Threshold For Statistical Significance Research Articles

Discussion on the relationship between gut microbiota and glioma through Mendelian randomization test based on the brain gut axis.

In the realm of Gut-Brain axis research, existing evidence points to a complex bidirectional regulatory mechanism between gut microbiota and the brain. However, the question of whether a causal relationship exists between gut microbiota and specific types of brain tumors, such as gliomas, remains unresolved. To address this gap, we employed publicly available Genome-Wide Association Study (GWAS) and MIOBEN databases, conducting an in-depth analysis using Two-Sample Mendelian Randomization (MR). We carried out two sets of MR analyses. The preliminary analysis included fewer instrumental variables due to a high genome-wide statistical significance threshold (5×10-8). To enable a more comprehensive and detailed analysis, we adjusted the significance threshold to 1×10-5. We performed linkage disequilibrium analysis (R2 <0.001, clumping distance = 10,000kb) and detailed screening of palindromic SNPs, followed by MR analysis and validation through sensitivity analysis. Our findings reveal a causal relationship between gut microbiota and gliomas. Further confirmation via Inverse Variance Weighting (IVW) identified eight specific microbial communities related to gliomas. Notably, the Peptostreptococcaceae and Olsenella communities appear to have a protective effect, reducing glioma risk. This study not only confirms the causal link between gut microbiota and gliomas but also suggests a new avenue for future glioma treatment.

Clinical Significance of the Large Fetal Vessel Lesions in Placental Fetal Vascular Malperfusion

Fetal vascular malperfusion (FVM) is an important pattern of placental injury. Although the significance of distal villous FVM (clusters of sclerotic and/or mineralized chorionic villi) is well documented, the clinical significance of proximal (large vessel) lesions of FVM is less clear, which is the aim of this retrospective analysis. To evaluate the clinical significance and placental associations of single and coexisting categories of lesions of large vessel FVM, 24 clinical and 44 placental phenotypes of 804 consecutive placentas with at least 1 lesion of proximal vessel FVM from the second half of pregnancy, divided according to the type or category of the individual FVM lesion (fetal vascular ectasia, fetal vascular thrombi, intramural fibrin deposition, and stem vessel obliteration): 689, 341, 286, and 267 placentas, respectively (first analysis) and single or coexisting large fetal vessel lesions (1, 2, 3, and 4 coexisting categories of lesions: 276, 321, 162, and 45 placentas, respectively) were statistically compared (analysis of variance, χ2, univariate analysis). Because of multiple comparisons, Bonferroni-corrected P < .001 was used as a threshold of statistical significance. In this population of high-risk pregnancies dominated by fetal congenital anomalies, single individual or 1 to 2 coexisting categories of lesions of the large vessel FVM, including fetal vascular thrombi, did not consistently correlate with clinical or placental variables and were not prognostically useful, but the coexistence of 3 or 4 lesions was associated with the most advanced gestational age, fetal congenital anomalies, distal villous FVM, particularly high-grade, chorangioma or chorangiomatosis, hypercoiled umbilical cord, perivascular stem edema, and marginate or vallate placenta. Therefore, the finding of multiple lesions of the large vessel FVM not only merits a diligent search for the distal villous lesions including the CD34 immunostaining, but also justifies putting the large vessel (global) FVM on the final placental diagnosis line, which in the case of up to only 2 lesions may not be justified.

#2526 Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate

Abstract Background and Aims Chronic kidney disease (CKD) is a growing global health concern. In recent years, studies have increasingly focused on the differential risk profile of diseases between men and women. Current evidence suggests that sex-linked biological and behavioral differences may play a key role in influencing the incidence, prevalence, and outcomes of diseases. Similarly, previous studies have demonstrated a differential risk profile in the prevalence, progression, and outcomes of CKD between men and women. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. Method We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150 ml/min per 1.73 m². The outcomes were CKD-related complications (hypertension, anemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. Values of eGFR over which the log-odds (for CKD-related complications outcomes) or log-hazard (for all-cause and cause-specific mortality outcomes) was found to be significantly different from zero (i.e., 95% CI for the smooth term did not contain zero) were identified as thresholds of statistical significance. Results The study included 49, 562 participants (50.31% women, 49.68% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modeling eGFR as a natural spline revealed varied significance thresholds between sexes for anemia and hyperparathyroidism. We found a significantly (P &amp;lt; 0.05) higher proportion of women with anemia downstream an eGFR cut-off of 69 mL/min per 1.73 m2, which was lower than the cut-off in men; a significantly higher proportion of men with anemia was observed downstream an eGFR cut-off of 76 mL/min per 1.73 m2. However, the relationship was more pronounced in women than in men; thus, at an eGFR cut-off of 41 mL/min per 1.73 m2, the proportion of women with anemia was significantly higher (P &amp;lt; .05) (Figure). Similarly, a higher proportion of women with hyperparathyroidism were observed downstream an eGFR cut-off of 73 mL/min per 1.73 m2, which was lower than in men; a significantly higher proportion of men (P &amp;lt; .05) was observed downstream an eGFR cut-off of 89 mL/min per 1.73 m2 (Figure). Furthermore, although no sex differences were observed in terms of eGFR thresholds for hyperphosphatemia, a more pronounced relationship was observed in men. Thus, at an eGFR cut-off of 38 mL/min per 1.73 m2, the proportion of men with hyperphosphatemia was significantly higher (P &amp;lt; .05) than that of women (Figure). We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR Conclusion Research shows sex disparities in most CKD-related complications. Men develop anemia and hyperparathyroidism earlier, women show steeper anemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

#2793 Improvement of bone mineral density in kidney transplant recipients: it is just denosumab?

Abstract Background and Aims Post-transplant bone disease is a common complication after a kidney transplant. Several factors, including pre-existing CKD-MBD, steroid, and CNI immunosuppressive treatment, contribute to this condition and increase the risk of bone loss and fractures. Among various therapeutic strategies, Denosumab, a human monoclonal antibody against RANK-L, can decrease the risk of fracture in Kidney Transplant Recipients (KTRs). The most reported side effects are episodes of hypocalcemia, which are associated with an increase in parathyroid hormone (PTH) levels. The FDA recommends treating these episodes with calcium supplements and cholecalciferol; another alternative is the use of receptor activators (VDRa). To our knowledge, there are only a few case reports in the literature analyzing the effect of combined treatment with VDRa and Denosumab. In this observational study, we evaluated changes in laboratory data and bone density (BMD) assessed by DXA in KTRs that received Denosumab with or without VDRa supplementation. Method This retrospective study evaluated 18 kidney transplant recipients who started Denosumab therapy after transplantation. The patients were divided into two groups: those who started or increased vitamin D receptor agonist therapy within the first 6 months before the second dose of Denosumab, and those who did not. We analyzed at baseline (T0) and after 1 year from first Denosumab administration (T1) creatinine, calcium, phosphate, PTH, bone alkaline phosphatase (BALP), osteocalcin (OC), carboxy-terminal cross-linked telopeptides of type 1 collagen (CTX), and 25-OH vitamin D and BMD at vertebral lumbar spine, femoral neck and total Hip. Furthermore, we evaluated Trabecular Bone Score (TBS). We performed ANOVA and Kruskal-Wallis for continuous variables based on distribution and Fisher's test for categorical variables. To assess the correlation between variables, we used linear regression and the Pearson correlation coefficient. Additionally, we conducted logistic regression to analyze the outcomes. Results A total of 18 patients were included in the study cohort. Of these, 66.7% were females, and 33.3% were males, with an average age of 67 years (Table 1). 13 patients started or uptitrated VDRa within the first 6 months (VDRa group), while 5 did not (Control group). At baseline, the VDRa group had a lower eGFR and higher PTH compared to the Control group, although both were at the threshold of statistical significance (37.38 vs 52.20 mL/min/1.73 m², p = 0.060 and 106.77 vs 72.60 pg/mL, p = 0.069). However, they had significantly lower serum calcium levels (8.96 vs 9.90 mg/dL, p = 0.039). In terms of baseline bone structure, there were no significant differences between the two groups at any of the three sites examined. At 1 year the VDRa group had a significantly greater gain at the Total Hip (+0.08 vs −0.03 g/cm3, p = 0.048 and +10.81 vs −4.16%, p = 0.037). Additionally, the VDRa group had an increase in TBS, while the Control group had a reduction, and this absolute and percentage variation between the two was statistically significant (+0.07 vs −0.02, p = 0.034 and +6.14 vs −1.62, p = 0.043) (Table 2). In linear correlation analysis higher doses of VDRa were significantly and positively associated with Delta BMD at the Total Hip (r = 0.65, p = 0.003). However, a significant correlation was highlighted between VDRa dosage and PTH reduction (r = −0.51, p = 0.027). Finally, in univariate logistic regression analysis, the dosage of VDRA was significantly and positively associated with 5% BMD gain at the Total Hip (OR = 1.54, CI 1.08 to 1.89, p = 0.046) (Fig. 1). Conclusion After conducting our study, we found that the use of Denosumab had a positive impact on bone mineral density. In addition to that, we observed that the association with VDRa led to further improvement in BMD and better control of PTH. Despite having a small sample size, our study demonstrates that VDRa not only helps in correcting hypocalcemia but also enhances the effect of Denosumab.

Generalizing Diffusion Tensor Imaging of the Physis and Metaphysis.

Current methods to predict height potential are inaccurate. Predicting height by using MRI of the physeal cartilage has shown promise but the applicability of this technique in different imaging setups has not been well-evaluated. To assess variability in diffusion tensor imaging of the physis and metaphysis (DTI-P/M) of the distal femur between different scanners, imaging parameters, tractography software, and resolution. Prospective. Eleven healthy subjects (five males and six females ages 10-16.94). 3 T; DTI single shot echo planar sequences. Physeal DTI tract measurements of the distal femur were compared between different scanners, imaging parameters, tractography settings, interpolation correction, and tractography software. Bland-Altman, Spearman correlation, linear regression, and Shapiro-Wilk tests. Threshold for statistical significance was set at P = 0.05. DTI tract values consistently showed low variability with different imaging and analysis settings. Vendor to vendor comparison exhibited strong correlation (ρ = 0.93) and small but significant bias (bias -5.76, limits of agreement [LOA] -24.31 to 12.78). Strong correlation and no significant difference were seen between technical replicates of the General Electric MRI scanner (ρ = 1, bias 0.17 [LOA -1.5 to 1.2], P = 0.42) and the Siemens MRI scanner (ρ = 0.89, bias = 0.56, P = 0.71). Different voxel sizes (1 × 1 × 2 mm3 vs. 2 × 2 × 3 mm3) did not significantly affect DTI values (bias = 1.4 [LOA -5.7 to 8.4], P = 0.35) but maintained a strong correlation (ρ = 0.82). Gap size (0 mm vs. 0.6 mm) significantly affects tract volume (bias = 1.8 [LOA -5.4 to 1.8]) but maintains a strong correlation (ρ = 0.93). Comparison of tractography algorithms generated significant differences in tract number, length, and volume while maintaining correlation (ρ = 0.86, 0.99, 0.93, respectively). Comparison of interobserver variability between different tractography software also revealed significant differences while maintaining high correlation (ρ = 0.85-0.98). DTI of the pediatric physis cartilage shows high reproducibility between different imaging and analytic parameters. 2 TECHNICAL EFFICACY: Stage 1.

Optimizing Treatment Quality in Head and Neck Cancer Therapy: Impact of Adaptive Intensity-Modulated Radiotherapy on Plan Quality and Tumor Volume Changes

Objective: This research analyses whether volumetric changes and PTV shifting affect adaptive intensity-modulated radiotherapy (IMRT) plan quality and head and neck cancer therapy. Methods: The research was carried out at the Sohag Cancer Centre in Egypt, including a sample of 36 individuals diagnosed with head and neck squamous cell carcinoma (HNSCC). Patients were chosen on the basis of the following criteria: locally progressed and node-positive malignancy, oropharyngeal cancer, oral cavity cancer, and unknown primary. The research used dynamic intensity-modulated radiation therapy (D-IMRT) to establish treatment plans and Siemens SOMATOM DEFINITION CT scanners to acquire 3D anatomical images. A range of 1.64 to 2.12 Gy was observed for the median dosage per fraction. Using the conformance index (CI) and the homogeneity index, the quality of the plan was assessed (HI). The threshold for statistical significance was set at 0.05. Results: The study analysed patients with unilateral and bilateral HNSCC tumors, with a majority having bilateral tumors. The findings demonstrated that the tumor PTV was significantly reduced as a consequence of the suggested adaptive radiation techniques. Both the homogeneity index and the conformity index were used to evaluate the plan's quality (HI). The maximal homogeneity index (HI) was reached after 7 and 14 fractions, respectively. The positive correlation between PTV reduction and CI after 7 fractions, while a negative correlation found after fractions 14 and 21. It was also shown that HI is positively correlated with PTV changes after 7 and 14. Conclusion: The use of adaptive radiotherapy in intensity-modulated radiation therapy (IMRT) treatment planning improves plan quality and decreases error rates due to tumor margin movement. Following radiation fractions, PTV shifting affects the homogeneity index (HI).

Belimumab corticosteroid-sparing treatment in systemic lupus erythematosus: a real-life observational study (BESST study).

Data about the impact of Belimumab on corticosteroid sparing in real life are scarce. To assess the corticosteroid-sparing effect among patients with systemic lupus erythematosus (SLE) treated with Belimumab in real-life settings. Multicentric observational retrospective study including patients with SLE and having received Belimumab for at least 6months between 2011 and 2020, in eight French hospitals. "Low dose" referred to patients receiving up to 7.5mg of prednisone a day and "Very low dose" to those receiving strictly ≤ 5mg prednisone a day The primary endpoint was the reduction of daily prednisone dose after six months of Belimumab. The secondary endpoint was a change in the proportion of patients with low or very low dose of prednisone as well as those without prednisone during the Belimumab course. Censoring occurred for patients who stopped Belimumab. Bivariate analyses were performed using the Wilcoxon signed-rank test. The threshold for statistical significance was set at p < 0.05. Thirty patients were included. All were female with a median age of 38years. A significant reduction in prednisone dose was observed at month 6 (10 [7-20] vs 6.75 [2-9] mg, p < 0.0001), continued until month 12 (10 [7-20] mg vs 5 [0-7.12] mg, p < 0.001) and was sustained until month 24. The proportion of patients with very low dose of prednisone and those without prednisone progressively increased during the Belimumab course. Introducing Belimumab in patients with SLE, in real-life conditions, is associated with early and sustained corticosteroid-sparing effect.

Effectiveness of a Smartphone App (Heia Meg) in Improving Decisions About Nutrition and Physical Activity: Prospective Longitudinal Study.

Obesity is a prevalent and serious chronic condition associated with abnormal or excessive fat buildup that poses significant health risks. The rates of overweight and obesity in adults and children continue to rise, with global rates of children with overweight or obesity aged 5-19 years growing from 4% to 18% between 1975 and 2016. Furthermore, in 2017, nearly 4 million people died due to complications arising from being overweight or obese. This study aims to investigate the potential impact of the mobile app Heia Meg on promoting healthier lifestyle choices regarding nutrition and physical activity. A prospective longitudinal study was conducted in collaboration with the Norwegian Directorate of Health. Participants were recruited through the Heia Meg app and were asked to complete a questionnaire before and after using the app. A total of 199 responses were included in the first (preintervention) questionnaire, while 99 valid responses were obtained in the second (postintervention) questionnaire. The majority (159/199, 79.9%) of participants were female, and their age ranged from 18 years to 70 years and older. The results show a reduction in BMI after the digital intervention. However, some variables influence the BMI reduction effect: sex, age, education, and smoking. The group that obtained the most benefit from the intervention consisted of those who were male, aged 30-39 years, highly educated, and nonsmokers. Although positive, some of the findings are slightly above the statistical significance threshold and therefore should be interpreted carefully. Our study found weak evidence to support the effectiveness of the Heia Meg app in promoting healthier lifestyle choices. However, limitations and confounding factors suggest that further research in different populations with larger sample sizes is needed to confirm or disprove our findings.

Measuring the effects of nurse-led frailty intervention on community-dwelling older people in Ethiopia: a quasi-experimental study

BackgroundDespite the critical need, interventions aimed at frailty in sub-Saharan Africa are scarce, attributed to factors such as insufficient healthcare infrastructure, the pressing need to address infectious diseases, maternal and child health issues, and a general lack of awareness. Hence, the aim of this research was to develop, implement, and evaluate the effect of a nurse-led program on frailty and associated health outcomes in community-dwelling older individuals in Ethiopia.MethodsThis study utilised a pre-test, post-test, and follow-up single-group quasi-experimental design. The main outcome measure was to determine changes in the frailty levels of older individuals living in communities at three different intervals: initially (T0), immediately after the intervention (T1), and 12 weeks following the intervention (T2). Secondary outcomes were the observed changes in daily living activities, nutritional status, depression levels, and quality of life (QOL), evaluated at each of these data collection points. To analyse changes in frailty and response variables over these periods, Friedman’s ANOVA and Cochran’s Q test were employed, setting the threshold for statistical significance at P < 0.05.ResultsSixty-six older people with a high adherence rate of 97% completed the intervention and the follow-up measurements. Participants had an average age of 66.7 ± 7.9 years, with females comprising 79.4% of the group. Notably, 12 weeks post-intervention, there was a marked decrease in frailty (χ2(2) = 101.05, p < 0.001) and depression scores (χ2(2) = 9.55, p = 0.008) compared to the baseline. However, the changes in depression, physical, mental, and environmental domains of QOL were not sustained for 12 weeks post-intervention. Study participants showed an improvement in nutritional status (χ2(2) = 25.68, p < 0.001), activity of daily living (χ2(2) = 6.00, p = 0.05), and global quality of life (χ2(2) = 20.64, p < 0.001).ConclusionsThe nurse-led intervention notably, 12 weeks post-intervention reduced frailty and depression. The intervention improved the nutritional status and some components of the quality of life of the participants. There is a need for further studies, especially with larger participant groups and stronger research designs such as randomized controlled trials (RCTs).Trial registrationClinicalTrials.gov: NCT05754398 (03/03/2023).

Machine Learning Prediction of Tongue Pressure in Elderly Patients with Head and Neck Tumor: A Cross-Sectional Study.

Background: This investigation sought to cross validate the predictors of tongue pressure recovery in elderly patients' post-treatment for head and neck tumors, leveraging advanced machine learning techniques. Methods: By employing logistic regression, support vector regression, random forest, and extreme gradient boosting, the study analyzed an array of variables including patient demographics, surgery types, dental health status, and age, drawn from comprehensive medical records and direct tongue pressure assessments. Results: Among the models, logistic regression emerged as the most effective, demonstrating an accuracy of 0.630 [95% confidence interval (CI): 0.370-0.778], F1 score of 0.688 [95% confidence interval (CI): 0.435-0.853], precision of 0.611 [95% confidence interval (CI): 0.313-0.801], recall of 0.786 [95% confidence interval (CI): 0.413-0.938] and an area under the receiver operating characteristic curve of 0.626 [95% confidence interval (CI): 0.409-0.806]. This model distinctly highlighted the significance of glossectomy (p = 0.039), the presence of functional teeth (p = 0.043), and the patient's age (p = 0.044) as pivotal factors influencing tongue pressure, setting the threshold for statistical significance at p < 0.05. Conclusions: The analysis underscored the critical role of glossectomy, the presence of functional natural teeth, and age as determinants of tongue pressure in logistics regression, with the presence of natural teeth and the tumor site located in the tongue consistently emerging as the key predictors across all computational models employed in this study.

Sex differences in chronic kidney disease-related complications and mortality across levels of glomerular filtration rate.

Chronic kidney disease (CKD) is a growing global health concern. Recent research has indicated sex disparities in CKD-related complications, yet the impact of sex differences on critical kidney function levels that trigger these complications and mortality remains inadequately documented. We investigated sex-specific disparities in CKD-related complications and mortality according to eGFR levels. We analyzed NHANES data spanning from 1999 to 2018, including adult participants with an eGFR of 15-150ml/min per 1.73m². The outcomes were CKD-related complications (hypertension, anaemia, CV diseases, acidosis, hyperphosphatemia, hyperparathyroidism) and all-cause and cause-specific mortality (CV mortality and non-CV mortality). Sex-stratified multivariable logistic and Cox regression models yielded odds ratios (ORs) and hazard ratios (HRs) for the relationship between eGFR categories and outcomes. Sex-stratified natural splines were used to explore the relationship between continuous eGFR and outcomes and identified eGFR thresholds of statistical significance. The study included 49558 participants (50.3% women, 49.7% men). Multivariable logistic regression demonstrated a significant eGFR association with all CKD-related complications, exhibiting a linear trend across eGFR categories. Modelling eGFR as a natural spline revealed varied significance thresholds between sexes for anaemia and hyperparathyroidism. Additionally, the eGFR-hyperphosphatemia association was more pronounced in men. We observed substantial but not statistically significant differences between men and women in the thresholds of statistical significance for CV (significance appeared at a higher eGFR in men) and non-CV mortality (significance appeared at a higher eGFR in women). Research shows sex disparities in most CKD-related complications. Men develop anaemia and hyperparathyroidism earlier, women show steeper anaemia increase. Men have higher CV mortality risk. As eGFR decreased, men faced a higher risk of CV mortality at a higher eGFR threshold than women.

The hierarchical structure of galactic haloes: differentiating clusters from stochastic clumping with astrolink

ABSTRACT We present astrolink, an efficient and versatile clustering algorithm designed to hierarchically classify astrophysically relevant structures from both synthetic and observational data sets. We build upon clustar-nd, a hierarchical galaxy/(sub)halo finder, so that astrolink now generates a 2D representation of the implicit clustering structure as well as ensuring that clusters are statistically distinct from the noisy density fluctuations implicit within the n-dimensional input data. This redesign replaces the three cluster extraction parameters from clustar-nd with a single parameter, S – the lower statistical significance threshold of clusters, which can be automatically and reliably estimated via a dynamical model-fitting process. We demonstrate the robustness of this approach compared to astrolink’s predecessors by applying each algorithm to a suite of simulated galaxies defined over various feature spaces. We find that astrolink delivers a more powerful clustering performance while being $\sim 27~{{\ \rm per \, cent}}$ faster and using less memory than clustar-nd. With these improvements, astrolink is ideally suited to extracting a meaningful set of hierarchical and arbitrarily shaped astrophysical clusters from both synthetic and observational data sets – lending itself as a great tool for morphological decomposition within the context of hierarchical structure formation.

Trends in Cognitive Function Before and After Diabetes Onset: The China Health and Retirement Longitudinal Study.

Individuals with prevalent diabetes were known to have a higher risk of dementia and lower cognitive function. However, trends of cognitive function before diabetes and in the short term after new-onset diabetes remain unclear. This study included participants without baseline diabetes from the China Health and Retirement Longitudinal Study. Cognitive tests were conducted at baseline (wave 1) and at least one time from wave 2 (2013) to wave 4 (2018). Cognitive function was assessed using a global cognition score which was the summary measure of 4 cognitive tests. A linear mixed model was constructed to fit the trends in cognitive function before and after diabetes onset and the trends among nondiabetes. The threshold of statistical significance was p < 0.05. During the 7-year follow-up, 1,207 (9.7% of 12,422, 59.1 ± 8.6 years, 39.9% male participants) participants developed new-onset diabetes. The cognitive function of both the without diabetes group and the diabetes group declined annually during the follow-up. The annual decline rate of the diabetes group before diabetes onset was similar to that of the without diabetes group during the whole follow-up period. After diabetes onset, participants experienced statistically significant faster cognitive declines in global cognition (-0.023 SD/year; 95% CI -0.043 to -0.004; p = 0.019) and visuospatial abilities test (-0.036 SD/year; -0.061 to -0.011; p = 0.004), but not in tests of episodic memory (-0.018 SD/year; -0.041 to 0.004; p = 0.116), attention and calculation (-0.017 SD/year; -0.037 to 0.003; p = 0.090), or orientation (0.001 SD/year; -0.018 to 0.020; p = 0.894), compared with the cognitive slope before diabetes. In subgroup analysis, compared with those who developed diabetes between 45-54 years, those developing diabetes older (55-64 years, p for interaction = 0.701; 65-74 years, p for interaction = 0.996) did not demonstrate different rates of global cognitive decline after diabetes. Individuals experienced faster rate of cognitive decline in a few years after diabetes onset, but not during the prediabetes period. Age did not modify the effect of diabetes on postdiabetes cognitive decline. Efforts in eliminating the adverse impacts on cognition should be started on diagnosis of diabetes.

Second-Order Motion-Compensated Echo-Planar Cardiac Diffusion-Weighted MRI: Usefulness of Compressed Sensitivity Encoding.

Cardiac diffusion-weighted imaging (DWI) using second-order motion-compensated spin echo (M2C) can provide noninvasive in-vivo microstructural assessment, but limited by relatively low signal-to-noise ratio (SNR). Echo-planar imaging (EPI) with compressed sensitivity encoding (EPICS) could address these issues. To combine M2C DWI and EPCIS (M2C EPICS DWI), and compare image quality for M2C DWI. Prospective. Ten ex-vivo hearts, 10 healthy volunteers (females, 5 [50%]; mean ± SD of age, 25 ± 4 years), and 12 patients with diseased hearts (female, 1 [8.3%]; mean ± SD of age, 44 ± 16 years; including coronary artery heart disease, congenital heart disease, dilated cardiomyopathy, amyloidosis, and myocarditis). 3-T, M2C EPICS DWI, and M2C DWI. The apparent SNR (aSNR) and the rating scores were used to evaluate and compared image quality of all three groups. The aSNR was calculated using , and the myocardium was segmented manually. Three observers independently rated subjective image quality using a 5-point Likert scale. Bland-Altman analysis and paired t-tests. The threshold for statistical significance was set at P < 0.05. In healthy volunteers, the aSNR with a b-value of 450 s/mm2 acquired by M2C EPICS DWI was significantly higher than M2C DWI at in-plane resolutions of 3.0 × 3.0, 2.5 × 2.5, and 2.0 × 2.0 mm2. In patients with diseased hearts, the aSNR ofM2C EPICS DWI was also significantly higher than that for M2C DWI (bias of M2C EPICS-M2C = 1.999, 95% limits of agreement, 0.362 to 3.636; mean ± SD, 7.80 ± 1.37 vs. 5.80 ± 0.81). The ADC values of M2C EPICS was significantly higher than M2C DWI in in-vivo hearts. Over 80% of the images with rating scores for M2C EPICS DWI were higher than M2C DWI in in-vivo hearts. Cardiac imaging by M2C EPICS DWI may demonstrate better overall image quality and higher aSNR than M2C DWI. 2 TECHNICAL EFFICACY: Stage 1.

A graduate medical education (GME) quality improvement curriculum leads to improved knowledge and participation in high quality improvement projects by trainees

BackgroundThere is increased awareness about the need for quality improvement (QI) education for trainees within clinical training programs. However, formal integration of a QI curriculum into graduate medical education (GME) remains a work-in-progress. We describe the creation and implementation of a novel, virtual QI curriculum complemented by virtual-based workshops. ObjectiveTo determine the impact of a GME QI curriculum on 1) trainee QI knowledge; 2) Quality of QI projects. MethodsThe GME Quality Improvement curriculum was transitioned to an optional formal curriculum in 2020. It is led by three faculty with expertise in QI training and education. The team developed four, web-based learning modules that focused on fundamental QI concepts. These modules are completed monthly and are paired with virtual workshops that facilitate applying learned QI concepts to project development.We evaluated the effectiveness of the curriculum by assessing participants’ performance on knowledge-based quizzes before and after each online module. We used IBM SPSS (version 28), to conduct a two-sided paired samples t-test, comparing each post-session test scores with their corresponding pre-session scores. The alpha, or statistical threshold significance threshold, was 0.05.Additionally, two independent judges with expertise in QI evaluated the quality of the projects presented at the annual QI showcase using a standardized scoring rubric. The poster evaluation forms included 8 questions, rated on a scale from 1 to 5. Projects were graded into 4 quartiles (poor, fair, good, excellent). ResultsIn the knowledge assessment quiz, the difference between the mean pre- and post-session quiz scores was statistically significant (p < 0.01). The average score of the quality of the projects presented at the annual showcase was 31, in the fourth quartile which was graded as “excellent” quality. ConclusionA GME-led QI curriculum was effective in improving knowledge of QI concepts and producing high-quality scholarly projects.

Neuromodulation for Cannabis Use: A Scoping Review.

This scoping review explores the use of neuromodulation techniques in individuals with cannabis use. Our goal was to determine whether cannabis use alters cortical excitation and inhibition in the context of neuromodulation and to determine whether neuromodulation affects craving and cannabis use patterns. A systematic search was conducted using PubMed, OVID Medline, and PsycINFO from inception to 20 December 2022. Our review identified ten relevant studies, eight of which used Transcranial Magnetic Stimulation (TMS), while two employed Transcranial Direct Current Stimulation (tDCS). Findings from TMS studies suggest that cannabis users exhibit altered cortical inhibition, with decreased short interval intracortical inhibition (SICI) compared to non-users. Single sessions of rTMS did not have any impact on cannabis craving. By contrast, two studies found that multiple sessions of rTMS reduced cannabis use, but these changes did not meet the threshold for statistical significance and both studies were limited by small sample sizes. The two included tDCS studies found contradictory results, with one showing reduced cannabis craving with active treatment and another showing no effect of active treatment on craving compared to sham. Future studies should further explore the effects of multiple treatment sessions and different neuromodulation modalities.

Statin utilization and cardiovascular outcomes in a real-world primary prevention cohort of older adults

BackgroundStatins are a cost-effective therapy for prevention of atherosclerotic cardiovascular disease (ASCVD). Guidelines on statins for primary prevention are unclear for older adults (>75 years). ObjectiveInvestigate statin utility in older adults without ASCVD events, by risk stratifying in a large healthcare network. MethodsWe included 8,114 older adults, without CAD, PVD or ischemic stroke. Statin utilization based on ACC/AHA 10-year ASCVD risk calculation, was evaluated in intermediate (7.5%-19.9%) and high-risk patients (≥ 20%); and categorized using low and ‘moderate or high’ intensity statins with a follow up period of ∼7 years. Cox regression models were used to calculate hazard ratios for incident ASCVD and mortality across risk categories stratified by statin utilization. Data was adjusted for competing risk using Elixhauser Comorbidity Index. ResultsCompared with those on moderate or high intensity statins, high-risk older patients not on any statin had a significantly increased risk of MI [HR 1.51 (1.17–1.95); p<0.01], stroke [HR 1.47 (1.14–1.90); p<0.01] and all-cause mortality [HR 1.37 (1.19–1.58); p<0.001] in models adjusted for Elixhauser Comorbidity Index. When comparing the no statin group versus the moderate or high intensity statin group in the intermediate risk cohort, although a trend for increased risk was seen, it did not meet statistical significance thresholds for MI, stroke or all-cause mortality. ConclusionLack of statin use was associated with increased cardiovascular events and mortality in high-risk older adults. Given the benefits appreciated, statin use may need to be strongly considered for primary ASCVD prevention among high-risk older adults. Future studies will assess the risk-benefit ratio of statin intervention in older adults.

Prevalence and Impact of Modifiable Risk Factors on Acute Coronary Syndrome: A Case Control Study

Highlights: 1. Smoking duration, dyslipidemia, hypertension, diabetes mellitus, obesity, and hyperuricemia, are significantly associated with ACS. 2. Obesity and hypertension are identified as risk factors for inpatient ACS. - Background: Acute coronary syndrome (ACS) is defined by the abrupt reduction or total obstruction of blood flow to the myocardium. Recognized risk factors for ACS include conditions such as hypertension, dyslipidemia, smoking, obesity, diabetes mellitus, hyperuricemia, as well as variables like age, gender, and family history of the ailment. The objective of this research was to examine the prevalence and importance of modifiable risk factors associated with ACS. Material and Methods: The study is structured as a prospective case-control study. The research sample comprises 100 ACS patients, categorized into three groups: STEMI, NSTEMI, and UAP. The Chi-Square test and logistic regression were used to examine the samples. The threshold for statistical significance was set at p&lt;0.05. Results: ACS occurred more frequently in male patients (54%) and those aged ≥ 40 years (85%). Several factors demonstrated significant associations with ACS, including smoking habits, dyslipidemia, hypertension, diabetes mellitus, obesity, and hyperuricemia. Among these, inpatient ACS was notably linked with obesity (OR: 7.42; 95% CI: 1.48-37.11; p=0.015) and hypertension (OR: 0.13; 95% CI: 0.03-0.53; p=0.005). The presence of ACS was also correlated with a notable increase in inpatient care, with obesity and hypertension emerging as risk factors for inpatient ACS. Conclusion: ACS was more common in males and individuals aged 40 or older, with significant associations identified between ACS and various factors, including smoking, dyslipidemia, diabetes, obesity, hyperuricemia, and hypertension, with obesity and hypertension specifically linked to inpatient ACS.

Systemic acylcarnitine levels are affected in response to multiple injuries and hemorrhagic shock: An analysis of lipidomic changes in a standardized porcine model.

Along with recent advances in analytical technologies, tricarboxylic acid-cycle intermediates are increasingly identified as promising makers for cellular ischemia and mitochondrial dysfunction during hemorrhagic shock. For traumatized patients, the knowledge of the role of lipid oxidation substrates is sparse. In this study, we aimed to analyze the dynamics of systemic acylcarnitine (AcCa) release in a standardized polytrauma model with hemorrhagic shock. Fifty-two male pigs (50 ± 5 kg) were randomized into two groups: group isolated fracture was subject to a standardized femur shaft fracture, and group polytrauma was subject to a femur fracture, followed by blunt chest trauma, liver laceration, and a pressure-controlled hemorrhagic shock for 60 minutes. Resuscitation was performed with crystalloids. Fractures were stabilized by intramedullary nailing. Venous samples were collected at six time points (baseline, trauma, resuscitation, 2 hours, 4 hours, and 6 hours). Lipidomic analysis was performed via liquid chromatography coupled mass spectrometry. Measurements were collated with clinical markers and near-infrared spectrometry measurements of tissue perfusion. Longitudinal analyses were performed with linear mixed models, and Spearman's correlations were calculated. A p value of 0.05 was defined as threshold for statistical significance. From a total of 303 distinct lipids, we identified two species of long-chain AcCas. Both showed a highly significant ( p < 0.001) twofold increase after hemorrhagic shock in group polytrauma that promptly normalized after resuscitation. This increase was associated with a significant decrease of the base excess ( p = 0.005), but recovery after resuscitation was faster. For both AcCas, there were significant correlations with decreased muscle tissue oxygen delivery ( p = 0.008, p = 0.003) and significant time-lagged correlations with the increase of creatine kinase ( p < 0.001, p < 0.001). Our results point to plasma AcCas as a possible indicator for mitochondrial dysfunction and cellular ischemia in hemorrhagic shock. The more rapid normalization after resuscitation in comparison with acid base changes may warrant further investigation.

Abstract 6130: Association of vitamin D-related genetic variants and prostate cancer risk in Black men

Abstract Background: What we know of the relationship between vitamin D status and prostate cancer has largely been characterized among men of European ancestry, hereafter referred to as “White”. Research among White men indicate positive associations between circulating vitamin D status, as measured by concentrations of 25-hydroxyvitamin D (25(OH)D), with prostate cancer risk, and that genetic scores based on genome-wide associated single nucleotide polymorphisms (SNPs) reflecting high vs. low 25(OHD) is positively associated with aggressive disease. Limited research exists elucidating this relationship among men of African ancestry, hereafter referred to as “Black”. This is despite the fact that Black populations experience chronically lower circulating 25(OH)D, and ancestry-specific differences in genetic variants in some vitamin D-related genes. Given the paucity of research in this area, we examined the role of genetic variants in six commonly studied genes in the vitamin D pathway involved in synthesis (CYP27A1 and CYP27B1), transport (GC), activity (VDR and RXR), and metabolism (CYP24A1) in relation to prostate cancer among Black men. Methods: We assessed a total of 78 candidate SNPs in six vitamin D pathway genes that were either previously associated with circulating 25(OHD) and/or associated with prostate cancer risk in studies of White men. We compared vitamin D gene SNP associations with prostate cancer in Black and White men using summary statistics from a large GWAS of over 10,000 prostate cancer cases and 10,000 controls among Black men and over 85,000 cases and 91,000 controls among White men. A statistical significance threshold of 0.00064 (0.05/78 candidate SNPs) was used to adjust for multiple comparisons. Results: None of the examined SNPs were significantly associated with prostate cancer risk among Black men after adjustment for multiple comparisons. However, four SNPs were nominally significant in Black men, including two in RXR [rs41400444 OR=1.09, 95% CI: 1.01-1.17, P = 0.024 and rs10881574 OR = 0.93, 0.867-0.999, P = 0.04556] and two in VDR [rs2853563 OR = 1.07, 1.012-1.13, P = 0.0173 and rs1156882 OR = 1.06, 1.00-1.12, P = 0.0495]. The latter SNP rs1156882 was also positively associated with prostate cancer risk in White men (OR = 1.035, 1.02-1.06, P = 0.00024), along with VDR SNP rs4516035 (OR = 1.027, 1.012-1.042, P = 0.00055), both after correction for multiple comparisons. Conclusions: We observed non-significant, though suggestive, associations between genetic variants in vitamin D pathway genes previously associated with prostate cancer or vitamin D levels in White populations and prostate cancer risk in Black men. Future research exploring the potential role of vitamin D pathway genes and prostate cancer in Black men – a population at high risk both for low circulating vitamin D and prostate cancer - will need to identify vitamin D-related genetic variants specific to carcinogenesis in Black men. Citation Format: Tracy M. Layne, Joseph H. Rothstein, Xiaoyu Song, Weiva Sieh, Robert J. Klein. Association of vitamin D-related genetic variants and prostate cancer risk in Black men [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 6130.