{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T06:00:23Z","timestamp":1785218423592,"version":"3.55.0"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Septic shock is clinically heterogeneous, and early perfusion failure may not be adequately captured by any single bedside variable. We aimed to derive a clinically interpretable early perfusion phenotyping framework within a landmark design and assess whether the high-risk phenotype contour could be transferred across critical care databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this retrospective observational study, MIMIC-IV was used for phenotype derivation and the eICU Collaborative Research Database for fixed-parameter external transportability assessment. Adults in the first intensive care unit stay were eligible if they had early vasopressor exposure and baseline lactate greater than 2 mmol\/L. At an 8-h landmark, phenotypes were derived using mean arterial pressure deficit burden, body-weight-standardized urine output, and lactate clearance. The primary outcome was in-hospital mortality, selected for cross-database harmonization because it was consistently available in both databases, whereas fixed-time 28- or 90-day mortality was not reliably harmonized. Secondary renal outcomes were summarized descriptively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The MIMIC landmark cohort included 4,374 patients, of whom 2,671 had complete data for phenotype assignment. Four early perfusion phenotypes were identified. Phenotype 1 was characterized by greater hypotensive burden, poorer lactate clearance, and lower urine output. In-hospital mortality was 47.0% in Phenotype 1 versus 17.7% in Phenotype 4. Phenotype 1 remained associated with higher mortality after primary adjustment for age, sex, and pre-landmark SOFA score (OR 3.67, 95% CI 2.74\u20134.93), but this estimate attenuated after expanded pre-landmark case-mix adjustment (OR 2.56, 95% CI 1.85\u20133.53). In eICU, the same high-risk contour remained detectable under frozen transfer among measured complete-case patients. However, the strict and relaxed transfer cohorts were small, monitoring-dense subsets, and class-prevalence drift with measurement-dependent complete-case formation precluded robust conclusions about transportability of the entire four-class model, particularly for Phenotypes 2\u20134.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>A landmark-based early perfusion phenotype identified a high-risk perfusion-failure contour among septic shock patients with sufficient early monitoring density. In eICU, this contour was recoverable only within measured complete-case subsets, and the external data do not establish robust transportability of the entire four-class model. The framework should be interpreted as an observational, hypothesis-generating prognostic stratification approach rather than as an independently validated bedside decision tool.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2026.1880921","type":"journal-article","created":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T05:37:39Z","timestamp":1785217059000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Landmark-based early perfusion phenotyping for prognostic stratification in septic shock: derivation in MIMIC-IV and fixed-parameter external transportability assessment in eICU"],"prefix":"10.3389","volume":"13","author":[{"given":"Shuo","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihao","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changsheng","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Oncology, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, The Third Hospital of Hebei Medical University, Shijiazhuang","place":["Hebei, China"]},{"name":"Orthopaedic Research Institute of Hebei Province, Shijiazhuang","place":["Hebei, China"]},{"name":"NHC Key Laboratory of Intelligent Orthopaedic Equipment (The Third Hospital of Hebei Medical University), Shijiazhuang","place":["Hebei, China"]},{"name":"Engineering Research Center of Orthopedic Minimally Invasive Intelligent Equipment, China Ministry of Education, Shijiazhuang","place":["Hebei, China"]},{"name":"Key Laboratory of Biomechanics of Hebei Province, Shijiazhuang","place":["Hebei, China"]},{"name":"Key Laboratory of Precise Assessment, Diagnosis, and Treatment of Soft Tissue Injury of Hebei Province, Shijiazhuang","place":["Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the global burden of disease study.","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The third international consensus definitions for sepsis and septic shock 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