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Frontiers in Endocrinology 2024This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.
PURPOSE
This study aims to investigate the impacts of phimosis on the health of the genitourinary system through Mendelian random analysis.
MATERIAL AND METHOD
A dual-sample Mendelian randomization (MR) analysis was conducted using the publicly available genome-wide association study (GWAS) data. The inverse variance weighted based on the random effects model (Re-IVW) method was used as the main statistical analysis. Complementary methods, including weighted median, MR-Egger regression, and MR pleiotropy residual sum and outlier (MR-PRESSO), were applied to detect or correct the impact of horizontal pleiotropy.
RESULT
Re-IVW showed a genetic predictive causal relationship of phimosis on glomerulonephritis (odds ratio [OR]: 1.37 [1.13-1.65], = 0.00149) and IgA glomerulonephritis (OR: 1.57 [1.18-2.09), = 0.00187). Suggestive evidence indicated that phimosis was associated with chronic nephritis syndrome (OR: 1.23 (1.00-1.51), p = 0.0481], acute nephritis syndrome (OR: 1.50 [1.13-2.01], = 0.0058), and impotence (OR: 1.39 [1.11-1.73], = 0.0035). Kidney and ureteral stone (OR: 1.14 [1.04-1.26], = 0.0069), urethral strictures (OR: 1.26 [1.07-1.48], = 0.0050), benign prostatic hyperplasia (OR: 1.07 [1.01-1.13], = 0.0242), and decreased testicular function (OR: 0.72 [0.56-0.94], = 0.0141) have genetically predictive causal relationships.
CONCLUSION
In summary, we employed a series of reliable analytical methods to investigate the association between phimosis and 26 urogenital diseases. We have reported several strong associations, but more research is needed to evaluate whether this discovery is replicated in other environments and to gain a better understanding of potential mechanisms.
Topics: Humans; Mendelian Randomization Analysis; Male; Genome-Wide Association Study; Phimosis; Female Urogenital Diseases; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease
PubMed: 38915890
DOI: 10.3389/fendo.2024.1308270 -
Physics and Imaging in Radiation... Apr 2024Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver...
BACKGROUND AND PURPOSE
Magnetic Resonance Imaging (MRI) guided stereotactic body radiotherapy (SBRT) of liver metastases is an upcoming high-precision non-invasive treatment. Interobserver variation (IOV) in tumor delineation, however, remains a relevant uncertainty for planning target volume (PTV) margins. The aims of this study were to quantify IOV in MRI-based delineation of the gross tumor volume (GTV) of liver metastases and to detect patient-specific factors influencing IOV.
MATERIALS AND METHODS
A total of 22 patients with liver metastases from three primary tumor origins were selected (colorectal(8), breast(6), lung(8)). Delineation guidelines and planning MRI-scans were provided to eight radiation oncologists who delineated all GTVs. All delineations were centrally peer reviewed to identify outliers not meeting the guidelines. Analyses were performed both in- and excluding outliers. IOV was quantified as the standard deviation (SD) of the perpendicular distance of each observer's delineation towards the median delineation. The correlation of IOV with shape regularity, tumor origin and volume was determined.
RESULTS
Including all delineations, average IOV was 1.6 mm (range 0.6-3.3 mm). From 160 delineations, in total fourteen single delineations were marked as outliers after peer review. After excluding outliers, the average IOV was 1.3 mm (range 0.6-2.3 mm). There was no significant correlation between IOV and tumor origin or volume. However, there was a significant correlation between IOV and regularity (Spearman's ρ = -0.66; p = 0.002).
CONCLUSION
MRI-based IOV in tumor delineation of liver metastases was 1.3-1.6 mm, from which PTV margins for IOV can be calculated. Tumor regularity and IOV were significantly correlated, potentially allowing for patient-specific margin calculation.
PubMed: 38912009
DOI: 10.1016/j.phro.2024.100592 -
Journal of Orthopaedic Case Reports Jun 2024The use of image-free robotic systems for total knee arthroplasty (TKA) is gaining popularity. Although the surgical transepicondylar axis (sTEA) is considered the...
Precise Calibration of Femoral Component Rotation Using the Posterior Condylar Axis as a Reference during Image-free Robot-assisted Total Knee Arthroplasty: A Technical Note.
INTRODUCTION
The use of image-free robotic systems for total knee arthroplasty (TKA) is gaining popularity. Although the surgical transepicondylar axis (sTEA) is considered the optimal femoral rotational reference during TKA, it is difficult to define intra-operatively. Conventional and image-free robot-assisted TKA (RA-TKA) therefore rely on the use of Whiteside's axis (WSA) or the posterior condylar axis (PCA) as surrogate references. The PCA is considered to be associated with less variability than the WSA. The authors present a simple technique to permit calibration of femoral component rotation (FCR) using the PCA as a reference for image-free robotic systems that do not permit this option.
TECHNIQUE
The image-free robotic systems used by the authors (Navio and CORI, Smith and Nephew, Memphis, TN, USA) permit calibration of FCR only when the perpendicular to WSA is used as a reference. When the PCA is selected as a reference, a fixed 3° of external rotation is set by the robot. The technique proposed by the authors involves the use of the former setting, followed by internal rotation of the perpendicular to the WSA to co-align it with the PCA. The planning menu subsequently permits virtual surgical planning using the PCA as the femoral rotational reference and permits adjustments in rotational positioning of the femoral component while displaying the effect of rotation on bony resection and vice versa in real time. In addition, coaligning the perpendicular to the anatomic trans-epicondylar axis (aTEA) displays the internal rotation of the PCA with respect to the aTEA. This information can be used for setting rotational boundaries with respect to the PCA while using various alternate alignment strategies, like functional alignment, since the relation between the aTEA and sTEA is less likely to be affected by dyplasia and wear when compared with the PCA or WSA.
CONCLUSION
This simple technique permits optimally calibrated rotational positioning of the femoral component during image-free RA-TKA, using the PCA as a reference. It can be applied for optimizing surgery in knees with altered or outlier anatomy, as well as routinely, especially when alternate alignment strategies are used.
PubMed: 38910981
DOI: 10.13107/jocr.2024.v14.i06.4548 -
Scientific Reports Jun 2024Type II diabetes mellitus (T2DM) is a rising global health burden due to its rapidly increasing prevalence worldwide, and can result in serious complications. Therefore,...
Type II diabetes mellitus (T2DM) is a rising global health burden due to its rapidly increasing prevalence worldwide, and can result in serious complications. Therefore, it is of utmost importance to identify individuals at risk as early as possible to avoid long-term T2DM complications. In this study, we developed an interpretable machine learning model leveraging baseline levels of biomarkers of oxidative stress (OS), inflammation, and mitochondrial dysfunction (MD) for identifying individuals at risk of developing T2DM. In particular, Isolation Forest (iForest) was applied as an anomaly detection algorithm to address class imbalance. iForest was trained on the control group data to detect cases of high risk for T2DM development as outliers. Two iForest models were trained and evaluated through ten-fold cross-validation, the first on traditional biomarkers (BMI, blood glucose levels (BGL) and triglycerides) alone and the second including the additional aforementioned biomarkers. The second model outperformed the first across all evaluation metrics, particularly for F1 score and recall, which were increased from 0.61 ± 0.05 to 0.81 ± 0.05 and 0.57 ± 0.06 to 0.81 ± 0.08, respectively. The feature importance scores identified a novel combination of biomarkers, including interleukin-10 (IL-10), 8-isoprostane, humanin (HN), and oxidized glutathione (GSSG), which were revealed to be more influential than the traditional biomarkers in the outcome prediction. These results reveal a promising method for simultaneously predicting and understanding the risk of T2DM development and suggest possible pharmacological intervention to address inflammation and OS early in disease progression.
Topics: Diabetes Mellitus, Type 2; Humans; Biomarkers; Machine Learning; Oxidative Stress; Male; Female; Middle Aged; Risk Assessment; Risk Factors; Blood Glucose; Inflammation; Algorithms
PubMed: 38909127
DOI: 10.1038/s41598-024-65044-x -
Public Health Jun 2024To describe the trends in the nature of general practices in Scotland between 2014/15 and 2023.
OBJECTIVES
To describe the trends in the nature of general practices in Scotland between 2014/15 and 2023.
STUDY DESIGN
Descriptive ecological study.
METHODS
We obtained data from Public Health Scotland and used general practitioner (GP) practice codes, practice names, and the General Medical Council (GMC) numbers of their listed GPs to describe trends in practice characteristics and to identify individual practices that were likely to be operating as a single entity.
RESULTS
Defining practice entities is difficult because different GP practice codes are often retained when GPs are performing across multiple practices. If GP practice codes alone are used, the median practice list size increased from 5094 to 5881, and the mean from 5588 to 6289, between 2013/14 and 2020/21. There was one outlier practice that grew to have over 45,000 patients registered by 2020/21. However, this underestimates the extent of this new mega-practice phenomenon. Using the GMC numbers of GPs listed as performers to identify where the same GPs are working across multiple GP practice codes, we identified a series of mega-practices that span across health board areas and which have experienced a dramatic increase in their list size (with the two largest having list sizes of over 101,000 and 77,000 patients, respectively).
CONCLUSIONS
Further research is needed to better understand: how mega-practices provide services and whether this differs from other practices; where financial rewards accumulate within mega-practices; differences in staffing between mega-practices and other models; and the impacts mega-practices have on the quality and continuity of care and on health and inequality outcomes.
PubMed: 38908308
DOI: 10.1016/j.puhe.2024.05.026 -
European Journal of Vascular and... Jun 2024Complex abdominal aortic aneurysms (cAAA) pose a clinical challenge. The aim of this study was to assess the 30 day mortality and morbidity for open aneurysm repair...
OBJECTIVE
Complex abdominal aortic aneurysms (cAAA) pose a clinical challenge. The aim of this study was to assess the 30 day mortality and morbidity for open aneurysm repair (OAR) and fenestrated/branched endovascular aortic repair (F/BEVAR), and the effect of hospital volume in patients with asymptomatic cAAA in Switzerland.
METHODS
Retrospective, cohort study using data from Switzerland's national registry for vascular surgery, Swissvasc, including patients treated from 1 January 2019 to 31 December 2022. All patients with asymptomatic, true, non-infected cAAA were identified. Primary outcome was 30 day mortality and morbidity reported using the Clavien-Dindo classification. Outcomes were compared between OAR and F/BEVAR after propensity score weighting.
RESULTS
Of the 461 patients identified, 333 underwent OAR and 128 underwent F/BEVAR for cAAA. At 30 days, overall mortality rate was 3.3% after OAR and 3.1% after F/BEVAR (p = .76). Propensity scores weighted analysis indicated similar morbidity rates for both approaches: F/BEVAR (OR 0.69, 95% CI 0.45 - 1.05, p = .055); intestinal ischaemia (1.8% after OAR, 3.1% after F/BEVAR, p = .47) and renal failure requiring dialysis (1.5% after OAR, 5.5% after F/BEVAR, p = .024) were associated with highest morbidity and mortality. Treatment specific complications with high morbidity were abdominal compartment syndrome and lower limb compartment syndrome following F/BEVAR. Overall treatment volume was low for most of the hospitals treating cAAA in Switzerland; outliers with increased mortality were identified among low volume hospitals.
CONCLUSION
Comparable 30 day mortality and morbidity rates were found between OAR and F/BEVAR for cAAA in Switzerland; lack of centralisation was also highlighted. Organ specific complications driving mortality were renal failure, intestinal ischaemia, and limb ischaemia, specifically after F/BEVAR. Treatment in specialised high volume centres, alongside efforts to reduce peri procedural kidney injury and mesenteric ischaemia, offers potential to lower morbidity and mortality in elective cAAA treatment.
PubMed: 38906370
DOI: 10.1016/j.ejvs.2024.06.022 -
Computers in Biology and Medicine Jun 2024Traumatic bone marrow lesions (BML) are frequently identified on knee MRI scans in patients following an acute full-thickness, complete ACL tear. BMLs coincide with...
INTRODUCTION
Traumatic bone marrow lesions (BML) are frequently identified on knee MRI scans in patients following an acute full-thickness, complete ACL tear. BMLs coincide with regions of elevated localized bone loss, and studies suggest these may act as a precursor to the development of post-traumatic osteoarthritis. This study addresses the labour-intensive manual assessment of BMLs by using a 3D U-Net for automated identification and segmentation from MRI scans.
METHODS
A multi-task learning approach was used to segment both bone and BML from T2 fat-suppressed (FS) fast spin echo (FSE) MRI sequences for BML assessment. Training and testing utilized datasets from individuals with complete ACL tears, employing a five-fold cross-validation approach and pre-processing involved image intensity normalization and data augmentation. A post-processing algorithm was developed to improve segmentation and remove outliers. Training and testing datasets were acquired from different studies with similar imaging protocol to assess the model's performance robustness across different populations and acquisition conditions.
RESULTS
The 3D U-Net model exhibited effectiveness in semantic segmentation, while post-processing enhanced segmentation accuracy and precision through morphological operations. The trained model with post-processing achieved a Dice similarity coefficient (DSC) of 0.75 ± 0.08 (mean ± std) and a precision of 0.87 ± 0.07 for BML segmentation on testing data. Additionally, the trained model with post-processing achieved a DSC of 0.93 ± 0.02 and a precision of 0.92 ± 0.02 for bone segmentation on testing data. This demonstrates the approach's high accuracy for capturing true positives and effectively minimizing false positives in the identification and segmentation of bone structures.
CONCLUSION
Automated segmentation methods are a valuable tool for clinicians and researchers, streamlining the assessment of BMLs and allowing for longitudinal assessments. This study presents a model with promising clinical efficacy and provides a quantitative approach for bone-related pathology research and diagnostics.
PubMed: 38905892
DOI: 10.1016/j.compbiomed.2024.108791 -
Medicine Jun 2024Maintaining a balanced bile acids (BAs) metabolism is essential for lipid and cholesterol metabolism, as well as fat intake and absorption. The development of obesity...
Maintaining a balanced bile acids (BAs) metabolism is essential for lipid and cholesterol metabolism, as well as fat intake and absorption. The development of obesity may be intricately linked to BAs and their conjugated compounds. Our study aims to assess how BAs influence the obesity indicators by Mendelian randomization (MR) analysis. Instrumental variables of 5 BAs were obtained from public genome-wide association study databases, and 8 genome-wide association studies related to obesity indicators were used as outcomes. Causal inference analysis utilized inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Sensitivity analysis involved MR-PRESSO and leave-one-out techniques to detect pleiotropy and outliers. Horizontal pleiotropy and heterogeneity were assessed using the MR-Egger intercept and Cochran Q statistic, respectively. The IVW analysis revealed an odds ratio of 0.94 (95% confidence interval: 0.88, 1.00; P = .05) for the association between glycolithocholate (GLCA) and obesity, indicating a marginal negative causal association. Consistent direction of the estimates obtained from the weighted median and MR-Egger methods was observed in the analysis of the association between GLCA and obesity. Furthermore, the IVW analysis demonstrated a suggestive association between GLCA and trunk fat percentage, with a beta value of -0.014 (95% confidence interval: -0.027, -0.0004; P = .04). Our findings suggest a potential negative causal relationship between GLCA and both obesity and trunk fat percentage, although no association survived corrections for multiple comparisons. These results indicate a trend towards a possible association between BAs and obesity, emphasizing the need for future studies.
Topics: Mendelian Randomization Analysis; Humans; Obesity; Genome-Wide Association Study; Bile Acids and Salts; Causality
PubMed: 38905395
DOI: 10.1097/MD.0000000000038610 -
Frontiers in Genetics 2024Previous studies have shown that Alzheimer's disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic...
The causal effect of Alzheimer's disease and family history of Alzheimer's disease on non-ischemic cardiomyopathy and left ventricular structure and function: a Mendelian randomization study.
BACKGROUND
Previous studies have shown that Alzheimer's disease (AD) can cause myocardial damage. However, whether there is a causal association between AD and non-ischemic cardiomyopathy (NICM) remains unclear. Using a comprehensive two-sample Mendelian randomization (MR) method, we aimed to determine whether AD and family history of AD (FHAD) affect left ventricular (LV) structure and function and lead to NICM, including hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM).
METHODS
The summary statistics for exposures [AD, paternal history of AD (PH-AD), and maternal history of AD (MH-AD)] and outcomes (NICM, HCM, DCM, and LV traits) were obtained from the large European genome-wide association studies. The causal effects were estimated using inverse variance weighted, MR-Egger, and weighted median methods. Sensitivity analyses were conducted, including Cochran's Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier, MR Steiger test, leave-one-out analysis, and the funnel plot.
RESULTS
Genetically predicted AD was associated with a lower risk of NICM [odds ratio (OR) 0.9306, 95% confidence interval (CI) 0.8825-0.9813, = 0.0078], DCM (OR 0.8666, 95% CI 0.7752-0.9689, = 0.0119), and LV remodeling index (OR 0.9969, 95% CI 0.9940-0.9998, = 0.0337). Moreover, genetically predicted PH-AD was associated with a decreased risk of NICM (OR 0.8924, 95% CI 0.8332-0.9557, = 0.0011). MH-AD was also strongly associated with a decreased risk of NICM (OR 0.8958, 95% CI 0.8449-0.9498, = 0.0002). Different methods of sensitivity analysis demonstrated the robustness of the results.
CONCLUSION
Our study revealed that AD and FHAD were associated with a decreased risk of NICM, providing a new genetic perspective on the pathogenesis of NICM.
PubMed: 38903751
DOI: 10.3389/fgene.2024.1379865 -
BMC Women's Health Jun 2024Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary...
BACKGROUND
Previous observational studies have indicated an inverse correlation between circulating sex hormone binding globulin (SHBG) levels and the incidence of polycystic ovary syndrome (PCOS). Nevertheless, conventional observational studies may be susceptible to bias. Consequently, we conducted a two-sample Mendelian randomization (MR) investigation to delve deeper into the connection between SHBG levels and the risk of PCOS.
METHODS
We employed single-nucleotide polymorphisms (SNPs) linked to serum SHBG levels as instrumental variables (IVs). Genetic associations with PCOS were derived from a meta-analysis of GWAS data. Our primary analytical approach relied on the inverse-variance weighted (IVW) method, complemented by alternative MR techniques, including simple-median, weighted-median, MR-Egger regression, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) testing. Additionally, sensitivity analyses were conducted to assess the robustness of the association.
RESULTS
We utilized 289 SNPs associated with serum SHBG levels, achieving genome-wide significance, as instrumental variables (IVs). Our MR analyses revealed that genetically predicted elevated circulating SHBG concentrations were linked to a reduced risk of PCOS (odds ratio (OR) = 0.56, 95% confidence interval (CI): 0.39-0.78, P = 8.30 × 10) using the IVW method. MR-Egger regression did not detect any directional pleiotropic effects (P intercept = 0.626). Sensitivity analyses, employing alternative MR methods and IV sets, consistently reaffirmed our results, underscoring the robustness of our findings.
CONCLUSIONS
Through a genetic epidemiological approach, we have substantiated prior observational literature, indicating a potential causal inverse relationship between serum SHBG concentrations and PCOS risk. Nevertheless, further research is needed to elucidate the underlying mechanism of SHBG in the development of PCOS.
Topics: Humans; Sex Hormone-Binding Globulin; Polycystic Ovary Syndrome; Female; Polymorphism, Single Nucleotide; Mendelian Randomization Analysis; Genome-Wide Association Study; Genetic Predisposition to Disease; Risk Factors
PubMed: 38902677
DOI: 10.1186/s12905-024-03144-6