ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted.

Development of a multivariable prediction model for congenital unilateral absence of the vas deferens in male partners of infertile couples.

BACKGROUND: Congenital unilateral absence of vas deferens has been diagnosed in fertile and normozoospermic males and is associated with the risk of unilateral renal absence or cystic fibrosis transmembrane conductance regulator mutations; but no prediction model currently exists to diagnose this condition. OBJECTIVES: The study aims to identify clinical and biological variables that may have a predictive value for the diagnosis of congenital unilateral absence of vas deferens in male partners of infertile couples MATERIALS AND METHODS: We designed a retrospective, cross-sectional, case-control study on electronic health records of a single tertiary-care andrological centre collected between 1998 and 2018. We included all subjects diagnosed with congenital unilateral absence of vas deferens using combined scrotal and transrectal ultrasounds. Controls were confirmed free of congenital unilateral absence of vas deferens by the same way. Both groups received standardised exploration procedures. Multivariable logistic regression model was built in a backward stepwise manner. Model performance and calibration were assessed. The study is reported according to TRIPOD statement. RESULTS: We included 69 congenital unilateral absence of vas deferens cases and 78 controls. Cases had a lower semen volume than controls. The congenital unilateral absence of vas deferens risk was associated with history of cryptorchidism and both levels of semen fructose and α-glucosidase. These predictors were confirmed by a random forest algorithm. The area under the curve was 0.886 (95% interval: 0.81-0.92). Calibration was performed with the Hosmer-Lemeshow test (p = 0.88). DISCUSSION AND CONCLUSION: History of cryptorchidism, semen fructose and α-glucosidase were identified as relevant and independent predictors for the diagnosis of congenital unilateral absence of vas deferens. The model enables to identify male patients with a high risk of congenital unilateral absence of vas deferens to whom a transrectal ultrasounds would be proposed to confirm the diagnosis, whatever their semen parameters. It will also help to address the risks of unilateral renal absence and of cystic fibrosis transmembrane conductance regulator mutations carrying during the management of infertile couples.

Genitourinary Emergencies in Older Adults.

Older adults are frequently seen in the emergency department for genitourinary complaints, necessitating that emergency physicians are adept at managing a myriad of genitourinary emergencies. Geriatric patients may present with acute kidney injury, hematuria, or a urinary infection and aspects of how managing these presentations differs from their younger counterparts is emphasized. Older adults may also present with acute urinary retention or urinary incontinence as a result of genitourinary pathology or other systemic etiologies. Finally, genital complaints as they pertain to older adults are briefly highlighted with emphasis on emergent management and appropriate referrals.

Chlamydia trachomatis intra-bacterial and total plasmid copy number in clinical urogenital samples.

Chlamydia trachomatis (CT) increases its plasmid numbers when stressed, as occurs in clinical trachoma samples. Most CT tests target the plasmid to increase the test sensitivity, but some only target the chromosome. We investigated clinical urogenital samples for total plasmid copy numbers to assess its diagnostic value and intra-bacterial plasmid copy numbers to assess its natural variation. Both plasmid and chromosome copies were quantified using qPCR, and the plasmid:chromosome ratio (PCr) calculated in two cohorts: (1) 383 urogenital samples for the total PCR (tPCr), and (2) 42 vaginal swabs, with one half treated with propium-monoazide (PMA) to prevent the quantification of extracellular DNA and the other half untreated to allow for both tPCr and intra-bacterial PCr (iPCr) quantification. Mann-Whitney U tests compared PCr between samples, in relation to age and gender. Cohort 1: tPCr varied greatly (1-677, median 16). Median tPCr was significantly higher in urines than vaginal swabs (32 vs. 11, p < 0.001). Cohort 2: iPCr was more stable than tPCr (range 0.1-3 vs. 1-11). To conclude, tPCr in urogenital samples was much more variable than previously described. Transport time and temperature influences DNA degradation, impacting chromosomal DNA more than plasmids and urine more than vaginal samples. Data supports a plasmid target in CT screening assays to increase clinical sensitivity.

[Proposals for the diagnosis and treatment of andrologic diseases during the novel coronavirus pneumonia epidemic].

In December, 2019, several cases of novel coronavirus pneumonia (NCP) were reported in Wuhan, Hubei. Since then, more and more NCP cases, confirmed or suspected, have been found in China and other parts of the world, and the virus is now showing a tendency towards a wider spread. During the NCP epidemic, all medical workers are confronted with special challenges in the diagnosis and treatment of various diseases and required of even more accurate therapeutic protocols as well as stricter observation of the principles for the prevention and control of NCP. Therefore, the Andrology Branch of Chinese Medical Association convened relevant experts to summarize the special points for andrologic clinicians to attend to in the diagnosis and treatment of male diseases during the NCP epidemic.

Recommendations on the diagnosis of male infertility - genetic testing [Rekomendacje dotyczace diagnostyki genetycznej w nieplodnosci meskiej].

Male infertility is the cause of couples' infertility in about 50% of cases. Current recommendations on the diagnosis and treatment of male infertility advance thorough medical history taking and physical examination, to provide the basis for further genetic evaluation. The extent of genetic testing itself depends on the semen analysis results, which allow the risk of inheritance of chromosomal aberrations to be determined and the root causes of habitual miscarriages to be explained. In azoospermia, once the type of microdeletion has been identified, a decision can be made as to whether a testicular biopsy is required to obtain sperm for the artificial reproductive technology (ART) procedure. The physical examination, genetic interview, and hormonal results are helpful in deciding which genetic tests to perform. Our research facilitates genetic testing in the diagnosis of male infertility.

Applications of neural networks in urology: a systematic review.

PURPOSE OF REVIEW: Over the last decade, major advancements in artificial intelligence technology have emerged and revolutionized the extent to which physicians are able to personalize treatment modalities and care for their patients. Artificial intelligence technology aimed at mimicking/simulating human mental processes, such as deep learning artificial neural networks (ANNs), are composed of a collection of individual units known as 'artificial neurons'. These 'neurons', when arranged and interconnected in complex architectural layers, are capable of analyzing the most complex patterns. The aim of this systematic review is to give a comprehensive summary of the contemporary applications of deep learning ANNs in urological medicine. RECENT FINDINGS: Fifty-five articles were included in this systematic review and each article was assigned an 'intermediate' score based on its overall quality. Of these 55 articles, nine studies were prospective, but no nonrandomized control trials were identified. SUMMARY: In urological medicine, the application of novel artificial intelligence technologies, particularly ANNs, have been considered to be a promising step in improving physicians' diagnostic capabilities, especially with regards to predicting the aggressiveness and recurrence of various disorders. For benign urological disorders, for example, the use of highly predictive and reliable algorithms could be helpful for the improving diagnoses of male infertility, urinary tract infections, and pediatric malformations. In addition, articles with anecdotal experiences shed light on the potential of artificial intelligence-assisted surgeries, such as with the aid of virtual reality or augmented reality.

Genetic diagnosis and sperm retrieval outcomes for Chinese patients with congenital bilateral absence of vas deferens.

BACKGROUND: Congenital bilateral absence of the vas deferens (CBAVD) is a frequent cause of obstructive azoospermia. CBAVD is mainly caused by mutations in the CFTR (cystic fibrosis transmembrane conductance regulator) gene and is also related to the X-linked ADGRG2 (adhesion G protein-coupled receptor G2) gene. Genetic screening and counseling strategies for Chinese CBAVD populations remain controversial because the genetic background of CBAVD in Chinese population is largely unknown. OBJECTIVES: In this study, we aimed to study the mutation spectrum of CFTR and ADGRG2 in a group of CBAVD patients and to evaluate sperm retrieval outcomes in a subset of CBAVD patients. MATERIALS AND METHODS: Next-generation targeted sequencing was used to identify mutations in the CFTR and ADGRG2 genes in 38 CBAVD patients. In addition, we followed and analyzed nine of the 38 patients who were undergoing sperm retrieval surgery. RESULTS: In total, 27 of 38 (71.05%) patients carried at least one likely pathogenic or pathogenic mutation in CFTR or ADGRG2. In addition to the IVS9-5T allele, 15 CFTR and 1 ADGRG2 mutations were identified, including 4 novel mutations. CFTR hot-spot mutations were not identified in our study. Spermatozoon was successfully obtained in all nine patients who underwent MESA or TESE surgery, but most patients had spermatozoa with relatively low motility and high abnormality rates. DISCUSSION AND CONCLUSION: Except for the IVS9-5T allele, hot-spot mutations of CFTR may not exist in Chinese CBAVD patients. Therefore, next-generation targeted sequencing for whole CFTR and ADGRG2 gene may be the appropriate genetic testing method, and genetic counseling may be different from Caucasian populations. We observed a high success rate of sperm retrieval with relatively low motility and high abnormality rates in Chinese CBAVD patients. However, this is only a weak conclusion due to the small sample size.

Stereotactic body radiotherapy with periprostatic hydrogel spacer for localized prostate cancer: toxicity profile and early oncologic outcomes.

BACKGROUND: Multiple phase I-II clinical trials have reported on the efficacy and safety of prostate stereotactic body radiotherapy (SBRT) for the treatment of prostate cancer. However, few have reported outcomes for prostate SBRT using periprostatic hydrogel spacer (SpaceOAR; Augmenix). Herein, we report safety and efficacy outcomes from our institutional prostate SBRT experience with SpaceOAR placement. METHODS: Fifty men with low- or intermediate-risk prostate cancer treated at a single institution with linear accelerator-based SBRT to 3625 cGy in 5 fractions, with or without androgen deprivation therapy (ADT) were included. All patients underwent SpaceOAR and fiducial marker placement followed by pre-treatment MRI. Toxicity assessments were conducted at least weekly while on treatment, 1 month after treatment, and every follow-up visit thereafter. Post-treatment PSA measurements were obtained 4 months after SBRT, followed by every 3-6 months thereafter. Acute toxicity was documented per RTOG criteria. RESULTS: Median follow up time was 20 (range 4-44) months. Median PSA at time of diagnosis was 7.4 (2.7-19.5) ng/ml. Eighteen men received 6 months of ADT for unfavorable intermediate risk disease. No PSA failures were recorded. Median PSA was 0.9 ng/mL at 20 months; 0.08 and 1.32 ng/mL in men who did and did not receive ADT, respectively. Mean prostate-rectum separation achieved with SpaceOAR was 9.6 ± 4 mm at the prostate midgland. No grade ≥ 3 GU or GI toxicity was recorded. During treatment, 30% of men developed new grade 2 GU toxicity (urgency or dysuria). These symptoms were present in 30% of men at 1 month and in 12% of men at 1 year post-treatment. During treatment, GI toxicity was limited to grade 1 symptoms (16%), although 4% of men developed grade 2 symptoms during the first 4 weeks after SBRT. All GI symptoms were resolving by the 1 month post-treatment assessment and no acute or late rectal toxicity was reported > 1 month after treatment. CONCLUSIONS: Periprostatic hydrogel placement followed by prostate SBRT resulted in minimal GI toxicity, and favorable early oncologic outcomes. These results indicate that SBRT with periprostatic spacer is a well-tolerated, safe, and convenient treatment option for localized prostate cancer.

A Survey of the Common Mutations and IVS8-Tn Polymorphism of Cystic Fibrosis Transmembrane Conductance Regulator Gene in Infertile Men with Nonobstructive Azoospermia and CBAVD in Iranian Population

Background: Studies have revealed a strong association between mutations of CFTR gene and the congenital bilateral absence of the vas deferens (CBAVD), but the role of this gene in other types of male infertility is still unclear. The purpose of this study was to investigate the frequency of the most common mutations of the CFTR gene (DF508, G542X, N1303K, G551D, and W1282X) in a population of infertile men with nonobstructive azoospermia (NOA) and CBAVD in Iran. Methods: Blood samples were obtained from 50 NOA, 50 CBAVD, and 100 normal males (control). Genomic DNA was isolated from whole blood leukocytes, and the presence of common mutations of the CFTR gene was assessed by an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Restriction fragment length polymorphism (PCR-RFLP) was also used to analyze IVS8-Tn polymorphism. Results: It was found that 16%, 8%, and 8% of patients with CBAVD were heterozygote for DF508, G542X, and N1303K, respectively. The frequency of the 5T allele was 34% and higher than the normal group (p < 0.001). None of the common CFTR gene mutations were detected in NOA patients, and no significant difference was found in the distribution of the 5T allele between the NOA patients and the control group (5 vs. 3 p = 0.721). Conclusion: Based on the present case-control study, the CFTR gene mutations and IVS8-Tn polymorphisms are correlated with CBAVD; however, extensive investigations are necessary to determine the exact relationship between the gene mutations and other forms of male infertility.

Genitourinary melioidosis: a descriptive study.

Melioidosis is the disease caused by the soil and water bacterium, Burkholderia pseudomallei. Our study aimed to delineate its genitourinary manifestations. Over a 10-year period (2006-2016), 20 adults with culture-confirmed genitourinary melioidosis were identified. The patients were all men with a mean age of 45.3 ± 12.3 years. The common risk factors were diabetes mellitus (65%) and alcoholism (25%); a majority of patients (90%) had chronic melioidosis. Most had disseminated disease (n = 17) and 55% were bacteraemic. The prostate was the organ most frequently involved (60%, n = 12), followed by the kidney, bladder and seminal vesicles. Diagnosis was established by blood and urine cultures and imaging. Patients were successfully treated with ceftazidime intensive therapy followed by eradicative therapy, with surgical debridement and guided aspiration, when deemed necessary. There was one case fatality and no relapses. Melioidosis is an important differential to be considered in chronic genitourinary infections in the appropriate setting.

Urological symptoms among 23,240 men in the general danish population - concerns about symptoms, their persistence and influence on primary care contacts.

OBJECTIVE: To analyse possible associations between men's likelihood of contacting a general practitioner (GP) for urological symptoms and the persistence of the symptoms, the influence on daily activities and the level of concern about the symptoms. DESIGN: Web-based nationwide cross-sectional questionnaire study. SETTING: The general population in Denmark. SUBJECTS: 48,910 randomly selected men aged 20+ years. MAIN OUTCOME MEASURES: Urological symptom prevalence and odds ratios for GP contact with urological symptoms in regard to concern for the symptom, influence on daily activities and the persistence of the symptom. RESULTS: Some 23,240 men responded to the questionnaire, yielding a response rate of 49.8%. The prevalence of at least one urological symptom was 59.9%. Among men experiencing at least one urological symptom almost one-fourth reported contact to general practice regarding the symptom. Approximately half of the symptoms reported to be extremely concerning were discussed with a GP. CONCLUSION: Increased symptom concern, influence on daily activities and long-term persistence increased the likelihood of contacting a GP with urological symptoms. This research points out that guidelines for PSA testing might be challenged by the high prevalence of urological symptoms. Key points The decision process of whether to contact the general practitioner (GP) is influenced by different factors, but contradictory results has been found in triggers and barriers for help-seeking with urological symptoms. • Increased symptom concern, influence on daily activities and long-term persistence consistently increased the likelihood of contacting a general practitioner with urological symptoms in men. • Only 50% of the symptoms reported to be extremely concerning were however discussed with the GP. • Guidelines for PSA testing might be challenged by the high prevalence of urological symptoms.

Urethral lichen sclerosus under the microscope: a survey of academic pathologists.

INTRODUCTION: Given the poor understanding of the pathophysiology of genital lichen sclerosus (GLS) and a lack of accepted definitive diagnostic criteria, we proposed to survey pathologists regarding their understanding of GLS. We hypothesized that significant disagreement about GLS will exist. MATERIALS AND METHODS: All urologists participating in the Trauma and Urologic Reconstruction Network of Surgeons identified genitourinary (GUP) and dermatopathologists (DP) at their respective institutions who were then invited to participate in an online survey regarding their experience with diagnosing GLS, GLS pathophysiology and its relationship to urethral stricture disease. RESULTS: There were 23 (12 DP, 11 GUP) pathologists that completed the survey. The most agreed upon criteria for diagnosis were dermal collagen homogenization (85.7%), loss of the normal rete pattern (33.3%) and atrophic epidermis (28.5%). No pathologists believed GLS had an infectious etiology (19% maybe, 42% unknown) and 19% believed GLS to be an autoimmune disorder (42% maybe, 38% unknown); 19% believed LS to be premalignant, but 52% believed it was associated with cancer; 80% believed that LS could involve the urethra (DP (92%) versus GUP (67%); p = 0.272). Of those diagnosing urethral GLS, 80% of DUP believed that GLS must first involve the glans/prepuce before involving the urethra, while all GUP believed that urethral disease could exist in isolation (p = 0.007). CONCLUSIONS: There was significant disagreement in this specialized cohort of pathologists when diagnosing GLS. A logical first step appears to be improving agreement on how to best describe and classify the disease. This may lead to improve treatments.

Utility of GeneXpert in the diagnosis, reliance on urine microscopy and clinical characteristics of genitourinary tuberculosis at a tertiary care hospital.

BACKGROUND: One-third of the world's population is infected with tuberculosis (TB) with new infection occurring every second. In humans, TB is primarily caused by Mycobacterium tuberculosis(MTB). Genitourinary TB (GUTB) is still a major health problem in many developing countries including India and had been declared by the World Health Organisation as 'public health emergency' in 1993. MATERIALS AND METHODS: This is a prospective study conducted at a tertiary care hospital involving 46 patients who presented with clinical feature suggestive of GUTB - urine specimens of these 46 patients were analysed for acid-fast bacilli (AFB), AFB culture, GeneXpert, and other relevant investigations were done to reach the diagnosis. Majority of patients were female (65.25%). This is especially relevant to rural and low socioeconomic areas in developing countries where women's health is worse than men's (in terms of nutrition); women's risk of disease may be increased. Most of our patients were above 30 years of age and exhibited nonspecific symptoms such as dysuria, haematuria and frequency. All patients were put on antitubercular drugs and followed as per the guidelines. CONCLUSION: The sample size in the present study is small to arrive at a brisk inference, but it may safely be postulated that yield of detection for GeneXpert may be improved using multiple sampling, especially the early morning ones. It is also pertinent to mention here that GeneXpert may not be able to pick up mutant genomes.