Significant Risk Association Research Articles

Association between type 2 diabetes mellitus and the risk of developing cataracts: based on the research of two-sample Mendelian randomization

Objective: To determine the causal relationship between cataracts and type 2 diabetes mellitus (T2D) by the Mendelian randomization (MR) analysis using the genome-wide association study (GWAS) data. Methods: Data on T2D and cataracts in the European population were obtained from the OpenGWAS database. The single nucleotide polymorphisms (SNPs) that met the genome-wide significance criteria (P<5×10⁻⁸) of T2D (48 286 cases, 250 671 controls) and cataracts (5 045 cases, 356 096 controls) were selected. The main method was random effects inverse variance weighting (IVW), and four other two-sample MR methods were also used, including MR Egger, Simple median, Weighted median, and Weighted mode, to assess the causal relationship using odds ratios (OR). Sensitivity analyses were conducted using the leave-one-out approach to evaluate the robustness of the results. Results: The MR Egger analysis showed a significant risk association between T2D and cataracts (OR=1.003, 95%CI=1.001-1.006; P=0.013). Using the methods of Weighted median (OR=1.002, 95%CI=1.000-1.004; P=0.029) and Weighted mode (OR=1.002, 95%CI=1.000-1.005; P=0.046), similar results were obtained. However, the IVW test failed to confirm the causality (P=0.149). The sensitivity analyses using the MR Egger and IVW tests did not show significant heterogeneity between T2D and cataracts (all P>0.05). With the leave-one-out analysis, the SNPs with significant effects were not identified, indicating the robustness of the MR results in this study. The MR Egger interception of the SNPs showed significant directional pleiotropy (P=0.038), suggesting a directional pleiotropy between T2D and cataracts. Conclusions: The results of the MR analysis suggest there is a causal relationship between T2D and cataracts, and T2D increases the risk of cataracts.

Chronic bronchitis and bronchial asthma: the impact of chronic occupational radiation exposure on incidence and mortality of Mayak nuclear workers.

The information about the radiation risk of non-cancer respiratory diseases is inconsistent and mainly corresponds to mortality. Previously, an increased risk of chronic bronchitis incidence was demonstrated in the cohort of workers employed at the first Russian nuclear facility Mayak Production Association who had been chronically exposed to gamma rays (externally) and to alpha-active plutonium aerosols (internally). Within this retrospective study, we performed analyses of incidence of and mortality from chronic bronchitis and bronchial asthma using improved estimates of radiation doses provided by the "Mayak Worker Dosimetry System (MWDS) - 2013". The cohort included 22,377 individuals hired in 1948-1982, and its follow-up was extended by 10 years (to the end of 2018). The excess relative risk of chronic bronchitis incidence per unit radiation dose (ERR/Gy) and the 95% confidence interval (95% CI) were: with the 0-year lag ERR/Gy=0.07 (95% CI -0.01, 0.17) for gamma exposure and ERR/Gy=0.36 (95% CI 0.13, 0.68) for alpha exposure; with the 10-year lag ERR/Gy=0.15 (95% CI 0.04, 0.30) for gamma exposure and ERR/Gy=0.54 (95% CI 0.19, 1.03) for alpha exposure. The chronic bronchitis mortality risk was significantly associated with internal alpha exposure only for certain worker categories: ERR/Gy=4.08 (95% CI 0.59, 14.3) in males; ERR/Gy=7.10 (95% CI 0.31, 70.44) in former smokers; ERR/Gy=7.94 (95% CI 1.71, 30.2) in workers with the smoking index above 20 pack×years. No association was observed in the chronic bronchitis mortality risk with external gamma exposure. No strong evidence was observed for the impact of gamma and alpha exposure on risk of mortality from chronic bronchitis. The study confirmed the significant positive linear association of the chronic bronchitis incidence risk with gamma and alpha radiation doses from occupational chronic external and internal exposure. However, the estimates of ERR/Gy of alpha particles from internal exposure appeared to be almost 2.4-3 times lower than those based on the MWDS-2008. The observed inconsistency requires further clarification. As for bronchial asthma in Mayak workers, no association was demonstrated in the incidence and mortality risks with occupational gamma and alpha radiation exposure.

Schistosomiasis endemicity and its role in sexually transmitted infections – a systematic review and meta-analysis

IntroductionSchistosomiasis, a tropical parasitic disease, affects 779 million people globally, with 85% of cases in Africa. The interplay between schistosomiasis and other sexually transmitted infections (STIs) can exacerbate health burdens, but most attention has focused on interactions with HIV, neglecting coinfections with other STIs. This systematic review and meta-analysis aims to understand the role Schistosoma infections play in STIs within schistosomiasis-endemic populations.MethodsThe study is a systematic review and meta-analysis investigating the link between Schistosoma infections and STIs in endemic regions. It uses PRISMA guidelines, electronic databases, and Google Scholar to assess prevalence, associations, and heterogeneity, reducing bias using a Meta-Mar statistical tool.ResultsA quantitative synthesis of 33 articles from 1975–2024 involved 22,587 participants from 13 countries, including regions in Africa, France, and China, examining coinfections of schistosomiasis and STIs, including HIV. The pooled estimates showed a significant risk association between schistosomiasis and STIs [RR (95% CI) = 1.18, (1.13–1.24); z/t = 7.55, p&amp;lt;0.0001] using a fixed effect model. Cochran’s Q test (Tau2 = 0.5061, Chi2 = 476.65, df = 32, p&amp;lt;0.01) indicated significant heterogeneity. The Higgins I2 statistic of 93.0% (91.5%–94.7%), H = 3.86 (3.43–4.33), highlighted substantial variance between studies. Subgroup analysis showed West Africa [Weight IV = 1.7%, RR (95% CI) = 1.78 (1.28–2.47), I2 = 59%], East Africa [Weight IV = 10.5%, RR (95% CI) = 0.99 (0.86–1.13), I2 = 54%], and Southern Africa [Weight IV = 82.0%, RR (95% CI) = 1.16 (1.10–1.21), I2 = 97%] contributed significantly to the high heterogeneity in the pooled analysis. Females had a notably higher risk of STIs in the context of schistosomiasis (k = 17, RR: 1.30, 95% CI: 1.23–1.37, Q = 316.78, I2 = 94.9%), compared to males (k = 6, RR: 0.94, 95% CI: 0.77–1.15, Q = 53.44, I2 = 90.6%) and the combined group of females and males (k = 9, RR: 0.95, 95% CI: 0.88–1.02, Q = 16.38, I2 = 50.2%).ConclusionThe study found a high risk of coinfections between schistosomiasis and STIs, particularly in West and Southern Africa, confirming female genital schistosomiasis as a major risk for STIs.

The impact of lipidome on five inflammatory skin diseases: a Mendelian randomization study.

Two-sample Mendelian randomization (TSMR) was employed to examine the association between lipidome and five inflammatory skin diseases. To evaluate the association between various molecular subtypes of lipidome and the risk of five inflammatory skin diseases, we analyzed a comprehensive GWAS dataset comprising 179 lipidome. The Two-Sample Mendelian Randomization (TSMR) method was employed to investigate causal relationships. Heterogeneity and pleiotropy were assessed using Cochran's Q test, MR-Egger intercept test, and MR-PRESSO global test. Additionally, a sensitivity analysis was conducted to evaluate the influence of individual single nucleotide polymorphisms on Mendelian Randomization study. Using 179 serum lipidome as exposures and five common inflammatory skin diseases as outcomes, we investigated their associations in this large-scale study. Our findings reveal significant impacts of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases. Glycerophospholipids were protective against pemphigus but predominantly posed risks for other inflammatory skin diseases. Specifically, phosphatidylcholine (16:0_0:0) exhibited the most significant risk association with lichen planus (OR = 1.25, 95% CI 1.11-1.40, P < 0.001). Conversely, glycerolipids showed no effect on lichen planus but were protective against pemphigus while potentially posing risks for other conditions. Triacylglycerol (46:2) showed the most substantial risk association with vitiligo (OR = 1.99, 95% CI 1.35-2.93, P < 0.001). Furthermore, sphingomyelins had no effect on atopic dermatitis but posed potential risks for other inflammatory skin diseases. Sphingomyelin (d40:1) notably emerged as a significant risk factor for pemphigus (OR = 1.91, 95% CI 1.37-2.66, P < 0.001). This study has elucidated the potential harmful effects of glycerophospholipids, glycerolipids, and sphingomyelins on inflammatory skin diseases, while also providing valuable insights for future research into the pathophysiology, prevention and treatment of these conditions.

Incidence risk of hepatobiliary malignant neoplasms in the cohort of workers chronically exposed to ionizing radiation

The increased risk of liver malignancies was found in workers of the first Russian nuclear production facility, Mayak Production Association, who had been chronically exposed to gamma rays externally and to alpha particles internally due to plutonium inhalation. In the present study, we updated the radiogenic risk estimates of the hepatobiliary malignancies using the extended follow-up period (1948–2018) of the Mayak worker cohort and the improved «Mayak worker dosimetry system–2013». The cohort comprised 22,377 workers hired at the Mayak PA between 1948 and 1982. The analysis considered 62 liver malignancies (32 hepatocellular carcinomas, 13 intrahepatic cholangiocarcinomas, 16 angiosarcomas, and 1 anaplastic cancer) and 33 gallbladder adenocarcinomas. The analysis proved the positive significant association of the liver malignancy risk (the total of histological types, hepatocellular carcinoma) with the liver absorbed alpha dose from internal exposure. The excess relative risk per Gy (95% confidence interval) of alpha dose (the linear model) was 7.56 (3.44; 17.63) for the total of histological types and 3.85 (0.95; 13.30) for hepatocellular carcinoma. Indications of non-linearity were observed in the dose–response for internal exposure to alpha radiation. No impact of external gamma-ray exposure on the liver malignancy incidence was found. In the study cohort, the number of angiosarcomas among various types of liver malignancies was very high (25.8%), and most of these tumors (73.3%) were registered in individuals internally exposed to alpha radiation at doses ranging between 6.0 and 21.0 Gy. No association with chronic occupational radiation exposure was observed for the incidence of gallbladder malignancies.

Association of muscle health impairment and atherosclerosis with major osteoporotic fracture risk in Taiwanese Vegetarians.

Despite the beneficial effects of "vegetarian style" diet on atherosclerosis, it is also proven potentially detrimental to bone health. The influence of muscle health or atherosclerosis on major osteoporotic fracture (MOF) risk in vegetarians has rarely been explored. This prospective study aimed to investigate an association of MOF risk with muscle health and atherosclerosis in vegetarians. We conducted a questionnaire survey with the Mini-Nutritional Assessment (MNA) on 39 vegetarians. The 10-year probability of MOF was determined using the Taiwanese Fracture Risk Assessment (FRAX®) calculator. Appendicular skeletal muscle (ASM) mass and bone mineral density were measured with dual-energy X-ray absorptiometry. Physical performance was evaluated using the 6-min walk test (6MWT). Common carotid artery intima-media thickness (ccIMT) was determined using sonography. Serum levels of parathyroid hormone (PTH), Vitamin D, adiponectin, and leptin were measured. Eleven (28.2%) of 39 vegetarians had a moderate-high risk of MOF, defined by FRAX-calculated risk ≥10%. These subjects had lower ASM (P < 0.005) and 6MWT distances (P < 0.01) but greater ccIMT than those with low risk. The MOF risk was negatively correlated with ASM (r = -0.51, P < 0.001) and 6MWT distances (r = -0.62, P < 0.001) but positively correlated with ccIMT (r = 0.56, P < 0.001). Linear regression analysis revealed that MOF risk scores were negatively associated with ASM and 6MWT distance while positively associated with ccIMT. There was no significant association of MOF risk with MNA scores, serum levels of PTH, Vitamin D, adiponectin, or leptin. Decreased ASM mass, reduced physical performance, and atherosclerosis are significantly associated with MOF risk in vegetarians.

Human P2X7 receptor variants Gly150Arg and Arg276His polymorphisms have differential effects on risk association and cellular functions in pancreatic cancer

BackgroundThe purinergic P2X7 receptor (P2X7R) plays an important role in the crosstalk between pancreatic stellate cells (PSCs) and cancer cells, thus promoting progression of pancreatic ductal adenocarcinoma (PDAC). Single nucleotide polymorphisms (SNPs) in the P2X7R have been reported for several cancers, but have not been explored in PDAC.Materials and methodsBlood samples from PDAC patients and controls were genotyped for 11 non-synonymous SNPs in P2X7R and a risk analysis was performed. Relevant P2X7R-SNP GFP variants were expressed in PSCs and cancer cells and their function was assayed in the following tests. Responses in Ca2+ were studied with Fura-2 and dye uptake with YO-PRO-1. Cell migration was monitored by fluorescence microscopy. Released cytokines were measured with MSD assay.ResultsRisk analysis showed that two SNPs 474G>A and 853G>A (rs28360447, rs7958316), that lead to the Gly150Arg and Arg276His variants, had a significant but opposite risk association with PDAC development, protecting against and predisposing to the disease, respectively. In vitro experiments performed on cancer cells and PSCs expressing the Gly150Arg variant showed reduced intracellular Ca2+ response, fluorescent dye uptake, and cell migration, while the Arg276His variant reduced dye uptake but displayed WT-like Ca2+ responses. As predicted, P2X7R was involved in cytokine release (IL-6, IL-1β, IL-8, TNF-α), but the P2X7R inhibitors displayed varied effects.ConclusionIn conclusion, we provide evidence for the P2X7R SNPs association with PDAC and propose that they could be considered as potential biomarkers.

Change in risk status of psychiatric patients admitted to Crisis and Home Treatment Team: an evaluation in the UK

IntroductionThe Crisis and Home Treatment Teams (CRHT) in psychiatry manages patients with risk to self and others in the community. The number of patents under CRHT who attempt or die of suicide is high in the UK (Hunt et al BJPsych Bull. 2016;40:172-4). The CRHT is an option to help support patients in managing their risk using various interventions and also aim to prevent admission to acute psychiatric wards where possible.ObjectivesWe intended to study the change in risk to self and others and the factors associated with it during the intervention from a CRHT taking care of adult patients in the West Midlands region of England.MethodsThe study was conducted as a service evaluation of patients admitted under the CRHT. Data was collected from the case records, for 100 patients for whom details were available. Risk to self and others were checked, along with overall risk as red (highest risk), amber (intermediate risk) and green (low risk). Demographic and clinical information was collected and the data quality was checked.ResultsThere were 46 male and 54 female patients in the study, with mean age of 40.4 ± 12.4 and 40.2 ± 12.8 Years respectively (not significant). They were comparable in number of diagnoses (mean 1.2 each) and number of days (22.2 ± 13.1 v 20.2 ± 17.8) in CRHT respectively. There was no significant association of risk with gender (56.3% females and 44.2% of males), being on benefits or type of accommodation the service users live at. Similarly, there was no significant difference of risk of self-harm based on ethnicity; it was noted that 61.2% of patients of British White ethnicity had a risk of self on admission compared to 41.7% Black and ethnic minority patients. On admission, 89% of patients were categorised as red, amber 8% and 1% green; which changed to 18%, 2% and 77% respectively (missing data was not included, so percentages do not add up to 100%). The risk to self was present in 46% on admission and 18% on discharge (p&lt;0.005); and in 14% this risk continued without change. The risk to others on admission was recorded in 12% which was at 1% on the point of discharge (p&lt;0.05). Eight people had both risk to self and others. In 15 patients the risk continued to remain in red category, while in two patients it changed from amber to red.ConclusionsThe risk levels for patients admitted under the CRHT improved. The majority with overall high risk changed to majority presenting as low risk on discharge. The percentage of patients portraying a risk to self and others also decreased from admission to discharge. Although there was considerable decrease in risk, a proportion of patients did not have any change, or even an increase in their risk, which highlights need for additional risk management strategy for these patients in CRHT.Disclosure of InterestNone Declared

IJCM_197A: A cross-sectional study to assess the risk of diabetes among undergraduate medical students in a tertiary care hospital

Background: Diabetes mellitus is one of the major public health problems that affects all age groups. Usually, medical students have sedentary lifestyle owing to academic requirements and there are only limited studies on diabetes screening have been conducted among them. Thus, this study aimed to assess risk of Type 2 Diabetes Mellitus and to study association of diabetes risk with other factors among undergraduate medical students. Objectives: 1. To assess the risk of Type 2 Diabetes Mellitus among undergraduate medical students in a tertiary care hospital. 2. To study the association of risk of Type 2 Diabetes Mellitus with other factors among undergraduate medical students. Methodology: A cross-sectional study conducted among 272 undergraduate medical students in a tertiary care hospital during July 2023 to October 2023. Data collection was done using sociodemographic questionnaire and risk for Type 2 Diabetes Mellitus was assessed using Indian Diabetes Risk Score (IDRS). Results: Among 272 study participants, about 21% had moderate risk score and 1.5% had severe risk score. About 64% medical students belonged to nuclear family, 44.6% had family history of diabetes mellitus and 38% were overweight/ obese. Statistically significant association of moderate-high diabetes risk with nuclear family, positive family history of diabetes, no/mild physical activity and body mass index (BMI) was seen. Conclusion: A significant proportion of undergraduate student had moderate to high risk of Type 2 Diabetes Mellitus. Risk of developing type 2 diabetes mellitus found to associated with nuclear family, family history of diabetes, no or mild physical activity and overweight.

Abstract 4429: Plasma metabolic profiles in association with subsequent risk of colorectal cancer in the UK Biobank cohort

Abstract Background: Dysregulation of metabolic processes contributes to colorectal cancer (CRC) etiology. We aimed to comprehensively evaluate the prospective associations between pre-diagnostic metabolic biomarkers and CRC risk in 230,420 UK Biobank participants. Methods: A total of 249 metabolic biomarkers were measured by nuclear magnetic resonance spectroscopy from baseline plasma samples. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of metabolic biomarkers with CRC risk after adjusting for potential confounders. Subgroup analyses were performed by sex and CRC subsites (i.e., proximal colon, distal colon, rectum). We also conducted factor analyses to identify latent factors and examined their associations with CRC risk. Results: During a median follow-up time of 9.7 years, 2,410 incident primary CRC cases were identified after excluding participants diagnosed with CRC within two years after blood collection. After correcting for multiple testing, 50 metabolic biomarkers, including lipids and lipoproteins, fatty acids, ketone bodies, and inflammation, were significantly associated with incident CRC risk. No statistically significant differences were observed for the biomarker-CRC associations by sex and CRC subsite. In the sensitivity analysis, excluding cholesterol-lowering medication users did not alter the main findings. In factor analyses, we identified a significant association of CRC risk (HR = 1.08; 95% CI = 1.04-1.13; P-value = 6.89×10-5) with a metabolite pattern which was positively correlated with triglycerides and inversely correlated with relative concentrations of omega-6 fatty acids and polyunsaturated fatty acids. Conclusion: We identified multiple metabolic biomarkers and a metabolite pattern associated with CRC risk in a large prospective cohort. These findings suggest lipid metabolism may contribute to carcinogenesis of the colorectum. Citation Format: Fangcheng Yuan, Guochong Jia, Wanqing Wen, Wei Zheng. Plasma metabolic profiles in association with subsequent risk of colorectal cancer in the UK Biobank cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4429.

Association of body composition indices with cardiovascular outcomes: a nationwide cohort study

BackgroundPrevious studies regarding BMI (kg/m2) and associated cardiovascular outcomes yield inconsistent results. ObjectivesWe aimed to investigate the association between body composition and cardiovascular outcomes according to BMI categories in the Korean general population. MethodsA total of 2,604,401 participants were enrolled in this nationwide cohort study using the National Health Insurance Service-Health Checkup data set. Predicted lean BMI (pLBMI), body fat mass index (pBFMI), and appendicular skeletal muscle mass index (pASMMI) were calculated using validated anthropometric prediction equations. A multivariable time-dependent Cox regression analysis was conducted to assess the association with cardiovascular outcomes. The results were presented with adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), considering BMI categories (BMI < 18.5, BMI 18.5–24.9, BMI 25–29.9, and BMI ≥ 30). ResultsHigher pLBMI and pASMMI were correlated with a reduced risk of composite cardiovascular outcomes. For pLBMI, HR was 0.910 (95% CI: 0.908, 0.913, P < 0.001) for males and 0.905 (95% CI: 0.899, 0.910, P < 0.001) for females. For pASMMI, HR was 0.825 (95% CI: 0.820, 0.829, P < 0.001) for males and 0.788 (95% CI: 0.777, 0.800, P < 0.001) for females. Conversely, a higher pBFMI was associated with an increased risk, with HR of 1.082 (95% CI: 1.071, 1.093, P < 0.001) for males and 1.181 (95% CI: 1.170, 1.192, P < 0.001) for females. Subgroup analysis based on BMI categories revealed no significant risk association for pBFMI in the BMI < 18.5 group. In the group with BMI ≥ 30, neither pLBMI nor pASMMI demonstrated a significant risk association. ConclusionsOur results highlight the value of pLBMI, pBFMI, and pASMMI as variables for assessing risk of composite cardiovascular outcomes. The significance of indicators may vary depending on BMI categories.

Risk association of the nitric oxide synthase VNTR intron 4 a/b variant with diabetic nephropathy – a pilot study

Diabetic nephropathy (DN) is known to be a leading complication of type 2 diabetes mellitus (T2D). This study evaluated whether the VNTR intron 4 a/b and rs1799983 polymorphisms of endothelial-derived nitric oxide synthase (eNOS) gene modulated the risk of developing DN in Asian Indian patients. The eNOS variants were genotyped in 200 patients, 100 with DN and 100 without DN. A significant risk association was observed for the VNTR intron 4 a/b (p < 0.05). Haplotype analysis revealed that the allele combination of rs1799983894 G/Intron 4b and rs1799983894 T/Intron 4b had a statistically significant inverse association with DN.

Маммографическая плотность и риск рака молочной железы (обзор литературы)

Abstract. Breast cancer is a significant global public health problem and one of the most common cancers among women. Mammography is the main method for screening and diagnosing breast cancer, and it is important to understand the relation of mammographic density and the risk of developing this disease. In this research we review existing works on this issue and analyze the available data to assess the association of mammographic density and breast cancer risk. Our results confirm a significant association of mammographic density and breast cancer risk, highlighting the importance of this parameter in screening and predicting the development of breast cancer. Mammographic density has clinical significance in breast cancer screening and prognosis and can be used to determine an individual’s risk of developing breast cancer and make decisions about further testing and treatment. Future research should be aimed at elucidating the mechanisms underlying this association, as well as developing innovative screening methods that incorporate mammographic density as a prognostic factor.

Risk of bone fracture by using dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors in patients with type 2 diabetes mellitus: a network meta-analysis of population-based cohort studies.

Type 2 diabetes mellitus (T2DM) is linked to a heightened likelihood of experiencing fractures. It is crucial to ascertain whether medications used to lower blood sugar levels can elevate the risk of fractures. We aimed to investigate and compare the effects of glucagon-like peptide 1 receptor agonists (GLP-1RA), Dipeptidyl Peptidase-4 Inhibitors (DPP-4i), and Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2i) on the fracture risk in patients with T2D in the real world. A network meta-analysis conducted an inclusive literature search in PubMed, Scopus, Web of Science, and Cochrane Library to select appropriate population-based cohort studies that investigated the risk of bone fractures of (GLP-1RA), (DPP-4i) or (SGLT-2i) in the real world. A network meta-analysis (NMA) was performed using R software to investigate the risk of total fractures as a primary outcome among patients who used (GLP-1RAs), (SGLT-2i) or (DPP-4i) versus each other or other glucose-lowering medications (GLMs). The odds ratio (OR) and 95% confidence interval (CI) were summarized overall network and for each pairwise direct and indirect comparison. The surface under the cumulative ranking curve (SUCRA) with the P-scores was calculated for each treatment in the network meta-analysis to detect their cumulative ranking probabilities in lowering the risk of total fractures. In our NMA, we identified a set of 13 population-based cohort studies comprising a total of 1,064,952 patients. The risk of fracture was identified with the follow-up duration for each class. We found a significant decrease in the fracture risk by about 87% associated with patients who used SGLT2 inhibitors in combination with other glucose-lowering medications, followed by SGLT2 inhibitors alone by about 67%, then GLP-1 receptor agonists by about 60%, and at last DPP-4 inhibitors by about 55%. Our study's collective findings suggest a significant association of the low risk of fracture with the use of SGLT2i with other GLMs combination, SGLT2i alone, GLP-1RA, and DPP-4i, respectively. This population-based analysis offers the best available evidence and might be helpful for clinicians in the decision of the most suitable T2DM treatment strategies, especially for elderly type 2 diabetic patients, as they may be safe in terms of fracture. https://www.crd.york.ac.uk/prospero/, identifier CRD42023448720.

Impact of single-nucleotide variants and individual characteristics on adverse events of L-asparaginase in children with acute lymphoblastic leukemia.

L-Asparaginase (L-Asp) is a key drug in the treatment of acute lymphoblastic leukemia (ALL); however, it is commonly associated with the occurrence of adverse events (AE). Risk factors such as age, sex, nutritional status, and some single nucleotide variants (SNVs) in specific genes could be related to hypersensitivity reactions to L-Asp. The objective of this study was to identify the influence of individual characteristics and three SNVs in the GRIA1 and NFATC2 genes on the occurrence of the most significant adverse events caused by the use of L-Asp in Mexican children with ALL. Eighty-five children from ages 0-17years old diagnosed with ALL were included. The patients were treated at two hospital centers in Mexico. The SNV genotypes of the GRI1A and NFATC2 genes studied were examined using real-time qPCR. The evaluation of AE was carried out according to the Common Terminology Criteria for adverse events, and the determination of anti-L-Asp antibodies was conducted using Western blot immunoassay. Homozygosity (AA) of the GRIA1 rs4958351 SNV was significantly associated with the occurrence of AE with the use of L-Asp (OR = 4.05; 95% CI = 1.06 to 15.40, p = 0.04) and was strongly associated with the development of anti-L-Asp antibodies (OR = 3.4375, 95% CI = 1.04 to 11.25, p = 0.04). With this, we found a significant risk association for the SNV rs4958351 of the GRIA1 gene. On the other hand, we did not find significant risk associations for the GRIA1 rs6889909 and NFATC2 rs6021191 SNVs, although other populations have shown a significant risk. Our study has some limitations, such as the small sample size, the heterogeneity in adverse events due to the patients' different regions of origin, and the limited ability to conduct a more detailed follow-up on pancreatitis. Additionally, since no significant associations were found between the NFATC2 rs6021191 and GRIA1 rs6889909 SNVs and the development of adverse events or the presence of antibodies due to the use of L-Asp, it is necessary to investigate new specific SNVs that may improve the efficacy and safety of treatment in Mexican children with ALL.

Ergonomic Risk Assessment for Musculoskeletal Disorders among Ultrasonologists of Peshawar: A Cross- Sectional Survey

Background: Ergonomics is the study of analyzing the demands of a task and aligning them with the abilities of the worker to establish an optimal work environment that minimizes the likelihood of injuries while maximizing efficiency. In safety and ergonomic literature, risk factors and consequent risks are common conceptions. Ergonomics has an impact on the adapted posture of workers developed due to the demand of their work procedure. Disorders related to bad posture and usage of different equipment and tools in a workplace can be solved through better ergonomics. Objective: To determine the ergonomic risk assessment for musculoskeletal disorders among Ultrasonologists of Peshawar. Methods: A cross-sectional study was conducted on a total of 117 participants from both public and private sector hospitals of Peshawar. Census sampling technique was used to select the participants. Consent was obtained and data was recorded using the Rapid Upper Limb Assessment (RULA) questionnaire. Results: Among the participants (n=117), majority were from the age group 31-40 years, n=48 (41%) with a mean age of 36 ± 7. Regarding the gender distribution, males were greater in number, n=88 (75.2%). The ergonomic risk for musculoskeletal disorders reveals that, majority of the participants fall in the medium risk, followed by low risk, negligible risk and very high risk, respectively. The analysis showed statistically significant association of ergonomics risk with age, gender, working hours, organization and work experience. Conclusions: It was concluded that the ergonomic risk for musculoskeletal disorders among Ultrasonologists is moderate to low followed by high risk. Males have higher ergonomic risk compared to females. Further investigations are needed.

Abstract 18543: Association of Nonalcoholic Steatohepatitis With Predicted 10-Year Cardiovascular Risk, Independent of Diabetes Status (NHANES 2017-2020)

Introduction: Evidence suggests patients with nonalcoholic steatohepatitis (NASH), particularly those with significant fibrosis (stages ≥F2), have elevated CV-event risk. Hypothesis: The association of NASH with diabetes may confound the relationship between NASH and CV-event risk. Goals/Aims: To estimate primary CV-event risk associated with presumed NASH, adjusting for diabetes. Methods: A cross-sectional analysis of the 2017-March 2020 NHANES cycle was conducted. Presumed NASH was defined as evidence of steatosis (controlled attenuation parameter [CAP] ≥302 dB/m), exclusion of excessive alcohol consumption or hepatitis B/C, and FibroScan-AST (FAST) score ≥0.48. Non-NASH controls were matched 3:1 based on age, sex, and race. The 10-year probability of a primary CV event was estimated using the Framingham Heart Study risk equations. Linear models were used to estimate the association of presumed NASH with CV risk, with and without adjustment for diabetes, and distinguishing fibrosis stages F0-F1 vs F2-F4 within presumed NASH. Results: The analysis included 123/369 matched participants with/without presumed NASH. Mean (SE, P value) incremental probability of a primary CV event associated with presumed NASH was 1.4% (1.2%, P =0.26) before adjustment for diabetes, and 1.8% (1.0%, P =0.10) after adjustment. In participants ages &lt;65, the association with presumed NASH was statistically significant at 2.3% (1.1%, P =0.05) before adjustment for diabetes, and 2.1% (1.0%, P =0.04) after adjustment, and elevated in fibrosis stages F2-F4 (see Table). Limited sample size challenged reliability of estimates for ages ≥65. Conclusions: Among individuals ages &lt;65, a significant association of presumed NASH and primary CV-event risk was observed, before and after adjusting for diabetes. The incremental risk was greater for fibrosis stages F2-F4, suggesting the importance of accounting for fibrosis stage in predicting CV risk.

Genetic association of PTPN22 polymorphisms with Type 1 diabetes in Pakistani children

ObjectiveType 1 diabetes, a multigenic autoimmune disorder, is caused by the destruction of pancreatic beta-cells leads to insufficient insulin production and hyperglycemia, resulting in early morbidities and mortality. This study was designed to explore the genetic association of PTPN22 gene polymorphisms with T1D susceptibility among Pakistani children. MethodsBlood samples of T1D patients were obtained from the Department of Diabetes and Endocrinology of Children Hospital & University of Child Health Sciences, Lahore. Genotyping of rs2476601, rs1310182, and rs1217414of the PTPN22 gene was performed by Tetra ARMS-PCR assay. Statistically, binary logistic regression was applied to determine variation in genotype distribution and association of PTPN22 gene polymorphism with T1D. ResultsGenetic analysis showed that the A allele of rs2476601 (OR = 0.53, 95 % CI = 0.31–0.90; P < 0.02) and T allele of rs1310182 was found to be risk allele for T1D development (OR = 0.51, 95 % CI = 0.36–0.76; P < 0.01) while the A allele of rs1217414 was a protective allele against T1D (OR = 1.19, 95 % CI = 0.80–1.77; P = 0.36). Genetic models revealed that GG genotypes of rs2476601 (OR = 2.01, 95 % CI = 1.13–3.58; P < 0.01), and AA genotypes of rs1310182 in the dominant model (OR = 1.83, 95 % CI = 1.03–3.24; P < 0.03) showed significant risk association with T1D. ConclusionFrom the results, it is concluded that PTPN22gene has a strong genetic association with SNP rs2476601andrs1310182with T1D in Pakistani children.

Identification of contributing factors, microorganisms and antimicrobial resistance involved in the complication of diabetic foot ulcer treatment

Diabetic foot ulcer (DFU) is a neurological and peripherical complication of diabetes with unknown etiology that is often associated with polymicrobial infections. The present study was conducted to investigate the contributing factors in 285 DFU patients, which included 200 patients with diabetic foot infections (DFI). Identification and characterization of infecting bacterial isolates were done followed by assessment of their pattern of susceptibility to commonly used antibiotics. Among the studied subjects, type 2 diabetes mellitus (T2DM), ulcer type, depth, grade, loss of sensation, infection type, affected foot, recurrence, smoking status, Body Mass Index (BMI), and obesity levels revealed significant disease risk association. Ulcer grades 1 and 2 were more common in males while grade 3 in females. Recurrent infections were significantly higher in females (P = 0.03). Diabetic duration, hyperglycemia, ulcer type, infection type and BMI were positively correlated with delayed wound healing. In DFI samples, 40.2% consisted of gram-negative bacteria, with Pseudomonas aeruginosa (37.5%) being the most common, while in the 60% gram-positive isolates Staphylococcus aureus (40.5%) was the predominant species. Staphylococcus epidermidis was found more frequently in females (P = 0.05). The isolated bacterial strains presented higher resistance against the tested antibiotics; however, ceftriaxone was effective against most of the pathogens. In the current study T2DM along with diabetes duration, obesity, ulcer severity with polymicrobial infection was found to play a strong role in DFI development, where gender predisposition was also observed in ulcer grade and infection. DFI was correlated with loss of sensation, infection type, affected foot, smoking status, BMI and obesity levels.

Association of 11 variants of the dopaminergic and cognitive pathways genes with major depression, schizophrenia and bipolar disorder in the Pakistani population

Background: The dopaminergic pathways control neural signals that modulate mood and behaviour along and have a vital role in the aetiology of major depression (MDD), schizophrenia (SHZ) and bipolar disorder (BD). Genome-wide association studies (GWAS) have reported several dopaminergic and cognitive pathway genes association with these disorders however, no such comprehensive data was available regarding the Pakistani population.Objective: The present study was conducted to analyse the 11 genetic variants of dopaminergic and cognitive system genes in MDD, SHZ, and BD in the Pakistani population.Methods: A total of 1237 subjects [MDD n = 479; BD n = 222; SHZ n = 146; and controls n = 390], were screened for 11 genetic variants through polymerase chain reaction (PCR) techniques. Univariant followed by multivariant logistic regression analysis was applied to determine the genetic association.Results: Significant risk associations were observed for rs4532 and rs1799732 with MDD; and rs1006737 and rs2238056 with BD. However, after applying multiple test corrections rs4532 and rs1799732 association did not remain significant for MDD. Moreover, a protective association was found for three variants; DRD4-120bp, rs10033951 and rs2388334 in the current cohort.Conclusions: The present study revealed the risk association of single nucleotide polymorphisms (SNPs) rs1006737 and rs2238056 with BD and the protective effect of the DRD4-120bp variant in MDD and BD, of rs2388334 in BD and of rs10033951 in MDD, BD, and SHZ in the current Pakistani cohort. Thus, the study is valuable in understanding the genetic basis of MDD, BD and SHZ in the Pakistani population, which may pave the way for future functional studies.