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PURPOSE: Small intestinal submucosa (SIS) graft urethroplasty has been employed to decrease buccal mucosa morbidity and facilitate the procedure. The first published series had a short follow-up, inhomogeneous patient selection, and a lack of a control group. Our purpose is to report treatment outcomes at 13 years in a propensity score-matched cohort comparing bulbar urethroplasty with SIS (SISU) or buccal mucosa (BMU). METHODS: From our institutional database of 1132 bulbar urethroplasties, we used propensity score matching with the nearest-neighbor method without replacement to generate a study sample of 25 BMU and 25 SISU. Failure was defined as any treatment after urethroplasty. Survival analyses were used to analyze treatment failure occurrence with data censored at 156mo. RESULTS: Matching resulted in a complete correction of bias between the two samples except for the follow-up duration, which was slightly longer in the SIS group. The cumulative treatment success probability of BMU and SISU at 156mo was 83.4% and 68%, respectively. At multivariable Cox regression, SIS graft, previous urethrotomy, stricture length, and lower postoperative Qmax (within 2mo after catheter removal) were predictors of failure. Stricture length had a more remarkable effect in SISU, with estimated survival probabilities from the Cox model lower than 80% in strictures > = 3 cm. CONCLUSION: SIS has poorer outcomes compared to BM but may still be useful when BM grafting is not possible. The best candidates for SISU, with similar success to BMU, are patients with strictures shorter than 3 cm, preferably without a history of DVIU.
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Estreitamento Uretral , Masculino , Humanos , Constrição Patológica/cirurgia , Estreitamento Uretral/cirurgia , Mucosa Bucal/transplante , Pontuação de Propensão , Procedimentos Cirúrgicos Urológicos Masculinos/métodos , Uretra/cirurgia , Resultado do TratamentoRESUMO
5α-Reductase inhibitors (5-ARIs) are widely prescribed for treatment of benign prostatic obstruction and androgenic alopecia. Several studies with controversial findings regarding 5-ARI exposure have been published over a number of years, and concerns were recently raised about the potential risks of depression and suicide associated with 5-ARIs. To investigate this association, we conducted a systematic review of the literature and a meta-analysis. Five studies involving 2213600 patients met our inclusion criteria. We found no statistically significant association between 5-ARI exposure and the risk of depression (adjusted hazard ratio [aHR] 1.30, 95% confidence interval [CI] 0.85-2.00; p = 0.23) or suicide (aHR 1.30, 95% CI 0.65-2.61; p = 0.45). Subgroup analyses for finasteride and dutasteride revealed similar results. When restricting the analysis to patients without a prior diagnosis of depression, we observed similar findings (aHR for suicide 1.00, 95% CI 0.68-1.46; p = 0.98). PATIENT SUMMARY: We reviewed study data for more than two million patients taking drugs called 5α-reductase inhibitors (5-ARIs), which are widely prescribed for urinary problems caused by benign prostate enlargement and for male-pattern hair loss. In a pooled analysis we found no evidence of an association between 5-ARI use and the risk of depression or suicide.
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Using high-throughput metagenomics on commercial microbial fermentation products, DNA from a new unauthorized genetically modified microorganism (GMM), namely the GM B. licheniformis strain producing alpha-amylase (GMM alpha-amylase2), was recently discovered and characterized. On this basis, a new qPCR method targeting an unnatural association of sequences specific to the GMM alpha-amylase2 strain was designed and developed in this study, allowing to strengthen the current GMM detection strategy. The performance of the newly developed qPCR method was assessed for its specificity and sensitivity to comply with the minimum performance requirements established by the European Network of GMO Laboratories for GMO analysis. Moreover, the transferability of the in house validated qPCR method was demonstrated. Finally, its applicability was confirmed by a pilot market surveillance of GMM contaminations conducted for the first time on 40 alpha-amylase food enzyme products labelled as containing alpha-amylase. This pilot market surveillance allowed also to highlight numerous contaminations with GMM alpha-amylase2, including frequent cross-contaminations with other GMM strains previously characterized. In addition, the presence of full-length AMR genes, raising health concerns, was also reported.
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The last decade, smoke and smokeless products claiming to be tobacco-free, including herbal cigarettes and herbal shisha, became available on the European market and gained popularity. This study proposes a new digital droplet PCR (ddPCR) method, designed based on a previously developed real-time PCR (qPCR) method being currently used by the U.S. Food and Drug Administration (FDA) to specifically detect the presence of tobacco DNA in targeting a sequence from the Nicotiana tabacum nia-1 gene. To ensure a harmonized and reliable control by enforcement laboratories, both of these qPCR and ddPCR methods were then evaluated and validated for their compliance to an international standard. First, the performance of these PCR-based methods was successfully assessed as specific and sensitive, and in line with minimum performance requirements from international standard. Secondly, the transferability to external laboratory was confirmed for these PCR-based methods. Finally, the applicability of these PCR-based methods was demonstrated using 7 ground tobacco reference materials from the Tobacco Research Center (TRC) Toronto University as well as 6 commercial smokeless and tobacco-free smoke and smokeless products. Based on this study, the previously developed qPCR method was confirmed as complying with international standard, ensuring a efficient and harmonize use by enforcement laboratories for tobacco control on the European market. Moreover, this study proposed to enforcement laboratories the possibility to use a ddPCR method, enabling the simultaneous detection and absolute quantification of tobacco DNA as well as a limited impact of PCR inhibitors.
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An urgent need for effective surveillance strategies arose due to the global emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although vaccines and antivirals are available, concerns persist about the evolution of new variants with potentially increased infectivity, transmissibility, and immune evasion. Therefore, variant monitoring is crucial for public health decision-making. Wastewater-based surveillance has proven to be an effective tool to monitor SARS-CoV-2 variants within populations. Specific SARS-CoV-2 variants are detected and quantified in wastewater in this study using a reverse transcriptase digital droplet polymerase chain reaction (RT-ddPCR) approach. The 11 designed assays were first validated in silico using a substantial dataset of high-quality SARS-CoV-2 genomes to ensure comprehensive variant coverage. The assessment of the sensitivity and specificity with reference material showed the capability of the developed assays to reliably identify target mutations while minimizing false positives and false negatives. The applicability of the assays was evaluated using wastewater samples from a wastewater treatment plant in Ghent, Belgium. The quantification of the specific mutations linked to the variants of concern present in these samples was calculated using these assays based on the detection of single mutations, which confirms their use for real-world variant surveillance. In conclusion, this study provides an adaptable protocol to monitor SARS-CoV-2 variants in wastewater with high sensitivity and specificity. Its potential for broader application in other viral surveillance contexts highlights its added value for rapid response to emerging infectious diseases. PRACTITIONER POINTS: Robust RT-ddPCR methodology for specific SARS-CoV-2 variants of concern detection in wastewater. Rigorous validation that demonstrates high sensitivity and specificity. Demonstration of real-world applicability using wastewater samples. Valuable tool for rapid response to emerging infectious diseases.
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COVID-19 , Doenças Transmissíveis Emergentes , Humanos , SARS-CoV-2/genética , Águas Residuárias , Reação em Cadeia da Polimerase , DNA Polimerase Dirigida por RNA , Teste para COVID-19RESUMO
BACKGROUND: The diagnostic process for prostate cancer after a negative biopsy is challenging. This study compares the diagnostic accuracy of micro-ultrasound (mUS) with multiparametric magnetic resonance imaging (mpMRI) for such cases. METHODS: A retrospective cohort study was performed, targeting men with previous negative biopsies and using mUS and mpMRI to detect prostate cancer and clinically significant prostate cancer (csPCa). RESULTS: In our cohort of 1397 men, 304 had a history of negative biopsies. mUS was more sensitive than mpMRI, with better predictive value for negative results. Importantly, mUS was significantly associated with csPCa detection (adjusted odds ratio [aOR]: 6.58; 95% confidence interval [CI]: 1.15-37.8; p = 0.035). CONCLUSIONS: mUS may be preferable for diagnosing prostate cancer in previously biopsy-negative patients. However, the retrospective design of this study at a single institution suggests that further research across multiple centers is warranted.
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The management of hypospadias during the neonatal period should be carried out exclusively in specialized medical centers because of the potential dire complications that may arise. In this report, we present a case of a 22-year-old male who underwent thirteen unsuccessful surgical procedures for his penoscrotal hypospadias in various hospitals. The purpose of this case report is to describe the surgical correction of severe corporal fibrosis and penile curvature that ensued from the multiple failed hypospadias corrections. We implanted an extra cavernosal malleable penile prosthesis and reconstructed the tunica albuginea defect with surgical meshes used in hernia repairs.
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Wastewater-based surveillance can be used as a complementary method to other SARS-CoV-2 surveillance systems. It allows the emergence and spread of infections and SARS-CoV-2 variants to be monitored in time and place. This study presents an RT-ddPCR method that targets the T19I amino acid mutation in the spike protein of the SARS-CoV-2 genomes, which is specific to the BA.2 variant (omicron). The T19I assay was evaluated both in silico and in vitro for its inclusivity, sensitivity, and specificity. Moreover, wastewater samples were used as a proof of concept to monitor and quantify the emergence of the BA.2 variant from January until May 2022 in the Brussels-Capital Region which covers a population of more than 1.2 million inhabitants. The in silico analysis showed that more than 99% of the BA.2 genomes could be characterized using the T19I assay. Subsequently, the sensitivity and specificity of the T19I assay were successfully experimentally evaluated. Thanks to our specific method design, the positive signal from the mutant probe and wild-type probe of the T19I assay was measured and the proportion of genomes with the T19I mutation, characteristic of the BA.2 mutant, compared to the entire SARS-CoV-2 population was calculated. The applicability of the proposed RT-ddPCR method was evaluated to monitor and quantify the emergence of the BA.2 variant over time. To validate this assay as a proof of concept, the measurement of the proportion of a specific circulating variant with genomes containing the T19I mutation in comparison to the total viral population was carried out in wastewater samples from wastewater treatment plants in the Brussels-Capital Region in the winter and spring of 2022. This emergence and proportional increase in BA.2 genomes correspond to what was observed in the surveillance using respiratory samples; however, the emergence was observed slightly earlier, which suggests that wastewater sampling could be an early warning system and could be an interesting alternative to extensive human testing.
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BACKGROUND: Recent years have seen the development of a new generation of temporary urethral stents as an adjuvant option after direct vision internal urethrotomy (DVIU). Despite some early promising results, large series addressing their safety and outcomes are still lacking. OBJECTIVE: To report complications and outcomes from the largest series of patients receiving a temporary bulbar urethral stent to date. DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective analysis of bulbar urethral stenting procedures after DVIU in seven centers. Patients either refused urethroplasty or were not fit for surgery. The stents were removed after at least 6 mo in place unless complications requiring earlier removal occurred. SURGICAL PROCEDURE: DVIU with a cold knife or laser is performed, followed by stent placement. At the end of the treatment period, the stent is removed under cystoscopy with gripping forceps. MEASUREMENTS: All patients underwent postoperative follow-up (FU) for assessment of complications while the stent was in place. After removal, the FU schedule consisted of office evaluation at 6 mo and 12 mo, and then annually. Failure was defined as any treatment for urethral stricture after stent removal. RESULTS AND LIMITATIONS: A total of 49% of the patients experienced complications. The most frequent were discomfort (23.8%), stress incontinence (17.5%), and stent dislocation (9.8%). Some 85% of the adverse events observed were Clavien-Dindo grade <3. The overall success rate at median FU of 38.2 mo was 76.9%. The success rate was significantly lower if the stent was removed before 6 mo (53.3% vs 79.7%; p = 0.026). CONCLUSIONS: Temporary urethral stents may be a safe choice with satisfactory results in patients not undergoing urethroplasty. A stent indwelling time shorter than 6 mo provides worse outcomes that are comparable to those with DVIU alone. PATIENT SUMMARY: We assessed complications and outcomes after placement of a temporary narrow tube in the urethra after surgery to widen a narrowing of the urethra. The treatment is safe and easily reproducible with satisfactory results. Further studies are needed to confirm our findings.
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Uretra , Estreitamento Uretral , Humanos , Masculino , Uretra/cirurgia , Estudos Retrospectivos , Estudos de Viabilidade , Resultado do Tratamento , Estreitamento Uretral/cirurgia , Stents , Procedimentos Cirúrgicos Urológicos Masculinos/efeitos adversos , Procedimentos Cirúrgicos Urológicos Masculinos/métodosRESUMO
INTRODUCTION: Inflatable penile prosthesis are the definitive treatment for erectile dysfunction. The two most used surgical approaches to position the implants are the penoscrotal and the infrapubic. Current trends showed that the penoscrotal approach is extensively preferred however, there is not conclusive evidence demonstrating the superiority of one technique over the other. The aim of this review is to summarize the scientific evidence available and to underline strengths and weaknesses of the two techniques. EVIDENCE ACQUISITION: We conducted a comprehensive search of MEDLINE, Cochrane Library, and National Center for Biotechnology Information PubMed to identify relevant published articles. The included studies had to explicitly examine the use of three-piece inflatable penile prosthesis with a focus on the surgical access method and complications. EVIDENCE SYNTHESIS: Twenty-six articles were included in the review: seven narrative reviews, five retrospective observational studies, five prospective observational studies, and nine mixed methodology studies. The most frequent approach was the penoscrotal, which was also found more comfortable (RG1) by the operators in one study. The infrapubic approach lasts less and one study demonstrated higher satisfaction by the patients. CONCLUSIONS: There is no evidence of significant differences in complications among the penoscrotal and infrapubic approaches. While the infrapubic approach is faster and patients were more satisfied, the penoscrotal approach is the most used by far. This is likely related to the more straightforward procedure through this access and the excellent surgical field exposure. For these reasons, it is also preferred in the most complex cases.
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Implante Peniano , Prótese de Pênis , Humanos , Masculino , Estudos Observacionais como Assunto , Satisfação do Paciente , Implante Peniano/métodos , Pênis/cirurgia , Estudos RetrospectivosRESUMO
Patients with pT1 high-grade (HG) urothelial carcinoma (UC) and a very high risk of progression might benefit from immediate radical cystectomy (RC), but this option remains controversial. Validation of a standardized method to evaluate the extent of lamina propria (LP) invasion (with recognized prognostic value) in transurethral resection (TURBT) specimens is still needed. The Rete Oncologica Lombarda (ROL) system showed a high predictive value for progression after TURBT in recent retrospective studies. The ROL system was supposed to be validated on a large prospective series of primary urothelial carcinomas from a single institution. From 2016 to 2020, we adopted ROL for all patients with pT1 HG UC on TURBT. We employed a 1.0-mm threshold to stratify tumors in ROL1 and ROL2. A total of 222 pT1 HG UC were analyzed. The median age was 74 years, with a predominance of men (73.8%). ROL was feasible in all cases: 91 cases were ROL1 (41%), and 131 were ROL2 (59%). At a median follow-up of 26.9 months (IQR 13.8-40.6), we registered 81 recurrences and 40 progressions. ROL was a significant predictor of tumor progression in both univariable (HR 3.53; CI 95% 1.56-7.99; p < 0.01) and multivariable (HR 2.88; CI 95% 1.24-6.66; p = 0.01) Cox regression analyses. At Kaplan-Meier estimates, ROL showed a correlation with both PFS (p = 0.0012) and RFS (p = 0.0167). Our results confirmed the strong predictive value of ROL for progression in a large prospective series. We encourage the application of ROL for reporting the extent of LP invasion, substaging T1 HG UC, and improving risk tables for urological decision-making.
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BACKGROUND: T1 high-grade (HG) non-muscle invasive bladder cancer (NMIBC) has a significant risk of recurrence and progression, and the European Association of Urology recommends a second transurethral resection of the bladder (ReTUR). Stage at ReTUR has been shown to be a reliable predictor of survival, therefore, we sought to assess clinical and pathological predictors associated with the persistence of T1 at ReTUR in our retrospective multicentric cohort. METHODS: This is a retrospective multicentric study of T1 HG patients at transurethral resection of the bladder (TURB) who underwent subsequent ReTUR. All histological samples were sub-classified according to Rete Oncologica Lombarda (ROL) T1 sub-staging system. RESULTS: One hundred and sixty-six patients were enrolled. Forty-four (26.5%) had T1 HG tumor at ReTUR while 93 (56%) had residual tumor of any stage. Lesion size was significantly greater in T1 HG patients at ReTUR, as well as the prevalence of multifocality. The multivariable logistic regression model showed lesion dimension and multifocality as predictors of T1 HG at ReTUR, after adjusting for significant covariables (CIS and detrusor muscle presence). ROL sub-staging system was not a significant predictor, but ROL2 prevalence was higher in the T1 HG at ReTUR group. CONCLUSIONS: Lesion size and multifocality were independent predictors of T1 HG persistence at ReTUR, and patients at risk should be promptly identified and treated accordingly. Our results could help physicians make patient-tailored decisions by identifying those most likely to benefit from a second resection.
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Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Estadiamento de Neoplasias , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Cistectomia/métodosRESUMO
BACKGROUND: One-stage buccal mucosa graft urethroplasty (BMGU) is advised for non-obstructing, simple penile strictures due to lichen sclerosus (LS), while a multistage approach is preferred for most complex cases. Our study aims to evaluate long-term treatment outcomes and patient-reported outcomes (PROs) in patients undergoing multistage BMGU for LS-associated penile strictures. METHODS: This is a retrospective analysis of prospectively collected data on multistage penile BMGU from 2001. All patients underwent a 2-stage (2St) or 3-stage (3St) BMGU with the final closure of the urethral plate. PROs were collected from a pre-defined questionnaire. RESULTS: Twenty patients were successfully treated, while five experienced recurrence. If a first-stage Johanson was only performed, a 3St-BMGU was more likely, and higher treatment success was observed. A time course between the first and last stages shorter than 12 m was an independent predictor of treatment failure. Patients reported high overall satisfaction and urinary flow improvement. Sexual life was not significantly affected, while aesthetic appearance was the most affected dimension. CONCLUSIONS: Staged approaches have satisfactory treatment success rates, likely depending on the duration from the first to the last stage. PROs do not differ based on the number of stages performed, and overall satisfaction with the procedure is high.
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(1) Background: Glucose metabolism derangements (GMD) and thyroid nodules (TNs) are the most frequent endocrine disorders, and their relationship is still controversial; little evidence is reported regarding sex differences. We aim to evaluate the association between GMDs and TNs according to sex and the sex differences in glucose metabolism and insulin sensitivity (IS). (2) Methods: We evaluated 342 patients (268 females and 74 males) at high GMD risk undergoing an oral glucose tolerance test and a thyroid ultrasound. (3) Results: The TN prevalence was 61% (n = 210), with no significant differences according to sex and GMD classes. The TN presence is significantly associated with age and impaired fasting glucose (IFG) in females. Males and females with normal fasting glucose (NFG) had a significantly lower OR of having TNs than females with IFG. IFG females had a significantly higher predicted probability of having TNs than NFG males and females but not IFG males. Impaired glucose tolerance/Type 2 diabetes mellitus (IGT/T2DM) is significantly associated with age and male sex, while IFG is associated with age. Females had significantly lower HOMA-index values than males. (4) Conclusions: No significant association between IGT/T2DM and TNs according to sex was found. IFG seems to play a role in TN development independently of sex. Further studies are needed to explore the relationship between TNs and GMD to identify subgroups with a higher TN risk.
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PURPOSE: To define predictors of malignancy after Testis sparing surgery (TSS) in patients referring to a fertility center with incidental small testicular lesions. Sub analyses were performed to assess predictors of Leydig cell hyperplasia and Leydig cell tumor. MATERIALS AND METHODS: We performed a retrospective analysis of a single institutional database including patients treated with TSS between 2002 and 2020. All patients who underwent TSS as a first line surgical approach for incidentally detected lesions found during fertility evaluation were included. RESULTS: Data of 64 patients were collected. The median follow up was 58 months and no recurrences were observed. At univariable logistic regression multifocal lesions, hypervascularization, microlithiasis, age and lesion size were significantly associated with malignancy. At multivariable logistic regression lesion dimension, hypervascularization and multifocal lesions were predictors of malignancy. Lesions smaller than 5 mm proved to be benign in 96.6% of the cases (32/33). Intraoperative color of the lesion and US pattern of vascularization were predictors at multivariable logistic regression for Leydig cell hyperplasia and Leydig cell tumor. CONCLUSION: Ultrasonographic characteristics and intraoperative appearance of the lesion can predict the malignant nature of small testicular lesions, guiding their surgical management in patients referring to a fertility center. Based on our experience, clinicians may safely perform TSS in carefully selected patients.
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Tumor de Células de Leydig , Neoplasias Testiculares , Humanos , Hiperplasia/patologia , Tumor de Células de Leydig/patologia , Tumor de Células de Leydig/cirurgia , Masculino , Orquiectomia , Estudos Retrospectivos , Neoplasias Testiculares/patologia , Neoplasias Testiculares/cirurgia , Testículo/diagnóstico por imagem , Testículo/patologia , Testículo/cirurgiaRESUMO
A PCR-based DNA walking analysis was performed on a protease product suspected to contain a new unauthorized genetically modified microorganism (GMM). Though the characterization of unnatural associations of sequences between the pUB110 shuttle vector and a Bacillus amyloliquefaciens gene coding for a protease, the presence of the GMM was shown. Based on these sequences of interest, a real-time PCR marker was developed to target specifically the newly discovered GMM, namely GMM protease2. The performance of the real-time PCR marker was assessed in terms of specificity and sensitivity. The applicability of the real-time PCR GMM protease2 marker was also demonstrated on microbial fermentation products. To confirm its use by other GMO enforcement laboratories, the transferability of the in-house validated real-time PCR marker was demonstrated by assays performed by an external laboratory.