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Background:The incidence of colorectal cancer (CRC) in patients under age 50 is rising for unclear reasons. We examined the effects of socioeconomic factors on outcomes for patients with early-onset CRC compared to late-onset CRC. Methods: Patients with CRC from 2004 to 2015 in the National Cancer Database were included and categorized by age (under or over 50 years). Differences in demographic and socioeconomic factors, disease characteristics, and survival outcomes between early-onset versus late-onset CRC patients were assessed by Chi-squared test and Cox models. Results: The study population included 1,061,204 patients, 108,058 (10.2%) of whom were under age 50. The proportion of patients diagnosed under age 50

Oncogenic activation of fibroblast growth factor receptor 2 (FGFR2) drives multiple cancers and represents a broad therapeutic opportunity, yet selective targeting of FGFR2 has not been achieved. While the clinical efficacy of pan-FGFR inhibitors (pan-FGFRi) validates FGFR2 driver status in FGFR2 fusion-positive intrahepatic cholangiocarcinoma, their benefit is limited by incomplete target coverage due to FGFR1- and FGFR4-mediated toxicities (hyperphosphatemia and diarrhea) and the emergence of FGFR2 resistance mutations. RLY 4008 is a highly selective, irreversible FGFR2 inhibitor designed to overcome these limitations. In vitro, RLY-4008 demonstrates >250- and >5000-fold selectivity over FGFR1 and FGFR4, respectively, and targets primary alterations and resistance mutations. In vivo, RLY-4008 induces regression in multiple xenograft models – including models with FGFR2 resistance mutations that drive clinical progression on current pan-FGFRi – while sparing FGFR1 and FGFR4. In early clinical testing, RLY-4008 induced responses without clinically significant off-isoform FGFR toxicities, confirming the broad therapeutic potential of selective FGFR2 targeting.

Background.People living with human immunodeficiency virus (PLWH) have been disproportionally affected by methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection, in particular by clones USA300 and USA500. However, the contribution of epidemiological, bacterial, and immunological risk factors to the excess of S aureus in PLWH remain incompletely understood.Methods.In this cross-sectional study, we determined the prevalence and molecular epidemiology of S aureus colonization in 93 PLWH attending an urban human immunodeficiency virus (HIV) clinic. Participants completed a structured interview assessing demographic information and risk factors for MRSA. Swabs were obtained from the nose, throat, and groin and cultured for S aureus and Staphylococcus epidermidis.Results.Most participants had well controlled HIV infection (89, 96% CD4 >200). Thirty-six (39%) individuals were colonized with S aureus at 1 or more body sites, including 6 (6%) with MRSA. Regular gym use was a risk factor for S aureus but not MRSA carriage. In contrast, S epidermidis was present in almost all individuals (n = 84, 90%), predominantly in the nares (n = 66, 71%). Using generalized estimating equation models, we observed that the odds of S aureus colonization were significantly and drastically reduced when S epidermidis was detected (P = .0001). After controlling for site, gender, and age, we identified that the odds of S aureus colonization were 80% less if S epidermidis was present (adjusted odds ratio, 0.20; 95% confidence interval, .09–.45; P < .0001).Conclusions.Taken together, we observed a lower prevalence of S aureus and MRSA colonization than has been previously reported in PLWH. In this cohort, colonization with S epidermidis was protective against S aureus colonization.

PURPOSE: The proportion of gastroesophageal junction adenocarcinoma is increasing. This study evaluated trends in early-onset gastric and esophageal cancers and compared socioeconomic and clinical characteristics between early-onset versus late-onset disease. MATERIALS AND METHODS: We included all patients with gastric and esophageal cancer from 2004 to 2015 from the National Cancer Database. Patients were categorized by age < 50, 50-69, and ≥ 70 years. Differences in pathologic and socioeconomic factors between early-onset and late-onset cancers were assessed by using chi-square test. The effects of demographic and socioeconomic factors on overall survival (OS) were assessed using Cox models. RESULTS: The proportion of patients with early-onset gastric cancer increased from 23.9% in 2004-2006 to 26.2% in 2013-2015, whereas the proportion of early-onset esophageal cancer decreased from 27.3% in 2004-2006 to 23.1% in 2013-2015. For both malignancies, the early-onset group was more likely to be Black or Hispanic and more likely to be diagnosed with stage IV cancer. Black patients had the worst median OS in both malignancies. In gastric cancer, within the Black patient group, patients experienced worse OS if they had government insurance versus private insurance (hazard ratio 1.2; 95% CI, 1.1 to 1.3; P value < .0001) or if they were in the lowest community median income category versus the highest category (hazard ratio 1.2; 95% CI, 1.1 to 1.3; P value < .0001). CONCLUSION: Early-onset gastric cancer is increasing, whereas early-onset esophageal cancer is declining. Early-onset gastric cancer disproportionately affects non-White patients, particularly Hispanic patients. Black patients have worse outcomes compared with other races for both gastric and esophageal cancer.