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INTRODUCTION: Hepatitis C virus (HCV) prevalence among transgender and gender-diverse individuals ranges from 1.8% to 15.7% versus 1% in the general population. Previous HCV studies inclusive of transgender and gender-diverse individuals primarily rely on convenience-based sampling methods or are geographically restricted. The purpose of this study is to compare the prevalence of HCV diagnoses, testing, and care engagement between transgender and gender-diverse and cisgender individuals. METHODS: Using Optums de-identified Clinformatics® Data Mart Database, in 2022, the unadjusted prevalence of HCV testing among all adults and people who inject drugs from January 2001 to December 2019 was measured. Multivariable logistic regression was used to compare the adjusted odds of HCV diagnoses and care engagement by gender subgroup. RESULTS: The overall unadjusted frequency of HCV diagnoses among transgender and gender-diverse individuals was approximately 3 times that of cisgender individuals (1.06% vs 0.38%, p

INTRODUCTION: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Previous studies have shown that the relationship of triglycerides (TGs) with outcomes changes across stages of CKD. Our objective was to examine the association of TG independent of other metabolic syndrome components with renal outcomes in diabetic patients with or without CKD. METHODS: This retrospective cohort study included diabetic US veteran patients with valid data on TGs, estimated glomerular filtration rate (eGFR), and albuminuria (urinary albumin/creatinine ratio) between fiscal years 2004 and 2006. Using Cox models adjusted for clinical characteristics and laboratory markers, we evaluated the relationship of TG with incident albuminuria (stratified by eGFR category) and based on eGFR (stratified by baseline albuminuria categories). To evaluate the relationship of TG with time to end-stage renal disease (ESRD), we stratified models by baseline CKD stage (eGFR category) and baseline albuminuria stage ascertained at time of TG measurement. RESULTS: In a cohort of 138,675 diabetic veterans, the mean ± SD age was 65 ± 11 years old and included 3% females and 14% African Americans. The cohort also included 28% of patients with non-dialysis-dependent CKD (eGFR

In the general population, elevated low-density lipoprotein (LDL) cholesterol levels are an important risk factor for cardiovascular disease (CVD) and mortality; however, the association of LDL with mortality risk and cardiovascular events are less clear in chronic kidney disease (CKD). We sought to examine the relationship of LDL with mortality and rates of atherosclerotic cardiovascular disease (ASCVD) and non-atherosclerotic cardiovascular-related (non-ASCVD) hospitalizations across CKD stages. Our analytical cohort consisted of 1,972,851 United States veterans with serum LDL data between 2004 and 2006. Associations of LDL with all-cause and cardiovascular mortality across CKD stages were evaluated using Cox proportional hazard models with adjustment for demographics, comorbid conditions, smoking status, prescription of statins and non-statin lipid-lowering drugs, body mass index, albumin, high-density lipoprotein, and triglycerides. Associations between LDL and ASCVD and non-ASCVD hospitalizations were estimated using negative binomial regression models across CKD stages. The cohort consisted of 5% female, 14% Black, 29% diabetic, 33% statin-users, and 44% current smokers, with a mean patient age of 64 ± 14 years. Patients with high LDL (≥160 mg/dL) had a higher risk of all-cause and cardiovascular mortality as well as ASCVD and non-ASCVD hospitalization rates across all CKD stages compared with the reference (LDL 70 to

ObjectiveTo determine the association between angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) use and coronavirus disease 2019 (COVID-19) severity and outcomes in US veterans.Patients and methodsWe retrospectively examined 27,556 adult US veterans who tested positive for COVID-19 between March to November 2020. Logistic regression and Cox proportional hazards models using propensity score (PS) for weight, adjustment, and matching were used to examine the odds of an event within 60 days following a COVID-19-positive case date and time to death, respectively, according to ACEI and/or ARB prescription within 6 months prior to the COVID-19-positive case date.ResultsThe overlap PS weighted logistic regression model showed lower odds of an intensive care unit (ICU) admission (odds ratio [OR] 95% CI 0.77, 0.61-0.98) and death within 60 days (0.87, 0.79-0.97) with an ACEI or ARB prescription. Veterans with an ARB-only prescription also had lower odds of an ICU admission (0.64, 0.44-0.92). The overlap PS weighted model similarly showed a lower risk of time to all-cause mortality in veterans with an ACEI or ARB prescription (HR [95% CI]: 0.87, 0.79-0.97) and an ARB only prescription (0.78, 0.67-0.91). Veterans with an ACEI prescription had higher odds of experiencing a septic event within 60 days after the COVID-19-positive case date (1.22, 1.02-1.46).ConclusionIn this study of a national cohort of US veterans, we found that the use of an ACEI/ARB in patients with COVID-19 was not associated with increased mortality and other worse outcomes. Future studies should examine underlying pathways and further confirm the relationship of ACEI prescription with sepsis.

BackgroundPrevious studies have suggested that metabolic syndrome (MetS) components are associated with renal outcomes, defined as a decline in kidney function or reaching end-stage renal disease (ESRD). Elevated triglycerides (TGs) are a component of MetS that have been reported to be associated with renal outcomes. However, the association of TGs with renal outcomes in chronic kidney disease (CKD) patients independent of the other components of the MetS remains understudied.MethodsWe examined 1,657,387 patients with data on TGs and other components of MetS in 2004-2006 and followed up until 2014. Patients with ESRD on renal replacement therapy were excluded. We examined time to ESRD, estimated glomerular filtration rate (eGFR) slope (renal function decline), and time to incident CKD (eGFR

Background High triglycerides are associated with atherosclerotic cardiovascular disease (ASCVD) risks. Among patients with advanced chronic kidney disease (CKD), the association of elevated triglycerides with mortality is diminished and, thus, we investigated the relationship of triglycerides with ASCVD and non-ASCVD hospitalizations across CKD stages. Methods and Results The cohort comprised 2 963 176 veterans who received care in 2004 to 2006 (baseline) and were followed up to 2014. Using Cox models, we evaluated baseline and time-varying triglycerides with time to ASCVD or non-ASCVD hospitalizations, stratified by baseline CKD stage, and adjusted for demographics and baseline or time-updated clinical characteristics. The cohort mean±SD age was 63±14 years, with a baseline median (interquartile range) triglycerides level of 127 (87-189) mg/dL, and a quarter had prevalent CKD. There was a linear association between baseline triglycerides and ASCVD risk; however, the risk with high triglycerides ≥240 mg/dL attenuated with worsening CKD stages (reference: triglycerides 120 to

BACKGROUND: The effect of gender affirming hormone therapy (GAHT) on clinical laboratory parameters, including levels of liver enzymes alanine aminotransferase (ALT) and aspartate transaminase (AST), is an area of uncertainty in transgender health. AIM: We sought to estimate the distribution parameters of liver enzyme levels among transmasculine (TM) and transfeminine (TF) persons receiving GAHT relative to the corresponding measures in cisgender reference groups, and to evaluate longitudinal changes in these laboratory measures following GAHT initiation. METHODS: The data for this longitudinal study included 624 TF and 438 transmasculine (TM) people as well as 4,090 cisgender males and 4,797 cisgender females enrolled in 3 integrated health systems. Time under observation was divided into 2 intervals: from the first blood test to the date of the first filled GAHT prescription and from GAHT initiation to the most recent ALT or AST measurement. Linear mixed models were used to compare changes in log-transformed ALT and AST values among transgender cohort members before and after GAHT initiation, and relative to the reference groups. The results were expressed as relative differences (in %) and the ratios of these differences (ratios-of-ratios) along with the 95% confidence intervals (CIs). OUTCOMES: Changes in ALT and AST levels among transgender people over time and relative to the corresponding changes in cisgender referents. RESULTS: Among TM study participants, the post GAHT ratios-of-ratios for AST were 1.61 (95% CI: 1.13, 2.31) and 1.57 (95% CI: 1.06, 2.31) relative to cisgender males and females respectively. For ALT, the corresponding comparisons yielded the ratios-of-ratios (95% CIs) of 2.06 (1.67, 2.54) and 1.90 (1.50, 2.40). No statistically significant changes were observed among TF participants. Other factors associated with higher liver enzyme levels included alcohol use/abuse and obesity. CLINICAL IMPLICATIONS: TM persons may experience modest increases in ALT and AST concentrations following testosterone initiation; however, clinical significance of the observed association remains unclear and requires further investigation. By contrast, feminizing GAHT is unlikely to induce appreciable changes in liver enzyme levels. STRENGTH AND LIMITATIONS: The strengths of this study are the longitudinal design and the ability to assemble an unselected cohort nested within large health systems. The main limitations include the lack of information on hormone levels and the inability to take into account GAHT doses and routes of administration. CONCLUSION: The influence of long-term GAHT on ALT and AST levels appears modest and not likely to reflect clinically meaningful changes in liver function. Hashemi L, Zhang Q, Getahun D, et al. Longitudinal Changes in Liver Enzyme Levels Among Transgender People Receiving Gender Affirming Hormone Therapy. J Sex Med 2021;18:1662-1675.

Purpose of reviewCardiovascular disease (CVD) is the leading cause of death in patients with chronic kidney disease (CKD). However, traditional CVD risk prediction equations do not work well in patients with CKD, and inclusion of kidney disease metrics such as albuminuria and estimated glomerular filtration rate have a modest to no benefit in improving prediction.Recent findingsAs CKD progresses, the strength of traditional CVD risk factors in predicting clinical outcomes weakens. A pooled cohort equation used for CVD risk prediction is a useful tool for guiding clinicians on management of patients with CVD risk, but these equations do not calibrate well in patients with CKD, although a number of studies have developed modifications of the traditional equations to improve risk prediction. The reason for the poor calibration may be related to the fact that as CKD progresses, associations of traditional risk factors such as BMI, lipids and blood pressure with CVD outcomes are attenuated or reverse, and other risk factors may become more important.SummaryLarge national cohorts such as the US Veteran cohort with many patients with evolving CKD may be useful resources for the developing CVD prediction models; however, additional considerations are needed for the unique composition of patients receiving care in these healthcare systems, including those with multiple comorbidities, as well as mental health issues, homelessness, posttraumatic stress disorders, frailty, malnutrition and polypharmacy. Machine learning over conventional risk prediction models may be better suited to handle the complexity needed for these CVD prediction models.

Background: High quality data pertaining to the size of the transgender and gender diverse (TGD) population are scant, however, several recently published studies may provide more reliable contemporary estimates. Aims: To summarize the estimated number and proportion of TGD individuals overall and across age groups, based on most accurate data. Methods: This systematic review focused on recent studies (published from 2009 through 2019) that utilized sound methodology in assessing the proportion of TGD people in the general population. Publications were included if they used clear definitions of TGD status, and calculated proportions based on a well-defined sampling frame. Nineteen eligible publications represented two broad categories of studies: those that used data from large health care systems; and those that identified TGD individuals from population surveys. Results: Among health system-based studies, TGD persons were identified using relevant diagnostic codes or clinical notes. The proportions of individuals with a TGD-relevant diagnosis or other recorded evidence ranged between 17 and 33 per 100,000 enrollees. In population surveys TGD status was ascertained based on self-report with either narrow or broad definitions. The survey-based estimates were orders of magnitude higher and consistent across studies using similar definitions. When the surveys specifically inquired about transgender identity, the estimates ranged from 0.3% to 0.5% among adults, and from 1.2% to 2.7% among children and adolescents. When the definition was expanded to include broader manifestations of gender diversity, the corresponding proportions increased to 0.5-4.5% among adults and 2.5-8.4% among children and adolescents. Upward temporal trends in the proportion of TGD people were consistently observed. Conclusions: Current data indicate that people who self-identify as TGD represent a sizable and increasing proportion of the general population. This proportion may differ, depending on inclusion criteria, age, and geographic location, but well-conducted studies of similar type and design tend to produce comparable results.

Although commonly detected early in life, alkaptonuria, a rare congenital metabolic disorder, can be challenging to diagnosis and treat in older patients.

Background: Despite the availability of chemotherapy drugs such as 5-fluorouracil (5-FU), the treatment of some cancers such as gastric cancer remains challenging due to drug resistance and side effects. This study aimed to investigate the effect of celastrol in combination with the chemotherapy drug 5-FU on proliferation and induction of apoptosis in human gastric cancer cell lines (AGS and EPG85-257). Materials and Methods: In this in vitro study, AGS and EPG85-257 cells were treated with different concentrations of celastrol, 5-FU, and their combination. Cell proliferation was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The synergistic effect of 5-FU and celastrol was studied using Compusyn software. The DNA content at different phases of the cell cycle and apoptosis rate was measured using flow cytometry. Results: Co-treatment with low concentrations (10% inhibitory concentration (IC10)) of celastrol and 5-FU significantly reduced IC50 (p < 0.05) so that 48 h after treatment, IC50 was calculated at 3.77 and 6.9 μM for celastrol, 20.7 and 11.6 μM for 5-FU, and 5.03 and 4.57 μM for their combination for AGS and EPG85-257 cells, respectively. The mean percentage of apoptosis for AGS cells treated with celastrol, 5-FU, and their combination was obtained 23.9, 41.2, and 61.9, and for EPG85-257 cells 5.65, 46.9, and 55.7, respectively. In addition, the 5-FU and celastrol-5-FU combination induced cell cycle arrest in the synthesis phase. Conclusions: Although celastrol could decrease the concentration of 5-fluorouracil that sufficed to suppress gastric cancer cells, additional studies are required to arrive at conclusive evidence on the anticancer effects of celastrol. [ABSTRACT FROM AUTHOR]

For patients who desire transgender care, providers must use appropriate language, know the basics of cross-sex hormone therapy, and understand the risks and adverse effects of treatment options.

After not responding to chemotherapy and monoclonal antibody therapy, a patient with late-stage non-small cell lung cancer benefited from treatment with erlotinib.

Introduction: Alzheimer’s disease (AD) is an age-dependent neurodegenerative disease. Beta-amyloid (Aβ)-induced neurotoxicity has a pivotal role in AD pathogenesis; therefore, the modulation of Aβ toxicity is the promising therapeutic approach to control the disease progression. Medicinal plants because of their multiple active ingredients are effective in complex diseases, such as AD. Therefore, several studies have studied medicinal plants to find an effective treatment for AD. Ferulago angulata is a medicinal plant with antioxidant and neuroprotective activity. The present study was done to assess the protective effect of the methanolic extract of Ferulago angulate on Aβ-induced toxicity and oxidative stress in PC12 cells. Methods: The methanolic extract of aerial parts of the plant was prepared by the maceration method. PC12 cells were cultured according to a standard protocol. PC12 cells were incubated for 24 hours with Aβ alone, and Aβ in combination with various concentrations of the F. angulata extract. Cell viability was determined by the methyl thiazole tetrazolium (MTT) assay. Also, reactive oxygen species (ROS) production and the activity of acetylcholine esterase (AChE), glutathione peroxidase (GPx), and caspase-3 enzymes were measured. Results:The extract dose-dependently protected PC12 cells against Aβ-induced cell death. Also, Aβ increased ROS production, AChE, and caspase-3 activity, and decreased the GPx activity, which all were ameliorated by F. angulata extract. Conclusion: F. angulata extract protects against Aβ-induced oxidative stress and apoptosis. These effects may be due to the antioxidant and anticholinesterase activity of the extract. It is recommended to assess F. angulata extract as an anti-AD agent. [ABSTRACT FROM AUTHOR]

This study explores the suitability of quasi-static pore-network modeling for simulating the transport of hydrogen in networks with box-shaped pores and square cylinder throats. The dynamic pore-network modeling results are compared with quasi-static pore-network modeling, and a good agreement is observed when the simulations reach steady-state, for a capillary number of N c ≤ 1 0 − 7 . This finding suggests that the quasi-static approach can be used as a reliable and efficient method for studying hydrogen transport in similar networks. [Display omitted] • Quasi-static PNM sensitivity analysis highlighted pore structure and contact angle effects. • Experimental contact angles were used in dynamic PNM, improving UHS dynamics understanding. • The results show dynamic simulation matches quasi-static PNM for UHS conditions (Ca ≤ 1 0 − 7 ). [ABSTRACT FROM AUTHOR]

The range of applications of RPAs in various industries indicates that their increased usage could reduce operational costs and time. Remotely piloted aircraft systems (RPASs) can be deployed quickly and effectively in numerous distribution systems and even during a crisis by eliminating existing problems in ground transport due to their structure and flexibility. Moreover, they can also be useful in data collection in damaged areas by correctly defining the condition of flight trajectories. Hence, defining a framework and model for better regulation and management of RPAS-based systems appears necessary; a model that could accurately predict what will happen in practice through the real simulation of the circumstances of distribution systems. Therefore, this study attempts to propose a multi-objective location-routing optimization model by specifying time window constraints, simultaneous pick-up and delivery demands, and the possibility of recharging the used batteries to reduce, firstly, transport costs, secondly, delivery times, and thirdly, estimated risks. Furthermore, the delivery time of the model has been optimized to increase its accuracy based on the uncertain conditions of possible traffic scenarios. It is also imperative to note that the assessment of risk indicators was conducted based on the Specific Operations Risk Assessment (SORA) standard to define the third objective function, which was conducted in a few previous studies. Finally, it shows how the developed NSGA-II algorithm in this study performed successfully and reduced the objective function by 31%. Comparing the obtained results using an NSGA-II meta-heuristic approach, through the rigorous method GAMS, indicates that the results are valid and reliable. [ABSTRACT FROM AUTHOR]