Chemotherapy-induced ileal crypt apoptosis and the ileal microbiome shape immunosurveillance and prognosis of proximal colon cancer

The prognosis of colon cancer (CC) is dictated by tumor-infiltrating lymphocytes, including follicular helper T (TFH) cells and the efficacy of chemotherapy-induced immune responses. It remains unclear whether gut microbes contribute to the elicitation of TFH cell-driven responses. Here, we show that the ileal microbiota dictates tolerogenic versus immunogenic cell death of ileal intestinal epithelial cells (IECs) and the accumulation of TFH cells in patients with CC and mice. Suppression of IEC apoptosis led to compromised chemotherapy-induced immunosurveillance against CC in mice. Protective immune responses against CC were associated with residence of Bacteroides fragilis and Erysipelotrichaceae in the ileum. In the presence of these commensals, apoptotic ileal IECs elicited PD-1+ TFH cells in an interleukin-1R1- and interleukin-12-dependent manner. The ileal microbiome governed the efficacy of chemotherapy and PD-1 blockade in CC independently of microsatellite instability. These findings demonstrate that immunogenic ileal apoptosis contributes to the prognosis of chemotherapy-treated CC

Treatment costs of diarrheal disease and all-cause pneumonia among children under-5 years of age

a b s t r a c t Objective: We estimate treatment costs associated with diarrheal disease and all-cause pneumonia among children under-5 years of age in Colombia and assess similarities or differences with previous cost estimations in developing countries of the Americas. Methods: Macro-costing methods were used to carry out an analysis of diarrhea and all-cause pneumonia costs in Colombia in 2010. The perspective of the health care system was taken. Data were extracted from a health insurer database that includes information on health service utilization among 130,800 children from low-income households. Lengths of stay for hospital admissions and frequencies of cases at all levels of care registered in the database were estimated. Results: There were 1456 diarrheal disease cases among the 130,800 children (aged ≥60 months) included in the study. The median cost per case was $27.10 (interquartile range [IQR]:$15.60-77.40). A total of 1545 all-cause pneumonia cases were reported to the insurer in 2010, resulting in a frequency of 1181 cases per 100,000 children (95% confidence interval [CI] = 1122, 1240). The overall cost of all-cause pneumonia cases was $858,791, and the median cost per case treated was$263 (IQR: $27-546). Comparisons by level of care showed that costs were significantly different for the two diseases (p < .05). Costs for the diseases did not differ by age group (p > .05). Conclusions: Diarrhea and all-cause pneumonia constitute a significant economic and health burden in Colombia. The relatively large size of our sample allowed us to provide reliable national estimates of the costs associated with these diseases. Our results for Colombia are similar to previous estimates from developing countries in the Americas. These data provide valid estimates that may be used decision makers in other countries to make appropriate recommendations on the introduction of rotavirus and pneumococcal vaccines