the receiver operating characteristic curve (AUC) of serum ALP and the combined assay were 0.738 and 0.792, respectively. Serum TPSA, FPSA, FIB, ALB, ALP and GS have significant diagnostic value in identifying prostate cancer bone metastasis. ALP is an independent risk factor for bone metastasis in prostate cancer. Combining these indicators can enhance diagnostic efficacy.

PMID:42299585 | DOI:10.1097/MD.0000000000049298

Medicine (Baltimore). 2026 Jun 12;105(24):e49296. doi: 10.1097/MD.0000000000049296.

ABSTRACT

Previous studies have confirmed that the ZJU index is effective in capturing trends in metabolic disorders and disease risk. However, no study has statistically analyzed the relationship between the ZJU Index and depression. This study included data from 16,008 participants sourced from the National Health and Nutrition Examination Survey 2005-2018. Weighted multivariable logistic regression and generalized additive models were used to explore the independent and nonlinear relationships between the ZJU index and depression. A 2-piece linear regression model was used to estimate threshold effects, along with subgroup analyses and interaction tests. To account for multiple testing in subgroup analyses, P values for interaction were additionally adjusted using the Benjamini-Hochberg false discovery rate procedure. A total of 16,008 participants were included, with 7.42% classified as having depression. The prevalence of depression initially decreased and then increased across the ZJU index quartiles (Q1: 6.35%; Q2: 5.38%; Q3: 6.83%; Q4: 11.32%; P < .0001). Both unadjusted and adjusted models demonstrated that higher ZJU index levels were associated with increased depression risk. In Model III, each unit increase in the ZJU index was associated with a 1.4% higher likelihood of depression (Model III: odds ratio (OR) = 1.014, 95% confidence interval (CI): 1.006, 1.022). Curve fitting indicated a J-shaped association between the ZJU index and depression, with a breakpoint (K) of 35.386. To the left of this breakpoint, the ZJU index showed a negative association with depression (OR = 0.948, 95% CI: 0.917-0.980), while to the right, a positive association was observed (OR = 1.022, 95% CI: 1.013-1.032). Subgroup analyses and interaction tests revealed that the association between the ZJU index and depression was dependent on drinking status and diabetes presence (P < .05). Among individuals who consumed alcohol or had diabetes, a positive association between the ZJU index and depression was observed, whereas no significant association was found among nondrinkers or those without diabetes, where the ZJU index and depression showed a nonlinear relationship. There is a J-shaped association between the ZJU index and depression, suggesting that a higher ZJU index may be linked to an increased risk of depression.

PMID:42299580 | DOI:10.1097/MD.0000000000049296

Cancer Med. 2026 Jun;15(6):e72042. doi: 10.1002/cam4.72042.

ABSTRACT

BACKGROUND: Many testicular cancer patients of reproductive age experience reproductive concerns. Metacognitions may alleviate patients’ fear of progression and reproductive concerns. However, this relationship has not been well established in testicular cancer patients of reproductive age.

OBJECTIVE: This study examines the level of reproductive concerns and explores how fear of progression mediates the relationship between metacognitions and reproductive concerns in testicular cancer patients of reproductive age in China.

METHODS: This study employed a quantitative cross-sectional design and was reported in accordance with the STROBE guidelines for observational research. A convenience sample of 192 testicular cancer patients of reproductive age was recruited from a tertiary specialized oncology hospital in Guangzhou, Guangdong, China. Data were collected through the WeChat mini program “Questionnaire Star” using “the general data questionnaire”, the Metacognitions Questionnaire-30 (MCQ-30), the Fear of Progression Questionnaire-Short Form (FoP-Q-SF), and the Reproductive Concerns After Cancer-Male scale (RCAC-M) instruments. The data were analyzed using descriptive statistics, Pearson correlation analyses, and simple mediation effect analysis via the PROCESS macro program.

RESULTS: Reproductive concerns were at a moderate level (57.86 ± 10.93), and positively associated with metacognitions (r = 0.358, p < 0.001) and fear of progression (r = 0.523, p < 0.001). Mediation analysis revealed that metacognitions had a total effect path coefficient of 0.317 on reproductive concerns (bootstrap 95% CI: 0.202-0.432). The direct effect path coefficient was 0.152 (bootstrap 95% CI: 0.026-0.277), while the mediating effect through fear of progression was 0.166 (bootstrap 95% CI: 0.094-0.239), representing 52.4% of the total effect.

CONCLUSIONS: In testicular cancer patients of reproductive age, metacognitions are significantly associated with reproductive concerns, and fear of progression acts as a mediating factor. Interventions aimed at improving metacognition levels and reducing fear of progression may help alleviate reproductive concerns in this population.

PMID:42298302 | DOI:10.1002/cam4.72042

J Am Med Inform Assoc. 2026 Jun 16:ocag083. doi: 10.1093/jamia/ocag083. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop privacy-enhancing statistical methods for estimating disease risk parameters across multiple electronic health record (EHR) sites with heterogeneous selection mechanisms, avoiding individual-level data sharing. We illustrate their utility via a cross-biobank analysis of smoking and 97 cancer subtypes using NIH All of Us (AOU) and Michigan Genomics Initiative (MGI) data sites.

MATERIALS AND METHODS: Distributed health platforms often render centralized algorithms infeasible due to patient privacy protection. We propose Sequential Pseudo-Likelihood (SPL) and Sequential Augmented Inverse Probability Weighting (SAIPW) to adjust for selection bias using summary statistics shared across sites and external population information. SAIPW employs flexible auxiliary models for multiple robustness. We compared SPL and SAIPW against unweighted and centralized/meta-learning benchmarks in simulations, applying them to harmonized MGI (n = 50 935) and AOU (n = 241 563) data.

RESULTS: Unweighted estimators exhibited substantial bias. SPL and SAIPW yielded unbiased estimates with valid coverage, with SAIPW remaining robust to selection model misspecification. Both approaches showed negligible efficiency loss relative to centralized methods. Meta-learning methods proved unstable for rare outcomes. Real-data analyses consistently identified strong associations between smoking and lung, bladder, and larynx cancers.

DISCUSSION: These findings highlight the necessity of adjusting for site-specific selection biases in distributed health networks. SPL and SAIPW offer practical, scalable solutions that bypass the instability of meta-analysis for rare events, successfully harmonizing diverse biobanks while strictly enhancing patient privacy.

CONCLUSION: Our framework enables valid, privacy-enhancing inference across EHR sites subject to heterogeneous selection, facilitating scalable, distributed research using real-world data.

PMID:42298300 | DOI:10.1093/jamia/ocag083

J Robot Surg. 2026 Jun 16;20(1):588. doi: 10.1007/s11701-026-03607-y.

ABSTRACT

To compare textbook outcome (TO) and postoperative pain trajectories between reduced-port robotic distal gastrectomy (rpRDG) and conventional robotic distal gastrectomy (cRDG) for gastric cancer (GC). This retrospective cohort study analyzed patients who underwent robotic distal gastrectomy for GC between September 2022 and March 2026 at a single tertiary center. Cumulative sum (CUSUM) analysis was applied to exclude 30 cases representing the initial learning curve, yielding 107 patients (cRDG, n = 60; rpRDG, n = 47). Following 1:1 propensity score matching (PSM), 39 matched pairs were analyzed. The primary endpoint was TO achievement; secondary endpoints included operative time, estimated blood loss (EBL), retrieved lymph nodes, and postoperative pain assessed by numeric rating scale (NRS) from postoperative day (POD) 1 to 3. The two groups were well-balanced after PSM (all absolute standardized mean differences < 0.1). TO achievement rates were comparable between groups (cRDG: 79.49% vs. rpRDG: 87.18%, p = 0.3621), with no significant differences in operative time (264.97 vs. 246.23 min, p = 0.0808), EBL (47.05 vs. 43.21mL, p = 0.7088), or retrieved lymph nodes (34.67 vs. 38.92, p = 0.2686). A linear mixed-effects model revealed a significant group-by-time interaction in pain scores (p = 0.0044), and the rpRDG group reported significantly lower NRS scores on POD 1 (2.62 vs. 3.13, p = 0.0155). rpRDG demonstrated comparable surgical and oncologic outcomes to cRDG, with statistically significant reduction in early postoperative pain on POD 1, representing a meaningful marginal gain within an ERAS-optimized setting. These findings support rpRDG as a feasible, patient-centered alternative warranting further multicenter validation.

PMID:42298275 | DOI:10.1007/s11701-026-03607-y

Biol Trace Elem Res. 2026 Jun 15. doi: 10.1007/s12011-026-05174-7. Online ahead of print.

ABSTRACT

Maize flour is widely consumed in Turkey and may contain trace elements originating from agricultural practices and environmental contamination during cultivation, processing, and storage. This study aimed to determine the concentrations of Fe, Zn, Cu, Ni, Mn, Cd, and Cr in 20 commercially available maize flour samples using Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES). In addition, potential non-carcinogenic health risks associated with maize flour consumption were evaluated. The accuracy and reliability of the analytical procedure were verified using certified reference material analysis and quality control procedures. The mean concentrations of Fe, Zn, Cu, Ni, and Mn in the analyzed samples were found to be 18.5, 13.1, 1.7, 0.2, and 3.9 mg/kg, respectively, while Cd and Cr concentrations were below the detection limits. The obtained concentrations were evaluated according to international regulatory limits and previously reported literature data. Non-carcinogenic health risk assessment was conducted using hazard quotient (HQ) and hazard index (HI) values, and the results indicated that the detected trace element concentrations are unlikely to pose significant non-carcinogenic health risks to consumers. In addition, descriptive statistical analysis, Spearman’s rank correlation analysis, and Principal Component Analysis (PCA) were performed to evaluate the distribution characteristics of the analyzed elements, investigate relationships among trace elements, and identify possible common sources. These findings may provide baseline data for future studies on trace element levels and dietary exposure assessment of maize flour consumed in Turkey.

PMID:42298271 | DOI:10.1007/s12011-026-05174-7