Risk Population Research Articles

Association between TERT gene polymorphisms (rs2736100 and rs2736109) and breast cancer risk in the Iranian population: A case-control study

BackgroundThe level of hormones and genetic predispositions increase the risk of breast cancer. Genetic variations in the genes of the telomere pathway, which can influence the activity of telomerase, may be decisive for the development of breast cancer. Due to a lack of studies on TERT gene polymorphisms (rs2736100 and rs2736109) in the Iranian population, in this study we investigated the association of these polymorphisms with breast cancer in the Iranian population. Patients & methodsA total of 300 individuals participated in this research, which included 150 breast cancer patients and 150 healthy controls. Participants' blood samples were collected before the beginning of treatment. The RFLP-PCR procedure was used for the genotyping of TERT gene rs2736109 and rs2736100 polymorphisms. ResultsThere are statistically significant differences in the age of menarche and the age of menopause (P-value <0.05). For rs2736100, the frequency of TT genotype in the case and control groups was 22.7 % and 16.7 %, respectively. However, these differences were not statistically significant (P-value >0.05). For rs2736109, the frequency of the AA genotype was lower in the case group (12.0 % vs. 19.3 %). These differences reach a statistically significant level (P-value = 0.012). Individuals carrying AA genotype have a lower risk of suffering from breast cancer (odds ratio = 0.403, 95 % CI: 0.196–0.827). ConclusionOur findings suggest that the rs27326109 polymorphism in the TERT gene is associated with a decreased risk of breast cancer. Also this study reveals that age of menarche and age of menopause are associated with risk of this disease.

Shared genetic architecture between COVID-19 and irritable bowel syndrome: a large-scale genome-wide cross-trait analysis.

It has been reported that COVID-19 patients have an increased risk of developing IBS; however, the underlying genetic mechanisms of these associations remain largely unknown. The aim of this study was to investigate potential shared SNPs, genes, proteins, and biological pathways between COVID-19 and IBS by assessing pairwise genetic correlations and cross-trait genetic analysis. We assessed the genetic correlation between three COVID-19 phenotypes and IBS using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL) methods. Two different sources of IBS data were combined using METAL, and the Multi-trait analysis of GWAS (MTAG) method was applied for multi-trait analysis to enhance statistical robustness and discover new genetic associations. Independent risk loci were examined using genome-wide complex trait analysis (GCTA)-conditional and joint analysis (COJO), multi-marker analysis of genomic annotation (MAGMA), and functional mapping and annotation (FUMA), integrating various QTL information and methods to further identify risk genes and proteins. Gene set variation analysis (GSVA) was employed to compute pleiotropic gene scores, and combined with immune infiltration algorithms, IBS patients were categorized into high and low immune infiltration groups. We found a positive genetic correlation between COVID-19 infection, COVID-19 hospitalization, and IBS. Subsequent multi-trait analysis identified nine significantly associated genomic loci. Among these, eight genetic variants were closely related to the comorbidity of IBS and COVID-19. The study also highlighted four genes and 231 proteins associated with the susceptibility to IBS identified through various analytical strategies and a stratification approach for IBS risk populations. Our study reveals a shared genetic architecture between these two diseases, providing new insights into potential biological mechanisms and laying the groundwork for more effective interventions.

Age at diagnosis of diabetes, obesity, and the risk of dementia among adult patients with type 2 diabetes.

While Type 2 Diabetes Mellitus (T2DM) prevalence is increasing among younger individuals, few studies have examined how age at T2DM diagnosis relates to dementia risk in diabetic populations. We aimed to investigate the association between age at T2DM diagnosis and subsequent dementia risk, and to determine whether obesity moderates this relationship. We conducted a prospective cohort study using data from the Health and Retirement Study (2002-2016) matched with its 2003 Diabetes Mail-Out Survey. The study included 1,213 dementia-free adults aged ≥50 with diagnosed T2DM. Primary exposures were age at T2DM diagnosis (categorized as <50, 50-59, 60-69, and ≥70 years) and obesity status (BMI ≥30 kg/m2). The outcome was incident dementia, assessed using the Telephone Interview for Cognitive Status. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic factors, health behaviors, health status, and diabetes medication use. Over a median follow-up of 10 (interquartile range, 6-14) years, 216 (17.8%) participants developed dementia. Compared to participants diagnosed with T2DM at age ≥70 years, those diagnosed at younger ages had increased dementia risk: HR 1.70 (95% CI, 1.03-2.80) for 60-69 years, 1.72 (95% CI, 1.06-2.79) for 50-59 years, and 1.90 (95% CI, 1.14-3.18) for <50 years. Obesity significantly moderated this relationship, with obese individuals diagnosed with T2DM before age 50 showing the highest dementia risk (HR 3.05; 95% CI 1.23-7.56) compared to non-obese individuals diagnosed at ≥50 years. Younger age at diagnosis of T2DM was significantly associated with a higher risk of dementia, particularly among individuals with obesity. Interventions specifically targeting obesity may be more effective in preventing dementia for adults with a younger onset of T2DM.

Abstract 4121454: Machine-extractable Markers in Chest Radiograph to Predict Cardiovascular Risk in Screening Population

Introduction: Recent research has shown that AI is able to assess biological aging and cardiovascular disease (CVD) risk using chest radiographs. However, the lack of explainability of such deep learning algorithms hinders clinical utility and adoption. This motivates the current study which searches for and tests the use of machine extractable quantitative features in chest radiographs to predict CVD risk in population screening. Method: Chest radiograph measurements characterizing cardiomediastinal geometry, aortic calcification and tortuosity were handpicked for development of a segmentation-based feature extraction algorithm. The algorithm was applied on the PLCO lung screening dataset for analysis. The association between measurement-based imaging features, clinical characteristics (age, sex, BMI, smoking status, hypertension, diabetes, liver disease) with CVD mortality and 10-year major adverse cardiovascular events (MACE) were analysed by using proportional hazard regression, with feature selection done by LASSO. Result: Of 29,453 eligible subjects, 5693 subjects from a single study centre were used for fitting of all models. The median follow-up time was 19 years. A total of 32 imaging features were extracted and analysed. For both 10-year MACE and CVD mortality, model using imaging features, age, and sex performed similarly to model using conventional risk factors, and a deep learning chest radiograph CVD risk model. Two imaging features, mediastinal width at valve-level [HR 1.36 (1.23-1.50)] and maximal lateral displacement of descending aorta [HR 1.29 (1.18-1.42)] were found to be prognostic. To the best of our knowledge, these features have not been reported previously. Conclusion: Quantitative imaging features can predict CVD risk in chest radiograph similar to deep learning models while providing feature interpretability and explainability. Two novel imaging features prognostic of CVD risk were found and shown to be complementary to conventional risk factors.

Abstract 4115832: Statin Intolerance due to Muscle Symptoms Affects Management of Patients: Insights from the CLEAR Outcomes Trial

Background: In CLEAR Outcomes the non-statin bempedoic acid (BA) 180 mg daily reduced MACE-4 (nonfatal MI, nonfatal stroke, coronary revascularization, or CV death) by 13% in 13970 patients at high CV risk with statin intolerance (SI) over a median of 40.6 months. This is the largest prospective database of patients with SI. Aims: To assess whether there were differences in SI symptom history and whether this influenced the clinical course during CLEAR Outcomes. Methods: SI symptoms and impact on activities of daily living (ADL) were recorded prior to randomization. Patients were grouped post hoc as reporting only statin associated muscle symptoms (SAMS), only non-muscle adverse effects (NonSAMS), or BOTH. Results: At baseline 6887 (49.3%) patients reported SAMS, 2485 (18%) NonSAMS, and 4587 (33%) BOTH. SI symptoms had a moderate/severe impact on ADL in 62% SAMS, 48% NonSAMS, and 69% BOTH. Use of any lipid modifying treatment at baseline was 43% SAMS, 36% NonSAMS, and 42% BOTH. Compared to placebo, BA reduced LDL-C at 6 months by 21% in SAMS, 22% in NonSAMS, and 21% in BOTH. There was no difference in the effect on MACE-4 by SI group. New use of moderate/high intensity statin during the study was relatively infrequent (3.2-8.0%) but higher in PBO than BA in all SI groups and was not generally maintained at study end (Table 1). Muscle adverse events (AE) were more frequent and resulted in higher rates of treatment DC in SAMS/BOTH vs NonSAMS (Table 2). There was no difference between BA and PBO in the rate of muscle related AE. Conclusion: SAMS are the predominant cause of SI in patients in CLEAR Outcomes. Patients with a history of SAMS had higher rates of muscle AE and study drug DC due to muscle AE versus NonSAMS. Muscle AE rates and study drug DC were balanced between BA and PBO within each SI symptom subgroup. CLEAR Outcomes exhibits the challenges of treating patients with SI. These data also demonstrate that BA can be useful in reducing CV risk in this patient population.

Abstract 4141457: Forms of Childhood Maltreatment and Subclinical Cardiovascular Disease Risk in Black men and women

Background: Exposure to specific forms of childhood maltreatment have been associated with cardiovascular disease (CVD) risk factors and CVD events in adulthood. Heterogenous experiences of childhood maltreatment across race and sex exist, yet there is little evidence regarding these relationships and CVD risk in Black populations. Aims: To investigate the association between various forms of childhood maltreatment (emotional, general, physical, and sexual abuse) and surrogate markers of vascular dysfunction and test whether sex modify these associations. Methods: Forms of childhood maltreatment and indices of vascular function were assessed in a cohort of healthy Black adults without known CVD (n=404) from a large metropolitan southeastern city. Childhood maltreatment was assessed using the Early Trauma Inventory short form (ETISR-SF) consisting of physical, sexual, emotional, and general domains. A trauma severity index score was calculated by summing the indexes for each of the four domains. Higher scores are indicative of higher traumatic life events before age 18 years. Outcomes of central augmentation index (cAIx) corrected for a heart rate of 75 bpm and carotid femoral pulse wave velocity (CfPWV) were measured as indices of wave reflections and arterial stiffness using applanation tonometry (Sphygmocor Inc.), and central pulse pressure (CPP) was calculated as the difference between the aortic systolic and diastolic blood pressures. Associations between each domain and outcomes were assessed using multivariate-adjusted and sex-stratified linear regression models. Results: Mean age of the cohort was 53 + 10.3 years, 61% women. Exposure to emotional [ b = -1.5%, 95%CI: -2.7,-0.3] and physical abuse [ b = -1.3%, 95%CI: -2.5,-0.2] was associated with cAIx overall but not CPP or CfPWV after adjusting for sociodemographic, clinical factors, health behaviors, and depressive symptoms. Significant emotional abuseXsex ( P= 0.014) and physical abuseXsex ( P=&lt; 0.001) interactions were identified for cAIx. Among women, physical abuse was associated with higher cAIx [ b =1.5%, 95%CI: 0.6, 2.4] and among men emotional [ b =-1.6%, 95%CI: -3.2, -0.0] and physical [ b =-1.7%, 95%CI: -3.1, -0.3] abuse was associated with lower cAIx. Conclusions: Exposure to emotional and physical abuse as children was associated with vascular dysfunction; moreover, exposure to physical abuse among women and not men have adverse clinical implications for CVD risk and prospects for enhanced preventive care.

Intergenerational crosstalk of brain-gut axis in parental Nd2O3 exposure-induced offspring neurotoxicity and cognitive dysfunction: a mechanistic study.

Rare earth elements (REEs) are widely used in plenty of fields. REEs have significant neurotoxicity and it may adversely affect the development of cognitive. For example, neodymium will causing neurological damage through penetrate the blood-brain barrier (BBB). However, whether it disrupts the balance of brain-gut axis (BGA) crosstalk and affects the intestinal microecology disorder of host is still unclear. This study investigated the neural damage on children caused by maternal exposure to Neodymium oxide (Nd2O3) during pregnancy, and its involved mechanism of BGA injury. We used rat model to investigated the mechanisms of the offspring's neural damage that Nd2O3 exposure in pregnancy. To verify the neural damage of offspring rats, we examed BBB-related factors, such like glutamate and ROS levels in brain tissue, behavioral tests, hippocampal and cortical damage, as well as changes in gut microbiota, intestinal mucosal barrier, and SCFAs in the intestine. Also, we observed some specific indicators of intestinal immune barrier function and gut nerve-related indicators. Maternal Nd2O3 exposure reduced the content of offspring tight junction proteins, increased BBB permeability, leading to Nd accumulation and brain tissue inflammation, affecting offspring's neural development and weakening their spatial learning ability. Nd2O3 also disrupted BBB integrity by regulating SCFAs and BGA. Probiotic intervention in the offspring rats exposed to 2% Nd2O3 showed significant recovery of inflammation in both brain and colon tissues, and reduced BBB permeability. Maternal exposure to Nd2O3 affects the offspring's BGA, targeting brain and colon tissues, increasing BBB permeability, affecting neural development, causing damage to the intestinal mucosa, and impacting children's gut development. Probiotics can alleviate these effects. These findings provide valuable insights into understanding the neurodevelopmental and intestinal developmental toxicity of Nd2O3 and its prevention and treatment. It also calls for a comprehensive assessment of the health risks of susceptible populations to Nd2O3, such as pregnant women. It may providing theoretical basis for preventing and controlling neodymium-induced harm in children by examing the repair mechanism of the damage through probiotic intervention.

Abstract 4143227: Incidence of Hemorrhagic Stroke in Hypertrophic Cardiomyopathy

Background: Individuals with hypertrophic cardiomyopathy (HCM) have an elevated risk of ischemic stroke, primarily driven by the increased risk of atrial fibrillation (AF) development in this patient population. This risk remains elevated regardless of CHADS2VASC score; thus, anticoagulation is recommended for all HCM patients with AF. Given the known association between anticoagulant medications and hemorrhagic events, there is likely an assumed risk of hemorrhagic stroke in these individuals. Currently, the incidence of hemorrhagic stroke in HCM and its relationship to AF and anticoagulation has not been well-established in the literature. The goal of this study was to establish the presence of and risk factors for hemorrhagic stroke in individuals with HCM. Methods: A retrospective review of all HCM patients ages 18 and older in our institution’s health system was performed from 2019-2023. ICD 10 codes were used to identify individuals with hemorrhagic stroke. Patient charts were reviewed for additional data including demographics, comorbid conditions, anticoagulant prescription, and other inciting factors prior to the hemorrhagic event. Results: The study cohort comprised 343 HCM patients, of which 47.1% were female and 72.7% were Caucasian. Concurrently, 30% (n=103) had a diagnosis of AF. The overall incidence of hemorrhagic stroke was 2.9% (5.8%, n=6 in those with AF vs 1.7%, n=4 in those without AF); furthermore, AF was associated with a non-statistically significant increased risk of hemorrhagic stroke (RR = 3.36, 95% CI 0.97-11.7). Anticoagulant use at the time of hemorrhagic event was observed in 4 individuals (67%) with AF and 1 individual (25%) without AF. Head trauma and falls were frequently observed as precipitating events prior to hospital admission for hemorrhagic stroke, occurring in 83% (n = 5) of patients with AF and 50% (n = 2) of those without AF. Conclusions: While ischemic stroke and anticoagulant use are commonly studied in those with HCM, the incidence of hemorrhagic stroke in this population is not negligible. Risk of hemorrhagic events in HCM appears largely influenced by anticoagulant use, particularly in those with concurrent AF, and by head trauma. Given the known benefits of anticoagulation on ischemic stroke risk in the HCM population, appropriate counseling and careful attention to individual patient factors may be warranted in the administration of anticoagulants.

Abstract 4132341: Systematic Examination of the AHA PREVENT Equations

Background: The novel AHA Predicting Risk of CVD Events (PREVENT) equations newly incorporate predictors (estimated glomerular filtration rate [eGFR]) and outcomes (heart failure [HF]) relevant to the novel construct of cardiovascular-kidney-metabolic (CKM) syndrome. Aims: We sought to characterize the intrinsic properties of the PREVENT equations by simulating different risk profiles across the age and CKM risk spectrum. Methods: We applied the PREVENT base equations to estimate 10-year predicted risk for total CVD, which includes atherosclerotic CVD and HF. First, we calculated risk estimates for a hypothetical individual varying age from 30-79 years with an average risk factor profile (mean population risk factor levels based on National Health and Nutrition Examination Survey 2011-2020 data without diabetes, not on anti-hypertensive or statin medication, and who does not smoke). Second, we examined at which age a hypothetical individual would exceed the previously defined intermediate risk threshold ≥7.5% established by national guidelines. Lastly, we examined the differences in predicted risk with or without diabetes and/or Stage 3 CKD (defined as eGFR 44.5 mL/min/1.73m 2 ). Results: For hypothetical individuals aged 30-79 years with average risk factor levels, predicted 10-year CVD risk is shown in the figure for females (Panel A) and males (Panel B). The predicted risk would exceed the intermediate risk threshold at age 68 years if female and 63 years if male. If the individual had Stage 3 CKD, the predicted risk would exceed the intermediate risk threshold at 60 if female and 55 years if male. If the individual had diabetes, the predicted risk would exceed the intermediate risk threshold at 59 if female and 52 years if male. If both diabetes and Stage 3 CKD were present, the predicted risk would exceed the intermediate risk threshold at age 42 years if female and 35 years if male. Conclusions: The PREVENT equations enable more granular differentiation of risk among individuals with varying CKM profiles. Understanding risk estimates across the spectrum of age and CKM can support interpretability among clinicians and patients.

Triglyceride to high-density lipoprotein cholesterol ratio is associated with diabetes incidence in non-obese individuals with normoglycemia: a retrospective cohort study based on individuals from East Asia.

Although several studies have explored the association between the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c) and diabetes risk, most of these studies are cross-sectional and typically involve small sample sizes, limiting the ability to draw causal inferences. Additionally, there is currently a few studies specifically focusing on non-obese individuals. Consequently, we conducted a retrospective cohort study to investigate the impact of TG/HDL-c on the risk of developing diabetes among non-obese, normoglycemic individuals across East Asian countries. This secondary retrospective cohort study recruited 85,029 non-obese individuals with normal glycemic levels from East Asian countries (China and Japan). We employed Cox proportional hazards regression models, incorporating cubic splines function for smooth curve fitting and using two-piecewise Cox regression for threshold effect analysis, to evaluate the nonlinear associations between baseline TG/HDL-c ratios and diabetes risk in non-obese individuals with normoglycemia. In addition, A range of subgroup and sensitivity analyses were performed to confirm the robustness of our results. Among the individuals included, the average age was 42.14 ± 11.88 years, and 37,944 participants (44.62%) were male. After adjusting for covariates, the study revealed a significant correlation between the TG/HDL-c ratio and the risk of diabetes among non-obese individuals (HR=1.37, 95%CI: 1.22-1.54). Furthermore, a non-linear correlation was observed between the TG/HDL-c ratios and the incidence of non-obese diabetes, with an inflection point of 1.36. Under this threshold, the TG/HDL-c ratio notably boosts diabetes risk in non-obese populations, with an HR of 2.38 (95% CI: 1.57-3.59). Conversely, beyond the critical juncture, the upsurge in diabetes risk seems to level off, displaying no significant variation, with an HR of 1.18 (95% CI: 0.98-1.41). This study reveals a non-linear association between the TG/HDL-c ratios and the likelihood of diabetes in non-obese individuals from East Asia. Maintaining a ratio of TG/HDL-C below 1.36 significantly reduces diabetes risk. However, once the ratio of TG/HDL-C exceeds 1.36, reducing it does not substantially lower diabetes onset risk.

Impact of Socioeconomic Deprivation on Care Quality and Surgical Outcomes for Early-Stage Non-Small Cell Lung Cancer in United States Veterans.

Background: Socioeconomic deprivation has been associated with higher lung cancer risk and mortality in non-Veteran populations. However, the impact of socioeconomic deprivation on outcomes for non-small cell lung cancer (NSCLC) in an integrated and equal-access healthcare system, such as the Veterans Health Administration (VHA), remains unclear. Hence, we investigated the impact of area-level socioeconomic deprivation on access to care and postoperative outcomes for early-stage NSCLC in United States Veterans. Methods: We conducted a retrospective cohort study of patients with clinical stage I NSCLC receiving surgical treatment in the VHA between 1 October 2006 and 30 September 2016. A total of 9704 Veterans were included in the study and assigned an area deprivation index (ADI) score, a measure of socioeconomic deprivation incorporating multiple poverty, education, housing, and employment indicators. We used multivariable analyses to evaluate the relationship between ADI and postoperative outcomes as well as adherence to guideline-concordant care quality measures (QMs) for stage I NSCLC in the preoperative (positron emission tomography [PET] imaging, appropriate smoking management, pulmonary function testing [PFT], and timely surgery [≤12 weeks after diagnosis]) and postoperative periods (appropriate surveillance imaging, smoking management, and oncology referral). Results: Compared to Veterans with low socioeconomic deprivation (ADI ≤ 50), those residing in areas with high socioeconomic deprivation (ADI > 75) were less likely to have timely surgery (multivariable-adjusted odds ratio [aOR] 0.832, 95% confidence interval [CI] 0.732-0.945) and receive PET imaging (aOR 0.592, 95% CI 0.502-0.698) and PFT (aOR 0.816, 95% CI 0.694-0.959) prior to surgery. In the postoperative period, Veterans with high socioeconomic deprivation had an increased risk of 30-day readmission (aOR 1.380, 95% CI 1.103-1.726) and decreased odds of meeting all postoperative care QMs (aOR 0.856, 95% CI 0.750-0.978) compared to those with low socioeconomic deprivation. There was no association between ADI and overall survival (adjusted hazard ratio [aHR] 0.984, 95% CI 0.911-1.062) or cumulative incidence of cancer recurrence (aHR 1.047, 95% CI 0.930-1.179). Conclusions: Our results suggest that Veterans with high socioeconomic deprivation have suboptimal adherence to care QMs for stage I NSCLC yet do not have inferior long-term outcomes after curative-intent resection. Collectively, these findings demonstrate the efficacy of an integrated, equal-access healthcare system in mitigating disparities in lung cancer survival that are frequently present in other populations. Future VHA policies should continue to target increasing adherence to QMs and reducing postoperative readmission for socioeconomically disadvantaged Veterans with early-stage NSCLC.

The psycho-social impact of cancer treatment on the caregivers of the patients

Objectives The incidence of cancer cases shows an increasing trend over the past two decades owing to several factors, such as increased life expectancy, aging population, behavioral, environmental, and occupational risk factors, and more. Consequently, a greater number of people are expected to take the role of principal caregivers in the near future. Cancer treatment can have a multifaceted impact on the quality of life and psychological well-being of not only the patients but also their families. Caregivers are expected and required to provide complex care and support for which they are neither prepared nor trained. The reports of feeling overwhelmed and stressed are high when the demands placed on them exceed their resources, resulting in a negative effect on the overall well-being of the caregivers, including the patients themselves. The impact covers a wide spectrum of emotional, physical, financial, social, cognitive, spiritual, and work-related effects. Material and Methods This is a cross-sectional study conducted (for over three months from May to July 2023) among the caregivers accompanying cancer patients attending a tertiary care hospital in a South Indian metropolitan city. All the adult caregivers of patients diagnosed with cancer at least two to six months before the time of the study were considered as the study population. A systematic random sample was applied to recruit a convenient sample of 150 caregivers, maintaining the enrollment of only one caregiver per patient. Sociodemographic details of the patients and their caregivers were collected. The Zarit Burden Interview (ZBI) based on a Likert scale was implemented to collect relevant data related to both the cancer patient and the family caregiver. Results Of the total 150 cancer patients, the most common type of cancer among the patients was head and neck (63, 42%), followed by cancers of the female reproductive system (44, 29.3%) and breast (24, 16%). Nearly 47% of caregivers were children of cancer patients, while 35.3% were spouses. Significantly higher burden scores on the “emotional strain” and “financial/physical strain” domains were observed among female caregivers. Higher burden scores on the “self-criticism” domain were independently associated with a shorter caregiver-patient contact time. Significantly higher burden scores on the “self-criticism” and “time/dependence” domains were observed among employed caregivers. Higher levels of burden on the “financial/physical strain” domain were reported by unemployed caregivers. Significantly higher burden scores on the “uncertainty” domain were observed among older caregivers and caregivers who were parents or spouses of the patients. Conclusion Caregiving impacts the physical, emotional, financial, and social aspects of the caregiver’s life. They adopt active coping strategies to overcome the impacts of caregiving. A majority of the caregivers experienced mild to moderate burden, while most scored low on quality of life. Attention to concerns and the psychological well-being of caregivers may improve the overall scenario.

Association of suture augmentation with graft failure and clinical outcomes following anterior cruciate ligament reconstruction: A systematic review and meta-analysis of comparative studies with a minimum 2-year follow-up.

To compare graft failure, nonrevision reoperation, complication, patient-reported outcome measures (PROMs) and return to sports (RTS) between patients who underwent anterior cruciate ligament reconstruction (ACLR) with and without suture augmentation (SA). A systematic search was performed on PubMed, Cochrane, Embase and Web of Science databases from the inception of databases to 18 April 2024, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies comparing clinical outcomes of SA- and standard ACLR with a minimum 2-year follow-up were included. Data extraction and quality appraisal were performed by two researchers independently. Eight retrospective cohort studies were included, with a total of 408 patients receiving SA-ACLR and 443 patients receiving standard ACLR. A meta-analysis of graft failure demonstrated a 62% relative risk reduction (RR [risk ratio], 0.38 [95% confidence interval {CI}, 0.19-0.73]; p = .004) in those receiving SA-ACLR compared with standard ACLR. An age-related heterogeneity in graft failure reduction was detected in the subgroup analysis, which was more pronounced in studies with mean ages of <20 years compared with ≥20 years (p = .05; I2 = 73.9%). No significant difference was observed in nonrevision reoperation or complication rates. No clinically relevant difference was observed in PROMs. SA-ACLR was associated with a significantly higher RTS rate compared with the standard ACLR (RR, 1.12 [95% CI, 1.00-1.24]; p = .04), whereas no significant difference was observed in time to RTS. SA-ACLR is associated with a reduced graft failure rate and increased RTS rate compared with standard ACLR without additional reoperations or complications. However, confidence in the evidence is limited by substantial heterogeneity. Future studies with a higher level of evidence are warranted to validate the benefit of SA and to determine the indication for different risk populations. Level III.

PCCA variant rs16957301 is a novel AKI risk genotype-specific for patients who receive ICI treatment: Real-world evidence from all of us cohort

IntroductionImmune checkpoint inhibitors (ICIs) enhance the immune system's ability to target and destroy cancer cells, but can also trigger immune-related adverse events (irAEs), such as acute kidney injury (ICI-AKI), complicating patient management. Limited knowledge of genetic predispositions to ICI-AKI highlights the need for genomic studies to improve therapeutic strategies. ObjectiveTo identify genetic predispositions for ICI-AKI using large-scale real-world data. MethodsA systematic literature search led to 14 candidate variants related to irAEs. We performed a candidate variant association study with these variants using the All of Us cohort. An ICI-treated cohort and a general cohort were established to evaluate ICI-AKI risk. Logistic regression, adjusted for sex, evaluated the impact of each candidate genotype, separately for self-reported and ancestry-estimated race. Kaplan-Meier survival analysis assessed genetic effects on AKI-free survival. ResultsThe ICI cohort (n = 414) showed a one-year AKI incidence rate of 23.2 %, significantly higher than the general cohort (6.5 %, n = 213,282). The rs16957301 variant (chr13:100324308, T > C) in the PCCA gene was a significant risk genotype for ICI-AKI among self-reported White (Beta=0.93, CI: 0.32 – 1.54, ORs= 2.53, Bonferroni-corrected P-value=0.047) and ancestry estimated Europeans (Beta = 0.94, CI: 0.31 – 1.57, ORs= 2.56, Bonferroni-corrected P-value=0.044). Self-reported White with the rs16957301 risk genotypes (TC/CC) developed AKI significantly earlier (3.6 months) compared to the reference genotype (TT, 7.0 months, log-rank P = 0.04). Consistent results were found in ancestry-estimated Europeans. This variant did not present significant AKI risks in the general cohort (Beta: −0.008–0.035, FDR: 0.75–0.99). ConclusionOur findings suggest that rs16957301 in PCCA may serve as an ICI-AKI risk marker in Caucasians. Further studies are needed to validate this association and explore risks in other populations.

Age Differences in the Correlation Between the Cardiometabolic Index and Chronic Kidney Disease Risk in Adults With Hypertension.

Literature on the association between the cardiometabolic index (CMI) and chronic kidney disease (CKD) risk is limited, especially in hypertensive populations. The objective of the present investigation was to assess the relationship between the CMI and CKD risk in a hypertensive population. The current cross-sectional study included a total of 13717 individuals with hypertension. The calculation of the CMI was based on the waist-to-height ratio and the triglyceride-to-high-density lipoprotein cholesterol ratio. The definition of CKD was based on an estimated glomerular filtration rate (eGFR) of less than 60mL/min/1.73 m2. The prevalence of CKD was found to be 4.24% in younger adults (aged < 65 years) and 14.93% in the elderly (aged ≥ 65 years). The results of the multivariate regression analysis indicated that in the elderly group, the CMI was positively associated with CKD risk (odd ratio [OR] 1.29; 95% confidence interval [CI]: 1.14, 1.46), while no significant relationship was observed in the younger group (OR 1.04, 95% CI: 0.85, 1.27). Furthermore, subgroup analyses did not identify any potential factors that could modify the relationship between the CMI and CKD risk (all p for interaction > 0.05). Among adults with hypertension, there was an independent and positive correlation between the CMI and CKD risk in the elderly, whereas such a correlation was not observed in younger adults. Trial Registration: ClinicalTrials.gov identifier: ChiCTR1800017274 [China Hypertension Registry Study].

Non-linear relationship between lipid accumulation products and risk of diabetes in Japanese adults

The lipid accumulation product (LAP) is a novel, sex-specific indicator of lipid accumulation. While previous studies have investigated the relationship between LAP and diabetes, they have not specifically addressed potential sex differences in this association. The present study explores the potential sex-specific differences in the relationship between LAP and diabetes mellitus (DM) risk in the Japanese population. From 2004 to 2015, a total of 15,263 Japanese individuals without DM underwent physical assessments at Murakami Memorial Hospital. The association between LAP and incident diabetes was analyzed using Cox proportional hazards regression models, incorporating cubic spline functions and smooth curve fitting to identify potential non-linear relationships. Subgroup and sensitivity analysis assessments were conducted to validate the robustness of our findings. After adjusting for covariates, a positive association between LAP and DM risk was observed in both females (HR: 1.02, 95% CI: 1.00-1.03, P = 0.0138) and males (HR: 1.01, 95% CI: 1.00-1.01, P = 0.0314). A non-linear association between LAP and incident DM was identified for both sexes. The inflection points for LAP were 16.58 for females and 11.11 for males. In females, the HR to the left and right of the inflection point were 1.09 (95% CI: 1.02–1.17) and 1.01 (95% CI: 1.00-1.03), respectively. In males, the HR to the left and right of the inflection point were 0.92 (95% CI: 0.86–0.98) and 1.01 (95% CI: 1.00-1.01), respectively. Sensitivity analysis indicated a stronger association between LAP and DM risk. Elevated baseline LAP levels were associated with an increased risk of incident DM, with the relationship exhibiting non-linear characteristics. These findings suggest that maintaining lower LAP levels may help mitigate the risk of developing diabetes.

Prevalence of oral submucous fibrosis across diverse populations: a systematic review and meta-analysis.

The aim is to offer a comprehensive overview of oral submucous fibrosis (OSF) prevalence and explore its epidemiological characteristics across various demographic groups and geographical locations, thereby helping the formulation of public health management policies. Studies reporting OSF prevalence were identified from electronic databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via PubMed, EMBASE via OVID, and Web of Science. Pooled prevalence and quality assessment using the New-Ottawa Scale were conducted. Two reviewers screened and selected records, assessed quality, and independently extracted data. This systematic review and meta-analysis followed the PRISMA guidelines and was registered on PROSPERO (CRD42024532975). Sixty-three studies, encompassing 11,434 cases in a total population of 769,860, reported OSF prevalence. The majority of studies (forty-one) were from India. The pooled prevalence of OSF across all populations was 3.0% (95% CI [2.8-3.2]%). In non-risk populations, risk populations, and consecutive dental patients, the pooled prevalence stood at 2.4% (95% CI [2.1-2.6]%), 4.5% (95% CI 3.5-5.6%), and 5.6% (95% CI [3.8-7.5]%), respectively. Subgroup analysis by age, sex, and geographical region revealed higher prevalence rates among those aged 50 and above (4.2%, 95% CI [3.0-5.4]%), males (3.3%, 95% CI [2.9-3.7]%), and in India (4.0%, 95% CI [3.7-4.3]%). As the exposure to risk factors exceeded 50% in the surveyed population, the prevalence of OSF notably increased. Most studies met satisfactory quality standards. Our research findings reveal a comprehensive prevalence of OSF across all populations at 3.0% (95% CI [2.8-3.2]%). And, existing evidence indicates a relatively low prevalence of OSF associated with tobacco, alcohol, and Areca (betel) nut use. However, further large-scale studies are recommended to validate these findings. Understanding the prevalence and distribution patterns of OSF may assist in healthcare intervention planning and alleviate the oral cancer burden associated with OSF.

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.

Electroconvulsive Therapy in a Left Ventricular Assist Device Recipient With Treatment-Resistant Depression.

Depression and heart failure are highly comorbid, with up to 35% of heart failure patients suffering from comorbid depression. Left ventricular assist devices (LVADs) serve as a major lifeline for patients with heart failure; however, despite the drastic improvement in cardiac function following LVAD implantation, up to 24% of LVAD recipients suffer from depression. Depression management in LVAD recipients is often complicated by the recipient's increased risk for antidepressant side effects, adverse drug reactions, and inability to safely receive certain interventional psychiatry therapies, as the LVAD is either a relative or absolute contraindication. Electroconvulsive therapy (ECT) is highly effective for treatment-resistant depression; although it carries increased cardiovascular risks for the LVAD population (particularly bradycardia/hypotension and tachycardia/hypotension), these can be continuously monitored, along with LVAD function, such that with the close cooperation of a multidisciplinary team, the risks of ECT can be minimized. To our knowledge, there is only one published case report of ECT in an LVAD recipient. We present a case of an LVAD recipient with treatment-resistant depression who was successfully treated with ECT. Our case describes an approach by which ECT can be safely delivered to LVAD recipients with a collaborative multidisciplinary team approach.

ASSESSMENT OF THE IMPACT OF A SLUDGE RESERVOIR FOR IRON-CONTAINING WASTE ON ENVIRONMENTAL COMPONENTS

The paper presents the results of the environmental impact assessment of the sludge pond for iron-containing waste generated as a result of the economic activities of the Zavolzhsky Chemical Factory located in the Ivanovo Region. In 2020, the sludge pond was included in the state register of objects of accumulated environmental damage. The accumulated sludge, with a volume of about 31 thousand m3, is a spent catalyst generated as a result of diphenylamine production. The main components of the waste are iron (III) oxide, silicon oxide and water, the total content of which is 95%. Heavy metals are also present in trace amounts - organic compounds, copper, nickel, zinc and chromium. The research assessed the quality of atmospheric air, the state of surface and groundwater, as well as the soil cover and soils on the territory of the site where the sludge pond is located. The assessments showed that the main negative impact is on the soil cover, groundwater and river Volga, flowing 185 m from the location of the object. To establish the quality of water in the Volga River, the hydrochemical index of water pollution was used, the value of which exceeded 10, i.e. the Volga River (in the area of the city of Zavolzhsk) according to the class and assessment of water quality belongs to the extremely dirty. In the area of the location of the object in the Volga River, there is an excess of heavy metals by 2-7 times compared to the background sample taken in the control section upstream. The quality of groundwater in the survey site does not meet environmental standards and varies from an emergency environmental situation to an environmental disaster zone. The value of the total indicator of chemical pollution of soils and grounds relates the studied area to the category of soil pollution as a high level of pollution (risk for the resident population). For citation: Izvekova T.V., Gusev G.I., Gordina N.E., Sitanov R.D., Gushchin A.A. Assessment of the impact of a sludge reservoir for iron-containing waste on environmental components. ChemChemTech [Izv. Vyssh. Uchebn. Zaved. Khim. Khim. Tekhnol.]. 2024. V. 67. N 11. P. 145-153. DOI: 10.6060/ivkkt.20246711.7140.