GEMIN4 Variants: Risk Profiling, Bioinformatics, and Dynamic Simulations Uncover Susceptibility to Bladder Carcinoma.

BACKGROUND: The relationship between GEMIN4 genetic variants and cancer, especially bladder carcinoma (BLCA), has been explored without conclusive results. This study aims to elucidate the link between GEMIN4 polymorphisms and BLCA susceptibility through genetic analyses, bioinformatics, and molecular dynamics (MD) simulations. METHODS: A cohort of 249 participants (121 BLCA patients and 128 unrelated controls) was enrolled. PCR was employed for allelic discrimination of GEMIN4 variants, followed by subgroup stratification, haplotype analyses, structural prediction using the AlphaFold2 prediction tool, subsequent MD simulations, structural analysis, and residue interaction mapping using Desmond, UCSF ChimeraX, and Cytoscape softwares. RESULTS: The rs.2740348*G variant demonstrated a protective role against BLCA in allelic (OR = 0.55, p = 0.002) and recessive (OR = 0.54, p = 0.017) models, whereas the rs.7813*T variant increased BLCA risk under the recessive model (OR = 1.90, p = 0.019). Haplotype analysis revealed a significant association between GEMIN4 haplotype (rs.2740348*C/rs.7813*T) with increased BLCA risk (OR = 2.01, p = 0.004). Univariate analysis revealed associations of the variants with albumin levels and absolute neutrophil count in BLCA patients. Pathogenicity evaluation categorized p.Gln450Glu as neutral and p.Arg1033Cys as deleterious. MD simulations revealed structural alterations and conformational shifts in the GEMIN4 protein induced by the Glu450 and Cys1033 mutations. CONCLUSIONS: The study highlights the dual role of GEMIN4 variants in BLCA susceptibility, with rs.2740348 conferring protection and rs.7813 increasing risk. The Glu450 residue positively impacted protein stability, while Cys1033 had a detrimental effect on protein function. These findings underscore the significance of GEMIN4 variants in BLCA susceptibility and pave the way for future diagnostic and therapeutic initiatives.

The effect of stone size on the results of extracorporeal shockwave lithotripsy versus semi-rigid ureteroscopic lithotripsy in the management of upper ureteric stones.

OBJECTIVES: To evaluate the role of stone size on the efficacy and safety of extracorporeal shockwave lithotripsy (ESWL) monotherapy vs ureteroscopy (URS) for managing upper ureteric stones. PATIENTS AND METHODS: The study design was a randomised prospective study of a total cohort of 180 patients with upper ureteric single stones of 0.5-1.5 cm. Half of the patients were managed by ESWL monotherapy, while the other half underwent URS with stone fragmentation using an ultrasound lithotripter (URSL). The success rate, re-treatment rate, auxiliary procedure (AP) rate, efficacy quotient, and complications were compared between the two groups. RESULTS: After single URSL and ESWL procedures 70/90 (77.8%) and 35/90 (38.9%) of the stones were successfully cleared, respectively (P < 0.001). The re-treatment rate after ESWL was significantly higher than in the URSL group (38.9% vs 11.1%, P < 0.001). Requiring an AP was not significantly different following ESWL (22.2%) and URSL (24.4%) treatment. The overall stone-free rate (SFR) at 3 months was significantly superior in the URSL group (88.9% vs 77.8%); however, both procedures had excellent results with no significant difference for stones of <1 cm (95.5% vs 92.9%, P > 0.05), compared to better results following URSL for stones of >1 cm (82.6% vs 64.6%, P < 0.05). CONCLUSION: Our present study supports that ESWL is recommended as a first-line non-invasive monotherapy for upper ureteric opaque stones of <1 cm, while URSL is recommended as a first-line treatment for stones of >1 cm. The results for URSL were superior with lower a re-treatment rate, rapid stone clearance in a very short time, and less radiation exposure. Therefore, stone size is an important factor for the final decision of the initial management of upper ureteric stones because it has a direct relation to the efficacy of ESWL, but it has no effect on the results of URSL.

Needle-stick and sharps injuries: awareness, prevalence and risk factors of a global problem in healthcare workers at Tanta University Hospitals, Egypt.

Objectives. This study aimed to assess the level of awareness, prevalence and risk factors of needle-stick and sharps injuries (NSSIs) in Tanta University Hospitals, Egypt to develop a well-established preventive strategy. Methods. A total of 662 healthcare workers (HCWs), including nurses and physicians, who attended work during the last 6 months of 2019 were included. Data were collected on a structured questionnaire distributed during their working time. Results. Of 662 participating HCWs, 486 were nurses and 176 were physicians. Good awareness (86.1 and 83.1%) of the participants about safe injection policy and sharp disposal after use was observed. Nurses showed a significantly higher percentage of poor awareness score (79.1%) than physicians (20.9%). NSSIs in our hospitals reached 60.4%. Nurses (67.9%) had higher risk of NSSIs than physicians (39.8%; p < 0.001). NSSIs were significantly less likely to occur for HCWs who were aware of safe injection and sharp disposal policies. NSSIs were frequent with specimen collection (16.4%), injections (15.5%) and sharp disposal (14.6%). Only 110 (27.5%) have reported their injuries. Conclusion. A comprehensive program that addresses institutional, behavioral and device-related factors that contribute to the occurrence of NSSIs and reporting systems is needed.

Management of 'forgotten' encrusted JJ stents using extracorporeal shockwave lithotripsy: A single-centre experience.

Objective: To evaluate the role of extracorporeal shockwave lithotripsy (ESWL) for the management of 'forgotten' encrusted stents. Patients and Method: This is a retrospective study of 133 patients with forgotten JJ stents, treated between January 2015 and January 2018. Encrustation was mainly found in the renal coil of the stent with distal concomitant encrustation in the vesical and/or ureteric segment. After laboratory and radiological assessment, treatment started with ESWL for the renal encrustation before successful extraction. Auxiliary endourological procedures were used for the encrusted vesical or ureteric segments. Failed cases underwent open surgery. Results: The mean (SD; range) JJ stent indwelling time was 25.84 (10; 14-70) months. In all, 96 (72.2%) patients were seen after treatment for stone disease. In total, 94 patients (70.7%) were managed by ESWL monotherapy, whilst in 36 (27%) additional endourological procedures were required before successful extraction including: cystolithotripsy 19 patients (52.8%), ureteroscopic lithotripsy eight (22.2%), and percutaneous nephrolithotomy nine (25%). Open surgery was required in only three patients (2.3%). A mean of 0.28 procedures per patient was required before smooth stent extraction. The encrusted stents were removed after the first, second, third, and fourth ESWL sessions in 44 patients (33.1%), 43 (32.3%), 26 (19.5%), and 17 (12.8%), respectively. Patients with forgotten indwelling JJ stents for >2 years had significantly larger and harder encrustation at both JJ coils. Conclusion: ESWL proved a feasible first-line treatment for forgotten encrusted JJ stents. The indwelling time of forgotten stents in the urinary tract is associated with greater encrustation burden, density and multiple sites of encrustation. Abbreviations: CLT: cystolithotripsy; ESWL: extracorporeal shockwave lithotripsy; HU: Hounsfield unit; KUB: plain abdominal radiograph of the kidneys, ureters and bladder; PCNL: percutaneous nephrolithotomy; URL: ureteroscopic lithotripsy.

Combined modality treatment with bladder preservation for muscle invasive bladder cancer.

OBJECTIVE: To evaluate the 5-year results of the following trimodal therapy for treatment of some selected cases of muscle invasive bladder cancer. MATERIALS AND METHODS: In this prospective study, we included 104 patients with transitional cell carcinoma (TCC) (T2 and T3a, N0, M0) who were amenable to complete transurethral resection. All patients received adjuvant chemo-radiotherapy (CRT) in the form of gemcitabine and cisplatin and conventional radiotherapy after the maximum resection of their tumors. Two weeks later, all cases had radiologic and cystoscopic evaluation. The patients who showed no evidence of the bladder tumors [complete response (CR)] went on to complete the CRT, while those with recurrent invasive tumors did not receive any more CRT and were assigned to have salvage cystectomy. Thereafter, all patients were subjected to a regular follow-up. RESULTS: This trimodal therapy was well tolerated in most of cases with no severe acute toxicities. Complete response was achieved in 78.8% of cases after the initial CRT, and tumor grade was found to be the most significant risk factor to predict this response (P = 0.004). With a median follow-up of 71 months for patients with initial CR, 16.2% of cases showed muscle invasive recurrences, and multifocality was the only significant risk factor for their development (P = 0.003). Meanwhile, superficial recurrences were detected in 8.1% of cases with initial CR and were successfully treated with transurethral resection and intravesical bacillus Calmette-Guerin (BCG). On the other hand, we reported distant metastasis in 24.3% of patients with initial CR, and tumor grade, stage and multifocality were the most significant risk factors for this complication (P = 0.002, 0.031, 0.006). No cases of contracted bladder or late gastrointestinal complications were demonstrated in this series. The 5-year overall survival rate for patients with initial CR was 67.6%, and for all the patients in this study it was 59.4%. CONCLUSIONS: This trimodal therapy can be considered as a treatment option for patients with localized muscle invasive TCC. The best candidates for such therapy are those with solitary T2, low grade tumors that are amenable to complete transurethral resection.

Ureteroscopic management of lower ureteric calculi: a 15-year single-centre experience.

OBJECTIVE: To review our 15-year experience with ureteroscopic treatment of distal ureteric calculi and to determine the impact of improved technology and techniques on the efficacy, success and complications of the procedure. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 4512 patients who underwent 5133 ureteroscopic procedures for the treatment of distal ureteric calculi at our institution from January 1991 to December 2005. The patient and stone characteristics, treatment variables and clinical outcomes were assessed. Factors such as type of ureteroscope, procedure duration, procedure success, complication rate and hospital stay were evaluated. Data obtained from a cohort of patients that underwent the procedure from 1991 to 1995 (group 1) were statistical compared with those obtained from a cohort of patients from 1996 to 2005 (group 2). Logistic regression analysis was used to identify associated factors with the major complications of ureteroscopy. RESULTS: Overall, the stone-free rate after the procedure was 94.6%, the mean (sd; range) operative duration was 43 (15.0; 25-120) min, the intraoperative complication rate was 6.67%, the postoperative complication rate was 9.9%, and the mean (sd) hospital stay was 1.7 (1.1) days. The clinical and radiological follow-up (mean 36.8 months) for 71.3% of eligible patients detected only 12 ureteric strictures (0.23%). On comparing group 1 with group 2, the overall success of ureteroscopic stone extraction improved from 85.7% to 97.3% (P < 0.001), significant ureteric perforation decreased from 3.3% to 0.5% (P = 0.05), ureteric avulsion decreased from 1.3 to 0.1% (P < 0.05), ureteric stricture decreased from 0.7% to 0.1% (P < 0.007), the mean (sd) procedure time significantly decreased from 75 (42.9) min to 36.5 (12.5) min (P < 0.001), and the mean hospital stay significantly decreased from 2.5 (1.6) days to 0.5 (1.2) days, with a trend toward outpatient treatment. Logistic regression analysis showed a significant association of the major ureteroscopic complications with increased operative duration, type of ureteroscope used, stone impaction, stone size and surgeon experience. CONCLUSION: The present series shows the high success rate, with minor complications, that can be achieved with ureteroscopic treatment of distal ureteric calculi. Improvements in ureteroscope design, accessories, technique and experience have led to a significant increase in the success rate and decrease in the complication rate.

Evaluation of intravesical potassium sensitivity test and bladder biopsy in patients with chronic prostatitis/chronic pelvic pain syndrome.

AIM: We evaluated the possibility that patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) might have similar histological and physiological bladder changes as that documented in patients with painful bladder syndrome/interstitial cystitis (PBS/IC). METHODS: Thirty-five known patients of CP/CPPS according to the clinical criteria of National Institutes of Health (NIH) were evaluated. The severity of the symptoms was evaluated according the NIH-Chronic Prostatitis Symptom Index. All patients underwent a potassium sensitivity test (PST) and bladder cystoscopy. Bladder biopsy was obtained from 17 patients with prostatitis and four control patients. RESULTS: Urinary symptoms were present in 31 (88.6%) patients. Pelvic pain was reported in all patients. PST was positive in 26 (84%) of 31 patients that presented with urinary symptoms in its filling phase. In the voiding phase, 10 (28.5%) patients experienced urethral pain. Of these patients, five had negative filling PST. There were only two (5.7%) patients that had negative PST in both of its phases for an overall positive PST rate of 94.3%. The severity of PST was not correlated with the total symptom score (P = 0.37). However, patients with severe urinary symptoms were more likely to score higher grades with PST (P = 0.01). Of the 17 patients who underwent bladder biopsy, a significant increase in the number of mast cells (MC) was present in 11 (64.7%) patients. Glomerulations with bladder cystoscopy was observed in 24 (68.6%) patients. CONCLUSIONS: The data of the present study support the opinion that PBS/IC is under-diagnosed in male patients that present with urgency, frequency and/or pain. In some patients diagnosed as CP/CPPS, the symptoms might be related to bladder dysfunction rather than prostatic inflammation.

Evaluation of direct versus non-refluxing technique and functional results in orthotopic Y-ileal neobladder after 12 years of follow up.

OBJECTIVES: We report on the long-term functional results of the orthotopic Y-ileal neobladder and compare the outcome of the antireflux technique for ureteral implantation versus direct anastomosis. PATIENTS AND METHODS: Between 1990 and 2002, 120 patients underwent cystoprostatectomy and orthotopic Y-shaped ileal neobladder for invasive bladder carcinoma. The direct Nesbit technique for ureteral reimplantation was applied in 58 patients (group 1) and in 62 patients the ureters were reimplanted using the Le Duc antirefluxing technique (group 2). The mean follow-up period was 72 months (range, 36-144 months). RESULTS: Of 62 patients who underwent the Le Duc technique, six (9.7%) had unilateral uretero-ileal anastomotic stricture and four (6.5%) had reflux. Of 58 patients who underwent direct anastomosis, six (10.3%) patients had unilateral reflux, four of them had dilated ureters preoperatively and no patient had uretero-ileal anastomotic stricture. The incidence of stricture formation in the Le Duc technique is significantly higher than direct anastomosis (P = 0.04). There was no significant difference in the overall incidence of reflux in both groups. However, the incidence of reflux in preoperatively dilated ureters was significantly higher in direct ureteral anastomosis than Le Duc technique (40% in group 1 vs 16.7% in group 2; P = 0.045). The incidence of stone formation, azotemia, pyelonephritis and bacteriuria was comparable in both groups. The urodynamic findings showed a mean increase in the neobladder capacity at 6 and 18 months after surgery by 340 and 560 mL, respectively. The mean of the maximum pressure was 22 +/- 10 cm H2O, 18 months after surgery. Daytime and nighttime continence was good or satisfactory in 93.3% and 85.5% of the patients, respectively, after 3 years of follow-up. CONCLUSIONS: The functional and voiding results of a Y-shaped neobladder pouch using 40 cm of ileum are similar to the more sophisticated larger pouches. Direct uretero-ileal anastomosis in orthotopic bladder replacement is more reasonable than the Le Duc antireflux technique in non-dilated ureters. The benefit of the antireflux technique has been overestimated despite of the frequency of stricture formation.