Univariable and multivariable mendelian randomization study revealed the modifiable risk factors of urolithiasis.

BACKGROUND: Urolithiasis is a common urological disease with increasing incidence worldwide, and preventing its risk poses significant challenges. Here, we used Mendelian randomization (MR) framework to genetically assess the causal nature of multifaceted risk factors on urolithiasis. METHODS: 17 potential risk factors associated with urolithiasis were collected from recently published observational studies, which can be categorized basically into lifestyle factors and circulating biomarkers. The instrumental variables of risk factors were selected from large-scale genome-wide association studies (N ≤ 607,291). Summary-level data on urolithiasis were obtained from UK Biobank (UKB) (3,625 cases and 459,308 noncases) and the FinnGen consortium (5,347 cases and 213,445 noncases). The univariable and multivariable MR analyses were applied to evaluate the causal, independent effect of these potential risk factors upon urolithiasis. Effects from the two consortia were combined by the meta-analysis methods. RESULTS: Higher genetically predicted sex hormone-binding globulin (SHBG, OR, 0.708; 95% CI, 0.555 to 0.903), estradiol (OR, 0.179; 95% CI, 0.042 to 0.751), tea intake (OR, 0.550; 95% CI, 0.345 to 0.878), alcoholic drinks per week (OR, 0.992; 95% CI, 0.987 to 0.997), and some physical activity (e.g., swimming, cycling, keeping fit, and bowling, OR, 0.054; 95% CI, 0.008 to 0.363) were significantly associated with a lower risk of urolithiasis. In the Multivariate Mendelian Randomization (MVMR) analyses, the significant causal associations between estradiol, SHBG, tea intake, and alcoholic drinks per week with urolithiasis were robust even after adjusting for potential confounding variables. However, the previously observed causal association between other exercises and urolithiasis was no longer significant after adjusting for these factors. CONCLUSIONS: The univariable and multivariable MR findings highlight the independent and significant roles of estradiol, SHBG, tea intake, and alcoholic drinks per week in the development of urolithiasis, which might provide a deeper insight into urolithiasis risk factors and supply potential preventative strategies.

Clinical Evaluation of Laparoscopic Surgery for Hirschsprung Disease Combined with Colorectal Anastomosis with a Stapling Technique in Infants.

Aim: To evaluate the effect of laparoscopic-assisted resection and colorectal anastomosis with a stapling technique in the treatment of Hirschsprung disease (HSCR) in infants. Methods: From June 2018 to January 2019, 25 cases of HSCR diagnosed by clinical examination and pathology were selected at the Children's Hospital, School of Medicine, Zhejiang University, China. All children were treated with standard laparoscopic-assisted transanal endorectal pull-through surgery (the modified Swenson technique). The short segment type and the typical type with a descending colon-rectum anastomosis were both included. The long segment type had an ascending colon-rectal anastomosis after ascending colon turnover. The colorectal anastomosis was divided into traditional manual anastomosis and straight intraluminal stapler (SIS) anastomosis. According to the different methods of anastomosis, the patients were divided into a traditional group and a SIS group. Age, gender, body weight, operation time, blood loss, postoperative anal exhaust and defecation time, postoperative hospitalization time, and postoperative short-term complications were analyzed retrospectively. Results: A total of 25 children were diagnosed with HSCR. There were 17 boys and 8 girls, and their average age was 10.20 months (interquartile range, 8.60-11.30). Their average body weight was 7.90 kg (interquartile range, 7.50-8.40). There were 17 cases of the typical type, 5 cases of the short segment type, and 3 cases of the long segment type. The different colorectal anastomosis methods were divided into 10 cases in the traditional group and 15 cases in the SIS group. There were no intraoperative complications, wound infections, or anastomotic fistula. Compared with the SIS group, children in the traditional group had an increased operative time (129.5 versus 103.00 minutes; P < .0001), increased intraoperative blood loss (20.00 versus 7.00 mL; P < .0001), increased postoperative hospitalization time (12.00 versus 9.00 days; P = .0003), and increased postoperative defecation time (18.40 versus 13.20 hours; P < .0001). After 6-12 months of follow-up, there was no anastomotic stenosis or enterocolitis in the SIS group. In the traditional group, 1 child had anastomotic stenosis, which improved 6 months after anal dilatation. One case of enterocolitis occurred 4 months after the operation and was cured after enema and infusion. Conclusion: Laparoscopic-assisted resection combined with colorectal anastomosis with the stapling technique in the treatment of HSCR in infants is feasible. It had a short operation time, less bleeding, less trauma, and a rapid recovery of postoperative intestinal function. The anastomosis was smooth, wide, and reliable, and anastomotic fistula and stenosis did not occur.