Risk factors of postoperative septic cardiomyopathy in perioperative sepsis patients.

OBJECTIVE: This study aimed to clarify the relevant risk factors of septic cardiomyopathy (SCM) in perioperative sepsis patients. METHODS: This retrospective study evaluated patients who were diagnosed with sepsis during the perioperative period and postoperatively admitted to the intensive care unit (ICU) in the Second Affiliated Hospital of Soochow University, the First Affiliated Hospital of Soochow University, and the Suzhou Municipal Hospital between January 2017 and November 2020. They were divided into two groups as the septic cardiomyopathy group (SCM group) and the non-SCM group (NSCM group). Factors with P < 0.1 were compared between groups and were analyzed by multivariate logistic regression to screen the risk factors of sepsis cardiomyopathy. The area under the receiver operating characteristic (ROC) curve was used to verify the discriminative ability of multivariate logistic regression results. Hosmer-Lemeshow goodness of fit test was used to verify the calibration ability of multiple logistic regression results. RESULT: Among the 269 patients, 49 patients had SCM. Sequential Organ Failure Assessment (SOFA) score (adjusted odds ratio [AOR] = 2.535, 95% confidence interval (CI): 1.186-1.821, P = 0.000]) and endoscopic surgery (AOR = 3.154, 95% CI: 1.173-8.477, P = 0.023]) were identified to be independent risk factors for SCM. Patients with a SOFA score ≥ 7 had a 46.831-fold higher risk of SCM (AOR =46.831, 95% CI: 10.511-208.662, P < 0.05). The multivariate logistic regression results had good discriminative (area under the curve: 0.902 [95% CI: 0.852-0.953]) and calibration (c2 = 4.401, P = 0.819) capabilities. The predictive accuracy was 86.2%. The rates of mechanical ventilation and tracheotomy were significantly higher in the SCM group than in the NSCM group (both P < 0.05). The SCM group also had a significantly longer duration of mechanical ventilation (P < 0.05) and significantly higher rates of continuous renal replacement therapy (CRRT) and CRRT-related mortality (P < 0.05). Further, the total length of stay and hospitalization cost were significantly higher in the SCM group than in the NSCM group (P < 0.05). CONCLUSION: Endoscopic surgery and SOFA score ≥ 7 during postoperative ICU admission were independent risk factors for SCM within 48 hours postoperatively in patients with perioperative sepsis.

Itraq-Based Quantitative Proteomic Analysis of Lungs in Murine Polymicrobial Sepsis with Hydrogen Gas Treatment.

Sepsis-associated acute lung injury (ALI), which carries a high morbidity and mortality in patients, has no effective therapeutic strategies to date. Our group has already reported that hydrogen gas (H2) exerts a protective effect against sepsis in mice. However, the molecular mechanisms underlying H2 treatment are not fully understood. This study investigated the effects of H2 on lung injuries in septic mice through the isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis. Male ICR mice used in this study were subjected to cecal ligation and puncture (CLP) or sham operation. And 2% H2 was inhaled for 1 h beginning at 1 and 6 h after sham or CLP operation. The iTRAQ-based liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis was preformed to investigate lung proteomics. Sepsis-challenged animals had decreased survival rate, as well as had increased bacterial burden in blood, peritoneal lavage, and lung sample, which were significantly ameliorated by H2 treatment. Moreover, a total of 4,472 proteins were quantified, and 192 differentially expressed proteins were related to the protective mechanism of H2 against sepsis. Functional enrichment analysis showed that H2-related differential proteins could be related to muscle contraction, oxygen transport, protein synthesis, collagen barrier membranes, cell adhesion, and coagulation function. These proteins were significantly enriched in four signaling pathways, and two of which are associated with coagulation. In addition, H2 alleviates ALI in septic mice through downregulating the expression of Sema 7A, OTULIN, and MAP3K1 as well as upregulating the expression of Transferrin. Thus, our findings provide an insight into the mechanism of H2 treatment in sepsis by proteomic approach, which may be helpful to the clinic application of H2 in patients with sepsis.

Molecular hydrogen inhalation attenuates postoperative cognitive impairment in rats.

Postoperative cognitive decline is a major clinical problem with high morbidity and mortality after surgery. Many studies have found that molecular hydrogen (H2) has significant neuroprotection against acute and chronic neurological injury by regulating inflammation and apoptosis. In this study, we hypothesized that H2 treatment could ameliorate the development of cognitive impairment following surgery. Adult male rats were subjected to stabilized tibial fracture operation under anesthesia. Two percent of H2 was inhaled for 3 h beginning at 1 h after surgery. Separate cohorts of rats were tested for cognitive function with fear conditioning and the Y-maze test, or euthanized to assess blood-brain barrier integrity, and systemic and hippocampal proinflammatory cytokine and caspase-3 activity. Surgery-challenged animals showed significant cognitive impairment evidenced by a decreased percentage of freezing time and an increased number of learning trials on days 1, 3, and 7 after operation, which were significantly improved by H2 treatment. Furthermore, H2 treatment significantly ameliorated the increase in serum and hippocampal proinflammatory cytokines tumor necrosis factor-α, interleukin-1ß, interleukin-6, and high-mobility group protein 1 in surgery-challenged animals. Moreover, H2 treatment markedly improved blood-brain barrier integrity and reduced caspase-3 activity in the hippocampus of surgery-challenged animals. These findings suggest that H2 treatment could significantly mitigate surgery-induced cognitive impairment by regulating inflammation and apoptosis.

Severity of sepsis is correlated with the elevation of serum high-mobility group box 1 in rats.

BACKGROUND: Sepsis is a leading cause of death in the intensive care units. The late inflammatory cytokine, high-mobility group box 1 (HMGB1), plays a critical role in sepsis. In the present study, we investigated the association between the serum HMGB1 levels and the severity of organ injury in the lipopolysaccharide-induced sepsis in rats. METHODS: To produce an animal model of sepsis with different degree of organ injury, animals were treated with three different doses of lipopolysaccharide (4, 8 and 16 mg/kg), and the animals in control group were treated with the same volume of the vehicle (saline). The levels of serum HMGB1 were measured at 0, 2, 4, 8, 16, 24, 32 and 48 hours after lipopolysaccharide (LPS) or vehicle injection, meanwhile the biochemical and histopathological indicators for the severity of organ injury were assessed. RESULTS: The level of HMGB1 had a positive, high correlation with the abnormal changes of serum cardiac troponin I, alanine aminotransferase, aspartate aminotransferase, creatinine and blood urea nitrogen, as well as the pathologic scores of heart, lung, liver and kidney. CONCLUSIONS: The level of serum HMGB1 is highly correlated with the severity of sepsis in rats, suggesting that HMGB1 could serve as a valuable adjunct in the diagnosis and management of sepsis.