No statistically significant difference in response or survival was found between the PERFECT and the nCRT cohort. Baseline expression of an established IFNγ signature was higher in responders compared with nonresponders ( = 0.043). On-treatment nonresponders showed either a high number of cytotoxic lymphocytes (CTL) with a transcriptional signature consistent with expression of immune checkpoints, or a low number of CTLs. Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups. . Combining nCRT with atezolizumab is feasible in patients with rEAC. On the basis of our exploratory biomarker study, future studies are necessary to elucidate the potential of neoadjuvant immunotherapy in patient subgroups.See related commentary by Catenacci, p. 3269. Actionable mutations can guide genotype-directed matched therapy. We evaluated the utility of tissue-based and plasma-based genotyping for the identification of actionable mutations and selection of matched therapy in patients with metastatic breast cancer (MBC). Patients with MBC who underwent tissue genotyping (institutional platform, 91-gene assay) or plasma-based cell-free DNA (cfDNA, Guardant360, 73-gene assay) between January 2016 and December 2017 were included. A chart review of records to identify subtype, demographics, treatment, outcomes, and tissue genotyping or cfDNA results was performed. The incidence of actionable mutations and the selection of matched therapy in tissue genotyping or cfDNA cohorts was determined. https://www.selleckchem.com/products/ly-411575.html The impact of matched therapy status on overall survival (OS) in tissue genotyping or cfDNA subgroups was determined with Cox regression analysis. Of 252 patients who underwent cfDNA testing, 232 (92%) had detectable mutations, 196 (78%) had actionable mutations, and 86 (34%) received matched therapy. Of 118 patients who underwent tissue genotyping, 90 (76%) had detectable mutations, 59 (50%) had actionable mutations, and 13 (11%) received matched therapy. For cfDNA patients with actionable mutations, matched versus nonmatched therapy was associated with better OS [HR 0.41, 95% confidence interval (CI) 0.23-0.73, = 0.002], and this remained significant in a multivariable analysis correcting for age, subtype, visceral metastases, and brain metastases (HR = 0.46, 95% CI 0.26-0.83, = 0.010). Plasma-based genotyping identified high rates of actionable mutations, which was associated with significant application of matched therapy and better OS in patients with MBC. . Plasma-based genotyping identified high rates of actionable mutations, which was associated with significant application of matched therapy and better OS in patients with MBC.See related commentary by Rugo and Huppert, p. 3275. Recent evidence has shown adverse oncological outcomes when minimally invasive surgery is used in early-stage cervical cancer. The objective of this study was to compare disease-free survival in patients that had undergone radical hysterectomy and pelvic lymphadenectomy, either by laparoscopy or laparotomy. We performed a multicenter, retrospective cohort study of patients with cervical cancer stage IA1 with lymph-vascular invasion, IA2, and IB1 (FIGO 2009 classification), between January 1, 2006 to December 31, 2017, at seven cancer centers from six countries. We included squamous, adenocarcinoma, and adenosquamous histologies. We used an inverse probability of treatment weighting based on propensity score to construct a weighted cohort of women, including predictor variables selected a priori with the possibility of confounding the relationship between the surgical approach and survival. We estimated the HR for all-cause mortality after radical hysterectomy with weighted Cox proportional hazard models. laparoscopy was associated with worse disease-free survival, compared to laparotomy. In this retrospective multicenter study, laparoscopy was associated with worse disease-free survival, compared to laparotomy. Predicting disease progression in patients with autosomal dominant polycystic kidney disease (ADPKD) poses a challenge, especially in early-stage disease when kidney function is not yet affected. Ongoing growth of cysts causes maximal urine-concentrating capacity to decrease from early on. We therefore hypothesized that the urine-to-plasma urea ratio, as a reflection of the urine-concentrating capacity, can be used as a marker to predict ADPKD progression. The urine-to-plasma urea ratio was calculated by dividing concentrations of early morning fasting spot urine urea by plasma urea. First, this ratio was validated as surrogate marker in 30 patients with ADPKD who underwent a prolonged water deprivation test. Thereafter, association with kidney outcome was evaluated in 583 patients with ADPKD with a broad range of kidney function. Multivariable mixed-model regression was used to assess association with eGFR slope, and logarithmic regression to identify patients with rapidly progressive disease, using a cu ratio, which is calculated from routine laboratory measurements, predicts disease progression in ADPKD in addition to other risk markers. This article contains a podcast at https//www.asn-online.org/media/podcast/CJASN/2021_01_27_CJN10470620_final.mp3. This article contains a podcast at https//www.asn-online.org/media/podcast/CJASN/2021_01_27_CJN10470620_final.mp3. While evidence shows considerable geographic variations in county-level racial inequities in infant mortality, the role of structural racism across urban-rural lines remains unexplored. The objective of this study was to examine the associations between county-level structural racism (racial inequity in educational attainment, median household income and jail incarceration) and infant mortality and heterogeneity between urban and rural areas. Using linked live birth/infant death data provided by the National Center for Health Statistics, we calculated overall and race-specific 2013-2017 5-year infant mortality rates (IMRs) per 1000 live births in every county. Racially stratified and area-stratified negative binomial regression models estimated IMR ratios and 95% CIs associated with structural racism indicators, adjusting for county-level confounders. Adjusted linear regression models estimated associations between structural racism indicators and the absolute and relative racial inequity in IMR. In urban counties, structural racism indicators were associated with 7%-8% higher black IMR, and an overall structural racism score was associated with 9% greater black IMR; however, these findings became insignificant when adjusting for the region.