There have been few published studies on differences between Blacks and Whites in the estimated effects of alcohol and tobacco use on the incidence of head and neck cancer (HNC) in the United States. Previous studies have been limited by small numbers of Blacks. Using pooled data from 13 US case-control studies of oral, pharyngeal, and laryngeal cancers in the International Head and Neck Cancer Epidemiology Consortium, this study comprised a large number of Black HNC cases (n = 975). Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) for several tobacco and alcohol consumption characteristics. Blacks were found to have consistently stronger associations than Whites for the majority of tobacco consumption variables. For example, compared to never smokers, Blacks who smoked cigarettes for > 30 years had an OR 4.53 (95% CI 3.22-6.39), which was larger than that observed in Whites (OR 3.01, 95% CI 2.73-3.33; p < 0.0001). The ORs for alcohol use were also larger among Blacks compared to Whites. Exclusion of oropharyngeal cases attenuated the racial differences in tobacco use associations but not alcohol use associations. These findings suggest modest racial differences exist in the association of HNC risk with tobacco and alcohol consumption.

Tubulointerstitial fibrosis (TIF) is recognized as a final phenotypic manifestation in the transition from chronic kidney disease (CKD) to end-stage renal disease (ESRD). Here we show that conditional inactivation of Sav1 in the mouse renal epithelium resulted in upregulated expression of profibrotic genes and TIF. Loss of Sav1 induced Stat3 activation and a senescence-associated secretory phenotype (SASP) that coincided with the development of tubulointerstitial fibrosis. Treatment of mice with the YAP inhibitor verteporfin (VP) inhibited activation of genes associated with senescence, SASPs, and activation of Stat3 as well as impeded the development of fibrosis. Collectively, our studies offer novel insights into molecular events that are linked to fibrosis development from Sav1 loss and implicate VP as a potential pharmacological inhibitor to treat patients at risk for developing CKD and TIF.

Cellular therapies are emerging as a standard approach for the treatment of several diseases. However, realizing the promise of cellular therapies across the full range of treatable disorders will require large-scale, controlled, reproducible culture methods. Bioreactor systems offer the scale-up and monitoring needed, but standard stirred bioreactor cultures do not allow for the real-time regulation of key nutrients in the medium. In this study, β-TC6 insulinoma cells were aggregated and cultured for 3 weeks as a model of manufacturing a mammalian cell product. Cell expansion rates and medium nutrient levels were compared in static, stirred suspension bioreactors (SSB), and continuously fed (CF) SSB. While SSB cultures facilitated increased culture volumes, no increase in cell yields were observed, partly due to limitations in key nutrients, which were consumed by the cultures between feedings, such as glucose. Even when glucose levels were increased to prevent depletion between feedings, dramatic fluctuations in glucose levels were observed. Continuous feeding eliminated fluctuations and improved cell expansion when compared with both static and SSB culture methods. Further improvements in growth rates were observed after adjusting the feed rate based on calculated nutrient depletion, which maintained physiological glucose levels for the duration of the expansion. Adjusting the feed rate in a continuous medium replacement system can maintain the consistent nutrient levels required for the large-scale application of many cell products. Continuously fed bioreactor systems combined with nutrient regulation can be used to improve the yield and reproducibility of mammalian cells for biological products and cellular therapies and will facilitate the translation of cell culture from the research lab to clinical applications.

Objective To assess the effect of length of hospital stay on postoperative outcomes after minimally invasive hysterectomy. Methods A retrospective cohort analysis was conducted of women who underwent minimally invasive hysterectomy (vaginal or laparoscopic) for benign conditions between January 1, 2014 and December 31, 2016, using the American College of Surgeons National Surgical Quality Improvement Program database. Patient information and 30‐day outcomes were compared using multivariable logistic regression after adjusting for patient demographics and medical and procedure variables. Results The analysis included 31 347 patients. Women discharged the day after surgery were more likely to be African‐American, older, have prior abdominal surgery, and a higher ASA classification. Prevalence of organ space infection and readmissions were lower in the same day discharge group. No differences between same‐ and next‐day discharge were found for surgical site infection or urinary tract infection (adjusted odds ratios (aORs) 0.83 (95% [CI] 0.65–1.07; P=0.156) and 0.85 (95% CI 0.68–1.06; P=0.151), respectively). Same‐day hospital discharge was associated with a reduced chance of readmission (aOR=0.68, 95% CI 0.54–0.87; P=0.002). Conclusion Same‐day hospital discharge after minimally invasive hysterectomy lowered the risk of readmission and did not increase the risk of postoperative complications.

Primary congenital glaucoma (PCG) is a rare but serious birth defect. Genetic mutations have been implicated in the development of PCG, but little is known about nongenetic risk factors. This study investigates potential risk factors for PCG in the National Birth Defects Prevention Study (NBDPS), a large population-based case-control study of major birth defects in the United States. The analysis includes case infants with PCG (N = 107) and control infants without birth defects (N = 10,084) enrolled in NBDPS from birth years 2000-2011. Pregnancy/infant clinical characteristics, demographics, and parental health history were collected through maternal interview. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were computed to examine associations with all PCG cases and isolated PCG cases without other major malformations.Associations with all the cases included term low birth weight (<2,500 g; aOR = 2.80, CI 1.59-4.94), non-Hispanic black maternal race/ethnicity (aOR = 2.42, CI 1.42-4.13), maternal history of seizure (aOR = 2.73, CI 1.25-5.97), maternal antihypertensive use (aOR = 3.60, CI 1.52-8.53), and maternal sexually transmitted infection (aOR = 2.75, CI 1.17-6.44). These factors were also associated with isolated PCG, as was maternal use of nonsteroidal anti-inflammatory drugs (aOR = 2.70, CI 1.15-6.34). This study is among the first to examine a wide array of potential risk factors for PCG in a population-based sample.