A three-gene expression score for predicting clinical benefit to anti-PD-1 blockade in advanced renal cell carcinoma.

In the advanced renal cell carcinoma (RCC) scenario, there are no consistent biomarkers to predict the clinical benefit patients derived from immune checkpoint blockade (ICB). Taking this into consideration, herein, we conducted a retrospective study in order to develop and validate a gene expression score for predicting clinical benefit to the anti-PD-1 antibody nivolumab in the context of patients diagnosed with advanced clear cell RCC enrolled in the CheckMate-009, CheckMate-010, and CheckMate-025 clinical trials. First, a three-gene expression score (3GES) with prognostic value for overall survival integrating HMGA1, NUP62, and ARHGAP42 transcripts was developed in a cohort of patients treated with nivolumab. Its prognostic value was then validated in the TCGA-KIRC cohort. Second, the predictive value for nivolumab was confirmed in a set of patients from the CheckMate-025 phase 3 clinical trial. Lastly, we explored the correlation of our 3GES with different clinical, molecular, and immune tumor characteristics. If the results of this study are definitively validated in other retrospective and large-scale, prospective studies, the 3GES will represent a valuable tool for guiding the design of ICB-based clinical trials in the aRCC scenario in the near future.

SATB2 as a Marker of the Proximal Nephron: Expression in Nephrogenic Adenoma and Correlation With Other Renal Tubular Markers.

Nephrogenic adenoma (NA) is an infrequent reactive urothelial lesion. The expression of immunohistochemical renal tubular markers has been reported in NA, although a proximal or distal nephron phenotype has not been established. Special AT-rich sequence-binding protein 2 (SATB2) is a marker of a colorectal origin of adenocarcinomas, occasionally reported in renal samples. We have analyzed SATB2 expression in NA, with correlation with other tubular markers, as well as in the normal kidney. Fifty cases of NA were immunostained with PAX8, SATB2, proximal nephron markers [CD10, renal cell carcinoma (RCC) marker, alpha-methylacyl-CoA racemase (AMACR), and CD15], and distal markers (Ksp cadherin, cytokeratin 7, E-cadherin (E-cad), and cytokeratin 19). Ten normal kidney sections were stained with a double method combining SATB2 plus CD10, RCC marker, AMACR, Ksp cadherin, cytokeratin 7, or E-cad. All NA were immunoreactive for PAX8 and 57% for SATB2. Every case was positive for proximal and distal nephron markers: 100% for cytokeratins 7 and 19, 84.1% E-cad +, 81.6% AMACR +, 68.9% Ksp cadherin +, 63% CD15 +, 53.3% CD10 +, and 28.6 % RCC +. In the normal kidney, SATB2 was detected in the straight part of the proximal tubules and the thin descending loops of Henle. NA shows a multiphenotypic pattern with coexpression of both proximal and distal nephron markers, and constant expression of PAX8, cytokeratins 7 and 19. SATB2 is often positive in NA, which should be kept in mind to avoid a possible misdiagnosis of intestinal adenocarcinoma. SATB2 is a marker of the normal proximal nephron.

Evaluation of the effect of triclosan coated sutures in the prevention of surgical site infections in a Spanish hospital setting: A prospective, observational study.

BACKGROUND: Surgical site infections (SSIs) are one of the most frequently reported types of hospital-acquired infection and are associated with substantial clinical and economic burden. AIM: To assess the incidence of SSIs and analyze contributing risk factors in a real-world Spanish hospital setting before and after the implementation of triclosan-coated sutures (TCS). METHODS: A prospective, observational study was conducted at Hospital Clínico Universitario de Santiago de Compostela, Spain. Enrolled patients underwent surgery in the following specialties: general surgery, urology, neurosurgery, gynaecology, and traumatology. The primary outcome of the study was SSI incidence, assessed at a 30-day follow-up. Secondary outcomes were length of hospital stay, and readmission, reintervention, and mortality rates, also at 30 days. FINDINGS: 5,081 patients were included in the study, of which 2,591 were treated using non-coated sutures (NCS) and 2,490 using TCS. After adjusting for potential confounders, TCS significantly reduced SSI rate by 36%, compared with NCS (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.48-0.85; P<0.003). When stratified by wound classification, a statistically significant reduction in SSI incidence, in favour of TCS use, was observed for Class IV (dirty) wounds (35.6% versus 22.7% for NCS and TCS, respectively; OR: 0.53; 95% CI: 0.31-0.90). CONCLUSION: The use of TCS reduced SSI risk when compared with NCS. This reduction was significant for Class IV wounds, providing evidence that supports the use of TCS for this type of wound.

The SCQ-SCORE: initial validation of a new scoring system for elective stone surgery prioritization in the COVID-19 era.

INTRODUCTION: Endourology waiting lists have increased during the COVID-19 pandemic and prioritization strategies are needed. Some tiered classifications have been put forward aimed at prioritizing patients by using criteria related with clinical severity or social impact of stone disease, yet no quantitative system has been published to date. The objective of this study is to present a new quantitative scoring system for elective stone surgery prioritization and show its intra- and inter-rater reliability. MATERIAL AND METHODS: A scoring system coined 'SCQ-score' was set up, which consists of 9 variables: infection (ranges 0-3), obstruction (0-3), indwelling time (0-3), admissions (0-3), symptoms (0-2), ureteral location (0-1), solitary or suboptimal kidney (0-1), chronic kidney disease (0-1) and presence of percutaneous nephrostomy (0-1).The intra- and inter-rater reliability of the SCQ-score was prospectively validated in 60 consecutive patients on the waiting list, by calculating the intraclass correlation coefficient (ICC). RESULTS: The SCQ-score demonstrated having an excellent interobserver agreement (ICC >0.75) for the final score and its different domains. After 4 weeks, a second analysis was carried out to measure its intra-rater reliability, which was also excellent. On average, 134.9 ±50 seconds were required to complete the SCQ-score. CONCLUSIONS: The SCQ-score is a new quantitative system to help prioritize elective stone surgeries, which has been shown to be user-friendly and to have an excellent intra- and inter-rater reliability. Initially developed to help during the COVID-19 pandemic, its utility will probably remain of interest in the post-COVID-19 era to ensure a fairer access to stone surgery.

Characterising endourologist learning curve during percutaneous nephrolithotomy: implications on occupational dose and patients.

In this study we have characterised the learning curve for percutaneous nephrolithotomy procedures over 301 cases for six years. Different surrogate parameters of clinical expertise have been used, such as dose area product, total procedure time, fluoroscopy time and personal equivalent doses. In addition, two different endourologists have been monitored; one of whom had specific Radiation Protection training (ICRP 85). Eye lens dose was estimated from thermoluminescent dosimeters. Significant differences were observed between both endourologists, especially in the fluoroscopy time. Finally, both entrance skin dose and effective doses of patients have been determined.

Characterizing endourologist learning curve during percutaneous nephrolithotomy: implications on occupational dose and patients.

In this study we have characterized the learning curve of percutaneous nephrolithotomy procedures over 301 cases for six years. Different surrogate parameters of clinical expertise have been used, such as dose area product, total procedure time, fluoroscopy time and personal equivalent doses. In addition, two different endourologists have been monitored; one of whom was subjected to a specific Radiation Protection training (ICRP 85). Eye lens dose is estimated from thermoluminescent dosimeters. Significant differences are observed between both endourologists, especially in the fluoroscopy time. Finally, both entrance skin dose and effective doses of patients have been determined.