Search

Objectives: To externally validate the previously published Mayo clinic model for the prediction of early (<30 days) postoperative renal failure, which relies solely on preoperative estimated glomerular filtration rate (eGFR) and develop a novel model for the prediction of long-term (>30 days) renal function after partial nephrectomy (PN) and radical nephrectomy (RN), including patient factors and nephrometry scores., Patients and Methods: Retrospective, single-center cohort study on patients who underwent PN or RN for a unilateral renal tumor between 2003 and 2019 with a preoperative eGFR of at least 15 ml/min/1.73m 2 . Early postoperative renal failure was defined as eGFR <15 ml/min/1.73 m 2 or receipt of dialysis within 30 days. We determined the area under the receiver operating characteristics curve (AUC) to assess the Mayo clinic model's discriminative power. We used hierarchical linear mixed models with backward selection of candidate variables to develop a prediction model for long-term eGFR following PN and RN, separately. Their predictive ability was quantified using the marginal and conditional R 2 GLMM and an internal validation., Results: We included 421 patients (7,548 eGFR observations) who underwent PN and 271 patients (6,530 eGFR observations) who underwent RN. The Mayo clinic model for prediction of early postoperative renal failure following PN and RN showed an AUC of 0.816 (95% CI 0.718-0.920) and 0.825 (95% CI 0.688-0.962), respectively. In multivariable models, long-term eGFR following PN was associated with age, diabetes, the presence of a solitary kidney, tumor diameter and preoperative eGFR, while long-term eGFR following RN was associated with age, body mass index, RENAL nephrometry score and preoperative eGFR. Marginal and conditional R 2 GLMM were 0.591 and 0.855 for the PN model, and 0.363 and 0.849 for the RN model, respectively., Conclusions: The Mayo clinic model for short-term renal failure prediction showed good accuracy on external validation. Our long-term eGFR prediction models depend mostly on host factors as opposed to tumor complexity and can aid in decision-making when considering PN vs. RN., Competing Interests: Declaration of Competing Interest Eduard Roussel has received an unrestricted research grant from Ipsen and Pfizer. Benoit Beuselinck received an unrestricted research grant from Bristol-Myers-Squibb and honorarium from Merck, Pfizer, Bristol-Myers-Squibb, Ipsen, and Astra-Zeneca and is a senior clinical investigator of ‘Fonds voor wetenschappelijk onderzoek Vlaanderen’ (Belgium). Maarten Albersen received an unrestricted research grant from Ipsen and Pfizer and is a clinical investigator of ‘Stichting tegen kanker’ (Belgium). All other authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Bacterial translocation (BTL) drives pathogenesis and complications of cirrhosis. Farnesoid X-activated receptor (FXR) is a key transcription regulator in hepatic and intestinal bile metabolism. We studied potential intestinal FXR dysfunction in a rat model of cholestatic liver injury and evaluated effects of obeticholic acid (INT-747), an FXR agonist, on gut permeability, inflammation, and BTL. Rats were gavaged with INT-747 or vehicle during 10 days after bile-duct ligation and then were assessed for changes in gut permeability, BTL, and tight-junction protein expression, immune cell recruitment, and cytokine expression in ileum, mesenteric lymph nodes, and spleen. Auxiliary in vitro BTL-mimicking experiments were performed with Transwell supports. Vehicle-treated bile duct-ligated rats exhibited decreased FXR pathway expression in both jejunum and ileum, in association with increased gut permeability through increased claudin-2 expression and related to local and systemic recruitment of natural killer cells resulting in increased interferon-γ expression and BTL. After INT-747 treatment, natural killer cells and interferon-γ expression markedly decreased, in association with normalized permeability selectively in ileum (up-regulated claudin-1 and occludin) and a significant reduction in BTL. In vitro, interferon-γ induced increased Escherichia coli translocation, which remained unaffected by INT-747. In experimental cholestasis, FXR agonism improved ileal barrier function by attenuating intestinal inflammation, leading to reduced BTL and thus demonstrating a crucial protective role for FXR in the gut-liver axis., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background: To evaluate the antitumor activity and toxicity of single-agent cetuximab in patients with recurrent high-grade glioma (HGG) after failure of surgery, radiation therapy, and chemotherapy., Patients and Methods: In this two-arm, open-label, phase II study patients were stratified according to their epidermal growth factor receptor (EGFR) gene amplification status. Cetuximab was administered intravenously at a dose of 400 mg/m(2) on week 1 followed by weekly dose of 250 mg/m(2). The primary end point for this study was the response rate in both study arms separately., Results: Fifty-five eligible patients (28 with and 27 without EGFR amplification) tolerated cetuximab well. Three patients (5.5%) had a partial response and 16 patients (29.6%) had stable disease. The median time to progression was 1.9 months [95% confidence interval (CI) 1.6-2.2 months]. Whereas the progression-free survival (PFS) was <6 months in the majority (n = 50/55) of patients, five patients (9.2%) had a PFS on cetuximab of >9 months. Median overall survival was 5.0 months (95% CI 4.2-5.9 months). No significant correlation was found between response, survival and EGFR amplification., Conclusions: Cetuximab was well tolerated but had limited activity in this patient population with progressive HGG. A minority of patients may derive a more durable benefit but were not prospectively identified by EGFR gene copy number.

Background: This study evaluated vascular brachytherapy (VBT) as a potent antiproliferative treatment to prevent in-stent restenosis (ISR) after coronary angioplasty of de novo lesions in patients carrying the D allele of the I/D polymorphism of the ACE gene and high ACE plasma levels (>34 U/l)., Methods and Materials: A prospective randomized trial was designed to detect a 30% improvement in the minimal lumen diameter (MLD) of the stenotic artery, as measured by quantitative coronary analysis (QCA), 6 months following VBT at the time of stented angioplasty. All patients were carriers of the D allele of the ACE gene, with plasma ACE levels >34 U/l., Results: Thirty-one patients (33 stenoses) were allocated to stent implantation (control group) and 30 patients (31 stenoses) to VBT and stented angioplasty. After angioplasty, in-stent MLD was similar in the two groups. At 6 months in the control group, in-stent MLD had decreased to 1.74+/-0.8 versus 2.25+/-1.05 mm in the VBT group (P=.04). The mean in-stent diameter was 2.3+/-0.8 mm in the control group versus 2.9+/-1.05 mm after VBT (P=.02), and the restenosis rate was 37.5% versus 17.9%, respectively (P=.08). At 6 months, a higher need for target vessel revascularization (TVR) was observed in the control group: 35.5% versus 13.3% (P=.04)., Conclusions: This randomized study confirms that patients with high plasma ACE concentrations are exposed to an increased risk for ISR after coronary stenting. The preventive use of VBT in these patients reduced neointimal formation by 65% such that the MLD at follow-up was increased by 29% compared with the control group.