{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:54:51Z","timestamp":1776142491221,"version":"3.50.1"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T00:00:00Z","timestamp":1776124800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite their disproportionately high mortality from community-acquired pneumonia (CAP), older adults remain understudied regarding inflammasome-mediated cell death pathways. We sought to determine whether distinct pyroptosis activation patterns exist in this population and how nutritional status modifies their prognostic impact.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort study enrolled 282 patients aged \u226575 years hospitalized for CAP. We quantified circulating pyroptosis effectors (gasdermin D [GSDMD], NLRP3, caspase-1) and assessed nutritional status using the Mini Nutritional Assessment-Short Form (MNA-SF). K-means clustering identified biological endotypes; generalized additive models (GAMs) characterized nonlinear biomarker-mortality relationships. The primary endpoint was 28-day all-cause mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Three pyroptosis endotypes emerged with markedly divergent outcomes: hyper-pyroptotic (n=73; mortality 57.5%), intermediate-pyroptotic (n=128; mortality 10.2%), and hypo-pyroptotic (n=81; mortality 1.2%). The hyper-pyroptotic endotype was characterized by severe malnutrition (48.2% with MNA-SF \u22647) and elevated cytokines (median IL-6: 98.4 pg\/mL). GAM analysis revealed threshold-dependent, nonlinear relationships\u2014mortality risk escalated sharply when GSDMD exceeded 3.5 ng\/mL but showed attenuation at extreme values. Notably, two-dimensional analyses demonstrated supra-additive risk in patients with concurrent nutritional compromise and pyroptosis activation. An integrated prognostic model achieved AUC 0.898 (95% CI: 0.847\u20130.943), significantly outperforming the Pneumonia Severity Index alone (AUC 0.793; P&amp;lt;0.001), with superior net benefit across clinically relevant decision thresholds (10\u201330%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Geriatric CAP comprises biologically distinct pyroptosis endotypes. Malnutrition was associated with a stronger relationship between pyroptosis markers and short-term mortality, consistent with effect modification. These findings support integrating nutritional assessment with pyroptosis biomarker profiling for risk stratification and generate hypotheses for prospective mechanistic and interventional studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1770810","type":"journal-article","created":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T04:20:38Z","timestamp":1776140438000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyroptosis endotypes and nonlinear biomarker-mortality relationships in older adults with community-acquired pneumonia: the amplifying role of malnutrition"],"prefix":"10.3389","volume":"17","author":[{"given":"Jingxian","family":"Liao","sequence":"first","affiliation":[{"name":"Department of Geriatrics, The Second People's Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University","place":["Lianyungang, 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