Clinical study of steroid receptors in nonmuscle invasive bladder cancer: A domain worth revisiting.

Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.

Perioperative and functional outcomes following robot-assisted partial nephrectomy: Descriptive analysis of Indian study group on partial nephrectomy database.

Introduction: There is an unmet need for high-quality data for Robot-assisted partial nephrectomy (RAPN) in the Indian population. Indian study group on partial nephrectomy (ISGPN) is a consortium of Indian centers contributing to the partial nephrectomy (PN) database. The current study is a descriptive analysis of perioperative and functional outcomes following RAPN. Methods: For this study, the retrospective ISGPN database was reviewed, which included patients who underwent RAPN for renal masses at 14 centers across India from September 2010 to September 2022. Demographic, clinical, radiological, perioperative, and functional data were collected and analyzed. Ethics approval was obtained from each of the participating centers. Results: In this study, 782 patients were included, and 69.7% were male. The median age was 53 years (interquartile range [IQR 44-62]), median operative time was 180 min (IQR 133-240), median estimated blood loss was 100 mL (IQR 50-200), mean warm ischemia time was 22.7 min and positive surgical margin rates were 2.5%. The complication rate was 16.2%, and most of them were of minor grade. Trifecta and pentafecta outcomes were attained in 61.4% and 60% of patients, respectively. Conclusions: This is the largest Indian multi-centric study using the Indian Robotic PN Collaborative database to evaluate the outcomes of robot-assisted PN, and has proven its safety and efficacy in the management of renal masses.

177Lu-PSMA-617 versus docetaxel in chemotherapy-naïve metastatic castration-resistant prostate cancer: a randomized, controlled, phase 2 non-inferiority trial.

PURPOSE: Lutetium-177 prostate-specific membrane antigen-617 (177Lu-PSMA-617) in end-stage metastatic castration-resistant prostate cancer (mCRPC) has reported favourable outcomes. In this study, we aimed to prospectively compare the efficacy and safety of 177Lu-PSMA-617 and docetaxel in chemotherapy-naïve mCRPC patients. METHODS: This was a randomized, parallel-group, open-label, phase 2, and non-inferiority trial. Chemotherapy-naïve patients with mCRPC and high PSMA-expressing lesions on 68 Ga-PSMA-11 PET/CT were randomly assigned in 1:1 ratio to 177Lu-PSMA-617 (6.0-7.4 GBq/cycle, every 8 weeks, up to 4 cycles) or docetaxel (75 mg/m2/cycle, every 3 weeks, up to 10 cycles). The primary end-point was best prostate-specific antigen response rate (PSA-RR), defined according to Prostate Cancer Clinical Trials Working Group-3 as proportion of patients achieving ≥ 50% decline in PSA from baseline. Non-inferiority margin of - 15% was pre-specified for PSA-RR. RESULTS: Between December 2019 and March 2021, 40 of the 45 patients assessed for eligibility underwent randomization. Fifteen of 20 patients in 177Lu-PSMA-617 arm and 20/20 patients in docetaxel arm received treatment per protocol. Of these, best PSA-RR in the 177Lu-PSMA-617 arm was 60% (9/15) versus 40% (8/20) in the docetaxel arm. The difference in the PSA-RRs between the two arms was 20% (95% confidence interval, CI: - 12-47, P = 0.25), meeting the pre-specified criterion for non-inferiority in per-protocol analysis. Further, progression-free survival rates at 6 months were 30% and 20% in the 177Lu-PSMA-617 and docetaxel arms respectively (difference 10%, 95% CI: - 18-38, P = 0.50). Overall, treatment-emergent grade ≥ 3 adverse events occurred less frequently with 177Lu-PSMA-617 than with docetaxel (6/20, 30% versus 10/20, 50%, respectively, P = 0.20). Quality-of-life outcomes improved significantly in 177Lu-PSMA-617 arm compared to docetaxel arm (P < 0.01). CONCLUSION: 177Lu-PSMA-617 was demonstrated to be safe and non-inferior to docetaxel in the treatment of mCRPC and could, thus, be potentially employed earlier in the disease course rather than being solely reserved for advanced end-stage disease. CLINICAL TRIAL REGISTRATION: Clinical Trials Registry-India, CTRI/2019/12/022282.

Characterization, genome analysis and in vitro activity of a novel phage vB_EcoA_RDN8.1 active against multi-drug resistant and extensively drug-resistant biofilm-forming uropathogenic Escherichia coli isolates, India.

AIM: We aimed to study host range, stability, genome and antibiofilm activity of a novel phage vB_EcoA_RDN8.1 active against multi-drug resistant (MDR) and extensively drug-resistant (XDR) biofilm-forming uropathogenic Escherichia coli isolates. METHODS AND RESULTS: A novel lytic phage vB_EcoA_RDN8.1 active against UPEC strains resistant to third-generation cephalosporins, fluoroquinolones, aminoglycosides, imipenem, beta-lactamase inhibitor combination and polymyxins was isolated from community raw sewage water of Chandigarh. It exhibited a clear plaque morphology and a burst size of 250. In the time-kill assay, the maximum amount of killing was achieved at MOI 1.0. vB_EcoA_RDN8.1 belongs to the family Autographiviridae, has a genome size of 39.5 kb with a GC content of 51.6%. It was stable over a wide range of temperatures and pH. It was able to inhibit biofilm formation which may be related to an endolysin encoded by ORF 19. CONCLUSIONS: The vB_EcoA_RDN8.1 is a novel lytic phage that has the potential for inclusion into phage cocktails being developed for the treatment of urinary tract infections (UTIs) caused by highly drug-resistant UPEC. SIGNIFICANCE AND IMPACT OF THE STUDY: We provide a detailed characterization of a novel lytic Escherichia phage with antibiofilm activity having a potential application against MDR and XDR UPEC causing UTIs.

Robot-assisted partial nephrectomy for moderate to highly complex renal masses. A systematic review and meta-analysis.

Introduction: Multiple studies have been published recently assessing feasibility of robot-assisted partial nephrectomy (RAPN) for moderate to highly complex renal masses. Some studies have even compared partial nephrectomy (PN) performed through various modalities such as open PN (OPN) versus RAPN and laparoscopic PN (LPN) versus OPN. The primary aim of this review was to analyze perioperative outcomes such as warm ischemia time (WIT), duration of surgery, estimated blood loss (EBL), complications, blood transfusion, length of stay, and margin status following RAPN for complex renal masses. Another objective was to compare perioperative outcomes following various surgical modalities, i.e., OPN, LPN, or RAPN. Methods: Literature search was conducted to identify studies reporting perioperative outcomes following RAPN for moderate (Radius, Endophytic/Exophytic, Nearness, Anterior/posterior location [RENAL] score 7-9 or Preoperative Aspects of Dimension used for anatomic classification [PADUA] score 8-9) to high complexity renal masses (RENAL or PADUA score ≥ 10). Meta-analysis of robotic versus OPN and robotic versus LPN was also performed. Study protocol was registered with PROPSERO (CRD42019121259). Results: In this review, 22 studies including 2,659 patients were included. Mean duration of surgery, WIT, and EBL was 132.5-250.8 min, 15.5-30 min, and 100-321 ml, respectively. From pooled analysis, positive surgical margin, need for blood transfusion, minor and major complications were seen in 3.9%, 5.2%, 19.3%, and 6.3% of the patients. No significant difference was noted between RAPN and LPN for any of the perioperative outcomes. Compared to OPN, RAPN had significantly lower EBL, complications rate, and need for transfusion. Conclusions: RAPN for moderate to high complexity renal masses is associated with acceptable perioperative outcomes. LPN and RAPN were equal in terms of perioperative outcomes for complex masses whereas, OPN had significantly higher blood loss, complications rate, and need for transfusion as compared to RAPN.

Safety and efficacy of bipolar versus monopolar transurethral resection of bladder tumor: a systematic review and meta-analysis.

PURPOSE: Transurethral resection of bladder tumor is the standard of care for the management of patients with bladder mass. Primary objective of this study was to compare safety and efficacy of the two energy modalities used for TURBT (monopolar and bipolar). MATERIALS AND METHODS: Systematic literature search of various electronic databases was conducted to include all the randomized studies comparing two groups. Standard PRISMA (Preferred reporting Items for Systematic reviews and Meta-analysis) guidelines were pursued for this review and study protocol was registered with PROSPERO (CRD42019139987). RESULTS: In the present review, eight RCTs including 1147 patients were included. Resection time, hospital stay and catheter duration were significantly shorter with bipolar group. There was no significant difference in incidence of obturator reflex (OR 0.65, CI [0.35, 1.2], p = 0.17), whereas incidence of bladder perforation was significantly higher in the monopolar group (6.4% versus 3.3%, p = 0.01. However, sensitivity analysis including 3 high quality studies revealed equal incidence of bladder perforations. Need for blood transfusion was similar in the two groups but fall in hemoglobin was significantly lower in bipolar group (MD - 0.45 CI [- 0.72, - 0.18], p = 0.0009). Bipolar group was found to have significantly lower incidence of tissue artifacts due to thermal energy on pathological examination (OR 0.27 CI [0.15, 0.47], p < 0.00001). CONCLUSIONS: Bipolar and monopolar devices are equally safe in terms of obturator jerk and bladder perforation. Bipolar group was significantly better as compared to monopolar for hospital stay, catheter duration and fall in hemoglobin; however, the clinical relevance of most of these parameters is little.

Primary primitive neuroectodermal tumour of the kidney in adults: Experience of managing 12 cases with systematic review and pooled analysis of literature.

INTRODUCTION: Primitive neuroectodermal tumor (PNET) of the kidney is unusual in adults. These tumours are diagnosed mainly on histopathology and that too sometimes has limitations. With this study, we aimed to review our clinical and histopathological data of patients with renal PNET and reviewing the world literature. METHODS: In this retrospective study, we reviewed our database from January 2006 to July 2018 to include all the cases of primary PNET of the kidney. We also performed systematic literature search to identify all the relevant series on renal PNET. RESULTS: A total of 12 patients including 5 men and 7 women were managed during the above mentioned period. Out of these 7 patients, 2 patients had metastasis at diagnosis, one had locally advanced disease, 6 underwent radical nephrectomy, 5 patients received adjuvant chemotherapy (two currently receiving) and only 1 patient received adjuvant radiotherapy (RT). On Immunohistochemistry (IHC), CD99 and FLI1 were positive in all the patients. Median survival was 10 months. In our review 10 studies were included, 38.6% of the patients had metastatic disease and 10.7% had locally advanced disease at diagnosis. Overall mean survival was 33.75 months. CD99 and FLI1 were positive in 94.3% and 78.5%, respectively. CONCLUSION: PNET remains a pathological diagnosis and IHC has important place in diagnosis of PNET. Locally advanced and metastatic disease is common at diagnosis leading to overall poor survival.

Development and validation of a novel prediction model for predicting renal function recovery after diversion in patients with obstructive uropathy.

OBJECTIVE: To develop and validate a novel prediction model predicting renal function recovery following diversion in patients with obstructive uropathy (OU) to the emergency department (ED). METHODS: After a systematic literature search, a novel prediction model called PGIMER Obstructive Uropathy Score (POUS) was constructed including five variables: age (<60 or >60 years), duration of symptoms (<4 or >4 weeks), presence of solitary functioning kidney, baseline hemoglobin levels and venous blood pH. This model was then validated in a prospective, observational single-center study of patients presenting with OU caused by various etiologies. Patients with OU and raised serum creatinine (>2 mg/dL) presenting to our ED were included. Renal function recovery was defined as creatinine value <1.5 mg/dL at 4 weeks following diversion. RESULTS: In this study, 174 consecutive patients with OU were recruited, and 74 (42.5%) patients had renal function recovery. All the variables included in the POUS were noted to be statistically significant on univariate analysis. On multivariate logistic regression analysis, only POUS was identified as an independent predictor of renal function recovery. On receiver operating curve analysis, the area under the curve for POUS was 0.832 for predicting recovery. A POUS of 5 or more had specificity and sensitivity of 83% and 73.6%, respectively, in predicting renal function recovery. The goodness of fit and calibration plots showed good concordance of the predicted values with the observed values. CONCLUSIONS: The POUS model is an accurate and simple-to-use tool for predicting renal function recovery. POUS model requires external validation prior to clinical use in different populations.

Safety and efficacy of "on-demand" tramadol in patients with premature ejaculation: an updated meta-analysis.

INTRODUCTION: Tramadol has been used for the treatment of premature ejaculation, however, the studies published for the same are not well designed. The primary objective of this study was to explore the literature pertaining to the use of tramadol in patients with PE to determine its safety and efficacy in this population. Materials ande methods: Systematic literature search of various electronic databases was conducted to include all the randomized studies and quasi-randomized studies. Standard PRISMA (Preferred reporting Items for Systematic reviews and Meta-analysis) guidelines were pursued for this review and study protocol was registered with PROSPERO (CRD42019123381). RESULTS: Out of 9 studies included in this review, 5 were randomized controlled trials, and rests of the 4 studies were quasi-randomized studies. Tramadol resulted in significantly higher improvement of IELT with the mean difference (MD) of 139.6 seconds and confidence interval (CI) 106.5-172.6 seconds with a p-value of p < 0.00001. All dosages except 25mg fared well as compared to placebo. Tramadol fared better than placebo at 1 month, 2 months, and 3 months after initiation of therapy as compared to the placebo. Tramadol group had reported a significantly higher number of adverse events with treatment as compared to placebo but none of them were serious. CONCLUSION: Tramadol appears to be an effective drug for the management of PE with a low propensity for serious adverse events. However, evidence obtained from this study is of low to moderate quality. Furthermore, effective dose and duration of therapy remain elusive.

Trifecta and pentafecta outcomes following robot-assisted partial nephrectomy for hilar versus nonhilar tumors: A propensity-matched analysis.

INTRODUCTION: Hilar tumors are a unique subset of complex renal masses posing a potential surgical challenge during partial nephrectomy. The outcomes of hilar masses have not been compared to non-hilar renal masses of similar RENAL nephrometry score (RNS). In this study, we analyzed the outcomes of hilar versus nonhilar masses after a propensity score matching. METHODS: Prospectively maintained database of patients who underwent robot assisted PN between November 2014 and December 2018 was abstracted for hilar and nonhilar tumors. We performed propensity matching for baseline variables such as age, sex, body mass index, comorbidities, preoperative glomerular filtration rate, and RNS for each patient on the basis of propensity scores. RESULTS: We included 48 patients with hilar tumors and 153 with nonhilar tumors. On propensity matching, 41 patients were included in each group. The mean operative time (162.4 ± 48.9 min vs. 144.1 ± 38.8 min, P = 0.48), warm ischemia time (29.0 ± 8.8 min vs. 24.4 ± 8.2 min, P = 0.12), and the estimated blood loss (201.8 ± 184.7 ml vs. 150.6 ± 160.5 ml, P = 0.37) were not significantly different between the hilar and the nonhilar groups. Trifecta was achieved in only 14/41 (34.1%) of the patients in the hilar group as compared to 24/41 (58.5%) in the nonhilar group (P = 0.027). Logistic regression analysis identified that hilar location of the tumors was not an independent predictor of overall complications (OR 6.37, confidence interval [CI] 0.5-69.4, P = 0.4), trifecta (OR 0.38, CI 0.14-1.0, P = 0.051), and pentafecta outcomes (OR 0.4, CI 0.1-1.51, P = 0.17). CONCLUSIONS: Hilar location was associated with poorer trifecta outcomes compared to the nonhilar tumors. However, hilar location per se was not an independent predictor of overall complications and trifecta and pentafecta outcomes.

Role of phosphodiesterase inhibitors in stent-related symptoms: a systematic review and meta-analysis.

PURPOSE: Stent-related symptoms are frequent following stent placement for various indications. Use of PDE inhibitors has expanded beyond their classical indication and has been tried in patients with stent-related symptoms. The systematic review was conducted to ascertain the efficacy of PDE inhibitors in ameliorating stent-related symptoms. METHODS: We performed systematic review and metanalysis on the use of PDE inhibitors for stent-related symptoms in patients who underwent stent placement for various reasons (postpercutaneous nephrolithotomy or ureterorenoscopy). We followed PRISMA guidelines while conducting this review and study protocol was registered with PROSPERO (CRD42019121781) RESULTS: Three studies with 280 participants were included in this review. There was considerable heterogeneity across all the outcome parameters assessed; thus, random-effect model was used for analysis. Comparison of PDE inhibitors with control arm revealed that PDE inhibitors were significantly more effective than placebo in all but one domain (Work performance) of the USSQ. On comparison with alfa blockers, PDE inhibitors were found to be equally effective for urinary symptoms, general health, and body pain parameters, but sexual health parameters improved significantly with PDE inhibitors. CONCLUSION: PDE inhibitors can be considered an option for patients with stent-related symptoms especially in patients with sexual dysfunction. Due to various limitations of the studies included in this review, we recommend conducting further high-quality studies.

ACTH increment post total bilateral adrenalectomy for Cushing's disease: a consistent biosignature for predicting Nelson's syndrome.

PURPOSE: Nelson's syndrome (NS) is regarded as an aggressive complication of total bilateral adrenalectomy (TBA) for Cushing's disease (CD). This challenge may be addressed by using clinical criteria to guide frequency of neuroimaging to enable timely management of NS and also avoid unnecessary frequent imaging. METHODS: All patients (n = 43) with CD subjected to TBA over 35 years at a tertiary care centre were included. NS was defined as a newly appearing or expanding (> 2 mm) pituitary adenoma with or without ACTH levels exceeding 500 pg/ml. Pre-and post-TBA parameters like clinical symptomatology, cortisol, ACTH and radiology were analysed for the prediction of NS. RESULTS: NS developed in 39.5% (n = 17) patients with a median follow-up of 7 years. Half of them had new appearance, while rest had an expansion of pre-existing pituitary tumour. Majority (90%) had ACTH above 500 pg/ml. On Cox proportional hazards analysis, frequent discriminatory features of protein catabolism (≥ 4) (HR 1.15, CI 0.18, 7.06), proximal myopathy (HR 8.82, CI 1.12, 69.58) and annual ACTH increment of 113 pg/ml (HR 12.56, CI 1.88, 88.76) predicted NS. First post-operative year ACTH indices predicting NS included ACTH rise of 116 pg/ml and absolute ACTH of 142 pg/ml (sensitivity, specificity exceeding 90%). Annual ACTH increment exceeding 113 pg/ml, ≥ 4 discriminatory features and uncontrolled hypertension had the best overall prediction. CONCLUSION: Patients who developed NS had higher rebound rise of ACTH following TBA and a more severe disease phenotype at baseline. Consistent ACTH increment can be used as a marker for predicting the development of NS.

Renal cell carcinoma in a pancake kidney: A rare entity.

Pancake kidney is a rare form of renal fusion anomaly. Renal cell carcinoma in such an entity is even rarer and poses a challenge in management due to anomalous vessels. We describe one such patient with an emphasis on successful performance of partial nephrectomy by meticulous planning, with good oncological and functional outcomes.

Arteriovenous malformation with a renal mass: A rare association.

Renal arteriovenous malformation can be rarely associated with a renal mass. A vigilant approach and careful planning is required to tackle both the pathologies in form of preoperative coil embolization followed by a minimally invasive radical nephrectomy.

Prolonged natural history of a cystic renal cell carcinoma: A case report.

We describe the successful management of a 50-year male who presented with gradually progressive abdominal swelling for over 20 years. The highlights of the case are giant renal mass occupying the whole abdomen and the absence of metastasis despite a long history.

Clinical spectrum, diagnosis, and sexual dysfunction after repair of fracture penis: Is no news good news?

INTRODUCTION: Penile fracture is a rare urological emergency, best managed by early surgical intervention, but the data on subsequent sexual function is sparse. This study was designed to analyze the clinical spectrum and sexual function after penile fracture repair at our tertiary care center. MATERIALS AND METHODS: Ambispective observational study was undertaken from July 2002 to August 2019 which included patients admitted with a history of trauma to the penis in the erect state. The clinical presentation, etiology and the details of the surgical management were noted. Patients were contacted telephonically and were called for follow-up. They were evaluated for the presence of penile nodules or curvature, and the erectile function was objectively recorded using the Sexual Health Inventory for Men (SHIM) questionnaire and the Erection Hardness Score (EHS). RESULTS: Median age at injury was 37 years, and injury during the sexual intercourse (33/43) was the most common etiology. Five patients presented with blood at the meatus. Ultrasound was performed in 27 patients and could detect the injury with a 55% sensitivity. All but one case were repaired through a subcoronal degloving incision. At a median follow-up of 36 months, follow-up data of 20 patients were available. Of the 20 patients, 14 were sexually active. The mean SHIM score was 21.36 ± 1.33 and the mean EHS was 3.21 ± 0.43. Four of the 20 patients developed penile nodule while 2 of them had penile curvature which was not bothersome. CONCLUSION: Penile fracture remains primarily a clinical diagnosis. Although prompt diagnosis and an emergent surgical exploration provides good outcomes in terms of preservation of erectile function, patients should be apprised about the problems of penile nodule and curvature.

Contraceptive efficacy of sperm agglutinating factor from Staphylococcus warneri, isolated from the cervix of a woman with inexplicable infertility.

BACKGROUND: Voluntary control of fertility is of paramount importance to the modern society. But since the contraceptive methods available for women have their limitations such as urinary tract infections, allergies, cervical erosion and discomfort, a desperate need exists to develop safe methods. Vaginal contraceptives may be the answer to this problem, as these are the oldest ways of fertility regulation, practiced over the centuries. With minimal systemic involvement, these are also the safest. Natural substances blocking or impairing the sperm motility offer as valuable non-cytotoxic vaginal contraceptives. Antimicrobial peptides (AMPs) isolated from plants, animals and microorganisms are known to possess sperm immobilizing and spermicidal properties. Following this, in the quest for alternative means, we have cloned, over expressed and purified the recombinant sperm agglutinating factor (SAF) from Staphylococcus warneri, isolated from the cervix of a woman with unexplained infertility. METHODS: Genomic library of Staphylococcus warneri was generated in Escherichia coli using pSMART vector and screened for sperm agglutinating factor (SAF). The insert in sperm agglutinating transformant was sequenced and was found to express ribonucleotide-diphosphate reductase-α sub unit. The ORF was sub-cloned in pET28a vector, expressed and purified. The effect of rSAF on motility, viability, morphology, Mg++-dependent ATPase activity and acrosome status of human sperms was analyzed in vitro and contraceptive efficacy was evaluated in vivo in female BALB/c mice. RESULTS: The 80 kDa rSAF showed complete sperm agglutination, inhibited its Mg2+-ATPase activity, caused premature sperm acrosomal loss in vitro and mimicked the pattern in vivo showing 100% contraception in BALB/c mice resulting in prevention of pregnancy. The FITC labeled SAF was found to bind the entire surface of spermatozoa. Vaginal application and oral administration of rSAF to mice for 14 successive days did not demonstrate any significant change in vaginal cell morphology, organ weight and tissue histology of reproductive and non-reproductive organs and had no negative impact in the dermal and penile irritation tests. CONCLUSION: The Sperm Agglutinating Factor from Staphylococcus warneri, natural microflora of human cervix, showed extensive potential to be employed as a safe vaginal contraceptive.

Phosphodiesterase inhibitors for lower urinary tract symptoms consistent with benign prostatic hyperplasia.

OBJECTIVES: To assess the effects of phosphodiesterase inhibitors (PDEI) compared to placebo and other standard of care drugs i.e alpha blockers (AB) and 5-alpha reductase inhibitors (5-ARI) in men with LUTS consistent with benign prostatic hyperplasia (BPH). METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Web of Science, and clinical trials registries of the World Health Organization (WHO) and the National Institutes of Health (NIH) (updated 2 August 2018). Citation tracking and hand-searching of abstracts and conference proceedings was done. We also attempted to contact the study authors in case additional information was needed. Randomised controlled trials (RCT) comparing PDEI versus placebo, AB, or 5-ARI used for at least four weeks in men with BPH-LUTS were included. Three review authors independently screened the literature and extracted data. Primary outcomes were effects on urinary symptoms as assessed by the International Prostate Symptom Score (IPSS-total; score ranging from 0 to 35, with higher values reflecting more symptoms), urinary bother as assessed by the Benign Prostatic Hyperplasia Impact Index (BPHII; score ranging from 0 to 13, with higher values reflecting more bother), and adverse events (AE). We used GRADE to rate the quality of evidence. We considered short-term (up to 12 weeks) and long-term (12 weeks or longer) results separately. RESULTS: We included a total of 16 randomised trials in this review. Primary outcomes: PDEI versus placebo: PDEI may result in a small improvement in IPSS-total score (mean difference (MD) 1.89 lower, 95% confidence interval (CI) 2.27 lower to 1.50 lower; n = 4293; low-quality evidence) compared to placebo, and may reduce the BPHII score slightly (MD 0.52 lower, 95% CI 0.71 lower to 0.33 lower; n = 3646; low-quality evidence). Rates of AEs may be increased (risk ratio (RR) 1.42, 95% CI 1.21 to 1.67; n = 4386; low-quality evidence). This corresponds to 95 more AEs per 1000 participants (95% CI 47 more to 151 more per 1000). Study results were limited to a treatment duration of six to 12 weeks. PDEI versus AB: PDEI and AB probably provide similar improvement in IPSS-total score (MD 0.22 higher, 95% CI 0.49 lower to 0.93 higher; n = 933; moderate-quality evidence) and may have a similar effect on BPHII score (MD 0.03 higher, 95% CI 1.10 lower to 1.16 higher; n = 550; low-quality evidence) and AE (RR 1.35, 95% CI 0.80 to 2.30; n = 936; low-quality evidence). This corresponds to 71 more AEs per 1000 participants (95% CI 41 fewer to 264 more per 1000). Study results were limited to a treatment duration of six to 12 weeks. PDEI and AB versus AB : The combination of PDEI and AB may provide a small improvement in IPSS-total score (MD 2.56 lower, 95% CI 3.92 lower to 1.19 lower; n = 193; low-quality evidence) compared to AB alone. We found no evidence for BPHII scores. AE may be increased (RR 2.81, 95% CI 1.53 to 5.17; n = 194; moderate-quality evidence). This corresponds to 235 more AE per 1000 participants (95% CI 69 more to 542 more per 1000). Study results were limited to treatment duration of four to 12 weeks. PDEI and AB versus PDEI alone: The combination of PDEI and AB may provide a small improvement in IPSS-total (MD 2.4 lower, 95% CI 6.47 lower to 1.67 higher; n = 40; low-quality evidence) compared to PDEI alone. We found no data on BPHII or AE. Study results were limited to a treatment duration of four weeks. PDEI and 5-ARI versus 5-ARI alone: in the short term (up to 12 weeks), the combination of PDEI and 5-ARI probably results in a small improvement in IPSS-total score (MD 1.40 lower, 95% CI 2.24 lower to 0.56 lower; n = 695; moderate-quality evidence) compared to 5-ARI alone. We found no evidence on BPHII scores or AE. In the long term (13 to 26 weeks), the combination of PDEI and 5-ARI likely results in a small reduction in IPSS-total score (MD 1.00 less, 95% CI 1.83 lower to 0.17 lower; n = 695; moderate-quality evidence). We found no evidence about effects on BPHII scores. There may be no difference in rates of AE (RR 1.07, 95% CI 0.84 to 1.36; n = 695; low-quality evidence). This corresponds to 19 more AE per 1000 participants (95% CI 43 fewer to 98 more per 1000). We found no trials comparing other combinations of treatments or comparing different PDEI for BPH-LUTS. CONCLUSIONS: Compared to placebo, PDEI likely leads to a small reduction in IPSS-total and BPHII sores, with a possible increase in AE. There may be no differences between PDEI and AB with regards to improvement in IPSS-total, BPHII, and incidence of AE. There appears to be no added benefit of PDEI combined with AB compared to PDEI or AB or PDEI combined with 5-ARI compared to ARI with regards to urinary symptoms. Most evidence was limited to short-term treatment up to 12 weeks and of moderate or low certainty.

Contraceptive Sperm Agglutinating Proteins Identified in Staphylococcus warneri, Natural Microflora of an Infertile Woman.

Staphylococcus warneri, isolated from the cervix of an adult female with unexplained infertility, was found to agglutinate human spermatozoa in vitro leading to their death. A genomic library of S. warneri was generated using pSMART-Escherichia coli vector-host system. Approximately 3500 transformants were screened and four showed sperm agglutinating activity. Sperm agglutinating proteins (SAPs) were partially purified from the positive transformants and were found to agglutinate sperms in vitro. Cloned ORFs in positive transformants were sequenced and ORF finder identified them as endonuclease, accessory secretory protein-Asp1, accessory secretory protein-Asp2 and signal transduction protein. Mannose was found to competitively inhibit sperm agglutination, indicating that SAPs in S. warneri bind to mannose in glycoprotein receptors on the surface of sperms for agglutination. This is the first report on identification of SAPs which may be responsible for unexplained infertility in women and may be used as contraceptive agents.

Efficacy of tamsulosin and tadalafil in relieving benign prostatic hyperplasia related symptoms: A randomized double blind placebo controlled cross-over study.

INTRODUCTION: Tadalafil and Tamsulosin have both been approved for use in the management of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). This study compared the differential effects of these two on BPH-LUTS using a cross over study design. METHODS: Men ≥45 years of age, with an International Prostate Symptom Score (IPSS) ≥8 due to BPH-LUTS were included. The patients were randomized into sequence AB (tadalafil 10 mg OD followed by tamsulosin 0.4 mg OD) or BA in a double blind manner. All patients received a placebo lead-in period for 2 weeks, followed by an active drug for 6 weeks; placebo wash out for 4 weeks and then crossed over to second active drug for another 6 weeks. IPSS scores, Uroflowmetry parameters and International Index of Erectile Function-5 scores were recorded. RESULTS: Out of the 40 patients, 36 completed the study. Demographic and baseline characteristics were comparable between the two groups (AB and BA). No significant placebo effects were observed. Tadalafil and tamsulosin significantly improved the total IPSS score and quality of life (P < 0.05) as compared to the baseline. However, there were no significant differences between the two drugs with respect to extent of observed effect and which drug was prescribed 1st in the sequence respectively (P > 0.05). Significant period effect was observed (P < 0.05) i.e., the symptoms did not return to the baseline before the second treatment. Half of the nonresponders to either of the drugs responded when the drug was changed to the other. Tadalafil showed better improvement in EF score as compared to Tamsulosin. CONCLUSION: Both Tadalafil and Tamsulosin improved LUTS and erectile function and those patients who did not respond to Tadalafil showed improvement with Tamsulosin and vice-a-versa.