Vitamin D and Anti-Müllerian Hormone Levels in Infertility Treatment: The Change-Point Problem

Background: Anti-Müllerian hormone (AMH) is considered to be one of the most significant indicators of women’s fertility. Many studies have shown that vitamin D may modify human reproductive functions; however, the results are conflicting. The composition of follicular fluid (FF) creates the biochemical environment of the oocyte and affects its quality, which later determines the embryo quality. In this study, we aimed to revise with advanced statistical techniques the relationship between AMH and vitamin D in FF. Methods: The study was designed as a prospective single-center study in infertile patients with AMH ≥ 0.7 ng/mL who underwent controlled ovarian hyperstimulation for in vitro fertilization. AMH and vitamin D levels in FF were measured. Next, the standard and advanced statistical (including segmented regression) techniques were applied. Results: We observed a negative linear correlation between levels of AMH in serum and FF and total vitamin D concentrations up to approximately 30 ng/ml; with a statistically significant relationship in FF. Beyond that concentration, the trend was positive but statistically insignificant. Conclusions: As an existing “change-point problem„ was noticed, we suggest segmentation in the relationship between vitamin D and AMH during infertility treatment

High Plasma Angiopoietin-2 Levels Predict the Need to Initiate Dialysis within Two Years in Patients with Chronic Kidney Disease

Volume status, congestion, endothelial activation, and injury all play roles in glomerular filtration rate (GFR) decline. In this study, we aimed to determine whether the plasma endothelial and overhydration markers could serve as independent predictors for dialysis initiation in patients with chronic kidney disease (CKD) 3b-5 (GFR 2) and preserved ejection fraction. A prospective, observational study in a single academic center was conducted from March 2019 to March 2022. Plasma levels of angiopoietin (Ang)-2, Vascular Endothelial Growth Factor-C (VEGF-C), Vascular Cell Adhesion Molecule-1 (VCAM-1), Copeptin (CPP), beta-trace protein (BTP), brain natriuretic peptide (BNP), and cardiac troponin I (cTnI) were all measured. Lung ultrasound (US) B-lines, bioimpedance, and echocardiography with global longitudinal strain (GLS) were recorded. The study outcome was the initiation of chronic dialysis (renal replacement therapy) during 24 months of follow-up. A total of 105 consecutive patients with a mean eGFR of 21.3 mL/min/1.73 m were recruited and finally analyzed. A positive correlation between Ang-2 and VCAM-1 and BTP was observed. Ang-2 correlated positively with BNP, cTnI, sCr, E/e′, and the extracellular water (ECW)/intracellular water (ICW) ratio (ECW/ICW). After 24 months, a deterioration in renal function was observed in 47 patients (58%). In multivariate regression analysis, both VCAM-1 and Ang-2 showed independent influences on risk of renal replacement therapy initiation. In a Kaplan-Meier analysis, 72% of patients with Ang-2 concentrations below the median (3.15 ng/mL) survived without dialysis for two years. Such an impact was not observed for GFR, VCAM, CCP, VEGF-C, or BTP. Endothelial activation, quantified by plasma levels of Ang-2, may play a key role in GFR decline and the need for dialysis initiation in patients with CKD 3b, 4, and 5

Lung Congestion Severity in Kidney Transplant Recipients Is Not Affected by Arteriovenous Fistula Function

Lung ultrasound is a bedside technique for the assessment of pulmonary congestion. The study aims to assess the severity of lung congestion in kidney transplant recipients (KTR) in relation to arteriovenous fistula (AVF) patency. One hundred fifty-seven patients at least 12 months after kidney transplantation were recruited to participate in a cross-sectional study. Apart from routine visits, lung ultrasound at 28 typical points was performed. The patients were assigned to either AVF+ or AVF− groups. The mean number of lung ultrasound B-lines (USBLs) was 5.14 ± 4.96 with no differences between groups: 5.5 ± 5.0 in AVF+ and 4.8 ± 4.9 in AVF−, p = 0.35. The number and proportion of patients with no congestion (0–5 USBLs), mild congestion (6–15 USBLs), and moderate congestion (16–30 USBLs) were as follows: 101 (64.7%), 49 (31.4%), and 6 (3.8%), respectively. In multivariate analysis, only symptoms (OR 5.90; CI 2.43,14.3; p = 0.0001), body mass index (BMI) (OR 1.09; CI 1.03,1.17; p = 0.0046), and serum cholesterol level (OR 0.994; CI 0.998,1.000; p = 0.0452) contributed significantly to the severity of lung congestion. Lung ultrasound is a valuable tool for the evaluation of KTR. Functioning AVF in KTR is not the major factor affecting the severity of pulmonary congestion

Restaging Transurethral Resection of Bladder Tumours after BCG Immunotherapy Induction in Patients with T1 Non-Muscle-Invasive Bladder Cancer Might not Be Associated with Oncologic Benefit

The European Association of Urology guidelines recommend restaging transurethral resection of bladder tumours (reTURB) 2-6 weeks after primary TURB. However, in clinical practice some patients undergo a second TURB procedure after Bacillus Calmette-Guérin immunotherapy (BCG)induction. To date, there are no studies comparing post-BCG reTURB with the classic pre-BCG approach. The aim of this study was to assess whether the performance of reTURB after BCG induction in T1HG bladder cancer is related to potential oncological benefits

Delaying BCG immunotherapy onset after transurethral resection of non-muscle-invasive bladder cancer is associated with adverse survival outcomes

Abstract Purpose This study was carried out to assess whether a prolonged time between primary transurethral resection of non-muscle-invasive bladder cancer (TURB) and implementation of bacillus Calmette–Guerin (BCG) immunotherapy (time to BCG; TTBCG) is associated with adverse oncological survival in patients with T1 high-grade (HG) non-muscle-invasive bladder cancer (NMIBC). Materials and methods Data on 429 patients from 13 tertiary care centers with primary T1HG NMIBC treated with reTURB and maintenance BCG between 2001 and 2019 were retrospectively reviewed. Change-point regression was applied following Muggeo’s approach. The population was divided into subgroups according to TTBCG, whereas the recurrence-free survival (RFS) and progression-free survival (PFS) were estimated with log-rank tests. Additionally, Cox regression analyses were performed. Due to differences in baseline patient characteristics, propensity-score-matched analysis (PSM) and inverse-probability weighting (IPW) were implemented. Results The median TTBCG was 95 days (interquartile range (IQR): 71–127). The change-point regression analysis revealed a gradually increasing risk of recurrence with growing TTBCG. The risk of tumor progression gradually increased until a TTBCG of approximately 18 weeks. When the study population was divided into two subgroups (time intervals: ≤ 101 and > 101 days), statistically significant differences were found for both RFS (p = 0.029) and PFS (p = 0.005). Furthermore, in patients with a viable tumor at reTURB, there were no differences in RFS and PFS. After both PSM and IPW, statistically significant differences were found for both RFS and PFS, with worse results for longer TTBCG. Conclusion This study shows that delaying BCG immunotherapy after TURB of T1HG NMIBC is associated with an increased risk of tumor recurrence and progression