{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T23:48:55Z","timestamp":1776383335364,"version":"3.51.2"},"reference-count":47,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"unspecified","delay-in-days":12,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100020084","name":"Guangzhou municipal science and technology bureau","doi-asserted-by":"crossref","award":["2023A04J0464, 2023A04J1170"],"award-info":[{"award-number":["2023A04J0464, 2023A04J1170"]}],"id":[{"id":"10.13039\/501100020084","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science and Technology Major Project of China","award":["2023ZD0505604)"],"award-info":[{"award-number":["2023ZD0505604)"]}]},{"DOI":"10.13039\/501100001809","name":"The National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82405450, 82305164"],"award-info":[{"award-number":["82405450, 82305164"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Guangdong Provincial Administration of Traditional Chinese Medicine","award":["20251294"],"award-info":[{"award-number":["20251294"]}]},{"name":"Chinese Medicine Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine","award":["YN2023MS05, YN2024MB026"],"award-info":[{"award-number":["YN2023MS05, YN2024MB026"]}]},{"name":"Chinese Medicine Science and Technology Research Project of Guangdong Provincial Hospital of Chinese Medicine","award":["YN2023MS05"],"award-info":[{"award-number":["YN2023MS05"]}]},{"name":"Guangdong Province key Laboratory of Research on Emergency in TCM","award":["2023B1212060062"],"award-info":[{"award-number":["2023B1212060062"]}]},{"name":"Postdoctoral Fund of Guangdong Hospital of Chinese Medicine","award":["414940"],"award-info":[{"award-number":["414940"]}]},{"name":"Top Talents Project of Guangdong Provincial Hospital of Chinese Medicine","award":["BJ2022YL15"],"award-info":[{"award-number":["BJ2022YL15"]}]},{"DOI":"10.13039\/501100012245","name":"Science and Technology Planning Project of Guangdong Province","doi-asserted-by":"crossref","award":["2023KT15469"],"award-info":[{"award-number":["2023KT15469"]}],"id":[{"id":"10.13039\/501100012245","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Science and Technology Plan Project of Liwan District in Guangzhou","award":["20250629"],"award-info":[{"award-number":["20250629"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,10,23]]},"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Sepsis is a life-threatening disease caused by a deregulated response to infection. This study aimed to investigate the linear and non-linear relationships between ionised calcium levels and 28-day mortality in patients with sepsis in the intensive care unit (ICU) and to generate hypotheses regarding laboratory index testing and calcium supplementation strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>A retrospective cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Adult patients admitted to the ICU, using data extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Participants<\/jats:title>\n                    <jats:p>A total of 17 955 adult patients with sepsis, defined according to the sepsis-3 criteria, were included. Patients lacking ionised calcium (iCa) data were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Outcome measures<\/jats:title>\n                    <jats:p>The exposure variable was iCa level measured within the first 24 hours of ICU admission, and the primary outcome was 28-day all-cause mortality. Covariates included demographics, vital signs, comorbidities, infection sites, organ support and medication use. Multivariable logistic regression models were applied with stepwise adjustment. Non-linear associations were assessed using generalised additive models (GAM) and two-piecewise linear regression. Sensitivity analyses using iCa quartiles and subgroup analyses stratified by Sequential Organ Failure Assessment (SOFA) score were also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The overall 28-day mortality rate was 18.3%. After full adjustment, patients in quartiles Q2\u2013Q4 had significantly lower mortality risks than those in Q1 (P for trend &lt;0.001). A U-shaped association was observed, with an inflection point at 1.16\u2009mmol\/L (95%\u2009CI 1.12 to 1.19). Below this threshold, each 0.1\u2009mmol\/L decrease in iCa was associated with a 13% higher risk of mortality (OR=0.87; 95%\u2009CI 0.82 to 0.92; p&lt;0.001); whereas, above this point, mortality increased by 6% per 0.1\u2009mmol\/L increment (OR=1.06; 95%\u2009CI 1.00 to 1.10; p=0.004). Subgroup analyses stratified by SOFA score (&lt;10\u2009vs \u226510) confirmed the robustness of the U-shaped relationship (p&gt;0.05).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The relationship between ionised calcium and 28-day mortality in patients with sepsis showed a U-shaped curve with an inflection point of 1.16\u2009mmol\/L, which is in the range of mild hypocalcaemia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-099781","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T13:00:15Z","timestamp":1763038815000},"page":"e099781","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":2,"title":["Non-linear relationship between ionised calcium and 28-day mortality in patients with sepsis: a retrospective cohort study from MIMIC-IV 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