Sepsis Survivors Research Articles

Characteristics and Readmission Risks Following Sepsis Discharges to Home

Objective: To examine the characteristics and risk factors associated with 30-day readmissions, including the impact of home health care (HHC), among older sepsis survivors transitioning from hospital to home. Research Design: Retrospective cohort study of the Medical Information Mart for Intensive Care (MIMIC)-IV data (2008–2019), using generalized estimating equations (GEE) models adjusting for patient sociodemographic and clinical characteristics. Subjects: Sepsis admission episodes with in-hospital stays, aged over 65, and discharged home with or without HHC were included. Measures: The outcome was all-cause hospital readmission within 30 days following sepsis hospitalization. Covariates, including the primary predictor (HHC vs. Home discharges), were collected during hospital stays. Results: Among 9115 sepsis admissions involving 6822 patients discharged home (66.8% HHC, 33.2% Home), HHC patients, compared with those discharged without services, were older, had more comorbidities, longer hospital stays, more prior hospitalizations, more intensive care unit admissions, and higher rates of septic shock diagnoses. Despite higher illness severity in the HHC discharges, both groups had high 30-day readmission rates (30.2% HHC, 25.2% Home). GEE analyses revealed 14% higher odds of 30-day readmission for HHC discharges after adjusting for risk factors (aOR: 1.14; 95% CI: 1.02–1.27; P=0.02). Conclusions: HHC discharges experienced higher 30-day readmission rates than those without, indicating the need for specialized care in HHC settings for sepsis survivors due to their complex health care needs. Attention to sepsis survivors, regardless of HHC receipt, is crucial given the high readmission rates in both groups. Further research is needed to optimize postacute care/interventions for older sepsis survivors.

Three-year mortality of ICU survivors with sepsis, an infection or an inflammatory illness: an individually matched cohort study of ICU patients in the Netherlands from 2007 to 2019.

Sepsis is a frequent reason for ICU admission and a leading cause of death. Its incidence has been increasing over the past decades. While hospital mortality is decreasing, it is recognized that the sequelae of sepsis extend well beyond hospitalization and are associated with a high mortality rate that persists years after hospitalization. The aim of this study was to disentangle the relative contribution of sepsis (infection with multi-organ failure), of infection and of inflammation, as reasons for ICU admission to long-term survival. This was done as infection and inflammation are both cardinal features of sepsis. We assessed the 3-year mortality of ICU patients admitted with sepsis, with individually matched ICU patients with an infection but not sepsis, and with an inflammatory illness not caused by infection, discharged alive from hospital. A multicenter cohort study of adult ICU survivors admitted between January 1st 2007 and January 1st 2019, with sepsis, an infection or an inflammatory illness. Patients were classified within the first 24 h of ICU admission according to APACHE IV admission diagnoses. Dutch ICUs (n = 78) prospectively recorded demographic and clinical data of all admissions in the NICE registry. These data were linked to ahealth care insurance claims database to obtain 3-year mortality data. To better understand and distinct the sepsis cohort from the non-sepsis infection and inflammatory condition cohorts, we performed several sensitivity analyses with varying definitions of the infection and inflammatory illness cohort. Three-year mortality after discharge was 32.7% in the sepsis (N = 10,000), 33.6% in the infectious (N = 10,000), and 23.8% in the inflammatory illness cohort (N = 9997). Compared with sepsis patients, the adjusted HR for death within 3 years after hospital discharge was 1.00 (95% CI 0.95-1.05) for patients with an infection and 0.88 (95% CI 0.83-0.94) for patients with an inflammatory illness. Both sepsis and non-sepsis infection patients had a significantly increased hazard rate of death in the 3 years after hospital discharge compared with patients with an inflammatory illness. Among sepsis and infection patients, one third died in the next 3 years, approximately 10% more than patients with an inflammatory illness. The fact that we did not find a difference between patients with sepsis or an infection suggests that the necessity for an ICU admission with an infection increases the risk of long-term mortality. This result emphasizes the need for greater attention to the post-ICU management of sepsis, infection, and severe inflammatory illness survivors.

Post-sepsis chronic muscle weakness can be prevented by pharmacological protection of mitochondria.

Sepsis, mainly caused by bacterial infections, is the leading cause of in-patient hospitalizations. After discharge, most sepsis survivors suffer from long-term medical complications, particularly chronic skeletal muscle weakness. To investigate this medical condition in detail, we previously developed a murine severe sepsis-survival model that exhibits long-term post-sepsis skeletal muscle weakness. While mitochondrial abnormalities were present in the skeletal muscle of the sepsis surviving mice, the relationship between abnormal mitochondria and muscle weakness remained unclear. Herein, we aimed to investigate whether mitochondrial abnormalities have a causal role in chronic post-sepsis muscle weakness and could thereby serve as a therapeutic target. Experimental polymicrobial abdominal sepsis was induced in 16-18months old male and female mice using cecal slurry injection with subsequent antibiotic and fluid resuscitation. To evaluate the pathological roles of mitochondrial abnormalities in post-sepsis skeletal muscle weakness, we utilized a transgenic mouse strain overexpressing the mitochondria-specific antioxidant enzyme manganese superoxide dismutase (MnSOD). Following sepsis development in C57BL/6 mice, we evaluated the effect of the mitochondria-targeting synthetic tetrapeptide SS-31 in protecting mitochondria from sepsis-induced damage and preventing skeletal muscle weakness development. In vivo and in vitro techniques were leveraged to assess muscle function at multiple timepoints throughout sepsis development and resolution. Histological and biochemical analyses including bulk mRNA sequencing were used to detect molecular changes in the muscle during and after sepsis RESULTS: Our time course study revealed that post sepsis skeletal muscle weakness develops progressively after the resolution of acute sepsis and in parallel with the accumulation of mitochondrial abnormalities and changes in the mitochondria-related gene expression profile. Transgenic mice overexpressing MnSOD were protected from mitochondrial abnormalities and muscle weakness following sepsis. Further, pharmacological protection of mitochondria utilizing SS-31 during sepsis effectively prevented the later development of muscle weakness. Our study revealed that the accumulation of mitochondrial abnormalities is the major cause of post-sepsis skeletal muscle weakness. Pharmacological protection of mitochondria during acute sepsis is a potential clinical treatment strategy to prevent post-sepsis muscle weakness.

Mitigating neuroinflammation in cognitive areas: exploring the impact of HMG-CoA reductase inhibitor.

Existing literature suggests that infection-specific mechanisms may play a significant role in the onset and progression of dementia, as opposed to the broader phenomenon of systemic inflammation. In addition, 3-hydroxy-3-methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors have been proposed as a potential therapeutic approach for sepsis, given their anti-inflammatory and antioxidant properties. We investigated the neuroprotective effect of an HMG-CoA reductase inhibitor (simvastatin) by analyzing neurodegenerative markers, mitochondrial respiration, and neuronal tracing in the prefrontal cortex (PFC) and thalamic nucleus reuniens (RE) of sepsis survivor animals. Adult Wistar rats were subjected to sepsis by cecal ligation and puncture or left non-manipulated. The animals were treated with simvastatin or vehicle for 4 days before and 10 days after surgery. The treatment preserved the non-associative memory (P < 0.05), recovered expression of Smad-3 in the hippocampus (P < 0.05), and prevented increased expression of calpain-1 (hippocampus: P < 0.0001; PFC: P < 0.05) and GSKβ (hippocampus: P < 0.0001; PFC: P < 0.0001) in the brain structures of the sepsis survivor animals. These animals also showed mitochondrial dysfunction and decreased axon terminals in the RE. Simvastatin seems to restore energy metabolism by improving the electron transfer system (ETS) values in the hippocampus (P < 0.01) and the oxidative phosphorylation/ETS (P/E) ratio in the PFC (P < 0.05), in addition to preventing the reduction of axon terminals in survivor animals. These results suggest a potential neuroprotective effect and the importance of considering HMG-CoA reductase inhibitors as a possible adjuvant therapy in sepsis.

Single cell RNA-seq reveals cellular and transcriptional heterogeneity in the splenic CD11b+Ly6Chigh monocyte population expanded in sepsis-surviving mice

BackgroundSepsis survivors exhibit immune dysregulation that contributes to poor long-term outcomes. Phenotypic and functional alterations within the myeloid compartment are believed to be a contributing factor. Here we dissect the cellular and transcriptional heterogeneity of splenic CD11b+Ly6Chigh myeloid cells that are expanded in mice that survive the cecal ligation and puncture (CLP) murine model of polymicrobial sepsis to better understand the basis of immune dysregulation in sepsis survivors.MethodsSham or CLP surgeries were performed on C57BL/6J and BALB/c mice. Four weeks later splenic CD11b+Ly6Chigh cells from both groups were isolated for phenotypic (flow cytometry) and functional (phagocytosis and glycolysis) characterization and RNA was obtained for single-cell RNA-seq (scRNA-seq) and subsequent analysis.ResultsCD11b+Ly6Chigh cells from sham and CLP surviving mice exhibit phenotypic and functional differences that relate to immune function, some of which are observed in both C57BL/6J and BALB/c strains and others that are not. To dissect disease-specific and strain-specific distinctions within the myeloid compartment, scRNA-seq analysis was performed on CD11b+Ly6Chigh cells from C57BL/6J and BALB/c sham and CLP mice. Uniform Manifold Approximation and Projection from both strains identified 13 distinct clusters of sorted CD11b+Ly6Chigh cells demonstrating significant transcriptional heterogeneity and expressing gene signatures corresponding to classical-monocytes, non-classical monocytes, M1- or M2-like macrophages, dendritic-like cells, monocyte-derived dendritic-like cells, and proliferating monocytic myeloid-derived suppressor cells (M-MDSCs). Frequency plots showed that the percentages of proliferating M-MDSCs (clusters 8, 11 and 12) were increased in CLP mice compared to sham mice in both strains. Pathway and UCell score analysis in CLP mice revealed that cell cycle and glycolytic pathways were upregulated in proliferating M-MDSCs in both strains. Notably, granule protease genes were upregulated in M-MDSCs from CLP mice. ScRNA-seq analyses also showed that phagocytic pathways were upregulated in multiple clusters including the classical monocyte cluster, confirming the increased phagocytic capacity in CD11b+Ly6Chigh cells from CLP mice observed in ex vivo functional assays in C57BL/6J mice.ConclusionThe splenic CD11b+Ly6Chigh myeloid populations expanded in survivors of CLP sepsis correspond to proliferating cells that have an increased metabolic demand and gene signatures consistent with M-MDSCs, a population known to have immunosuppressive capacity.

Cost-effectiveness of Procalcitonin (PCT) guidance for antibiotics management of adult sepsis patients in the Egyptian context

BackgroundSepsis, which is described as a life-threatening organ malfunction brought on by an unbalanced host response to infection, continues to be a significant healthcare issue that affects millions of individuals each year. It is well-known that sepsis can affect anyone around the world, but the employed survey results showed that there are significant regional variations in sepsis incidence as well as mortality rates. Although there are no definite estimates for Egypt, the highest rates were in Low-Middle-Income Countries (LMICs).Procalcitonin (PCT) is a host response marker with high specificity for bacterial infections, unlike C-reactive protein (CRP) or white blood cell count (WBC), which represent the traditional methods of detecting inflammation and infection. Its dynamic profile and superior prognostic prediction make it invaluable for assessing response to antibiotic treatment and improving clinical care for sepsis patients.Our main purpose was to evaluate the cost-effectiveness of PCT guidance compared to no PCT guidance in the antibiotic management of adult sepsis patients according to the Egyptian context.MethodsWe developed a decision tree model to compare the PCT-guided antibiotic management duration endpoint versus the conventional laboratory culture-based antibiotic management in adult sepsis patients. We employed the“Delphi technique” to reach a satisfactory consensus regarding the resources attributed to each compared alternative. The primary measure of the study was the additional cost associated with each Quality-Adjusted Life Year (QALY) gained by sepsis survivors over a one-year time horizon.Base-case, deterministic and probabilistic sensitivity analyses were conducted using TreeAge, Software.ResultsBase-case analysis showed no dominance for either alternative and resulted in an Incremental Cost-Effectiveness Ratio (ICER) value of 297,783.57 Egyptian Pounds per Quality Adjusted Life Year (L.E/QALY) in favor of the PCT guidance alternative, Deterministic sensitivity analysis revealed that the highest impact magnitudes on ICER reside with seven input parameters, the top two parameters that had the most significant influence were the costs of ICU stay with and without PCT guidance. The CEAC showed a slightly higher probability in terms of acceptability in favor of the no PCT guidance choice along the WTP scale till reaching equal probabilities at the willingness-to-pay (WTP) value point of 390,000 (state currency) after which the - probability supports the PCT guidance choice. ConclusionsIn the Egyptian context, PCT guidance has no cost-effectiveness domination over no PCT guidance in Antibiotics management for adult sepsis patients. This may be attributed to the high cost of PCT investigation that shall be resolved by standardization of its cost when applying the approach of DRG cost packages.

The Geographic Puzzle of Sepsis Recovery: Patterns in U.S. Rural and Urban Sepsis Survivors.

The Geographic Puzzle of Sepsis Recovery: Patterns in U.S. Rural and Urban Sepsis Survivors.

Exploring the prognostic and diagnostic value of lactylation-related genes in sepsis

The discovery of Lactylation may pave the way for novel approaches to investigating sepsis. This study focused on the prognostic and diagnostic significance of lactylated genes in sepsis. RNA sequencing was performed on blood samples from 20 sepsis patients and 10 healthy individuals at Southwest Medical University in Luzhou, Sichuan, China. Genes associated with sepsis were identified through analysis of RNA sequencing data. Afterward, the genes that were expressed differently were compared with the lactylation genes, resulting in the identification of 55 lactylation genes linked to sepsis. The overlapping genes underwent analysis using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Protein-Protein Network Interactions were used to screen for the core genes. The datasets GSE65682, GSE69528, GSE54514, GSE63042, and GSE95233 were obtained from the GEO database to validate core genes. Survival analysis evaluated the predictive significance of central genes in sepsis, while Receiver Operating Characteristic (ROC) Curve analysis was employed to establish the diagnostic value of genes. Additionally, a meta-analysis was conducted to confirm the precision of RNA-seq data. We obtained five peripheral blood samples, including two from healthy individuals, one from a patient with systemic inflammatory response syndrome (SIRS), and two from patients with sepsis. These samples were used to identify the specific location of core genes using 10×single-cell sequencing. High-throughput sequencing and bioinformatics techniques identified two lactylation-related genes (S100A11 and CCNA2) associated with sepsis. Survival analysis indicated that septic patients with reduced levels of S100A11 had a decreased 28-day survival rate compared to those with elevated levels. Conversely, individuals exhibiting decreased CCNA2 levels demonstrated a greater likelihood of surviving for 28 days than those in the high expression category, indicating a favorable association with survival rates among sepsis patients (P < 0.05). Both genes showed high sensitivity and specificity based on the ROC curve, with AUC values of 0.961 for S100A11 and 0.890 for CCNA2. The meta-analysis revealed that S100A11 exhibited high levels of expression in the sepsis survivors, whereas it displayed low levels of expression in the non-survivors; on the other hand, CCNA2 demonstrated low expression in the sepsis survivors and high expression in the non-survivors (P < 0.05). Single-cell RNA sequencing ultimately showed that monocyte macrophages, T cells, and B cells exhibited high expression levels of the crucial genes associated with sepsis-induced lactylation. In conclusion, the lactylation genes S100A11 and CCNA2 are strongly linked to sepsis and could be valuable markers for diagnosing, predicting outcomes, and providing guidance for sepsis.

Long-term Risk of Stroke After New-Onset Atrial Fibrillation in Sepsis Survivors: A 2-Year Follow-Up Study.

Background: Cardiovascular complications such as new-onset atrial fibrillation (NOAF) are common in sepsis and are known to increase the risk of in-hospital mortality and stroke. However, only a handful of studies have evaluated the long-term risk of stroke after NOAF in sepsis survivors. As part of our efforts to address this issue, we conducted the first-ever follow-up study in a developing country evaluating the long-term risk of stroke for sepsis survivors following NOAF. Methods: This retrospective study evaluated all adult patients admitted at the Aga Khan University Hospital between July 2019 and December 2019 with the diagnosis of sepsis. Data was collected from medical records of the included patients. Outcome measures included in-hospital mortality and ischemic stroke within 2 years. Results: Seven hundred thirty patients were included in the study; 415 (57%) were males and 315 (43%) females; mean age was 59.4 ± 18 years. 59 (8%) patients developed NOAF. The risk of stroke within 2 years in sepsis survivors was 3.5%. Six out of 30 (20%) patients in the atrial fibrillation (AF) group developed stroke, whereas 11 out of 448 (2%) patients in the non-AF group developed stroke. NOAF was associated with an increased risk of ischemic stroke within 2 years (OR = 6.6; 95% CI, 2.3-12.8; P = <.001). Conclusion: We conclude that AF occurred frequently in sepsis patients and was also associated with a 6-fold increase in the risk of ischemic stroke within 2 years. Reliable interventions for identifying high-risk patients for ischemic stroke are still poorly characterized, and this study may serve as a basis for more extensive multicenter studies to identify patients at high risk for ischemic stroke in the aftermath of septic AF and develop precise interventions for preventing it.

Elevated total bile acid levels as an independent predictor of mortality in pediatric sepsis.

The close relationship between bile acid (BA) metabolism and sepsis has been investigated in recent years, as knowledge of the role of the gut microbiome and metabolomics in sepsis has grown and become more comprehensive. Patients with sepsis who were admitted to the PICU of the Children's Hospital, Zhejiang University School of Medicine from January 2016 to December 2021 were enrolled in this study. Preoperative non-infectious pediatric patients undergoing elective surgeries in our hospital's department of surgery were recruited as controls during the same period. Clinical data were collected and analyzed. 702 children were enrolled, comprising 538 sepsis survivors, 164 sepsis fatalities, and 269 non-infected controls. Statistical analysis revealed that total BA (TBA) increased in both the early and severe stages of pediatric sepsis. In the severe stage, TBA (OR = 2.898, 95% CI 1.946-4.315, p < 0.05) was identified as a risk factor for sepsis. A clinical model identified TBA (the cut-off value is >17.95 µmol/L) as an independent predictor of sepsis mortality with an AUC of 0.842 (95% CI 0.800-0.883), sensitivity of 54.9%, specificity of 96.6%, and HR = 7.658 (95% CI 5.575-10.520). The study showed that elevated TBA was associated with a heightened risk of mortality in pediatric sepsis. Many clinical indicators show differences between children with sepsis and the control group, among which the difference in serum total bile acid levels is the most significant. During the hospitalization of the patients, the overall bile acid levels in the sepsis death group were higher and exhibited greater fluctuations compared to the survival group, with significant differences. Serum total bile acid levels can serve as effective biomarker for predicting the prognosis of children with sepsis.

Long-term ill health in sepsis survivors: an ignored health-care challenge?

Long-term ill health in sepsis survivors: an ignored health-care challenge?

Readmissions in Sepsis Survivors: Discharge Setting Risks.

Sepsis is a complex condition with high morbidity and mortality. Prompt treatment can improve survival, but for survivors the risk of deterioration and readmission remains high. Little is known about the association between discharge setting and readmission among sepsis survivors. To examine 30-day hospital readmission rates in adult sepsis survivors by the type of setting to which patients were discharged. The Medical Information Mart for Intensive Care database was used to identify adult sepsis survivors and evaluate 30-day readmission by discharge setting. A χ2 contingency analysis was used with each factor and presence/absence of readmission. The Kruskal-Wallis test was used to compare readmissions across discharge settings. From our sample (N = 7107; mean age 66.5 years; 46.2% women), 23.6% (n = 1674) were readmitted within 30 days and of those readmitted, 30% were readmitted between 1 and 3 times. Discharge setting (P < .001) and age (P = .02) were significantly associated with readmission, but sex, ethnicity, and insurance type were not. High numbers of readmissions were seen in patients discharged to skilled nursing facilities (29.6%), home health care (26.9%), and home (15.0%). Similar high comorbidity burden and acuteness of illness were seen in patients discharged to these settings. Sepsis survivors discharged to skilled nursing facilities, home health care, and home are at high risk for 30-day readmission. The rates of readmission from home health care and home settings were alarming. Often patients are discharged to inappropriate settings, placing them at risk for residual sepsis and readmission. Future research should focus on appropriate timing of hospital discharge and transition to the most appropriate discharge setting.

Impact of Abnormal Ankle Brachial Index on Sepsis Survival: One-Year Prospective Study Results.

Lower extremity peripheral artery disease (LE-PAD) has been linked to unfavorable cardiovascular outcomes. The impact of potentially undiagnosed LE-PAD, suspected by abnormal ankle-brachial index (ABI), on the survival of sepsis patients admitted to the intensive care unit (ICU) remains uncertain. We conducted a prospective cohort study and recruited adult patients admitted to the ICU with a primary diagnosis of sepsis (defined by a quick Sepsis-Related Organ Failure Assessment score of ≥ 2) between November 23, 2017 and July 22, 2018. ABI measurements were obtained within 24 hours of admission. The study compared the 30-day and 1-year all-cause mortality rates as well as the incidence of major adverse cardiovascular events (MACEs) between the groups with normal and abnormal ABI values. Of the 102 sepsis patients admitted to the ICU, 38 (37%) were diagnosed with LE-PAD based on their ABI measurements. The overall 30-day mortality rate was 30.0% in patients with LE-PAD and 25.8% in those with normal ABI (p = 0.56). At 1 year, the overall mortality rate was 52.6% in the patients with abnormal ABI and 40.6% in those with normal ABI (p = 0.24). Additionally, the incidence of MACEs was significantly higher in the patients with abnormal ABI compared to those with normal ABI at 1-year follow-up (21.1% vs. 3.1%, respectively; p = 0.003). The patients with abnormal ABI had a higher incidence of MACEs within one year following hospital discharge. Future studies are needed to improve cardiovascular outcomes among sepsis survivors (ClinicalTrials.gov number, NCT03372330).

Pre-implementation planning for a sepsis intervention in a large learning health system: a qualitative study

BackgroundSepsis survivors experience high morbidity and mortality. Though recommended best practices have been established to address the transition and early post hospital needs and promote recovery for sepsis survivors, few patients receive recommended post-sepsis care. Our team developed the Sepsis Transition and Recovery (STAR) program, a multicomponent transition intervention that leverages virtually-connected nurses to coordinate the application of evidence-based recommendations for post-sepsis care with additional clinical support from hospitalist and primary care physicians. In this paper, we present findings from a qualitative pre-implementation study, guided by the Consolidated Framework for Implementation Research (CFIR), of factors to inform successful STAR implementation at a large learning health system prior to effectiveness testing as part of a Type I Hybrid trial.MethodsWe conducted semi-structured qualitative interviews (n = 16) with 8 administrative leaders and 8 clinicians. Interviews were transcribed and analyzed in ATLAS.ti using a combination deductive/inductive strategy based on CFIR domains and constructs and the Constant Comparison Method.ResultsSix facilitators and five implementation barriers were identified spanning all five CFIR domains (Intervention Characteristics, Outer Setting, Inner Setting, Characteristics of Individuals and Process). Facilitators of STAR included alignment with health system goals, fostering stakeholder engagement, sharing STAR outcomes data, good communication between STAR navigators and patient care teams/PCPs, clinician promotion of STAR with patients, and good rapport and effective communication between STAR navigators and patients, caregivers, and family members. Barriers of STAR included competing demands for staff time and resources, insufficient communication and education of STAR’s value and effectiveness, underlying informational and technology gaps among patients, lack of patient access to community resources, and patient distrust of the program and/or health care.ConclusionsCFIR proved to be a robust framework for examining facilitators and barriers for pre-implementation planning of post-sepsis care programs within diverse hospital and community settings in a large LHS. Conducting a structured pre-implementation evaluation helps researchers design with implementation in mind prior to effectiveness studies and should be considered a key component of Type I hybrid trials when feasible.Trial registrationClinicaltrials.gov, NCT04495946. Registered August 3, 2020.

Caspase-11 signaling promotes damage to hippocampal CA3 to enhance cognitive dysfunction in infection

BackgroundCognitive dysfunction caused by infection frequently emerges as a complication in sepsis survivor patients. However, a comprehensive understanding of its pathogenesis remains elusive.MethodsIn our in vivo experiments, an animal model of endotoxemia was employed, utilizing the Novel Object Recognition Test and Morris Water Maze Test to assess cognitive function. Various techniques, including immunofluorescent staining, Western blotting, blood‒brain barrier permeability assessment, Limulus Amebocyte Lysate (LAL) assay, and Proximity-ligation assay, were employed to identify brain pathological injury and neuroinflammation. To discern the role of Caspase-11 (Casp11) in hematopoietic or non-hematopoietic cells in endotoxemia-induced cognitive decline, bone marrow chimeras were generated through bone marrow transplantation (BMT) using wild-type (WT) and Casp11-deficient mice. In vitro studies involved treating BV2 cells with E. coli-derived outer membrane vesicles to mimic in vivo conditions.ResultsOur findings indicate that the deficiency of Casp11-GSDMD signaling pathways reverses infection-induced cognitive dysfunction. Moreover, cognitive dysfunction can be ameliorated by blocking the IL-1 effect. Mechanistically, the absence of Casp11 signaling significantly mitigated blood‒brain barrier leakage, microglial activation, and synaptic damage in the hippocampal CA3 region, ultimately leading to improved cognitive function.ConclusionThis study unveils the crucial contribution of Casp11 and GSDMD to cognitive impairments and spatial memory loss in a murine sepsis model. Targeting Casp11 signaling emerges as a promising strategy for preventing or treating cognitive dysfunction in patients with severe infections.

Strategies for early identification and management of sepsis in children

Pediatric sepsis continues to be a major public health concern, leading to considerable morbidity and mortality despite progress in medical treatments. This review explores methods for the prompt detection and management of sepsis in children, highlighting the importance of early recognition and intervention. Diagnosing sepsis in children is difficult because of its non-specific symptoms and the diverse ways it presents in different age groups. Key strategies include enhancing parental education, improving pre-hospital recognition by emergency medical services (EMS), and leveraging the pivotal role of nurses in emergency settings. Effective management involves prompt administration of antimicrobials, appropriate use of vasoactive agents, and comprehensive post-sepsis care to improve long-term outcomes. Advanced diagnostic tools and rapid, reliable biomarkers are crucial for early detection. Additionally, antimicrobial stewardship programs and public health campaigns play a vital role in reducing sepsis incidence. By focusing on these strategies, healthcare providers can significantly improve the early identification and management of sepsis in children, enhancing survival rates and long-term quality of life for pediatric sepsis survivors.

Healthcare Use and Expenditures in Rural Survivors of Hospitalization for Sepsis.

Sepsis survivors have greater healthcare use than those surviving hospitalizations for other reasons, yet factors associated with greater healthcare use in this population remain ill-defined. Rural Americans are older, have more chronic illnesses, and face unique barriers to healthcare access, which could affect postsepsis healthcare use. Therefore, we compared healthcare use and expenditures among rural and urban sepsis survivors. We hypothesized that rural survivors would have greater healthcare use and expenditures. To test this hypothesis, we used data from 106,189 adult survivors of a sepsis hospitalization included in the IBM MarketScan Commercial Claims and Encounters database and Medicare Supplemental database between 2013 and 2018. None. We identified hospitalizations for severe sepsis and septic shock using the International Classification of Diseases , 9th Edition (ICD-9) or 1CD-10 codes. We used Metropolitan Statistical Area classifications to categorize rurality. We measured emergency department (ED) visits, inpatient hospitalizations, skilled nursing facility admissions, primary care visits, physical therapy visits, occupational therapy visits, and home healthcare visits for the year following sepsis hospitalizations. We calculated the total expenditures for each of these categories. We compared outcomes between rural and urban patients using multivariable regression and adjusted for covariates. After adjusting for age, sex, comorbidities, admission type, insurance type, U.S. Census Bureau region, employment status, and sepsis severity, those living in rural areas had 17% greater odds of having an ED visit (odds ratio [OR] 1.17; 95% CI, 1.13-1.22; p < 0.001), 9% lower odds of having a primary care visit (OR 0.91; 95% CI, 0.87-0.94; p < 0.001), and 12% lower odds of receiving home healthcare (OR 0.88; 95% CI, 0.84-0.93; p < 0.001). Despite higher levels of ED use and equivalent levels of hospital readmissions, expenditures in these areas were 14% (OR 0.86; 95% CI, 0.80-0.91; p < 0.001) and 9% (OR 0.91; 95% CI, 0.87-0.96; p < 0.001) lower among rural survivors, respectively, suggesting these services may be used for lower-acuity conditions. In this large cohort study, we report important differences in healthcare use and expenditures between rural and urban sepsis survivors. Future research and policy work is needed to understand how best to optimize sepsis survivorship across the urban-rural continuum.

Lung-brain crosstalk: Behavioral disorders and neuroinflammation in septic survivor mice

Although studies have suggested an association between lung infections and increased risk of neuronal disorders (e.g., dementia, cognitive impairment, and depressive and anxious behaviors), its mechanisms remain unclear. Thus, an experimental mice model of pulmonary sepsis was developed to investigate the relationship between lung and brain inflammation. Male Swiss mice were randomly assigned to either pneumosepsis or control groups. Pneumosepsis was induced by intratracheal instillation of Klebsiella pneumoniae, while the control group received a buffer solution. The model's validation included assessing systemic markers, as well as tissue vascular permeability. Depression- and anxiety-like behaviors and cognitive function were assessed for 30 days in sepsis survivor mice, inflammatory profiles, including cytokine levels (lungs, hippocampus, and prefrontal cortex) and microglial activation (hippocampus), were examined. Pulmonary sepsis damaged distal organs, caused peripheral inflammation, and increased vascular permeability in the lung and brain, impairing the blood-brain barrier and resulting in bacterial dissemination. After sepsis induction, we observed an increase in myeloperoxidase activity in the lungs (up to seven days) and prefrontal cortex (up to 24 h), proinflammatory cytokines in the hippocampus and prefrontal cortex, and percentage of areas with cells positive for ionized calcium-binding adaptor molecule 1 (IBA-1) in the hippocampus. Also, depression- and anxiety-like behaviors and changes in short-term memory were observed even 30 days after sepsis induction, suggesting a crosstalk between inflammatory responses of lungs and brain.

Factor Impacting Quality of Life Among Sepsis Survivors During and After Hospitalization: A Systematic Review of Current Empirical Evidence.

There remains a gap in understanding post-sepsis outcomes, particularly regarding the factors that influence the quality of life (QOL) among sepsis survivors during and after hospitalization. To determine factors impacting QOL among sepsis survivors during and after hospitalization based on the evaluation and synthesis of current evidence. This review encompassed studies published from January 2020 to December 2024, sourced from Scopus, PubMed, Medline, ScienceDirect, CINAHL Plus with Full Text, and Web of Science. The process of identifying, screening, excluding, and including articles followed the guidelines set by the Preferred Reporting Items for Systematic Reviews (PRISMA). Data synthesis for theme generation was conducted using the convergent integrated analysis framework as recommended by the Joanna Briggs Institute. A total of 1164 records were identified from the databases. After removing 130 duplicates, 1034 articles remained for screening based on their titles and abstracts according to the inclusion and exclusion criteria. At this stage, 1021 articles did not meet the criteria and were excluded, leaving 13 articles eligible for full-text screening. During this phase, 5 articles were excluded for various reasons, resulting in eight studies being included in the systematic review. Data synthesis of these studies revealed seven themes related to factors impacting QOL among sepsis survivors during and after hospitalization: 1) Physical Health Dimension, 2) Mental Health Dimension, 3) Treatment During Hospitalization, 4) Spiritual Dimension, 5) Social Support, 6) Mortality, and 7) Blood Biomarkers. This systematic review provides valuable insights into the factors affecting the quality of life among sepsis survivors during and after hospitalization. These findings enhance the current knowledge base and offer clinicians, researchers, and policymakers actionable insights to improve outcomes and well-being for sepsis survivors.

EHR Solutions for Information Transfer Deficits During Transitions in Care for Sepsis Survivors.

In a previous study, sepsis was noted as a diagnosis on the home health record only 4% of the time for 165,000 sepsis survivors transitioning from hospital to home health care in America. If sepsis and other conditions are not clearly documented in the transitional care record this can lead to unpreparedness, missed, care, and poor patient outcomes. Our implementation science study discovered a source of this problem regarding the sepsis documentation in 16 hospitals referring to five home care agencies. Together, researchers, hospital, and home care personnel developed and implemented two information technology solutions to address this deficit in seven hospitals. The automated method was more readily adopted and effective in improving information transfer between hospital and home health care.