Critical care explorations最新文献

{"title":"Immunomodulation Therapy to Treat Severe Malaria With Multiple Organ Failure.","authors":"Saige Camara, Amy Buck, Mikayla Burrell, H David Humes, Stuart L Goldstein, Carlie N Myers, Michael Humes","doi":"10.1097/CCE.0000000000001471","DOIUrl":"10.1097/CCE.0000000000001471","url":null,"abstract":"<p><strong>Background: </strong>Malaria causes more than 600,000 deaths annually. Severe malaria is frequently complicated by acute kidney injury (AKI) and multiple organ failure driven by dysregulated host hyperinflammation. Elevated cytokines, including interleukin-6 and tumor necrosis factor alpha, are associated with disease severity and mortality, yet effective adjunctive immunomodulatory therapies are lacking. We report the first clinical use of the selective cytopheretic device (SCD), an extracorporeal immunomodulatory therapy, in severe malaria.</p><p><strong>Case summary: </strong>A 5-year-old girl returning from the Democratic Republic of the Congo presented with fever, shock, 10.9% parasitemia, AKI, and evolving multiple organ dysfunction. Despite IV artesunate and RBC exchange, she developed refractory shock and severe lactic acidosis. Continuous renal replacement therapy with adjunctive SCD therapy was initiated, after which inflammatory markers, vasopressor requirements, and metabolic acidosis improved with progressive organ recovery.</p><p><strong>Conclusions: </strong>Targeted extracorporeal immunomodulation may represent a promising adjunctive strategy for severe malaria.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 9","pages":"e1471"},"PeriodicalIF":2.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteomic Immune Signatures of Severe HIV-Associated Tuberculosis in Sub-Saharan Africa: A Prospective, Multicenter Analysis From Uganda.","authors":"Jesse E Ross, Alin S Tomoiaga, Nicholas Owor, Xuan Lu, Joseph Shinyale, Tonny Kiyingi, Ignatius Asasira, Peter James Eliku, John Bosco Nsubuga, Christopher Nsereko, Irene Nayiga, Stephen Kyebambe, Thomas Ochar, Moses Kiwubeyi, Rittah Nankwanga, Kai Nie, Hui Xie, Sam Miake-Lye, Bryan Villagomez, Jingjing Qi, Steven J Reynolds, Martina Cathy Nakibuuka, John Kayiwa, Mercy Haumba, Joweria Nakaseegu, Xiaoyu Che, Risa Hoffman, John A Belperio, Julius J Lutwama, Seunghee Kim-Schulze, Max R O'Donnell, Barnabas Bakamutumaho, Matthew J Cummings","doi":"10.1097/CCE.0000000000001439","DOIUrl":"10.1097/CCE.0000000000001439","url":null,"abstract":"<p><strong>Objectives: </strong>Severe tuberculosis (TB) is a major cause of critical illness and death in people living with HIV (PLWH) worldwide. Despite this, the immunopathology of severe HIV-associated TB (HIV/TB) is poorly understood. We aimed to identify an immunopathologic signature of severe HIV/TB in sub-Saharan Africa.</p><p><strong>Design and setting: </strong>We analyzed proteomic data from two prospective observational cohorts of adults hospitalized with severe undifferentiated infection in Uganda: an urban discovery cohort (Entebbe, n = 241) and a rural validation cohort (Tororo, n = 253).</p><p><strong>Patients: </strong>Adults (age ≥ 18 yr) hospitalized with severe febrile illness.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>Across both cohorts, severe HIV/TB was common, affecting 18% of participants in the discovery cohort and 21% in the validation cohort. Overall mortality was significant (30-d mortality of 22% in the discovery cohort and 60-d mortality of 26% in the validation cohort). Participants were stratified into three HIV/TB phenotypes: HIV-negative without TB, PLWH without TB, and PLWH with microbiologically diagnosed TB. We applied ordinal random forest models in the discovery cohort as a supervised feature-selection approach to identify proteins associated with progressive HIV/TB phenotype. In both cohorts, PLWH with microbiologically diagnosed TB were at highest risk of critical illness and death (30-d mortality of 42% in the discovery cohort and 60-d mortality of 52% in the validation cohort). An eight-protein signature reliably distinguished this phenotype, reflecting mediators of macrophage/dendritic cell activation (lysosome-associated membrane glycoprotein 3), natural killer cell and T-cell stimulation and cytotoxicity (cluster of differentiation 70, class I-restricted T-cell-associated molecule), B-cell activation (immunoglobulin lambda constant 2), protease-mediated tissue injury (protease, serine 2 [trypsin-2]), dysregulated coagulation (serpin peptidase inhibitor, clade A [alpha-1 antitrypsin], member 5), extracellular matrix remodeling (epidermal growth factor-containing fibulin-like extracellular matrix protein 1), and growth hormone/insulin-like growth factor axis dysregulation (insulin-like growth factor binding protein 3).</p><p><strong>Conclusions: </strong>We identified an immunologic signature of severe HIV/TB defined by mediators of macrophage/dendritic cell and cytotoxic lymphocyte activation, extracellular matrix remodeling, and dysregulated coagulation. These findings offer new insight into HIV/TB pathobiology and highlight potential targets for host-directed therapies in this high-risk population.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 9","pages":"e1439"},"PeriodicalIF":2.9,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13521507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148835661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Descriptive Overview of Deviations From an Institutional Peripheral Vasopressor Protocol and Its Effects on Safety Across an Academic Health System.","authors":"Daniel Shyu, Nicholas E Ingraham, Bailey McCarville, Christopher A Linke, Nicole Newman, Lianne K Siegel, Jared A Larson, Anna R Benson, Kathryn M Pendleton","doi":"10.1097/CCE.0000000000001469","DOIUrl":"10.1097/CCE.0000000000001469","url":null,"abstract":"<p><strong>Objectives: </strong>This study characterized deviations from an institutional peripheral vasopressor protocol and assessed associated extravasation events.</p><p><strong>Design: </strong>Retrospective observational study of electronic medical records data.</p><p><strong>Setting: </strong>Ten hospitals in an academic health system from October 2020 to May 2023.</p><p><strong>Patients: </strong>All admitted adult patients who received vasopressor infusions.</p><p><strong>Interventions: </strong>Implementation of a peripheral vasopressor protocol in October 2020.</p><p><strong>Measurements and main results: </strong>Three thousand five hundred eighteen patients were identified as having received peripheral vasopressors from October 2020 to May 2023, with 1258 patients suspected of having a deviation from the protocol. One hundred sixty-two patients were randomly selected for chart review, and 73 patients had confirmed deviation. Sixty-three (86.3%) exceeded the maximum allowed dose, 23 had multiple simultaneously infusing peripheral vasopressors, 13 had a peripheral vasopressor infusing longer than 24 hours, and 13 received peripheral vasopressin. Most deviations (79.4%) occurred due to worsening shock while waiting for central access. Extravasation occurred in 10 patients (13.7%), with three patients requiring phentolamine treatment. Fifty-six patients (76.7%) subsequently required central access for continued vasopressor support. In a secondary analysis of the original source population, 47 of 3518 patients (1.3%) received phentolamine for peripheral vasopressor extravasation, of whom the majority (72.4%) were protocol concordant at the time of extravasation.</p><p><strong>Conclusions: </strong>Deviations from a peripheral vasopressor protocol primarily involved exceeding the protocol dose limit in the setting of worsening shock while awaiting central access. Clinically significant extravasations were infrequent even among patients with protocol deviations and most treated extravasations occurred in protocol-concordant patients, supporting the overall safety of peripheral vasopressors.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 9","pages":"e1469"},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506231/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820486","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What Are We Actually Feeding ICU Patients? The Case for Studying Formula Composition.","authors":"Michael J Morowitz, Dennis M Simon, David T Huang, Enid E Martinez, Nilesh M Mehta","doi":"10.1097/CCE.0000000000001465","DOIUrl":"10.1097/CCE.0000000000001465","url":null,"abstract":"<p><p>Large randomized controlled trials testing the quantity and timing of enteral nutrition (EN) in critically ill patients have consistently failed to demonstrate benefit. We propose that these negative results may partly reflect an unexamined variable: the composition of EN formulas themselves. Most widely used formulas rely on corn-derived simple carbohydrates, isolated functional fibers, dairy-based proteins, and omega-6-rich vegetable oils, ingredients selected largely for manufacturing efficiency and shelf stability rather than clinical evidence. These components bear little resemblance to whole foods, and their distinct effects on metabolism, inflammation, and gut function have received little study in critical illness. Commercially available whole-food and plant-based EN formulas now offer compositionally distinct alternatives, yet no rigorous trials have compared them to conventional formulas in critically ill patients. We argue for a paradigm shift from volume-based to composition-focused nutrition research, pairing patient-centered clinical outcomes with mechanistic endpoints, including effects on the gut microbiome.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 9","pages":"e1465"},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Butyrylcholinesterase Activity as a Mortality Marker in ICU Patients: An Individual Participant Data Meta-Analysis.","authors":"Ricardo Esper Treml, Iago T C Grillo, Anna Hrabovska, Tomas Fazekas, Florian Espeter, Karsten Schmidt, Tulio Caldonazo, Felipe S Passos, Paulo Ricardo Gessolo Lins, Thais Dimidega, Johannes Ehler, Anibal Basile Filho, Sebastian O Decker, Aleksandar R Zivkovic, Joao Manoel da Silva","doi":"10.1097/CCE.0000000000001476","DOIUrl":"10.1097/CCE.0000000000001476","url":null,"abstract":"<p><strong>Objectives: </strong>To determine whether butyrylcholinesterase (BChE) activity independently predicts in-hospital mortality in critically ill adults and to derive a prognostic threshold from patient-level data.</p><p><strong>Data sources: </strong>Six databases (PubMed, MEDLINE, Embase, Scopus, Web of Science, Cochrane CENTRAL) were searched from inception to data lock. The protocol was registered with PROSPERO (CRD42024558631); reporting followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses of individual participant data (IPD).</p><p><strong>Study selection: </strong>Eligible studies were observational cohorts of critically ill adults measuring BChE by the Ellman or Worek method. Six prospective European and South American ICU cohorts contributed 482 adults (92.9% with sepsis; in-hospital mortality, 39%). Risk of bias was appraised with the Quality in Prognosis Studies tool.</p><p><strong>Data extraction: </strong>Deidentified IPD from corresponding authors and one public repository were checked for integrity, harmonized, and converted to U/L. Variables included demographics, sepsis status, severity indices (Sequential Organ Failure Assessment, Acute Physiology and Chronic Health Evaluation II), and biochemical markers.</p><p><strong>Data synthesis: </strong>Analyses included receiver operating characteristic curves (DeLong area under the curve [AUC], bias-corrected bootstrap), multivariable logistic regression, generalized estimating equation models, Kaplan-Meier and Cox regression, and random-effects meta-analysis (Hartung-Knapp). Admission BChE was lower among non-survivors, with moderate discrimination (pooled AUC, 0.72; 95% CI, 0.65-0.83; DeLong AUC, 0.671; 95% CI, 0.644-0.697). Higher Day-1 BChE was independently associated with lower mortality (odds ratio [OR] per 100 U/L, 0.979; 95% CI, 0.967-0.990; p < 0.001), with a significant ICU day interaction (p = 0.029) and attenuation by Day 4. BChE below 1615 U/L predicted higher mortality (hazard ratio, 1.69; 95% CI, 1.11-2.59; log-rank p = 0.015). Meta-analysis confirmed the inverse association (pooled OR per 1 sd, 0.22; 95% CI, 0.06-0.73; p = 0.023).</p><p><strong>Conclusions: </strong>BChE enzymatic activity was an integrative, time-dependent prognostic marker of in-hospital mortality, particularly in sepsis. Reduced ICU admission levels and persistently suppressed trajectories identified higher-risk patients. BChE may complement organ dysfunction scores; the 1615 U/L threshold is exploratory and requires prospective external validation.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 9","pages":"e1476"},"PeriodicalIF":2.9,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Approximating Molecular Sepsis Subtypes Using Bedside Data in Resource-Limited Settings: A Multicenter Analysis From Uganda.","authors":"Barnabas Bakamutumaho, Julius J Lutwama, Nicholas Owor, Xuan Lu, Peter James Eliku, Joyce Namulondo, John Kayiwa, Jesse E Ross, Christopher Nsereko, John Bosco Nsubuga, Joseph Shinyale, Ignatius Asasira, Tonny Kiyingi, Steven J Reynolds, Kai Nie, Seunghee Kim-Schulze, Matthew J Cummings","doi":"10.1097/CCE.0000000000001463","DOIUrl":"10.1097/CCE.0000000000001463","url":null,"abstract":"<p><strong>Importance: </strong>Biologically defined sepsis subtypes have been identified in low- and middle-income countries (LMICs), but limited access to molecular diagnostics constrains broader evaluation and implementation in resource-limited settings.</p><p><strong>Objectives: </strong>To determine whether bedside-accessible variables could approximate molecular sepsis subtype assignments among Ugandan adults with sepsis.</p><p><strong>Design, setting, and participants: </strong>Secondary analysis of two prospective observational sepsis cohorts conducted at Tororo General Hospital (Research in the Epidemiology of Severe and Emerging Infections in Uganda-2-Tororo [RESERVE-U-2-TOR]) and Entebbe Regional Referral Hospital (Research in the Epidemiology of Severe and Emerging Infections in Uganda-1-Entebbe [RESERVE-U-1-EBB]), Uganda. Participants were adults 18 years old or older hospitalized with sepsis who underwent transcriptomic (n = 355) and/or proteomic (n = 495) profiling.</p><p><strong>Main outcomes and measures: </strong>Prespecified clinical and clinico-microbiologic models were evaluated for discrimination and calibration against Uganda-derived transcriptomic and proteomic sepsis subtypes and, secondarily, high-income country (HIC)-derived sepsis subtypes and immune dysregulation frameworks.</p><p><strong>Results: </strong>In RESERVE-U-2-TOR, clinical models incorporating demographic and physiologic variables showed moderate discrimination for transcriptomic and proteomic subtypes (area under the receiver operating characteristic curve [AUROC], 0.75 [95% CI, 0.69-0.81] and 0.73 [95% CI, 0.66-0.80], respectively), with generally acceptable calibration. Adding rapid HIV, malaria, and tuberculosis test results did not meaningfully improve performance. In RESERVE-U-1-EBB, discrimination was more variable (AUROC range, 0.63-0.75), with generally acceptable calibration. Performance was similarly modest for HIC-derived sepsis subtypes and immune dysregulation axes.</p><p><strong>Conclusions and relevance: </strong>Bedside-accessible clinical variables, with or without rapid microbiologic testing, only partially approximated molecular sepsis frameworks in Uganda. Scalable molecular biomarker platforms are needed to advance precision medicine for sepsis in LMICs.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 8","pages":"e1463"},"PeriodicalIF":2.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Regulation of Protein Biomarkers in Pediatric Acute Respiratory Distress Syndrome.","authors":"Guy Helman, Rui Feng, Joshua E Motelow, Nadir Yehya","doi":"10.1097/CCE.0000000000001468","DOIUrl":"https://doi.org/10.1097/CCE.0000000000001468","url":null,"abstract":"<p><strong>Objectives: </strong>Acute respiratory distress syndrome (ARDS) is a significant contributor to ICU admissions, morbidity, and mortality. Biomarkers have increasingly been used to dissect heterogeneity and mechanisms underlying pediatric ARDS. We sought to assess the genetic contribution to the levels of protein biomarkers currently used to subphenotype pediatric ARDS patients.</p><p><strong>Design, setting, and participants: </strong>Retrospective, single-center cohort study at a tertiary care PICU of children (< 18 yr) with pediatric ARDS diagnosis.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>Genome-wide protein quantitative trait loci (pQTL) analysis was performed on biomarkers measured on day 0 of ARDS, which were previously associated with outcomes from a single-center cohort using linear regression models. We then assessed the genetic association with longitudinal biomarker levels (on days 0, 3, and 7) and with 28-day survival using linear mixed-effects models and Cox proportional hazard models, respectively. From 333 children with ARDS, 267 underwent pQTL analysis against 6 preselected protein biomarkers. Among the patients, 49.4% had ARDS attributed to infectious pneumonia, and 21.7% had ARDS resulting from nonpulmonary sepsis. The hypoinflammatory phenotype was identified in 74.2% of patients, and overall mortality was 14.6%. One single nucleotide polymorphism (SNP) was identified in SFTPD with presumed cis-regulatory effect. Linear mixed-effect modeling confirmed the effect of the SNP on biomarker levels in heterozygous or homozygous carriers on day 0 of ARDS course. Survival analysis demonstrated no significant impact on mortality risk.</p><p><strong>Conclusions: </strong>We identified a gene-associated SNP in SFTPD that impacts relevant biomarker levels in pediatric ARDS. Further characterization is needed to better understand subphenotypes in pediatric ARDS, including genetic determinants of the biomarker levels used to define them.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 8","pages":"e1468"},"PeriodicalIF":2.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485844/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Impact of Child Opportunity on PICU Utilization and the Role of Public Insurance.","authors":"Carlie N Myers, Qing Duan, Paula M Magee, Zachary Pitkowsky, Carley L Riley, Andrew F Beck","doi":"10.1097/CCE.0000000000001464","DOIUrl":"10.1097/CCE.0000000000001464","url":null,"abstract":"<p><strong>Objectives: </strong>Public insurance reduces financial barriers to healthcare but may not fully mitigate the influence of neighborhood opportunity on pediatric critical care utilization. We examined the association between neighborhood opportunity and PICU utilization, including costs, and assessed whether public insurance modified these relationships.</p><p><strong>Design: </strong>Population-level retrospective observational study.</p><p><strong>Setting: </strong>A single, free-standing quaternary children's hospital in southwestern Ohio.</p><p><strong>Patients: </strong>Children 18 years or younger admitted to the PICU between January 1, 2016, and December 31, 2022, residing within the hospital's primary service area.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>Primary outcomes were census tract (CT) level PICU admission rates and median PICU costs. Very low opportunity neighborhoods had the highest PICU admission rates (3.41 vs. 1.76 admissions per 1000 children in very high opportunity neighborhoods; p < 0.001). Overall CT level median PICU costs did not differ by Child Opportunity Index (COI; p = 0.582). Publicly insured children were more likely to reside in very low opportunity neighborhoods (44% vs. 10%; p < 0.001). Within very low opportunity neighborhoods, publicly insured children had lower median PICU costs than children with other insurance ($16,693 vs. $22,585; p = 0.008); costs were similar across insurance groups in other COI quintiles. In multivariable analyses, the interaction between insurance status and neighborhood opportunity was not statistically significant (p = 0.099).</p><p><strong>Conclusions: </strong>Children from low opportunity neighborhoods experienced higher PICU admission rates, while neighborhood opportunity and public insurance jointly influenced patterns of PICU resource utilization. Expanding insurance coverage alone is unlikely to eliminate disparities; improving neighborhood conditions and implementing place-based strategies may help mitigate PICU utilization.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 8","pages":"e1464"},"PeriodicalIF":2.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803148","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Subphenotypes and Short-Term Outcomes in PICU Patients Receiving Continuous Blood Purification.","authors":"Kaizong Huang, Jiahua Ke, Zhiyuan Wang, Xuhua Ge, Zhe Zhao, Feiyan Chen, Lei Zhang, Jingwen Ni, Jing Zhao, Senquan Liang, Shengxin Zhang, Qiang Qu, Hui Sun, Puyi Wang, Nan Gong, Hongxia Shen, Jiangwei Zhu, Hongwei Fan, Shujun Li","doi":"10.1097/CCE.0000000000001460","DOIUrl":"10.1097/CCE.0000000000001460","url":null,"abstract":"<p><strong>Objectives: </strong>To characterize clinical heterogeneity among PICU patients receiving continuous blood purification (CBP) and identify data-driven subphenotypes associated with distinct short-term outcomes.</p><p><strong>Design: </strong>Multicenter, retrospective cohort study.</p><p><strong>Setting: </strong>Fifteen PICUs (from January 2019 to August 2024).</p><p><strong>Patients: </strong>Children (1 mo to 18 yr) receiving CBP during PICU hospitalization.</p><p><strong>Interventions: </strong>None.</p><p><strong>Measurements and main results: </strong>In this multicenter cohort of 598 CBP-treated children, unsupervised clustering at CBP initiation identified three reproducible subphenotypes using a seven-variable signature comprising aspartate aminotransferase, hemoglobin, oxygenation index, Pediatric Logistic Organ Dysfunction-2 score, procalcitonin, weight, and pH. These subphenotypes showed distinct multidomain physiologic profiles rather than a simple severity gradient. Subphenotype I had the most favorable short-term survival profile, subphenotype II had the poorest survival, and subphenotype III showed an intermediate pattern, with significant separation in 28-day survival across groups. Subphenotypes also differed in ICU length of stay, and exploratory analyses suggested subphenotype-dependent associations between high-volume hemofiltration exposure and ICU discharge. Cross-validated supervised models showed high discriminability of subphenotype assignment.</p><p><strong>Conclusions: </strong>CBP-treated children exhibited distinct subphenotypes at CBP initiation with divergent short-term prognoses, highlighting marked heterogeneity at this treatment stage. Subphenotype-based stratification may support risk characterization and trial enrichment and facilitate hypothesis generation regarding heterogeneity of treatment associations. Prospective validation is warranted.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 8","pages":"e1460"},"PeriodicalIF":2.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association Between Community-Level Social Determinants of Health and Sepsis Incidence and Mortality: A Scoping Review.","authors":"Sahil Angelo, Fatima Sheikh, Maniraj Neupane, Sushil Pant, Elena Puccio, Christopher Schumacher, Alyson Lee, Swetha Jasti, Christina F Mair, Diane Cooper, Kristina E Rudd","doi":"10.1097/CCE.0000000000001462","DOIUrl":"https://doi.org/10.1097/CCE.0000000000001462","url":null,"abstract":"<p><strong>Objectives: </strong>To summarize the research methods, patient populations, and measures used to examine the associations between community-level social determinants of health (SDoH) and sepsis risk, and to describe the findings of the current evidence.</p><p><strong>Data sources: </strong>PubMed, Embase, Web of Science, Global Health, Cochrane Library, Scopus, Web of Science-Core Collection, and Latin American and Caribbean Literature on Health Sciences Database from January 1, 1991, to October 31, 2024.</p><p><strong>Study selection: </strong>Studies were included if they evaluated the quantitative association between at least one community-level SDoH, measured at a spatial level smaller than a country and larger than a household, and sepsis incidence and/or mortality.</p><p><strong>Data extraction: </strong>Titles, abstracts, and full-text articles were independently screened in duplicate. Data extraction was performed in duplicate using a standardized form capturing study design, sepsis definition, patient population, community-level SDoH domains, and outcomes.</p><p><strong>Data synthesis: </strong>Of the 10,504 studies retrieved, 63 studies were included in the final analysis. The majority of studies (n = 39, 62%) were published between 2020 and 2024. Children (n = 10, 16%) and people in low- or middle-income countries (n = 9, 14%) were the least represented study populations. The most common domains of evaluated SDoH were demographic (n = 31, 49%), health access (n = 17, 27%), and economic (n = 16, 25%), with the most frequent variables being rurality (n = 24, 40%) and median household income by ZIP code (n = 10, 16%). There were 10 (16%) prospective cohort studies, 43 (68%) retrospective cohort, 6 (10%) case-control, and 4 (6%) ecological. Most studies (n = 54, 86%) reported a significant association between at least one community-level SDoH and sepsis incidence and/or mortality.</p><p><strong>Conclusions: </strong>There is a growing but heterogeneous body of evidence on the associations between community-level SDoH and sepsis risk. Future research requires better representation from populations with the highest sepsis burden, more consistent definitions, and more rigorous, innovative methods to elucidate the mechanisms driving associations between multiple community-level SDoH and sepsis.</p>","PeriodicalId":93957,"journal":{"name":"Critical care explorations","volume":"8 8","pages":"e1462"},"PeriodicalIF":2.9,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13485937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}