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  • br Methods br Discussion The current


    Discussion The current analysis among a prospective cohort of community-dwelling participants afforded two major contributions to the current literature gap; the opportunity to examine long-term risk for sepsis between cancer survivors and no cancer history participants and to examine whether these differences were modified by race/ethnicity. Our research hypothesis was derived from the biological plausible connection between cancer survivorship and sepsis. Possible physiological mechanisms that could explain the association between cancer survivorship and long-term risk of sepsis are: 1) the underlying malignancy causing an increase in circulating cytokines and thus causing a chronic inflammatory state [[39], [40], [41], [42], [43]], and/or 2) degradation of healthy MitoPY1 due to cancer treatment and therapy, both of which may lead cancer survivors to having a more immune-compromised physiology at baseline which would in turn lead to increased risk for infection and sepsis [44]. Using the large population-based study of community-dwelling adults from REGARDS cohort, we observed that cancer survivors were at more than a two-fold greater risk of sepsis when compared with community-dwelling REGARDS participants with no cancer history. Further, this association remained even after several adjustments for confounders, secondary analyses that excluded participants with a cancer death within three years of study follow-up, and accounting for all-cause mortality as competing risk. We observed no racial differences in risk and incidence rates of sepsis after cancer. To date, this is the first study to utilize a cohort of community-dwelling adults to examine the association between cancer survivorship and future risk of sepsis. Only a limited number of studies have investigated an association between cancer and sepsis. Moreover, prior studies that have examined this association have been based on data collected during hospitalization (i.e., cross-sectional), after major cancer surgical procedures, or only among cancer populations [[45], [46], [47], [48], [49], [50]]. For instance, one of the first studies to examine the association between cancer and sepsis utilized hospital discharge data from six US states (Florida, Massachusetts, New Jersey, New York, Virginia, and Washington) linked with SEER cancer prevalence data [50]. In this study, Williams et al. reported that sepsis was a very common complication among cancer patients, being responsible for more than 126,000 sepsis cases per year and that when compared to the overall population cancer patients were at nearly a 4-fold increased risk of developing sepsis [50]. In another study, Danai et al examined the prevalence of sepsis among hospitalized patients with a history of cancer complemented with data from the SEER with hospital discharge data from the National Hospital Discharge Survey (NHDS) spanning over 20 years from 1979 through 2001 [4]. The authors reported that, compared to no cancer history patients, cancer patients had nearly a 10-fold increased risk of having sepsis [4]. The results of prior studies indicate that cancer patients hospitalized or undergoing surgery are at an increased risk of sepsis [[45], [46], [47], [48], [49], [50]]. Similarly, the results of our study illuminate that cancer survivors of any type are at more than a two-fold increased risk of sepsis when compared with other community dwelling adults. The results of our study suggest that even after surviving cancer for greater than two years, cancer survivors remain at increased risk of community-acquired sepsis. Among patients hospitalized for infection, cancer survivors represent a very pertinent population for mitigation, infection prevention, and early detection and treatment of infection with necessary antibiotics. We also understand that cancer is a heterogeneous disease that has many underlying risk factors such as obesity, diet, exercise, and genetics. While we were unable to examine the risk of sepsis by specific cancers in the current study, we elucidated that cancer survivors considered to be healthy enough to be considered community-dwelling and participate in a longitudinal prospective cohort study were still at nearly a 2.5 to 3-fold increased risk of sepsis infection regardless of the cancer type, race, and accounting for multiple risk factors such as obesity, health behaviors, and comorbidities. Thus, cancer is a very pertinent risk factor in the treatment of sepsis and expeditious and urgent care should be taken when dealing treating patients with a history of cancer.