Long-term trends in the burden of nasopharyngeal carcinoma in China: A comprehensive analysis from 1990 to 2021 and projections to 2030 based on the global burden of disease study 2021.

BACKGROUND AND PURPOSE: Nasopharyngeal carcinoma (NPC) is a significant public health issue in China, with distinctive epidemiological characteristics and evolving trends. This study aims to analyze long-term trends in NPC burden from 1990 to 2021 and provide projections. MATERIALS AND METHODS: Data from the Global Burden of Disease (GBD) database (1990-2021) was utilized to evaluate NPC metrics, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs). Joinpoint regression identified significant changes over time. Age-period-cohort (APC) analyses assessed the effects of age, period, and cohort. A decomposition analysis identified factors influencing changes in NPC incidence, prevalence, and DALYs. Projections were made for future trends up to 2030. RESULTS: In 2021, NPC significantly impacted China, with males experiencing higher incidence (5.16 per 100,000) and mortality rates (2.32 per 100,000) than females. NPC prevalence was 342,477 cases, with males accounting for 260,164. DALYs totaled 982,657, predominantly affecting males. From 1990 to 2021, the age-standardized incidence rate (ASIR) in China decreased from 4.64 to 3.42 per 100,000, while globally it declined from 1.74 to 1.38 per 100,000. Between 1990 and 2021, trends showed an initial decline in ASIR and ASPR, followed by a steady increase from 2006 onwards, with males experiencing more significant rises. Mortality rates showed a general downward trend, yet males remained disproportionately affected. Comparative global data indicated that while NPC metrics are declining worldwide, the burden remains higher in China. Decomposition analysis highlighted aging and population growth as major contributors to the NPC burden. BAPC projections indicated a continuing rise in age-standardized incidence and prevalence rates for both males and females up to 2030. CONCLUSIONS: The burden of NPC in China remains significant, particularly among the male population. Despite declining mortality rates, the increasing prevalence suggests that more people are living with NPC. Targeted public health interventions are urgently needed to address these gender-specific trends and reduce the disease burden.

The association of adolescent to midlife weight change with age at natural menopause: a population study of 263,586 women in Norway.

Age at menopause varies considerably among women and is linked to health after menopause. Body mass index is associated with age at natural menopause, but the influence of weight change remains unclear. Thus, we studied associations of adolescent to midlife weight change with age at natural menopause. We performed a retrospective population-based cohort study of 263,586 women aged 50-69 years attending BreastScreen Norway (2006-2015). The associations were estimated as hazard ratios (HRs) for having reached menopause using Cox proportional hazard models. We included nine categories of weight change based on recalls of adolescent weight compared to peers and quartiles of midlife weight in kilograms. We adjusted for year and country of birth, education, number of childbirths, height, smoking, and exercise. Women with the largest estimated weight loss had highest hazard of reaching menopause (adjusted HR 1.11, 95% CI: 1.06-1.17) compared to women with estimated stable average weight. Conversely, women with the largest estimated weight gain had lower hazard (adjusted HR 0.96, 95% CI: 0.93-0.99). Women with estimated stable high weight had lowest hazard of reaching menopause (adjusted HR 0.93, 95% CI: 0.90-0.95). Our findings suggest that changes in body weight across the life course may influence the timing of menopause.

Association between stress hyperglycemia ratio and postoperative major adverse cardiovascular and cerebrovascular events in noncardiac surgeries: a large perioperative cohort study.

BACKGROUND: There has been a concerning rise in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) following noncardiac surgeries (NCS), significantly impacting surgical outcomes and patient prognosis. Glucose metabolism abnormalities induced by stress response under acute medical conditions may be a risk factor for postoperative MACCE. This study aims to explore the association between stress hyperglycemia ratio (SHR) and postoperative MACCE in patients undergoing general anesthesia for NCS. METHODS: There were 12,899 patients in this perioperative cohort study. The primary outcome was MACCE within 30 days postoperatively, defined as angina, acute myocardial infarction, cardiac arrest, arrhythmia, heart failure, stroke, or in-hospital all-cause mortality. Kaplan-Meier curves visualized the cumulative incidence of MACCE. Cox proportional hazard models were utilized to assess the association between the risk of MACCE and different SHR groups. Restricted cubic spline analyses were conducted to explore potential nonlinear relationships. Additionally, exploratory subgroup analyses and sensitivity analyses were performed. RESULTS: A total of 592 (4.59%) participants experienced MACCE within 30 days after surgery, and 1,045 (8.10%) within 90 days. After adjusting for confounding factors, compared to the SHR T2 group, the risk of MACCE within 30 days after surgery increased by 1.34 times (95% CI 1.08-1.66) in the T3 group and by 1.35 times (95% CI 1.08-1.68) in the T1 group respectively. In the non-diabetes group, the risk of MACCE within 30 days after surgery increased by 1.60 times (95% CI 1.21-2.12) in the T3 group and by 1.61 times (95% CI 1.21-2.14) in the T1 group respectively, while no statistically significant increase in risk was observed in the diabetes group. Similar results were observed within 90 days after surgery in the non-diabetes group. Additionally, a statistically significant U-shaped nonlinear relationship was observed in the non-diabetes group (30 days: P for nonlinear = 0.010; 90 days: P for nonlinear = 0.008). CONCLUSION: In this large perioperative cohort study, we observed that both higher and lower SHR were associated with an increased risk of MACCE within 30 and 90 days after NCS, especially in patients without diabetes. These findings suggest that SHR potentially plays a key role in stratifying cardiovascular and cerebrovascular risk after NCS.

Long-term trends and future projections of larynx cancer burden in China: a comprehensive analysis from 1990 to 2030 using GBD data.

Larynx cancer poses a significant public health challenge in China, with rising incidence and mortality rates over the past decades. Understanding the long-term trends and underlying factors is crucial for effective intervention and policy formulation. Data were utilized from the global burden of disease (GBD) Study 2021 to analyze the incidence, prevalence, mortality, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) due to larynx cancer in China from 1990 to 2021. Joinpoint regression analysis identified key changes in trends, while age-period-cohort (APC) analysis and decomposition analysis quantified the contributions of aging, epidemiological changes, and population growth to these trends. Our study found a significant increase in the incidence and prevalence of larynx cancer in China, particularly among males. The age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for males were substantially higher than those for females. Decomposition analysis revealed that aging was the primary driver of increasing incidence and mortality rates, while epidemiological changes had a mitigating effect. Joinpoint analysis identified periods of rapid urbanization and economic growth as key turning points for increased incidence. Bayesian APC models projected a continued upward trend in incidence rates up to 2030. The rising burden of larynx cancer in China underscores the need for targeted public health interventions, including smoking cessation programs, environmental pollution control, and early detection strategies. Addressing gender disparities and implementing effective prevention measures are crucial to mitigating the impact of larynx cancer in China.

The effect of lipidomes on the risk of endometrioid endometrial cancer: a Mendelian randomization study.

Objective: This study aimed to explore the potential effects between various human plasma lipidomes and endometrioid endometrial cancer (EEC) by using Mendelian randomization (MR) methods. Methods: This study designated a total of 179 human plasma lipidomes from the genome-wide association study (GWAS) database as the exposure variable. An EEC-related dataset from the GWAS (GCST006465) served as the outcome variable. MR analyses used the inverse variance-weighted method (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods for regression calculations, accounting for possible biases induced by linkage disequilibrium and weak instrument variables. Any lipidomes failing to pass heterogeneity and horizontal pleiotropy tests were deemed to lack significant causal impact on the outcome. Results: The results of IVW analysis disclosed that a variety of human plasma lipidomes (n = 15) exhibited a significant causal effect on EEC (p < 0.05). A subset of these lipidomes (n = 13) passed heterogeneity and horizontal pleiotropy tests, which demonstrated consistent and viable causal effects (p < 0.05) including glycerophospholipids, glycerolipids, and sterols. Specifically, phosphatidylcholine (odds ratio [OR]: 1.065-1.129, p < 0.05) exhibited a significant positive causal effect on the occurrence of EEC. Conversely, sterol ester (OR = 0.936, p = 0.007), diacylglycerol (OR = 0.914, p = 0.036), phosphatidylcholine (OR: 0.903-0.927, p < 0.05), phosphatidylethanolamine (OR = 0.907, p = 0.046) and triacylglycerol (OR: 0.880-0.924, p < 0.05) showed a notable negative causal association with EEC, suggesting their inhibitory effects on the EEC occurrence. Conclusions: The study revealed that human plasma lipidomes have complex impacts on EEC through Mendelian randomization. This indicated that the diversity of structural changes in lipidomes could show different effects on subtypes and then affect EEC occurrence. Although these lipids had the potential to be promising biomarkers, they needed to be further clinically validated nevertheless.

Breast cancer in women with previous gestational diabetes: a nationwide register-based cohort study.

BACKGROUND: Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk. METHODS: We conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test. RESULTS: Of 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83-1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk. CONCLUSIONS: This large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized.

Improved clinical and radiographic outcomes with expandable cages in transforaminal lumbar interbody fusion: a propensity-matched cohort analysis.

OBJECTIVE: The restoration of sufficient overall lumbar lordosis (LL) and segmental LL (SL) is associated with achieving optimal sagittal balance, decreasing back pain, and enhancing functional outcomes for patients. Expandable cages were developed in hopes of improving radiographic parameters and clinical outcomes, although current clinical evidence is inconclusive. Here, the authors aimed to evaluate the clinical and radiographic outcomes in patients undergoing one- or two-level open transforaminal lumbar interbody fusion (TLIF) with expandable versus static cage placement, using propensity-matched cohorts. METHODS: An institutional retrospective cohort of patients who underwent one- or two-level open TLIF with either expandable cage or static cage placement was identified. Using relevant preoperative covariates, including age, primary versus revision operation, number of cages implanted, and surgical level implanted, the authors built propensity-matched cohorts. They identified clinical outcomes in both cohorts, including operative characteristics and complication rates, along with pain, weakness, and sensory deficits over follow-up. Furthermore, they extracted and examined preoperative, postoperative, and last follow-up radiographic parameters. RESULTS: A total of 148 patients were included, and they were followed for a mean of 1.7 years (range 0.5-4.3 years). Propensity matching was used to create cohorts of patients who were similar with respect to age, surgical indication, revision status, number of cages implanted, surgical level implanted, and length of follow-up. Patients in both groups had similar preoperative radiographic parameters. Patients with expandable cages saw larger increases in SL, both postoperatively (5.3° ± 7.5° vs 1.6° ± 5.6°, p = 0.006) and at last follow-up (5.7° ± 7.4° vs 1.0° ± 6.1°, p = 0.003). They also saw significant improvements in pelvic incidence minus LL mismatch at last follow-up (-4.4° ± 13.2° vs 5.8° ± 13.8°, p = 0.009). No differences in intraoperative or perioperative complications were found, but patients with expandable cages were less likely to require readmission, develop adjacent-segment disease, or require revision surgery. They were also more likely to be symptom free at 1 month after surgery and at last follow-up. CONCLUSIONS: Expandable cages lead to better restoration of radiographic features, including SL and improvements in clinical outcomes, compared with static cages in propensity-matched cohorts in patients undergoing one- or two-level open TLIFs.

Concordant and discordant breast density patterns by different approaches for assessing breast density and breast cancer risk.

PURPOSE: To examine the discrepancy in breast density assessments by radiologists, LIBRA software, and AI algorithm and their association with breast cancer risk. METHODS: Among 74,610 Korean women aged ≥ 34 years, who underwent screening mammography, density estimates obtained from both LIBRA and the AI algorithm were compared to radiologists using BI-RADS density categories (A-D, designating C and D as dense breasts). The breast cancer risks were compared according to concordant or discordant dense breasts identified by radiologists, LIBRA, and AI. Cox-proportional hazards models were used to determine adjusted hazard ratios (aHRs) [95% confidence intervals (CIs)]. RESULTS: During a median follow-up of 9.9 years, 479 breast cancer cases developed. Compared to the reference non-dense breast group, the aHRs (95% CIs) for breast cancer were 2.37 (1.68-3.36) for radiologist-classified dense breasts, 1.30 (1.05-1.62) for LIBRA, and 2.55 (1.84-3.56) for AI. For different combinations of breast density assessment, aHRs (95% CI) for breast cancer were 2.40 (1.69-3.41) for radiologist-dense/LIBRA-non-dense, 11.99 (1.64-87.62) for radiologist-non-dense/LIBRA-dense, and 2.99 (1.99-4.50) for both dense breasts, compared to concordant non-dense breasts. Similar trends were observed with radiologists/AI classification: the aHRs (95% CI) were 1.79 (1.02-3.12) for radiologist-dense/AI-non-dense, 2.43 (1.24-4.78) for radiologist-non-dense/AI-dense, and 3.23 (2.15-4.86) for both dense breasts. CONCLUSION: The risk of breast cancer was highest in concordant dense breasts. Discordant dense breast cases also had a significantly higher risk of breast cancer, especially when identified as dense by either AI or LIBRA, but not radiologists, compared to concordant non-dense breast cases.

Association between urinary cotinine level and hypertensive disorders of pregnancy in women with uterine myoma: findings from the Japan Environment and Children's Study.

The effect of smoking on hypertensive disorders of pregnancy is a public concern. Recent evidence suggests that the risk of hypertensive disorders of pregnancy is influenced by the presence of uterine fibroids. We explored the association between maternal smoking exposure and the risk of hypertensive disorders of pregnancy in relation to the presence of uterine fibroids using data from Japan's largest birth cohort study. This study focused on first-time mothers, and the study population comprised 2752 and 35,294 first-time mothers with and without uterine fibroids, respectively. Hypertensive disorders of pregnancy was categorized as early-onset (before 34 weeks) and late-onset (after 34 weeks). Maternal smoking exposure was assessed by measuring the urinary cotinine concentration during the mid-trimester. Participants were classified into four quartiles based on their urinary cotinine levels as follows: Q1 (low concentration) to Q4 (high concentration). Multivariate analysis adjusted for potential confounders revealed that in women without uterine fibroids, the Q3 urinary cotinine level was associated with a modified risk of early-onset hypertensive disorders of pregnancy (adjusted odds ratio: 0.63, 95% confidence interval: 0.44-0.89). Conversely, for women with uterine fibroids, Q4 urinary cotinine level was associated with an increased risk of hypertensive disorders of pregnancy (adjusted odds ratio: 1.68, 95% confidence interval: 1.05-2.72). In conclusion, this study indicated that the impact of maternal smoking exposure varied based on the presence of uterine fibroids, underscoring the importance of personalized preconception care.

The association between pan-immune-inflammation value and chronic obstructive pulmonary disease: data from NHANES 1999-2018.

Background: The pan-immune-inflammation value (PIV) is an emerging biomarker quantitatively reflecting the systemic immune-inflammatory status. The predictive value of PIV has been well-established across various clinical settings. However, its role in chronic obstructive pulmonary disease (COPD) remains unclear and necessitates further investigation. Methods: Data from NHANES 1999-2018 were filtered. Logistic regression analyses were used to assess the correlation between COPD prevalence and PIV in all participants. COX regression analyses and Kaplan-Meier survival curves were used to investigate the relationship between COPD all-cause mortality and PIV in COPD patients. Restricted cubic spline (RCS) analyses and piecewise linear regression analyses were additionally employed to explore the correlation between PIV and COPD. Subgroup analyses were performed to further clarify the effects of other covariates on the associations. Sensitivity analyses were employed to assess the robustness of the results. Results: A total of 28,485 participants aged 40 years and older were recruited for this study. After fully adjusting for covariates, higher PIV levels were independently associated with increased COPD prevalence (OR = 1.67; 95% CI: 1.39-2.01) and all-cause mortality (HR = 2.04; 95% CI: 1.41-2.95). The COPD prevalence curve exhibited an inflection point at Log10-PIV of 2.24, showing no significant correlation on the left side (OR = 0.86; 95% CI: 0.45-1.64) but a positive correlation on the right side (OR = 2.00; 95% CI: 1.57-2.55). The COPD all-cause mortality curve displayed an inflection point at Log10-PIV of 2.38, indicating a negative correlation on the left side (HR = 0.23; 95% CI: 0.12-0.44) and a positive correlation on the right side (HR = 4.12; 95% CI: 2.62-6.48). Subgroup analyses with interaction tests showed that the strength of the correlation between PIV and COPD prevalence was influenced by race, smoking status, and BMI (all p for interaction <0.05). The relationship between PIV and COPD all-cause mortality was unaffected by any covariates (all p for interaction >0.05). Conclusion: Elevated PIV levels are associated with increased COPD prevalence. COPD patients with either elevated or reduced PIV levels experience higher all-cause mortality. Further large-scale, longitudinal studies are required to corroborate these findings.

Kidney function, uric acid, and risk of atrial fibrillation: experience from the AMORIS cohort.

BACKGROUND: Uric acid closely relates to both kidney disease and atrial fibrillation (AF), yet the extent to which it influences the kidney-AF association remains uncertain. We examined the relationship between kidney function and risk of AF, accounting for uric acid levels. METHODS: A total of 308,509 individuals in the Swedish Apolipoprotein-Related Mortality Risk (AMORIS) cohort were included and their serum creatinine and uric acid were measured during 1985-1996. Ten-year incident AF was identified via linkage with the national registers. Glomerular filtration rate (eGFR) (ml/min/1.73 m2) was calculated with the 2009 Chronic Kidney Disease Epidemiology Collaboration equation. Hyperuricemia was defined as > 420 µmol/L for men and > 360 µmol/L for women. RESULTS: Over a mean follow-up of 9.4 years, 10,007 (3.2%) incident AF cases occurred. After adjusting for age, sex, cardiovascular diseases, total cholesterol, triglycerides, and glucose, individuals with low eGFR (< 30 and 30-59 ml/min/1.73 m2 ) had a higher risk of AF compared to those with normal eGFR (60-89) (hazard ratio (HR) = 1.72, 95% confidence interval (CI):1.29-2.30; HR = 1.10, 95% CI: 1.03-1.18, respectively). After further adjusting for uric acid levels, the association disappeared (HR = 0.97, 95% CI: 0.72-1.30; HR = 0.93, 95% CI: 0.86-1.00, respectively). When stratifying by hyperuricemia yes/no, eGFR < 30 ml/min/1.73 m2 was associated with higher AF risk in a small group of individuals without hyperuricemia (HR = 2.58, 95% CI: 1.64-4.07). CONCLUSION: Uric acid largely accounted for the relationship between eGFR and AF in this study. However, in individuals without hyperuricemia, eGFR in the lowest range (< 30 ml/min/1.73 m2) was still associated with increased risk of AF.

Functional and radiological outcomes and complications of bernese periacetabular osteotomy through modified Stoppa approach.

BACKGROUND: The Smith-Peterson approach and its modifications provide an extensive exposure and allow osteotomies through a single incision. However, the risk of complications increases when the quadrilateral surface, ischial and pubic osteotomy sites cannot be seen. This study aimed to evaluate the surgical characteristics, complications, and functional and radiological outcomes of patients with acetabular dysplasia who underwent Bernese periacetabular osteotomy (PAO) through modified Stoppa approach and plate-screw fixation. METHODS: The study included 31 patients (41 hips) who had undergone PAO using a modified Stoppa approach. The characteristics of patients and the surgical procedure were described. The lateral centre-edge angle (LCEA) and Tönnis roof angle were evaluated in the radiological outcome evaluation. The modified Harris Hip Score (mHHS) was used to evaluate functional outcome. Furthermore, complications were described. RESULTS: The mean age of the patients was 20.4 ± 9.0 years. Of the 31 patients, 21 underwent unilateral Bernese PAO and 10 underwent bilateral Bernese PAO. The mean follow-up period was 25.1 ± 8.8 months. Postoperatively, the mean mHHS improved significantly (68.8 ± 9.4 vs. 88.8 ± 10.0, p < 0.001). Postoperatively, the mean LCEA and Tönnis roof angle improved significantly (17.7 ± 6.0 vs. 42.2 ± 4.8, p < 0.001 for LCEA and 18.3 ± 5.5 vs. 8.0 ± 2.2, p < 0.001 for Tönnis roof angle). There was no significant correlation between preoperative to postoperative improvement in LCEA or Tönnis roof angle and improvement and mHHS (p > 0.005). 5 complications were identified: 1 transient sciatic nerve palsy, 1 external iliac vein injury, 1 infection, and 2 screw irritations of acetabulum. CONCLUSIONS: Performing Bernese PAO through a modified Stoppa approach with plate-screw fixation results in acceptable complication rates, immediate early weight-bearing opportunity, and improved functional and radiological outcomes in patients with acetabular dysplasia.

The ENDOMIX perspective: how everyday chemical mixtures impact human health and reproduction by targeting the immune system†.

Endocrine disruptor chemicals (EDCs) are natural and synthetic compounds found ubiquitously in the environment that interfere with the hormonal-immune axis, potentially impacting human health and reproduction. Exposure to EDCs has been associated with numerous health risks, such as neurodevelopmental disorders, metabolic syndrome, thyroid dysfunction, infertility, and cancers. Nevertheless, the current approach to establishing causality between EDCs and disease outcomes has limitations. Epidemiological and experimental research on EDCs faces challenges in accurately assessing chemical exposure and interpreting non-monotonic dose response curves. In addition, most studies have focused on single chemicals or simple mixtures, overlooking complex real-life exposures and EDC mechanistic insights, in particular regarding their impact on the immune system. The ENDOMIX project, funded by the EU's Horizon Health Program, addresses these challenges by integrating epidemiological, risk assessment, and immunotoxicology methodologies. This systemic approach comprises the triangulation of human cohort, in vitro, and in vivo data to determine the combined effects of EDC mixtures. The present review presents and discusses current literature regarding human reproduction in the context of immunotolerance and EDC mode of action. It further underscores the ENDOMIX perspective to elucidate the impact of EDCs on immune-reproductive health.

A comprehensive study of genetic regulation and disease associations of plasma circulatory microRNAs using population-level data.

BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Perturbations in plasma miRNA levels are known to impact disease risk and have potential as disease biomarkers. Exploring the genetic regulation of miRNAs may yield new insights into their important role in governing gene expression and disease mechanisms. RESULTS: We present genome-wide association studies of 2083 plasma circulating miRNAs in 2178 participants of the Rotterdam Study to identify miRNA-expression quantitative trait loci (miR-eQTLs). We identify 3292 associations between 1289 SNPs and 63 miRNAs, of which 65% are replicated in two independent cohorts. We demonstrate that plasma miR-eQTLs co-localise with gene expression, protein, and metabolite-QTLs, which help in identifying miRNA-regulated pathways. We investigate consequences of alteration in circulating miRNA levels on a wide range of clinical conditions in phenome-wide association studies and Mendelian randomisation using the UK Biobank data (N = 423,419), revealing the pleiotropic and causal effects of several miRNAs on various clinical conditions. In the Mendelian randomisation analysis, we find a protective causal effect of miR-1908-5p on the risk of benign colon neoplasm and show that this effect is independent of its host gene (FADS1). CONCLUSIONS: This study enriches our understanding of the genetic architecture of plasma miRNAs and explores the signatures of miRNAs across a wide range of clinical conditions. The integration of population-based genomics, other omics layers, and clinical data presents opportunities to unravel potential clinical significance of miRNAs and provides tools for novel miRNA-based therapeutic target discovery.

Epigenetic aging and fecundability: the Norwegian Mother, Father and Child Cohort Study.

STUDY QUESTION: Is there an association between male or female epigenetic age acceleration (EAA) or deceleration (EAD) and fecundability? SUMMARY ANSWER: We do not find compelling evidence of an association between EAA or EAD and fecundability. WHAT IS KNOWN ALREADY: Prior research has shown that female accelerated epigenetic aging is associated with unfavorable clinical fecundity outcomes and use of in vitro fertilization, and that epigenetic aging in sperm cells is associated with unfavorable sperm parameters. Studies of epigenetic aging and fecundability among individuals who conceive naturally are lacking. STUDY DESIGN, SIZE, DURATION: This study is based on the Norwegian Mother, Father and Child Cohort Study (MoBa), a population-based pregnancy cohort which recruited pregnant couples between 1999 and 2008. We used data from 1657 couples (women and men) with planned naturally conceived pregnancies and available blood samples. PARTICIPANTS/MATERIALS, SETTING, METHODS: Methylation levels were measured in DNA from blood samples taken recruitment (at ∼18 gestational weeks) from pregnant women and their partners using the Illumina Methylation EPIC Array. To obtain a measure of EAA/EAD, we performed a linear regression of each of seven different established epigenetic biomarkers (DNAmAge by Horvath, DNAmAge by Hannum et al., PhenoAge by Levine et al., DunedinPoAm by Belsky et al., DunedinPACE by Belsky et al., DNAmTL by Lu et al., and GrimAge by Lu et al.) against chronological age. We fitted proportional probability regression models to obtain fecundability ratios (FRs) for each standard deviation increase in epigenetic aging, and obtained crude and adjusted (for body mass index, smoking, and education level) estimates. Results were evaluated at a false discovery rate (FDR) of 5%. We evaluated all models for non-linear associations using categories of epigenetic age where appropriate. MAIN RESULTS AND THE ROLE OF CHANCE: Although the DunedinPACE clock in males demonstrated slightly increasing fecundability with increasing EAA (adjusted FR 1.05 per one standard deviation increase in EAA, 95% CI 1.00-1.10), this was not robust when evaluated at an FDR of 5%. We found evidence of non-linearity between biological aging and fecundability in two models in females and three models in males, but non-linear associations were weak and conflicting. LIMITATIONS, REASONS FOR CAUTION: As MoBa is a pregnancy cohort, our findings may not be generalizable to all couples attempting conception. Fecundability is a couple-level measure, and any impacts of epigenetic aging in each partner may be obscured by effects of the other partner. WIDER IMPLICATIONS OF THE FINDINGS: Our findings contrast with those of prior studies, which have indicated an association between EAA and unfavorable clinical fertility outcomes in populations using fertility treatments, possibly due to less important effects of epigenetic aging among couples who conceive naturally. More research is needed on the association between blood-based EAA and clinical fertility parameters in both sexes. STUDY FUNDING/COMPETING INTEREST(S): The study was supported by the Research Council of Norway through its Medical Student Research Program funding scheme (project number 271555/F20), its Centres of Excellence funding scheme (project number 262700), and a grant from the Women's Health Program (320656). Co-funding was also received from the Strategic Research Council (SRC), FLUX consortium, decision numbers 345130 and 345131; the National Institute on Aging (R01AG075208); grants to the Max Planck-University of Helsinki Center from the Max Planck Society (decision number 5714240218), Jane and Aatos Erkko Foundation, Faculty of Social Sciences at the University of Helsinki, and Cities of Helsinki, Vantaa, and Espoo; and the European Research Council; and the European Research Council (ERC Synergy, BIOSFER, grant number 101071773, and the Horizon 2020 research and innovation program, grant number 947684). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Association Between Consumption of Foods Containing Vitamin D and All-Cause Mortality in Korea.

Sufficient vitamin D levels are reported to be a factor in reducing various chronic diseases and resulting mortality rates. Well-dried mushrooms and blue-backed fish are known to be rich in vitamin D. In this study, the association between mortality rates and the intake of vitamin D-rich foods was confirmed using data from the Korean Genome and Epidemiological Study (KoGES). Among the KoGES database, we followed up a total of 6844 adults who participated in the Ansung-Ansan cohort study recruited from 2001 to 2002 and continued for an average of 16.7 years until 2018. The main findings were analyzed using Cox regression analysis. During follow-up, 439 cases of all-cause mortality, 149 cases of cancer-related mortality, and 91 cases of cardiovascular mortality were confirmed. In the fully adjusted model, the hazard ratio (HR) for all-cause mortality in quartile 3 of mushroom consumption was 0.709 (95% confidence interval [CI], 0.525-0.958) compared with quartile 1. In addition, the HRs for cardiovascular mortality in quartile 3 of mushroom consumption were 0.348 (95% CI, 0.154-0.787) compared with those in quartile 1. The HRs of cardiovascular mortality for quartiles 3 and 4 of fish consumption were 0.442 (95% CI, 0.226-0.865) and 0.533 (95% CI, 0.285-0.998), respectively, compared with quartile 1. In conclusion, moderate consumption of mushrooms was related to decreased risk of all-cause and cardiovascular mortality, while heightened fish consumption was inversely related to cardiovascular mortality.

Plasma proteome and incident myocardial infarction: sex-specific differences.

BACKGROUND AND AIMS: Few population-based cohort studies, including both men and women, have explored circulating proteins associated with incident myocardial infarction (MI). This study investigated the relationships between circulating cardiometabolic-related proteins and MI risk using cohort-based and Mendelian randomization (MR) analyses and explored potential sex-specific differences. METHODS: The discovery cohort included 11 751 Swedish adults (55-93 years). Data on 259 proteins assessed with Olink proximity extension assays, biochemical, and questionnaire-based information were used. Participants were followed up for incident MI and death over 8 years through linkage to Swedish registers. Replication analyses were conducted on the UK Biobank sample (n = 51 613). In MR analyses, index cis-genetic variants strongly related to the proteins were used as instrumental variables. Genetic association summary statistic data for MI were obtained from the CARDIoGRAMplusC4D consortium and FinnGen. RESULTS: Forty-five proteins were associated with incident MI in discovery and replication samples following adjustment for potential confounders and multiple testing. In the secondary analysis, 13 of the protein associations were sex-specific, with most associations identified among women. In MR analysis, genetically predicted higher levels of renin, follistatin, and retinoic acid receptor responder protein 2 were linked to an increased risk of MI. Tissue factor pathway inhibitor, tumor necrosis factor receptors 1 and 2, placenta growth factor had an inverse association with MI. CONCLUSIONS: This study identified both new and confirmed previously established associations between circulating proteins and incident MI and, for the first time, suggested sex-specific patterns in multiple protein-MI associations.

Cancer-related Fear and Worry in Patients with Low-Risk Thyroid Cancer: A Longitudinal Cohort Study.

CONTEXT: Little is known about how patients' emotions impact the choice between hemi- and total thyroidectomy (TT) for low-risk thyroid cancer (LR-TC) and how these emotions change after treatment. OBJECTIVE: To investigate thyroid cancer-specific fear and worry both before and after treatment of LR-TC with hemi- or TT. METHODS: This prospective cohort study enrolled adults with confirmed or likely LR-TC at 15 institutions. Participants completed measures of thyroid cancer-related fear and worry at the time of their treatment decision and 9-months later. Participants were categorized as having low, medium, or high levels of fear and worry in accordance with the literature. Those choosing hemi-thyroidectomy were compared to those choosing TT. RESULTS: Of 177eligible patients, 125 (70.6%) enrolled and 114 completed both surveys (91.2% retention). Overall, 41 (36.0%) participants chose hemi-thyroidectomy and 73 (64.0%) chose TT. Across all participants, thyroid cancer-related fear and worry both decreased significantly after surgery (fear 25.8±6.4 to 23.1±7.4; worry 8.2±2.4 to 5.4±2.1, p<0.001). The proportion of participants with high fear decreased from 64.9% to 50.9%, while the proportion with high worry decreased from 75.4% to 41.2% (p<0.001 for both). At both time points, no differences existed between those choosing hemi- and TT in levels of worry or fear. CONCLUSION: Patients with LR-TC report lower levels of fear and worry 9-months after surgery regardless of the extent of surgery, suggesting that both surgeries provide an emotional benefit to some patients. Thyroid cancer-related fear and worry do not appear to influence patients' decisions to undergo hemi- or TT.

Disparities in lung cancer screening utilization at two health systems in the Southeastern USA.

PURPOSE: Low-dose computed tomography lung cancer screening is effective for reducing lung cancer mortality. It is critical to understand the lung cancer screening practices for screen-eligible individuals living in Alabama and Georgia where lung cancer is the leading cause of cancer death. High lung cancer incidence and mortality rates are attributed to high smoking rates among underserved, low income, and rural populations. Therefore, the purpose of this study is to define sociodemographic and clinical characteristics of patients who were screened for lung cancer at an Academic Medical Center (AMC) in Alabama and a Safety Net Hospital (SNH) in Georgia. METHODS: A retrospective cohort study of screen-eligible patients was constructed using electronic health records between 2015 and 2020 seen at an Academic Medical Center (AMC) and a Safety Net Hospital (SNH) separately. Chi-square tests and Student t tests were used to compare screening uptake across patient demographic and clinical variables. Bivariate and multivariate logistic regressions determined significant predictors of lung cancer screening uptake. RESULTS: At the AMC, 67,355 were identified as eligible for LCS and 1,129 were screened. In bivariate analyses, there were several differences between those who were screened and those who were not screened. Screening status in the site at Alabama-those with active tobacco use are significantly more likely to be screened than former smokers (OR: 3.208, p < 0.01). For every 10-unit increase in distance, the odds of screening decreased by about 15% (OR: 0.848, p < 0.01). For every 10-year increase in age, the odds of screening decrease by about 30% (OR: 0.704, p < 0.01). Each additional comorbidity increases the odds of screening by about 7.5% (OR: 1.075, p < 0.01). Those with both private and public insurance have much higher odds of screening compared to those with only private insurance (OR: 5.403, p < 0.01). However, those with only public insurance have lower odds of screening compared to those with private insurance (OR: 0.393, p < 0.01). At the SNH-each additional comorbidity increased the odds of screening by about 11.9% (OR: 1.119, p = 0.01). Notably, those with public insurance have significantly higher odds of being screened compared to those with private insurance (OR: 2.566, p < 0.01). CONCLUSION: The study provides evidence that LCS has not reached all subgroups and that additional targeted efforts are needed to increase lung cancer screening uptake. Furthermore, disparity was noticed between adults living closer to screening institutions and those who lived farther.

Long-term efficacy of mepolizumab in patients with eosinophilic granulomatosis with polyangiitis: a propensity score matching analysis in the multicenter REVEAL cohort study.

Background: Mepolizumab (MPZ) has demonstrated efficacy in clinical trials for eosinophilic granulomatosis with polyangiitis (EGPA); however, few studies compare the disease course between patients treated with MPZ (MPZ group) and those who were not treated with MPZ (non-MPZ group) in real-world settings. Objectives: This study aimed to compare the disease course and outcomes between the two groups and assess the long-term efficacy of MPZ in a multicenter cohort in Japan. Methods: We enrolled 113 EGPA patients registered in the cohort until June 2023. Data on clinical characteristics, disease activity, organ damage, treatments, and outcomes were retrospectively collected. To minimize potential confounding factors, we conducted propensity score matching (PSM). Results: After PSM, 37 pairs of matched patients were identified. Clinical characteristics, including age at disease onset, sex, disease duration at last observation, antineutrophil cytoplasmic antibody positivity at disease onset, Birmingham Vasculitis Activity Score (BVAS) at disease onset, and Five-factor score at disease onset, were comparable between the groups. The median BVAS at the last observation was 0 in both groups; however, more cases in the non-MPZ group exhibited elevated BVAS, resulting in a significantly higher BVAS in the non-MPZ group at the last observation (median; MPZ group: 0, non-MPZ group: 0, p=0.028). The MPZ group had significantly lower glucocorticoid (GC) doses at the last observation (median; MPZ group: 4 mg/day, non-MPZ group: 5 mg/day, p=0.011), with a higher proportion achieving a GC dose ≤ 4 mg/day at the last observation (MPZ group: 51.4%, non-MPZ group: 24.2%, p=0.027). Three models of multivariable logistic regression analyses were performed to identify factors associated with GC doses ≤ 4 mg/day at the last observation. In all models, achieving a GC dose ≤ 4 mg/day was positively associated with MPZ administration and inversely associated with asthma at disease onset. Finally, we evaluated the survival rates between the groups, and the 5-year survival rates were significantly higher in the MPZ group compared to the non-MPZ group (MPZ group: 100%, non-MPZ group: 81.3%, p=0.012). Conclusion: Mepolizumab not only contributes to disease activity control but also reduces the GC dose, which may lead to improved survival in EGPA patients.