Mesenchymal Stem Cells in Regenerative Medicine, Possible Applications in The Restoration of Spermatogenesis: A Review.

Infertility is a common clinical condition and about half of the major causes are due to male-related infertility. Pathogenesis of this abnormality is generally undefined; so establishing a proper treatment option is relatively uncertain. In recent years, several evidences demonstrated that mesenchymal stem cells (MSCs) can be a hope for innovative and efficient treatment of male infertility. This study reviews possible applications of MSCs in the restoration of spermatogenesis in male infertility of both humans and animals to suggest new avenues for future clinical practices. Articles published in "PubMed" and "Google Scholar" from January 1, 2000, to August 1, 2023, were investigated by searching items of "mesenchymal stem cells", "cell therapy", "cell transplantation", and, "regenerative medicine" keywords, in addition to the "urology", "andrology", "reproductive medicine", "male infertility", "azoospermia", and "spermatogenesis". The results obtained from the transplantation of MSCs in the treatment of male infertility seemed encouraging and they revealed the safety and efficacy of these cells to recover spermatogenesis; eventhough further stem cell research is still required before recruiting clinical application of MSCs in the treatment of human male infertility. Undertaking more well-defined, standardized, and reproducible protocols and enrolling larger sample sizes during a longer follow-up period can benefit the relevance of MSC transplantation in the restoration of spermatogenesis and treatment of male infertility. It seems that developing and utilizing stem cell transplantations, exosomes, scaffold delivery systems, and three dimensional (3D) culture methods may open a new window to getting more benefits from cell therapy in the treatment of men infertility.

Predictive factors of delayed bleeding after percutaneous nephrolithotomy requiring angioembolization.

Objectives: To investigate the predictive factors of delayed post-percutaneous nephrolithotomy (PCNL) haemorrhage because of arteriovenous fistula (AVF) or pseudoaneurysm (PA) and compare the factors between AVF and PA. Patients and methods: This is a case-control study with a case-to-control ratio of 1:3. Out of 5077 patients who underwent PCNL from April 2015 to April 2018 in three different teaching hospitals, 113 had post-PCNL haemorrhages because of AVF and/or PA. Seventy-two patients met the inclusion criteria and entered the study as cases, while 216 patients without any postoperative complications were selected as controls. Results: Of all 72 studied patients with complications after PCNL, 35 (48.6%) had AVF, and the rest had PA. The regression model revealed that a history of diabetes (odds ratio [OR]: 2.799, 95% confidence interval [CI]: 1.392-5.630, p-value = 0.004) and renal anomalies (OR: 2.929, 95% CI: 1.108-7.744, p-value = 0.03) were associated with developing delayed post-PCNL haemorrhage. However, no differences were seen between AVF and PA regarding selected variables (p-value > 0.05). Conclusion: History of diabetes and renal anomalies were predictive factors for delayed post-PCNL haemorrhage, but no predictive factors were found to differentiate PA and AVF from one another.

Has the COVID-19 pandemic affected ureteral stone management in pregnant women? A retrospective single-center study.

INTRODUCTION: This study aimed to evaluate the effect of coronavirus disease (COVID-19) on the patients' referral in the pregnant population and also investigate each treatment approach's advantages and disadvantages for acute renal colic in pregnancy. METHODS: In this retrospective study, we included all pregnant women with ureteral stones referred to a referral center between January 2019 and March 2021. RESULTS: Among 53 pregnant women, 18 (33.9%) were on conservative therapy, which passed the stone without any complications. Double J stent or nephrostomy tube insertion was done for 24 patients (45.2%). Seventeen of these patients (70.8%) presented post-surgical complications, including hematuria (29.2%), pyelonephritis (20.8%), and lower urinary tract symptoms (20.8%). Transurethral lithotripsy (TUL) was done in 11 patients (20.7%). Only one of these patients developed hematuria following TUL. Thus, in our population study, double J stent or nephrostomy insertion was associated with a higher chance of postoperative complications than TUL (p-value = 0.001). Thirty-six patients were referred within 13 months before the entry of COVID-19, while 17 were referred during a similar approximate duration after the COVID-19 entry into the country. Only the initial presentation had a significant difference between these two periods (p-value = 0.034). CONCLUSIONS: When conservative treatment fails, we recommend TUL as the second-line treatment over temporary procedures, such as double J stent or nephrostomy insertion. Of note, in a group of patients with an emergent clinical setting, including active infection, deteriorating renal function, signs of preterm labor, solitary kidney, etc., double J or nephrostomy tube insertion remains the preferred management method for its fast resolution of obstruction and infection. Besides, a decrease in visits with an increase in complicated cases after COVID-19 was observed, maybe due to a delay in referring.

Outcome of Mini-Percutaneous Nephrolithotomy in Patients Under the Age of 18: An Experience With 112 Cases.

Purpose: Renal calculi are becoming more common among children. Although, extracorporeal shock wave lithotripsy (ESWL) is the first choice in this age group, minimal invasive surgeries, such as percutaneous nephrolithotomy (PCNL), are indicated for some patients. Recently, PCNL devices have become smaller in size with acceptable efficacy and lower complications. We evaluated the outcomes and complications of mini-PCNL (MPCNL) surgery in our referral training centers. Materials and Methods: Between September 2012 and January 2020, a total of 112 children under the age of 18, who had shown failure of ESWL, and/or their parents refused to do it, underwent MPCNL (15 Fr). The patients' profiles were reviewed for data collection including preoperative and stone data, operation information, and postoperative complications. Results: Of 112 patients, 69 were boys, and 43 were girls. Their mean age was 8.6 years (14 months to 18 years). Mean stone size was 20 mm (14-34 mm). Seventy-four cases had renal pelvic stone, 22 had pelvis and lower pole, and 16 had staghorn. The mean operation time was 65 min (35-100 min), and mean radiation time was 0.6 min (0.2-1.4 min). Low-grade fever was detected in 14 patients (12.5%). Four patients needed blood transfusion and two had increased creatinine, which improved with conservative management. One patient developed urosepsis that resolved with antibiotic therapy. None of the patients had kidney perforation or other organ injury or death. Early stone-free rate (SFR) after operation was 90.2% (101 patients). Six patients had residual fragment <5 mm, which passed spontaneously in 2 weeks after operation (total SFR 95.3%). Three patients underwent second-look nephroscopy, and ureteroscopy was done for two patients due to migrated stone fragments to the distal ureter. Conclusion: MPCNL is recommended as a safe alternative option for treatment of the nephrolithiasis in children with good outcome and acceptable complications.

Predicting the Postoperative Outcome of Percutaneous Nephrolithotomy with Machine Learning System: Software Validation and Comparative Analysis with Guy's Stone Score and the CROES Nomogram.

Purpose: To validate the output of a machine learning-based software as an intelligible interface for predicting multiple outcomes after percutaneous nephrolithotomy (PCNL). We compared the performance of this system with Guy's stone score (GSS) and the Clinical Research Office of Endourological Society (CROES) nomogram. Patients and Methods: Data from 146 adult patients (87 males, 59%) who underwent PCNL at our institute were used. To validate the system, accuracy of the software for predicting each postoperative outcome was compared with the actual outcome. Similarly, preoperative data were analyzed with GSS and CROES nomograms to determine stone-free status as predicted by these nomograms. A receiver operating characteristic (ROC) curve was generated for each scoring system, and the area under the ROC curve (AUC) was calculated and used to assess the predictive performance of all three models. Results: Overall stone-free rate was 72.6% (106/146). Forty of 146 patients (27.4%) were scheduled for 42 ancillary procedures (extracorporeal shockwave lithotripsy [SWL] [n = 31] or repeat PCNL [n = 11]) to manage residual renal stones. Overall, the machine learning system predicted the PCNL outcomes with an accuracy ranging between 80% and 95.1%. For predicting the stone-free status, the AUC for the software (0.915) was significantly larger than the AUC for GSS (0.615) or CROES nomograms (0.621) (p < 0.001). Conclusion: At the internal institutional level, the machine learning-based software was a promising tool for recording, processing, and predicting outcomes after PCNL. Validation of this system against an external dataset is highly recommended before its widespread application.

The association between dietary intakes and stone formation in patients with urinary stones in Shiraz.

Background: Kidney stone is a common and costly disease, but it may be improved by a healthy diet. The aim of this study was to evaluate the association between dietary intake and stone formation in patients with urinary stones in Shiraz. Methods: In this cross sectional study, 110 patients with kidney stone were selected from Faghihi hospital, Shiraz. Demographic information was collected, and anthropometric indices, disease-related variables, physical activity (using IPAQ), and dietary intake (using food frequency questionnaire, analyzed by Nut 4 software, to estimate micro and macro nutrients) were evaluated. Independent sample t test and one-way ANOVA were used to compare the quantitative variables between the 2 groups and multi groups, respectively. Chi square test was also used to compare qualitative variables. The correlation between variables was determined using Pearson test. Results: Out of 110 participants in this study, 37 (33.6%) were female, with the mean BMI of 27.0 ± 4.68 kg/m2, and 73 (66.4%) were male, with the mean BMI of 24.21±2.96 kg/m2. The mean intake of calcium-containing foods (p=0.02) and high-fructose beverages (p=0.03) was significantly greater in patients with calcium stones compared to those with uric acid stones. The mean intake of high-purine foods was significantly higher in patients with uric acid stones than in those with calcium stones (p=0.007). The mean intake of vitamin A (p=0.02), beta-carotene (p=0.03), and fructose (p=0.03) was significantly higher in patients with calcium stones than in those with uric acid stones, while caffeine intake was significantly higher in patients with uric acid than in those with calcium stones (p=0.01). There was a significant correlation between consumption of high-oxalic beverages (p=0.005, correlation coefficient = 0.26) and high-fructose (p=0.048, correlation coefficient = 0.18) with spontaneous stone expulsion. Conclusion: There was a significant relationship between consuming vitamin A, beta-carotene, and foods containing calcium, purine, fructose, and oxalate and formation of kidney stones. Therefore, adopting a healthy diet and increasing physical activity may be effective in the treatment of kidney stones.

Shock Wave Lithotripsy is More Effective for Residual Fragments after Percutaneous Nephrolithotomy than for Primary Stones of the Same Size: A Matched Pair Cohort Study.

AIMS: To compare the outcome of shock wave lithotripsy (SWL) on post-percutaneous nephrolithotomy (PCNL) residual fragments (RFs) versus primary stones of the same size through a matched pair study. METHODS: Patients with a single 5-15 mm fragment 3 months after PCNL were enrolled (study group n = 59). The control group (n = 67) consisted of all adult patients with a single 5-15 mm renal stone. RESULTS: The success rate of SWL was significantly higher in the study group (81.4 vs. 59.7%; p = 0.008; OR: 2.95). With a cutoff point of Hounsfield units (HU) 750: the success rate was significantly lower in patients with a stone HU ≥ 750 (OR: 3.488). This HU cutoff value had no effect on the outcome of SWL in patients with post-PCNL RF (p = 0.14). On the other hand, the outcome of SWL was significantly more favorable in control group when HU < 750 (p = 0.02). CONCLUSION: The success rate of SWL was 2.95-fold higher for post-PCNL RFs than in a stone burden-matched control group. The likelihood of stone clearance after SWL was 3.488-fold greater when HU was less than 750. This effect of HU was more prominent in patients receiving SWL for their primary stones while SWL was evenly effective on post PCNL RFs with different HUs.

Artificial Neural Network System to Predict the Postoperative Outcome of Percutaneous Nephrolithotomy.

PURPOSE: To construct, train, and apply an artificial neural network (ANN) system for prediction of different outcome variables of percutaneous nephrolithotomy (PCNL). We calculated predictive accuracy, sensitivity, and precision for each outcome variable. METHODS: During the study period, all adult patients who underwent PCNL at our institute were enrolled in the study. Preoperative and postoperative variables were recorded, and stone-free status was assessed perioperatively with computed tomography scans. MATLAB software was used to design and train the network in a feed forward back-propagation error adjustment scheme. Preoperative and postoperative data from 200 patients (training set) were used to analyze the effect and relative relevance of preoperative values on postoperative parameters. The validated adequately trained ANN was used to predict postoperative outcomes in the subsequent 254 adult patients (test set) whose preoperative values were serially fed into the system. To evaluate system accuracy in predicting each postoperative variable, predicted values were compared with actual outcomes. RESULTS: Two hundred fifty-four patients (155 [61%] males) were considered the test set. Mean stone burden was 6702.86 ± 381.6 mm3. Overall stone-free rate was 76.4%. Fifty-four out of 254 patients (21.3%) required ancillary procedures (shockwave lithotripsy 5.9%, transureteral lithotripsy 10.6%, and repeat PCNL 4.7%). The accuracy and sensitivity of the system in predicting different postoperative variables ranged from 81.0% to 98.2%. CONCLUSION: As a complex nonlinear mathematical model, our ANN system is an interconnected data mining tool, which prospectively analyzes and "learns" the relationships between variables. The accuracy and sensitivity of the system for predicting the stone-free rate, the need for blood transfusion, and post-PCNL ancillary procedures ranged from 81.0% to 98.2%.The stone burden and the stone morphometry were among the most significant preoperative characteristics that affected all postoperative outcome variables and they received the highest relative weight by the ANN system.

Glutathione Peroxidase 1 Gene Polymorphism in Nephrolithiasis Patients From South of Iran.

INTRODUCTION: Nephrolithiasis is a common multifactorial kidney disease with worldwide distribution. Compelling evidence, regarding the function of kidney in maintaining the body homeostasis, suggests the role of oxidative stress in the pathogenesis of nephrolithiasis. Glutathione peroxidase 1 is a major antioxidant enzyme, preventing oxidative damage to renal cells by detoxifying hydrogen and lipid peroxides, which may involve in its pathogenesis. The purpose of the present study was to determine the possible association of glutathione peroxidase 1 gene (GPX1) proline-to-leucine substitution at amino acid 198 (Pro198Leu polymorphism) with the risk of developing nephrolithiasis in south Iranian patients. MATERIALS AND METHODS: Association of Pro198Leu polymorphism in exon 2 of GPX1 gene was investigated in 150 patients with nephrolithiasis and 184 healthy age-, sex-, and ethnically-matched control group using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Regression analysis demonstrated that the frequency of the genotypes carrying at least 1 Leu allele, in both dominant and codominant model for this allele, was significantly higher in patients compared with the controls. However, significant association was found neither with wild-type allele, nor with polymorphic allele with the risk of nephrolithiasis. CONCLUSIONS: Findings of our study provide potential support in favor of the role of oxidative stress in the pathogenesis of nephrolithiasis in patients from south of Iran. The results indicate that GPX1 may be a key player in nephrolithiasis development.

The management of large staghorn renal stones by percutaneous versus laparoscopic versus open nephrolithotomy: a comparative analysis of clinical efficacy and functional outcome.

The objective of this study was to analyze the outcome of percutaneous nephrolithotomy (PCNL), laparoscopic and open anatrophic nephrolithotomy (AN) for management of patients with large staghorn renal stones. We analyzed the peri-operative parameters, overall treatment costs and changes in the function of the affected kidney on technetium-99 dimercaptosuccinic acid renal scintigraphy, done before the operation and before the final follow-up visit, in 45 adults who underwent PCNL (n = 16) versus laparoscopic (n = 15) versus open (n = 14) AN for large staghorn renal stones. All three groups had statistically similar preoperative characteristics, including the function of the operated kidney on renal scan. On the discharge day, the PCNL group had the lowest stone-free rate (43.75 %) compared to the laparoscopic (80 %) and open AN groups (92.85 %) (P = 0.009). After a mean follow-up period of 12.1 months, the decrease in the function of the operated kidney was greatest in the open AN group (-8.66 ± 4.97) compared to the laparoscopic AN (-6.04 ± 6.52) and PCNL group (-2.12 ± 2.77) (P = 0.003). The need for ancillary procedures to manage residual stones was greatest in the PCNL group and lowest in the open AN group. A similar trend was seen in overall treatment costs (P < 0.001). For management of large staghorn renal stones, the more invasive the procedure, the higher the one-session stone-free rate and the lower the need for ancillary procedures; however, greater renal functional loss can be anticipated. The need for ancillary procedures is a major determining factor in the overall cost of treatment, which was highest in the PCNL group.

Trace elements in urinary stones: a preliminary investigation in Fars province, Iran.

In view of the high incidence rate of urinary stones in the south and southwest of Iran, this paper investigates trace elements content including heavy metals in 39 urinary stones, collected from patients in Fars province, Iran. The mineralogy of the stones is investigated using X-ray diffractometry. The samples are classified into five mineral groups (calcium oxalate, uric acid, cystine, calcium phosphate and mixed stone). Major and trace elements in each group were determined using ICP-MS method. P and Ca constitute the main elements in urinary stones with Ca being more affine to oxalates while other alkali and alkaline earths precipitate with phosphate. Significant amounts of trace elements, especially Zn and Sr, were found in urinary calculi (calcium oxalate and phosphates) relative to biominerals (uric acid and cystine). Among urinary calculi, calcium phosphate contains greater amounts of trace metal than calcium oxalate. Phosphates seem to be the most important metal-bearing phases in urinary stones. Results indicate that concentrations of elements in urinary stones depend on the type of mineral phases. Significant differences in elements content across various mineralogical groups were found by applying statistical methods. Kruskal-Wallis test reveals significant difference between Ca, P, K, Na, Mg, S, Zn, Sr, Se, Cd, and Co content in different investigated mineral groups. Moreover, Mann-Whitney test differentiates Ca, Na, Zn, Sr, Co, and Ni between minerals in oxalate and uric acid stones. This study shows that urinary stone can provide complementary information on human exposure to elements and estimate the environmental risks involved in urinary stones formation.

Massive hemorrhage after percutaneous nephrolithotomy: saving the kidney when angioembolization has failed or is unavailable.

OBJECTIVES: To describe the management protocol in cases with massive hemorrhage after percutaneous nephrolithotomy (PCNL) with a failed angioembolization or when angioembolization is not available. PATIENTS AND METHODS: Between October 2006 and December 2012, the charts of patients who had undergone PCNL and were complicated with massive post procedural bleeding unresponsive to conservative management were reviewed. Those cases in whom angioembolization had failed, or was unavailable, or could not be afforded by the patient were selected and studied. These patients underwent open surgical exploration through a midline transperitoneal or a flank retroperitoneal approach. In both approaches, kidney mobilization outside the Gerota's fascia, temporal renal pedicle clamping and partial nephrectomy or renorrhaphy were done in a stepwise manner. RESULTS: During the study period, we had 8 patients for whom angioembolization had failed (n = 4), was not available (n = 2) or the patient could not afford it (n = 2). Median patients' age was 31 years (range 16-59 years). We did a partial nephrectomy in 2 and renorrhaphy in 6 of patients with a successful outcome. Median operative time was 2.25 h and median warm ischemia time was 26 min (range 24-42 min). After a median follow up period of 21 months, the involved renal unit, in all cases, remained functional in the postoperative intravenous urography. CONCLUSION: Massive hemorrhage after PCNL when angioembolization failed or was not feasible due to any reason could be controlled by partial nephrectomy or renorrhaphy with the same principles as that used for surgical exploration in patients with high grade renal trauma.

Metabolic abnormalities in patients with nephrolithiasis: comparison of first-episode with recurrent cases in Southern Iran.

BACKGROUND: Metabolic disorders are one of the etiologic factors in renal stone formation. The aim of present study was to evaluate prevalence of metabolic disorders in patients with renal stone. METHODS: From 572 patients referring to our urologic clinics, 376 patients participated in the study. Patients were divided to first time stone former (group A) and recurrent renal stone (group B). Twenty-four hour urine specimens were obtained for urinary calcium, oxalate, magnesium, citrate, uric acid, phosphor and 24-h urine volume. Venous blood samples were obtained evaluating serum phosphate, uric acid, and calcium. The prevalence of each metabolic disorder was detected, and two groups were compared regarding metabolic disorders. RESULTS: The prevalence of renal stone in male patients was 63.04% versus 36.96% in female patients (P < 0.05). The most common abnormality observed in patients was low 24-h urine volume (58.24%) followed by hypercalciuria (17.18%) and hyperuricosuria (15.15%). Hyperuricemia was found in 6 first time stone former patients and 14 patients with recurrent renal stone (P = 0.04). There was no statistically significant difference between group A and B in other metabolic abnormalities (P > 0.05). CONCLUSION: Low 24-h urine volume was the most common abnormalities in patients with nephrolithiasis in our region. Metabolic evaluation must be performed in all patients with renal stone even those with first time stone formation.

Efficacy of extracorporeal shock wave lithotripsy monotherapy in complex urolithiasis in the era of advanced endourologic procedures.

PURPOSE: It is believed that extracorporeal shock wave lithotripsy (ESWL) may be less effective than other modalities for treating stones in complex calculi. In this study, we investigated the efficacy of ESWL for treatment of complex stones. MATERIALS AND METHODS: Between September 2002 and October 2003, 250 complex cases of urolithiasis, including ureteral stones, staghorn stones, and stones in children, high risk patients, single kidneys, steinstrasse, and horseshoe kidneys were selected to be treated with Siemens Lithostar (Siemens AG, Munich, Germany) on an outpatient basis. Data were collected prospectively and the results of ESWL monotherapy on these complex patients were reviewed. RESULTS: The overall success rate was 91.2% for children and 77.7% for patients with single kidneys. Also, ESWL was efficient in the treatment of ureteral stones at the rate of 70.5% to 83.3%, depending on the location of the stone in the ureter and its size. The success rate of ESWL for patients with horseshoe kidneys, staghorn stones, and steinstrasse were marginal (66.6%, 66.0% and 33.3%, respectively). All of the cases were managed on outpatient basis and hospital admission was not required. CONCLUSION: Outpatient ESWL can be safely performed as a minimally invasive treatment after proper patient selection, even for complex patients. Its successfulness in children, patients with solitary kidney, and for almost all of ureteral stones is quite acceptable. However, its usage in patients with horseshoe kidneys or steinstrasse, and those with staghorn stones is questionable and should be done only in carefully selected cases. Thus, with appropriate patient selection, significant improvements in stone-free rates may also be achieved in these cases.