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Journal of Applied Toxicology : JAT Jun 2024Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using... (Review)
Review
Steroids stand for a class of hormones (natural and synthetic) known to be helpful for a number of disorders. Despite the aforementioned beneficial effects of using these hormones, anabolic-androgenic steroids (AAS) are also widely abused in a non-therapeutic manner for muscle-building and strength-increasing properties that may lead to genotoxicity in different tissues. The present study aims to understand whether genotoxicity may be a suitable biomarker for AAS exposure in vivo in both experimental animal and human studies. All studies published in PubMed/Medline, Scopus, and Web of Science electronic databases that presented data on DNA damage caused by AAS were analyzed. A total of 15 articles were included in this study, and after thoroughly reviewing the studies, a total of 8 articles were classified as Strong, 6 were classified as Moderate, and only 1 was classified as Weak, totaling 14 studies being considered either Strong or Moderate. This classification makes it possible to consider the present findings as reliable. The meta-analysis data revealed a statistically significant difference in Wistar rat testis cells with AAS compared to control for tail length and % tail DNA (p < 0.001), so that the selected articles were considered homogeneous and the I of 0% indicated low heterogeneity. In summary, genotoxicity can be considered a suitable biomarker for monitoring AAS exposure as a result of DNA breakage and oxidative DNA damage.
PubMed: 38840431
DOI: 10.1002/jat.4656 -
Virology Journal Jun 2024Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Limited data is available regarding the severity and mortality of Mpox in individuals with immunocompromised conditions. Therefore, we performed this meta-analysis to understand the impact of HIV- or non-HIV-associated immunosuppression on the severity of Mpox requiring hospitalization and mortality.
METHODS
A thorough literature search was performed from 2022 up to January 2024. The results were presented as odds ratios (ORs). We only included patients who required hospitalization for severity rather than isolation.
RESULTS
A total of 34 studies were included in this analysis. Our analysis did not find a significant difference in the hospitalization risk between HIV-positive individuals and those who were HIV-negative (OR = 1.03; P = 0.85; 7 studies; CD4 count of fewer than 200 cells/µL was less than 0.5% across all studies). Patients with a CD4 count lower than 200 cells/µL or an unsuppressed RNA viral load (> 200 copies/ml) had a significantly higher hospitalization risk (OR = 5.3, P < 0.001) and (OR = 3, P < 0.001), respectively. Most of the reported deaths were reported in patients with HIV with CD4 counts below 200 cells/µL, with some fatal cases occurring in non-HIV immunosuppressed patients, particularly organ transplant recipients. Based on the autopsy findings, Mpox was confirmed in multiple organs, particularly the digestive tract, lung, and testes. Furthermore, some studies documented cases of death that were suspected to be related to hemophagocytic lymphohistiocytosis (HLH) and immune reconstitution inflammatory syndrome (IRIS). Most of the death reports showed concomitant non-Mpox infections at the time of hospitalization and death CONCLUSIONS: Our finding shows that Mpox acts as an opportunistic pathogen in immunocompromised individuals. These individuals should be prioritized for early care and closely monitored for signs of deteriorating clinical conditions. Clinical manifestations and autopsy findings strongly suggest Mpox dissemination to multiple organs, particularly the digestive tract, and lungs. However, the presence of concomitant non-Mpox infections complicates the assessment of the attribution of Mpox to death. Caution should be exercised when interpreting data suggesting poorer outcomes in individuals with non-HIV immunosuppression, as current evidence is scarce and further research is needed.
Topics: Humans; Hospitalization; Immunocompromised Host; HIV Infections; CD4 Lymphocyte Count; Mpox (monkeypox); Disease Outbreaks; Immunosuppression Therapy; Viral Load
PubMed: 38840177
DOI: 10.1186/s12985-024-02392-0 -
European Urology Focus May 2024Penile shaft sparing (PSS) surgery for localised penile cancer (PeCa) aims to balance oncological and functional outcomes. (Review)
Review
CONTEXT
Penile shaft sparing (PSS) surgery for localised penile cancer (PeCa) aims to balance oncological and functional outcomes.
OBJECTIVE
To summarise the published evidence on different PSS approaches.
EVIDENCE ACQUISITION
We performed a systematic review adhering to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The systematic search was performed on PubMed, EMBASE, and Scopus databases up to February 14, 2023. The inclusion criteria encompassed retrospective or prospective studies including patients ≥18 yr of age with localised PeCa treated with different PSS approaches, classified as laser ablation, circumcision, wide local excision, glansectomy with or without split skin graft, glans resurfacing, and mixed technique excision. The risk of bias was assessed using the Newcastle-Ottawa scale. A quantitative synthesis was not performed due to anticipated data heterogeneity and a lack of comparative studies.
EVIDENCE SYNTHESIS
Out of 4343 articles identified, 47 met our inclusion criteria, including 10 847 patients. The year of publication ranged between 1983 and 2021. Nine studies were prospective case series, while the remaining studies were retrospective. No comparative studies were identified. Most of the cases included in these studies were Ta and T1. The oncological outcomes were good for all the approaches, with cancer-specific mortality ranging between 0% and 18%. Sexual and cosmetic outcomes, despite being under-reported, were good for all the approaches, with almost all patients being satisfied with their quality of life after surgery. The Newcastle and Ottawa scale revealed a high or severely high risk of bias in all the included studies.
CONCLUSIONS
PSS approaches were safe and had good functional outcomes, considering however the overall low quality of the studies on this issue.
PATIENT SUMMARY
The perioperative, function, and oncological outcomes of penile shaft sparing approaches are good. However, high-quality studies are needed to determine whether these approaches benefit patients with localised penile cancer.
PubMed: 38749879
DOI: 10.1016/j.euf.2024.05.004 -
Asian Journal of Andrology May 2024Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with...
Association between anti-Müllerian hormone concentrations and sperm retrieval outcomes in patients with idiopathic nonobstructive azoospermia: a systematic review and meta-analysis.
Microdissection testicular sperm extraction (mTESE) is commonly performed to retrieve sperm in the testes for assisted reproductive techniques in patients with idiopathic nonobstructive azoospermia (iNOA). However, the success rate of sperm retrieval varies among individuals. We aim to investigate the association between clinical parameters and sperm retrieval outcomes in patients with iNOA. We searched PubMed, EMBASE, and Web of Science from database inception to August 2, 2023. The main measure was whether sperm retrieval was successful in patients with iNOA who underwent mTESE. Pooled estimates of the sperm retrieval rate and weighted mean differences were calculated using random-effects models. The overall sperm retrieval rate was 36.8% (95% confidence interval [CI]: 27.5%-46.0%, I2 = 95.0%) in nine studies comprising 1892 patients with iNOA. No significant differences were found in age, testicular volume, serum total testosterone concentrations, or inhibin B concentrations between positive and negative sperm retrieval outcomes. Lower anti-Müllerian hormone concentrations in patients with iNOA were associated with a positive outcome of mTESE (weighted mean differences: -2.70; 95% CI: -3.94--1.46, I2 = 79.0%). In conclusion, this study shows a significant relationship between anti-Müllerian hormone and sperm retrieval outcomes in patients with iNOA, while age, testicular volume, total testosterone, and inhibin B show no significant association. These findings have important implications for assessing the potential success of sperm retrieval and selecting appropriate treatment strategies in patients with iNOA.
PubMed: 38748861
DOI: 10.4103/aja202419 -
F1000Research 2023This study performed a systematic review and meta-analysis to compare the outcomes of the staged laparoscopic Fowler-Stephens Laparoscopic Orchiopexy (FSLO) and Staged... (Meta-Analysis)
Meta-Analysis Comparative Study
BACKGROUND
This study performed a systematic review and meta-analysis to compare the outcomes of the staged laparoscopic Fowler-Stephens Laparoscopic Orchiopexy (FSLO) and Staged Laparoscopic Traction Orchiopexy (SLTO) in patients with intra-abdominal testes (IAT).
METHODS
This study reviewed literature published from 2016 to 2024. A systematic literature search was conducted on three databases: PubMed, ScienceDirect, and Google Scholar, using keywords (High intra abdominal testis) AND (("Fowler Stephens laparoscopic orchiopexy" OR (FSLO)) OR (Staged Laparoscopic traction orchiopexy OR (SLTO)). Non-randomized trials and observational studies comparing staged laparoscopic FSLO and SLTO, without any time range restriction are included. Studies without FLSO orchidopexy as a control, case reports, case studies, duplicate publication, no full text and non-English studies are excluded. This study used the PRISMA protocol, the Jadad Scale, and the Newcastle Ottawa Scale (NOS) to evaluate the included studies. To analyze statistical data, the Review Manager (RevMan) software was used. The Chi-squared test was used to calculate statistical heterogeneity in the meta-analysis.
RESULTS
There were 240 patients from 5 studies (109 in the SLTO group and 131 FSLO in group). The primary outcome of this study is testicular descent and atrophy. There were no significant differences in testicular descent (RR:1.08[0.96 - 1.23],p<0.20,I :0%) and atrophy rate (RR:0.45[0.19 - 1.09],p<0.08,I :0%). Secondary outcomes are the duration of operation in both the first and second stages. Statistical analysis reveals a significantly lower first-stage operation time in the FSLO group (MD:9.31[7.08,11.55], p<0.05;I :94%). At the same time, lower second-stage operation times are significantly reported in the SLTO group (MD:-4.05[-7.99,-0.12],p<0.05; I :60%).
CONCLUSIONS
In terms of testicular descent and testicular atrophy the SLTO technique yields similar results to the FSLO technique. Both techniques have advantages and disadvantages, and we recommend SLTO as the first choice in children with a high IAT of <4 cm.
PROSPERO REGISTRATION
CRD42023412407.
Topics: Humans; Cryptorchidism; Laparoscopy; Male; Orchiopexy; Child; Testis; Treatment Outcome
PubMed: 38726300
DOI: 10.12688/f1000research.141110.2 -
European Urology Oncology May 2024Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear.... (Review)
Review
CONTEXT
Mutations in the speckle-type POZ (SPOP) gene are frequently identified in prostate cancer (PC); yet, prognostic implications for affected patients remain unclear. Limited consensus exists regarding tailored treatments for SPOP-mutant (SPOPmut) PC.
OBJECTIVE
To elucidate the prognostic and predictive significance of SPOP mutations across distinct PC stages and treatments.
EVIDENCE ACQUISITION
A systematic literature search of PubMed, Embase, and Scopus was conducted up to January 29, 2024. The meta-analysis included studies comparing survival outcomes between SPOPmut and SPOP wild-type (SPOPwt) PC.
EVIDENCE SYNTHESIS
From 669 records, 26 studies (including five abstracts) were analyzed. A meta-analysis of metastasis-free survival in localized (hazard ratio [HR]: 0.72, 95% confidence interval [CI]: 0.59-0.88; p < 0.01) and overall survival (OS) in metastatic PC (HR: 0.64, 95% CI: 0.53-0.76; p < 0.01) showed a favorable prognosis for patients with SPOPmut PC. In metastatic settings, SPOP mutations correlated with improved progression-free survival (PFS) and OS in patients undergoing androgen deprivation therapy ± androgen receptor signaling inhibitor (HR: 0.51, 95% CI: 0.35-0.76, p < 0.01, and HR: 0.60, 95% CI:0.46-0.79, p < 0.01, respectively). In metastatic castration-resistant PC, only abiraterone provided improved PFS and OS to patients with SPOP mutations compared with patients with SPOPwt, but data were limited. SPOP mutations did not correlate with improved PFS (p = 0.80) or OS (p = 0.27) for docetaxel.
CONCLUSIONS
Patients with SPOPmut PC seem to exhibit superior oncological outcomes compared with patients with SPOPwt. Tailored risk stratification and treatment approaches should be explored in such patients.
PATIENT SUMMARY
Speckle-type POZ (SPOP) mutations could be a favorable prognostic factor in patients with prostate cancer (PC) and may also predict better progression-free and overall survival than treatment with hormonal agents. Therefore, less intensified treatments omitting chemotherapy for patients with SPOP-mutant PC should be explored in clinical trials.
PubMed: 38704358
DOI: 10.1016/j.euo.2024.04.011 -
Children (Basel, Switzerland) Mar 2024The effect of pediatric inguinal hernia repair (IHR) on testicular vascularization remains unclear. Manipulating the spermatic cord during surgery may reduce blood flow... (Review)
Review
BACKGROUND
The effect of pediatric inguinal hernia repair (IHR) on testicular vascularization remains unclear. Manipulating the spermatic cord during surgery may reduce blood flow due to edema and vasoconstriction. This can lead to testicular atrophy. The study aims to review current knowledge of testicular vascular impairment following IHR in children.
METHODS
A systematic literature search was conducted in PubMed/Medline, Embase, Cochrane Library, and Web of Science. Methodological quality was assessed using validated tools. Data were extracted, and a pooled data analysis was performed.
RESULTS
Ten studies were included in the systematic review. Six of these studies were eligible for meta-analysis. This revealed a significant decrease in testicular vascularization during the short-term follow-up (1 day-1 week) after IHR using the open surgical approach. This decrease was not present after laparoscopic intervention. There was no more increased resistance in the vessels at long-term follow-up (1 month-6 months), suggesting that the impaired vascularity is only temporary.
CONCLUSIONS
There seems to be a short-term transient vascular impairment of the testis after open IHR in children. This might be of clinical relevance to prefer the laparoscopic approach for IHR in children, even though the open approach is the gold standard, in contrast to adult IHR. The impact on testicular function and sperm quality later in life remains unclear. Comparative studies of both techniques are needed to determine if there is a significant difference in testicular vascularity. Long-term studies are necessary to assess the impact of transiently reduced vascularity on sperm quality and fertility later in life.
PubMed: 38671625
DOI: 10.3390/children11040409 -
JAMA Network Open Mar 2024Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1)... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Immune checkpoint inhibitors (ICIs) have broadened the metastatic urothelial carcinoma (mUC) therapeutic scenario. The association of programmed death ligand 1 (PD-L1) with response and survival in patients treated with ICIs is still controversial.
OBJECTIVES
To evaluate the association of PD-L1 with response rate and overall survival among patients with mUC treated with ICIs.
DATA SOURCES
PubMed, Embase, American Society of Clinical Oncology and European Society for Medical Oncology Meeting Libraries, and Web of Science were searched up to December 10, 2023.
STUDY SELECTION
Two authors independently screened the studies. Included studies were randomized and nonrandomized clinical trials enrolling patients with mUC receiving ICIs with available overall survival (OS), progression-free survival (PFS), or overall response rate (ORR) data, separated between patients with PD-L1-positive and -negative tumors.
DATA EXTRACTION AND SYNTHESIS
The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was followed. Two reviewers independently extracted data. Fixed- or random-effects models were used depending on the heterogeneity among the studies.
MAIN OUTCOMES AND MEASURES
Primary outcomes were odds ratios (ORs) for ORR and hazard ratios (HRs) for OS, comparing patients with PD-L1-positive tumors and patients with PD-L1-negative tumors. Secondary outcomes were the PFS HR between patients with PD-L1-positive and -negative tumors and OS HR between ICI arms and non-ICI arms of only randomized clinical trials.
RESULTS
A total of 14 studies were selected, comprising 5271 patients treated with ICIs (2625 patients had PD-L1-positive tumors). The ORR was 13.8% to 78.6% in patients with PD-L1-positive tumors and 5.1% to 63.2% in patients with PD-L1-negative tumors, with an association between PD-L1 status and ORR favoring patients with PD-L1-positive tumors (OR, 1.94; 95% CI, 1.47-2.56; P < .001). Median OS ranged from 8.4 to 24.1 months in patients with PD-L1-positive tumors and from 6.0 to 19.1 months in patients with PD-L1-negative tumors. The pooled HR showed a significant reduction for patients with PD-L1-positive tumors compared with those with PD-L1-negative tumors in the risk of death (HR, 0.71; 95% CI, 0.57-0.89; P = .003) and risk of progression (HR, 0.55; 95% CI, 0.44-0.69; P < .001) when ICIs were administered. PD-L1 is not likely to be a predictive biomarker of ICI response.
CONCLUSIONS AND RELEVANCE
This systematic review and meta-analysis suggests that PD-L1 expression is associated with improved ORR, OS, and PFS for patients with mUC who receive ICIs, but it is unlikely to be useful as a predictive biomarker. Developing predictive biomarkers is essential to select patients most likely to benefit from ICIs and avoid toxic effects and financial burden with these agents.
Topics: Humans; B7-H1 Antigen; Immune Checkpoint Inhibitors; Carcinoma, Transitional Cell; Urinary Bladder Neoplasms; Biomarkers; Randomized Controlled Trials as Topic
PubMed: 38446479
DOI: 10.1001/jamanetworkopen.2024.1215 -
Urology Annals 2024Laparoscopic exploration is currently considered the gold standard for managing nonpalpable intraabdominal testes. The problem of short vascular pedicle is addressed in...
BACKGROUND
Laparoscopic exploration is currently considered the gold standard for managing nonpalpable intraabdominal testes. The problem of short vascular pedicle is addressed in Fowler-Stephen (FS) technique by the division of testicular vessels and in Shehata technique (ST) by traction on testicular vessels. There is a lack of the consensus among pediatric surgeons on the choice of one technique over other. This analysis compares the reported outcomes of staged laparoscopic orchidopexy by ST with the time tested FS technique in managing high intraabdominal undescended testis.
MATERIALS AND METHODS
The present systematic review and meta-analysis was conducted as per the preferred reporting items for the systematic review and meta-analyses guidelines. Only randomized controlled trials and comparative studies were included. The primary outcomes compared were the incidence of testicular atrophy, testicular retraction/ascent rate, and operative time of Stage I and Stage II orchidopexy.
RESULTS
The present analysis was based on three randomized studies with a total of 119 undescended testes in 117 patients satisfying the inclusion criteria. The operative time was less in Stage I FS technique; however, there was no statistically significant difference in operative time of both procedures during the Stage II laparoscopic orchidopexy. Pooled analysis of postintervention testicular atrophy, testicular retraction rate, and duration of postoperative hospitalization showed no difference between both procedures.
CONCLUSION
Both FS and STs are comparable in terms of postintervention testicular atrophy, testicular retraction/ascent; however, the mean operative time is significantly less with FS technique in Stage I laparoscopic orchidopexy.
PubMed: 38415237
DOI: 10.4103/ua.ua_11_23 -
Archivio Italiano Di Urologia,... Feb 2024The COVID-19 can affect human testicles, thus will interfere the production of important male sexual hormone such as testosterone. Our study provides scientific evidence... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The COVID-19 can affect human testicles, thus will interfere the production of important male sexual hormone such as testosterone. Our study provides scientific evidence through systematic reviews and meta-analyses that focus on the effects of SARS-CoV-2 virus infection on male sexual hormonal disorders in patients post-exposure to COVID-19.
METHODS
This meta-analysis was made in accordance with the PRISMA guidelines. The outcomes of this study were the level of total testosterone, free testosterone, LH and FSH. Chi-square and I2 tests were used to evaluate heterogeneity between studies. The standardized mean deviation (SMD) with 95% CI were used and analysis was performed using the Review Manager 5.4 software.
RESULTS
The four included studies reported a total of 256 patients with COVID-19 with time of follow-up time post COVID-19 varying from one month to 7 months. The mean age distribution in the study was 34-57 years old. Total testosterone level (SMD = -158.71; 95% CI= -205.30 - -112.12; p<0.00001) was significantly higher at follow-up post COVID-19, while LH (SMD = 0.40; 95% CI = 0.15-0.65; p=0.002) was lower. The free testosterone level and FSH level showed no significant difference between baseline and after following up post COVID-19.
CONCLUSIONS
At follow up, the total testosterone level in patients with SARS-CoV-2 infection appeared to be elevated while LH was lower compared to the baseline.
Topics: Humans; Male; Adult; Middle Aged; COVID-19; SARS-CoV-2; Testosterone; Testis; Follicle Stimulating Hormone
PubMed: 38363236
DOI: 10.4081/aiua.2024.12113