Methodological rigour in preclinical urology: a systematic review reporting research quality over a 14-year period.

OBJECTIVE: To investigate the prevalence and trends of essential study design elements in preclinical urological studies, as well as key factors that may improve methodological rigour, as the demand for methodological rigour in preclinical studies is increasing since research reproducibility and transparency in the medico-scientific field are being questioned. METHODS AND RESULTS: PubMed was searched to include preclinical urological studies published between July 2007 to June 2021. A total of 3768 articles met the inclusion criteria. Data on study design elements and animal models used were collected. Citation density was also examined as a surrogate marker of study influence. We performed an analysis of the prevalence of seven critical study design elements and temporal patterns over 14 years. Randomisation was reported in 50.0%, blinding in 15.0%, sample size estimation in 1.0%, inclusion of both sexes in 6.3%, statistical analysis in 97.1%, housing and husbandry in 47.7%, and inclusion/exclusion criteria in 5.0%. Temporal analysis showed that the implementation of these study design elements has increased, except for inclusion of both sexes and inclusion/exclusion criteria. Reporting study design elements were associated with increased citation density in randomisation and statistical analysis. CONCLUSIONS: The risk of bias is prevalent in 14-year publications describing preclinical urological research, and the quality of methodological rigour is barely related to the citation density of the article. Yet five study design elements (randomisation, blinding, sample size estimation, statistical analysis, and housing and husbandry) proposed by both the National Institutes of Health and Animal Research: Reporting of In Vivo Experiments guidelines have been either well reported or are being well reported over time. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022233125.

Comparative effectiveness of N95, surgical or medical, and non-medical facemasks in protection against respiratory virus infection: A systematic review and network meta-analysis.

The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.

The global case fatality rate of coronavirus disease 2019 by continents and national income: A meta-analysis.

The aim of this study is to provide a more accurate representation of COVID-19's case fatality rate (CFR) by performing meta-analyses by continents and income, and by comparing the result with pooled estimates. We used multiple worldwide data sources on COVID-19 for every country reporting COVID-19 cases. On the basis of data, we performed random and fixed meta-analyses for CFR of COVID-19 by continents and income according to each individual calendar date. CFR was estimated based on the different geographical regions and levels of income using three models: pooled estimates, fixed- and random-model. In Asia, all three types of CFR initially remained approximately between 2.0% and 3.0%. In the case of pooled estimates and the fixed model results, CFR increased to 4.0%, by then gradually decreasing, while in the case of random-model, CFR remained under 2.0%. Similarly, in Europe, initially, the two types of CFR peaked at 9.0% and 10.0%, respectively. The random-model results showed an increase near 5.0%. In high-income countries, pooled estimates and fixed-model showed gradually increasing trends with a final pooled estimates and random-model reached about 8.0% and 4.0%, respectively. In middle-income, the pooled estimates and fixed-model have gradually increased reaching up to 4.5%. in low-income countries, CFRs remained similar between 1.5% and 3.0%. Our study emphasizes that COVID-19 CFR is not a fixed or static value. Rather, it is a dynamic estimate that changes with time, population, socioeconomic factors, and the mitigatory efforts of individual countries.

Association of peripubertal blood lead levels with reproductive hormones and semen parameters in a longitudinal cohort of Russian men.

STUDY QUESTION: Are peripubertal blood lead levels (BLLs) associated with semen parameters and serum reproductive hormones among young Russian men? SUMMARY ANSWER: We observed a suggestion of lower ejaculate volume with higher peripubertal BLL but no associations of BLLs with reproductive hormones measured throughout adolescence or with other sperm parameters measured at adulthood. WHAT IS KNOWN ALREADY: Lead is a known reproductive toxicant and endocrine disruptor. Previous literature has shown associations between high lead exposure and poorer semen quality both in occupationally and environmentally exposed men. However, to our knowledge, no longitudinal studies have explored the association of childhood lead exposure with semen parameters and reproductive hormones in young men. STUDY DESIGN, SIZE, DURATION: The Russian Children's Study is a prospective cohort study that enrolled 516 boys at age 8-9 years in 2003-2005 and followed them annually for 10 years. BLLs were measured at entry and lifestyle and health questionnaires were completed. Reproductive hormones were measured in blood samples collected every 2 years. PARTICIPANTS/MATERIALS, SETTING, METHODS: Among the 516 boys enrolled, 481 had BLLs measured at entry. Of these, 453 had at least one measurement of serum testosterone, follicle stimulating hormone (FSH) or luteinizing hormone (LH) (median = 5 samples per boy) and 223 had semen samples collected ∼10 years after enrolment. Semen assessment included ejaculated volume, sperm concentration, progressive motility and total sperm count, and parameters were categorized using published andrology standards for low semen quality based on sperm count and motility. Linear mixed models were used to examine the associations of log-transformed BLLs (and BLL categories) with reproductive hormones and semen parameters, adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 223 young men with peripubertal BLLs and at least one semen sample (total samples = 438), the median (interquartile range) BLL was 3 (2, 5) µg/dl and 27% had BLL ≥5 µg/dl. Overall, 49% of the semen samples fell below reference levels for sperm count and/or motility. Men with peripubertal BLL ≥5 µg/dl had significantly lower ejaculated volume than those with BLL <5 µg/dl (mean = 2.42 vs 2.89 ml, P = 0.02), but this difference was attenuated in adjusted models (mean = 2.60 vs 2.83 ml, P = 0.25). No associations were observed between BLL measured at age 8-9 years and reproductive hormone levels or sperm parameters, including sperm concentration, total count, progressive motility and total progressive motile sperm count, or with the probability of having low semen quality based on sperm count/motility. LIMITATIONS, REASONS FOR CAUTION: Only a subset of the original cohort participated in the semen quality portion of the study, although inverse probability weighting was used to account for possible selection bias. BLLs were only measured at a single time in peripuberty, and other exposure time periods, including later or longer-term childhood exposure, may be more predictive of semen quality. The young men were also exposed to other chemical contaminants before and during pubertal development. WIDER IMPLICATIONS OF THE FINDINGS: While semen volume often receives less attention than other sperm parameters, it is an important component of male fertility. Additional prospective studies covering different exposure windows and including other seminal plasma biomarkers are warranted to explore our finding of potentially lower ejaculated volume with higher BLLs and to confirm the lack of associations for other semen parameters among youth exposed to environmental BLLs. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided through grants R01ES0014370 and P30ES000002 from the National Institute of Environmental Health Sciences, grant R82943701 from the U.S. Environmental Protection Agency, and grant 18-15-00202 from the Russian Science Foundation (O.S and Y.D.). All authors report no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. AIM: To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. METHODS: The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). OUTCOMES: Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. RESULTS: Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 - 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. CLINICAL IMPLICATIONS: Discussing sexual concerns with women with LS could empower them to seek treatment. STRENGTHS AND LIMITATIONS: Few articles met criteria for inclusion. CONCLUSION: A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function. Pope R, Lee MH, Myers A, et al. Lichen Sclerosus and Sexual Dysfunction: A Systematic Review and Meta-Analysis. J Sex Med 2022;19:1616-1624.

Semen parameter variability among users of at-home sperm testing kits.

BACKGROUND: Despite the generally accepted World Health Organization guidelines on semen analysis, an individual's results can display significant variation when performed across time or in different laboratories. Semen parameters are in fact highly variable measures that can differ significantly between various analyses. Numerous researchers have discovered a wide range of semen parameters within each individual male, but only a few studies included the analysis of semen parameters variability in patients with infertility. The aim of this study was to evaluate the inter- and intra-individual variability of semen parameters in men of reproductive age with normozoospermia and those with oligozoospermia. METHODS: Five hundred and thirteen who provided ≥ 2 semen samples (798 samples in total) using an at-home mail-in kit over a period of about 2 years were enrolled in the study. Semen samples collection using Give Legacy at-home mail-in semen collection kit; semen analysis at a CLIA-certified laboratory. RESULTS: The degree of intra-subject variation across all semen parameters was lower in men with normozoospermia compared to men with oligozoospermia. Men with normozoospermia furthermore demonstrated a level of intra-subject variation that was lower than inter-subject variation across all measured parameters. No association was observed between intra-subject coefficients of variation in any of the semen parameters, including sperm concentration, sperm count, motile sperm count, total motility, progressive motility, the percentage of sperm with normal morphology, and the age, duration of abstinence, and BMI of the men. CONCLUSION: The results of this observational study confirm the significant variability in semen parameters in men with normozoospermia and oligozoospermia, as measured from at-home semen collection kit samples. This further underscore the importance of securing multiple samples for analysis to provide a robust assessment of male fertility.

Physical activity and the risk of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related mortality in South Korea: a nationwide cohort study.

PURPOSE: To determine the potential associations between physical activity and risk of SARS-CoV-2 infection, severe illness from COVID-19 and COVID-19 related death using a nationwide cohort from South Korea. METHODS: Data regarding 212 768 Korean adults (age ≥20 years), who tested for SARS-CoV-2, from 1 January 2020 to 30 May 2020, were obtained from the National Health Insurance Service of South Korea and further linked with the national general health examination from 1 January 2018 to 31 December 2019 to assess physical activity levels. SARS-CoV-2 positivity, severe COVID-19 illness and COVID-19 related death were the main outcomes. The observation period was between 1 January 2020 and 31 July 2020. RESULTS: Out of 76 395 participants who completed the general health examination and were tested for SARS-CoV-2, 2295 (3.0%) were positive for SARS-CoV-2, 446 (0.58%) had severe illness from COVID-19 and 45 (0.059%) died from COVID-19. Adults who engaged in both aerobic and muscle strengthening activities according to the 2018 physical activity guidelines had a lower risk of SARS-CoV-2 infection (2.6% vs 3.1%; adjusted relative risk (aRR), 0.85; 95% CI 0.72 to 0.96), severe COVID-19 illness (0.35% vs 0.66%; aRR 0.42; 95% CI 0.19 to 0.91) and COVID-19 related death (0.02% vs 0.08%; aRR 0.24; 95% CI 0.05 to 0.99) than those who engaged in insufficient aerobic and muscle strengthening activities. Furthermore, the recommended range of metabolic equivalent task (MET; 500-1000 MET min/week) was associated with the maximum beneficial effect size for reduced risk of SARS-CoV-2 infection (aRR 0.78; 95% CI 0.66 to 0.92), severe COVID-19 illness (aRR 0.62; 95% CI 0.43 to 0.90) and COVID-19 related death (aRR 0.17; 95% CI 0.07 to 0.98). Similar patterns of association were observed in different sensitivity analyses. CONCLUSION: Adults who engaged in the recommended levels of physical activity were associated with a decreased likelihood of SARS-CoV-2 infection, severe COVID-19 illness and COVID-19 related death. Our findings suggest that engaging in physical activity has substantial public health value and demonstrates potential benefits to combat COVID-19.

The role of iron in mediating testosterone's effects on erythropoiesis in mice.

Testosterone stimulates iron-dependent erythropoiesis and suppresses hepcidin. To clarify the role of iron in mediating testosterone's effects on erythropoiesis, we induced iron deficiency in mice by feeding low iron diet. Iron-replete and iron-deficient mice were treated weekly with testosterone propionate or vehicle for 3 weeks. Testosterone treatment increased red cell count in iron-replete mice, but, surprisingly, testosterone reduced red cell count in iron-deficient mice. Splenic stress erythropoiesis was stimulated in iron-deficient mice relative to iron-replete mice, and further increased by testosterone treatment, as indicated by the increase in red pulp area, the number of nucleated erythroblasts, and expression levels of TfR1, GATA1, and other erythroid genes. Testosterone treatment of iron-deficient mice increased the ratio of early-to-late erythroblasts in the spleen and bone marrow, and serum LDH level, consistent with ineffective erythropoiesis. In iron-deficient mice, erythropoietin levels were higher but erythropoietin-regulated genes were generally downregulated relative to iron-replete mice, suggesting erythropoietin resistance. Conclusion: Testosterone treatment stimulates splenic stress erythropoiesis in iron-replete as well as iron-deficient mice. However, testosterone worsens anemia in iron-deficient mice because of ineffective erythropoiesis possibly due to erythropoietin resistance associated with iron deficiency. Iron plays an important role in mediating testosterone's effects on erythropoiesis.

The association of socioeconomic status with semen parameters in a cohort of men in the United States.

BACKGROUND: Socioeconomic differences are present within the population of men who experience infertility and seek treatment. OBJECTIVE: To study the association of socioeconomic status with semen parameters in a group of men using mail-in semen analyses. MATERIALS AND METHODS: The records of 11,134 men that used mail-in semen analyses from a fertility company were identified. Their demographic information, semen parameters, and ZIP codes were collected. Area deprivation index (ADI) was used as a proxy for socioeconomic status and was calculated for each individual using their ZIP codes in order to measure their level of socioeconomic deprivation. A higher ADI signifies a more deprived area. The association between ADI and the semen parameters of this group was measured using linear regression analysis adjusted for age. RESULTS: 11,134 men were included in the study with a median age of 35 years (interquartile range (IQR): 32-40) and a median ADI of 83 (IQR: 68-97). The cohort had a median sperm concentration of 31 million/mL (IQR: 14-59), median total sperm count of 123 million (IQR: 57-224), median total motile sperm of 35 million (IQR: 9-95), median total motility of 32% (IQR: 15-52), progressive motility of 22% (IQR: 9-38), and morphology percent normal of 4% (IQR: 2-7). Higher ADI, indicating lower socioeconomic status, was negatively associated with various semen parameters, including sperm concentration, total sperm count, total motile sperm, and total and progressive motility. DISCUSSION AND CONCLUSION: Men who live in more deprived areas are more likely to have worse semen parameters. Further research is needed to thoroughly examine the impact of socioeconomic status on male fertility. A comprehensive approach that targets upstream social, economic, and healthcare factors can possibly alleviate the negative association of socioeconomic status with fertility and semen parameters.

Driving Time and Compliance With Postvasectomy Semen Analysis Drop-Off.

OBJECTIVE: Current literature demonstrates low rates of compliance with postvasectomy semen analysis (PVSA). This study sought to determine factors that correlate with noncompliance with PVSA. METHODS: A retrospective chart review was conducted for patients who underwent vasectomy within our institution. ArcGIS was used to securely calculate the shortest driving time from each patient's home to the single PVSA drop-off site. Kruskal-Wallis and chi-square tests analyzed characteristics of patients who did and did not submit PVSA samples, and odds ratios were calculated via multivariable logistic regression. RESULTS: Overall, 515 of 850 patients met inclusion criteria and 219 (42.5%) of these had no recorded PVSA. Of those with a PVSA, 59% were completed within 16 weeks. Compliance with PVSA was associated with a shorter median driving time (30.6 minutes vs 34.2 minutes), more vasectomy in the operating room (19% vs 10%), and attending a follow-up appointment (40% vs 17%) (P < .005 for all). Age at vasectomy, race, ethnicity, BMI, paternity, and location of preoperative consultation did not significantly differ between the groups. Each 30 minutes of driving time was associated with a 48% reduction in the odds of a patient submitting PVSA at any time (OR 0.52 [0.37, 0.73]). CONCLUSION: As driving time to a drop-off center appears to be a significant barrier to PVSA compliance, providers should consider alternative collection methods such as at-home or in-office semen analysis.

Uncovering the interhospital price variations for vasectomies in the United States.

Due to the historic lack of transparency in healthcare pricing in the United States, the degree of price variation for vasectomy is largely unknown. Our study aims to assess characteristics of hospitals reporting prices for vasectomy as well as price variation associated with hospital factors and insurance status. A cross-sectional analysis was performed in October, 2022 using the Turquoise Database which compiles publicly available hospital pricing data. The database was queried for vasectomy prices to identify the cash (paid by patients not using insurance), commercial (negotiated by private insurers) and Medicare and Medicaid prices for vasectomies. Hospital characteristics of those that reported a price for vasectomy and those that did not were compared and pricing differences based on hospital ownership and reimbursement source were determined using multivariable linear regression analysis. Overall, only 24.7% (1657/6700) of hospitals reported a price for vasectomy. Those that reported a price had more beds (median 117 vs 80, p < 0.001), more physicians (median 1745 vs 1275, p < 0.001). They were also more likely to be nonprofit hospitals (77% vs 14%, p < 0.001) and to be in well-resourced areas (ADI 91.7 vs 94.4, p < 0.001). Both commercial prices and cash prices for vasectomy were lower at nonprofit hospitals than at for-profit hospitals (commercial: $1959.47 vs $2861.56, p < 0.001; cash: $1429.74 vs $3185.37, p < 0.001). Our study highlights the current state of pricing transparency for vasectomy in the United States. Patients may be counseled to consider seeking vasectomy at a nonprofit hospital to reduce their costs, especially when paying with cash. These findings also suggest a need for new policies to target areas with decreased price transparency to reduce price disparities.

The Racial and Socioeconomic Characteristics of Men Using Mail-in Semen Testing Kits in the United States.

OBJECTIVE: To describe the racial and socioeconomic characteristics of men using mail-in semen testing kits for their fertility care in the United States over 3 years. METHODS: A cross-sectional analysis was conducted of men who used mail-in semen analyses from a single direct-to-consumer (DTC) fertility platform between 2020 and 2022. Age, race/ethnicity, place of residence, and education level of men using mail-in semen analysis kits was collected from user questionnaires. Zip code level socioeconomic status was estimated using the Area Deprivation Index (ADI). These characteristics were compared to the overall population of the United States. RESULTS: 4342 men used mail-in semen analyses from a single DTC fertility company between 2020 and 2022 and completed the questionnaire. The median age of this cohort was 36 (IQR: 32,40) years. The group consisted of predominantly white men (72%), with 7.9% Asian and only 5.1% Black, 3.2% Hispanic, 0.4% Indian American, 0.1% pacific islander, 5.8% mixed race, and 2.8% other groups. 45.8% of the group had completed college, 22% had a master's degree, and 9% had a doctoral degree. The mean ADI was 83.47 (SD 21.44) compared to the average ADI of 100 for the general US population (P < .005). CONCLUSION: DTC mail-in semen analyses have the potential to improve access to affordable fertility care. Racial and ethnic minorities and lower socioeconomic classes are underrepresented for men seeking DTC fertility testing as they are for men presenting for in-office fertility care. Additional studies are needed to determine the factors responsible for these discrepancies.

The Variability of Semen Parameters With Sexual Abstinence Using Mail-in Sperm Testing Is Similar to That Seen With Traditional In-Office Semen Analysis.

The impact of ejaculatory abstinence on semen parameters using in-office semen analyses has been well-established; however, their variability has not been evaluated in men using mail-in semen analysis kits. Our study aims to describe how the sperm parameters using mail-in semen analysis tests change with abstinence and validate their equivalence to those seen with in-office semen analysis tests. We retrospectively reviewed the semen analysis results of men using mail-in semen analysis tests provided by Give Legacy, Inc (Legacy) facilities from 2019 to 2021. We collected their demographic information, abstinence duration, and semen parameters (conventional and kinematic) from their records. Semen samples were categorized as normozoospermic and oligozoospermic based on concentration. The shape of the relationship between abstinence duration and semen parameters was assessed via generalized additive models. We have collected 3,469 unique samples provided by 2,609 (75%) normozoospermic men and 860 (25%) oligozoospermic from all over the United States. In normozoospermic men, longer periods of sexual abstinence were linked to higher levels of sperm concentration, total sperm count, and total motile sperm. However, there was a decline in both total and progressive motility. Conversely, in oligozoospermic men, extended periods of abstinence led to a rapid decline in total motile sperm, as well as total and progressive motility. There was no significant correlation observed between sexual abstinence and variations in sperm morphology. Our study shows that variability of sperm parameters with abstinence, as measured through mail-in semen analysis tests, is comparable to the patterns observed with conventional in-office sperm testing.

Impact and Implications of the COVID-19 Pandemic on Urological Training.

INTRODUCTION: COVID-19 has forever impacted health care in the U.S. Changes to health and hospital policies led to disruptions to both patient care and medical training. There is limited understanding of the impact on urology resident training across the U.S. Our aim was to examine trends in urological procedures, as captured by the Accreditation Council for Graduate Medical Education resident case logs, throughout the COVID-19 pandemic. METHODS: Retrospective review of publicly available urology resident case logs between July 2015 and June 2021 was performed. Average case numbers were analyzed via linear regression with different models specifying different assumptions regarding the impact of COVID-19 on procedure in 2020 and onward. Statistical calculations utilized R (version 4.0.2). RESULTS: Analysis favored models which assumed the impact of COVID-related disruptions were specific to 2019-2020. Analysis of procedures performed indicate an average upward trend of urology cases nationally. An average annual increase of 26 procedures between 2016 and 2021 was noted, except for 2020 which saw an average drop of approximately 67 cases. However, in 2021 case volume dramatically increased to the same rate as projected had there not been a disruption in 2020. Stratifying by category of urology procedure revealed evidence for variability between categories in the magnitude of the 2020 decrease. CONCLUSIONS: Despite widespread pandemic-related disruptions in surgical care, urological volume has rebounded and increased, likely having minimal detriment to urological training over time. Urological care is essential and in high demand as evidenced by the uptick in volume across the U.S.

Cardiovascular events and safety outcomes associated with remdesivir using a World Health Organization international pharmacovigilance database.

On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.

Evaluating the quality of reported outcomes for microsurgical TESE in men with non-obstructive azoospermia: A methodological analysis.

BACKGROUND: Publications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices. OBJECTIVE: To study the quality and heterogeneity of published mTESE outcomes via a methodological analysis. MATERIALS/METHODS: A systematic methodological analysis of all published literature on the use of mTESE in men with non-obstructive azoospermia from 1999 to the July 2020 was performed. PubMed and MEDLINE searches were performed using the search terms "microdissection TESE OR microsurgical TESE." Publications were evaluated on their reporting of pre-operative factors, intraoperative techniques, surgical and clinical outcomes, and adverse events. RESULTS: Fifty-five studies met inclusion criteria. Surgical technique and sperm retrieval rates were the most reported criteria. Reporting on the presence of an embryologist intraoperatively was observed in approximately 30% of articles, while other procedural details including method of sperm quantification, quantity retrieved, and number of cryopreserved vials were observed in fewer than 10% of articles. Clinical outcomes, including pregnancy rates and live birth rates, were reported in fewer than 40% of the articles. Fetal outcomes including fetal and neonatal anomalies were rarely reported. Fetal growth restriction, preterm delivery, small or large for gestational age, and NICU admissions were never reported. CONCLUSION: There are inconsistencies in reporting quality of mTESE outcomes, specifically a lack of information on the quantity and quality of sperm retrieved, the role of embryology intraoperatively, and clinical outcomes, such as live birth rate and fetal anomalies. These gaps may guide development of standardized reporting guidelines to better assess and compare clinical outcomes across institutions and maintain focus on couples-centric fertility outcomes in future mTESE studies.

Inability to obtain sperm for fresh IVF cycles: analysis and incidence of outcomes using a database from the United States.

BACKGROUND: Azoospermia is present in 10% of men presenting with infertility and surgical sperm retrieval rates for men with azoospermia due to spermatogenic dysfunction remain low. We investigated the incidence of failed fresh IVF cycles due to inability to obtain sperm and describe predictors for subsequent IVF. METHODS: A national IVF database was used to identify fresh IVF cycles in which there was failure to obtain sperm. Patient linkage was utilized to determine outcomes of subsequent IVF. RESULTS: 243,291 fresh IVF cycles were identified; 719 (0.3%) listed "inability to obtain sperm" as reason for embryo non-transfer. Male infertility was a factor in 537 (75%) and ejaculation was the most common anticipated sperm source (414, 57%). 713 (99.2%) cycles resulted in retrieved oocytes, but only 627 (87.2%) cryopreserved oocytes. 265 (37%) of couples underwent subsequent IVF. On multivariable analysis, lack of initial oocyte cryopreservation (OR 0.34, p = 0.01) and male infertility (OR 0.14, p = 0.01) were associated with having no subsequent cycles. Partner sperm was used in 213 (80%) second cycles and sperm retrieval method was largely conserved (181/213, 85%). Embryos were transferred in 186 (70%) second cycles. Failed embryo transfers were due to repeat inability to obtain sperm in 5 (6%) cycles. CONCLUSIONS: Failure to obtain sperm during fresh IVF is rare, but most affected couples will not pursue further cycles of IVF after their initial failed attempt.

The acute scrotum: Frequency and range of etiologies in a Middle Eastern setting.

AIM: To investigate the frequency of different etiologies of acute scrotal pain in males presenting to the emergency department at American University of Beirut Medical Center in Beirut, Lebanon. MATERIALS AND METHODS: In all, 94 patients between the ages 18 and 40 years presenting to the emergency room at American University of Beirut Medical Center with acute scrotum were recruited. The scrotum was inspected with palpation, and Doppler Ultrasound of the testicle was performed by a radiology resident to confirm the diagnosis. The study results were then collected after the official reports were signed by a board-certified radiology attending with expertise in ultrasound. RESULTS: Of the 94 patients presenting with acute scrotal pain, 23.4% (95% confidence interval (0.70-0.87)) had no ultrasound findings and were considered normal. On the other hand, 54.3% (95% confidence interval (0.45-0.66)) were diagnosed with varicocele, 9.6% (95% confidence interval (0.04-0.16)) were diagnosed with epididymo-orchitis, and 9.6% (95% confidence interval (0.04-0.16)) had a history of trauma to the testicle. Patients presenting with acute scrotum had a pain duration of 13.2 ± 4.5 h, with 10.6% (95% confidence interval (0.04-0.17)) having associated urinary symptoms, 18.1% (95% confidence interval (0.09-0.25)) have had sexual activity within 48 h of presentation, and 10.6% (95% confidence interval (0.04-0.17)) were pre-diagnosed with varicocele. CONCLUSION: Varicocele is the most common cause of acute scrotal pain in patients presenting to American University of Beirut Medical Center in Beirut. This should direct varicocele to the top of our differential when a patient with acute scrotum presents to the emergency department. Nevertheless, ruling out torsion remains the first step in the workup.

COVID-19 and Adverse Pregnancy Outcome: A Systematic Review of 104 Cases.

(1) Background: Until now, several reports about pregnant women with confirmed coronavirus disease 2019 (COVID-19) have been published. However, there are no comprehensive systematic reviews collecting all case series studies on data regarding adverse pregnancy outcomes, especially association with treatment modalities. (2) Objective: We aimed to synthesize the most up-to-date and relevant available evidence on the outcomes of pregnant women with laboratory-confirmed infection with COVID-19. (3) Methods: PubMed, Scopus, MEDLINE, Google scholar, and Embase were explored for studies and papers regarding pregnant women with COVID-19, including obstetrical, perinatal, and neonatal outcomes and complications published from 1 January 2020 to 4 May 2020. Systematic review and search of the published literature was done using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). (4) Results: In total, 11 case series studies comprising 104 pregnant women with COVID-19 were included in our review. Fever (58.6%) and cough (30.7%) were the most common symptoms. Other symptoms included dyspnea (14.4%), chest discomfort (3.9%), sputum production (1.0%), sore throat (2.9%), and nasal obstruction (1.0%). Fifty-two patients (50.0%) eventually demonstrated abnormal chest CT, and of those with ground glass opacity (GGO), 23 (22.1%) were bilateral and 10 (9.6%) were unilateral. The most common treatment for COVID-19 was administration of antibiotics (25.9%) followed by antivirals (17.3%). Cesarean section was the mode of delivery for half of the women (50.0%), although no information was available for 28.8% of the cases. Regarding obstetrical and neonatal outcomes, fetal distress (13.5%), pre-labor rupture of membranes (9.6%), prematurity (8.7%), fetal death (4.8%), and abortion (2.9%) were reported. There are no positive results of neonatal infection by RT-PCR. (5) Conclusions: Although we have found that pregnancy with COVID-19 has significantly higher maternal mortality ratio compared to that of pregnancy without the disease, the evidence is too weak to state that COVID-19 results in poorer maternal outcome due to multiple factors. The number of COVID-19 pregnancy outcomes was not large enough to draw a conclusion and long-term outcomes are yet to be determined as the pandemic is still unfolding. Active and intensive follow-up is needed in order to provide robust data for future studies.

Peripubertal serum concentrations of organochlorine pesticides and semen parameters in Russian young men.

BACKGROUND: Epidemiologic literature on the relation of organochlorine pesticides (OCPs) with semen quality among adult men has been inconclusive, and no studies have prospectively explored the association between peripubertal serum OCPs and semen parameters in young men. OBJECTIVE: To evaluate prospective associations of peripubertal serum concentrations of hexachlorobenzene (HCB), ß-hexachlorocylohexane (ß-HCH), and p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE) with semen parameters among young Russian men. METHODS: This prospective cohort study included 152 young men who enrolled in the Russian Children's Study (2003-2005) at age 8-9 years and were followed annually until young adulthood. HCB, ß-HCH, and p,p'-DDE concentrations were measured at the CDC by mass spectrometry in serum collected at enrollment. Between 18 and 23 years, semen samples (n = 298) were provided for analysis of volume, concentration, and progressive motility; we also calculated total sperm count and total progressive motile count. Linear mixed models were used to examine the longitudinal associations of quartiles of serum HCB, ß-HCH and p,p'-DDE with semen parameters, adjusting for total serum lipids, body mass index, smoking, abstinence time and baseline dietary macronutrient intake. RESULTS: Lipid-adjusted medians (IQR) for serum HCB, ßHCH and p,p-DDE, respectively, were 150 ng/g lipid (102-243), 172 ng/g lipid (120-257) and 275 ng/g lipid (190-465). In adjusted models, we observed lower ejaculated volume with higher serum concentrations of HCB and ßHCH, along with reduced progressive motility with higher concentrations of ßHCH andp,p-DDE. Men in the highest quartile of serum HCB had a mean (95% Confidence Interval, CI) ejaculated volume of 2.25 mL (1.89, 2.60), as compared to those in the lowest quartile with a mean (95% CI) of 2.97 mL (2.46, 3.49) (p = 0.03). Also, men in the highest quartile of serum p,p-DDE had a mean (95% CI) progressive motility of 51.1% (48.6, 53.7), as compared to those in the lowest quartile with a mean (95% CI) of 55.1% (51.7, 58.5) (p = 0.07). CONCLUSION: In this longitudinal Russian cohort study, peripubertal serum concentrations of selected OCPs were associated with lower ejaculated volume and progressive motility highlighting the importance of the peripubertal window when evaluating chemical exposures in relation to semen quality.