Daily Sepsis Research Analysis
Three impactful sepsis-related studies stand out today: a murine neuroimaging paper shows sex-dependent brain connectivity changes after sepsis, a porcine translational model reveals muscle-driven amino acid flux sustaining gluconeogenesis in acute sepsis, and a 55-study meta-analysis defines ICU bloodstream infection risk factors in COVID-19. Together, they advance pathophysiological insight and inform targeted prevention strategies.
Summary
Three impactful sepsis-related studies stand out today: a murine neuroimaging paper shows sex-dependent brain connectivity changes after sepsis, a porcine translational model reveals muscle-driven amino acid flux sustaining gluconeogenesis in acute sepsis, and a 55-study meta-analysis defines ICU bloodstream infection risk factors in COVID-19. Together, they advance pathophysiological insight and inform targeted prevention strategies.
Research Themes
- Sex-dependent neuroimmune and functional connectivity changes after sepsis
- Metabolic reprogramming and interorgan substrate flux in acute sepsis
- ICU bloodstream infection risk stratification in COVID-19
Selected Articles
1. Functional connectivity within sensorimotor cortical and striatal regions is regulated by sepsis in a sex-dependent manner.
Using a polymicrobial intra-abdominal sepsis model, the authors show sex-dependent neuroimmune and functional connectivity responses: males exhibit stronger splenic expansion, intracerebral gliosis, and increased intra-striatal connectivity, while females show attenuated network alterations. Both sexes had reduced gut microbiome diversity and recovered body weight by day 7.
Impact: This study provides novel evidence that sepsis differentially reshapes brain networks by sex, suggesting distinct recovery trajectories and therapeutic windows. It integrates immune, microbiome, and fMRI metrics to bridge systemic inflammation with neural circuitry.
Clinical Implications: While preclinical, findings argue for incorporating sex as a biological variable in neurocognitive assessment and rehabilitation after sepsis, and motivate clinical fMRI studies to identify at-risk survivors (particularly males) for tailored interventions.
Key Findings
- Both male and female mice survived sepsis, regained body weight by 7 days, and showed reduced gut microbiome diversity.
- Post-septic males exhibited stronger splenic cell expansion and intracerebral glial proliferation compared with females.
- Resting-state fMRI showed increased intra-striatal connectivity in males, with female mice maintaining near-baseline intra-striatal connectivity and reduced alterations in PAG→SC and ACC–striatal projections.
Methodological Strengths
- Polymicrobial intra-abdominal sepsis model with multimodal readouts (immune profiling, microbiome, resting-state fMRI).
- Inclusion of both sexes enables sex-specific inference on neuroimmune and connectivity responses.
Limitations
- Preclinical murine model limits direct generalizability to humans; exact sample sizes per group are not specified in the abstract.
- Functional connectivity changes were not linked to behavioral outcomes or causal neural manipulations.
Future Directions: Couple rs-fMRI with behavioral testing and causal circuit manipulations; dissect hormonal and microglial drivers of sex differences; translate to longitudinal clinical neuroimaging in sepsis survivors.
Sepsis is a state of systemic immune dysregulation and organ failure that is frequently associated with severe brain disability. Epidemiological studies have indicated that younger females have better prognosis and clinical outcomes relative to males, though the sex-dependent response of the brain to sepsis during post-sepsis recovery remains largely uncharacterized. Using a modified polymicrobial intra-abdominal murine model of surgical sepsis, we characterized the acute effects of intra-abdominal sepsis on peripheral inflammation, brain inflammation and brain functional connectivity in young adult mice of both sexes. Following sepsis, both male and female mice survived the procedure, regained body weight within 7 days post-sepsis and showed reduced diversity in their gut microbiome. Interestingly, compared to the sepsis-induced changes observed in female mice, the post-septic male mice exhibited a comparatively robust profile of splenic cell expansion and intracerebral glial proliferation relative to their healthy counterparts. Analysis of resting-state functional Magnetic Resonance Imaging (fMRI) data collected from the post-septic mice revealed that while connectivity to the somatosensory cortex were affected equally in both sexes, intra-network connectivity strength in the striatum preferentially increased in post-septic males but remained near baseline in post-septic female mice. Additionally, the female mice showed reduced network connectivity alterations in the projections from periaqueductal gray to the superior colliculus as also between the anterior cingulate cortex and the striatum. Coupled with the sustained intracerebral gliosis response, the intra-striatal fMRI response patterns in males could signify a delayed recovery from sepsis. Together, our study provides evidence that peripheral sepsis influences peripheral immunity, brain immunity and brain connectivity in a sex-dependent manner, with the fMRI response strongly indicating cognitive benefits in young females recovering from sepsis relative to their male counterparts.
2. Risk factors for bloodstream infection in COVID-19 patients in intensive care units: a systematic review and meta-analysis.
A meta-analysis of 55 studies identified ten risk factors for ICU bloodstream infection in COVID-19, notably invasive devices (intubation, mechanical ventilation, central lines), immunosuppression (methylprednisolone ± tocilizumab), male sex, diabetes, higher SAPS II, and prolonged ICU stay. Results support early targeted prevention and risk prediction model development.
Impact: By consolidating robust effect estimates across diverse cohorts, this work provides actionable ICU-BSI risk factors to guide prevention bundles and stewardship in high-risk COVID-19 patients.
Clinical Implications: Prioritize infection prevention bundles for intubated, ventilated, and central-line patients; reassess steroid/immunomodulator use and duration; incorporate identified factors into ICU-BSI risk prediction to trigger early diagnostics and line care protocols.
Key Findings
- Across 55 studies, male sex increased ICU-BSI risk (OR 1.28, 95% CI 1.10–1.50, P=0.006); diabetes also increased risk (OR 1.34, 95% CI 1.04–1.73, P=0.022).
- Invasive support strongly associated with BSI: tracheal intubation (OR 8.68), mechanical ventilation (OR 22.00), central venous cannulation (OR 9.33), all P<0.001.
- Higher illness severity (SAPS II WMD 6.43, P=0.042), prolonged ICU stay (WMD 10.37, P<0.001), ECMO (OR 2.70, P=0.020), and methylprednisolone (OR 2.24, P=0.008) or methylprednisolone+tocilizumab (OR 4.54, P=0.037) were additional risk factors.
Methodological Strengths
- Comprehensive multi-database search up to July 2024 with 55 included studies.
- Appropriate pooling (OR for categorical, WMD for continuous variables) enabling quantitative synthesis across heterogeneous cohorts.
Limitations
- Observational evidence limits causal inference; heterogeneity and variable BSI definitions across studies likely.
- PRISMA adherence, risk-of-bias and publication bias assessments are not detailed in the abstract.
Future Directions: Develop and validate ICU-BSI prediction models incorporating identified risk factors; test targeted prevention bundles and stewardship strategies in high-risk subgroups in pragmatic trials.
BACKGROUND: Risk factors for bloodstream infection in patients with COVID-19 in the intensive care unit (ICU) remain unclear. The purpose of this systematic review was to study the risk factors for BSI in patients admitted to ICUs for COVID-19. METHODS: A systematic search was performed on PubMed, EMBASE, Cochrane Library, and Web of Science up to July 2024. Data were reported as combined odds ratio (OR) for categorical variables and weighted mean difference (WMD) for continuous variables. RESULTS: 6914 studies were retrieved, of which 55 were included in the meta-analysis. Men (OR = 1.28, 95% CI: 1.10-1.50, P = 0.006), high SAPS II score (WMD = 6.43, 95% CI: 0.23-12.63, P = 0.042), diabetes (OR = 1.34, 95% CI: 1.04-1.73, P = 0.022), tracheal intubation (OR = 8.68, 95% CI: 4.68-16.08, P < 0.001), mechanical ventilation (OR = 22.00, 95% CI: 3.77-128.328, P < 0.001), ECMO (OR = 2.70, 95% CI: 1.17-6.26, P = 0.020), central venous cannulation (OR = 9.33, 95% CI: 3.06-28.43, P < 0.001), prolonged ICU stay (WMD = 10.37, 95% CI: 9.29-11.44, P < 0.001), methylprednisolone use (OR = 2.24, 95% CI: 1.24-4.04, P = 0.008), and the combination of methylprednisolone and Tocilizumab (OR = 4.54, 95% CI: 1.09-18.88, P = 0.037) were risk factors for ICU-BSI in COVID-19 patients. CONCLUSION: We identified 10 risk factors for ICU-BSI in COVID-19 patients. In future studies, these factors can be combined to establish a more comprehensive and accurate prediction model for ICU-BSI in COVID-19 patients. Targeted measures can be taken earlier to control BSI.
3. The role of adipose and muscle tissue breakdown on interorgan energy substrate fluxes in a Pseudomonas aeruginosa induced sepsis model in female pigs.
In female pigs with Pseudomonas aeruginosa–induced sepsis, plasma glucose fell despite increased splanchnic glucose release driven by reduced portal-drained viscera uptake and unchanged hepatic production. Hindquarter released more alanine, glutamine, and lactate (but not glycerol), implicating muscle proteolysis and altered intestinal amino acid handling in fueling gluconeogenesis.
Impact: This large-animal, organ-flux study clarifies how muscle-derived amino acids, rather than glycerol, support gluconeogenesis in early sepsis, refining metabolic targets for nutritional therapy.
Clinical Implications: Suggests prioritizing protein/AA support and strategies to mitigate muscle catabolism in early sepsis, while recognizing limits of glycolysis-derived substrates; warrants human validation before practice change.
Key Findings
- Plasma glucose decreased in sepsis (p=0.0028) despite increased splanchnic net glucose release (p=0.0049) due to reduced portal-drained viscera uptake (p=0.0032) and unchanged hepatic production (p=0.7861).
- Hindquarter released more alanine (p=0.0002), glutamine (p=0.003), and lactate (p=0.0007), but not glycerol (p=0.5718), indicating muscle proteolysis fuels gluconeogenesis.
- Diminished PDV uptake and increased hepatic uptake of gluconeogenic amino acids (p<0.05) did not translate into higher net hepatic glucose output.
Methodological Strengths
- Translational large-animal model with arterio-venous sampling across splanchnic, portal-drained viscera, liver, and hindquarter.
- Quantitative metabolite profiling using HPLC and LCMS with controlled septic vs. saline groups.
Limitations
- Female pigs only; findings may not generalize to males or other pathogens; short 18-hour acute window.
- Potential confounding from anesthesia/critical care support not fully detailed.
Future Directions: Extend to longer timeframes and mixed sexes; integrate stable isotope tracers to quantify fluxes; test nutrition/anti-catabolic interventions and validate in human sepsis.
Sepsis leads to an acute breakdown of muscle to support increased caloric and amino acid requirements. Little is known about the role of adipose and muscle tissue breakdown and intestinal metabolism in glucose substrate supply during the acute phase of sepsis. In a translational porcine model of sepsis, we explored the across organ net fluxes of gluconeogenic substrates. In 13 pigs, acute sepsis was induced by IV infusion of Pseudomonas aeruginosa, while in 9 pigs saline (control) was given for 18 h. Blood samples were collected between 12 and 18 h and analyzed with HPLC and LCMS. In sepsis, glucose plasma concentration was reduced (p = 0.0028). A concordant increase in splanchnic area net release of glucose (p = 0.0049), due to reduced uptake in the portal drained viscera (PDV) (p = 0.0032) with an unchanged liver production (p = 0.7861). The hindquarter showed a higher release of alanine (p = 0.0002), glutamine (p = 0.003), and lactate (p = 0.0007), but not for glycerol (p = 0.5718). Diminished PDV uptake of gluconeogenic amino acids, increased liver uptake of these substrates (p < 0.05), while no change in liver glycerol uptake (p = 0.3170), did not lead to an increased net liver glucose release. In the acute phase of sepsis, we hypothesize an important role of altered intestinal amino acid metabolism and breakdown of muscle proteins, but not of glycolysis to support gluconeogenesis.