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.

[Penile cancer with perineural invasion is more prone to postoperative recurrence].

OBJECTIVE: To explore the correlation between perineural invasion and postoperative recurrence in patients surgically treated for penile cancer. METHODS: We conducted a retrospective analysis of the clinical data on 18 penile cancer patients surgically treated in our hospital from January 2018 to December 2021, 8 with postoperative recurrence (the recurrence group) and the other 10 without (the non-recurrence control group). We compared the two groups of patients in the age of onset, tumor-node-metastasis (TNM) stages, American Joint Committee on Cancer (AJCC) prognosis stages, surgical methods, perineural invasion and recurrence time. We analyzed the differences in postoperative recurrence using the Kaplan Meier plotted survival curve and in independent risk factors in predicting postoperative recurrence using the ROC curve. RESULTS: Compared with the non-recurrence controls, the patients in the recurrence group had a significantly older age of onset (P=0.0411) and severer perineural invasion (P<0.001), and those with perineural invasion had a shorter recurrence time (P<0.001), which was an independent risk factor for postoperative recurrence. The areas under the ROC curves for perineural invasion and age were 0.885 and 0.213, respectively. CONCLUSION: Penile cancer with perineural invasion is more prone to and perineural invasion is an independent risk factor for postoperative recurrence of the malignancy.

Serum Human Epididymis Protein 4 is a Potential Biomarker for Early Chronic Kidney Disease in an Obese Population.

BACKGROUND: At present, it is difficult to clinically diagnose early chronic kidney disease (CKD). As a novel biomarker of malignancies in the female reproductive tract, the human epididymis protein 4 (HE4) has been reported to be significantly expressed in CKD patients. AIM: We sought to assess whether HE4 can be used as a potential biomarker of early-stage CKD. METHODS: The association between serum HE4 levels and CKD was analyzed in a retrospective study. A cohort of 506 patients with diabetic nephropathy who were hospitalized at Weihai Central Hospital, China, from January 2016 to November 2019 were included. RESULTS: Serum HE4 levels were increased with increasing stage of CKD and significantly elevated in patients with CKD3-5 than CKD1-2 (P<0.001). In multivariate linear regression analyses, HE4 levels were strongly correlated with the estimated glomerular filtration rate (eGFR) in CKD patients (Model 2, P<0.001). HE4 (area under the curve; AUC=0.934) had better diagnostic value than serum creatinine (SCr; AUC=0.770) and blood urea nitrogen (BUN; AUC=0.647) for patients with early-stage CKD (CKD1-2). Additionally, HE4 levels increased with increasing glomerular lesion (GL) and renal interstitial fibrosis (IF)/tubular atrophy (TA) scores in 51 CKD patients (P<0.001). CONCLUSION: Serum HE4 levels can be positively associated with the severity of CKD and are a very valuable clinical biomarker for predicting early-stage CKD.