SHOCKPub Date : 2026-09-01Epub Date: 2025-12-30DOI: 10.1097/SHK.0000000000002794
Alejandra L Lorenzen, Susan M Shea, Leslie E Neidert, Clifford G Morgan, Sylvain Cardin, Michael M Tiller
{"title":"Evaluation of Rhesus and Cynomolgus Macaque Whole Blood During Prolonged Cold Storage.","authors":"Alejandra L Lorenzen, Susan M Shea, Leslie E Neidert, Clifford G Morgan, Sylvain Cardin, Michael M Tiller","doi":"10.1097/SHK.0000000000002794","DOIUrl":"10.1097/SHK.0000000000002794","url":null,"abstract":"<p><strong>Background: </strong>Care for massively bleeding patients has seen a return of focus to the use of cold-stored whole blood (WB) as the primary resuscitation treatment. Nonhuman primates (NHP) are the ideal trauma animal model for preclinical hemostatic research as they are most physiologically akin to humans, yet study designs use autologous shed WB, which does not fully recapitulate what occurs in human medicine. We sought to evaluate the effects of prolonged 4°C storage of NHP WB.</p><p><strong>Methods: </strong>WB was collected from 10 anesthetized male rhesus macaques and five male cynomolgus macaques into 10% citrate phosphate dextrose adenine in 300 mL storage bags. WB units were tested at baseline before storage at 4°C and aseptically sampled daily for the first 4 days, then weekly at day 7 through day 28 of storage. Biochemical, hematologic, and hemostatic function parameters were assayed. Data were analyzed using a mixed-effects analysis with multiple comparisons if significant.</p><p><strong>Results: </strong>In both species, red cell, hemoglobin, and hematocrit counts remained stable through day 28, while lactate and potassium levels significantly increased as sodium and pH decreased significantly. Hemostatic function significantly declined for both species from day 7 onward.</p><p><strong>Conclusions: </strong>This study describes a viable method of manufacturing NHP stored WB and characterizes the storage lesion in both rhesus and cynomolgus macaques. Observationally, no overt differences were seen between species. Future resuscitation studies utilizing NHP models could improve translational relevance using stored allogenic WB.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"810-819"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2025-12-02DOI: 10.1097/SHK.0000000000002766
Courtney Collins, Bommana Raghunath Reddy, Sumit Verma, Ryan Harkless, Clark Ingram, Anahita Jalilvand, Manjula Karpurapu, Chandan K Sen, Kanhaiya Singh, Savita Khanna, John Christman, Jon R Wisler
{"title":"DNMT1 mRNA Transfer VIA Macrophage-Derived Extracellular Vesicles Following LPS Exposure Regulates TNFα Gene Methylation.","authors":"Courtney Collins, Bommana Raghunath Reddy, Sumit Verma, Ryan Harkless, Clark Ingram, Anahita Jalilvand, Manjula Karpurapu, Chandan K Sen, Kanhaiya Singh, Savita Khanna, John Christman, Jon R Wisler","doi":"10.1097/SHK.0000000000002766","DOIUrl":"10.1097/SHK.0000000000002766","url":null,"abstract":"<p><strong>Background: </strong>Lipopolysaccharide (LPS) exposure results in prolonged immune dysfunction in human macrophages. Emerging evidence supports the hypothesis that epigenetic methylation of key pro-inflammatory genes contributes to this phenotype. Our data have shown that in response to LPS exposure, extracellular vesicles (EVs) contain high amounts of DNA methyltransferase (DNMT) mRNA cargo that is transferred to recipient cells with resultant methylation events and gene silencing at tumor necrosis factor alpha (TNFα). It is unknown which DNMT isoform is responsible for these methylation events.</p><p><strong>Methods: </strong>EVs containing DNMT mRNA were generated by exposing human macrophages to LPS. Using siRNAs targeting the individual isoforms of DNMT (1, 3A, and 3B), we generated EVs with selectively packaged DNMT mRNAs for each isoform. Recipient macrophages were treated with these EVs, and methylation was assessed using bisulfate sequencing.</p><p><strong>Results: </strong>siRNAs targeting DNMTs 1, 3A, and 3B achieved successful knockdown. Macrophages exposed to LPS only demonstrated significant increases in DNMT1 mRNA. siRNAs directed at DNMT1 successfully knocked down mRNA expression. EVs generated from LPS exposure showed a 2-fold reduction in DNMT1 mRNA ( P < 0.001). In recipient cells exposed to these EVs, methylation of TNFα was reduced (58.3% vs. 31.3%). This reduction in methylation correlates with increased expression of TNFα mRNA after LPS exposure.</p><p><strong>Conclusions: </strong>These data demonstrate that DNMT1 is the dominant mRNA isoform responsible for the methylation events and gene silencing seen in human macrophages after LPS exposure. Several pharmacologic therapies exist that selectively target DNMT1 function, which potentially can be utilized to limit the methylation events that occur at TNFα following LPS exposure.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"676-681"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2026-02-02DOI: 10.1097/SHK.0000000000002786
Jennifer M Leonard, Sarbani Ghosh, Grant V Bochicchio, Philip C Spinella, Isaiah R Turnbull
{"title":"Acute Trauma and Critical Illness Cause Increases in G-CSF that Correlate with Post-Injury Outcomes and are Associated with Changes in Bone Marrow Progenitor Populations.","authors":"Jennifer M Leonard, Sarbani Ghosh, Grant V Bochicchio, Philip C Spinella, Isaiah R Turnbull","doi":"10.1097/SHK.0000000000002786","DOIUrl":"10.1097/SHK.0000000000002786","url":null,"abstract":"<p><strong>Background: </strong>Critical illness dramatically increases the demand for and consumption of leukocytes. This demand induces emergency hematopoiesis (EH) whereby the hematopoietic stem and progenitor cells in the bone marrow become activated and proliferate to increase leukocyte production. Recent studies in murine models of trauma demonstrate that trauma induces EH through interleukin (IL)-1-dependent production of granulocyte colony-stimulating factor (G-CSF). We hypothesized that nonseptic critical illness (NSCI) would similarly drive IL-1 and G-CSF-mediated EH in critically ill humans.</p><p><strong>Methods: </strong>Two independent prospective observational trials were conducted. Plasma cytokine levels were measured in a cohort of 55 critically injured trauma patients. G-CSF levels were measured on arrival and at 1, 6, 24, and 72 hours after arrival. Correlation between G-CSF levels and injury severity, length of stay, intensive care unit (ICU) length of stay, and inflammatory cytokine levels was measured. Bone marrow was isolated from an independent cohort six nonseptic critically ill organ-donation candidates and five healthy donors. Hematopoietic stem and progenitor cells were measured by flow cytometry.</p><p><strong>Results: </strong>Critical injury induced a rapid and significant increase in plasma G-CSF levels, detectable within 1 hour of hospital arrival, with peak levels measured 6 hours after injury. G-CSF levels 1 hour after arrival correlated with injury severity, length of stay, and ICU length of stay. Six-hour G-CSF levels correlated with ICU LOS. Six-hour G-CSF levels correlated strongly with 6-hour levels of IL-1β, IL-6, and IL-8. NSCI caused a significant increase in hematopoietic stem cells and common myeloid progenitors and a significant decrease in multipotent progenitors and common lymphoid progenitors as compared with healthy controls.</p><p><strong>Conclusions: </strong>Trauma induces a rapid increase in plasma G-CSF levels that is strongly correlated with plasma IL-1β, suggesting that, as in murine models, IL-1 may be driving G-CSF production. As in mice, NSCI induced EH, characterized by expansion of the hematopoietic stem cells cohort and a shift toward myelopoiesis. In critically ill humans, these data suggest that sterile injury induces IL-1 and G-CSF-mediated EH, recapitulating the murine finding.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"638-648"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147284924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2026-03-16DOI: 10.1097/SHK.0000000000002807
Sergio M Navarro, Riley J Thompson, Grant M Spears, Kent R Bailey, Theresa K Kelly, Christina Wheeler, Jing-Fei Dong, Dong Chen, Rosemary A Kozar, Myung S Park
{"title":"Circulating Nucleosomes are Elevated in Trauma Patients with Venous Thromboembolism: A Prospective Case-Cohort Study.","authors":"Sergio M Navarro, Riley J Thompson, Grant M Spears, Kent R Bailey, Theresa K Kelly, Christina Wheeler, Jing-Fei Dong, Dong Chen, Rosemary A Kozar, Myung S Park","doi":"10.1097/SHK.0000000000002807","DOIUrl":"10.1097/SHK.0000000000002807","url":null,"abstract":"<p><strong>Objective: </strong>The identification of reliable biomarkers in trauma patients (pts) remains a clinical challenge. Nucleosomes, which are DNA wrapped around histone protein cores, have been used as reliable markers for quantification in sepsis, acute respiratory distress syndrome, and lymphoma. We hypothesized that: 1) levels of circulating nucleosomes quantified after traumatic injury, specifically histone H3.1 and its citrullinated R8 posttranslation modification (H3R8 Cit), would be increased after trauma and 2) that levels of circulating nucleosomes would be further, increased in pts who went on to develop venous thromboembolism (VTE), as these nucleosomes may be clot-enhancing mediators.</p><p><strong>Methods: </strong>Trauma pts presenting to a Level I trauma center were evaluated for inclusion in a prospective case-cohort study, and citrated blood samples were collected within 12 hours of injury. Pts were followed for up to 90 days and VTE occurrence was confirmed via autopsy or imaging. Pts who developed incident, symptomatic VTE, and those who did not develop VTE were selected at a 1:3 ratio. The effect of trauma was assessed by comparison with healthy volunteer samples. Circulating nucleosomes were quantified using Nu.Q H3.1 and Nu.Q H3R8 Cit assays. Data are presented as median [interquartile range] or n (%), with Wilcoxon Rank-Sum or chi-squared test performed between trauma pts who developed symptomatic VTE versus those who did not, with a P value < 0.05 as statistically significant.</p><p><strong>Results: </strong>A total of 639 trauma pts were analyzed [51 years (33, 65), 71.0% male, 94.1% blunt, injury severity scores 17 (9, 27)]. Both H3.1 [359.7 (58.4, 1769.3) vs. 21.5 (15.3, 26.6) ng/mL, P < 0.001] and H3R8 Cit levels [209.4 (45.4, 665.5) vs. 22.3 (16.2, 28.9) ng/mL, P < 0.001] were greater in trauma pts than in 10 healthy volunteers. The 160 pts with VTE were then compared with 479 without VTE. VTE pts had a median time to VTE of 8.5 days, with 91 developing symptomatic deep venous thrombosis, 48 with pulmonary embolism, and 21 with both deep venous thrombosis and pulmonary embolism. No significant differences were found in age, sex, or mechanism between pts with or without VTE. However, VTE pts had higher injury severity scores [24 (14, 34), 14 (9, 24), P < 0.001] and body mass index [29.1 (24.3, 34.2), 27.6 (24.2, 32.0) kg/m 2 , P = 0.037]. A greater percentage of VTE pts underwent surgery requiring general anesthesia (53.1%, 34.0%, P < 0.001) and received blood transfusions within 24 hours of injury (51.9%, 24.0%, P < 0.001). H3.1 levels were significantly greater in trauma pts who developed VTE compared with those who did not [828.4 (112.0, 3186.5), vs. 276.7 (50.3, 1237.0) ng/mL, P < 0.001], as were H3R8 Cit levels [350.4 (77.4, 729.5), vs. 189.2 (40.8, 632.6) ng/mL, P = 0.005]. No differences in levels of H3.1 and H3R8 Cit were found between early (diagnosed day 0-7 after injury) and late (diagnosed > day 7)","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"666-675"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13507992/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2025-09-22DOI: 10.1097/SHK.0000000000002724
Ryuichiro Kakizaki, Kan Nakamoto, Tsend-Ayush Batsaikhan, Perenlei Enkhbaatar
{"title":"Nebulized Epinephrine Improves Oxygenation During Extracorporeal Membrane Oxygenation in Sheep with Smoke Inhalation-Induced Acute Respiratory Distress Syndrome.","authors":"Ryuichiro Kakizaki, Kan Nakamoto, Tsend-Ayush Batsaikhan, Perenlei Enkhbaatar","doi":"10.1097/SHK.0000000000002724","DOIUrl":"10.1097/SHK.0000000000002724","url":null,"abstract":"<p><strong>Introduction: </strong>Smoke inhalation injury induces airway edema, obstruction, and bronchospasm, leading to hypoxia and acute respiratory distress syndrome (ARDS). When ARDS is refractory to conventional therapy, veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a rescue strategy. We hypothesized that nebulized epinephrine improves oxygenation by alleviating airway dysfunction during VV ECMO support.</p><p><strong>Methods: </strong>Twelve female Merino sheep were surgically instrumented and subjected to smoke inhalation injury. VV ECMO was initiated when the PaO 2 /FiO 2 ratio dropped below 150 mmHg. The sheep were randomized to receive either saline nebulization (control group, n = 7) or epinephrine nebulization (treatment group, n = 5) every 4 hours. Extracorporeal membrane oxygenation (ECMO) blood flow was maintained at 60-80 mL/kg/min; the sheep remained conscious in cages after ECMO initiation. Cardiopulmonary variables, blood gases, and respiratory mechanics were monitored for 72 hours.</p><p><strong>Results: </strong>Survival was significantly higher in the treatment group ( P = 0.03). The PaO 2 /FiO 2 ratio improved significantly in the treatment group at 30 and 36 hours compared with the control group ( P < 0.05), with a positive correlation between oxygenation and time (correlation coefficient = 0.8, P < 0.01). The tracheal wet-to-dry weight ratio was lower in the treatment group ( P < 0.05), indicating reduced airway edema. No significant systemic cardiovascular effects were observed.</p><p><strong>Conclusions: </strong>This study demonstrates that nebulized epinephrine improved oxygenation, reduced airway edema, and enhanced survival in an ovine model of smoke inhalation-induced ARDS supported with VV ECMO. These findings suggest that epinephrine nebulization may provide a promising adjunctive therapy to improve outcomes and facilitate shorter ECMO duration in smoke inhalation-associated ARDS.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"792-799"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Factors Associated with Acute Kidney Injury and Clinical Outcomes in Patients with Renal and Perinephric Abscess: A National Inpatient Sample Analysis (2016-2022).","authors":"Xiaocong Wu, Yanfei Wang, Junfen Cheng, Jian Wang, Boqi Geng, Junde Mo, Guorong Zhong, Binbin Tian","doi":"10.1097/SHK.0000000000002753","DOIUrl":"10.1097/SHK.0000000000002753","url":null,"abstract":"<p><strong>Background: </strong>Patients diagnosed with renal and perinephric abscesses (RPA) frequently experience acute kidney injury (AKI), which is associated with poor clinical outcomes. However, large-scale, nationwide studies examining factors associated with AKI in this patient population are lacking.</p><p><strong>Objectives: </strong>The current research aimed to identify factors associated with AKI in patients with RPA.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted using data obtained from the National Inpatient Sample database spanning January 1, 2016, through December 31, 2022. The primary outcome assessed was the development of AKI. To identify factors associated with AKI, we performed multivariable logistic regression analysis.</p><p><strong>Results: </strong>In total, 4,896 patients (32.1%) developed AKI during hospitalization, with the occurrence rising from 29.9% in 2016 to 34.8% by 2022. Multivariable logistic regression revealed several factors associated with AKI, such as age ≥45 years, male sex, Black race, comorbidities (acquired immune deficiency syndrome, coagulopathy, fluid and electrolyte disorders, obesity and chronic kidney disease excluding end-stage renal disease), and complications (hyperkalemia, acute respiratory failure, arrhythmia, gastrointestinal hemorrhage, pneumonia, blood transfusion, urinary tract infection). Patients with AKI were associated with longer median hospital stays (9 vs. 5 days), higher median costs ($82,741 vs. $43,282), increased mortality (5.0% vs. 0.9%), and greater use of mechanical ventilation (3.4% vs. 0.9%), dialysis (4.8% vs. 0.8%), and percutaneous nephrostomy drainage (32.4% vs. 25.6%) (P < 0.001).</p><p><strong>Conclusions: </strong>AKI commonly occurs among patients with RPA and is significantly associated with worse outcomes, highlighting the critical need for early risk assessment and prompt interventions.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":"66 3","pages":"765-772"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148724410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2025-12-11DOI: 10.1097/SHK.0000000000002768
Fan Sun, Min Shi, Xiaodong Li, Xueyun Liu, Xiaowei Wang
{"title":"Risk Model Based on Neutrophil-Related Genes Constructs to Assess Prognosis and Immune Landscape in Sepsis.","authors":"Fan Sun, Min Shi, Xiaodong Li, Xueyun Liu, Xiaowei Wang","doi":"10.1097/SHK.0000000000002768","DOIUrl":"10.1097/SHK.0000000000002768","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a persistent systemic inflammatory disease involving multiple organ failure caused by a dysregulated immune response to infection. As primary effector cells in innate immunity, neutrophils significantly contribute to combating infections and mediating inflammatory responses. The aim of this study was to evaluate the prognostic significance of neutrophil-related genes (NRGs) in sepsis and their relationship with the immune microenvironment.</p><p><strong>Methods: </strong>This study drew on transcriptomic data and clinical characterization of sepsis patients from the gene expression omnibus (GEO) database. Sepsis prognostic genes were discovered through a combination of differential analysis, weighted gene co-expression network analysis, and univariate Cox regression analysis. Molecular subtypes of sepsis were identified by consensus clustering methods, survival differences between subtypes were compared, and gene enrichment analysis was performed. Further univariate Cox regression analysis and least absolute shrinkage and selection operator combined were performed to identify sepsis feature genes. Utilizing multivariate Cox regression analysis, a prognostic model was developed, and its predictive capability was subsequently examined through receiver operating characteristic curve and Kaplan-Meier survival analyses. Subsequently, immune cell infiltration and gene enrichment were assessed in the various risk groups.</p><p><strong>Results: </strong>This study identified the presence of two molecular subtypes in sepsis, with Cluster1 patients having significantly better survival than Cluster2. The prognostic model based on NRGs (RCBTB2, KRT23, KLF9, GIMAP4, and CD84) in this study significantly differentiated the survival prognosis of high-risk and low-risk patients. The low-risk patient group showed significant enrichment in immune-related pathways (T cell receptor signaling and primary immunodeficiency), while the high-risk group primarily exhibited significant enrichment in metabolism-related pathways (glycine serine and threonine metabolism).</p><p><strong>Conclusions: </strong>Risk models constructed on the basis of NRGs are effective in predicting survival outcomes and immune profiles of sepsis patients, providing a new perspective on the link between NRGs and sepsis.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"591-601"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2025-12-02DOI: 10.1097/SHK.0000000000002770
Neven Stevic, René Ferrera, Delphine Baetz, Laurent Argaud, Martin Cour
{"title":"Effects of Lactate Administration on Postcardiac Arrest Myocardial Dysfunction: An Ex Vivo Study.","authors":"Neven Stevic, René Ferrera, Delphine Baetz, Laurent Argaud, Martin Cour","doi":"10.1097/SHK.0000000000002770","DOIUrl":"10.1097/SHK.0000000000002770","url":null,"abstract":"<p><strong>Background: </strong>In vivo studies have reported cardiovascular benefits of lactate administration after cardiac arrest (CA). However, it remains unclear whether these improvements are due to direct or indirect myocardial effects of lactate. Therefore, we investigated the effects of lactate administration in an ex vivo CA model.</p><p><strong>Methods: </strong>Isolated rat hearts were subjected to 20 minutes of nonshockable CA followed by 40 minutes of reperfusion. Four groups were analyzed: Control (n = 9), reperfused with standard Krebs buffer; lactate (n = 9), reperfused with Krebs containing 20 mmol/L L-lactate; Lact 5min (n = 5), reperfused with Krebs for 5 minutes and then with Krebs containing 20 mmol/L L-lactate; Lact Hyper (n = 6), reperfused with hypertonic (Na + 163 mmol/L) Krebs containing 20 mmol/L L-lactate. Endpoints included rate-pressure product, left ventricular end-diastolic pressure, coronary flow, and arrhythmia incidence. Troponin and creatine kinase release, mitochondrial calcium retention capacity, and mitochondrial respiration were assessed.</p><p><strong>Results: </strong>Rate-pressure product recovery at the end of reperfusion was 47% ± 4% of baseline in Control versus 45% ± 4%, 40% ± 3%, and 42% ± 3% in Lactate, Lact 5min , and Lact Hyper ( P = ns). Left ventricular end-diastolic pressure and coronary flow were comparable across the groups. Ventricular arrhythmias occurred in 44%, 33%, 40%, and 50% of hearts, respectively ( P = ns). Troponin and creatine kinase levels were similar ( P = ns) between Controls and Lactate-treated hearts. Mitochondrial functions, which were significantly impaired by CA, did not differ significantly between the two groups.</p><p><strong>Conclusions: </strong>Lactate administration did not improve post-CA myocardial function and was not deleterious. These findings suggest that the in vivo benefits of lactate administration are unlikely due to direct myocardial effects.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"863-869"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
SHOCKPub Date : 2026-09-01Epub Date: 2026-02-03DOI: 10.1097/SHK.0000000000002812
Zhiyu Leng, Jie Li, Kexin Tang, Jianmin Shi
{"title":"Effect of Bystander CPR on Survival After Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.","authors":"Zhiyu Leng, Jie Li, Kexin Tang, Jianmin Shi","doi":"10.1097/SHK.0000000000002812","DOIUrl":"10.1097/SHK.0000000000002812","url":null,"abstract":"<p><strong>Background: </strong>Out-of-hospital cardiac arrest (OHCA) is a leading cause of death globally. The timely initiation of bystander cardiopulmonary resuscitation (CPR) is considered a critical determinant of survival.</p><p><strong>Objective: </strong>To evaluate the association of bystander CPR with survival after OHCA.</p><p><strong>Methods: </strong>We conducted a systematic review and meta-analysis, searching PubMed, EMBASE, Web of Science, and Scopus through July 31, 2025. We included observational studies that compared survival outcomes between OHCA patients who received bystander CPR and those who did not. The primary outcomes assessed were survival to hospital admission, survival to hospital discharge, and 30-day survival. A random-effects model was used to pool adjusted odds ratios (ORs). Potential sources of heterogeneity were examined using subgroup analyses and meta-regressions. Risk of bias was evaluated using Risk Of Bias In Nonrandomized Studies of Interventions.</p><p><strong>Results: </strong>Our analysis included 72 studies, comprising 2,914,595 OHCA events. The pooled analysis showed a 26% increase in odds of survival to hospital admission [12 studies; OR, 1.26; 95% confidence interval (CI), 1.09-1.46; I 2 = 77.9%]. The benefit was more pronounced for survival to hospital discharge, with a 44% increase in odds (43 studies; OR, 1.44; 95% CI, 1.33-1.56; I 2 = 83.8%), and was greatest for 30-day survival, with a 50% increase in odds (23 studies; OR, 1.50; 95% CI, 1.34-1.67; I 2 = 95.6%). The survival benefit varied significantly by continent. Meta-regression analyses showed the benefit was attenuated in studies with higher mean patient age and a higher proportion of female patients. The certainty of evidence was moderate.</p><p><strong>Conclusions: </strong>Bystander-initiated CPR is consistently associated with a significant improvement in survival after OHCA. These findings provide a strong evidence base to justify strategic investment in public first aid and CPR training policies to improve OHCA outcomes.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"579-590"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Pancreatic Stone Protein as an Early Prognostic Biomarker of Outcome in Clostridioides Difficile Infection.","authors":"Renatos-Nikolaos Tziolos, Christos Psarrakis, Panagiotis Koufargyris, George Chrysos, Styliani Sympardi, Konstantina Iliopoulou, Evangelos J Giamarellos-Bourboulis","doi":"10.1097/SHK.0000000000002759","DOIUrl":"10.1097/SHK.0000000000002759","url":null,"abstract":"<p><strong>Background: </strong>Clostridioides difficile infection (CDI) remains a major healthcare-associated infection, leading to severe complications. Early identification of patients at high risk for unfavorable outcomes remains challenging. Pancreatic stone protein (PSP) has emerged as a promising biomarker in sepsis; however, its role in CDI has not been investigated.</p><p><strong>Materials and methods: </strong>We conducted a prospective multicenter study of adult patients with CDI from 13 study sites in Greece. PSP was measured within 24 hours of CDI onset. The primary outcome was the association between PSP and unfavorable outcome, defined as at least one of the following: organ failure, severe disease progression, relapse, or death. Receiver operating characteristic curve was performed to assess diagnostic performance, and multivariate logistic regression to evaluate independent predictors of adverse outcome.</p><p><strong>Results: </strong>One hundred forty-seven patients were enrolled, and unfavorable outcomes occurred in 52. PSP levels were significantly higher in these patients. PSP showed an area under the curve of 0.648 [95% confidence interval (CI) 0.550-0.746, P = 0.003] for predicting adverse outcome and an optimal cutoff of 300 ng/mL, which increased the risk significantly (odds ratio 3.73, 95% CI 1.822-7.638, P < 0.001). C-reactive protein (CRP) was also associated with adverse outcome (area under the curve 0.619, 95% CI 0.512-0.726, P : 0.03), with an optimal cutoff ≥90 mg/L. Combined elevation of PSP and CRP conferred stronger prognostic value (odds ratio 7.04, 95% CI 2.78-17.85, P < 0.001). In multivariate analysis, PSP ≥300 ng/mL ( P : 0.006) and CRP ≥90 mg/L ( P : 0.04) remained independently associated with unfavorable outcome.</p><p><strong>Conclusions: </strong>This is the first study evaluating PSP in CDI. PSP, especially combined with CRP, may serve as complementary biomarkers for early risk stratification.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"787-791"},"PeriodicalIF":2.7,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145805487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}