Purpose: The purpose of this study was to determine if somatic mutations are associated with clinical and pathologic outcomes in patients with borderline resectable pancreatic cancer (BRPC) or locally advanced pancreatic cancer (LAPC) who were treated with neoadjuvant chemotherapy and stereotactic body radiotherapy (SBRT). Materials and Methods: Patients treated with neoadjuvant chemotherapy and SBRT followed by surgical resection from August 2016 to January 2019 and who underwent next generation sequencing of their primary tumor were included in the study. Next-generation sequencing was performed either in-house with a Solid Tumor Panel or with FoundationOne CDx. Univariate (UVA) and multivariable analyses (MVA) were performed to determine associations between somatic mutations and pathologic and clinical outcomes. Results: Thirty-five patients were included in the study. Chemotherapy consisted of modified FOLFIRINOX, gemcitabine and nab-paclitaxel, or gemcitabine and capecitabine. Patients were treated with SBRT in 33 Gy in 5 fractions. On UVA and MVA, tumors with KRAS G12V mutation demonstrated better pathologic tumor regression grade (TRG) to neoadjuvant therapy when compared to tumors with other KRAS mutations (odds ratio = 0.087; 95% confidence interval [CI], 0.009–0.860; p = 0.036). On UVA and MVA, mutations in NOTCH1/2 were associated with worse overall survival (hazard ratio [HR] = 4.15; 95% CI, 1.57–10.95; p = 0.004) and progression-free survival (HR = 3.61; 95% CI, 1.41–9.28; p = 0.008). On UVA, only mutations in NOTCH1/2 were associated with inferior distant metastasis-free survival (HR = 3.38; 95% CI, 1.25–9.16; p = 0.017). Conclusion In BRPC and LAPC, the KRAS G12V mutation was associated with better TRG following chemotherapy and SBRT. Additionally, NOTCH1/2 mutations were associated with worse overall survival, distant metastasis-free survival, and progression-free survival.

Background: and Purpose Infarct volume and other imaging markers are increasingly used as surrogate measures for clinical outcome in acute ischemic stroke research, but how improvements in these imaging surrogates translate into better clinical outcomes is currently unclear. We investigated how changes in infarct volume at 24 hours alter the probability of achieving good clinical outcome (modified Rankin Scale [mRS] 0–2). Methods: Data are from endovascular thrombectomy patients from the randomized controlled ESCAPE-NA1 (Efficacy and Safety of Nerinetide for the Treatment of Acute Ischaemic Stroke) trial. Infarct volume at 24 hours was manually segmented on non-contrast computed tomography or diffusion-weighted magnetic resonance imaging. Probabilities of achieving good outcome based on infarct volume were obtained from a multivariable logistic regression model. The probability of good outcome was plotted against infarct volume using linear spline regression. Results: A total of 1,099 patients were included in the analysis (median final infarct volume 24.9 mL [interquartile range: 6.6–92.2]). The relationship between total infarct volume and good outcome probability was nearly linear for infarct volumes between 0 mL and 250 mL. In this range, a 10% increase in the probability of achieving mRS 0–2 required a decrease in infarct volume of approximately 34.0 mL (95% confidence interval: -32.5 to -35.6). At infarct volumes above 250 mL, the probability of achieving mRS 0–2 probability was near zero. The relationships of tissue-specific infarct volumes and parenchymal hemorrhage volume generally showed similar patterns, although variability was high. Conclusion There seems to be a near-linear association between total infarct volume and probability of achieving good outcome for infarcts up to 250 mL, whereas patients with infarct volumes greater than 250 mL are highly unlikely to have a favorable outcome.

Oxidative stress is prevalent among infertile men and is a significant cause of sperm DNA damage. Since sperm DNA damage may reduce embryo quality and increase miscarriage rates, it is possible that untreated sperm oxidative stress may impair in vitro fertilization (IVF) live birth rates. Given that the antioxidant Menevit is reported to reduce sperm DNA damage, it was hypothesized that men's consumption of this supplement may alter IVF outcomes. Therefore, a retrospective cohort study was conducted analyzing outcomes for couples undergoing their first fresh embryo transfer. Men were classified as controls if they were taking no supplements, health conscious controls if taking "general health" supplements, or Menevit users. Men with karyotype abnormalities, or cycles using donated, frozen and surgically extracted sperm were excluded. Among the final study cohort of 657 men, live birth rates were significantly higher in Menevit users than controls (multivariate adjusted odds ratio [OR]: 1.57, 95% confidence interval [CI]: 1.01-2.45, P= 0.046), but not between controls taking no supplements and those using general health supplements, thereby suggesting that potential health conscious behavior in supplement users is unlikely responsible for the superior outcomes in Menevit users. Interestingly, in a post hoc sensitivity analysis, live birth rates among Menevit users were statistically superior to controls for lean men (OR: 2.73, 95% CI: 1.18-6.28; P= 0.019), not their overweight/obese counterparts (OR: 1.29, 95% CI: 0.75-2.22, P = 0.37). The results of this large cohort study therefore support a positive association between men's use of the Menevit antioxidant during IVF treatment and live birth rates, especially in lean individuals.