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With the budding interest in testosterone therapy (TTh), online health information plays a significant role in patients' health care decisions. Therefore, we evaluated the source and readability of web-based information available to patients regarding TTh on Google. From Google search terms "Testosterone Therapy" and "Testosterone Replacement", 77 unique sources were identified. Sources were categorized as Academic, Commercial, Institutional, or Patient Support, then evaluated using validated readability and English language text assessment tools: the Flesch Reading Ease score, Flesch Kincade, Gunning Fog, Simple Measure of Gobbledygook (SMOG), Coleman-Liau Index and Automated Readability index. The average grade level for understanding academic sources was 16 (college senior); commercial, institutional, and patient support sources were 13 (college freshman); 8 and 5 grade levels, respectively, above the average U.S. adult. Patient support sources were most prevalent, while commercial sources were the least at 35 and 14%, respectively. The average reading ease score was 36.8, indicative of difficult-to-read material overall. These results indicate that the most immediate online sources for TTh information exceed the average reading level of most adults within the U.S., hence more effort should be taken to publish accessible and readable material to improve patient health literacy., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Non-obstructive azoospermia (NOA) is a common, but complex problem, with multiple therapeutic options and a lack of clear guidelines. Hence, there is considerable controversy and marked variation in the management of NOA. This survey evaluates contemporary global practices related to medical and surgical management for patients with NOA., Materials and Methods: A 56-question online survey covering various aspects of the evaluation and management of NOA was sent to specialists around the globe. This paper analyzes the results of the second half of the survey dealing with the management of NOA. Results have been compared to current guidelines, and expert recommendations have been provided using a Delphi process., Results: Participants from 49 countries submitted 336 valid responses. Hormonal therapy for 3 to 6 months was suggested before surgical sperm retrieval (SSR) by 29.6% and 23.6% of participants for normogonadotropic hypogonadism and hypergonadotropic hypogonadism respectively. The SSR rate was reported as 50.0% by 26.0% to 50.0% of participants. Interestingly, 46.0% reported successful SSR in <10% of men with Klinefelter syndrome and 41.3% routinely recommended preimplantation genetic testing. Varicocele repair prior to SSR is recommended by 57.7%. Half of the respondents (57.4%) reported using ultrasound to identify the most vascularized areas in the testis for SSR. One-third proceed directly to microdissection testicular sperm extraction (mTESE) in every case of NOA while others use a staged approach. After a failed conventional TESE, 23.8% wait for 3 months, while 33.1% wait for 6 months before proceeding to mTESE. The cut-off of follicle-stimulating hormone for positive SSR was reported to be 12-19 IU/mL by 22.5% of participants and 20-40 IU/mL by 27.8%, while 31.8% reported no upper limit., Conclusions: This is the largest survey to date on the real-world medical and surgical management of NOA by reproductive experts. It demonstrates a diverse practice pattern and highlights the need for evidence-based international consensus guidelines., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations., Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 countries were analyzed descriptively, with a Delphi process used for expert recommendations., Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoospermia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differentiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate., Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA)., Materials and Methods: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD)., Results: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%)., Conclusions: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Objective: To determine the most financially optimal surgical approach for testicular sperm retrieval for men with non-obstructive azoospermia., Design: A decision tree was created examining five potential surgical approaches for men with non-obstructive azoospermia pursuing one cycle of intracytoplasmic sperm injection. An expected financial net loss was determined for each surgical option based on couples' willingness to pay for one cycle of intracytoplasmic sperm injection resulting in pregnancy. The branch with the lowest expected net loss was defined as the most optimal financial decision (minimizing loss to a couple). Fresh testicular sperm extraction implied testicular sperm extraction was performed in conjunction with programmed ovulation induction. Frozen testicular sperm extraction implied testicular sperm extraction was performed initially, and ovulation induction/intracytoplasmic sperm injection was canceled if sperm retrieval failed.  The surgical options included fresh conventional testicular sperm extraction, with and without "back-up" sperm cryopreservation, fresh microsurgical testicular sperm extraction, with and without "back-up" sperm cryopreservation, and frozen microsurgical testicular sperm extraction. Success was defined as pregnancy after one intracytoplasmic sperm injection cycle., Materials and Methods: Probabilities of successful sperm retrieval with conventional testicular sperm extraction/microsurgical testicular sperm extraction, post-thaw sperm cellular loss following frozen microsurgical testicular sperm extraction, ovulation induction/intracytoplasmic sperm injection cycle out-of-pocket costs, intracytoplasmic sperm injection pregnancy rates for men with non-obstructive azoospermia, standard conventional testicular sperm extraction cost and average willingness to pay for intracytoplasmic sperm injection cycle were gathered from the systematic literature review. Costs were in USD and adjusted to inflation (as of April 2020). Two-way sensitivity analysis was performed on varying couples' willingness to pay for one cycle of intracytoplasmic sperm injection and varying microsurgical testicular sperm extraction out-of-pocket costs., Results: According to our decision tree analysis (assuming minimum microsurgical testicular sperm extraction cost of $1,000 and willingness to pay of $8,000), the expected net loss for each branch was as follows: -$17,545 for fresh conventional testicular sperm extraction, -$17,523 for fresh microsurgical testicular sperm extraction, -$9,624 for frozen microsurgical testicular sperm extraction, -$17,991 for fresh conventional testicular sperm extraction with "backup", and -$18,210 for fresh microsurgical testicular sperm extraction with "backup". Two-way sensitivity analysis with a variable willingness to pay values and microsurgical testicular sperm extraction and in-vitro fertilization costs confirmed that frozen microsurgical testicular sperm extraction consistently presented the lowest net loss compared to other options. Interestingly, when directly comparing fresh microsurgical testicular sperm extraction and conventional testicular sperm extraction with "back-up", scenarios with decreasing willingness to pay and lower microsurgical testicular sperm extraction costs demonstrated fresh conventional testicular sperm extraction with "back-up" as more optimal than fresh microsurgical testicular sperm extraction with "back-up"., Conclusions: For those couples who must pay out of pocket, our study suggests that frozen microsurgical testicular sperm extraction is the most financially optimal decision for the surgical management of non-obstructive azoospermia, regardless of microsurgical testicular sperm extraction cost and the couple's willingness to pay., (© 2023 American Society of Andrology and European Academy of Andrology.)

Purpose: The purpose of this meta-analysis is to study the impact of varicocele repair in the largest cohort of infertile males with clinical varicocele by including all available studies, with no language restrictions, comparing intra-person conventional semen parameters before and after the repair of varicoceles., Materials and Methods: The meta-analysis was performed according to PRISMA-P and MOOSE guidelines. A systematic search was performed in Scopus, PubMed, Cochrane, and Embase databases. Eligible studies were selected according to the PICOS model (Population: infertile male patients with clinical varicocele; Intervention: varicocele repair; Comparison: intra-person before-after varicocele repair; Outcome: conventional semen parameters; Study type: randomized controlled trials [RCTs], observational and case-control studies)., Results: Out of 1,632 screened abstracts, 351 articles (23 RCTs, 292 observational, and 36 case-control studies) were included in the quantitative analysis. The before-and-after analysis showed significant improvements in all semen parameters after varicocele repair (except sperm vitality); semen volume: standardized mean difference (SMD) 0.203, 95% CI: 0.129-0.278; p<0.001; I²=83.62%, Egger's p=0.3329; sperm concentration: SMD 1.590, 95% CI: 1.474-1.706; p<0.001; I²=97.86%, Egger's p<0.0001; total sperm count: SMD 1.824, 95% CI: 1.526-2.121; p<0.001; I²=97.88%, Egger's p=0.0063; total motile sperm count: SMD 1.643, 95% CI: 1.318-1.968; p<0.001; I²=98.65%, Egger's p=0.0003; progressive sperm motility: SMD 1.845, 95% CI: 1.537%-2.153%; p<0.001; I²=98.97%, Egger's p<0.0001; total sperm motility: SMD 1.613, 95% CI 1.467%-1.759%; p<0.001; l2=97.98%, Egger's p<0.001; sperm morphology: SMD 1.066, 95% CI 0.992%-1.211%; p<0.001; I²=97.87%, Egger's p=0.1864., Conclusions: The current meta-analysis is the largest to date using paired analysis on varicocele patients. In the current meta-analysis, almost all conventional semen parameters improved significantly following varicocele repair in infertile patients with clinical varicocele., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to the use of SDF assays and investigate the barriers and limitations that clinicians face in incorporating these tests into their practice., Materials and Methods: Clinicians managing male infertility were invited to complete an online survey on practices related to SDF diagnostic and treatment approaches. Their responses related to the technical aspects of SDF testing, current professional society guidelines, and the literature were used to generate expert recommendations via the Delphi method. Finally, challenges related to SDF that the clinicians encounter in their daily practice were captured., Results: The survey was completed by 436 reproductive clinicians. Overall, terminal deoxynucleotidyl transferase deoxyuridine triphosphate Nick-End Labeling (TUNEL) is the most commonly used assay chosen by 28.6%, followed by the sperm chromatin structure assay (24.1%), and the sperm chromatin dispersion (19.1%). The choice of the assay was largely influenced by availability (70% of respondents). A threshold of 30% was the most selected cut-off value for elevated SDF by 33.7% of clinicians. Of respondents, 53.6% recommend SDF testing after 3 to 5 days of abstinence. Although 75.3% believe SDF testing can provide an explanation for many unknown causes of infertility, the main limiting factors selected by respondents are a lack of professional society guideline recommendations (62.7%) and an absence of globally accepted references for SDF interpretation (50.3%)., Conclusions: This study represents the largest global survey on the technical aspects of SDF testing as well as the barriers encountered by clinicians. Unified global recommendations regarding clinician implementation and standard laboratory interpretation of SDF testing are crucial., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such as machine learning, artificial neural networks, and deep learning, have shown great potential in andrology and reproductive medicine. AI-based tools are poised to become valuable assets with abilities to support and aid in diagnosing and treating male infertility, and in improving the accuracy of patient care. These automated, AI-based predictions may offer consistency and efficiency in terms of time and cost in infertility research and clinical management. In andrology and reproductive medicine, AI has been used for objective sperm, oocyte, and embryo selection, prediction of surgical outcomes, cost-effective assessment, development of robotic surgery, and clinical decision-making systems. In the future, better integration and implementation of AI into medicine will undoubtedly lead to pioneering evidence-based breakthroughs and the reshaping of andrology and reproductive medicine., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: To evaluate the relationship between regional geography and sperm parameters in a cohort of American men using at-home mail-in semen collection kits with no previous self-reported history of male factor infertility., Materials and Methods: In this study, 5,822 men from six different regions of the United States (Northeast, Southeast, Midwest, West, Pacific, and Southwest) who self-requested semen analysis between 2019 and 2021 were enrolled., Results: Across the entire cohort, the mean sperm concentration was 43.79±55.43 ×10 6 sperm/mL; total sperm count 138.93±149.96 ×10 6 sperm/mL; total motile sperm 54.73±81.90 ×10 6 /ejaculate; total motility 30.18%±22.87%; progressive motility 21.61%±17.32%; sperm with normal morphology 8.79%±8.87%. Patients from the West region displayed lower median sperm concentration, total motile sperm, and total motility than men from the other four regional areas. A lower median total sperm count, and lower median progressive motility were also detected among patients in the Southwest region. Conversely, higher results were detected in patients from the Midwest (higher median total motile sperm, total and motility) and from the Northeast (higher median sperm concentration and total sperm count) regions. Men from the Southeast (OR, 1.3168; 95% CI, 1.1142-1.5563) and Southwest (OR, 1.3145; 95% CI, 1.0735-1.6096) regions were more likely to have oligozoospermia than those living elsewhere., Conclusions: This study provides the most comprehensive and up-to-date report on semen parameter variability among a cohort of men living in six different regions of the continental USA. This study will pave the way into a deeper discussion of the interplay between geography, social determinants of fertility care and semen quality., Competing Interests: Yana Aznavour, Jad Badreddine and Stephen Rhodes have no financial and personal relationships to disclose. Ramy Abou Ghayda, Felipe Navarrete, Vrushab Gowda, and Paul Simon are the Chief Medical Officer, Head of Research and Development, Head of Regulatory Affairs, and VP of Operations at Give Legacy, Inc, respectively. The authors declare that they have no competing interests regarding to the research described in this paper. They did not receive any additional funding, or financial or non-financial gains associated with this research. GiveLegacy, Inc. did not intervene nor influence the design, outcomes, materials, methods, or results of this manuscript. There is no direct or indirect gain for GiveLegacy, Inc. in relation to the publication of this study., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition., Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method., Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4-6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated., Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Patients may turn to social media websites, such as Reddit, for information on erectile dysfunction prior to seeking care from a physician. We sought to identify, characterize, and assess the quality of the erectile dysfunction treatments discussed on the highly influential Reddit website. We assessed 2634 comments from two subreddits, r/AskMen and r/ErectileDysfunction, for positive and negative statements regarding treatments for erectile dysfunction. A total of 45 unique treatments were discussed and consisted of changes in sexual behavior (30%), lifestyle changes (29%), medical interventions (23%), talking with a partner about ED (10%), and use of supplements (8%). Only 24.4% of all treatments discussed are in line with current American Urological Association guidelines. Only 43.8% of all positive statements made endorsed a guidelines-based treatment, indicating a high rate of self-proclaimed success with alternative therapies. Our results indicate that there is active discussion of erectile dysfunction treatment on Reddit with a wide range of therapies recommended, however, the majority of the recommendations are not supported by strong clinical evidence., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations., Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus., Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing., Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Melatonin is an endogenous indoleamine that has been shown to inhibit tumor growth in laboratory models of prostate cancer. Prostate cancer risk has additionally been associated with exogenous factors that interfere with normal pineal secretory activity, including aging, poor sleep, and artificial light at night. Therefore, we aim to expand on the important epidemiological evidence, and to review how melatonin can impede prostate cancer. More specifically, we describe the currently known mechanisms of melatonin-mediated oncostasis in prostate cancer, including those that relate to the indolamine's ability to modulate metabolic activity, cell cycle progression and proliferation, androgen signaling, angiogenesis, metastasis, immunity and oxidative cell status, apoptosis, genomic stability, neuroendocrine differentiation, and the circadian rhythm. The outlined evidence underscores the need for clinical trials to determine the efficacy of supplemental, adjunct, and adjuvant melatonin therapy for the prevention and treatment of prostate cancer.

Study Question: Are occupational factors associated with markers of testicular function among men attending a fertility center?, Summary Answer: Men working non-daytime/rotating shifts and those with physically demanding jobs have higher sperm concentration and total sperm count as well as higher estradiol and total testosterone concentrations., What Is Known Already: Semen quality has declined during recent decades and has been negatively correlated with higher risks of common chronic diseases and mortality, highlighting its public health importance beyond fertility and reproduction. While most of the previous epidemiology literature on male fertility has focused on environmental exposures, dietary factors, and other related variables, little attention has been paid to occupational factors., Study Design, Size, Duration: This observational study included 377 men who were male partners in couples seeking infertility treatment at a fertility center, who enrolled in the Environment and Reproductive Health (EARTH) study between 2005 and 2019., Participants/materials, Setting, Methods: Self-reported information on lifting/moving heavy objects, typical shift, and physical level of exertion at work was collected from a take-home questionnaire. Semen samples were analyzed following World Health Organization guidelines. Enzyme immunoassays were used to assess reproductive hormone concentrations. Linear regression models were used to evaluate the association between occupational factors and measures of testicular function, while adjusting for covariates such as age, BMI, education, race, smoking, and abstinence time, and accounting for multiple semen samples (mean = 2, min-max = 1-9) in analyses for semen parameters., Main Results and the Role of Chance: Men had a median (interquartile range) age of 36 (33, 39) years and were predominantly Caucasian (87%). Of the men who completed the survey, 12% reported often lifting or moving heavy objects at work, 6% reported heavy physical exertion at work, and 9% reported evening or rotating shifts. Men who reported often lifting or moving heavy objects at work had 46% higher sperm concentrations (P = 0.01) and 44% higher total counts (P = 0.01) compared with men who reported never lifting or moving heavy objects at work. Similar results were found for men working in rotating shifts compared to those in day shifts, as well as for men involved in heavy levels of physical exertion compared to those with light levels at work. We also found that men involved in heavy/moderate levels of physical exertion at work had higher circulating testosterone concentrations compared to those with lighter exertion (adjusted means of 515 and 427 ng/dl, respectively, P = 0.08), and men who often moved/lifted heavy objects at work had higher estradiol concentrations, compared to those who never did (adjusted means of 36.8 and 27.1 pg/ml, respectively, P = 0.07). Men working evening/rotating shifts had 24% higher testosterone (P = 0.04) and 45% higher estradiol concentrations (P = 0.01), compared to men working day shifts. No associations were observed for ejaculated volume, total motility, morphologically normal sperm, or serum FSH and LH concentrations., Limitations, Reasons for Caution: Due to our study design which recruited men from couples seeking fertility treatment, it may not be possible to generalize our findings to men from the general population. Also, as is the case of all studies based on self-reported questionnaires, measurement error and misclassification of the exposure are potential concerns., Wider Implications of the Findings: Physically demanding jobs and rotating or evening shift occupations may be associated with higher testicular function in men measured as higher sperm concentrations and counts as well as higher serum testosterone and estradiol levels. Confirmation of these findings in other non-fertility clinic study populations is warranted., Study Funding/competing Interest(s): NIH grants R01ES022955, R01ES009718, R01ES033651, and R01ES000002 from the National Institute of Environmental Health Sciences (NIEHS) and Legacy, Inc. R.A.G. works part time for Legacy, Inc., which provided funds to perform this analysis. There are no other conflicts of interest., Trial Registration Number: N/A., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with an increasing prevalence of male infertility. This suggests an urgent need to implement further basic and clinical research in Andrology. Andrology developed as a branch of urology, gynecology, endocrinology, and, dermatology. The first scientific journal devoted to andrological sciences was founded in 1969. Since then, despite great advancements, andrology has encountered several obstacles in its growth. In fact, for cultural reasons, the male partner has often been neglected in the diagnostic and therapeutic workup of the infertile couple. Furthermore, the development of assisted reproductive techniques (ART) has driven a strong impression that this biotechnology can overcome all forms of infertility, with a common belief that having a spermatozoon from a male partner (a sort of sperm donor) is all that is needed to achieve pregnancy. However, clinical practice has shown that the quality of the male gamete is important for a successful ART outcome. Furthermore, the safety of ART has been questioned because of the high prevalence of comorbidities in the offspring of ART conceptions compared to spontaneous conceptions. These issues have paved the way for more research and a greater understanding of the mechanisms of spermatogenesis and male infertility. Consequently, numerous discoveries have been made in the field of andrology, ranging from genetics to several "omics" technologies, oxidative stress and sperm DNA fragmentation, the sixth edition of the WHO manual, artificial intelligence, management of azoospermia, fertility in cancers survivors, artificial testis, 3D printing, gene engineering, stem cells therapy for spermatogenesis, and reconstructive microsurgery and seminal microbiome. Nevertheless, as many cases of male infertility remain idiopathic, further studies are required to improve the clinical management of infertile males. A multidisciplinary strategy involving both clinicians and scientists in basic, translational, and clinical research is the core principle that will allow andrology to overcome its limits and reach further goals. This state-of-the-art article aims to present a historical review of andrology, and, particularly, male infertility, from its "Middle Ages" to its "Renaissance", a golden age of andrology., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

The recently emerged novel coronavirus, "severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)," caused a highly contagious disease called coronavirus disease 2019 (COVID-19). It has severely damaged the world's most developed countries and has turned into a major threat for low- and middle-income countries. Since its emergence in late 2019, medical interventions have been substantial, and most countries relied on public health measures collectively known as nonpharmaceutical interventions (NPIs). We aimed to centralize the accumulative knowledge of NPIs against COVID-19 for each country under one worldwide consortium. International COVID-19 Research Network collaborators developed a cross-sectional online survey to assess the implications of NPIs and sanitary supply on the incidence and mortality of COVID-19. The survey was conducted between January 1 and February 1, 2021, and participants from 92 countries/territories completed it. The association between NPIs, sanitation supplies, and incidence and mortality were examined by multivariate regression, with the log-transformed value of population as an offset value. The majority of countries/territories applied several preventive strategies, including social distancing (100.0%), quarantine (100.0%), isolation (98.9%), and school closure (97.8%). Individual-level preventive measures such as personal hygiene (100.0%) and wearing facial masks (94.6% at hospitals; 93.5% at mass transportation; 91.3% in mass gathering facilities) were also frequently applied. Quarantine at a designated place was negatively associated with incidence and mortality compared to home quarantine. Isolation at a designated place was also associated with reduced mortality compared to home isolation. Recommendations to use sanitizer for personal hygiene reduced incidence compared to the recommendation to use soap. Deprivation of masks was associated with increased incidence. Higher incidence and mortality were found in countries/territories with higher economic levels. Mask deprivation was pervasive regardless of economic level. NPIs against COVID-19 such as using sanitizer, quarantine, and isolation can decrease the incidence and mortality of COVID-19., (© 2022 Wiley Periodicals LLC.)

Purpose: Seminal oxidative stress (OS) is a recognized factor potentially associated with male infertility, but the efficacy of antioxidant (AOX) therapy is controversial and there is no consensus on its utility. Primary outcomes of this study were to investigate the effect of AOX on spontaneous clinical pregnancy, live birth and miscarriage rates in male infertile patients. Secondary outcomes were conventional semen parameters, sperm DNA fragmentation (SDF) and seminal OS., Materials and Methods: Literature search was performed using Scopus, PubMed, Ovid, Embase, and Cochrane databases. Only randomized controlled trials (RCTs) were included and the meta-analysis was conducted according to PRISMA guidelines., Results: We assessed for eligibility 1,307 abstracts, and 45 RCTs were finally included, for a total of 4,332 infertile patients. We found a significantly higher pregnancy rate in patients treated with AOX compared to placebo-treated or untreated controls, without significant inter-study heterogeneity. No effects on live-birth or miscarriage rates were observed in four studies. A significantly higher sperm concentration, sperm progressive motility, sperm total motility, and normal sperm morphology was found in patients compared to controls. We found no effect on SDF in analysis of three eligible studies. Seminal levels of total antioxidant capacity were significantly higher, while seminal malondialdehyde acid was significantly lower in patients than controls. These results did not change after exclusion of studies performed following varicocele repair., Conclusions: The present analysis upgrades the level of evidence favoring a recommendation for using AOX in male infertility to improve the spontaneous pregnancy rate and the conventional sperm parameters. The failure to demonstrate an increase in live-birth rate, despite an increase in pregnancy rates, is due to the very few RCTs specifically assessing the impact of AOX on live-birth rate. Therefore, further RCTs assessing the impact of AOX on live-birth rate and miscarriage rate, and SDF will be helpful., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Purpose: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility., Materials and Methods: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field., Results: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available., Conclusions: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men., Competing Interests: The authors have nothing to disclose., (Copyright © 2023 Korean Society for Sexual Medicine and Andrology.)

Testosterone deficiency is known to affect men with increasing incidence throughout their lifespan. The clinical manifestations of testosterone deficiency, in turn, negatively impact men's quality of life and perception of overall health. The interaction of chronic systemic disease and androgen deficiency represent an area for potential intervention. Here, we explore the topic of testosterone deficiency amongst men with end-stage organ failure requiring transplantation in order to elucidate the underlying pathophysiology of androgen deficiency of chronic disease and discuss whether intervention, including testosterone replacement and organ transplantation, improve patients' outcomes and quality of life., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Direct-to-consumer telemedicine platforms have expanded their reach to include services for the evaluation and treatment of testosterone deficiency., Aim: We aim to (i) evaluate the treatment practices and costs associated with receiving testosterone therapy through direct-to-consumer telemedicine platforms; (ii) compare these practices to the American Urological Association guidelines; and (iii) compare the cost of receiving similar care at a tertiary center., Methods: Google was queried to identify telemedicine platforms offing testosterone therapy. Websites were analyzed for information regarding the initial consultation, initial laboratory evaluation, follow up, treatment monitoring regimen, and associated costs of receiving testosterone therapy. The costs for similar services at a tertiary care center were estimated using a single institution's online cost estimator for a patient with no insurance, private insurance, or Medicare., Outcomes: Evaluation and treatment practices of each platform were compared to the American Urological Association guidelines, and a cost analysis was completed for the cost of (i) undergoing an initial evaluation, and (ii) receiving 12 months of treatment through each platform and at a tertiary center., Results: Three online platforms met inclusion criteria: Hone, Regenex Health, and TRT Nation. The initial evaluation and follow up of patients on TTh were similar between the online platforms and practice guidelines. The costs of the initial consultation were lowest for the patient with Medicare at a tertiary center and via the telemedicine platforms. Conversely, the cost of 12 months of intramuscular testosterone treatment was highest via the telemedicine platforms, ranging from $1,586 to $4,200, as compared to the tertiary center, which ranged from $134.01 to $1,333.04 with varying insurance models. Costs of ongoing treatment with transdermal testosterone are similarly higher via DTC platforms., Clinical Implications: Patients with private insurance or Medicare should be counseled that ongoing treatment through telemedicine platforms will likely incur a greater cost than receiving such care at a tertiary center that can utilize insurance coverage., Strengths & Limitations: Practice and cost comparisons include accurate, up-to-date information based on each platform's website. Limitations include the analysis of only three telemedicine platforms, and the ability to describe only the information provided on each website. In addition, cost estimates for the tertiary center only include a single type of private and public insurance, limiting generalizability., Conclusion: This observational study indicates that direct-to-consumer telemedicine platforms are largely following practice guidelines in the evaluation and treatment of testosterone, however, there is a high cost associated with ongoing treatment. Jesse E, Sellke N, Rivero M-J, et al. Practice Comparison and Cost Analysis of Direct-to-Consumer Telemedicine Platforms Offering Testosterone Therapy. J Sex Med 2022;19:1608-1615., (Copyright © 2022 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.)

Aim: To prospectively investigate the associations of urinary phthalate metabolite concentrations measured at four time points spanning pubertal development with semen parameters in Russian men., Design: 516 boys were enrolled at ages 8-9 years (2003-2005) and followed annually., Methods: Urine samples were collected annually and pooled into four exposure windows [prepuberty, early puberty, late puberty and sexual maturity] based on physician assessed Tanner genitalia stages and testicular volume. Fifteen phthalate metabolites were quantified using isotope dilution HPLC-MS/MS at Moscow State University. We calculated molar sums (∑) of di-2-ethylhexyl phthalate (DEHP), di-isononyl phthalate (DiNP), di-isodecyl phthalate (DiDP) and anti-androgenic phthalate (AAP) metabolites. At sexual maturity (ages 18-19 years), the men provided 1-2 semen samples for analysis. We estimated the associations of quintiles of urinary ∑phthalate metabolites as well as mono-butyl phthalate (MnBP), mono-isobutyl phthalate (MiBP), and mono-benzyl phthalate (MBzP) at each pubertal window, with semen parameters by fitting generalized linear mixed models with random intercepts and adjusting for confounders., Results: A total of 223 men who provided semen samples had phthalates measured at one or more pubertal windows. Higher urinary concentrations of ∑DiNP metabolites during late puberty were related to poorer semen quality (men with the highest quintile of urinary ∑DiNP had 30% lower sperm concentration, 32% lower count and 30% lower progressive motile count, compared to men in the lowest quintile). Also, young men with higher urinary concentrations of MiBP metabolites in early puberty tended to have poorer semen quality. No associations were observed for ∑DEHP metabolites, ∑DiDP metabolites, ∑AAP, MBzP or MnBP metabolites with semen quality parameters., Conclusions: ∑DiNP metabolites measured during late puberty and MiBP metabolites at early puberty were related to poorer semen quality, highlighting the importance of considering specific windows of exposure when investigating chemical exposures in relation to measures of reproductive health in men., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Objective: The aim of this study is to compare the risk of venous thromboembolic events (VTE) between patients suspending and continuing estrogen therapy perioperatively, in male to female gender-affirming surgery (vaginoplasty)., Materials and Methods: The authors conducted a systematic review and meta-analysis of existing research on male to female gender-affirming study, which compared the risk of VTE among the usage of estrogen perioperatively., Results: A total of 209 studies were identified as potentially eligible among PubMed, Embase, and Cochrane library databases. Among the studies, 191 studies were excluded due to their abstract inappropriateness. Out of the remaining 18 studies, only 3 articles were eligible and were finally included. Meta-analysis was performed and showed odds ratio of 0.77 (95% CI: 0.04, 14.01)., Conclusions: Perioperative estrogen therapy does not increase VTE risk on male to female gender-affirming surgery. Therefore, estrogen therapy may be continued perioperatively in vaginoplasty. More prospective studies are needed.

Background: To date, no attempt has been made to collate literature on the relationship between the social environmental impact of COVID-19 and erectile dysfunction. The aim of this explorative review was to assess and compare the prevalence of erectile dysfunction (ED) in male healthcare workers and males during the COVID-19 pandemic., Methods: A systematic review of major databases from inception to February 2021 was conducted. Prevalence data were extracted, and a random-effects meta-analysis was undertaken., Outcomes: The pooled prevalence of ED amongst healthcare workers working in COVID-19 specific environments, and non-healthcare during the COVID-19 pandemic., Results: Of 52 initial studies, six were included for the final analysis. The pooled prevalence of ED in healthcare workers working in a COVID-19 environment was 63.6% (95% CI 20.3-92.3%), and in non-healthcare workers during the COVID-19 pandemic was 31.9% (95% CI 19.5-47.6%)., Conclusion: The prevalence of ED in healthcare workers working in COVID-19 environments was higher than representative samples and is of concern. Sexual health (and by extension, overall health), should be a priority when considering ways to care for this population. Considering the social environmental impact of COVID-19 on sexual health and in particular on ED, it is important to provide adequate psychological support systems and to promote quality of life with particular attention to sexual health., (© 2021. Italian Society of Endocrinology (SIE).)

Purpose: Ejaculatory dysfunction (EjD) and erectile dysfunction after cancer treatment are clinically important complications, but their exact prevalence by various kinds of cancer site and type of treatment is unknown. The aim of this systematic review and meta-analysis was to examine the available evidence and provide pooled estimates for prevalence of EjD and erectile dysfunction in relation to all cancer sites and identify characteristics associated with EjD in cancer patients., Materials and Methods: We performed a systematic review and meta-analysis of cross-sectional and case-control studies. We searched 4 electronic databases (Medline®, CINAHL, PsychInfo and Embase®) until July 22, 2020. All retrospective or prospective studies reporting the prevalence of EjD in male patients with cancer were included in this review. A random effects meta-analysis was conducted calculating prevalence proportions with 95% confidence intervals. Prevalence proportions were calculated for the incidences of EjD by cancer site and type of treatment., Results: A total of 64 studies (a total of 10,057 participants) were included for analysis. The most common cancer sites were bladder, colon, testis and rectum. The prevalence rates of EjD after surgical intervention ranged from 14.5% (95% CI 2.2-56.3) in colon cancer to 53.0% (95% CI 23.3-80.7) in bladder cancer. The prevalence rates of erectile dysfunction ranged from 6.8% (95% CI 0.8-39.1) in bladder cancer to 68.7% (95% CI 55.2-79.6) in cancer of the rectum., Conclusions: In a large study-level meta-analysis, we looked at a high prevalence of EjD and erectile dysfunction at various cancer sites and across different treatment types. Prospective studies of EjD and erectile dysfunction after various kinds of cancer treatments are warranted.

Background: There are no prospective studies on the association between multimorbidity and urinary incontinence (UI), while mediators in this association are unknown. Thus, we aimed to (i) investigate the longitudinal association between multimorbidity and UI in a large sample of Irish adults aged ≥50 years and (ii) investigate to what extent physical activity, polypharmacy, cognitive function, sleep problems, handgrip strength and disability mediate the association., Methods: Data on 5,946 adults aged ≥50 years old from the Irish Longitudinal Study on Aging were analysed. The baseline survey was conducted between 2009 and 2011 and follow-up after 2 years was conducted. Information on self-reported occurrence of UI in the past 12 months and lifetime diagnosis of 14 chronic conditions were obtained. Multivariable logistic regression and mediation analysis were conducted., Results: After adjustment for potential confounders, compared to having no chronic conditions at baseline, having three (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.30-2.48) and four or more (OR = 1.86; 95% CI = 1.32-2.60), chronic conditions were significantly associated with incident UI. Mediation analysis showed that polypharmacy, sleep problems and disability explained 22.7, 17.8 and 14.7% of the association between multimorbidity (i.e. two or more chronic conditions) and incident UI, respectively., Conclusion: A greater number of chronic conditions at baseline were associated with a higher risk for incident UI at 2-year follow-up among adults aged ≥50 years in Ireland. Considering the effects of different medications on UI and improving sleep quality and disability among people aged ≥50 years with multimorbidity may reduce the incidence of UI., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to other chemotherapeutics in EGFR-mutated NSCLC., Materials and Methods: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.gov were searched for articles or trials meeting the inclusion criteria. After filtering, 230 eligible studies were initially identified. Data extraction followed PRISMA and included outcomes were progression-free survival (PFS), overall survival (OS), and severe adverse events (SAEs). Direct and indirect meta-analyses were generated in the context of log-linear mixed-effects models, with fixed effects for each relative comparison and random effects for each study., Results: The results showed that EGFR-TKI therapy had improved PFS with a hazard ratio (HR) of 0.40 (95% CI: 0.36-0.44, p<0.001) compared to standard chemotherapy. Nevertheless, the EGFR-TKIs showed no benefit on OS (HR: 0.96, 95% CI: 0.83-1.10, p=0.556). In the analysis of adverse events, EGFR-TKIs had fewer SAEs than standard chemotherapy (HR: 0.29, 95% CI: 0.26-0.33, p<0.001)., Conclusions: Our systemic review indicates that EGFR-TKI therapy has improved PFS, and reduced SAEs compared to standard chemotherapy in advanced EGFR-mutated NSCLC.

Objective: Coronavirus disease 2019 (COVID-19) is a pandemic and leading cause of death. Beyond the deaths directly caused by the virus and the suicides related to the psychological response to the dramatic changes as socioeconomic related to the pandemic, there might also be suicides related to the inflammatory responses of the infection. Infection induces inflammation as a cytokine storm, and there is an increasing number of studies that report a relationship between infection and suicide., Materials and Methods: We searched the World Health Organization status report and the PubMed database for keywords (COVID-19, suicide, infection, inflammation, cytokines), and reviewed five cytokine pathways between suicide and inflammation using two meta-analyses and two observational studies starting from November 31, 2020, focusing on the relationship between suicide and inflammation by infection. First, we discussed existing evidence explaining the relationship between suicidal behaviors and inflammation. Second, we summarized the inflammatory features found in COVID-19 patients. Finally, we highlight the potential for these factors to affect the risk of suicide in COVID-19 patients., Results: Patients infected with COVID-19 have high amounts of IL-1β, IFN-γ, IP10, and MCP1, which may lead to Th1 cell response activation. Also, Th2 cytokines (e.g., IL-4 and IL-10) were increased in COVID-19 infection. In COVID-19 patients, neurological conditions, like headache, dizziness, ataxia, seizures, and others have been observed., Conclusions: COVID-19 pandemic can serve as a significant environmental factor contributing directly to increased suicide risk; the role of inflammation by an infection should not be overlooked.

Remdesivir has demonstrated clinical benefits in randomized placebo-controlled trials (RCTs) in patients with coronavirus disease 2019 (COVID-19) 1-4 and was first approved for COVID-19 patients. 5 However, whether remdesivir causes gastrointestinal adverse drug reaction (GI-ADRs) including hepatotoxicity is less clear. 1-4 , 6 Therefore, we aimed to detect a diverse spectrum of GI-ADRs associated with remdesivir using VigiBase, the World Health Organization's international pharmacovigilance database of individual case safety reports., (Copyright © 2021 AGA Institute. Published by Elsevier Inc. All rights reserved.)

It is well established that resident's exposure and training are of primary importance and positively correlated with patient and health quality outcomes. We aimed to compare and contrast urology residents' self-reported perspectives and attitudes toward exposure and education of andrology and male infertility during residency in both the United States and Europe. We performed a cross-sectional design study using a survey that was distributed to a representative sample of American and European urology residents. The survey included questions regarding demographics, and the residents' perception and description of their training in this specific subspecialty. Response data were analyzed using Chi-square tests. Sixty-five percent of European and thirty-five percent American urology residents reported feeling uncomfortable in a new consultation evaluating an infertile patient and interpreting semen analyses. Surprisingly, more than half of responders replied that they would not go to their own training institutions seeking for male fertility care (78% US and 58% Europeans). In the comparative analysis, although no differences were observed in the very low number (18%) of hospitals that offer formal microsurgical training for urology residents between the US and Europe, more US institutions were reported to have an operating microscope for urology (68% vs. 41%), and more US residents replied reported participating in at least one urologic surgery using the microscope (65% vs. 34%). In conclusion, both American and European residents shared the same frustration regarding their education and exposure to andrology and male infertility during residency training. Collaborative efforts between stakeholders are needed to establish a clear and focused curriculum and training objectives to eliminate this educational gap., (© 2020. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS)., Materials and Methods: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected., Results: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS., Conclusions: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.

Objective: Although some previous meta-analyses have demonstrated a relationship between statin therapy and all-cause mortality in patients with chronic kidney disease (CKD), conflicting results have been reported. Thus, we performed an umbrella review to understand the strength of evidence and validity of the claimed associations between statin use and all cause and cardiovascular mortality in CKD patients, including patients on dialysis (CKD stage 5D) and transplant recipients., Materials and Methods: We comprehensively re-analyzed the data of 14 meta-analyses of observational studies and randomized controlled trials on associations between statin use and different CKD groups - CKD, CKD stage 5D, and kidney transplant recipients. We also assessed the strength of evidence of the re-analyzed outcomes, which were determined from the criteria, including the statistical significance of the p-value of random-effects, as well as fixed-effects meta-analyses, small-study effects, between-study heterogeneity, and a 95% prediction interval., Results: For CKD patients, statin use showed suggestive evidence for an association with reduced all-cause mortality [relative risk (RR) 0.77, 95% confidence interval (0.69-0.87)]. For kidney transplant recipients, statin use showed suggestive evidence for an association with reduced cardiovascular mortality [RR 0.67, 95% CI (0.50-0.90)]. However, for patients on dialysis, statins showed neither cardiovascular [RR 0.93, 95% CI (0.86-1.01)] nor all-cause mortality [RR 0.98, 95% CI (0.89-1.08)] benefits., Conclusions: Our finding indicates that statin could improve all-cause and cardiovascular mortality in patients with non-dialysis CKD.

Objective: Although previous research has reported beneficial effects of statins on infectious diseases, these have yet to be concluded. Therefore, we conducted an umbrella review to provide a comprehensive understanding of the strength of evidence and validity of claimed associations between statins (hydroxymethyl glutaryl-CoA reductase inhibitors) and infectious diseases., Patients and Methods: We conducted an umbrella review and re-analyzed data from meta-analyses of randomized controlled trials and observational studies on associations between statin use and different infectious diseases such as bacteremia/sepsis and pneumonia. We also evaluated the level of evidence for each re-analyzed outcome based on the criteria using p-values of random and fixed-effects, 95% prediction intervals, small-study effects, between-study heterogeneity, and concordance between the effect estimate of the largest study and summary estimates of the meta-analysis. Moreover, publication bias was also examined., Results: Through a systematic literature search, we obtained 14 eligible articles including 25 meta-analyses. All 4 meta-analyses on overall infection, 3 out of 14 meta-analyses on bacteremia/sepsis, and 5 out of 7 meta-analyses on pneumonia demonstrated that statin use was associated with reduced mortality due to infections (caused by infections). Nonetheless, most significant results only showed a weak level of evidence, and one study with convincing evidence prior to adjustment also showed weak evidence after adjustment., Conclusions: The present review identified a protective effect of statins on infection-related mortality, but all available studies had a weak level of evidence. Therefore, further studies with a strong level of evidence are needed, and it is also necessary to investigate the types of statins and to study clinical outcomes other than mortality to gain further insights.

Objective: Alzheimer's disease (AD) is a leading cause of years lived with disability in older age, and several cerebrospinal fluid (CSF) markers have been proposed in individual meta-analyses to be associated with AD but field-wide evaluation and scrutiny of the literature is not available., Materials and Methods: We performed an umbrella review for the reported associations between CSF biomarkers and AD. Data from available meta-analyses were reanalyzed using both random and fixed effects models. We also estimated between-study heterogeneity, small-study effects, excess significance, and prediction interval., Results: A total of 38 meta-analyses on CSF markers from 11 eligible articles were identified and reanalyzed. In 14 (36%) of the meta-analyses, the summary estimate and the results of the largest study showed non-concordant results in terms of statistical significance. Large heterogeneity (I2≥75%) was observed in 73% and small-study effects under Egger's test were shown in 28% of CSF biomarkers., Conclusions: Our results suggest that there is an excess of statistically significant results and significant biases in the literature of CSF biomarkers for AD. Therefore, the results of CSF biomarkers should be interpreted with caution.

Rationale: Coronavirus disease 2019 (COVID-19) has spread worldwide and poses a threat to humanity. However, no specific therapy has been established for this disease yet. We conducted a systematic review to highlight therapeutic agents that might be effective in treating COVID-19. Methods: We searched Medline, Medrxiv.org, and reference lists of relevant publications to identify articles of in vitro , in vivo , and clinical studies on treatments for severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and COVID-19 published in English until the last update on October 11, 2020. Results: We included 36 studies on SARS, 30 studies on MERS, and 10 meta-analyses on SARS and MERS in this study. Through 12,200 title and 830 full-text screenings for COVID-19, eight in vitro studies, 46 randomized controlled trials (RCTs) on 6,886 patients, and 29 meta-analyses were obtained and investigated. There was no therapeutic agent that consistently resulted in positive outcomes across SARS, MERS, and COVID-19. Remdesivir showed a therapeutic effect for COVID-19 in two RCTs involving the largest number of total participants (n = 1,461). Other therapies that showed an effect in at least two RCTs for COVID-19 were sofosbuvir/daclatasvir (n = 114), colchicine (n = 140), IFN-β1b (n = 193), and convalescent plasma therapy (n = 126). Conclusions: This review provides information to help establish treatment and research directions for COVID-19 based on currently available evidence. Further RCTs are required., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: South Korea is one of the few countries that has succeeded in flattening the curve of new COVID-19 cases and avoiding a second outbreak by implementing multiple strategies, ranging from an individual level to the population level., Objective: We aim to discuss the unique strategies and epidemiological characteristics of COVID-19 in South Korea and present a summary of policies implemented by the Korean government during the COVID-19 pandemic., Methods: We designed a cross-sectional study of epidemiological data published by the Korea Centers for Disease Control and Prevention on October 1, 2020. We analyzed detailed epidemiological information of COVID-19 cases, including the number of confirmed cases and resulting deaths., Results: As of October 1, 2020, a total of 23,889 confirmed COVID-19 cases and 415 deaths were reported in South Korea. In this paper, we present data on the epidemiological characteristics and transmission of the disease and discuss how the South Korean government, health care providers, and society responded to the COVID-19 outbreak., Conclusions: Understanding the epidemiological characteristics of COVID-19 in South Korea and the government's successful efforts in managing the spread of the disease can provide important insights to other countries dealing with the ongoing pandemic., (©Gwang Hun Jeong, Hyo Jeong Lee, Jinhee Lee, Jun Young Lee, Keum Hwa Lee, Young Joo Han, Sojung Yoon, Seohyun Ryu, Da Kyung Kim, Myung Bae Park, Jae Won Yang, Maria Effenberger, Michael Eisenhut, Sung Hwi Hong, Andreas Kronbichler, Ramy Abou Ghayda, Jae Il Shin. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 10.12.2020.)