Letter to the editor: "Sex-related mortality differences in septic shock: A propensity score-matched study"

This letter offers methodological and interpretative reflections on the study by Fresilli and colleagues. We first identify a critical data inconsistency in Table 1, where variable counts far exceed the cohort size and reported mean ages contradict the inclusion criteria, suggesting encounter-level rather than patient-level data extraction-a violation of fundamental statistical assumptions. Second, the site of infection, a well-established strong predictor of sepsis outcomes with known sex differences in distribution, was not adequately controlled for, potentially confounding the observed survival advantage in young women. Third, the paradoxical finding of higher 28-day mortality in older women cannot be fully explained by declining estrogen levels alone, but likely reflects a complex interplay of immunosenescence, comorbidity patterns, frailty, and treatment biases. We recommend that the authors clarify the unit of data extraction, perform infection site-stratified analyses, and adopt a multidimensional framework in future research to better elucidate the role of sex in septic shock outcomes.