Male Cohort Research Articles

Low psoas muscle index has a negative impact on survival after minimal invasive esophagectomy for cancer in European men

IntroductionSarcopenia, a key component of frailty in cancer patients, is associated with complicated procedures and worse survival after esophageal resection. The psoas muscle index (PMI) has been implicated as a possible sarcopenia imaging marker. This retrospective study aims to elucidate the effect of PMI and BMI in a cohort in Europe after totally minimally invasive esophagectomy for cancer. MethodsThe study included 318 consecutive adult patients (261 men and 57 women) who underwent minimally invasive esophagectomy for cancer between January 2016 and April 2021 in a German University Hospital. The PMI was measured at the third lumbar vertebra in the preoperative CT scan. The endpoints postoperative complication rates and survival rates were analysed and correlated with PMI and BMI according to gender. ResultsMale patients with low PMI (< 5.3 cm2/ m2) had a significantly higher rate of postoperative pulmonary and cardiac complications (p = 0.016, respectively p = 0.018). Low PMI and low BMI (<25 kg/m2) were associated with decreased survival rates in the univariate (p < 0.001) and multivariate analysis in male patients (p = 0.024, respectively 0.004). Having a low PMI (< 5.3 cm2/ m2) was significantly associated with worse overall survival in normal and underweight men (p < 0.001), but not in obese men with a BMI ≥ 25kg/m2 (p = 0.476). ConclusionPreoperative PMI and BMI are valid risk factors regarding postoperative survival after minimal invasive esophagectomy for cancer especially in a male European cohort.

Diversity on the American Academy of Orthopaedic Surgeons National Meeting Podium: Changes Over Two Decades.

There has been an increase in diversity initiatives regarding selecting speakers for the American Academy of Orthopaedic Surgeons (AAOS) annual meeting and courses. The purpose of this study was to determine the percentage of female or underrepresented minority (URM) speakers for instructional course lectures (ICLs) and AAOS courses over the past 2 decades including a surrogate for expertise. For 2002, 2012, and 2022, the academic and demographic information of speakers and the number of publications at the time of their speaking role were obtained and compared by sex and URM status. Owing to the unequal sample sizes between male versus female cohorts and URM versus non-URM cohorts, the Welch t -test was used. The percentage of ICL and AAOS course speakers who were female increased over time (ICL, AAOS courses): 2002 (2.6%, 3.3%), 2012 (3.9%, 6.3%), and 2022 (11.8%, 15.5%) ( P < 0.001, P < 0.001). The percentage of female AAOS fellows in these years was 2.9%, 4.7%, and 7.4%, respectively. For ICLs and AAOS course speakers, female presenters had fewer publications than male counterparts (ICL, AAOS courses): 2002 ( P < 0.001, P = 0.048), 2012 ( P = 0.003, P < 0.001), and 2022 ( P < 0.001, P < 0.001). For ICLs in 2022, URM speakers had a similar number of publications compared with non-URM speakers. In 2022, URMs comprised 6.9% of ICL speakers and 4% of AAOS fellows. For 2022 ICLs, there were no significant differences in academic institution, position, or region when compared by sex or URM status. For AAOS courses, the percentage of URM speakers increased over time: 2002 (1.1%), 2012 (4.5%), and 2022 (8.6%). For AAOS courses, URM presenters had similar publications compared with non-URM presenters in 2002 and 2022 but less in 2012 ( P = 0.027). The percentage of women and URMs presenting ICLs and AAOS courses has increased over the past 2 decades and exceeded the percentage they represent in the AAOS by over 50%. The female cohort has fewer publications, on average, than the male cohort for all years evaluated, indicating no institutional bias against female speakers.

Microbiome variations induced by delta9-tetrahydrocannabinol predict weight reduction in obese mice

IntroductionObesity and high-fat diets induce consistent alterations in gut microbiota composition. Observations from epidemiological reviews and experiments also illustrate weight regulation effects of delta9-tetrahydrocannabinol (THC) with microbiome shifts. Therefore, we investigated the weight-loss potential of THC in obese mice models and to elucidate the contribution of specific gut microbiome changes in THC-induced weight loss.MethodsHigh-fat diet induced obese mice were treated with oral THC supplementation for two weeks and compared with controls. In addition to measuring weight, fecal samples were obtained at various timepoints, sequenced for bacterial 16s rRNA content and analyzed using QIIME2. Alpha and beta diversity were computed followed by linear mixed effects (LME) modeling of bacterial relative abundance relationship to THC treatment and weight change.ResultsIn both male and female mice, the THC group had significantly greater average weight loss than controls (−17.8% vs. −0.22%, p&amp;lt;0.001 and −13.8% vs. +2.9%, p&amp;lt;0.001 respectively). Male mice had 8 bacterial taxonomic features that were both significantly different in relative abundance change over time with THC and correlated with weight change. An LME model using three bacterial features explained 76% of the variance in weight change with 24% of variation explained by fixed effects of feature relative abundance alone. The model also accurately predicted weight change in a second male mouse cohort (R=0.64, R2=0.41, p=&amp;lt;0.001). Female mice had fewer significant predictive features and were difficult to model, but the male-produced 3-feature model still accurately predicted weight change in the females (R=0.66, R2=0.44, p&amp;lt;0.001).ConclusionUsing a stepwise feature selection approach, our results indicate that sex-specific gut microbiome composition changes play some role in THC-induced weight loss. Additionally, we illustrated the concept of microbiome feature-based modeling to predict weight changes.

Assessing the Validity of Two Non-Exercise Regression Equations for Predicting Maximal Oxygen Consumption

ABSTRACT Purpose: This study aimed to develop two regression equations to predict maximal oxygen consumption (VO2max) using non-exercise data from a substantial cohort of healthy Iranian adult males. Additionally, this study sought to examine the predictive accuracy of these equations across four different levels of physical activity. Methods: A total of 126 participants (age: 34.9 ± 11.3 years, body mass index [BMI]: 24.9 ± 2.7 kg/m², and body fat percentage [BF%]: 18.3 ± 4.9) completed a maximal graded exercise test to measure VO2max, with a mean of 45.0 ± 3.4 ml.kg−1.min−1. Participants also provided information on age, current physical activity rating (PA-R), and either BMI or BF% to estimate VO2max using Jackson and colleagues’ regression equations. The PA-R was assessed via a standardized questionnaire and categorized into four levels: sedentary, low, moderate, and high. Results: The key findings from this study indicate that both original models significantly underestimated actual VO2max in a large cohort of Iranian adults (both, p < .001 and mean differences exceeding 2.19 ml.kg−1.min−1). Nevertheless, these models provided accurate predictions for VO2max among individuals with moderate levels of physical activity (both, p > .08 and mean differences between 0.51 and 1.03 ml.kg−1.min−1). Furthermore, the models demonstrated moderate validity, as evidenced by an intraclass correlation coefficient (ICC) of 0.841 and a coefficient of variation averaging 10.9%, with a range from 8.5% to 13.6%. Conclusions: While Jackson’s two non-exercise models showed limited accuracy in predicting VO2max among Iranian healthy male adults, they exhibited reasonable precision, particularly among moderately active men.

Identification of Data-Driven Preoperative Hemoglobin Strata That Predict the Likelihood of Blood Transfusion and the Risk of Major Complications and Prosthetic Joint Infection After Total Hip Arthroplasty.

Preoperative anemia is an independent risk factor of complications after primary total hip arthroplasty (THA). Currently used hemoglobin thresholds are not developed for risk stratification of arthroplasty patients and do not provide surgery-specific information on postoperative complication risk. Thus, we aimed to calculate THA-specific preoperative hemoglobin strata that observe the likelihood of 90-day blood transfusion and determine whether these strata are associated with increased risk of 90-day complications and 2-year prosthetic joint infection (PJI). A retrospective cohort analysis identified 56,101 patients who underwent primary THA from 2013 to 2022. Using the lowest hemoglobin value for each patient one month before THA, stratum-specific likelihood ratio (SSLR) analysis calculated sex-based hemoglobin strata associated with the likelihood of 90-day postoperative blood transfusion. Propensity score matching was performed. Incidence rates and risk of 90-day major complications and 2-year PJI were observed for each identified preoperative hemoglobin stratum. SSLR analysis identified five male (strata, likelihood ratio [<10.4 g/dL, 12.5; 10.5 to 11.4 g/dL, 8.0; 11.5 to 12.4 g/dL, 2.4; 12.5 to 13.4 g/dL, 1.3; 13.5 to 13.9 g/dL, 0.5]) and five female (<8.9 g/dL, 10.7; 9.0 to 10.9 g/dL, 4.0; 11.0 to 11.4 g/dL, 2.0; 12.0 to 12.9 g/dL, 1.0; 13.0 to 13.4 g/dL, 0.6) preoperative hemoglobin strata associated with varying likelihoods of 90-day blood transfusion after THA. After matching in both male and female cohorts, as the calculated preoperative hemoglobin strata decreased, the relative risk of overall 90-day major complications and 2-year PJI increased incrementally (all P < 0.05). SSLR analysis established THA-specific sex-based preoperative hemoglobin strata that observe the likelihood of 90-day blood transfusion and predict the risk of 90-day medical complications and 2-year PJI. These strata are a first of their kind in THA research. While preoperatively optimizing patients, we recommend using these hemoglobin thresholds to help guide decisions on presurgery anemia optimization and to reduce the need for postoperative blood transfusion. Level III.

Novel machine learning algorithm in risk prediction model for pan-cancer risk: application in a large prospective cohort

ObjectiveTo develop and validate machine-learning models that predict the risk of pan-cancer incidence using demographic, questionnaire and routine health check-up data in a large Asian population.Methods and analysisThis study is...

Analysis of Cephalometric Differences of the Midface and Upper Face in Males and Females: A Radiographic Study.

Gender affirmation facial surgery (GAFS) is an important component in treating gender dysphoria among transgender individuals by addressing gender incongruence of the face. There is a paucity of literature describing objective characterizations of the anatomic differences between male and female faces. In this study, cephalometric measurements were taken on routine CT imaging performed on cisgender patients between 2017 and 2020. Specifically defined cephalometric landmarks of the upper and midface were measured and compared between male and female cohorts. Thirty-eight patients, 19 male and 19 female, were identified for this study. Significant differences were identified in the frontal prominence, orbital size, malar height, bizygomatic width, nose, and upper lip, with moderate rates of specificity for each gender. Some important ratios are also presented. Differences in the malar region and the orbit highlight the importance of these areas as a point of focus for GAFS. These cephalometric findings provide objective evidence and parameters for perceived anatomic differences in male and female faces. In addition, they help both corroborate current surgical techniques as well as guide future approaches to GAFS.

Trends in lung cancer incidence in Spain (1990-2019): insights from Global Burden of Diseases data.

This study examines lung cancer incidence in Spain (1990-2019) through age-period-cohort (A-P-C) analysis and Global Burden of Diseases (GBD) data, unravelling the complex interplay of age, period, and birth cohort in shaping these trends. Utilizing GBD and Spanish population data, the study calculates age-standardized incidence rates (ASIRs) and employs Joinpoint analysis to identify significant trends. A-P-C analysis dissects the individual effects of age, calendar period, and birth cohort on incidence patterns. Between 1990 and 2019, almost 738,000 cases of lung cancer were diagnosed in Spain, with an average annual increase of 1.7%. The ASIR of lung cancer in Spain from 1990 to 2019 showed a sustained upward trend in women (Average Annual Per cent Change: 2.5%, P < 0.05), reaching 23.3 cases per 100,000 in 2019, whilst men experienced a significant decrease in incidence rates (AAPC: -0.6%, P < 0.05), falling to 108.9 in 2019. The male-to-female incidence ratio decreased from 12.2 in 1992 to 4.9 in 2019. Joinpoint analysis identified distinct periods for both sexes, with men showing stability, decline and then a significant decrease, whereas women showed an initial increase followed by a decrease. The longitudinal age curves showed a consistently higher incidence risk in men, peaking in the 80-84 age group. Male cohorts since the 1920s showed a decreasing relative risk, whereas women showed fluctuations in risk over time. Lung cancer rates are falling in Spain, especially amongst men, due to lower smoking rates. The gender gap is closing, but prevention targeted at women is needed. Tighter tobacco control and research into other risk factors are essential. Understanding the long-term effects of smoking and early exposure is key to better prevention and treatment in Spain.

Renal Hyperfiltration as a New Mechanism of Smoking-Related Mortality.

Renal hyperfiltration (RHF), an established risk factor for mortality, is prevalent among tobacco smokers. The aim of this study was to assess the mediating role of RHF in the association between smoking and mortality. Data of this study were retrieved from the cohort of the Kuopio Ischemic Heart Disease Risk Factor Study (KIHD), including 2064 males from Finland. Study participants were followed over a 35-year period. Using classic and counterfactual mediation analysis approaches, we estimated the mediative effect of RHF in the association between smoking and each of the following outcomes: All-cause mortality, cardiovascular disease (CVD) mortality, and non-CVD mortality. The risk of all-cause mortality in smokers was twice that in nonsmokers (hazard ratio [HR], 2.06; 95% confidence interval [CI]: 1.84 to 2.31). Under the counterfactual framework the direct effect of smoking on all-cause mortality, controlled for RHF, corresponded to an HR of 2.00 (95% CI: 1.78 to 2.30). Of the effect of smoking on mortality, 5% (p-value = .016) was mediated by RHF. This finding concerned particularly non-CVD mortality. RHF mediated the effect of smoking on non-CVD and all-cause mortality, but not on CVD mortality. The generalizability of our study results is however limited by its focus on a Finnish male cohort, underscoring the need for further investigation into RHF's broader implications across diverse populations. This study elucidates the complex interplay between smoking, renal hyperfiltration (RHF), and mortality, offering novel insights into the mediating role of RHF. Our findings demonstrate that RHF significantly mediates the relationship between smoking and non-cardiovascular disease (non-CVD), but not CVD mortality. This distinction underscores the multifaceted role of RHF beyond its established association with cardiovascular events. By highlighting the specific pathways through which RHF mediates some of the smoking-attributed mortality, this research contributes to our understanding of the mechanisms linking smoking to mortality.

A unified approach for Parkinson's disease recognition: imbalance mitigation and grid search optimized boosting with LightGBM.

The work elucidates the importance of accurate Parkinson's disease classification within medical diagnostics and introduces a novel framework for achieving this goal. Specifically, the study focuses on enhancing disease identification accuracy utilizing boosting methods. A standout contribution of this work lies in the utilization of a light gradient boosting machine (LGBM) coupled with hyperparameter tuning through grid search optimization (GSO) on the Parkinson's disease dataset derived from speech recording signals. In addition, the Synthetic Minority Over-sampling Technique (SMOTE) has also been employed as a pre-processing technique to balance the dataset, enhancing the robustness and reliability of the analysis. This approach is a novel addition to the study and underscores its potential to enhance disease identification accuracy. The datasets employed in this work include both gender-specific and combined cases, utilizing several distinctive feature subsets including baseline, Mel-frequency cepstral coefficients (MFCC), time-frequency, wavelet transform (WT), vocal fold, and tunable-Q-factor wavelet transform (TQWT). Comparative analyses against state-of-the-art boosting methods, such as AdaBoost and XG-Boost, reveal the superior performance of our proposed approach across diverse datasets and metrics. Notably, on the male cohort dataset, our method achieves exceptional results, demonstrating an accuracy of 0.98, precision of 1.00, sensitivity of 0.97, F1-Score of 0.98, and specificity of 1.00 when utilizing all features with GSO-LGBM. In comparison to AdaBoost and XGBoost, the proposed framework utilizing LGBM demonstrates superior accuracy, achieving an average improvement of 5% in classification accuracy across all feature subsets and datasets. These findings underscore the potential of the proposed methodology to enhance disease identification accuracy and provide valuable insights for further advancements in medical diagnostics.

Steroid-induced dermatoses: a challenge for modern dermatology

The aim of this work is to determine the variability and significance of motivating and provoking factors associated with the uncontrolled use of topical glucocorticosteroids, psychological features of this condition. Materials and methods. 50 patients with exacerbation of inflammatory dermatoses after long-term topical application of drugs with glucocorticosteroids as an active substance were examined. The key diagnostic measures were a clinical examination, an anamnesis collection with clarification of the activity class of the used agent, duration and potential reason for its systematic or periodic use. Assessment of the psycho-emotional state in relation to self-perception of one’s own body was carried out using the dermatological version of the dysmorphic disorder questionnaire – BDDQ-DV. Results. The main pathology for which patients of both sexes used this group of drugs were rosacea, perioral dermatitis, and seborrheic dermatitis. Taking into account anamnestic data, the mean duration of application of topical corticosteroids in creams, ointments or lotions was 10.25 ± 3.50 months for women and 8.3 ± 1.6 months for the male cohort. Most patients received information about the need to use a topical steroid from acquaintances / friends and pharmacists. The most frequent pharmacological agent was betamethasone dipropionate. Analyzing the psychopathological aspect of the studied group, dysmorphic manifestations are prevalent and the most well argued. 32 individuals (64 %) from the cohort met the criteria for concern about the body or its parts. Conclusions. Regional clinical features of steroid-induced dermatoses, which are mostly represented by chronic inflammatory conditions located in aesthetically significant areas, have been determined. 64 % of patients with steroid-induced dermatoses develop a psychopathological profile. An important aspect remains the necessity to raise the awareness of medical, pharmaceutical workers, and the public about the need and correct use of topical corticosteroids.

Indian Hand Anthropometry: Computer Tomography-Based Morphometric Analysis of Metacarpal.

Introduction Metacarpal fractures are common and have various treatment options, but understanding their morphometry is crucial for optimizing fixation techniques and reducing complications. Accurate assessment of metacarpal anatomy is challenging in conventional radiographs but feasible with computed tomography (CT) scans, which offer precise views. This study aimed to provide accurate anatomical data on metacarpals within an Indian population using CT scans and to compare the results with existing literature. The findings have implications for surgical procedures, including plating, pinning, and intramedullary screw fixation. Materials and Methods This retrospective analysis utilized CT scans of 100 hands, including 50 males and 50 females, from two hospitals in India. Inclusion criteria included complete metacarpal visualization with a slice thickness of 0.6 mm, while exclusion criteria involved trauma, deformity, or underlying pathologies. Various parameters of all metacarpals were measured using RadiAnt DICOM Viewer 2021.1, providing accurate anteroposterior and lateral views. Results Male and female cohorts had mean ages of 38.58 ± 12.02 and 43.60 ± 13.61 years, respectively. The study showed good to excellent reliability in measurements. The 2nd metacarpal was consistently the longest, and the general length pattern was 3rd > 4th > 5th > 1st metacarpal in both genders. Men generally had larger metacarpal dimensions than women, except for intramedullary diameter, which showed minimal sex-related differences. Notably, the medullary cavity's narrowest part was at the 4th metacarpal, and the thumb had the widest intramedullary diameter. Conclusion This study provides valuable anatomical reference data for metacarpals in an Indian population, aiding in optimizing surgical techniques for metacarpal fractures. The 2nd metacarpal consistently stood out as the longest, and men generally had larger metacarpal dimensions than women. These insights into anatomical variations can inform clinical decisions and stimulate further research in this field. However, a larger and more diverse sample would enhance the study's representativeness.

Prediction of subsequent fragility fractures: application of machine learning

BackgroundMachine learning (ML) has shown exceptional promise in various domains of medical research. However, its application in predicting subsequent fragility fractures is still largely unknown. In this study, we aim to evaluate the predictive power of different ML algorithms in this area and identify key features associated with the risk of subsequent fragility fractures in osteoporotic patients.MethodsWe retrospectively analyzed data from patients presented with fragility fractures at our Fracture Liaison Service, categorizing them into index fragility fracture (n = 905) and subsequent fragility fracture groups (n = 195). We independently trained ML models using 27 features for both male and female cohorts. The algorithms tested include Random Forest, XGBoost, CatBoost, Logistic Regression, LightGBM, AdaBoost, Multi-Layer Perceptron, and Support Vector Machine. Model performance was evaluated through 10-fold cross-validation.ResultsThe CatBoost model outperformed other models, achieving 87% accuracy and an AUC of 0.951 for females, and 93.4% accuracy with an AUC of 0.990 for males. The most significant predictors for females included age, serum C-reactive protein (CRP), 25(OH)D, creatinine, blood urea nitrogen (BUN), parathyroid hormone (PTH), femoral neck Z-score, menopause age, number of pregnancies, phosphorus, calcium, and body mass index (BMI); for males, the predictors were serum CRP, femoral neck T-score, PTH, hip T-score, BMI, BUN, creatinine, alkaline phosphatase, and spinal Z-score.ConclusionML models, especially CatBoost, offer a valuable approach for predicting subsequent fragility fractures in osteoporotic patients. These models hold the potential to enhance clinical decision-making by supporting the development of personalized preventative strategies.

Clinical utility of circulating tumor tissue-modified viral HPV DNA testing in HPV-driven oropharyngeal cancer arising in women.

e18032 Background: HPV+OPSCC is rare in womenand may indicate a different biology. The purpose of this study was to evaluate the clinical utility of circulating tumor tissue modified viral (TTMV)-HPV DNA testing in women with HPV+ OPSCC, and to compare the results to our male cohort. Methods: A total of 88 TTMV-HPV DNA tests were collected on 23 women with OPSCC, treated with curative intent. 87% pts (20/23) had pre-treatment TTMV testing. Initial HPV status was assessed by p16 marker IHC and then by TTMV-HPV DNA assay. There were 22/23 pts with p16+ by IHC. One pt with p16- IHC had a positive pre-Tx TTMV score of 185. Post treatment TTMV testing was performed at 3-month intervals. The pre-Tx TTMV median score was 1047 normalized frags/ml. (range: 7-16909). Median number of surveillances TTMV tests were 2.5 (range 1-7). Test results were correlated with imaging to assess clinical utility. Results: 23 women were included. Median age 65.9 (Range: 49-79). Median follow-up was 25.6 months (Range 1.4-52.7). There were 20 pre-treatment tests, 19/20 pts were p16+ IHC. 14 TTMV tests were true positive, with a per-test and per-patient sensitivity of 76.5% (95% CI: 56.3 – 96.6%). For p16+ males, the per-test sensitivity was 54/59, 91.5%, (95% CI: 84.4 – 98.6%) and the per-pt sensitivity is 50/55, 90.9% (95% CI: 83.8 – 98.5%). Fisher’s exact test was used to determine if there is a relationship between biological sex and pre-treatment sensitivity. The per-test p-value was 0.0575, and the per-pt p-value was 0.1119. 5 pts with p16+ IHC had negative baseline TTMV tests, one of which had TTMV-HPV16 DNA subsequently confirmed by FFPE. Clinical staging included T1-T2 (N=19; 82.6%), T3-T4 (N=4, 17.4%), N0-N1 (65.2%: N0=3, N1=12), N2-N3 (34.8%: N2=7, N3=1). There was no correlation between pre-treatment TTMV score and T stage. There was a significant difference in pre-treatment score for pts with N0 vs N+ (Mann-Whitney U test, p = 0.0392). However, the N0 group only had 3 tests, compared to 15 tests in the N1/N2/N3 group. The median score of the N0 group was 7 and the median score of the N1/N2/N3 group was 371. All TTMV tests resolved to zero after treatment completion. 9/14 (64.3%) TTMV scores resolved within 3 months after treatment completion. These pts had post treatment imaging and clinical examination without evidence of disease. We have not observed to date any rise in TTMV-HPV ctDNA in this cohort. Conclusions: This is the first single institutional report evaluating the clinical utility of TTMV-HPV DNA in a female cohort treated for HPV+ OPSCC. Utilization of this testing in a female population appears feasible in a community-based hospital setting. All pts had TTMV resolution after treatment and remained undetectable without recurrence. Despite the apparent trend toward lower sensitivity in females, the difference was not statistically significant and warrant further investigation in a larger multi-institutional study.

Sugar-sweetened beverage intake and risk of oral cavity cancer: Results from 3 prospective US cohort studies.

10570 Background: Approximately 65% of adults in the US consume sugar-sweetened beverages (SSBs) daily, and consumption of SSBs substantially increased across successive birth cohorts in the US until 2000. Previous authors have identified an association between early-onset digestive tract cancers and SSBs. Recently, early-onset (&lt;50 years) oral cavity squamous cell carcinoma has been observed in non-smoking, non-drinking individuals. The objective of this study was to investigate the association between SSBs and development of oral cavity cancer (OCC) in smokers, non-smokers, and those &lt;50 years of age. Methods: We prospectively examined the association between SSB intake and OCC risk among 165,212 women in Nurses’ Health Study (NHS, 1986-2014) and Nurses’ Health Study II (NHSII, 1991-2015), and 45,790 men in the Health Professionals Follow-Up Study (HPFS, 1986-2014). All participants completed validated food frequency questionnaires (FFQs) every 4 years. Cox proportional hazards models adjusted for age, caloric intake, tobacco pack-years, alcohol intake, and BMI were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between SSB intake and OCC incidence. Results: We identified 129 incident OCC cases in NHS/NHSII over 36 years of follow-up and 99 cases in HPFS over 30 years of follow-up for HPFS. The mean age at study baseline was 44.4 years for NHS/NHSII and 54.1 years for HPFS. Notably, in the multivariable adjusted model, increasing SSB intake was associated with a higher risk of OCC only among female participants in NHS/NHSII. Specifically, those in the highest quartile of SSB intake had a 229% increased risk of OCC compared to the lowest quartile (95% CI 1.29-4.07, ptrend=0.04). In non- or light-drinkers (&lt;5g/day) in NHS/NHSII, SSBs was associated with OCC (HR=2.58, 95% 1.16-5.70, ptrend=0.10, N=81 cases). However, in non- or light-smokers (&lt;5 pack-years), SSB intake was not associated with risk of OCC, though power was limited due to low case numbers (HR=1.56, 95% 0.66-3.68, ptrend=0.45, N=64). In contrast, no association of SSB intake with OCC risk was observed in the male HPFS cohort, overall (N=99) or among non-smokers (N=44). Early-onset OCC (&lt;50 years) was limited to 9 patients, and thus a subset analysis could not be performed. Conclusions: Higher SSB intake was associated with a higher risk of developing OCC in women, but not men, after controlling for known risk factors. Reduction of SSB consumption may serve as a potential strategy to address the increase in OCC observed in recent years.

Prospective “common arm” comparison of US SWOG S0424 and Japanese JME studies in early-stage non-small cell lung cancer (NSCLC): Survival differences in the context of race, gender and smoking.

8036 Background: In NSCLC, overall frequencies and subtype distribution of EGFR and KRAS mutations differ significantly between Japanese and US patients. In many NSCLC clinical trials, Japanese patient outcomes appear superior to those in western populations. Since 2009, SWOG and Japanese investigators have used the “Common Arm” analytic method to interpret globally-conducted lung cancer clinical trials, providing a mechanism for direct patient-level comparisons in matching trials performed in the US and Japan. S0424 and the Japanese Molecular Epidemiology Study (JME) are large prospective molecular epidemiology studies conducted by SWOG and Japanese investigators and prospectively planned for “Common Arm” analysis. We investigated the effects of mutation distribution on overall survival in early stage NSCLC using data from JME and S0424. Methods: Both studies were designed to accrue representative proportions of ever-smokers (ES) versus never-smokers (NS) in male and female cohorts. Accrual to S0424 was completed in 2011 with 981 pts enrolled (Cheng et al JNCI 2018); JME was completed in 2012 with 957 pts (Kawaguchi et al JCO 2016). A comprehensive questionnaire was used to capture lifestyle, carcinogenic exposures, demographic and clinical data. Five years of follow-up was completed for each study. The association between baseline characteristics and mutation types were analyzed using multivariate logistic regression. The product-limit method was used to estimate overall survival and Cox regression models were fit to estimate hazard ratios. p-values were two-sided and p-values &lt; 0.05 were considered significant. Results: Evaluable pts: 876 for JME; 957 for S0424. Demographic distribution: S0424: 87% Caucasian, 5% Asian, 4% Black; JME: 100% Japanese. As expected, multivariate logistic models adjusting for age, smoking status, gender and BMI showed JME were more likely to have EGFR mutations (p &lt; 0.0001) and less likely to have KRAS mutations (p = 0.02). EGFR mutations were associated with never-smoking (p &lt; 0.0001) and female sex (p &lt; 0.0001); KRAS was associated with smoking (p &lt; 0.0001). Adjusting for age, smoking status and gender, overall survival was greater in JME patients (p &lt; 0.0001,HR = 0.49 (95% CI: 0.40-0.60)). In the subset of pts without an EGFR mutation, survival still favored the JME cohort (p &lt; 0.001, HR = 0.68 (0.53-0.86). Conclusions: Patient level comparison of US (SWOG) and Japanese (JME) patients with early stage NSCLC demonstrated longer survival in Japanese patients even after adjusting for EGFR mutation frequency. Identification of factors that contribute to this finding are under investigation. Female sex remained a risk factor for EGFR mutation-driven disease in both populations. This analysis forms the basis for applying this population-related model in other clinical settings.

Sex differences among S-ICD recipients: a propensity-matched, multicenter, international analysis from the i-SUSI project

Abstract Background Women have been historically underrepresented in implantable cardioverter defibrillator (ICD) trials, despite sex differences in the epidemiology and clinical presentation of ventricular arrhythmias (VAs). So far, no data on sex differences among subcutaneous-ICD (S-ICD) recipients have ever been described. Purpose To investigate sex-related differences in patients undergoing S-ICD implantation. Methods Consecutive patients enrolled in the multicenter i-SUSI project were analyzed. The iSUSI (International SUbcutaneouS Implantable cardioverter defibrillator) is a multi-center, open-label, independent, and physician-initiated observational project, involving 22 Public and Private Healthcare Institutions from 5 different countries in Europe and in the US. Comparisons between sexes were performed using an adjusted analysis with 1:1 propensity matching for age, body mass index (BMI), left ventricular function (LVEF) and underlying myocardial substrate (ischemic vs non-ischemic cardiomyopathy). The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. Results A total of 1698 patients were enrolled in the current project. Females represented the 23.5% (n=399) of the study cohort. After propensity matching, two cohorts of 374 matched patients with similar baseline characteristics served as the study cohort for this analysis (Figure 1, panel A). Despite similar procedural characteristics and a matched BMI, female S-ICD recipients had a lower calculated risk of ventricular arrhythmias conversion failure as per PRAETORIAN score (females at low-risk 73.4% vs males 81.3%, p=0.049). Over a median follow-up time of 26.5 [12.7–42.5] months (without differences between the two cohorts), n=68 (9.1%) patients experienced appropriate shocks and n=105 (14.0%) patients suffered from a device-related complication, including 75 (10.3%) cases of inappropriate shock therapy (Figure 1). Appropriate shocks were more common in the male cohort (rate/y 3.4% vs 1.7%; log-rank p=0.049), while no significant differences in device-related complications (rate/y: 6.3% vs 5.8%; log-rank p=0.595) and inappropriate shocks (rate/y: 4.3% vs 3.1% log-rank p=0.375) were observed among groups. Survival analysis for primary and secondary outcomes has been reported in Figure 1, panel B-C-D. At multivariate analysis, male sex remained significantly associated with the primary outcome of interest (aHR 1.591 CI 0.975–2.595, p=0.063). Conclusion In a large S-ICD registry, females were overall underrepresented. In a propensity-matched cohort of S-ICD recipients, women were less likely to experience appropriate ICD therapy, while not showing higher risk of device related-complications and inappropriate shocks. Despite similar BMI and peri-procedural characteristics, women showed a lower risk of conversion failure according to PRAETORIAN score.Figure 1

#1854 Prevalence of Fabry disease in chronic hemodialysis patients: a multicenter screening approach

Abstract Background and Aims Fabry disease (FD), an X-linked lysosomal storage disorder caused by alpha-galactosidase A (α-Gal A) deficiency, leads to significant morbidity and early mortality due to progressive organ failure. Given the availability of enzyme replacement therapy, early identification of FD is crucial for improving patient outcomes. Method A multicenter screening was conducted among chronic hemodialysis patients across six centers. We utilized a two-tiered diagnostic approach. Initially, α-Gal A activity was measured from dried blood spots on filter paper. Subsequently, those with reduced enzyme levels underwent GLA gene mutation analysis. Results Out of 428 patients, 255 (102 females and 153 males) were selected for testing, leading to the analysis of 239 patients. In the male cohort, the average α-Gal A activity was 21.84 ± 11.9 µmol/L/h, with 34 males below the cut-off value (&amp;lt;15.3 µmol/L/h) but with normal lyso-Gb3 levels and no mutations. Among females, α-Gal A levels were typically within the normal range. Notably, one female was found to have a heterozygous variant of uncertain significance in the GLA gene [p.(Asp313Tyr)] in exon 6, with normal α-Gal A and lyso-Gb3 levels. Screening of other family members was not possible, as they resided abroad although we recommended it. Conclusion Screening for AFD in high-risk groups, such as hemodialysis patients, is challenging yet essential. Implementing α-Gal A measurement as a standard procedure for newly registered hemodialysis patients could prospectively identify potential Fabry carriers, offering more excellent utility than our cross-sectional study. While identifying index patients at a late disease stage may not benefit the patients themselves, it is crucial for early detection of family members, potentially altering their disease course. This proactive approach, supported by national and international guidelines, could significantly impact the management and outcomes of AFD.

#2539 Effects of relative blood volume and ultrafiltration volume on pulse wave characteristics during hemodialysis

Abstract Background and Aims Measures of non-invasive pulse wave (PW) analysis can help to assess the status of the central cardiovascular system and to predict clinical outcomes, including morbidity and mortality. During hemodialysis (HD), fluid is extracted from blood. The resulting reduction in relative blood volume (RBV) and collected ultrafiltration volume (UFV) were hypothesized to substantially influence PW characteristics during HD. Volume overload (VO) is common in HD patients and may affect the chance of improving the cardiovascular status of patients during HD. The present study aimed to explore associations between RBV, UFV, VO and a wide range of PW parameters. Method In a single center in Vienna, Austria, 24 patients on maintenance HD underwent four HD sessions each, with whole-body bioimpedance spectroscopy (BIS) before, and automated, cuff-based PW measurements every 15 minutes, RBV- and UFV-monitoring throughout each session. Associations between RBV or UFV as independent variable and 26 different PW characteristics as dependent variables (52 separate models) were tested using confounder-adjusted generalized estimating equations with sandwich estimator and multilevel nested working covariance structure, reporting standardized effect estimates and drop-in-R² to assess variable importance. Sensitivity models including both RBV and UFV as predictors (26 models) were used to assess effects adjusted for confounding and mediation, respectively. The intra-patient correlation between BIS-derived VO and PW parameters at the start of sessions and PW parameter change by end of sessions was assessed using repeated measures correlation analysis. Results Data from 990 PW measurements were available for analysis from an 88% male cohort with median age of 66 years. In half of the PW parameters analyzed, each percent RBV was significantly associated with in summary about 4.3 to 5.7% (95% confidence intervals [CI] 0.9 to 10.46) of the PW parameter's respective standard deviation (SD), negatively so only in heart rate and R-Peak. UFV was negatively associated with a third of PW parameters (effects ranging from −2.5 to −5.47% SD [95% CIs −0.9 to −10.0]), mostly in classical peripheral and central pressures and peripheral resistance. In models including both predictors, RBV overall exhibited greater effect size and variance capture than UFV, except for peripheral resistance. On within-patient level, VO was positively correlated with initial medians of pressure excess (r=0.34, p=0.034), augmentation-index (0.34, p=0.031) and augmentation-pressure (0.32, p=0.042), increase in heart rate (0.32, p=0.04) and decreases in peripheral resistance (0.31, p=0.05), peripheral (systolic: 0.34, p=0.032; diastolic: 0.45, p=0.004; mean: 0.41, p=0.008) and central (diastolic: 0.46, p=0.003) blood pressures during HD. Conclusion The observed PW characteristics were associated with RBV and UFV during HD and may represent modifiable targets for intervention studies. Pressure excess, S-Peak, R-Peak, cardiac and preload parameters were more closely associated with RBV, while classic (especially diastolic) blood pressure parameters, ejection duration and S/D-Ratio were more associated with UFV, in models using both predictors. On average, blood pressure and peripheral resistance tended to decrease less when a patient began HD in a volume-expanded state, which may affect day-to-day feasibility of more classical pressure targets, but perhaps not of other PW parameters. Multiple PW characteristics have previously been shown to be associated with mortality and morbidity and are potential target parameters for future intervention trials. Utilizing RBV modification as an intervention may offer superior precision compared to UFV goals, requiring further studies. PW technology could also be adopted by HD-machine manufacturers at low cost, enabling more precise and individualized treatment options.

Adenylate kinase phosphate energy shuttle underlies energetic communication in flagellar axonemes.

The complexities of energy transfer mechanisms in the flagella of mammalian sperm flagella have been intensively investigated and demonstrate significant diversity across species. Enzymatic shuttles, particularly adenylate kinase (AK) and creatine kinase (CK), are pivotal in the efficient transfer of intracellular ATP, showing distinct tissue- and species-specificity. Here, the expression profiles of AK and CK were investigated in mice and found to fall into four subgroups, of which Subgroup III AKs were observed to be unique to the male reproductive system and conserved across chordates. Both AK8 and AK9 were found to be indispensable to male reproduction after analysis of an infertile male cohort. Knockout mouse models showed that AK8 and AK9 were central to promoting sperm motility. Immunoprecipitation combined with mass spectrometry revealed that AK8 and AK9 interact with the radial spoke (RS) of the axoneme. Examination of various human and mouse sperm samples with substructural damage, including the presence of multiple RS subunits, showed that the head of radial spoke 3 acts as an adapter for AK9 in the flagellar axoneme. Using an ATP probe together with metabolomic analysis, it was found that AK8 and AK9 cooperatively regulated ATP transfer in the axoneme, and were concentrated at sites associated with energy consumption in the flagellum. These findings indicate a novel function for RS beyond its structural role, namely, the regulation of ATP transfer. In conclusion, the results expand the functional spectrum of AK proteins and suggest a fresh model regarding ATP transfer within mammalian flagella.