Familial aggregation of urolithiasis: findings from a Nationwide Middle Eastern study.

This study aimed to determine the potential effect of genetic factors and positive family history on the familial aggregation of urolithiasis in Iran. Of the total 44,186 participants in the Iran National Stone Survey (INSS) database, 34,953 individuals who were members of 8629 nuclear families were included in this study. The mean prevalence of urolithiasis was 5.7% [95%CI: 5.5 - 6.0%] in this subpopulation. Familial aggregation of urolithiasis was analyzed in 34,745 participants (99.6% of those originally included) utilizing a multivariable logistic regression with second order generalized estimating equations approach (GEE2) to adjust for sex, age, urbanization status and ethnicity. Recurrence risk ratios (λ) were used to evaluate the degree of familial aggregation. Our multivariable analysis demonstrated a strong familial aggregation of urolithiasis within sibling pairs (λs = 78.35), parent-offspring pairs (λo = 40.12) and spouse pairs (λsp = 21.62). The respective ORs were 5.65 [95%CI: 3.49, 9.14] for siblings, 2.85 [95%CI: 2.20, 3.68] for parents and 1.27 [95%CI: 1.06, 1.54] for spouses. Urinary stone disease tends to aggregate in families with a positive history of urolithiasis in either the parents or siblings. Siblings have a more prominent effect in inducing familial aggregation compared to parents. Despite the prominent role of familial genetic components in urolithiasis aggregation, shared environmental factors appear to partake in this phenomenon to some extent, as suggested by urolithiasis aggregation among spouse pairs.

Exploring the Impact of Family History, Demographics and Ecological Factors on Urolithiasis Prevalence: Insights from a Nationwide Study.

OBJECTIVE:  This study aimed to evaluate the potential risk factors of lifetime urolithiasis occurrence on a nationwide scale in Iran. METHODS:  All data regarding urinary stone events were extracted from the cross-sectional Iran National Stone Survey (INSS) study, and the possible determinants of urolithiasis incidence were evaluated. RESULTS:  Our multivariable logistic regression suggested that while older age at presentation, male sex, and a positive family history of urolithiasis in either of the patient's parents or siblings were all significantly associated with an increased odds of lifetime urolithiasis occurrence (all P < .001), a positive family history in one's sister (odds ratio; OR=5.56) or brother (OR=4.70) were the most significant predictors. Moreover, belonging to Baluch ethnicity (i.e., an ethnical group indigenous to the south eastern regions of Iran) and residing in regions with higher water hardness (i.e., total concentration of dissolved minerals) were also associated with an increased odds of urolithiasis occurrence (P < .001 and P=.023, respectively). Conversely, living in regions with higher mean humidity decreased the chances of developing a urinary stone event during one's lifetime (OR=0.62, P <.001). CONCLUSION:  Our results indicated that a constellation of demographic, ecological, and familial risk factors are associated with an elevated risk of developing urinary stones during one's lifetime. These findings can assist in implementing novel regional healthcare policies, considering the specific demographic and ecological characteristics. They also support tailoring personalized preventive strategies, particularly for individuals with multiple nonmodifiable risk factors.

Determination of voiding pressure in infants with normal lower urinary tracts: Exploring the possible effect of sacral development.

OBJECTIVE: To investigate the association between sacral underdevelopment, as defined by subnormal sacral ratio (SR) measurements, with increased maximum detrusor voiding pressure (P det. Max) in infants. METHODS: In this 2007-2015 retrospective cohort study, the medical records of all infants who underwent a pyeloplasty due to congenital ureteropelvic junction obstruction were added. Their P det. Max was evaluated through the suprapubic catheter utilized for urinary drainage intraoperatively, without imposing any additional risk of urethral catheterization on the infant. SR was calculated via the plain kidney, ureter, and bladder (KUB) radiography film obtained during the voiding cystourethrogram (VCUG) evaluation before the surgery. Participants were categorized into SR < 0.74 or SR ≥ 0.74. P det. Max was subsequently compared between these two groups. RESULTS: A total of 45 patients were included in our analysis. Twenty-eight (62.2%) patients had a (SR < 0.74), while 17 (37.8%) had a (SR ≥ 0.74). P det. Max was shown to be significantly higher in the SR < 0.74 compared to the SR ≥ 0.74 group (167.5 ± 60.8 vs. 55.7 ± 17.9 cmH2O, p < 0.001). After adjusting for age and sex, SR remained a significant contributor to P det. Max (p < 0.001). Physiologic detrusor sphincter dyscoordination (PDSD) rate was significantly higher in the SR < 0.74 versus SR ≥ 0.74 group (100.0% vs. 70.6%, respectively; p = 0.005). CONCLUSION: Lumbosacral underdevelopment, as indicated by subnormal sacral ratios, is associated with sphincter-detrusor dyscoordination, which causes PDSD and can ultimately result in higher P det. Max in infants.

Does sacral ratio have any impact on success rate of biofeedback therapy in children with lower urinary tract dysfunction?

INTRODUCTION: To evaluate the possible impact of patients' sacral ratios (SRs) on response to biofeedback (BF) therapy in pediatric patients with lower urinary tract dysfunction (LUTD). MATERIALS AND METHODS: In this retrospective cohort conducted from 2016 to 2018 in our tertiary medical center, we included the medical records of all pediatric patients with LUTD who were nominated for BF due to having abnormal uroflowmetry patterns and simultaneous increase in electromyography (EMG) activity. Ten sessions of weekly animated BF were performed for each patient. All patients underwent a complete urological evaluation, uroflowmetry with simultaneous EMG and post-void residual measurement before and after treatment. SRs were calculated based on plain anteroposterior lumbosacral radiographs. Patients were then divided into normal SR (≥0.74) and low SR (<0.74) and outcomes were compared between them. RESULTS: Of the total 86 patients included in our study, 48 (55.8%) had a normal SR (≥0.74), while 38 (44.2%) had a low SR (<0.74). Our data revealed that BF therapy significantly improved maximum and average urinary flow rates, urine volume, daytime urinary incontinence, enuresis, urinary urgency and constipation; irrespective of the patients' SRs (all P < 0.001). Our between-groups analyses showed that after the completion of BF, the SR ≥ 0.74 group had significantly higher maximum urinary flow rate (mean difference [95%CI]: 7.7 [5.4, 10.0], P < 0.001) (Figure) and urine volume (mean difference [95%CI]: 49.9 [19.5, 80.4], P = 0.002) and significantly lower diurnal urinary incontinence (4.2% vs. 21.1%, P = 0.020), enuresis (4.2% vs. 18.4%, P = 0.040) and constipation (2.1% vs. 23.7%, P = 0.004) compared to the SR < 0.74 group. DISCUSSION: SR has been proposed as a reliable indicator of bony pelvis growth and subsequent lumbosacral neurodevelopment. Additionally, larger SR values are associated with better postoperative sphincter function in children with urological and anorectal malformations. Our results demonstrated that after completion of BF, the normal SR group had a significantly better improvement of some of the uroflowmetry indicators and LUTD-associated symptoms compared to the low SR group. CONCLUSION: Our findings implied that although BF therapy is an efficient treatment for children with LUTD, irrespective of their sacral development; children with enhanced sacral development may benefit from better clinical response, especially in terms of LUTD-associated symptoms.

Predictors of Recurrent Urolithiasis in Iran: Findings from a Nationwide Study.

BACKGROUND: Prevention of urinary stone recurrence is the ultimate goal in urolithiasis patients. In this study, we aimed to investigate the national prevalence rate and possible determinants of increased urolithiasis recurrence risk in a nationwide study in Iran. METHODS: All data regarding stone occurrence and recurrence episodes were extracted from the cross-sectional Iran National Stone Survey (INSS) study, and the possible determinants of recurrence were evaluated in the subset of 2913 patients who had a positive history of at least one episode of urolithiasis. RESULTS: The national prevalence rate of recurrent urolithiasis was 2.6% (95% CI: 2.5, 2.8) in Iran. Moreover, the relative ratio of recurrent stone formers to all stone formers was 39.8% (95% CI: 38.0, 41.6). Our univariable truncated negative binomial regressions suggested that a positive history of urolithiasis in the patient's father (prevalence ratio [PR] [95% CI]=1.83 [1.39, 2.41], P<0.001), mother (PR [95% CI]=1.92 [1.39, 2.66], P<0.001) or brother (PR [95% CI]=1.32 [1.03, 1.69], P=0.026); and residence in urban areas (PR [95% CI]=1.27 [1.04, 1.55], P=0.016) were significant predictors of repetitive recurrence episodes. However, when incorporated into a multivariable truncated negative binomial regression model, the only significant predictors of more frequent recurrence episodes were a positive history in father (PR [95% CI]=1.66 [1.24, 2.22], P<0.001) and mother (PR [95% CI]=1.68 [1.20, 2.36], P=0.002); and urban residence (PR [95% CI]=1.24 [1.01, 1.51], P=0.031). CONCLUSION: Our results indicate that a positive family history of urolithiasis in mother and father and residence in urban areas are the significant predictors of recurrence risk in urolithiasis patients in Iran.

Outcomes of Different Donor and Recipient Vessel and Ureteral Anastomoses in En Bloc Kidney Transplant From Pediatric Deceased Donors: A Retrospective Cohort.

OBJECTIVES: This study aimed to investigate the possible role of different donor and recipient vessel and ureteral anastomoses on survival and functional outcomes in en bloc kidney transplants. MATERIALS AND METHODS: This retrospective cohort included 99 en bloc kidney transplants performed from December 2005 to March 2022. Recipients were grouped based on donor's vessel (distal [n = 84] or proximal [n = 15] abdominal aorta), recipient's vessel (abdominal aorta [n = 3], external [n = 21], internal [n = 50], or common [n = 25] iliac artery), and ureteral anastomosis (separate [n = 32] or common [n = 67]). Patient and graft survival, complication rates, and estimated glomerular filtration rate trends were compared between groups. RESULTS: Pediatric brain dead donors had a mean age and weight of 37 ± 22 months and 14 ± 4 kg, respectively. Donor and recipient vessel and ureteral anastomoses did not affect overall survival (P = .306, .296, and .225), graft survival (P = .720, .172, and .124), and vascular (P = .347, .689, and .264) and urinary (P = .587, .172, and .385) complication rates. Lymphoceles requiring intervention were significantly more prevalent in the recipient external iliac artery group (P = .008) but were independent of donor vessel and ureteral anastomosis (P = .587 and 1.00). Estimated glomerular filtration rate trend was independentofdonor(P=.921) andrecipient vessel(P=.878 and .536). CONCLUSIONS: We found that different arterial and ureteral anastomoses appear to have comparable outcomes in en bloc kidney transplant with the exception of recipient external iliac artery, which may be slightly inferior because of the relatively higher rate of lymphoceles requiring intervention.

Non-coding RNAs in Recurrent implantation failure.

Recurrent implantation failure (RIF), defined as the inability to achieve conception following multiple consecutive in-vitro fertilization (IVF) attempts, represents a complex and multifaceted challenge in reproductive medicine. The emerging role of non-coding RNAs in RIF etiopathogenesis has only gained prominence over the last decade, illustrating a new dimension to our understanding of the intricate network underlying RIF. Successful embryo implantation demands a harmonious synchronization between an adequately decidualized endometrium, a competent blastocyst, and effective maternal-embryonic interactions. Emerging evidence has clarified the involvement of a sophisticated network of non-coding RNAs, including microRNAs, circular RNAs, and long non-coding RNAs, in orchestrating these pivotal processes. Disconcerted expression of these molecules can disrupt the delicate equilibrium required for implantation, amplifying the risk of RIF. This comprehensive review presents an in-depth investigation of the complex role played by non-coding RNAs in the pathogenesis of RIF. Furthermore, it underscores the vast potential of non-coding RNAs as diagnostic biomarkers and therapeutic targets, with the ultimate goal of enhancing implantation success rates in IVF cycles. As ongoing research continues to unravel the intercalated web of molecular interactions, exploiting the power of non-coding RNAs may offer promising avenues for mitigating the challenges posed by RIF and improving the outcomes of assisted reproduction.

Successful re-implantation of eroded penile prostheses: Report of two cases and review of the literature.

Prompt removal of eroded penile prostheses is recommended in most cases. However, saving and reimplanting eroded implants may be considered in patients without signs of sepsis, local infection or necrosis during preoperative evaluations and surgical exploration. Notably, close postoperative surveillance is crucial in this setting.

Three rare etiologies of urinary retention in pediatrics: A case series and review of the literature.

Etiology of urinary retention in pediatric age differs significantly from adults and the elderly. Therefore, a comprehensive diagnosis is crucial before specific treatment. Every effort must be made to minimize invasive procedures as far as possible in children.

Comparison of different urinary diversions after radical cystectomy in Iran: Assessment of health-related quality of life and financial burden in a Middle Eastern country.

OBJECTIVES: To compare health-related quality of life (HRQOL), cost-effectiveness, and survival among different types of urinary diversion (UD) utilized after radical cystectomy (RC) for bladder cancer with consideration of the unique economic and cultural context in Iran. PATIENTS AND METHODS: In this retrospective study, we examined all patients who underwent RC from May 2017 to December 2021 at two specialized centers by the same surgical team. Patients were grouped based on their UD. Post-surgical HRQOL (obtained from EORTC QLQ-C30 and QLQBLM-30), financial burden, surgical complications, and survival were compared. Kruskal-Wallis H test, One-way ANOVA, and Kaplan-Meier analyses were utilized; accordingly. RESULTS AND LIMITATIONS: In total 187 patients were identified-orthotopic neobladder (ONB) (N = 75), ileal conduit (IC) (N = 57), and cutaneous ureterostomy (CU) (N = 55)-and were followed for a median 17.5 (Interquartile range: 7.0, 47.0) months. ONB was associated with better HRQOL, especially in the domains addressing physical, role and social functioning (p = 0.003, 0.011, 0.045) as well as better body image (p < 0.001), lower short- and long-term financial burden (p = 0.034 and <0.001, respectively), marginally lower complication rate (p = 0.049), and better 5-year overall survival (p < 0.001), in comparison with other UDs. Patients who underwent CU had the lowest HRQOL and worst survival. Limitations were retrospective design and possibility of selection bias. CONCLUSIONS: In this first study that assesses a Middle Eastern collective; ONB seems to be the UD of choice with regard to HRQOL and economic burden when there is no contraindication.

Sildenafil Vs. Tadalafil for The Treatment of Benign Prostatic Hyperplasia: A Single-arm Self-controlled Clinical Trial.

PURPOSE: To compare the efficacy and adverse events of sildenafil monotherapy for benign prostatic hyperplasia (BPH) with its FDA-approved counterpart, tadalafil. MATERIALS AND METHODS: In this single-arm self-controlled clinical trial, 33 patients were enrolled. All patients underwent a 6-week treatment with sildenafil, followed by a 4-week washout period and finally a 6-week treatment with tadalafil. Patients were examined on each appointment and post-void residual (PVR) urine, International Prostate Symptom Score (IPSS) and Quality of life index (IPSS-QoL index) were recorded subsequently. Efficacy of each drug regimen was then evaluated by comparing these outcome parameters. RESULTS: Both sildenafil and tadalafil were shown to improve PVR (both p < .001), IPSS (both p < .001) and IPSS- QoL index (both p < .001) significantly. Sildenafil was more effective than tadalafil in reducing PVR (mean difference (95%CI) = 9.91% (4.11, 15.72), p < .001) and ameliorating IPSS-QoL index (mean difference (95%CI) = 19.3% (4.47, 34.41), p = .027). Moreover, although not significant, sildenafil reduced IPSS more than tadalafil (mean difference (95%CI) = 3.33% (-0.22, 6.87), p = .065). Concurrent erectile dysfunction did not affect responsiveness to therapy with either sildenafil or tadalafil but age was inversely related to post-treatment IPSS in both sildenafil (B = 0.21 (0.04, 0.37), p = .015) and tadalafil (B = 0.14 (0.02, 0.26), p = .021) regimens with a more prominent role in responsiveness to sildenafil (ß = 0.31) compared to tadalafil (ß = 0.19). CONCLUSION: Considering the significantly better improvement of PVR and IPSS-Qol index with sildenafil, this drug can be nominated as a suitable alternative for tadalafil as a BPH treatment, especially in younger patients who don't have any contraindications.

Current status and future perspectives of wilms tumor treatment in Iran.

Wilms tumor (WT) is among the most common pediatric malignancies. In this study, the authors tried to evaluate the adherence to internationally-approved WT treatment protocols in our tertiary medical center in Iran. Methods: In this retrospective study, the medical records of 72 pathologically confirmed WT patients who underwent treatment from April 2014 to February 2020 were evaluated. Demographic characteristics, histologic features of the tumors and metastases, utilized treatments, and survival rates were subsequently investigated. Results: From the total of 72 patients, 31 (43.1%) and 41 (56.9%) were males and females, respectively. The median age at the time of diagnosis was 44.0 (interquartile range: 18.5, 72.0) months. Among the patients, favorable histology was observed in 68 (94.6%) patients, while 4 (5.4%) patients had unfavorable histology. Regarding chemotherapy, 34/56 (60.7%), 4/56 (7.1%), and 18/56 (32.2%) received adjuvant, neoadjuvant, and combined chemotherapy, respectively. The mean numbers of neoadjuvant and adjuvant chemotherapy sessions were 9.4±5.6 and 14.5±11.1, respectively. 32/72 (44.4%) of the patients received adjuvant radiotherapy with a mean number of 7.3±3.6 sessions. Overall survival rates were 86% at 1-year, 74% at 3-year, and 62% at 5-year. Conclusion: Our results suggested that while the demographic characteristics of WT patients in Iran resemble those in other countries, abidance to internationally recommended protocols is relatively low. Moreover, survival rates were rather dismal in our study compared to those from other developing countries, further signifying the need for the development of a nation-specific treatment protocol for WT.

Pharmacological evidence for the possible involvement of the NMDA receptor pathway in the anticonvulsant effect of tramadol in mice.

Background: Previous studies have shown controversial results regarding the pro- or anticonvulsant effects of tramadol. Additionally, the underlying mechanism of seizure induction or alleviation by tramadol has not been fully understood. In the current study, the effects of tramadol on pentylenetetrazole (PTZ)-induced seizure and the possible involvement of the N-methyl-D-aspartate (NMDA) pathway were assessed in mice. Methods: Male Naval Medical Research Institute (NMRI) mice were treated with intravenous infusion of PTZ in order to induce clonic seizures and determine seizure threshold. Tramadol was injected intraperitoneally (0.1-150 mg/kg) 30 minutes prior to elicitation of seizures. The possible effects of intraperitoneal injections of NMDA receptor antagonists, ketamine (0.5 mg/kg) and MK-801 (0.5 mg/kg) on the anticonvulsant property of tramadol were investigated subsequently. Results: Tramadol (1-100 mg/kg) increased PTZ-induced seizure threshold in a dose-dependent, time-independent manner, with optimal anticonvulsant effect at a dose of 100 mg/kg. Acute administration of either ketamine (0.5 mg/kg) or MK-801 (0.5 mg/kg) potentiated the anticonvulsant effect of a subeffective dose of tramadol (0.3 mg/kg). Conclusion: These results suggest a possible role of the NMDA pathway in the anticonvulsant effect of tramadol.

Activation of cannabinoid receptors elicits antidepressant-like effects in a mouse model of social isolation stress.

Social isolation stress (SIS) paradigm is a chronic stress procedure able to induce profound behavioral and neurochemical changes in rodents and evokes depressive and anxiety-like behaviors. Recent studies demonstrated that the cannabinoid system plays a key role in behavioral abnormalities such as depression through different pathways; however, there is no evidence showing a relation between SIS and the cannabinoid system. This study investigated the role of the cannabinoid system in depressive-like behavior and anxiety-like behavior of IC animals. For this purpose, NMRI mice were treated with WIN55, 212-2 (non-selective cannabinoid receptor agonist) and AM-251 (cannabinoid receptor type 1 antagonist) and AM-630 (cannabinoid receptor type 2 antagonist). We found that behavioral abnormality followed by SIS was mitigated after administration of WIN55, 212-2. Also, depressive-like effects induced by SIS were significantly increased following administration of AM-251 and AM-630. Co-administration of cannabinoid receptor antagonists (AM-251 and AM-630), significantly reversed the antidepressant effect of WIN55, 212-2 in IC animals. Our findings suggest that the cannabinoid system is involved in depressive-like behaviors induced by SIS. We showed that activation of cannabinoid receptors (type 1 and 2) could mitigate depression-like behavior induced by SIS in a mouse model.