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International Urology and Nephrology Oct 2023Some authors have estimated that the incidence of testicular germ cell tumors in individuals with trisomy 21 is more than fivefold higher than that in the general... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Some authors have estimated that the incidence of testicular germ cell tumors in individuals with trisomy 21 is more than fivefold higher than that in the general population.
OBJECTIVE
This systematic review aimed to estimate the incidence of urological tumors in patients with Down's syndrome.
STUDY DESIGN
We conducted a search strategy in MEDLINE (OVID), EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. We assessed the risk of bias and performed a meta-analysis. Also, the heterogeneity between trials was evaluated by the I test. We completed the subgroup analysis based on the type of urological tumor (testis, bladder, kidney, upper urological tract, penile, retroperitoneum).
RESULTS
We found 350 studies by the search strategy. After carefully reviewing, full-text studies were included. 16,248 individuals with Down's syndrome were included, and 42 patients presented with urological tumors. There was a total incidence of 0.1%, 95%CI (0.06-0.19), I 61%. The most common urological tumor reported was testicular. We found six studies describing 31 events and an overall incidence of 0.19%, 95%CI (0.11-0.33), I: 51%. Other studies reported kidney, penile, upper urinary tract, bladder, and retroperitoneum tumors with a very low incidence, 0.02%, 0.06%, 0.03%, 0.11%and 0.07%, respectively.
DISCUSSION
Regarding non-testicular urological tumors, we found incidences as low as 0.02% in kidney cancer or 0.03% in the upper-urothelial tract tumors. It is also lower than the general population. Compared to the age of onset of patients, it is also lower than the general population, perhaps related to a shorter life expectancy. As a limitation, we found a high heterogeneity and a lack of information regarding non-testicular tumors.
CONCLUSION
There was a very low incidence of urological tumors in people with Down's syndrome. Testis tumor was the most frequently described in all cohorts and within a normal distribution range.
Topics: Male; Humans; Down Syndrome; Incidence; Testicular Neoplasms; Urologic Neoplasms
PubMed: 37368086
DOI: 10.1007/s11255-023-03656-4 -
Frontiers in Endocrinology 2023Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in... (Meta-Analysis)
Meta-Analysis
Protective effects of melatonin against oxidative stress induced by metabolic disorders in the male reproductive system: a systematic review and meta-analysis of rodent models.
BACKGROUND
Male infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility.
MATERIAL AND METHODS
We systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen's d) and 95% confidence interval.
RESULTS
24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high-fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen's testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress.
CONCLUSIONS
Melatonin can reduce damage to male rodents' gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.
Topics: Animals; Male; Mice; Rats; Body Weight; Diabetes Mellitus; Hyperthyroidism; Infertility, Male; Melatonin; Metabolic Diseases; Obesity; Oxidative Stress; Rodentia; Semen; Testis
PubMed: 37476491
DOI: 10.3389/fendo.2023.1202560 -
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 Research & Practice Sep 2023Scrotal tumors of nerve origin are extremely rare and occur mostly in the extratesticular tissues of scrotum, such as the spermatic cord and epididymis. A systematic...
Scrotal tumors of nerve origin are extremely rare and occur mostly in the extratesticular tissues of scrotum, such as the spermatic cord and epididymis. A systematic search of the literature in PubMed, Medline, and Google Scholar databases concerning intrascrotal nerve tumors was performed by 2 independent investigators. The systematic search retrieved 45 male adults, with a mean age of included patients at 43.9 ± 18.8 years. The majority of nerve tumors were extra-testicular (86.7%), and only 13.3% originated from the testis. Out of that, 51.1% of neoplasms were histologically proved as schwannomas, 44.4% as neurofibromatosis, and 4.4% as malignant peripheral nerve sheath tumors. The majority of patients presented with atypical symptoms such as scrotal swelling (51.1%), while only 4.4% of patients were asymptomatic. Ultrasonography is the diagnostic modality of choice (97.2%) for the detection of primary lesion, while magnetic resonance imaging and computed tomography comprise supplementary diagnostic tools. Surgical excision of the mass was the preferred type of surgery performed (75.6%), whereas orchiectomy was performed only in 22.2% of patients. Intrascrotal tumors of nerve origin are extremely rare neoplasms that present mainly in middle-aged males. Increased clinical suspicion is required for accurate diagnosis of this rare entity.
PubMed: 37877874
DOI: 10.5152/tud.2023.23050 -
HRB Open Research 2018Testicular cancer (TC) is among the most commonly diagnosed cancers in men aged 15-40 years. The incidence of TC is on the rise. Benign testicular disorders, such as...
Testicular cancer (TC) is among the most commonly diagnosed cancers in men aged 15-40 years. The incidence of TC is on the rise. Benign testicular disorders, such as testicular torsion and epididymitis, can lead to testicular ischemia, sepsis, and infertility if left untreated. This updated systematic review aims to evaluate the effectiveness of studies promoting men's knowledge and awareness of testicular disorders and/or self-examination, behaviours and/or intentions to examine their testes, and help-seeking behaviours and/or intentions for testicular disorder symptoms. Academic Search Complete, Medline, CINAHL, PsycINFO, ERIC, the Cochrane Library, the World Health Organisation International Clinical Trials Registry Platform, and Clinicaltrials.gov were searched for studies published between April 2018 and August 2023. Methodological quality was assessed and results were synthesised meta-narratively. Five studies were included. The majority of the reviewed interventions were successful in increasing men's awareness of TC and self-examination, including a PowerPoint presentation, an online educational brochure, video-assisted teaching, a motivational video, and a virtual reality game. Only one study addressed help-seeking for testicular symptoms and promoted men's awareness of benign as well as malignant testicular diseases. This review highlights the importance of evaluating innovative educational interventions aimed at younger men, whilst raising their awareness of testicular disorders and increasing their help-seeking intentions for testicular disorder symptoms. Given the lack of consensus around scheduled testicular self-examination among younger men, clinicians are encouraged to instruct men to familiarise themselves with the look and feel of their own testes and to seek timely medical attention for abnormalities. The protocol of the previous version of this review was registered with the International Prospective Register of Systematic Reviews (PROSPERO) under the registration number CRD42018093671.
PubMed: 32002508
DOI: 10.12688/hrbopenres.12837.3 -
Frontiers in Toxicology 2023Japanese medaka () is an acceptable small laboratory fish model for the evaluation and assessment of endocrine-disrupting chemicals (EDCs) found in the environment. In...
Japanese medaka () is an acceptable small laboratory fish model for the evaluation and assessment of endocrine-disrupting chemicals (EDCs) found in the environment. In this research, we used this fish as a potential tool for the identification of EDCs that have a significant impact on human health. We conducted an electronic search in PubMed (http://www.ncbi.nlm.nih.gov/pubmed) and Google Scholar (https://scholar.google.com/) using the search terms, Japanese medaka, , and endocrine disruptions, and sorted 205 articles consisting of 128 chemicals that showed potential effects on estrogen-androgen-thyroid-steroidogenesis (EATS) pathways of Japanese medaka. From these chemicals, 14 compounds, namely, 17β-estradiol (E2), ethinylestradiol (EE2), tamoxifen (TAM), 11-ketotestosterone (11-KT), 17β-trenbolone (TRB), flutamide (FLU), vinclozolin (VIN), triiodothyronine (T3), perfluorooctanoic acid (PFOA), tetrabromobisphenol A (TBBPA), terephthalic acid (TPA), trifloxystrobin (TRF), ketoconazole (KTC), and prochloraz (PCZ), were selected as references and used for the identification of apical endpoints within the EATS modalities. Among these endpoints, during classification, priorities are given to sex reversal (masculinization of females and feminization of males), gonad histology (testis-ova or ovotestis), secondary sex characteristics (anal fin papillae of males), plasma and liver vitellogenin (VTG) contents in males, swim bladder inflation during larval development, hepatic vitellogenin () and choriogenin () genes in the liver of males, and several genes, including estrogen-androgen-thyroid receptors in the hypothalamus-pituitary-gonad/thyroid axis (HPG/T). After reviewing 205 articles, we identified 108 (52.68%), 46 (22.43%), 19 (9.26%), 22 (17.18%), and 26 (12.68%) papers that represented studies on estrogen endocrine disruptors (EEDs), androgen endocrine disruptors (AEDs), thyroid endocrine disruptors (TEDs), and/or steroidogenesis modulators (MOS), respectively. Most importantly, among 128 EDCs, 32 (25%), 22 (17.18%), 15 (11.8%), and 14 (10.93%) chemicals were classified as EEDs, AEDs, TEDs, and MOS, respectively. We also identified 43 (33.59%) chemicals as high-priority candidates for tier 2 tests, and 13 chemicals (10.15%) show enough potential to be considered EDCs without any further tier-based studies. Although our literature search was unable to identify the EATS targets of 45 chemicals (35%) studied in 60 (29.26%) of the 205 articles, our approach has sufficient potential to further move the laboratory-based research data on Japanese medaka for applications in regulatory risk assessments in humans.
PubMed: 38090358
DOI: 10.3389/ftox.2023.1272368 -
Frontiers in Oncology 2023Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To...
Nuclear protein of the testis (NUT) midline carcinoma (NMC) is a rare tumor, with particularly low incidence in the lungs, and a correspondingly poor prognosis. To determine the clinicopathological characteristics, outcomes, and prognostic factors of primary pulmonary NMC, a case was reported and a systematic review was performed. Twenty-nine records, including ours, involving 62 cases, were finally included. The median age at diagnosis was 29.5 years. At presentation, the most common symptoms at presentation were cough (47.50%) and chest/back pain (37.50%). In terms of diagnosis, 32.14% of NMC cases were identified through immunohistochemistry (IHC); However, a greater number of cases may be misdiagnosed initially, and ultimately, the diagnosis of NMC was confirmed through a combination of IHC and fluorescence hybridization (FISH). Despite the clinical application of various chemotherapy-based treatments, the actual effectiveness remains unsatisfactory. Furthermore, Cox regression analysis of multiple factors identified male gender and concurrent presence of pleural effusion as indicators of shorter survival time in patients. These results emphasize the importance of increased diagnostic awareness among clinical and pathology practitioners concerning NMC. While there is currently no established standard for treating NMC, a treatment approach combining multiple methods shows promise for future research. Concurrently, clinical and foundational investigations addressing variables such as gender and the presence of pleural effusion may yield valuable insights into the diagnosis and treatment of NMC.
PubMed: 38264746
DOI: 10.3389/fonc.2023.1308432 -
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 -
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 -
Translational Andrology and Urology Dec 2023The testicular sperm instead of ejaculated sperm for intracytoplasmic sperm injection (ICSI) in infertile men with high sperm DNA fragmentation (SDF) is a controversial...
Outcomes comparison of testicular versus ejaculated sperm for intracytoplasmic sperm injection in infertile men with high DNA fragmentation: updated systematic review and meta-analysis.
BACKGROUND
The testicular sperm instead of ejaculated sperm for intracytoplasmic sperm injection (ICSI) in infertile men with high sperm DNA fragmentation (SDF) is a controversial topic. This updated systematic review and meta-analysis aims to evaluate whether couples with high level of SDF will benefit more from intracytoplasmic sperm injection with testicular sperm (Testi-ICSI) as compared to intracytoplasmic sperm injection with ejaculated sperm (Ejac-ICSI).
METHODS
A systematic search was conducted according to PRISMA guidelines, using PubMed, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL), encompassing studies from the earliest record until May 2022. We included studies analyzing comparative pregnancy outcomes of testicular versus ejaculated sperm for ICSI in infertile men with high DNA fragmentation. The risks of bias and certainty of evidence were assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework, respectively.
RESULTS
Eleven studies were included. Meta-analysis showed that SDF levels revealed a significant difference association [odds ratio (OR) =-25.81; 95% confidence interval (CI): -34.82, -16.81; I=94%; P<0.00001] between testicular and ejaculated sperm. Compared with Ejac-ICSI, a non-significant tendency was observed for fertilization rates (FRs) in the Testi-ICSI group (OR =0.87; 95% CI: 0.67, 1.12; I=81%; P=0.28). However, there was significant difference pointing to better outcomes for Testi-ICSI in clinical pregnancy rates (CPRs) (OR =2.36; 95% CI: 1.71, 3.24; I=0%; P<0.00001), live birth rates (LBRs) (OR =3.10; 95% CI: 2.13, 4.51; I=4%; P<0.00001) and miscarriage rates (MRs) (OR =0.28; 95% CI: 0.13, 0.60; I=0%; P=0.001).
CONCLUSIONS
Results of this updated meta-analysis reveal that SDF rates are lower in testicular sperm than in ejaculated sperm and that Testi-ICSI is correlated with better clinical outcomes, including higher CPRs, higher LBRs, and lower MRs in infertile males with high SDF levels. Nevertheless, with the overall low to moderate quality of the studies, further well-designed controlled studies are required.
PubMed: 38196694
DOI: 10.21037/tau-23-415