Significant Increase In Risk Research Articles

Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case-control study within the E3N-Generations cohort.

Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk. We used data from a nested case-control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects). The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00-5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13-4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93-4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05-1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75-1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol. Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.

The contribution of attention-deficit/hyperactivity disorder polygenic load to metabolic and cardiovascular health outcomes: a large-scale population and sibling study.

Emerging evidence suggests that ADHD is associated with increased risk for metabolic and cardiovascular (cardiometabolic) diseases. However, an understanding of the mechanisms underlying these associations is still limited. In this study we estimated the associations of polygenic scores (PGS) for ADHD with several cardiometabolic diseases and biomarkers. Furthermore, we investigated to what extent the PGS effect was influenced by direct and indirect genetic effects (i.e., shared familial effects). We derived ADHD-PGS in 50,768 individuals aged 18-90 years from the Dutch Lifelines Cohort study. Using generalised estimating equations, we estimated the association of PGS with cardiometabolic diseases, derived from self-report and several biomarkers measured during a physical examination. We additionally ran within-sibling PGS analyses, using fixed effects models, to disentangle direct effects of individuals' own ADHD genetic risk from confounding due to indirect genetic effects of relatives, as well as population stratification. We found that higher ADHD-PGS were statistically significantly associated with several cardiometabolic diseases (R-squared [R2] range = 0.03-0.50%) and biomarkers (related to inflammation, blood pressure, lipid metabolism, amongst others) (R2 range = 0.01-0.16%) (P < 0.05). Adjustment for shared familial factors attenuated the associations between ADHD-PGS and cardiometabolic outcomes (on average 56% effect size reduction), and significant associations only remained for metabolic disease. Overall our findings suggest that increased genetic liability for ADHD confers a small but significant risk increase for cardiometabolic health outcomes in adulthood. These associations were observable in the general population, even in individuals without ADHD diagnosis, and were partly explained by familial factors shared among siblings.

RADT-05. VASCULAR OVERLAP PROVIDES PROTECTION FROM GAMMA-KNIFE-INDUCED RADIATION NECROSIS IN A METASTATIC BRAIN TUMOR COHORT

Abstract INTRODUCTION Radiation necrosis (RN) is a long-term complication of Gamma-Knife (GK) Radiosurgery, an established treatment for metastatic brain tumors. Few dosimetric parameters have shown to predict RN, including tumor target volume, treatment dose, and V12 Gy (volume of normal brain receiving 12 Gy). Vascularity has yet to be explored as an independent predictor of RN. OBJECTIVE To evaluate the role of vascular overlap in GK-induced RN. METHODS All metastatic brain tumor patients treated with GK between 2014-2019 were retrospectively screened for post-treatment radiographic RN. Vascular overlap, defined by the MCA-ACA and MCA-PCA border regions, was determined by two blinded neurosurgeons and one radiation oncologist. Multivariate logistic regression analysis was performed to determine factors predictive of RN using variables determined significant by univariate analysis and clinical relevance. Covariates included V12 as a binary variable (≥8 vs. &amp;lt;8 cm3), vascular overlap, supratentorial location, and eloquent location. RESULTS 6% (20/321) of all metastatic brain tumor patients developed RN and were included for analysis, with the final cohort being 60% (12/20) female with a mean age of 59 years, comprising 77 lesions. V12 (≥8 cm3) showed a significant increase in risk of developing RN [OR = 8.18; (coef, 95% CI: 2.10 (0.49, 3.72), p=0.011)]. Conversely, vascular overlap showed a protective effect against RN [OR = 0.23 (-1.49 (-2.79, -0.19), p=0.024)], with a lower rate of RN in areas of vascular overlap (10%) than non-vascular overlap (26%). Neither supratentorial location [OR = 3.31 (1.20 (-0.76, 3.16), p=0.231)] nor location within eloquent brain [OR = 0.96 (-0.04 (-1.48, 1.39), p=0.95)] showed significance. CONCLUSION For the first time, we show that patients with metastatic brain lesions in anatomical regions of vascular overlap treated with GK are less likely to develop RN. Future work should validate these findings with the goal of optimizing radiation dosing to mitigate RN incidence and recurrence rates.

Beta-Blocker Use in Patients Undergoing Non-Cardiac Surgery: A Systematic Review and Meta-Analysis

Background: The use of beta-blockers in the perioperative period has been widely investigated due to their potential to reduce the risk of major adverse cardiovascular and cerebrovascular events (MACCE) and mortality; yet their overall impact on various postoperative outcomes remains debated. This study constitutes a systematic review and meta-analysis of the impact of beta-blockers on mortality, MI, stroke, and other adverse effects such as hypotension and bradycardia in patients undergoing non-cardiac surgery. Methods: A comprehensive systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Searches were performed across PubMed, Cochrane, Web of Science, Scopus, EMBASE, and CINAHL databases; we included randomized controlled trials and cohort and case-control studies published from 1999 to 2024. Results: This meta-analysis included data from 28 studies encompassing 1,342,430 patients. Perioperative beta-blockers were associated with a significant increase in stroke risk (RR 1.42, 95% CI: 1.03 to 1.97, p = 0.03, I2 = 62%). However, no statistically significant association was found between beta-blocker use and mortality (RR 0.62, 95% CI: 0.38 to 1.01, p = 0.05, I2 = 100%). Subgroup analyses revealed a protective effect on mortality for patients with high risks, such as patients with a history of atrial fibrillation, chronic heart failure, and other arrhythmias. For myocardial infarction (RR 0.82, 95% CI: 0.53 to 1.28, p = 0.36, I2 = 86%), a reduction in events was observed in the subgroup of randomized controlled trials. Beta-blockers significantly increased the risk of hypotension (RR 1.46, 95% CI: 1.26 to 1.70, p &lt; 0.01, I2 = 25%) and bradycardia (RR 2.26, 95% CI: 1.37 to 3.74, p &lt; 0.01, I2 = 64%). Conclusions: Perioperative beta-blockers show increasing rates of stroke events following non-cardiac surgery but do not significantly impact the incidence of MI or mortality. The increased risks of hypotension and bradycardia necessitate careful patient selection and monitoring. Future research should aim to refine patient selection criteria and optimize perioperative management to balance the benefits and risks of beta-blocker use in surgical settings.

Re-evaluating cardiovascular risk in systolic-dominant, diastolic-dominant and parallelly-elevated hypertension: insights from northeast rural cardiovascular health study

BackgroundHypertension is a major risk factor for cardiovascular disease (CVD), with a high prevalence in rural northeastern China. This study assesses the cardiovascular risk associated with different blood pressure patterns: systolic dominant, diastolic dominant, and parallel elevation.MethodsWe analyzed data from the Northeast Rural Cardiovascular Health Study (NCRCHS), which included 8,189 participants aged 35 and above. Baseline surveys from 2012 to 2013 and follow-ups in 2015 and 2018 provided a median follow-up of 4.66 years. Participants were categorized into ten subgroups based on systolic and diastolic blood pressure elevations. Kaplan-Meier curves and Cox regression models were used to examine CVD incidence and cardiovascular risk across these groups.ResultsThe incidence of CVD varied significantly among hypertension categories. Patients with grade 1 hypertension had no significant increase in cardiovascular risk at nearly 5 years. Notably, parallel elevations in systolic and diastolic pressures posed the highest cardiovascular risk, while a predominant rise in diastolic pressure alone did not significantly increase risk. This highlights the importance of analyzing blood pressure comprehensively for cardiovascular risk stratification and suggests rethinking treatment strategies for diastolic dominant hypertension.ConclusionsOur findings call for a nuanced approach to cardiovascular risk assessment in hypertension, taking into account distinct patterns of systolic and diastolic blood pressure. The study supports personalized treatment interventions and reinforces current hypertension treatment guidelines. We advocate for prioritizing non-pharmacological management in grade 1 hypertension and further clinical evaluation of treatment thresholds for diastolic dominant hypertension.

The impact of recipient hypernatremia on pediatric liver transplantation outcomes.

In pediatric liver transplants, dysnatremias have been found to have an impact on pre- and post-transplant outcomes. However, much of the current literature has focused on wait-list survival, secondary organ damage, and dysnatremia in donors rather than in recipients. To understand the effect of recipient immediate pre-transplant hypernatremia on post-transplant mortality, we conducted a multivariable retrospective review analyzing data from 8,011 pediatric patients undergoing liver transplantation provided by the United Network for Organ Sharing (UNOS). Multivariable analysis of hypernatremia showed an increased risk of mortality (odds ratio [OR]: 2.49, 95% confidence interval [CI]: 1.75, 3.54 for a serum sodium between 150-155mEq/L) while hyponatremia did not show a significant increase in relative risk for mortality (HR: 1.11, 95% CI: 0.75, 1.63 for a serum sodium between 125-130mEq/L). Kaplan-Meier (KM) curves stratified by sodium level showed statistically significant differences in outcomes with progressively increasing mortality associated with increasing serum sodium levels. In particular, there is a statistically significant increase in 90-day mortality with serum sodium levels above 150mEq/L. Hyponatremia had a moderate impact on mortality but was not statistically significant. Our analysis of immediate pre-transplantation resolution of hypernatremia also showed improved survival outcomes with a decreased mortality compared to transplant patients with unresolved hypernatremia. In conclusion, immediate pre-transplant recipient hypernatremia has a substantial impact on pediatric post-liver transplantation survival. Corrected hypernatremia resulted in decreased mortality compared to uncorrected hypernatremia. Recipient hypernatremia is an important indicator of disease processes and a predictor of poor post-transplantation mortality outcomes.

The association between plant-based diet indices and risk of mortality in patients with cirrhosis: a cohort study

BackgroundFollowing a plant-based diet is associated with a wide range of health benefits. The current study aimed to investigate the association between plant-based diet indices, specifically the plant-based diet index (PDI), healthful PDI (hPDI), and unhealthful PDI (uPDI) and risk of mortality in cirrhotic patients.MethodsThis cohort study included a total of 121 patients with cirrhosis, who were followed for four years. Plant-based diet indices were calculated based on a validated semi-quantitative food frequency questionnaire consisting of 168 items. The Hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were estimated using the Cox proportional risk models.ResultsDuring 414 person-year of follow-up, 43 deaths (7 women, 36 men) were documented. After adjusting all confounders, it has been found that the PDI (HR T3 vs. T1 = 0.16, 95% CI = 0.03–0.89, P trend = 0.024) and hPDI (HR T3 vs. T1 = 0.04, 95% CI = 0.02–0.61, P trend = 0.020) were inversely associated with the risk of mortality. While uPDI was directly associated with a significant increase in mortality risk (HR T3 vs. T1 = 8.74, 95% CI = 0.33–17.14, P trend = 0.018). The 4-year survival rate among patients showed a significant relationship with all three indices.ConclusionsOur findings highlight that higher scores of PDI and hPDI can significantly reduce the risk of mortality in patients with cirrhosis, while a significant increase in mortality risk was found in those with higher uPDI. However, confirmation of these findings requires further studies.

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

BackgroundThere 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.MethodsThere 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.ResultsA 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).ConclusionIn 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.

Residential Environment and Parental Lifestyle as Risk Factors of The Co-Occurrence of Cleft Lip and Palate Birth Defect Cases in Indonesia

Cleft lip and palate (CLP) are multifactorial birth defects, and the etiology behind their occurrence remains insufficiently understood. This case-control study aimed to investigate the association between residential environmental factors, parental lifestyle, and the risk of CLP in Indonesia. A total of 213 participants from 14 provinces were selected using stratified random sampling. Multivariable logistic regression was employed to determine the odds ratios (ORs) with 95% confidence intervals (CIs) for each risk factor. The study identified significant associations between several residential environmental factors and CLP. Proper kitchen ventilation was found to be protective (OR = 0.245, 95% CI: 0.096–0.624, p = 0.003), while proximity to industrial sites significantly increased the risk (OR = 3.595, 95% CI: 1.029–12.558, p = 0.045). Additionally, using treated drinking water showed a protective effect (OR = 0.39, 95% CI: 0.16–0.95, p = 0.038), whereas concerns about water sources displayed a marginally significant risk increase (OR = 2.841, 95% CI: 0.876–9.211, p = 0.082). Regarding parental lifestyle factors, maternal active smoking exhibited a marginal protective association (OR = 0.052, 95% CI: 0.002–1.09, p = 0.057), while paternal passive smoking presented a marginally significant risk (OR = 2.309, 95% CI: 0.897–5.942, p = 0.083). Furthermore, paternal radiation exposure was associated with an elevated risk of CLP (OR = 3.489, 95% CI: 0.828–14.703, p = 0.089). These findings highlight the need for targeted public health interventions to mitigate environmental exposures and promote safer parental lifestyle behaviors in Indonesia.

No Increased Injury Risk on Artificial Turf in Finnish Premier Division Football.

To compare the injury risk between natural grass and artificial turf in the male Finnish premier division (Veikkausliiga) matches during the 2019 league season. A retrospective reanalysis of prospectively collected season-long injury surveillance cohort study. Finnish elite-level male football. All 12 teams of Veikkausliiga participated in the study. All players were eligible to participate. Two hundred thirty-six players took part in the follow-up between February and November 2019. Matches were played between April and November 2019. Injury data were collected using standard injury reports from the team medicals and weekly player questionnaires. Individual player exposure in matches was collected. Artificial turf was classified as exposure and natural grass as control in the analyses. Match-related injury incidence and incidence rate ratios (IRR) with 95% confidence intervals (CI) on natural grass and artificial turf. A total of 113 injuries (65 on artificial turf, 48 on natural grass) in 167 matches (90 on artificial turf, 77 on natural grass) were included. Injury incidence was 27.2/1000 hours on artificial turf and 23.9/1000 hours on natural grass and (IRR, 1.1; 95% CI, 0.8-1.7). There was no difference in injury types, anatomical regions, injury recurrence, injury severity, or injury contact. Forwards may have had an increased injury incidence on artificial turf compared with natural grass (IRR, 3.4; 95% CI, 1.0-11.8). This study supports previous reports that there is no significant increase in the overall risk of injury in professional football played on artificial turf compared with that on natural grass.

Comparative Cardiovascular Risks of Radical Prostatectomy and External Beam Radiation Therapy in Early-Stage Prostate Cancer: A Comprehensive Retrospective Analysis.

The risk of cardiac disease mortality has recently become a focal point of concern within the medical community for patients with prostate cancer (PCa). Given that radical prostatectomy (RP) and external beam radiation therapy (EBRT) are the main treatment modalities for localized PCa, their specific impact on cardiovascular-specific mortality (CSM) remains unclear. This study explored the specific effects of RP and EBRT on CSM risk to guide clinical treatment decisions. Data from patients aged 45-74years, who were diagnosed with T1-2N0M0 stage PCa from the SEER database (2010-2015), were used. Multivariate statistical methods, including propensity score matching (PSM), competing risk regression, COX regression analysis, and Fine-Gray testing, were applied to assess the impact of RP and EBRT on CSM risk. Among 146,082 T1-2 stage PCa patients, cardiac disease emerged as the primary cause of death, surpassing PCa itself. Multifactorial COX regression and competing risk regression analyses indicated that local treatments do not increase CSM risk. Further analysis revealed a significant increase in CSM risk for patients undergoing only EBRT compared with those undergoing only RP (hazard ratio [HR] = 2.71, 95% confidence interval [CI] 1.96-3.74, P < 0.001), with subsequent PSM adjustment, further confirming a significantly reduced risk in the RP treatment group (HR 0.23, 95% CI 0.13-0.40, P < 0.001). T1-2 stage PCa patients face a significant risk of CSM, with RP offering a potential advantage over EBRT in reducing this risk. These findings encourage clinicians to comprehensively consider the potential impact on cardiac health when formulating treatment plans, providing crucial guidance for optimizing treatment strategies.

Effects of short-term exposures to lower air temperature and cold spells on myocardial infarction hospital admissions: a nationwide study in Sweden

Abstract Background Exposures to lower air temperature and cold spells have been associated with an increased risk of various diseases. However, the short-term effect of lower air temperature and cold spells on myocardial infarction (MI) remains incompletely understood. Purpose We aimed to evaluate the short-term effects of lower air temperature and cold spells on MI hospital admissions within the nationwide SWEDEHEART registry. Methods This population-based nationwide study included 120,380 MI cases admitted to hospitals in Sweden during the cold season (October to March) from 2005 to 2019. Daily mean air temperature was estimated at 1 km2 spatial resolution across Sweden using a three-stage machine learning approach and percentiles of daily temperatures experienced by individuals in the same municipality were employed as individual exposure indicators to account for potential geographic adaptation. Cold spells were defined as periods of at least two consecutive days with a daily mean temperature below the 10th percentile of the temperature distribution for each municipality. A time-stratified case-crossover design incorporating a conditional logistic regression model with distributed lag non-linear model using lag 0-1 and lag 2-6 days was employed to evaluate the short-term effects of lower air temperature and cold spells on total MI, non-ST-segment elevation MI (NSTEMI) and ST-segment elevation MI (STEMI). Results We found significant increases in risk for total MI, NSTEMI, and STEMI in association with a decrease of one percentile in temperature at a lag of 2-6 days, indicated by ORs (95% CI) of 1.099 (1.057-1.142), 1.110 (1.06-1.164), and 1.076 (1.004-1.153), respectively. Additionally, we found that cold spells were significantly associated with increased risks for total MI, NSTEMI, and STEMI at a lag of 2-6 days, with ORs (95% CI) of 1.077 (1.037-1.12), 1.069 (1.02-1.119), and 1.095 (1.023-1.172), respectively. Moreover, independent effects of lower air temperature and cold spells on MI occurrence were found after adjusting for each other. Conversely, we observed that lower air temperature and cold spells were associated with decreased risks for MI at a lag of 0-1 days. Conclusions This nationwide case-crossover study demonstrated a novel biphasic pattern in MI risk following exposure to lower air temperatures and cold spells, characterized by an initial transient reduction in risk at lags 0-1 day, followed by a significant increase in risk at lags 2-6 days. As climate change continues to induce complex shifts in regional weather patterns, enhancing protections to reduce future cold-related cardiac hospitalizations is crucial.

Impact of age on clinical characteristics and 1-year outcomes of non-disabling ischemic cerebrovascular events: A multicenter prospective cohort study

BackgroundThe exploration of age-related clinical features and adverse outcomes of non-disabling ischemic cerebrovascular disease (NICE) has been largely unaddressed in current research. This study aimed to analyze the differences in clinical characteristics and prognostic outcomes of NICE across various age groups, utilizing data from the Xi’an Stroke Registry Study in China.MethodsThe age distribution of NICE was categorized into four groups: age ≤ 54 years, age 55–64 years, age 65–74 years, and age ≥ 75 years. Multivariate Cox logistic regression analysis was employed to evaluate the 1-year risk of outcome events in each age group of patients with NICE. A subgroup analysis was conducted to explore interaction factors influencing age-dependent outcomes in patients with NICE.ResultsThis study included 1,121 patients with NICE aged between 23 and 96 years, with an average age of 63.7 ± 12.2 years. Patients aged ≥ 75 years had a higher proportion of women, lower education levels, and a greater likelihood of having urban employee medical insurance. Those aged < 55 years had a higher prevalence of smoking, while individuals aged > 65 years showed a higher prevalence of comorbidities. Furthermore, there was a significant decrease in body mass index among patients aged ≥ 75 years. Laboratory tests indicated well-controlled blood lipids, liver function, and inflammation across all age groups, but renal function was notably reduced in patients with NICE aged ≥ 75 years. Adjusting for potential confounding factors revealed a significant increase in the one-year risk of all-cause mortality and poor prognosis among patients aged ≥ 75 years compared to those aged < 55 years, with no significant gender difference observed. Subgroup analysis indicated that patients with NICE who consumed alcohol were more prone to experience all-cause mortality with advancing age.ConclusionsAge significantly influences the clinical characteristics and prognostic outcomes of NICE patients. Clinicians should consider age-specific characteristics when diagnosing, treating, and developing prevention strategies. Tailored prevention and treatment strategies for different age groups can enhance prognosis and reduce adverse outcomes in NICE patients.

Increased risk of genitourinary cancer in kidney transplant recipients: a large-scale national cohort study and its clinical implications.

To investigate the risk of genitourinary (GU) cancer in kidney transplant recipients (KTRs) compared to that in the general population, focusing on potential risk factors and clinical implications. Using a national cohort of approximately 360,000 individuals, including 31,542 KTRs, we conducted a retrospective analysis of the data from 2007 to 2018. Propensity score matching was used to compare KTRs with a healthy population, adjusting for age, sex, diabetes, hypertension, and hypercholesterolemia. We identified a significantly increased risk of GU cancers, particularly bladder and kidney cancers, in KTRs. Multivariate analysis revealed a higher risk of GU cancer associated with kidney transplantation [hazard ratio (HR) 2.133, 95% confidence interval (CI) 1.641-2.772] and hypercholesterolemia (HR 1.725, 95% CI 1.227-2.425), with older age and male sex also being significant risk factors. Conversely, no significant increase in prostate cancer risk was observed in KTRs compared to the general population. This national cohort-based study indicated an increased risk of GU cancer in KTRs, underscoring the need for targeted cancer surveillance and pre- and post-transplant counseling. These findings provide valuable insights for the development of cancer surveillance programs for KTRs and highlight the necessity for further research in this field.

Strong association of single nucleotide polymorphisms in BRCA1, ATM, and CHEK2 with breast cancer susceptibility in a sub-population of Iranian women.

Breast cancer (BC) is the most prevalent malignancy in females worldwide. Mutations in the DNA repair pathway genes contribute to a significant increase in BC risk. The present study aimed to assess the frequency of polymorphisms in BRCA1, ATM, and CHEK2 genes and their association with BC susceptibility in the Kurdish population from the West of Iran. In the present case-control study, the distribution of single nucleotide polymorphisms (SNPs) in CHEK2 (rs17879961), ATM (rs28904921), and BRCA1 (rs80357906, rs1555576855, rs1555576858, and rs397509247) genes were investigated in 335 BC cases and 354 healthy-matched controls by Taqman allelic discrimination assay. The chi-square goodness-of-fit test was employed for the assessment of Hardy-Weinberg Equation. Relative risk and odds ratios were calculated based on the Koopman asymptotic score and the Baptista-Pike method, respectively. Also, the sensitivity and specificity of each polymorphism were assessed using the Wilson-Brown test and a P-value < 0.05 indicating significant differences between the two groups in all assessments. Data showed there was a strong association between rs397509247 (OR = 7.53, 95% CI 1.88-90.91, p = 0.004), rs1555576858 (OR = 10.53, 95% CI 0.01-0.51, p = 0.0005), and rs80357906 (OR = 6.33, 95% CI 0.05-0.043, p < 0.0001) in BRCA1 gene and rs17879961 (OR = 3.52, 95% CI 0.084-0.946, p = 0.02) in CHEK2 gene, with BC risk in the population of interest. Among these, rs28904921 in ATM gene demonstrated the strongest association (OR = 72.66, 95% CI 0.007-0.214, p < 0.0001). This suggests that these SNPs, particularly rs28904921, are significantly associated with an increased risk of BC in the studied population. Our results indicated that BRCA1, ATM, and CHEK2 polymorphisms have a high frequency in the Iranian breast cancer population, with some mutant allele frequencies being much higher than those reported in other populations. We have also provided a simple, multiplex, rapid, and accurate genotyping assay that is useful in clinical settings.

Multiple Sclerosis: Appearance after Covid Vaccination

Background: Multiple sclerosis (MS) is a chronic autoimmune disease that primarily affects the central nervous system, often emerging in young adults. In the context of the global COVID-19 vaccination campaign, concerns have been raised about the potential link between vaccination and autoimmune conditions, including MS. This study aims to assess the incidence of MS post-COVID-19 vaccination across different age groups and vaccine types, with a specific focus on identifying at-risk populations. Methods: A retrospective cohort study was conducted using publicly available registries, case reports, and clinical data. The study included 450 individuals who developed MS after receiving a COVID-19 vaccine, with an analysis performed on incidence rates, relative risk (RR), and demographic factors such as age, sex, and vaccine type. The data was compared with a control group of 3,000 vaccinated individuals without MS onset. Results: The overall incidence of MS among vaccinated individuals was 15 per 100,000. Adults aged 18-40 years had the highest incidence (18 per 100,000), while children under 12 had the lowest (3 per 100,000). Females were disproportionately affected, accounting for 63.3% of MS cases, with an incidence of 18 per 100,000 compared to 12 per 100,000 in males. A higher proportion of cases were linked to mRNA vaccines, particularly Pfizer-BioNTech (54.4% of total cases), though no statistically significant difference was observed among vaccine types. The relative risk of MS in vaccinated adults was 1.35 (95% CI: 1.12-1.60) compared to the general population. Conclusion: While there is a slight increase in the incidence of MS among adults following COVID-19 vaccination, particularly with mRNA vaccines, the overall risk remains low. No significant increase in MS risk was observed in younger populations. The benefits of vaccination against severe COVID-19 far outweigh the potential risks of MS onset. Ongoing surveillance and further research are essential to better understand vaccine-related autoimmune responses.

Risk of developing a subsequent primary cancer among adult cancer survivors.

Improvements in cancer control have led to a drastic increase in cancer survivors who may be at an elevated risk of developing subsequent primary cancers (SPC). In this study, we assessed the risk and patterns of SPC development among 196,858 adult cancer survivors in Alberta, Canada. We used data from the Alberta Cancer Registry to identify all first primary cancers occurring between 2004 and 2020. A SPC was considered as the next primary cancer occurring in a different site. We estimated standardized incidence ratios (SIR) for SPC development as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up. The risk of developing a SPC up to fifteen years after an initial cancer was 16.2% for males and 12.2% for females. Overall, both males (SIR=1.50) and females (SIR=1.58) had an increased risk of a SPC. There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors diagnosed between ages 18-39. Screen-detectable cancers including colorectal, lung, cervix, and breast accounted for 46% and 27% of SPCs among females and males. Cancer survivors of nearly every initial site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and highlights the need to investigate optimal strategies for screening the growing population of cancer survivors.

Mechanical complications and revision following total joint arthroplasty in acromegalic patients: A nationwide US-based study

BackgroundAcromegaly is associated with significant osteoarthritis (OA) and increased risk of vertebral and hip fractures. There is limited data on total joint arthroplasty (TJA) outcomes in patients with acromegaly. MethodsIn this retrospective study, we identified patients with acromegaly who underwent total hip arthroplasty (THA), total knee arthroplasty (TKA), and total shoulder arthroplasty (TSA) between 2010 and 2022 using the PearlDiver national database. Patients with a prior history of osteoporosis and follow-up duration of less than one year were excluded. Non-acromegalic control groups were selected through matching based on confounding factors. We compared all-cause revision and implant-related complications between the groups using R software integrated with the PearlDiver database. ResultsWe identified 1440 patients with acromegaly: 665 underwent THA, 618 underwent TKA, and 157 underwent TSA. Compared to the control group (2634 THA, 2445 TKA, and 600 TSA), there was no significant association with post-op revision following THA (OR(1-year) = 0.76[0.42–1.28], OR(5-year) = 0.68[0.42–1.06]), TKA (OR(1-year) = 0.89[0.48–1.55], OR(5-year) = 0.78[0.49–1.17]), and TSA (OR(1-year) = 0.19[0.02–1.40], OR(5-year) = 0.32[0.10–1.07]). Additionally, the risk of mechanical complications did not significantly increase in patients with acromegaly, either one year or five years post-operation. ConclusionThe study showed no significant increase in risk of revisions or mechanical complications in patients with acromegaly compared to controls. These findings bridge an important gap in the understanding of post-arthroplasty complications in patients with acromegaly and offer valuable insights into surgical expectations.

Genetic association of gut microbiota with osteoarthritis: a multivariable Mendelian randomization study considering medication use.

Background. The interplay among human gut microbiota (GM) composition, osteoarthritis (OA) and OA-related medication use has been extensively discussed. However, to date, there has been no exploration of the genetic correlation among these three factors.Hypothesis/Gap. The potential causal link between GM and OA), and whether medications influence this relationship, remains unclear.Methods. We utilized bidirectional Mendelian randomization (MR) to explore the genetic associations between GM and OA. We leveraged genome-wide association study (GWAS) summary statistics from the MiBioGen and GO consortia, which provided data on GM taxa and OA cases, respectively. We identified outlier single-nucleotide polymorphisms using radial-MR and assessed causal associations using inverse variance weighting (IVW), weighted median and MR-Egger methods. Robust outcomes, consistent across these methods, were reported. We addressed potential biases through tests for horizontal pleiotropy and heterogeneity, supplemented by the Mendelian randomization pleiotropy residual sum and outlier method. Multivariable MR techniques were applied to adjust for OA medication use using UK Biobank data.Results. IVW estimates revealed a significant increase in hip OA risk for Gordonibacter and Eubacterium (brachy group) [odds ratio (OR): 1.09, 95% confidence interval (CI): 1.04-1.15, P=7.82E-04; OR: 1.09, 95% CI: 1.03-1.16, P=4.67E-03, respectively]. Conversely, Senegalimassilia, Slackia and Streptococcus exhibited protective effects (OR: 0.88, P=2.14E-02; OR: 0.88, P=3.33E-02; 0.91, P=4.29E-02). Sutterella increased the risk of knee OA (OR=1.15, 95% CI: 1.07-1.25, P=4.06E-04), while Haemophilus decreased it (OR=0.94, 95% CI: 0.88-1.00, P=4.26E-02). No significant heterogeneity or horizontal pleiotropy was observed in the results. Even after accounting for the potential confounding effect of medication, the results remained consistent. No reverse causation was detected.Conclusions. Our MR study reveals gut microbiome links to OA risk. Associations hold after adjusting for medication, indicating a potential causal connection between GM and OA.

Evaluation relationship between VDR gene and clinical and inflammatory factors in patients with RRMS.

Adipocyte levels including leptin and FABS-4 levels, adiponectin, obesity, and vitamin D can be related to the occurrence and exacerbation of MS disease. This research aimed at determining the relationship between VDR gene changes and clinical and inflammatory factors in patients with relapsing-remitting multiple sclerosis (RRMS). This case/control study was conducted based on the ethical principles of Helsinki. RRMS disease was confirmed based on history, clinical signs, radiological signs, and neurologist's diagnosis. The research population consisted of healthy people and patients with RRMS referring to Hazrat Rasool Akram Hospital between 2021 and 2023 who met the criteria for entering the research. FokI polymorphism is associated with a substantial increase in risk, with an odds ratio of 7.28, for those with the FF genotype who have RRMS compared to healthy individuals (OR=7.28: 95% CI; 1.86, 28.41). The presence of FokI polymorphism significantly raises the likelihood of developing RRMS in persons with the FF genotype compared to healthy individuals, with an odds ratio of 28.7. RRMS patients with genotypes did not exhibit a significant increase in risk compared to controls for FokI, ApaI, TaqI, and BsmI polymorphisms. None of the studied polymorphisms revealed a significant risk in obese patients with different genotypes compared to the obese people. Further research, including more cases, is needed to avoid results that could be inflated by small samples or low frequencies of minor alleles.