Nationwide Patterns in Mortality and Demographic Variations in Appendiceal Disease Complicated by Septicemia in the United States, 1999 to 2020.

Introduction Mortality from appendiceal disease in high-income settings is uncommon but not negligible, and septicemia is a recognized pathway to fatal outcome. The population-level burden of appendiceal disease deaths complicated by septicemia, along with its demographic distribution and temporal trends, has not been well characterized at the national level in the United States. Aims To quantify age-adjusted mortality from appendiceal disease with septicemia as a contributing cause among U.S. adults aged ≥25 years over 1999 to 2020, identify demographic subgroups with the highest age-adjusted mortality burden, and characterize temporal trends in age-adjusted mortality across the study period. Methodology We conducted a retrospective, population-based analysis using the CDC WONDER Multiple Cause of Death database. Cases were adults aged ≥25 years for whom appendiceal disease (International Classification of Diseases, Tenth Revision (ICD-10) K35-K38) was assigned as the underlying cause of death and septicemia (A41.0-A41.9) appeared among the multiple causes of death. Crude and age-adjusted mortality rates (AAMRs) per 1,000,000 population were calculated with 95% confidence intervals, age-standardized to the 2000 U.S. standard population. Temporal trends were analyzed using joinpoint regression to estimate annual percent changes (APCs). Results A total of 3,923 deaths met the inclusion criteria, representing 45.9% of all 8,549 appendiceal disease deaths in this population over the same period. The overall AAMR was 0.8 per million (95% CI 0.8-0.9). Age-adjusted mortality was higher in men than in women (1.1 vs 0.6 per million). Although White individuals accounted for the largest absolute number of deaths (n = 3,270; 83.4%), the highest AAMRs were observed among American Indian or Alaska Native (1.1 per million) and Black or African American (1.0 per million) populations, indicating that the per-population burden is disproportionately borne by these groups. Age-adjusted rates were essentially flat across urbanization categories, and 84.3% of deaths occurred in inpatient settings. Joinpoint analysis demonstrated a significant decline in AAMR between 2002 and 2016 (APC -2.55%; p < 0.05), followed by an increase between 2016 and 2020 (APC +5.79%; p < 0.05) that overlaps with the COVID-19 pandemic period and warrants cautious interpretation. Trend analysis was not feasible for racial groups other than White owing to suppression of cells with counts below 10. Conclusions Septicemia is implicated in nearly half of all fatal appendiceal disease in U.S. adults and is therefore a frequent contributing pathway in fatal appendiceal disease. Age-adjusted mortality declined significantly through 2016 but rose thereafter, with the most recent segment coinciding with pandemic-era disruptions to surgical and emergency care. The disproportionate age-adjusted burden among American Indian or Alaska Native, Black or African American, and male populations supports continued surveillance and further investigation into the clinical and structural factors that drive these inequities.