Voiding and renal function 10 years after radical cystectomy and orthotopic neobladder in women.

OBJECTIVES: To assess long-term voiding and renal function (RF) changes after radical cystectomy (RC) and orthotopic neobladder (ONB) surgery in women without disease recurrence. MATERIAL AND METHODS: Women who underwent RC and ONB reconstruction between 1995 and 2011 were included in this study. Patients who developed disease failure or were lost to follow-up were excluded. The study outcomes were long-term voiding function and the incidence and predictors of RF deterioration (defined as >20% decline of baseline). Analysis was performed using the log-rank test and Cox regression analysis. RESULTS: The study included 195 patients with a median (interquartile range) follow-up of 98 (53-151) months, of whom 95 had >10 years of follow-up. Daytime continence, night-time continence and chronic urine retention (CUR) were identified in 170 (87%), 134 (69%) and 52 patients (27%), respectively. Among patients with >10 years of follow-up, 82 (86%), 66 (70%) and 31 (33%) had daytime continence, night-time continence and CUR at the last follow-up visit, respectively. RF deterioration events occurred in 74 patients throughout the follow-up and chronic kidney disease (CKD) stage III-V developed in 80 patients. Patients' age (hazard ratio [HR] 1.41, 95% confidence interval [CI]1.06-1.89; P = 0.02) and serous-lined extramural tunnel diversion (HR 0.43, 95% CI 0.19-0.86; P = 0.02) were the independent predictors of RF deterioration. Among patients with >10 years of follow-up, RF deteriorated in 46 patients (49%) and CKD stage III-V developed in 40 (42%). CONCLUSION: Women surviving more than 10 years after RC and ONB maintained acceptable continence status, apart from having a higher CUR rate, compared to those followed for <10 years. However, RF deterioration developed in nearly half of them.

Predictive value of immunological markers after bacille Calmette-Guérin induction in bladder cancer.

OBJECTIVES: To investigate the predictive value of different immunological markers on treatment outcomes after bacille Calmette-Guérin (BCG) induction in high-risk non-muscle-invasive bladder cancer (NMIBC). PATIENTS AND METHODS: Patients who underwent transurethral resection of bladder tumour for NMIBC were assessed for study eligibility. Urine and blood samples were taken from patients at baseline (immediately before first dose of induction) and after induction (4 h after last [sixth] dose). Urine samples were evaluated for interleukin (IL)-2 and IL-10 by solid-phase enzyme-linked immunosorbent assay. Blood samples were evaluated for tumour necrosis factor α (TNF-α), cytotoxic T-lymphocyte antigen 4 (CTLA-4) and transcription factors (TFs) (GATA-binding protein 3 [GATA3], T-box expressed in T cells [T-bet], and forkhead box protein 3 [FoxP3]) using quantitative reverse transcriptase-polymerase chain reaction analysis. Change pattern and fold change of each evaluable marker was assessed in relation to different treatment outcomes (initial complete response [ICR]/recurrence/progression). RESULTS: Between July 2013 and May 2019, 204 patients were included. Among evaluable markers, urinary IL-2 and serum TNF-α increased in all patients, serum CTLA-4 and FoxP3+ showed a predominant decreased pattern in 188 (92.2%) and 192 (94.1%) patients, respectively. An ICR was achieved in 186 (91.2%) patients. Serum TNF-α fold change and urinary IL-10 change pattern were significantly associated with an ICR (P = 0.001 and P = 0.03, respectively). At a median (range) follow-up of 37 (20-88) months, 104 (56%) patients developed recurrence. Urinary IL-10, serum CTLA-4, T-bet+ , FoxP3+ change patterns and GATA3+ /T-bet+ ratio were significantly associated with tumour recurrence (P = 0.001, P = 0.001, P = 0.02, P = 0.009 and P = 0.001, respectively). Tumour progression occurred in 34 (18.3%) patients. Urinary IL-10, serum CTLA-4, serum T-bet+ change patterns and GATA3+ /T-bet+ ratio were independent predictors of tumour progression (P = 0.001, P = 0.001, P = 0.02 and P = 0.001, respectively). CONCLUSIONS: Urinary IL-10 and serum TNF-α can significantly predict ICR. Moreover, change pattern of urinary IL-10, serum CTLA-4, TFs (GATA3, T-bet and FoxP3) and GATA3+ /T-bet+ ratio after BCG induction can independently predict further BCG response. These markers could be implemented in clinical practice when management options are discussed or in systems with severe BCG shortage.

Omega-3 polyunsaturated fatty acids: a modified approach for chemo-prevention of bladder cancer in a rat model and molecular studies of antineoplastic mechanisms.

OBJECTIVES: To test the chemo-preventative effects of omega-3 against bladder cancer (BC) induction in a rat model and its potential antineoplastic mechanisms. MATERIAL AND METHODS: Ninety male Fisher rats were divided into three groups during a 22-week protocol: group 1 (control), group 2 (Placebo + N-butyl-N-4- hydroxybutyl nitrosamine (BBN) for induction of BC and group 3 received omega-3 (1200 mg/kg/day) + BBN. At the end, blood samples and bladder tissues were collected and checked for the presence of malignancy, markers of angiogenesis (VEGF relative gene expression), inflammation (IL-6), proliferation (KI-67 expressions), oxidative stress (serum MDA and serum SOD) and epigenetic control (miRNA-145 level). RESULTS: At the end of the study, 60% and 86.6% rats survived in group 2 and 3 with significant weight loss among rats in group 2 when compared with other groups. In group 2, all rats developed visible bladder lesions of which five and 13 developed squamous cell carcinoma (SCC) and transitional cell carcinoma (TCC). In omega3-treated group, only one developed low grade SCC and one developed high grade non- invasive TCC. Bladders from omega-3-treated rats showed lower expression ofKI-67 (p < 0.05), VEGF (p < 0.001) and IL-6 (p < 0.001) and significant higher expression of mi-RNA (p < 0.001). Also, omega-3-treated group showed statistically significant lower MDA level (p < 0.001). CONCLUSION: Omega-3 inhibits bladder tumor growth in the BBN-induced BC rat model, due to anti-inflammatory, antioxidant, anti-proliferative, and anti-angiogenic properties together with epigenetic control.

Mirabegron for treatment of erectile dysfunction concomitant with lower urinary tract symptoms in patients with benign prostatic obstruction: A randomized controlled trial.

OBJECTIVE: To assess the efficacy of mirabegron in the treatment of erectile dysfunction concomitant with lower urinary tract symptoms in benign prostatic obstruction patients. METHODS: In this randomized controlled trial, 55 sexually active lower urinary tract symptoms/benign prostatic obstruction patients with concomitant erectile dysfunction were randomly allocated in two groups: the first received mirabegron 50 mg plus doxazosin 2 mg once daily (mirabegron group) and the second received tolterodine 4 mg plus doxazosin 2 mg (tolterodine group) for 12 weeks. The evaluation was based on the International Index of Erectile Function questionnaire, Erection Hardness Score questionnaire, International Prostate Symptom Score, quality of life, uroflowmetry and post-voiding residual. The therapeutic outcomes were assessed at 4 and 12 weeks compared with the baseline. RESULTS: Only the mirabegron group achieved significant improvement in sexual functions after 4 and 12 weeks. By using ≥5 points difference from the baseline as a cut-off point of change, there was a significant difference in change of direction of the International Index of Erectile Function-15 total score in favor of the mirabegron group; after 12 weeks, the International Index of Erectile Function-15 total score decreased in 0%, was unchanged in 8.3% and improved in 91.7% in the mirabegron group compared with 8.7%, 65.2% and 26.1%, respectively, in the tolterodine group (P < 0.001). Regarding the urinary characteristics, both groups showed significant improvement in the International Prostate Symptom Score, quality of life, and post-voiding residual after 4 and 12 weeks, with no significant difference among them. CONCLUSION: Mirabegron improves urinary characteristics and the associated sexual dysfunction in patients with lower urinary tract symptoms/benign prostatic obstruction.

Baicalein and Αlpha-Tocopherol Inhibit Toll-like Receptor Pathways in Cisplatin-Induced Nephrotoxicity.

Cisplatin (CP) is a conventional chemotherapeutic agent with serious adverse effects. Its toxicity was linked to the stimulation of oxidative stress and inflammation. As a result, this study explored the protective effect of baicalein and alpha-tocopherol in nephrotoxicity induced by cisplatin. Until receiving an intraperitoneal injection of CP (3 mg/kg BW), rats were given baicalein orally 100 mg/kg for seven days or/and a single intraperitoneal injection of α-tocopherol 250 mg/kg. Renal function was tested to explore whether baicalein and α-tocopherol have any beneficial effects; blood urea nitrogen (BUN), serum creatinine, malondialdehyde (MDA) content, antioxidant activity biomarkers and histopathology of renal tissue, oxidative stress biomarkers, inflammatory response markers, and histopathological features of kidney architecture were measured. Cisplatin treatment resulted in extreme renal failure, as measured by high serum creatinine and BUN levels and severe renal changes. Cisplatin therapy resulted in increased lipid peroxidation and decreased glutathione and superoxide dismutase levels, reflecting oxidative stress. Upon treatment with α-tocopherol, baicalein, and combined therapy, there was augmentation in the antioxidant status as well as a reduction in IL-6, NF-κB, TNF, TLR2, and TLR4 and a significant increase in Keap-1 and NRF-2. The combined treatment was the most effective and the nearest to the normal status. These findings suggest that baicalein and α-tocopherol may be useful in preventing cisplatin-induced nephrotoxicity.

Low energy shock wave-delivered intravesical botulinum neurotoxin-A potentiates antioxidant genes and inhibits proinflammatory cytokines in rat model of overactive bladder.

PURPOSE: To study the effect of intravesical instillation of botulinum neurotoxin-A (BoNT-A) combined with low energy shock wave (LESW) for treatment of overactive bladder (OAB) in a rat model and to investigate its effect on the associated inflammatory and oxidative stress process. MATERIAL AND METHODS: Forty rats were subdivided into four equal groups: normal control group, OAB group, LESW group, and BoNT-A plus LESW group. Cystometrogram (CMG) changes and histopathological changes in the bladder mucosa were assessed in the different groups. Oxidative stress markers (malondialdehyde [MDA] and superoxide dismutase [SOD]) and proinflammatory cytokines (tumor necrotic factor-α [TNF-α] and interleukin-6 [IL-6]) were compared among groups. RESULTS: BoNT-A plus LESW group showed statistically significant lower amplitude (p = .001) and lower frequency of detrusor contractions (p = .01) compared to LESW, which showed no statistically significant difference in comparison to the OAB group. Also, the combined group significantly reduced submucosal edema and inflammatory cell infiltrate scores compared to all groups (p < .05). LESW was associated with 42% reduction of MDA expression while, LESW plus BoNT-A decreased it by 68% (p < .001). Also, LESW and LESW plus BoNT-A increased SOD expression by 43% and 75%, respectively (p < .001). LESW plus BoNT-A was associated with statistically significant lower expression of TNF-α and IL-6 expression by 37% and 66% in comparison to LESW group (p = .001). CONCLUSION: Intravesical instillation of BoNT-A plus LESW is an effective method for increasing the urothelial permeability to BoNT-A and enhancing its therapeutic effect against OAB in rat model through the expression of a substantial anti-inflammatory and antioxidative stress effect.

The short-term effects of tolterodine on nocturnal incontinence after ileal orthotopic neobladder: a randomised crossover placebo-controlled study.

OBJECTIVES: To assess the effect of tolterodine in the treatment of nocturnal urinary incontinence (NUI) after ileal orthotopic neobladder (ONB). PATIENTS AND METHODS: This is a prospective randomised placebo-controlled crossover study (clinicaltrials.gov: NCT02877901). Patients with NUI after ONB were randomly allocated into two equal groups. Group T received 4 mg extended-release tolterodine at bed-time and Group P received placebo for 4 weeks followed by 2 weeks of washout, then crossed over to the alternate therapy for 4 weeks. Patients were assessed by the number of pads used per night (PPN) and with the Arabic version of the International Consultation on Incontinence Modular Questionnaire-Short Form (ICIQ-SF) at both phases of the study. The outcomes were the rate of NUI improvement and medication adverse events. RESULTS: Out of 172 patients, 150 and 122 patients were evaluated at both phases of the study. The mean ICIQ-SF scores and PPN were significantly decreased in Group T compared to Group P in both study phases (P < 0.001). In Group T, 15 (10%) and 11 (9%) patients became dry after the first allocation and crossover, respectively. In Group T, 60 (77.9%) patients reported improvement vs four (5.5%) in Group P (P < 0.001) after the first allocation. Similarly, 46 (73%) and seven (11.9%) patients showed improvement in groups T and P after the crossover, respectively (P < 0.001). Dry mouth occurred in 31 (20.8%) patients. CONCLUSIONS: Tolterodine seems to be a good choice for treatment of NUI after radical cystectomy and ONB. However, further studies are needed to delineate the long-term effects and the associated urodynamic characteristics.

Transradial versus transfemoral approach for diagnostic coronary angiography and percutaneous coronary intervention in people with coronary artery disease.

BACKGROUND: Cardiovascular disease (CVD) is the major cause of mortality worldwide. Coronary artery disease (CAD) contributes to half of mortalities caused by CVD. The mainstay of management of CAD is medical therapy and revascularisation. Revascularisation can be achieved via coronary artery bypass grafting (CABG) or percutaneous coronary intervention (PCI). Peripheral arteries, such as the femoral or radial artery, provide the access to the coronary arteries to perform diagnostic or therapeutic (or both) procedures. OBJECTIVES: To assess the benefits and harms of the transradial compared to the transfemoral approach in people with CAD undergoing diagnostic coronary angiography (CA) or PCI (or both). SEARCH METHODS: We searched the following databases for randomised controlled trials on 10 October 2017: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and Web of Science Core Collection. We also searched ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform in August 2017. There were no language restrictions. Reference lists were also checked and we contacted authors of included studies for further information. SELECTION CRITERIA: We included randomised controlled trials that compared transradial and transfemoral approaches in adults (18 years of age or older) undergoing diagnostic CA or PCI (or both) for CAD. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. At least two authors independently screened trials, extracted data, and assessed the risk of bias in the included studies. We contacted trial authors for missing information. We used risk ratio (RR) for dichotomous outcomes and mean difference (MD) or standardised mean difference (SMD) for continuous data, with their 95% confidence intervals (CIs). All analyses were checked by another author. MAIN RESULTS: We identified 31 studies (44 reports) including 27,071 participants and two ongoing studies. The risk of bias in the studies was low or unclear for several domains. Compared to the transfemoral approach, the transradial approach reduced short-term net adverse clinical events (NACE) (i.e. assessed during hospitalisation and up to 30 days of follow-up) (RR 0.76, 95% CI 0.61 to 0.94; 17,133 participants; 4 studies; moderate quality evidence), cardiac death (RR 0.69, 95% CI 0.54 to 0.88; 11,170 participants; 11 studies; moderate quality evidence). However, short-term myocardial infarction was similar between both groups (RR 0.91, 95% CI 0.81 to 1.02; 19,430 participants; 11 studies; high quality evidence). The transradial approach had a lower procedural success rate (RR 0.97, 95% CI 0.96 to 0.98; 25,920 participants; 28 studies; moderate quality evidence), but was associated with a lower risk of all-cause mortality (RR 0.77, 95% CI 0.62 to 0.95; 18,955 participants; 10 studies; high quality evidence), bleeding (RR 0.54, 95% CI 0.40 to 0.74; 23,043 participants; 20 studies; low quality evidence), and access site complications (RR 0.36, 95% CI 0.22 to 0.59; 16,112 participants; 24 studies; low quality evidence). AUTHORS' CONCLUSIONS: Transradial approach for diagnostic CA or PCI (or both) in CAD may reduce short-term NACE, cardiac death, all-cause mortality, bleeding, and access site complications. There is insufficient evidence regarding the long-term clinical outcomes (i.e. beyond 30 days of follow-up).

Family Medicine in Egypt From Medical Students' Perspective: A Nationwide Survey.

UNLABELLED: PHENOMENON: Attitudes of medical students toward family medicine as a specialty choice can provide information on the future supply of family physicians. Due to the current worldwide shortage of family physicians, these attitudes, with their subsequent effects on the state and dynamics of the healthcare system, are important to investigate. APPROACH: A web-based questionnaire was sent to 600 medical students, selected by a systematic random sampling technique, in 7 Egyptian medical schools. Participants were surveyed to assess their perception of the family medicine specialty as a future career and explore the impact of different factors, including undergraduate family medicine clerkships, on their attitudes toward family medicine. FINDINGS: We had a response rate of 75.2% (n = 451). Although 90.7% of students believed in the vital role that family medicine can play in Egypt's healthcare system, only 4.7% showed an intention to choose it as a future career. Students choosing family medicine as a first-career choice were more likely to have a prior contact with family physicians as consumers. Exposure to an undergraduate family medicine curriculum was associated with increased knowledge about family medicine but not the intentions to pursue it as a career. INSIGHTS: Medical students in Egypt have a positive perception of family medicine as an important specialty but low interest in its choice as a future career.

Health-related quality of life after radical cystectomy and neobladder reconstruction in women: impact of voiding and continence status.

OBJECTIVES: To assess health-related quality of life, and the impact of night-time incontinence and chronic urinary retention on health-related quality of life in women with bladder cancer after radical cystectomy and orthotopic neobladder. METHODS: The study included 74 women who underwent radical cystectomy and orthotopic neobladder, and completed 1 year of follow up. Health-related quality of life was evaluated using the questionnaires of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire and the Functional Assessment of Cancer Therapy bladder cancer-specific form. Health-related quality of life was compared with an age-matched control group. The impact of night-time incontinence and chronic urinary retention on health-related quality of life was assessed. RESULTS: The study group included 18 completely continent patients with spontaneous voiding, 29 with night-time incontinence and 27 with chronic urinary retention. The study group was statistically significantly lower in all domains of health-related quality of life than the control group. In all domains of the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire and Functional Assessment of Cancer Therapy bladder cancer-specific form, completely continent women were comparable with those with chronic urinary retention. Women with night-time incontinence had a significantly worse health-related quality of life than completely continent women, shown by the mean global health score (P = 0.038), social functioning score (P = 0.012), pain European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire score (P = 0.04), and functional well-being Functional Assessment of Cancer Therapy bladder cancer-specific form (P = 0.049) score. CONCLUSIONS: After radical cystectomy and orthotopic neobladder in women, health-related quality of life is lower than that of the normal population. Night-time incontinence has a negative impact on social life and most domains of health-related quality of life. Thus, night-time incontinence has a higher social impact than chronic urinary retention.

Salvage of grafts with vascular thrombosis during live donor renal allotransplantation: a critical analysis of successful outcome.

OBJECTIVES: To report a high-volume institution experience with salvage techniques for vascular accidents during live donor renal allotransplantation. METHODS: Between March 1976 and January 2011, 2208 recipients underwent live donor renal allotransplantation. A retrospective review of recipients with vascular accidents - renal artery thrombosis and renal vein thrombosis - was carried out. Salvage procedures were recorded and their outcomes were assessed. RESULTS: A total of 23 (1%) vascular accidents occurred, including renal artery thrombosis and renal vein thrombosis in 19 (0.8%) and four (0.18%) recipients, respectively. All renal artery thrombosis patients were treated by open revascularization and the graft was salvaged in 12 patients (63%). Two renal vein thrombosis events were resolved by percutaneous catheter-directed thrombolytic therapy. Of the other two allografts, one was salvaged by thrombectomy and revascularization, and the other was lost. On univariable analysis, older recipients (P = 0.003), pretransplant hypertension (P = 0.001), more human leukocyte antigen mismatches (≥3; P = 0.036), shorter ischemia time (≤45 min; P = 0.004) and longer time to diagnosis (>3.5 days; P = 0.013) were significantly associated with non-salvage of the graft after vascular accidents. Nevertheless, none of these variables were significant on the multivariable analysis. Over a median follow up of 35 months, the median (range) serum creatinine was 2 mg/dL (range 0.8-8.8 mg/dL), and 11 (79%) recipients were living with functioning grafts. CONCLUSIONS: Despite the devastating complications, vascular accidents are salvageable and revascularization is crucial for graft salvage. Angiographic percutaneous techniques are viable alternatives for renal vein thrombosis.

Deep learning-based scoring method of the three-chamber social behaviour test in a mouse model of alcohol intoxication. A comparative analysis of DeepLabCut, commercial automatic tracking and manual scoring.

Background: Alcohol consumption and withdrawal alter social behaviour in humans in a sex-dependent manner. The three-chamber test is a widely used paradigm to assess rodents' social behaviour, including sociability and social novelty. Automatic tracking systems are commonly used to score time spent with conspecifics, despite failing to score direct interaction time with conspecifics rather than time in the nearby zone. Thereby, the automatically scored results are usually inaccurate and need manual corrections. New method: New advances in artificial intelligence (AI) have been used recently to analyze complex behaviours. DeepLabCat is a pose-estimation toolkit that allows the tracking of animal body parts. Thus, we used DeepLabCut, to introduce a scoring model of the three-chamber test to investigate alcohol withdrawal effects on social behaviour in mice considering sex and withdrawal periods. We have compared the results of two automatic pose estimation methods: automatic tracking (AnyMaze) and DeepLabCut considering the manual scoring method, the current gold standard. Results: We have found that the automatic tracking method (AnyMaze) has failed to detect the significance of social deficits in female mice during acute withdrawal. However, tracking the animal's nose using DeepLabCut showed a significant social deficit in agreement with manual scoring. Interestingly, this social deficit was shown only in females during acute and recovered by the protracted withdrawal. DLC and manually scored results showed a higher Spearman correlation coefficient and a lower bias in the Bland-Altman analysis. Conclusion: our approach helps improve the accuracy of scoring the three-chamber test while outperforming commercial automatic tracking systems.

Impact of successful antegrade and retrograde CTO PCI on short-term prognosis.

BACKGROUND: Chronic total occlusion (CTO) percutaneous coronary intervention (PCI) carries risk of complications and should be attempted when the anticipated benefits exceed the potential risks. The primary indication for CTO-PCI is symptom improvement. However, the impact of CTO-PCI on angina and subsequent incidence of major adverse cardiovascular event (MACE) rate remains controversial. Our aim was to study the impact of technically successful elective CTO-PCI on the procedural success rate and short-term MACE. The current study was a prospective cohort study that included a total of 80 patients who were referred to our center (Ain Shams University Hospitals) for elective CTO-PCI and underwent technically successful CTO-PCI. Data were collected on patient arrival to our department, and then, the patients were observed during hospital admission to record any In-Hospital MACE. These patients were then followed up for 6 months to record improvement or worsening of their symptoms and to assess occurrence of any MACE including hospitalization and undergoing symptom-driven coronary angiography. RESULTS: The mean age of our patients was 56 ± 9.6 years, and 73 patients (91%) were men. Sixty-two patients (77.5%) were done via an antegrade approach, and 18 patients (22.5%) were done via a retrograde approach with an overall procedural success rate of 91.25% (antegrade 93.5%, retrograde 83.3%). The overall mean procedure time was 102 min, the mean contrast volume used was 371 ml, and the mean cumulative air kerma dose was 7.2 Gy. The retrograde group required longer procedure times, larger volumes of contrast and higher exposure to radiation. The overall in-hospital MACE was 8.75%. Sixty-five patients in our study (81.25%) showed an improvement in the grade of their exertional dyspnea or angina within the 6-month follow-up period. Thirteen patients in our study (16.25%) needed re-hospitalization within a 6-month period after PCI. The overall target lesion revascularization rate at 6 months was 8.75%. CONCLUSIONS: Technically successful CTO PCI in a well-equipped center with highly qualified CTO operators resulted in high procedural success rates and low incidence of short-term MACE.

The impact of chemotherapy-naïve open radical cystectomy delay and perioperative transfusion on the recurrence-free survival: A perioperative parameters-based nomogram.

Objective: To develop and internally validate a nomogram to predict recurrence-free survival (RFS) including the time to radical cystectomy (RC) and perioperative blood transfusion (PBT) as potential predictors. Methods: Patients who underwent open RC and ileal conduit between January 1996 to December 2016 were split into developing (n=948) and validating (n=237) cohorts. The time to radical cystectomy (TTC) was defined as the interval between the onset of symptoms and RC. The regression coefficients of the independent predictors obtained by Cox regression were used to construct the nomogram. Discrimination, validation, and clinical usefulness in the validation cohort were assessed by the area under the curve, the calibration plot, and decision curve analysis. Results: In the developing dataset, the 1-, 5-, and 10-year RFS were 83.0%, 47.2%, and 44.4%, respectively. On multivariate analysis, independent predictors were TTC (hazards ratio [HR] 1.07, 95% confidence interval [CI] 1.05-1.08, p<0.001), PBT (one unit: HR 1.40, 95% CI 1.03-1.90, p=0.03; two or more units: HR 1.72, 95% CI 1.29-2.29, p<0.001), bilateral hydronephrosis (HR 1.54, 95% CI 1.21-1.97, p<0.001), squamous cell carcinoma (HR 0.60, 95% CI 0.45-0.81, p=0.001), pT3-T4 (HR 1.77, 95% CI 1.41-2.22, p<0.001), lymph node status (HR 1.53, 95% CI 1.21-1.95, p<0.001), and lymphovascular invasion (HR 1.28, 95% CI 1.01-1.62, p=0.044). The areas under the curve in the validation dataset were 79.3%, 69.6%, and 76.2%, for 1-, 5-, and 10-year RFS, respectively. Calibration plots showed considerable correspondence between predicted and actual survival probabilities. The decision curve analysis revealed a better net benefit of the nomogram. Conclusion: A nomogram with good discrimination, validation, and clinical utility was constructed utilizing TTC and PBT in addition to standard pathological criteria.

Two-dimensional speckle tracking echocardiography in chemotherapy-induced cardiotoxicity in females with breast cancer.

BACKGROUND: Cancer and cardiovascular diseases are the main causes of mortality worldwide. Although the incidence of cancer is rising, modern comprehensive management including surgery, chemotherapy, and radiotherapy led to decreased mortality, but also different cardiovascular complications. Conventional EF measurement fails to detect subtle changes in LV function, so a more sensitive tool is needed. METHODS: The study included 101 asymptomatic female patients with newly diagnosed breast cancer who received anthracycline ± trastuzumab-based chemotherapy regimen. A comprehensive echocardiographic examination was performed before receiving the chemotherapy (T0), at 3 months (T1), and at 6 months after (T2). All patients had pre-treatment normal LV EF. Asymptomatic CTRCD is defined as: severe if new LVEF reduction to < 40%, moderate if new LVEF reduction by ≥ 10 percentage points to an LVEF of 40-49% or new LVEF reduction by, 10 percentage points to an LVEF of 40- 49% and either new relative decline in GLS by .15% from baseline or new rise in cardiac biomarkers and mild if LVEF ≥ 50% and new relative decline in GLS by .15% from baseline and/or new rise in cardiac biomarkers. Symptomatic CTRCD is defined as: very severe if HF requiring inotropic support, mechanical circulatory support, or consideration of transplantation, severe if required hospitalization, moderate if required outpatient intensification of diuretic and HF therapy and mild if there are mild HF symptoms and no intensification of therapy required according to the latest ESC cardio oncology guidelines. The Lower reference value set for RV S' was less than 10cm/s to define RV systolic dysfunction according to ASE guidelines. RESULTS: CTRCD occurred in 24 patients (25.5%) while RV systolic dysfunction was more common occurring in 37 patients (39.4%). LV GLS at (T1) (cut-off value < -15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS & RV FWLS was the strongest (AUC = 0.947, sensitivity = 91.67%, specificity = 90%). CONCLUSION: Chemotherapy induces biventricular changes with more prevalent deterioration in RV values. Low LV & RV strain values at baseline together with reduction of these values after chemotherapy treatment can predict later CTRCD development. Combining LV GLS with RV GLS & FWLS values at (T1) is the strongest predictor of subsequent CTRCD.

The relationship between Coronavirus Disease-19 (COVID-19) and ischemic priapism: a case-control study.

This multicentre retrospective study was conducted in 3 university hospitals in Egypt between April 2020 and June 2022. The aim was to assess the relation between Coronavirus Disease-19 (COVID-19) and ischemic priapism. Forty-three ischemic priapism patients were diagnosed and divided into two groups (30 in group I with ischemic priapism only, and 13 in group II with both ischemic priapism and COVID-19). Further sub-classification of COVID-19 patients according to the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection severity was done. Cavernosal aspiration was successful in 25 patients (83.3%) in group I and 12 (92.3%) in group II. Long term follow-up proved moderate to severe erectile dysfunction in 6 patients (20.0%) and 1 (7.7%) in group I and II, respectively. All those with severe erectile dysfunction were managed by distal shunt and prepared for penile prosthesis placement. The median duration of ischemic priapism was significantly longer in patients with severe erectile dysfunction [19 vs. 7 h, P = 0.01]. There was no statistically significant difference between both groups regarding patients' age (p = 0.8), required priapism management (p = 0.4), priapism recurrence (p = 0.1), and erectile dysfunction severity (p = 0.5). Ischemic priapism in COVID-19 patients can occur not only in severe, but also in mild or even asymptomatic cases. COVID-19 did not influence the ischemic priapism treatment protocol and post-treatment erectile function. COVID-19 and ischemic priapism seem to have a coincidence relation rather than a causal.

Effect of bulbospongiosus muscle injection with botulinum-A toxin for treatment of lifelong premature ejaculation; a randomized controlled trial.

This study aimed at assessing a new line of treatment for lifelong premature ejaculation which is botulinum-A toxin injection into the bulbospongiosus muscle. Sixty patients with lifelong premature ejaculation were independently randomized into 2 groups; group I, 100 U botulinum-A toxin at 10 U/ml saline was injected with ultrasound guidance into the bulbospongiosus muscle and group II which was injected with similar volume of saline. The primary outcome was to compare both groups for changes in the Premature Ejaculation Profile (PEP), Intravaginal Ejaculatory Latency Time (IELT) and partner's satisfaction at 1, 3 and 6 months after intervention. The second outcome was to compare the adverse events in both groups. Fifty-seven patients completed the study. In group I, the mean PEP increased significantly at 1- (P = 0.02) and 3- months (P = 0.04) with insignificant increase at 6-month (P = 0.6) of follow-up. Also, no significant changes had been noted in IELT or partner's satisfaction scores throughout the study duration (P > 0.05). In group II, no significant changes had been noted in the PEP, IELT and partner's satisfaction scores throughout the study duration (P > 0.05). There were insignificant differences in the changes in the mean PEP (P = 0.7, 0.6 and 0.4), IELT (P = 0.6,0.6 and 0.5) and partner's satisfaction scores (P = 0.5,0.7 and 0.3) in comparison to the baseline values at 1-, 3- and 6- months, respectively between both groups. Adverse events were observed in only 3 patients (5.3%). In group I, mild erectile dysfunction and post micturition dribbling were reported in one patient each. Where in group II, one patient reported bleeding per urethra (P = 0.5). To conclude, injection of botulinum-A toxin into bulbospongiosus seems to be safe but failed to prove clinical efficacy for treatment of lifelong premature ejaculation when compared to placebo.

ACE Inhibitors and Angiotensin Receptor Blockers for the Primary and Secondary Prevention of Cardiovascular Outcomes: Recommendations from the 2024 Egyptian Cardiology Expert Consensus in Collaboration with the CVREP Foundation.

INTRODUCTION: The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events. METHODS: A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process. RESULTS: The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker. CONCLUSION: RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated.

Overstimulation of the renin­angiotensin­aldosterone system­a key regulator of blood pressure, and fluid and electrolyte balance­is known to cause an increase in blood pressure (also known as "hypertension") and other diseases of the heart and blood vessels (the cardiovascular system). As such, treatments to block (or inhibit) this overstimulation are an essential part of medical strategies designed for the prevention of cardiovascular disease, especially in patients with hypertension (in whom the risk of death due to cardiovascular causes is high). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are two types of medication that block overstimulation of the renin­angiotensin­aldosterone system, but they work in different ways. Angiotensin-converting enzyme inhibitors are superior to angiotensin receptor blockers after heart attacks (acute myocardial infarction), in patients with heart failure, for the prevention of stroke in individuals who have already had a stroke, and in patients with diabetes. Both types of medication have beneficial effects on the kidneys and associated outcomes, but only angiotensin-converting enzyme inhibitors have been shown to significantly reduce death due to cardiovascular causes, as well as death due to any cause. Overall, the protective effects of angiotensin-converting enzyme inhibitors on the heart are substantially greater than those of angiotensin receptor blockers, meaning that treatment with an angiotensin-converting enzyme inhibitor is preferred in all patients, except those who cannot tolerate the side effects of this drug class.

Evaluation of The Three-Dimensional Endoscopy in Basic and Extended Nasal Procedures: A Clinical and Cadaveric Study.

Introduction The three-dimensional (3D) endoscope is considered a new surgical tool used in different approaches in intranasal and anterior skull base surgical procedures. There are many advantages of 3D over two-dimensional (2D) endoscopy that have been demonstrated in clinical applications, surgical training, and different experimental studies. Objective To show the difference between using the 3D and 2D endoscopes during endonasal and anterior skull base surgery and its importance. Methods Our study is divided into two phases (clinical and cadaveric phases). In the clinical study we, have performed 52 endonasal and anterior skull base surgical procedures (26 study cases and 26 control cases). We recorded accuracy, duration, and intraoperative complication for each case. The cadaveric study was performed on three cadavers. Differences in accuracy and dissection time were recorded using 3D and 2D endoscopy for each side chosen by randomization. Results In the clinical study, the cases done by 3D endoscope were significantly faster and more accurate with less intraoperative complications compared with cases done using 2D endoscope. In cadaveric dissection, while using 3D endoscope, there was better depth of perception regarding the anatomical landmarks compared with 2D endoscope. Conclusion Three-dimensional endoscopy is an advanced instrument that allows better training for the coming generation of ear, nose, and throat surgeons. Both clinical and cadaveric studies offer a promising outcome in both endonasal and anterior skull base surgery.

Azoospermia and Sperm Retrieval in Post-Pubertal Testicular Torsion; Benefits and limitations.

OBJECTIVES: To assess the risk of azoospermia development and the value of sperm retrieval in post-pubertal testicular torsion (TT). MATERIALS AND METHODS: This prospective study included patients with post-pubertal TT. Surgical exploration was urgently performed with either orchiopexy or orchiedectomy and contralateral orchiopexy. With the intention of cryopreservation, all cases underwent conventional testicular sperm extraction. Patients were followed-up after 1, 3, and 6 months with semen analysis and hormonal assay (FSH, LH and testosterone). Sperm retrieval rate (SRR), azoospermia rate and changes in hormonal profile were evaluated. RESULTS: The study included 62 patients with a median (IQR) age of 19 (18-20.7) years and duration of testicular torsion of 32.5 (18.3-48) hours. Testicular salvage was successful in 20 (32.3%) while orchiedectomy was performed on 42 patients. The duration of torsion [OR, 95% CI = 0.75 (0.61-0.93), P = .008] was the independent predictor of testicular salvage. Successful SR was achieved in 58 patients (93.5%); (40 from the affected testis and 18 from the contralateral side). After 6 months, 21 patients (33.8%) developed azoospermia [19 (45.2%) in orchidectomy group and 2 (10%) in orchiopexy group, P = .006]. Abnormal contralateral testis was the independent predictor of azoospermia [OR, 95% CI = 92(8.4-101.5), P < .001]. Azoospermia patients showed a statistically significant increase in FSH and LH and decrease in testosterone level as compared to the non-azoospermia group (P < .001). CONCLUSION: Azoospermia is not rare in post-pubertal TT patients; therefore, SR at time of intervention seems to be a good option for them to preserve their fertility potentials.