Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene () cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the gene result either in severe AME or a milder phenotype (type 2 AME). To date, ∼40 causative mutations have been identified. As part of the International Consortium for Rare Steroid Disorders, we have diagnosed and followed the largest single worldwide cohort of 36 AME patients. Here, we present the genotype and clinical phenotype of these patients, prominently from consanguineous marriages in the Middle East, who display profound hypertension and hypokalemic alkalosis. To correlate mutations with phenotypic severity, we constructed a computational model of the HSD11B2 protein. Having used a similar strategy for the in silico evaluation of 150 mutations of, the disease-causing gene in congenital adrenal hyperplasia, we now provide a full structural explanation for the clinical severity of AME resulting from each known missense mutation. We find that mutations that allow the formation of an inactive dimer, alter substrate/coenzyme binding, or impair structural stability of HSD11B2 yield severe AME. In contrast, mutations that cause an indirect disruption of substrate binding or mildly alter intramolecular interactions result in type 2 AME. A simple in silico evaluation of novel missense mutations could help predict the often-diverse phenotypes of an extremely rare monogenic disorder.

Objective: We aimed to retrospectively evaluate the effectiveness and safety of flexible ureteroscopy (f-URS), semirigid ureteroscopy (sr-URS), and shock wave lithotripsy (SWL) to treat single 11-20 mm stones in the proximal ureter. Materials and methods: Patients treated at our clinic for 11-20 mm single stones in the proximal ureter who underwent f-URS, sr-URS or SWL as initial lithotripsy methods were compared in terms of their clinical characteristics and treatment outcomes. Results: A comparison among 201 patients who had undergone f-URS, 119 patients who had undergone sr-URS, and 162 patients who had undergone SWL showed no significant baseline differences in patients’ demographic and stone characteristics. Stone-free rates on the 15th day and 3rd month were higher with f-URS (89.6% and 97%, respectively) than with sr-URS (67.2% and 94.1%, respectively) and SWL (41.4% and 79.0%, respectively; all p < 0.001). Retreatment rates were significantly higher with SWL than with the other two modalities (p < 0.001); auxiliary procedure rates were significantly lower with f-URS than with the other two modalities (p < 0.001). Treatment-related complication rate at the end of the 3rd month was lower with f-URS than with SWL (p = 0.022). Furthermore, f-URS was more effective than sr-URS for treating impacted stones. Conclusions: We found that f-URS was highly successful as an initial lithotripsy procedure for medium-sized proximal ureteral stones, and it helped achieve early stone-free outcomes with a lower need for retreatment and auxiliary procedures, lower complication rates, and higher effectiveness on the impacted stones compared with sr-URS and SWL.

Life expectancy has become longer, thus the number of elderly people who require treatment for nephrolithiasis has increased. We aimed to analyze the efficacy of flexible ureterorenoscopy (f-URS) and miniaturized percutaneous nephrolithotomy (mPNL) in the management of 10 and 30 mm renal stones in patients aged >60 years. In prospective non-randomized series, the data of patients who underwent f-URS or mPNL for kidney stones between July 2013 and July 2016 were analyzed. The procedure was accepted as successful if the patient was achieved complete stone clearance according to CT imaging between 1-3 months postoperatively. In total 60 patients and 58 patients were underwent f-URS and mPNL, respectively. The mean operation time, fluoroscopy time and hospitalization time were significantly shorter for the f-URS (p < 0.001, p < 0.001, p < 0.001, respectively). According to Clavien classification system, complication rates were not significantly different between the groups (p = 0.673). The stone-free rate was 81.7% for the f-URS group and 77.6% for the mPNL group after a single-session procedure (p = 0.747). Calcium oxalate monohydrate stones were the most common stone type in both groups. In multivariate analysis, multiple stones localization was only independent factor to predict complications. Our study had showed that both f-URS and mPNL are effective treatment modalities for 10-30-mm renal stones in elderly patients. Additionally, presence of stones in multiple location was the only predictive factor for complication development.

CYP2B6*6 and *9 variant alleles had a significant decreasing effect on sertraline metabolism in major depression patients which might result as variations in sertraline therapy.

The effects of ureteral stent diameters on ureteral stent‐related symptoms were evaluated by using Turkish‐validated Ureteral Stent Related Symptoms Questionnaire (USSQ). Datas on 126 patients underwent uncomplicated flexible ureterorenoscopy and 62 patients underwent uncomplicated semirigid ureteroscopy surgery without stent insertion (group 3) were collected. Patients were randomized preoperatively in a double‐blind fashion to 4.8 French (group 1) and 6 French (group 2) ureteral JJ stents groups. The first follow‐up visit was done at one week after surgery for all groups. Stents were removed on the third postoperative week for stented groups. The second follow‐up visit was done at one week after stent removal for group 1 and group 2, and four week after surgery for group 3. Preoperative characteristics, operation time and hospitalization times were similar in both groups. Total USSQ scores were 91.9, 103.0, 44.2 at first visit and 54.3, 58.7, 28.5 at second visit in group 1, group 2, and group 3, respectively. At both first and second visits, the group 2 had significantly higher USSQ scores than the group 1 (p = 0.01 and p < 0.001, respectively). Group 1 and 2 had higher scores than group 3 at both visits. Ureteral stents are associated with poor effects on patients' comfort and high USSQ scores. Using 4.8 Fr JJ stents improves stent‐related symptoms and decreases the USSQ score more than 6 Fr JJ stents. Therefore, if ureteral stent is to be used after URS, we recommend using 4.8 Fr stent.