5α-reductase inhibitors with or without alpha-blockers and risk of incident upper tract urothelial carcinoma in men with benign prostatic hyperplasia: Analysis of US insurance claims data.

BACKGROUND: Increasing data suggests that androgen receptor signaling may play an important role in the carcinogenesis of urothelial cancers. While the chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results, the evidence regarding 5-ARi treatment, and the risk of incident Upper Tract Urothelial Carcinoma (UTUC) development is lacking. Therefore, our objective was to investigate the impact of the 5-ARi administration on the incidence of new UTUC cases using a large US database. METHODS: The MerativeTM Marketscan® database was used to identify men ≥ 50 years old with a diagnosis of BPH and an active 5-ARi prescription between 2007 and 2021 and were subsequently matched with paired controls. A multivariable Cox regression model was implemented to ascertain the association of 5-ARi and/or alpha-blocker (α-B) medications on the incidence of UTUC. Additional subgroup analyses were conducted based on exposure risk (with a 2-year threshold) to investigate the relationship between 5-ARi and UTUC over time. RESULTS: Overall, n=1,103,743 men BPH without prescriptions for BPH, n=31,142 men on 5-ARi, and n=160,049 using 5-ARi + α-B were identified. Over the follow-up period, a total of n=4,761 patients were diagnosed with UTUC. After matching, UTUC incidence ranged from 0.36% to 0.41% in men without active BPH therapy vs. 0.30% and 0.52% for the 5-ARi and 5-ARi + α-B groups, respectively. In multivariable analysis, the chemoprotective effect on UTUC risk was not observed for either 5-ARi monotherapy (adjusted hazard ratio [aHR]: 0.91, 95% CI: 0.58-1.44) or 5-ARi + α-B combination (aHR: 1.02, 95% CI: 0.87-1.19). This remained true for both short-term (≤ 2 years) and long-term (> 2 years) follow-up periods. CONCLUSIONS: The use of 5-ARi for BPH, whether used alone or in combination with α-B, is not associated with incident UTUC.

Assessing Artificial Intelligence-Generated Responses to Urology Patient In-Basket Messages.

INTRODUCTION: Electronic patient messaging utilization has increased in recent years and has been associated with physician burnout. ChatGPT is a language model that has shown the ability to generate near-human level text responses. This study evaluated the quality of ChatGPT responses to real-world urology patient messages. METHODS: One hundred electronic patient messages were collected from a practicing urologist's inbox and categorized based on the question content. Individual responses were generated by entering each message into ChatGPT. The questions and responses were independently evaluated by 5 urologists and graded on a 5-point Likert scale. Questions were graded based on difficulty, and responses were graded based on accuracy, completeness, harmfulness, helpfulness, and intelligibleness. Whether or not the response could be sent to a patient was also assessed. RESULTS: Overall, 47% of responses were deemed acceptable to send to patients. ChatGPT performed better on easy questions with 56% of responses to easy questions being acceptable to send as compared to 34% of difficult questions (P = .03). Responses to easy questions were more accurate, complete, helpful, and intelligible than responses to difficult questions. There was no difference in response quality based on question content. CONCLUSIONS: ChatGPT generated acceptable responses to nearly 50% of patient messages with better performance for easy questions compared to difficult questions. Use of ChatGPT to help respond to patient messages can help to decrease the time burden for the care team and improve wellness. Artificial intelligence performance will likely continue to improve with advances in generative artificial intelligence technology.

GDF11 protects against mitochondrial-dysfunction-dependent NLRP3 inflammasome activation to attenuate osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) is a highly prevalent degenerative disease worldwide, and tumor necrosis factor (TNF-α) is closely associated with its development. Growth differentiation factor 11 (GDF11) has demonstrated anti-injury and anti-aging abilities in certain tissues; however, its regulatory role in OA remains unclear and requires further investigation. OBJECTIVES: To identify whether GDF11 can attenuate osteoarthritis. To exploring the the potential mechanism of GDF11 in alleviating osteoarthritis. METHODS: In this study, we cultured and stimulated mouse primary chondrocytes with or without TNF-α, analyzing the resulting damage phenotype through microarray analysis. Additionally, we employed GDF11 conditional knockout mice OA model to examine the relationship between GDF11 and OA. To investigate the target of GDF11's function, we utilized NLRP3 knockout mice and its inhibitor to verify the potential involvement of the NLRP3 inflammasome. RESULTS: Our in vitro experiments demonstrated that endogenous overexpression of GDF11 significantly inhibited TNF-α-induced cartilage matrix degradation and inflammatory expression in chondrocytes. Furthermore, loss of GDF11 led to NLRP3 inflammasome activation, inflammation, and metabolic dysfunction. In an in vivo surgically induced mouse model, intraarticular administration of recombinant human GDF11 alleviated OA pathogenesis, whereas GDF11 conditional knockout reversed this effect. Additionally, findings from the NLRP3-knockout DMM mouse model revealed that GDF11 exerted its protective effect by inhibiting NLRP3. CONCLUSION: These findings demonstrate the ability of GDF11 to suppress TNF-α-induced inflammation and cartilage degeneration by preventing mitochondrial dysfunction and inhibiting NLRP3 inflammasome activation, suggesting its potential as a promising therapeutic drug for osteoarthritis.

Prenatal exposure to dibutyl phthalate contributes to erectile dysfunction in offspring male rats by activating the RhoA/ROCK signalling pathway.

Prenatal exposure to dibutyl phthalate (DBP) has been reported to cause erectile dysfunction (ED) in adult offspring rats. However, its underlying mechanisms are not fully understood. Previously, we found that DBP activates the RhoA/ROCK pathway in the male reproductive system. This study investigated how prenatal exposure to DBP activates the RhoA/ROCK signalling pathway, leading to ED in male rat offspring. Pregnant rats were stratified into DBP-exposed and NC groups, with the exposed group receiving 750 milligrams per kilogram per day (mg/kg/day) of DBP through gavage from days 14-18 of gestation. DBP exposure activated the RhoA/ROCK pathway in the penile corpus cavernosum (CC) of descendants, causing smooth muscle cell contraction, fibrosis, and apoptosis, all of which contribute to ED. In vitro experiments confirmed that DBP induces apoptosis and RhoA/ROCK pathway activation in CC smooth muscle cells. Treatment of DBP-exposed offspring with the ROCK inhibitor Y-27632 for 8 weeks significantly improved smooth muscle cell condition, erectile function, and reduced fibrosis. Thus, prenatal DBP exposure induces ED in offspring through RhoA/ROCK pathway activation, and the ROCK inhibitor Y-27632 shows potential as an effective treatment for DBP-induced ED.

Sociodemographic Trends and Perinatal Outcomes in Fathers 50 Years and Older.

Importance: The age of fathers at childbirth is rising, with an increasing number of births attributed to older fathers. While the impact of advanced paternal age has been documented, sociodemographic data about fathers aged 50 years and older remain scarce. Objectives: To explore sociodemographic and temporal trends among the oldest US fathers (age ≥50 years) and their associations with perinatal outcomes. Design, Setting, and Participants: This retrospective cross-sectional study included data from all US births from 2011 to 2022 using the National Vital Statistics System. Data were analyzed from August 2023 and May 2024. Exposures: Reported paternal age at childbirth. Main Outcomes and Measures: Outcomes of interest were sociodemographic factors, temporal trends in older fatherhood, and perinatal outcomes, including preterm birth, low birth weight, gestational diabetes, gestational hypertension, assisted reproductive technology (ART), rates of maternal primiparity, and the infant sex ratio. Results: From 2011 to 2022, the US recorded 46 195 453 births, with an overall mean (SD) paternal age of 31.5 (6.8) years and 484 507 (1.1%) involving fathers aged 50 years or older, 47 785 (0.1%) aged 60 years or older, and 3777 (0.008%) aged 70 years or older. Births to fathers aged 50 years or older increased from 1.1% in 2011 to 1.3% in 2022 (P for trend < .001). Fathers aged 50 years or older were more diverse, with variations in educational achievement and race and ethnicity. Marital status and maternal racial and ethnic and educational backgrounds also varied by paternal age and race. Despite controlling for maternal age and other sociodemographic and perinatal factors, every 10-year increase in paternal age was consistently associated with greater use of ART (eg, age 50-59 years: adjusted odds ratio [aOR], 2.23; 95% CI, 2.19-2.27), higher likelihood of first maternal birth (eg, age 50-59 years: aOR, 1.16; 95% CI, 1.15-1.17), and increased risks of preterm birth (eg, age 50-59 years: aOR, 1.16; 95% CI, 1.15-1.18) and low birth weight (eg, age 50-59 years: aOR, 1.14; 95% CI, 1.13-1.15) compared with fathers aged 30 to 39 years. No significant changes in the infant sex ratio were observed, except among fathers aged 70 years or older (aOR, 0.92; 95% CI, 0.86-0.99) and 75 years or older (aOR, 0.84; 95% CI, 0.73-0.97), who showed a decreased likelihood of having male offspring. Conclusions and Relevance: In this cross-sectional study of all US births from 2011 to 2022, the percentage attributed to older fathers, while small, increased. Notable variations in paternal and maternal race and education were identified. Older fatherhood was associated with increased ART use, first-time maternal births, adverse perinatal outcomes, and altered sex ratio. Further research of this population is crucial for improving patient counseling and family planning.

Acute Effects of Breath-Hold Conditions on Aerobic Fitness in Elite Rugby Players.

The effects of face immersion and concurrent exercise on the diving reflex evoked by breath-hold (BH) differ, yet little is known about the combined effects of different BH conditions on aerobic fitness in elite athletes. This study aimed to assess the acute effects of various BH conditions on 18 male elite rugby players (age: 23.5 ± 1.8 years; height: 183.3 ± 3.4 cm; body mass: 84.8 ± 8.5 kg) and identify the BH condition eliciting the greatest aerobic fitness activation. Participants underwent five warm-up conditions: baseline regular breathing, dynamic dry BH (DD), static dry BH (SD), wet dynamic BH (WD), and wet static BH (WS). Significant differences (p < 0.05) were found in red blood cells (RBCs), red blood cell volume (RGB), and hematocrit (HCT) pre- and post-warm-up. Peak oxygen uptake (VO2peak) and relative oxygen uptake (VO2/kgpeak) varied significantly across conditions, with BH groups showing notably higher values than the regular breathing group (p < 0.05). Interaction effects of facial immersion and movement conditions were significant for VO2peak, VO2/kgpeak, and the cardiopulmonary optimal point (p < 0.05). Specifically, VO2peak and peak stroke volume (SVpeak) were significantly higher in the DD group compared to that in other conditions. Increases in VO2peak were strongly correlated with changes in RBCs and HCT induced by DD warm-up (r∆RBC = 0.84, r∆HCT = 0.77, p < 0.01). In conclusion, DD BH warm-up appears to optimize subsequent aerobic performance in elite athletes.

Construction of a predictive nomogram for functional recovery after Bernese periacetabular osteotomy.

Background and purpose: Surgical indications for Bernese periacetabular osteotomy (PAO) are well-established. However, the extent of postoperative functional recovery varies widely, as observed in clinical follow-ups. Thus, preoperative evaluation is crucial. This study aims to identify factors that influence functional recovery post-PAO and to develop a predictive nomogram. Patients and methods: Retrospective data were collected between December 2016 and March 2022 at The First Affiliated Hospital of Shandong First Medical University. The dataset included demographic and imaging data of patients who underwent PAO. The least absolute shrinkage and selection operator (LASSO) regression was utilized to identify influencing factors, which were further analyzed using multivariate logistic regression to construct a predictive nomogram for post-PAO functional recovery. Result: The analysis identified critical factors affecting functional recovery post-PAO, namely, the preoperative distance from the innermost surface of the femoral head to the ilioischial line, the surgical approach, preoperative acetabular depth, and the continuity of the preoperative Calve line. A nomogram was developed using these significant predictors. The model's validity was demonstrated by the receiver operating characteristic curve, with an area under the curve of 0.864. Additionally, the calibration curve confirmed the nomogram's accuracy, showing a strong correlation between observed and predicted probabilities, indicating high predictive accuracy. Conclusion: This predictive nomogram effectively identifies patients most suitable for PAO, providing valuable guidance for selecting surgical candidates and determining the appropriate surgical approach.

Increased risk of cardiovascular disease among kidney cancer survivors: a nationwide population-based cohort study.

Background: Cardiovascular disease (CVD) is a major concern of morbidity and mortality among cancer survivors. However, few evidence exists on the short- and long-term risk of CVD in kidney cancer (KCa) survivors. Methods: In this nationwide, large population-based retrospective cohort study, we used the Korean national health insurance and medical checkup survey linkage database (2007-2021), drawn from the entire Korean population. We included adults diagnosed with KCa as the first primary cancer and matched them to an individual without KCa at a 1:5 ratio. The primary outcome was CVD incidence, including myocardial infarction, stroke, atrial fibrillation, heart failure, peripheral arterial occlusion, and venous thromboembolism (VTE). We evaluated CVD risk at 6 months, 1 year, and 5 years following cancer diagnosis, using Fine-Gray competing risk models that accounted for death as a competing factor. Results: A total of 149,232 participants were included (KCa survivors: N=20,093 and matched non-KCa individuals: N=129,139). After 6-month follow-up, KCa survivors showed an increased risk of CVD compared to the general population (subdistribution hazard ratio (HR) 2.70, 95% confidence interval (CI) 2.31-3.15). After 1 year, KCa survivors had a higher risk of CVD (HR=1.77, 95% CI: 1.56-2.00). After 5 years, this elevated CVD risk remained (HR=1.10, 95% CI: 1.03-1.18), with VTE identified as the primary contributing disease (HR=3.05, 95% CI:2.59-3.59). Conclusion: KCa survivors had an increased risk of CVD up to 5 years after cancer diagnosis compared to the general population. Our findings emphasize the importance of comprehensive healthcare management for both CVD and KCa throughout cancer survivorship.

Monolithic integrated chip of AWG and PD for an FBG interrogation system.

To advance the development of a compact and highly integrated fiber Bragg grating (FBG) interrogation system, to the best of our knowledge, this paper is the first to present the design and fabrication of a monolithic integration chip based on silicon-on-insulator (SOI), which is specifically intended for application in fiber grating sensing interrogation systems. By considering the impact of coupling structure dimensions on coupling efficiency as well as the effect of the photodetector (PD) parameters on the optical absorption efficiency of the device, we refine the structure of the monolithic integrated chip for arrayed waveguide grating (AWG) and PD. The test results reveal that the coupling loss between AWG and PD is -2.4 dB. The monolithic integrated interrogation chip achieves an interrogation accuracy of approximately 6.79 pm within a dynamic range of 1.56 nm, accompanied by a wavelength resolution of 1 pm. This exceptional performance highlights the potential of the monolithic integrated chip to enhance the integration of AWG-based fiber grating interrogation systems.

Online, home-based dystrophic epidermolysis bullosa registry.

Genetic testing is the gold standard for diagnosing different epidermolysis bullosa (EB) subtypes; however, testing rates are low. We conducted a pilot study to test feasibility of a novel, home-based registry that involved patients with EB submitting self-reported clinical symptoms using secure, online surveys (REDCap) and submitting buccal swabs for exome sequencing of EB-related genes (GeneDx). In total, 50 EB participants were enrolled, with an average age of 17 years and an average distance of 198 miles from EB specialty centers. All buccal swabs (N = 24) provided sufficient DNA for sequencing without causing mucosal trauma and 80% of participants were found to have pathogenic variants in COL7A1, the gene mutated in DEB. Participants with recessive dystrophic EB (RDEB) reported a higher prevalence of esophageal dilations (65.7% vs. 0%, p = .009) and mitten deformities of the feet (57.1% vs. 0%, p = .047) compared to non-RDEB participants.

Effect of low-degree astigmatism on the objective visual quality.

AIM: To evaluate the effect of low-degree astigmatism on objective visual quality through the Optical Quality Analysis System (OQAS). METHODS: This study enrolled 46 participants (aged 23 to 30y, 90 eyes) with normal or corrected-to-normal vision. The cylindrical lenses (0, 0.5, 0.75, 1.0, and 1.25 D) were placed at the axial direction (180°, 45°, 90°, and 135°) in front of the eyes with the best correction to form 16 types of regular low-degree astigmatism. OQAS was used to detect the objective visual quality, recorded as the objective scattering index (OSI), OQAS values at contrasts of 100%, 20%, and 9% predictive visual acuity (OV100%, OV20%, and OV9%), modulation transfer function cut-off (MTFcut-off) and Strehl ratio (SR). The mixed effect linear model was used to compare objective visual quality differences between groups and examine associations between astigmatic magnitude and objective visual quality parameters. RESULTS: Apparent negative relationships between the magnitude of low astigmatism and objective visual quality were observed. The increase of OSI per degree of astigmatism at 180°, 45°, 90°, and 135° axis were 0.38 (95%CI: 0.35, 0.42), 0.50 (95%CI: 0.46, 0.53), 0.49 (95%CI: 0.45, 0.54) and 0.37 (95%CI: 0.34, 0.41), respectively. The decrease of MTFcut-off per degree of astigmatism at 180°, 45°, 90°, and 135° axis were -10.30 (95%CI: -11.43, -9.16), -12.73 (95%CI: -13.62, -11.86), -12.75 (95%CI: -13.79, -11.70), and -9.97 (95%CI: -10.92, -9.03), respectively. At the same astigmatism degree, OSI at 45° and 90° axis were higher than that at 0° and 135° axis, while MTFcut-off were lower. CONCLUSION: Low astigmatism of only 0.50 D can significantly reduce the objective visual quality.

The impact of venous thromboembolism before open or minimally-invasive radical cystectomy in the USA: insurance claims data on perioperative outcomes and healthcare costs.

BACKGROUND: The relationship between venous thromboembolism (VTE) and solid malignancy has been established over the decades. With rising projected rates of bladder cancer (BCa) worldwide as well as increasing number of patients experiencing BCa and VTE, our aim is to assess the impact of a preoperative VTE diagnosis on perioperative outcomes and health-care costs in BCa cases undergoing radical cystectomy (RC). METHODS: Patients ≥18 years of age with BCa diagnosis and undergoing open or minimally invasive (MIS) RC were identified in the Merative™ Marketscan® Research Databases between 2007 and 2021. The association of previous VTE history with 90-day complication rates, postoperative VTE events, rehospitalization, and total hospital costs (2021 USA dollars) was determined by multivariable logistic regression modeling adjusted for patient and perioperative confounders. Sensitivity analysis on VTE degree of severity (i.e., pulmonary embolism [PE] and/or peripheral deep venous thrombosis [DVT]) was also examined. RESULTS: Out of 8759 RC procedures, 743 (8.48%) had a previous positive history for any VTE including 245 (32.97%) PE, 339 (45.63%) DVT and 159 (21.40%) superficial VTE. Overall, history of VTE before RC was strongly associated with almost any worse postoperative outcomes including higher risk for any and apparatus-specific 90-days postoperative complications (odds ratio [OR]: 1.21, 95% CI, 1.02-1.44). Subsequent incidence of new VTE events (OR: 7.02, 95% CI: 5.93-8.31), rehospitalization (OR: 1.25, 95% CI: 1.06-1.48), other than home/self-care discharge status (OR: 1.53, 95% CI: 1.28-1.82), and higher health-care costs related to the RC procedure (OR: 1.43, 95% CI: 1.22-1.68) were significantly associated with a history of VTE. CONCLUSIONS: Preoperative VTE in patients undergoing RC significantly increases morbidity, post-procedure VTE events, hospital length of stay, rehospitalizations, and increased hospital costs. These findings may help during the BCa counseling on risks of surgery and hopefully improve our ability to mitigate such risks.

The characterization of functional conduction block in patients with multiple types of atrial tachycardia- A discussion on the mechanism of multiple atrial tachycardia.

BACKGROUND: High-resolution mapping offers superior accuracy in delineating conduction features; however, certain characteristics are still linked to elevated recurrence rates of atrial tachycardia (AT), suggesting the influence of additional mechanisms. This study systematically assessed the substrate of functional conduction block (FCB) regions in relation to the mechanisms of multiple ATs. METHODS: In this study, the Carto system facilitated the mapping of ATs in 13 patients undergoing ablation, each presenting with more than two AT variants. FCB regions were marked and further analyzed. RESULTS: A total of 33 sustained ATs were mapped across the patient cohort. FCB regions showed convertibility in 7 of 13 patients (54%). Three kinds of presentations can be summarized by the FCB region: Firstly, the FCB region could act as the main obstacle sustaining the localized reentrant pathway, for which rounding obviously has a direct correlation with the mechanism of the AT (27%). Secondly, the FCB regions could act as obstacle lines to reorganize the propagation of the reentry in localized AT and macroreentrant AT (55%). Lastly, the FCB region could act as a bystander and may not be related to the mechanism of the ATs (18%). The potentials in FCB regions mostly performed low voltages or fragmented potentials (FPs) in the ATs which they did not perform the conduction block (90%). CONCLUSION: In multiple ATs, FCB regions may not be uncommon. The participation of FCB regions in the mechanism of ATs showed three different kinds of performance. The dynamic nature of this substrate may provide insight into the reasons for the high recurrence of related ATs.

Vitamin C regulates skeletal muscle post-injury regeneration by promoting myoblast proliferation through its direct interaction with the Pax7 protein.

Previous studies have shown that vitamin C (VC), an essential vitamin for the human body, can promote the differentiation of muscle satellite cells (MuSCs) in vitro and play an important role in skeletal muscle post-injury regeneration. However, the molecular mechanism of VC regulating MuSC proliferation has not been elucidated. In this study, the role of VC in promoting MuSC proliferation and its molecular mechanism were explored using cell molecular biology and animal experiments. The results showed that VC accelerates the progress of skeletal muscle post-injury regeneration by promoting MuSC proliferation in vivo. VC can also promote skeletal muscle regeneration in the case of atrophy. Using the C2C12 myoblast murine cell line, we observed that VC also stimulated cell proliferation. In addition, after an in vitro study establishing the occurrence of a physical interaction between VC and Pax7, we observed that VC also upregulated the total and nuclear Pax7 protein levels. This mechanism increased the expression of Myf5 (Myogenic Factor 5), a Pax7 target gene. This study establishes a theoretical foundation for understanding the regulatory mechanisms underlying VC-mediated MuSC proliferation and skeletal muscle regeneration. Moreover, it develops the application of VC in animal muscle nutritional supplements and treatment of skeletal muscle-related diseases.

Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.

ABSTRACT: Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 ( Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.

The Impact of Venous Thromboembolism on Upper Tract Urothelial Carcinomas Undergoing Open or Minimally Invasive Radical Nephroureterectomy in the USA: Perioperative Outcomes and Health Care Costs from Insurance Claims Data.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Our aim was to assess the impact of a preoperative VTE diagnosis on perioperative outcomes in the RNU context. METHODS: Patients aged 18 yr or older with a UTUC diagnosis undergoing RNU were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of VTE prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism [PE] and/or deep venous thrombosis [DVT]) was examined. KEY FINDINGS AND LIMITATIONS: Within the investigated cohort of 6922 patients, history of any VTE preceding RNU was reported in 568 (8.21%) cases, including DVT (n = 290, 51.06%), PE (n = 169, 29.75%), and superficial VTE (n = 109, 19.19%). The history of VTE before RNU was predictive of higher rates of complications, the most prevalent being respiratory complications (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.43-2.22). Preoperative VTE was found to be associated with an increased risk of VTE following RNU (OR: 14.3, 95% CI: 11.48-17.82), higher rehospitalization rates (OR: 1.26, 95% CI 1.01-1.56) other than home discharge status (OR: 1.44, 95% CI: 1.18-1.77), and higher costs (OR 1.42, 95% CI: 1.20-1.68). Limitations include the retrospective nature and the use of an insurance database that relies on accurate coding and does not include information such as pathologic staging. CONCLUSIONS AND CLINICAL IMPLICATIONS: The presented findings will contribute to the counseling process for patients. These patients may benefit from enhanced pre/postoperative anticoagulation. More research is needed before the following results can be used in the clinical setting. PATIENT SUMMARY: Patients aged 18 yr or older with an upper tract urothelial carcinoma (UTUC) diagnosis undergoing radical nephroureterectomy (RNU) were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of venous thromboembolism (VTE) prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism and/or deep venous thrombosis) was examined. The presented findings will contribute to the counseling of patients with UTUC and preoperative VTE.

Leu promotes C2C12 cell differentiation by regulating the GSK3ß/ß-catenin signaling pathway through facilitating the interaction between SESN2 and RPN2.

BACKGROUND: Leucine (Leu) is an essential amino acid that facilitates skeletal muscle satellite cell differentiation, yet its mechanism remains underexplored. Sestrin2 (SESN2) serves as a Leu sensor, binding directly to Leu, while ribophorin II (RPN2) acts as a signaling factor in multiple pathways. This study aimed to elucidate Leu's impact on mouse C2C12 cell differentiation and skeletal muscle injury repair by modulating RPN2 expression through SESN2, offering a theoretical foundation for clinical skeletal muscle injury prevention and treatment. RESULTS: Leu addition promoted C2C12 cell differentiation compared to the control, enhancing early differentiation via myogenic determinant (MYOD) up-regulation. Sequencing revealed SESN2 binding to and interacting with RPN2. RPN2 overexpression up-regulated MYOD, myogenin and myosin heavy chain 2, concurrently decreased p-GSK3ß and increased nuclear ß-catenin. Conversely, RPN2 knockdown yielded opposite results. Combining RPN2 knockdown with Leu rescued increased p-GSK3ß and decreased nuclear ß-catenin compared to Leu absence. Hematoxylin and eosin staining results showed that Leu addition accelerated mouse muscle damage repair, up-regulating Pax7, MYOD and RPN2 in the cytoplasm, and nuclear ß-catenin, confirming that the role of Leu in muscle injury repair was consistent with the results for C2C12 cells. CONCLUSION: Leu, bound with SESN2, up-regulated RPN2 expression, activated the GSK3ß/ß-catenin pathway, enhanced C2C12 differentiation and expedited skeletal muscle damage repair. © 2024 Society of Chemical Industry.

Variation and disparity in awareness of atrial fibrillation in China: A national cross-sectional study.

BACKGROUND: The latest information regarding the awareness of atrial fibrillation (AF) remains limited in China. OBJECTIVES: The present study aimed to understand the variation and disparity in awareness of AF in China. METHODS: The cross-sectional study used data from the 2020 nationwide epidemiology survey on AF among adults aged 18 years or older in mainland China to assess the prevalence of AF awareness. The awareness of AF diagnostic methods and outcomes was also assessed using an interviewer-administered questionnaire. RESULTS: Of the 114,039 adults responding to the survey, 1463 (age-standardized prevalence, 55.3% (95% confidence interval [CI], 47.7-62.9%) and 10,202 (8.2%, 95%CI 5.4-10.9%) were aware of AF in participants with and without AF, respectively. Of these, 36.4% (95%CI 30.0-42.9%) and 6.3% (95%CI 3.6-9.1%) considered electrocardiogram as a method of diagnosing AF, and 30.0% (95% CI 3.2-8.2%) and 5.2% (95%CI 2.7-7.6%) considered stroke as an outcome of AF. The proportion of participants who being aware of AF varied significantly across sociodemographic and cardiovascular disease subgroups, and was almost consistently lower in rural areas than those in urban areas. Overall, lack of AF awareness was associated with rural areas, geographical region, lower education levels, and without history and had no risk factors of cardiovascular disease. CONCLUSIONS: Nearly half of adults with AF, and >90% non-AF population are unaware of AF in China, with significant variation and disparity. Focused public health initiatives are needed to improve awareness and knowledge of AF among high-risk populations.