SHOCK最新文献

{"title":"Delayed Immunomodulation Improves Immune Dysfunction in a Murine Model of Pics.","authors":"Satarupa Sengupta, Nagham Alatrash, Dennis Vaysburg, Vanessa Nomellini","doi":"10.1097/SHK.0000000000002803","DOIUrl":"10.1097/SHK.0000000000002803","url":null,"abstract":"<p><p>Persistent Inflammation, Immunosuppression, and Catabolism Syndrome can occur after sepsis when there is an overwhelming systemic inflammatory response that leads to multiple organ dysfunction, significant morbidity, and chronic critical illness. Despite the increasing recognition of this clinical problem, there are no interventions that can reverse this response. This study aims to characterize the immune responses in a murine Persistent Inflammation, Immunosuppression, and Catabolism Syndrome model using cecal ligation and puncture (CLP) and assess the efficacy of various immunomodulatory agents, including granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, and anti-programmed death-ligand 1 (PD-L1) antibody, in reversing the immune dysfunction when given after day 4, once the typical acute response to sepsis starts to subside. Our results showed that anti-PD-L1 therapy showed greater efficacy than granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in reversing immunosuppression post-CLP, as evidenced by improved immune cell numbers, immune function, MHC-II, and CD11b expression on innate immune cells, and interferon gamma production from T cells. However, while improving certain immune parameters, anti-PD-L1 treatment did not allow for effective bacterial clearance when the mice were inoculated with Pseudomonas aeruginosa 8 days after CLP. Interestingly, despite this decreased bacterial clearance, anti-PD-L1 therapy did not affect survival for CLP mice (100% survival) compared with untreated CLP mice (60% survival). These findings suggest that anti-PD-L1 therapy may improve some of the immune dysfunction seen after CLP and allow for improved survival following secondary bacterial infections.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"1038-1044"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158241","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":"Mortality in the Sepsis-3 Era: A Systematic Review of Multicenter Randomized Controlled Trials.","authors":"Marko Nemet, Ibrahim Serhat Karakus, Cameron Gray Gmehlin, Gabriele Alves Halpern, Kimia Ghafouri, Sergej Abramovich, Roshini Raghu, Mila Pastrak, Nasrin Nikravangolsefid, Dana J Gerberi, Svetlana Herasevich, Yewande Odeyemi, Amos Lal, Ognjen Gajic","doi":"10.1097/SHK.0000000000002687","DOIUrl":"10.1097/SHK.0000000000002687","url":null,"abstract":"<p><p>This systematic review examined multicenter randomized controlled trials conducted during the Sepsis-3 era that evaluated pharmaceutical and mechanistic interventions in adult patients with sepsis or septic shock, with a focus on identifying interventions that demonstrated mortality benefit. A comprehensive search was performed across Ovid MEDLINE, Embase, Cochrane Central, ClinicalTrials.gov, World Health Organization's ICTRP, and Web of Science for trials published since 2016. Studies were included if they enrolled adult patients with sepsis or septic shock using Sepsis-3 criteria and reported mortality as either a primary or secondary outcome. Data were extracted by two independent reviewers and included trial design characteristics, funding source, randomization methods, and reported outcomes. Among the 31 eligible multicenter randomized controlled trials enrolling over 7,000 patients across 550 centers, only four trials showed a mortality benefit. These included three studies from China-two evaluating herbal anti-inflammatory compounds and one evaluating aminophylline-and one European study assessing corticosteroid therapy in vasopressor-dependent septic shock. The remaining 27 trials reported no mortality benefit, and substantial heterogeneity was observed in patient populations, sepsis definitions, and outcome reporting. Median mortality in control arms was 31.6% (interquartile range 24.1-45.5), and 35.4% (interquartile range 25.7-49.6) in intervention arms. These findings suggest that despite extensive efforts, most interventions have not reduced mortality in multicenter sepsis trials. Future research should focus on optimizing trial design, refining patient selection, and incorporating patient-centered outcomes beyond mortality.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"874-881"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150688","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":"Bioengineered M13 Bacteriophage-Gelma Construct Modulates Immune Responses in a Preclinical Model of Sepsis.","authors":"Arezou Rahimi, Sara Soudi, Saeid Vakilian, Fatemeh Jamshidi-Adegani, Majid Sadeghizadeh, Ali Hazrati, Khamis Al-Riyami, Zohreh Safari, Reza Alimohammadi, Sulaiman Al-Hashmi","doi":"10.1097/SHK.0000000000002787","DOIUrl":"10.1097/SHK.0000000000002787","url":null,"abstract":"<p><p>A life-threatening condition, sepsis is defined by dysregulated immune system responses and multi-organ dysfunction. There is still no drug or treatment that can completely guarantee to cure this condition; available treatments mainly focus on controlling the infection with antibiotics, supporting organ function, and managing symptoms. Although artificial lymphoid tissues (aLTs) have potential for localized immunomodulation, their application is often limited by inadequate biological function and poor structural integrity. To address these issues, we developed a novel bioink that combines gelatin methacryloyl (GelMA) with M13 bacteriophage, a filamentous, nonlytic virus recognized for its immunomodulatory activity, self-assembling capacity, and biocompatibility. Male C57BL/6 mice (8-10 weeks, 22-25 g) were randomly assigned to six groups: sham + normal saline (NS), cecal ligation and puncture (CLP) + NS, CLP + M13, 3D - M13, 3D + M13, and 3D + M13 + CLP. The CLP procedure was applied to induce polymicrobial sepsis. Cell-laden, three-dimensional (3D) bio-printed GelMA scaffolds with or without M13 bacteriophage were surgically implanted on the spleen 35 days before sepsis induction. Subsequently, immune, histological, and biochemical parameters were assessed. Compared with GelMA-only scaffolds, M13-containing scaffolds demonstrated improved printability, mechanical stability, cellularity, and angiogenesis. Mice implanted with 3D + M13 scaffolds exhibited significantly reduced levels of proinflammatory cytokines, tumor necrosis factor alpha, and interleukin-6, as well as higher levels of anti-inflammatory cytokines interleukin-10 and transforming growth factor beta. Additionally, the bacterial load was reduced, and organ injury in the liver, lungs, and kidneys was reduced. Circulating liver enzyme levels were also reduced, suggesting precautionary measures against sepsis-induced hepatic dysfunction. The integration of M13 bacteriophage into GelMA bioink is a distinctive approach that simultaneously enhances the stability of artificial lymphoid tissue and stimulates anti-inflammatory immune modulation. This dual structural-immunological effect defines a new paradigm for the development of multifunctional biomaterials in the fields of immune regulation and tissue engineering.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"1021-1037"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030747","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":"Optimization of Platelet-Derived Extracellular Vesicle Preparation for Hemostatic Efficacy During Major Traumatic Hemorrhage.","authors":"Ava K Mokhtari, Sowmya Shree Gopal, Mandeep Kaur, Baron K Osborn, Marissa Pokharel, Charles E Wade, Amit K Srivastava, Jessica C Cardenas","doi":"10.1097/SHK.0000000000002823","DOIUrl":"10.1097/SHK.0000000000002823","url":null,"abstract":"<p><strong>Background: </strong>Platelet-derived extracellular vesicles (PEVs) are a potential alternative to apheresis platelets (PLTs) for hemorrhage control; however, the PLT fraction that yields the most pro-hemostatic PEVs remains unknown. The objective of this study was to determine whether PEVs derived from platelet additive solution (PAS) supernatant or from washed PLTs exhibit greater hemostatic efficacy.</p><p><strong>Methods: </strong>Apheresis PLTs from six healthy donors were processed to generate PAS supernatant and washed PLTs. PEVs were isolated using tangential flow filtration and characterized. Procoagulant activity was assessed using calibrated automated thrombogram (CAT) and plasma clotting assays. In vivo efficacy was evaluated using a rat liver laceration model of uncontrolled hemorrhage.</p><p><strong>Results: </strong>PAS-derived PEVs supported faster clot initiation ( P = 0.0187) and clot formation ( P = 0.0019) compared with washed PLT-derived PEVs. Thrombin generation was significantly increased in PAS-derived PEVs, with higher peak thrombin and faster thrombin generation rates ( P = 0.0431 and P = 0.0463). In vivo , PAS-derived PEVs reduced cumulative blood loss at 60 minutes after liver laceration ( P = 0.049). Posthemorrhage plasma from PAS-PEV-treated rats demonstrated enhanced thrombin generation kinetics and increased endogenous thrombin potential ( P ≤ 0.040). Procoagulant activity was positively correlated with surface phosphatidylserine expression.</p><p><strong>Conclusions: </strong>PAS-derived PEVs exhibit superior hemostatic activity compared with washed PLT-derived PEVs across ex vivo and in vivo models. These findings support PAS as a preferred source for PEV isolation and inform optimization of PEV production for development as a transfusion alternative for hemorrhage control.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"1045-1054"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147345112","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":"Impact of Intensivist-Performed Transesophageal Echocardiogram Program on Patient Management: A 5-Year Single-Center Experience.","authors":"Andrew A Alberter, Taylor Miller, William A Teeter, Daniel J Haase, Justin E Richards, Samuel M Galvagno, Thomas M Scalea, Elizabeth K Powell","doi":"10.1097/SHK.0000000000002789","DOIUrl":"10.1097/SHK.0000000000002789","url":null,"abstract":"<p><strong>Purpose: </strong>Transesophageal echocardiography (TEE) has been slow to be incorporated in intensivist practice despite several studies showing how this diagnostic modality can change clinical management with improved reliability and clinical certainty. This study aimed to explore the feasibility of an intensivist-performed TEE program and its potential impact on the management of critically ill patients.</p><p><strong>Materials and methods: </strong>This single-center, retrospective cohort study used data from a multidisciplinary intensivist-performed TEE database at a quaternary care academic hospital. Consecutive TEE studies performed between January 1, 2020, and March 31, 2025, were reviewed.</p><p><strong>Results: </strong>A total of 120 examinations were reviewed. Intensivist-performed TEE altered clinical management in 83% of cases (99 of 120 patients). The most frequent abnormalities identified were right ventricular dysfunction (23%), reduced left ventricular ejection fraction (21%), and valvular pathologies (19%). The most common changes in management included fluid administration (23%), inotrope initiation (17%), and extracorporeal membrane oxygenation cannula repositioning or confirmation (13%). There was one minor complication of TEE (0.8%) without any incidence of bleeding or esophageal perforation.</p><p><strong>Conclusions: </strong>Our results support that an intensivist-performed TEE program is feasible, safe, and clinically useful in changing management in a diverse population of critically ill medical and surgical patients in a variety of clinical environments.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"912-917"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202601","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":"Regulation of Inflammatory Responses and Apoptosis: sgp130Fc as a Potential Therapeutic Agent for Sepsis-Associated Kidney Injury.","authors":"Xuefang Liu, Ya Liu, Yuhong Chen, Congcong Zhao, Pan Zhou, Zhenjie Hu","doi":"10.1097/SHK.0000000000002843","DOIUrl":"10.1097/SHK.0000000000002843","url":null,"abstract":"<p><strong>Objective: </strong>This study aims to evaluate the therapeutic potential and underlying mechanisms of sgp130Fc, a selective inhibitor of interleukin-6 (IL-6) trans-signaling, in mitigating sepsis-associated kidney injury (SAKI).</p><p><strong>Methods: </strong>A cohort of 60 patients was stratified into three groups: Sepsis group (n = 20), SAKI Stages I-II group (n = 20), and SAKI Stage III group (n = 20). A positive correlation was observed between acute kidney injury severity and IL-6 levels. In vivo , sepsis was induced in male C57BL/6J mice via cecal ligation and puncture. The therapeutic effects of sgp130Fc, a selective inhibitor of IL-6 trans-signaling, were investigated. Transcriptomic analysis (RNA-seq) of renal tissue from septic mice identified differentially expressed genes. Gene ontology (GO) enrichment analysis confirmed significant enrichment of inflammation-related pathways, further validated using hypergeometric testing with an inflammation-specific gene set. Expression of downstream signaling molecules [signal transducer and activator of transcription 3 (STAT3), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)], apoptosis-related proteins [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax)], and renal injury biomarkers [kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL)] was also assessed.</p><p><strong>Results: </strong>Administration of sgp130Fc attenuated SAKI through inhibition of IL-6/sIL-6R signaling and modulation of the STAT3/NF-κB pathway. This intervention resulted in reduced release of pro-inflammatory mediators and decreased apoptosis as evidenced by downregulation of Bax, upregulation of Bcl-2, and reductions in renal injury markers KIM-1 and NGAL.</p><p><strong>Conclusion: </strong>sgp130Fc confers renoprotective effects in a murine model of sepsis by selectively targeting the IL-6 trans-signaling pathway and modulating STAT3/NF-κB signaling to inhibit inflammation and apoptosis. These findings highlight the therapeutic potential of sgp130Fc in SAKI and support further clinical investigation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"960-972"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521800","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":"Diagnostic Value of miR-126-5p in Sepsis-Induced Acute Kidney Injury and its Molecular Mechanism via CASP3.","authors":"Xiaowei Yuan, Wanyi Tan, Yuan Zhang, Lin He","doi":"10.1097/SHK.0000000000002905","DOIUrl":"10.1097/SHK.0000000000002905","url":null,"abstract":"<p><strong>Background: </strong>As a common and devastating complication of sepsis, sepsis-induced acute kidney injury (SAKI) confers a significant risk of mortality.</p><p><strong>Purpose: </strong>This work focused on the utility of miR-126-5p as a biomarker for SAKI.</p><p><strong>Methods: </strong>A total of 95 patients with SAKI and 70 patients with sepsis alone were enrolled. Serum levels of miR-126-5p and Caspase-3 (CASP3) were measured using reverse transcription quantitative polymerase chain reaction. The regulatory interaction between miR-126-5p and CASP3 was validated using a dual-luciferase reporter assay. Cell proliferation, apoptosis, inflammatory cytokine levels, and oxidative stress markers were evaluated using the cell counting kit-8 assay, flow cytometry, enzyme-linked immunosorbent assay, and corresponding commercial kits, respectively.</p><p><strong>Results: </strong>Serum miR-126-5p levels were downregulated in SAKI patients and showed significant negative correlations with kidney injury markers, including serum creatinine, cystatin C, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Overexpression of miR-126-5p in lipopolysaccharide-stimulated HK-2 cells was shown in vitro to facilitate cell proliferation, restrain apoptosis, and suppress the production of interleukin-1β, interleukin-6, and tumor necrosis factor-α. Concurrently, it reduced oxidative stress markers, reactive oxygen species, and malondialdehyde, and enhanced superoxide dismutase activity. Mechanistically, CASP3 was identified as a direct downstream target of miR-126-5p, and its expression was negatively regulated by miR-126-5p. Furthermore, overexpression of CASP3 significantly reversed the protective effects of miR-126-5p in vitro .</p><p><strong>Conclusions: </strong>miR-126-5p showed diagnostic value for SAKI and exerted a protective effect in vitro through targeted regulation of CASP3 expression.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"950-959"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387679","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":"Integrative Analysis Identifies Lactylation-Associated Hub Genes in Septic Cardiomyopathy.","authors":"Rui Jin, Jinwei Dai, Xiaolei Zhang, Yiting Chen, Wei Xiong, Zhaoxin Qian","doi":"10.1097/SHK.0000000000002819","DOIUrl":"10.1097/SHK.0000000000002819","url":null,"abstract":"<p><strong>Objective: </strong>Septic cardiomyopathy (SCM) is a critical complication contributing to high mortality in septic patients, yet its precise molecular mechanisms remain incompletely elucidated.</p><p><strong>Methods: </strong>Publicly available human transcriptomic data for SCM were obtained from the Gene Expression Omnibus database (GSE79962). Our integrated analytical workflow consisted of several steps. First, Weighted Gene Co-expression Network Analysis pinpointed key co-expression modules. Subsequently, a consensus approach combining three machine learning algorithms, Boruta, Random Forest, and Support Vector Machine-Recursive Feature Elimination, was used to screen for hub genes. The diagnostic potential of these genes was then assessed using receiver operating characteristic curves. Further investigations included functional pathway enrichment via Gene Set Enrichment Analysis, immune infiltration profiling with CIBERSORT, and the construction of a protein-protein interaction network using the STRING database. To validate the bioinformatic findings, key results were experimentally confirmed in a lipopolysaccharide-induced septic mouse model.</p><p><strong>Results: </strong>Our analysis identified three hub genes [growth arrest and DNA damage-inducible protein 45 beta (GADD45B), signal transducer and activator of transcription 3 (STAT3), and solute carrier family 7 member 5 (SLC7A5)] that were significantly dysregulated in SCM. These genes demonstrated exceptional diagnostic power, with area under the curve values exceeding 0.95. Gene set enrichment analysis indicated a pronounced activation of innate immune and inflammatory pathways. Concurrently, we observed a sustained suppression of critical cardiac energy metabolic pathways. The hub genes were also closely linked to the cS-STING signaling pathway. Their expression levels showed significant correlations with the infiltration of specific immune cell subsets, including resting natural killer cells, M0 and M2 macrophages, and resting CD4+ memory T cells. Critically, the dysregulation of these hub genes was successfully corroborated in heart tissues from the lipopolysaccharide-induced mouse model.</p><p><strong>Conclusions: </strong>This study, through integrated bioinformatics and initial experimental validation, identifies growth arrest and DNA damage-inducible protein 45 beta, signal transducer and activator of transcription 3, and solute carrier family 7 member 5 as central hub genes in SCM and proposes their potential regulation by lactylation as a novel hypothesis for future mechanistic investigation.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"996-1010"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147521598","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":"Targeting Cellular Senescence Enhances Post-Burn Wound Healing in Aged Mice.","authors":"Sara Faour, Fadi Khalaf, Yufei Chen, Shayahati Bieerkehazhi, Lauar de Brito Monteiro, Ayesha Aijaz, Najath Abdulkareem, Anna Matveev, Boris Hinz, Marc G Jeschke","doi":"10.1097/SHK.0000000000002898","DOIUrl":"10.1097/SHK.0000000000002898","url":null,"abstract":"<p><p>-Despite advancements in burn care, older burn patients continue to experience disproportionately high mortality rates. Impaired wound healing is a major prognostic indicator of burn patient survival, yet the mechanisms underlying delayed repair in older adults remain poorly understood. Cellular senescence, a hallmark of aging, contributes to tissue dysfunction and impaired regeneration, making it a potential mediator of age-associated deficits in burn wound healing. Here, we investigated the role of cellular senescence in postburn wound repair using a validated adult and aged murine full-thickness scald burn model and evaluated whether senolytic treatment with Dasatinib and Quercetin improves healing outcomes in aged mice. Thermal injury increased senescence-associated features in burn wounds, including senescence-associated beta-galactosidase-positive skin cells, and was associated with reduced myofibroblast-associated marker expression, increased extracellular matrix-degrading components, and delayed wound healing in aged mice. In contrast, senolytic treatment in aged burn mice reduced cellular senescence, demonstrated by a 4.4-fold decrease in senescence-associated beta-galactosidase-positive skin cells to baseline levels, increased alpha smooth muscle actin and type I collagen expression, and improved macroscopic burn wound healing. Together, these findings suggest that cellular senescence is associated with impaired skin repair after burn injury and that senescence-targeting therapies may represent a potential strategy to improve wound healing outcomes in older burn patients.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"918-929"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148284366","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":"Vasoactive Agent Therapy in Septic Shock: From Monotherapy Battles to Tailored Hemodynamic Optimization.","authors":"Mingyang Zhu, Yuxiang Zhang, Wenming Liu","doi":"10.1097/SHK.0000000000002781","DOIUrl":"10.1097/SHK.0000000000002781","url":null,"abstract":"<p><p>Hemodynamic stabilization and preservation of organ perfusion are central elements in the management of septic shock. This is achieved by fluid resuscitation and by administration of vasoactive agents to secure a time window for definitive cause-directed therapy. Guided by the Surviving Sepsis Campaign, the optimization of vasoactive agent strategies, namely protective hemodynamic management, has become a central focus. Tracing key research over the past 25 years reveals a paradigm shift in vasopressor therapy, from empiricism to goal-directed strategy. This evolution has deepened our understanding of the benefit-risk profile of vasoactive agents and fostered a new conceptual framework regarding organ perfusion and protection. Under this framework, management strategies have advanced from the mere pursuit of hemodynamic parameters to care bundles that integrate the monitoring of organ perfusion, microcirculation, and oxygen metabolism. These advances have optimized agent selection, established safe dosing ranges, and ultimately promoted the widespread adoption of combined and multimodal therapy concepts. This review delineates this transformative journey, synthesizing evidence on the reappraisal of traditional agents and exploring \"de-catecholaminization\" strategies, thereby aiming to broaden the therapeutic landscape. The integration of artificial intelligence and genomic medicine is expected to further advance personalized management strategies for septic shock.</p>","PeriodicalId":21667,"journal":{"name":"SHOCK","volume":" ","pages":"882-891"},"PeriodicalIF":2.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13557484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145850769","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}