Which Drug to Discontinue 3 Months After Combination Therapy of Tadalafil plus Tamsulosin for Men with Lower Urinary Tract Symptom and Erectile Dysfunction? Results of a Prospective Observational Trial.

BACKGROUND: Safety and efficacy of tamsulosin and tadalafil for men with benign prostatic enlargement (BPE) and/or erectile dysfunction (ED) are defined. However, there are only a few pilot studies on combination therapy with these drugs for men with lower urinary tract symptom (LUTS)/BPE and ED. Moreover, preliminary reports are limited to 12 wk, without any information about subsequent therapies. OBJECTIVE: To evaluate the impact of discontinuation of tamsulosin versus tadalafil 12 wk after combination therapy. DESIGN, SETTING, AND PARTICIPANTS: Fifty consecutive patients with moderate-to-severe LUTS (International Prostate Symptom Score [IPSS] > 7) and mild-to-severe ED (International Index of Erectile Function-5 [IIEF-5] < 22) were treated with combination therapy (tamsulosin 0.4mg/d plus tadalafil 5mg/d) for 12 wk. After 12 wk, 25 patients discontinued tamsulosin (Group TAD), while 25 patients discontinued tadalafil (Group TAM). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Efficacy variables were IPSS (total, voiding, storage) and IIEF-5. Paired samples t test and analysis of variance were used. RESULTS AND LIMITATIONS: Groups TAD and TAM presented similar features (age, BMI, metabolic profile) including symptoms scores at baseline. Similar and significant improvements in IPSS (total, voiding, and storage) and IIEF-5 were recorded in both groups after 12 wk of combination therapy (all p< 0.001). Total IPSS was similar between the two groups at the end of the trial. However, we found between-group significant differences from baseline to 24 wk and from 12 to 24 wk in storage-IPSS (Group TAD: -3.32 vs Group TAM: -1.24, p= 0.002; Group TAD: +0.24 vs Group TAM: +1.20, p= 0.040, respectively) and in IIEF-5 (Group TAD: +4.64 vs Group TAM: +0.16, p< 0.001; Group TAD: -1.64 vs Group TAM: -4.40, p= 0.003). No significant treatment-related adverse event was recorded in both groups. CONCLUSIONS: After 12 wk of combination therapy, monotherapy with tadalafil for further 12 wk allows to preserve the improvement of storage IPSS and IIEF-5, in addition to total IPSS. PATIENT SUMMARY: In this report we evaluated the discontinuation of tamsulosin or tadalafil after 12 wk of combination therapy. We found that tadalafil monotherapy, for a further 12 wk, aids in retaining the improvement of storage symptoms and erectile function.

Tadalafil 5 mg Alone or in Combination with Tamsulosin 0.4 mg for the Management of Men with Lower Urinary Tract Symptoms and Erectile Dysfunction: Results of a Prospective Observational Trial.

Tadalafil 5 mg represents the standard for men with Erectile dysfunction (ED) and lower urinary tract symptoms (LUTS)/benign prostatic enlargement (BPE). We carried out an observational trial aiming to assess the efficacy and safety of Tadalafil compared with Tadalafil plus Tamsulosin. Seventy-five patients complaining of ED and LUTS were treated for 12-weeks with Tadalafil plus placebo (TAD+PLA-group) or with combination therapy tadalafil plus tamsulosin (TAD+TAM-group). Efficacy variables were: International Index of Erectile Function (IIEF), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Qmax) and safety assessments. Data were evaluated using paired samples T-test (baseline vs. 12-weeks) and analysis of variance (Δgroup-TAD+PLA vs. Δgroup-TAD+TAM). At baseline, both groups presented similar characteristics and symptoms scores (all: p > 0.05). From baseline to 12-weeks, all the subjects showed a significant improvement of IIEF, total-IPSS, storage-IPSS, Qmax (all: p < 0.001). Conversely, a significant improvement of voiding-IPSS was observed in TAD+TAM-group (-3.5 points, p < 0.001). Indeed, TAD+PLA-group showed a not significant improvement of voiding-IPSS (-2.0 points, p = 0.074). When we compared between-groups differences at 12-weeks, IIEF (p = 0.255), total-IPSS (p = 0.084) and storage-IPSS (p = 0.08) did not show any statistically significant differences, whereas, voiding-IPSS and Qmax were significantly better in TAD+TAM-group (p = 0.006 and p = 0.027, respectively). No severe treatment adverse events (TAEs) were reported in both groups. Tadalafil achieved the same improvements of IIEF, total-IPSS, storage-IPSS when compared to combination therapy. Instead, Qmax and voiding-IPSS were better managed with combination therapy, without change of TAEs.

Association between metabolic syndrome and intravesical prostatic protrusion in patients with benign prostatic enlargement and lower urinary tract symptoms (MIPS Study).

OBJECTIVE: To investigate the association between metabolic syndrome (MetS) and morphological features of benign prostatic enlargement (BPE), including total prostate volume (TPV), transitional zone volume (TZV) and intravesical prostatic protrusion (IPP). PATIENTS AND METHODS: Between January 2015 and January 2017, 224 consecutive men aged >50 years presenting with lower urinary tract symptoms (LUTS) suggestive of BPE were recruited to this multicentre cross-sectional study. MetS was defined according to International Diabetes Federation criteria. Multivariate linear and logistic regression models were performed to verify factors associated with IPP, TZV and TPV. RESULTS: Patients with MetS were observed to have a significant increase in IPP (P < 0.01), TPV (P < 0.01) and TZV (P = 0.02). On linear regression analysis, adjusted for age and metabolic factors of MetS, we found that high-density lipoprotein (HDL) cholesterol was negatively associated with IPP (r = -0.17), TPV (r = -0.19) and TZV (r = -0.17), while hypertension was positively associated with IPP (r = 0.16), TPV (r = 0.19) and TZV (r = 0.16). On multivariate logistic regression analysis adjusted for age and factors of MetS, hypertension (categorical; odds ratio [OR] 2.95), HDL cholesterol (OR 0.94) and triglycerides (OR 1.01) were independent predictors of TPV ≥ 40 mL. We also found that HDL cholesterol (OR 0.86), hypertension (OR 2.0) and waist circumference (OR 1.09) were significantly associated with TZV ≥ 20 mL. On age-adjusted logistic regression analysis, MetS was significantly associated with IPP ≥ 10 mm (OR 34.0; P < 0.01), TZV ≥ 20 mL (OR 4.40; P < 0.01) and TPV ≥ 40 mL (OR 5.89; P = 0.03). CONCLUSION: We found an association between MetS and BPE, demonstrating a relationship with IPP.

Adaptive changes of telocytes in the urinary bladder of patients affected by neurogenic detrusor overactivity.

Urinary bladder activity involves central and autonomic nervous systems and bladder wall. Studies on the pathogenesis of voiding disorders such as the neurogenic detrusor overactivity (NDO) due to suprasacral spinal cord lesions have emphasized the importance of an abnormal handling of the afferent signals from urothelium and lamina propria (LP). In the LP (and detrusor), three types of telocytes (TC) are present and form a 3D-network. TC are stromal cells able to form the scaffold that contains and organizes the connective components, to serve as guide for tissue (re)-modelling, to produce trophic and/or regulatory molecules, to share privileged contacts with the immune cells. Specimens of full thickness bladder wall from NDO patients were collected with the aim to investigate possible changes of the three TC types using histology, immunohistochemistry and transmission electron microscopy. The results show that NDO causes several morphological TC changes without cell loss or network interruption. With the exception of those underlying the urothelium, all the TC display signs of activation (increase in Caveolin1 and caveolae, αSMA and thin filaments, Calreticulin and amount of cisternae of the rough endoplasmic reticulum, CD34, euchromatic nuclei and large nucleoli). In all the specimens, a cell infiltrate, mainly consisting in plasma cells located in the vicinity or taking contacts with the TC, is present. In conclusion, our findings show that NDO causes significant changes of all the TC. Notably, these changes can be interpreted as TC adaptability to the pathological condition likely preserving each of their peculiar functions.

Which method is best for an early accurate diagnosis of acute heart failure? Comparison between lung ultrasound, chest X-ray and NT pro-BNP performance: a prospective study.

Acute heart failure is a common condition among adults presenting with dyspnea in the Emergency Department (ED), still the diagnosis is challenging as objective standardized criteria are lacking. First line work-up, other then clinical findings, is nowadays made with lung ultrasound imaging study, chest X-ray study and brain natriuretic peptide (BNP) level determination; however, it is not clear which is the best diagnostic test to be used and whether there is any real benefit for clinical judgement. We set up this study to compare the performances of these three diagnostic tools; furthermore, we combined them to find the best possible approach to dyspneic patients. This is a prospective observational study based in the ED. We enrolled adults presenting with dyspnea not trauma-related, they underwent lung ultrasound, and chest X-ray studies, and NT pro-BNP level determination. Then we compared the results with the diagnosis of acute heart failure established by an independent panel of experts. 236 patients were enrolled in the study. We find sensitivity and specificity for lung ultrasound of 57.73 and 87.97 %, for chest X-ray 74.49 and 86.26 %, for NT pro-BNP 97.59 and 27.56 %, respectively. Combining together the chest X-ray and lung ultrasound, we find the best overall performance with 84.69 % sensitivity, 77.69 % specificity and 87.07 % negative predictive value. From our results, we could not identify the "best test" to diagnose acute heart failure in an emergency setting, although we could suggest that a stepwise workup combining chest X-ray and lung ultrasound at first, then for those negative, a determination of NT pro-BNP assay would be a reasonable approach to the dyspneic patient.

Robotic vesico-vaginal fistula repair with no omental flap interposition.

INTRODUCTION AND HYPOTHESIS: A vesico-vaginal fistula (VVF) is a fistulous tract that connects bladder and vagina, causing urine leakage via the vagina. In the developed world, iatrogenic postoperative VVF is the most common case. Classically, when treating a VVF via the abdominal route, an abdominal flap is mobilized and interposed between the bladder and the vagina. METHODS: In our video, we describe a robotic VVF repair technique with no omental flap interpositioning for a vaginal vault-located fistula. RESULTS: Duration of surgery was 95 min, estimated blood loss was <50 ml. The postoperative course was uneventful. At the 6-month follow-up, which included clinical and cystographic examinations, the patient had not experienced any recurrence. CONCLUSION: In our opinion, a two-layered suturing technique using two semi-continuous sutures for vaginal closure and perpendicular interrupted stitches for bladder closure does not require omental flap mobilization, reducing operating time and possible complications related to accidental peritoneal injuries.