Sepsis-associated liver injury:Mechanisms and potential therapeutic targets

In this editorial,we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury(SLI)and its treatment.SLI is a serious complication of sepsis,primarily caused by microcirculatory disturbances,the gut-liver axis,and inflammatory responses.Specific treatment recommendations for SLI are lacking.The gut-liver axis represents a potential therapeutic target,with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function.Although immunomodulatory therapies are being explored,anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits.Statins may reduce liver inflammation and prevent injury in sepsis,but their clinical application is limited.Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients,indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency.Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results,likely due to inadequate assessment of the immune status of the host.Future research should prioritize the development of personalized immunotherapy tailored to patients’immune profiles,focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

Timing of Continuous Renal Replacement Therapy Initiation in Sepsis-Associated Acute Kidney Injury: A Comprehensive Review and Future Directions

This review examines the application of continuous renal replacement therapy(CRRT)in patients with sepsis-associated acute kidney injury(S-AKI),with a particular focus on the timing of CRRT initiation.This review addresses the controversy surrounding initiation timing and proposes future research directions.Through a systematic review of recent literature on CRRT for S-AKI,working principles,therapeutic mechanisms,initiation timing of CRRT,and related meta-analyses were summarized.Current studies indicate that the optimal timing for CRRT initiation in S-AKI patients remains inconclusive,with ongoing debate regarding whether early initiation significantly improves patient survival and renal function.This lack of consensus reflects the heterogeneity of the S-AKI patient population and the limitations of existing research methodologies.Future studies should focus on advancing the application of precision medicine in S-AKI and developing individualized treatment strategies by integrating multidimensional information to optimize CRRT utilization and improve patient outcomes.

Bibliometric study of sepsis-associated liver injury from 2000 to 2023

BACKGROUND Sepsis-associated liver injury(SLI)is a severe and prevalent complication of sepsis.AIM To explore the literature on SLI via a bibliometric approach.METHODS Reviews and articles correlated with SLI published from January 1,2000 to October 28,2023 were searched from the Web of Science Core Collection.Then,the searched data were analyzed using VOSviewer,CiteSpace,and R language.RESULTS There were 787 publications involved in this paper,comprising 745 articles and 42 reviews.China,the United States,and Germany are the primary publication sources in this area.Studies related to SLI primarily focused on mechanisms of pathogenesis,as evidenced by analyzing keywords,references,and the counting of original research.These studies mainly involved tumor necrosis factor alpha,inflammation,oxidative stress,and nuclear factor-kappa B.CONCLUSION There is significant growth in the research on SLI.Current investigations primarily involve basic experiments that aimed at uncovering pathogenic mechanisms.According to the analyzed literature,the identified pathogenic mechanisms and potential therapeutic targets serve as the foundation for translating findings from basic research to clinical applications.

Data driven analysis reveals prognostic genes and immunological targets in human sepsis-associated acute kidney injury

BACKGROUND:The molecular mechanism of sepsis-associated acute kidney injury(SA-AKI)is unclear.We analyzed co-differentially expressed genes(co-DEGs)to elucidate the underlying mechanism and intervention targets of SA-AKI.METHODS:The microarray datasets GSE65682,GSE30718,and GSE174220 were downloaded from the Gene Expression Omnibus(GEO)database.We identified the co-DEGs and constructed a gene co-expression network to screen the hub genes.We analyzed immune correlations and disease correlations and performed functional annotation of the hub genes.We also performed single-cell and microenvironment analyses and investigated the enrichment pathways and the main transcription factors.Finally,we conducted a correlation analysis to evaluate the role of the hub genes.RESULTS:Interleukin 32(IL32)was identified as the hub gene in SA-AKI,and the main enriched signaling pathways were associated with hemopoiesis,cellular response to cytokine stimulus,inflammatory response,and regulation of kidney development.Additionally,IL32 was significantly associated with mortality in SA-AKI patients.Monocytes,macrophages,T cells,and NK cells were closely related to IL32 and were involved in the immune microenvironment in SA-AKI patients.IL32 expression increased significantly in the kidney of septic mouse.Toll-like receptor 2(TLR2)was significantly and negatively correlated with IL32.CONCLUSION:IL32 is the key gene involved in SA-AKI and is significantly associated with prognosis.TLR2 and relevant immune cells are closely related to key genes.

Comparing gastrointestinal dysfunction score and acute gastrointestinal injury grade for predicting short-term mortality in critically ill patients

BACKGROUND The prognosis of critically ill patients is closely linked to their gastrointestinal(GI)function.The acute GI injury(AGI)grading system,established in 2012,is extensively utilized to evaluate GI dysfunction and forecast outcomes in clinical settings.In 2021,the GI dysfunction score(GIDS)was developed,building on the AGI grading system,to enhance the accuracy of GI dysfunction severity assessment,improve prognostic predictions,reduce subjectivity,and increase reproducibility.AIM To compare the predictive capabilities of GIDS and the AGI grading system for 28-day mortality in critically ill patients.METHODS A retrospective study was conducted at the general intensive care unit(ICU)of a regional university hospital.All data were collected during the first week of ICU admission.The primary outcome was 28-day mortality.Multivariable logistic regression analyzed whether GIDS and AGI grade were independent risk factors for 28-day mortality.The predictive abilities of GIDS and AGI grade were compared using the receiver operating characteristic curve,with DeLong’s test assessing differences between the curves’areas.RESULTS The incidence of AGI in the first week of ICU admission was 92.13%.There were 85 deaths(47.75%)within 28 days of ICU admission.There was no initial 24-hour difference in GIDS between the non-survival and survival groups.Both GIDS(OR 2.01,95%CI:1.25-3.24;P=0.004)and AGI grade(OR 1.94,95%CI:1.12-3.38;P=0.019)were independent predictors of 28-day mortality.No significant difference was found between the predictive accuracy of GIDS and AGI grade for 28-day mortality during the first week of ICU admission(Z=-0.26,P=0.794).CONCLUSION GIDS within the first 24 hours was an unreliable predictor of 28-day mortality.The predictive accuracy for 28-day mortality from both systems during the first week was comparable.

Impact of interleukin 6 levels on acute lung injury risk and disease severity in critically ill sepsis patients

BACKGROUND Sepsis is a life-threatening condition characterized by a dysregulation of the host response to infection that can lead to acute lung injury(ALI)and multiple organ dysfunction syndrome(MODS).Interleukin 6(IL-6)is a pro-inflammatory cytokine that plays a crucial role in the pathogenesis of sepsis and its complications.AIM To investigate the relationship among plasma IL-6 levels,risk of ALI,and disease severity in critically ill patients with sepsis.METHODS This prospective and observational study was conducted in the intensive care unit of a tertiary care hospital between January 2021 and December 2022.A total of 83 septic patients were enrolled.Plasma IL-6 levels were measured upon admission using an enzyme-linked immunosorbent assay.The development of ALI and MODS was monitored during hospitalization.Disease severity was evaluated by Acute Physiology and Chronic Health Evaluation II(APACHE II)and Sequential Organ Failure Assessment(SOFA)scores.RESULTS Among the 83 patients with sepsis,38(45.8%)developed ALI and 29(34.9%)developed MODS.Plasma IL-6 levels were significantly higher in patients who developed ALI than in those without ALI(median:125.6 pg/mL vs 48.3 pg/mL;P<0.001).Similarly,patients with MODS had higher IL-6 levels than those without MODS(median:142.9 pg/mL vs 58.7 pg/mL;P<0.001).Plasma IL-6 levels were strongly and positively correlated with APACHE II(r=0.72;P<0.001)and SOFA scores(r=0.68;P<0.001).CONCLUSIONElevated plasma IL-6 levels in critically ill patients with sepsis were associated with an increased risk of ALI andMODS.Higher IL-6 levels were correlated with greater disease severity,as reflected by higher APACHE II andSOFA scores.These findings suggest that IL-6 may serve as a biomarker for predicting the development of ALI anddisease severity in patients with sepsis.

Diagnostic value of tissue plasminogen activator-inhibitor complex in sepsis-induced liver injury:A single-center retrospective casecontrol study

BACKGROUND Sepsis often causes severe liver injury and leads to poor patient outcomes.Early detection of sepsis-induced liver injury(SILI)and early treatment are key to improving outcomes.AIM To investigate the clinical characteristics of SILI patients and analyze the associated risk factors,to identify potential sensitive biomarkers.METHODS Retrospective analysis of clinical data from 546 patients with sepsis treated in the intensive care unit of the 908th Hospital of Chinese People’s Liberation Army Joint Logistic Support Force between May 2018 and December 2022.The patients were divided into the sepsis group(n=373)and SILI group(n=173)based on the presence of acute liver injury within 2 hours of admission.We used the random forest algorithm to analyze risk factors and assessed potential diagnostic markers of SILI using the area under the receiver operating characteristic curve,Kaplan-Meier survival curves,subgroup analysis and correlation analysis.RESULTS Compared with the sepsis group,tissue plasminogen activator-inhibitor complex(t-PAIC)levels in serum were significantly higher in the SILI group(P<0.05).Random forest results showed that t-PAIC was an independent risk factor for SILI,with an area under the receiver operating characteristic curve of 0.862(95%confidence interval:0.832-0.892).Based on the optimal cut-off value of 11.9 ng/mL,patients at or above this threshold had significantly higher levels of lactate and Acute Physiology and Chronic Health Evaluation II score.The survival rate of these patients was also significantly worse(hazard ratio=2.2,95%confidence interval:1.584-3.119,P<0.001).Spearman’s correlation coefficients were 0.42 between t-PAIC and lactate,and 0.41 between t-PAIC and aspartate transaminase.Subgroup analysis showed significant differences in t-PAIC levels between patients with different severity of liver dysfunction.CONCLUSION T-PAIC can serve as a diagnostic indicator for SILI,with its elevation correlated with the severity of SILI.

Study of the OPG/RANKL/RANK signaling pathway in mice treated with sepsis-related acute kidney injury

Objective:The objective of this study was to investigate the alterations and potential implications of the Osteoprotegerin(OPG)/Receptor Activator of Nuclear Factor-kappa B Ligand(RANKL)/Receptor Activator of Nuclear Factor-kappa B(RANK)signaling pathway factors in a murine model of sepsis-associated acute kidney injury(SA-AKI).This research aimed to offer novel insights into the mechanistic exploration of SA-AKI.Methods:The SA-AKI model group(CLP group)was established through cecal ligation and puncture surgery(CLP),while the control group consisted of sham-operated animals(Sham group)subjected only to laparotomy without cecal ligation and puncture.Blood samples were collected 24 h post-surgery,and murine kidney tissues were harvested upon euthanasia.Serum levels of Serum Creatinine(Scr)and Blood Urea Nitrogen(BUN)were quantified using assay kits.Furthermore,serum levels of interleukin-6(IL-6),tumor necrosis factor-alpha(TNF-α),and interleukin-1 beta(IL-1β)were assessed through enzyme-linked immunosorbent assay(ELISA).Renal tissue pathological alterations were examined employing hematoxylin-eosin staining(HE),and the mRNA and protein levels of OPG,RANKL,and RANK in murine kidney tissues were determined via reverse transcription-quantitative polymerase chain reaction(RT-qPCR)and Western blotting.Results:Comparative analysis revealed that,in comparison to the Sham group,the CLP group demonstrated a significant elevation in the levels of Scr,BUN,IL-6,TNF-α,and IL-1β,with statistically significant disparities(all P<0.05).Histopathological examination of the CLP group's kidneys unveiled glomerular congestion,edema,partial ischemic wrinkling,enlargement of interstitial spaces,the presence of necrotic epithelial cells in select renal tubules,tubular luminal dilation,varying degrees of interstitial edema,and infiltration by a limited number of inflammatory cells.In parallel,relative to the Sham group,the CLP group exhibited substantial upregulation in mRNA expression of OPG and RANK in renal tissues,while RANKL mRNA expression experienced marked downregulation,with statistically significant distinctions(all P<0.05).Moreover,in comparison with the Sham group,the CLP group demonstrated an elevation in protein expression of OPG and RANK in kidney tissues,whereas RANKL protein expression displayed significant downregulation,with statistically significant differences(all P<0.05).Conclusion:In a murine sepsis model,augmented expression of OPG and RANK,coupled with diminished RANKL expression,suggests the potential involvement of the OPG/RANKL/RANK signaling pathway in the pathophysiological progression of SA-AKI.

Wedelolactone attenuates sepsis-associated acute liver injury by regulating the macrophage M1/M2 polarization balance through the PI3K/AKT/NF-κB signalling pathway

Background:Liver injury caused by sepsis seriously impairs the normal physiology of the liver.Wedelactone(WED)has an obvious anti-inflammatory effect against liver damage caused by various factors.Nevertheless,further research is needed to determine if WED might mitigate acute liver damage linked to sepsis by influencing macrophage polarization.Methods:We first assessed the effect of WED on lipopolysaccharides-triggered liver injury by biochemistry assay and tissue staining.Inflammatory factors were assessed using the ELISA kits.The expression of Cluster of Differentiation 86(CD86)and Cluster of Differentiation 206(CD206)was measured by immunofluorescence assay.The protein levels of inducible nitric oxide sythase(iNOS),Arginase 1(Arg-1),phosphatidylinositol 3-kinase(PI3K),protein kinase B(AKT),PI3K phosphorylation(p-PI3K),AKT phosphorylation(p-AKT),inhibitor of kappa B kinase(IKK),inhibitor of kappa B(IκB),and nuclear factor kappa-B(NF-κB)p65 were quantified by western blot analysis.Results:WED decreased the level of alanine aminotransferase(ALT),aspartate aminotransferase(AST),alkaline phosphatase(ALP)and malondialdehyde,and increased the activity of superoxide dismutase(SOD)and glutathione peroxidase(GSH-PX).Moreover,WED exerted effective anti-inflammatory effects by decreasing the level of Tumor necrosis factor-α(TNF-α)and Interleukin 6(IL-6)and increasing the level of Interleukin 10(IL-10)in serum and cells.WED not only decreased CD86 and iNOS expression but also increased CD206 and Arg-1 expression.WED also downregulated the increased expression of PI3K,AKT,p-PI3K,p-AKT,IKK,and NF-κB p65 induced by lipopolysaccharides,while up-regulated the decreased expression of IκB.Besides,LY294002 with WED decreased the expression of protein PI3K,AKT,p-PI3K,p-AKT,IKK and NF-κB p65,and raised the expression of IκBα.Conclusion:Wedelolactone could attenuate sepsis-associated acute liver injury,and its mechanism may be associated with balancing pro-inflammatory and anti-inflammatory by the regulation of M1/M2 macrophage polarization via the PI3K/AKT/NF-κB signaling pathway.

Cardioprotective effect of erythropoietin on sepsisinduced myocardial injury in rats

BACKGROUND:Sepsis-induced myocardial injury is one of the major predictors of morbidity and mortality of sepsis.The cytoprotective function of erythropoietin(EPO) has been discovered and extensively studied.However,the cardioprotective effects of EPO on sepsis-induced myocardial injury in the rat sepsis model has not been reported.METHODS:The rat models of sepsis were produced by cecal ligation and perforation(CLP)surgery.Rats were randomly(random number) assigned to one of three groups(n=8 for each group):sham group,CLP group and EPO group(1000 lU/kg erythropoietin).Arterial blood was withdrawn at3,6,12,and 24 hours after CLP.cTnl,BNP,CK-MB,LDH,AST,TNF-a,IL-6,IL-10,and CRP were tested by the ELISA assay.Changes of hemodynamic parameters were recorded at 3,6,12,24 hours after the surgery.Histological diagnosis was made by hematoxylin and eosin.Flow cytometry was performed to examine cell apoptosis,myocardium mitochondrial inner membrane potential,and NF-κB(p65).Survival rate at 7 days after CLP was recorded.RESULTS:In the CLP group,myocardial enzyme index and inflammatory index increased at3,6,12 and 24 hours after CLP compared with the sham group,and EPO significantly blocked the increase.Compared with the CLP group,EPO significantly improved LVSP,LV +dpldt_(max) LV-dp/dt_(min),and decreased LVEDP at different time.EPO blocked the reduction of mitochondrial transmembrane potential,suppressed the cardiomyocyte apoptosis,inhibited the activation of NF-κB,and reduced the production of proinflmmatory cytokines.No difference in the survival rate at 7 days was observed between the CLP group and the EPO group.CONCLUSION:Exogenous EPO has cardioprotective effects on sepsis-induced myocardial injury.

Heparanase inhibition leads to improvement in patients with acute gastrointestinal injuries induced by sepsis

BACKGROUND Patients with sepsis are at high risk for acute gastrointestinal injury(AGI),but the diagnosis and treatment of AGI due to sepsis are unsatisfactory.Heparanase(HPA)plays an important role in septic AGI(S-AGI),but its specific mechanism is not completely understood,and few clinical reports are available.AIM To explore the effect and mechanism of HPA inhibition in S-AGI patients.METHODS In our prospective clinical trial,48 patients with S-AGI were randomly assigned to a control group to receive conventional treatment,whereas 47 patients were randomly assigned to an intervention group to receive conventional treatment combined with low molecular weight heparin.AGI grade,sequential organ failure assessment score,acute physiology and chronic health evaluation II score,D-dimer,activated partial thromboplastin time(APTT),anti-Xa factor,interleukin-6,tumour necrosis factor-α,HPA,syndecan-1(SDC-1),LC3B(autophagy marker),intestinal fatty acid binding protein,D-lactate,motilin,gastrin,CD4/CD8,length of intensive care unit(ICU)stay,length of hospital stay and 28-d survival on the 1^(st),3^(rd) and 7^(th) d after treatment were compared.Correlations between HPA and AGI grading as well as LC3B were compared.Receiver operator characteristic(ROC)curves were generated to evaluate the diagnostic value of HPA,intestinal fatty acid binding protein and D-lactate in S-AGI.RESULTS Serum HPA and SCD-1 levels were significantly reduced in the intervention group compared with the control group(P<0.05).In addition,intestinal fatty acid-binding protein,D-lactate,AGI grade,motilin,and gastrin levels and sequential organ failure assessment score were significantly decreased(P<0.05)in the intervention group.However,LC3B,APTT,anti-Xa factor,and CD4/CD8 were significantly increased(P<0.05)in the intervention group.No significant differences in interleukin-6,tumour necrosis factor-α,d-dimer,acute physiology and chronic health evaluation II score,length of ICU stay,length of hospital stay,or 28-d survival were noted between the two groups(P>0.05).Correlation analysis revealed a significant negative correlation between HPA and LC3B and a significant positive correlation between HPA and AGI grade.ROC curve analysis showed that HPA had higher specificity and sensitivity in diagnosis of S-AGI.CONCLUSION HPA has great potential as a diagnostic marker for S-AGI.Inhibition of HPA activity reduces SDC-1 shedding and alleviates S-AGI symptoms.The inhibitory effect of HPA in gastrointestinal protection may be achieved by enhanced autophagy.

A pulmonary source of infection in patients with sepsis-associated acute kidney injury leads to a worse outcome and poor recovery of kidney function

BACKGROUND:Hospital mortality rates are higher among patients with sepsis-associated acute kidney injury(SA-AKI)than among patients with sepsis.However,the pathogenesis underlying SA-AKI remains unclear.We hypothesized that the source of infection affects development of SA-AKI.We aim to explore the relationship between the anatomical source of infection and outcome in patients with SA-AKI.METHODS:Between January 2013 and January 2018,113 patients with SA-AKI admitted to our Emergency Center were identifi ed and divided into two groups:those with pulmonary infections and those with other sources of infection.For each patient,we collected data from admission until either discharge or death.We also recorded the clinical outcome after 90 days for the discharged patients.RESULTS:The most common source of infection was the lung(52/113 cases,46%),followed by gastrointestinal(GI)(25/113 cases,22.1%)and urinary(22/113,19.5%)sources.Our analysis showed that patients with SA-AKI had a significantly worse outcome(30/52 cases,P<0.001)and poorer kidney recovery(P=0.015)with pulmonary sources of infection than those infected by another source.Data also showed that patients not infected by a pulmonary source more likely experienced shock(28/61 cases,P=0.037).CONCLUSION:This study demonstrated that the source of infection infl uenced the outcome of SA-AKI patients in an independent manner.Lung injury may influence renal function in an asyet undetermined manner as the recovery of kidney function was poorer in SA-AKI patients with a pulmonary source of infection.

Severity of acute gastrointestinal injury grade is a good predictor of mortality in critically ill patients with acute pancreatitis

BACKGROUND Gastrointestinal(GI)dysfunction is a common and important complication of acute pancreatitis(AP),especially in patients with severe AP.Despite this,there is no consensus means of obtaining a precise assessment of GI function.AIM To determine the association between acute gastrointestinal injury(AGI)grade and clinical outcomes in critically ill patients with AP.METHODS Patients with AP admitted to our pancreatic intensive care unit from May 2017 to May 2019 were enrolled.GI function was assessed according to the AGI grade proposed by the European Society of Intensive Care Medicine in 2012,which is mainly based on GI symptoms,intra-abdominal pressure,and feeding intolerance in the first week of admission to the intensive care unit.Multivariate logistic regression analysis was performed to assess the association between AGI grade and clinical outcomes in critically ill patients with AP.RESULTS Among the 286 patients included,the distribution of patients with various AGI grades was 34.62%with grade I,22.03%with grade II,32.52%with grade III,and 10.84%with grade IV.The distribution of mortality was 0%among those with grade I,6.35%among those with grade II,30.11%among those with grade III,and 61.29%among those with grade IV,and AGI grade was positively correlated with mortality(χ2=31.511,P<0.0001).Multivariate logistic regression analysis showed that age,serum calcium level,AGI grade,persistent renal failure,and persistent circulatory failure were independently associated with mortality.Compared with the Acute Physiology and Chronic Health Evaluation II score(area under the curve:0.739 vs 0.854;P<0.05)and Ranson score(area under the curve:0.72 vs 0.854;P<0.01),the AGI grade was more useful for predicting mortality.CONCLUSION AGI grade is useful for identifying the severity of GI dysfunction and can be used as a predictor of mortality in critically ill patients with AP.

Value of early diagnosis of sepsis complicated with acute kidney injury by renal contrast-enhanced ultrasound

BACKGROUND The incidence of acute kidney injury(AKI)in patients with sepsis is high,and the prognosis of patients with septic AKI is poor.The early diagnosis and treatment of septic AKI is of great significance in improving the prognosis of patients with sepsis.AIM To explore the value of contrast-enhanced ultrasound(CEUS),serum creatinine(Scr),and other indicators in the early diagnosis of septic AKI.METHODS Ninety patients with sepsis during hospitalization at Tongji Hospital of Tongji University were recruited as subjects.Each patient was recorded with relevant basic data,clinical indicators,and CEUS results.The patients were divided into AKI group and non-AKI group according to the results of renal function diagnosis after 48 h.On the 7th day,the renal function of the non-AKI group was re-evaluated and the patients were further divided into AKI subgroup and non-AKI subgroup.The differences of the indicators in different groups were compared,and the diagnostic value of each indicator and their combination for septic AKI was analyzed.RESULTS Systemic inflammatory response score(2.58±0.75),blood lactic acid(3.01±1.33 mmol/L),Scr(141.82±27.19μmol/L),blood urea nitrogen(4.41±0.81mmol/L),and rise time(10.23±2.63 s)in the AKI group were higher than those in the non-AKI group.Peak intensity(PI)(10.78±3.98 dB)and wash in slope(WIS)(1.07±0.53 dB/s)were lower than those in the non-AKI group.The differences were statistically significant(P<0.05).The PI(12.83±3.77 dB)and WIS(1.22±0.68 dB/s)in the AKI subgroup were lower than those in the non-AKI subgroup,and the differences were statistically significant(P<0.05).The area under curve(AUC)of Scr for the diagnosis of septic AKI was 0.825 with a sensitivity of 56.76% and a specificity of 100%.The AUCs of WIS and PI(0.928 and 0.912)were higher than those of Scr.Their sensitivities were 100%,but the specificities were 71.70% and 75.47%.The AUC of the combination of three indicators for the diagnosis of septic AKI was 0.943,which was significantly higher than the AUC diagnosed by each single indicator.The sensitivity was 94.59%,and the specificity was 81.13%.CONCLUSION The combination of Scr,PI,and WIS can improve the diagnostic accuracy of septic AKI.PI and WIS are expected to predict the occurrence of early septic AKI.

Effects of permissive hypocaloric vs standard enteral feeding on gastrointestinal function and outcomes in sepsis

BACKGROUND Intestinal mucosal barrier injury and gastrointestinal dysfunction are important causes of sepsis.However,few studies have investigated the effects of enteral underfeeding on gastrointestinal function in sepsis.Moreover,no consensus on goal enteral caloric intake has been reached in sepsis.AIM To investigate the effects of different goal caloric requirements of enteral nutrition on the gastrointestinal function and outcomes in the acute phase of sepsis.METHODS Patients were randomly assigned to receive 30%(defined as group A),60%(group B),or 100%(group C)of goal caloric requirements of enteral nutrition in this prospective pilot clinical trial.The acute gastrointestinal injury(AGI)grades,incidence of feeding intolerance(FI),daily caloric intake,nutritional and inflammatory markers,and biomarkers of mucosal barrier function were collected during the first 7 d of enteral feeding.The clinical severity and outcome variables were also recorded.RESULTS A total of 54 septic patients were enrolled.The days to goal calorie of group C(2.55±0.82)were significantly longer than those of group A(3.50±1.51;P=0.046)or B(4.85±1.68;P<0.001).The FI incidence of group C(16.5%)was higher than that of group A(5.0%)or B(8.7%)(P=0.009).No difference in the incidence of FI symptoms was found between groups A and B.The serum levels of barrier function biomarkers of group B were significantly lower than those of group A(P<0.05)on the 7th day of feeding.The prealbumin and IL-6 levels of group A were lower than those of group B(P<0.05)on the 7th day of feeding.No significant differences in the clinical outcome variables or 28-d mortality were found among the three groups.CONCLUSION Early moderate enteral underfeeding(60%of goal requirements)could improve the intestinal barrier function and nutritional and inflammatory status without increasing the incidence of FI symptoms in sepsis.However,further large-scale prospective clinical trials and animal studies are required to test our findings.Moreover,the effects of different protein intake on gastrointestinal function and outcomes should also be investigated in future work.

Epigenetic effects of ethanol on liver and gastrointestinal injury

Alcohol consumption causes cellular injury. Recent developments indicate that ethanol induces epigenetic alterations, particularly acetylation, methylation of histones, and hypo- and hypermethylation of DNA. This has opened up a new area of interest in ethanol research and is providing novel insight into actions of ethanol at the nucleosomal level in relation to gene expression and patho-physiological consequences. The epigenetic effects are mainly attributable to ethanol metabolic stress (Emess), generated by the oxidative and non-oxidative metabolism of ethanol, and dysregulation of methionine metabolism. Epigenetic changes are important in ethanol-induced hepatic steatosis, fibrosis, carcinoma and gastrointestinal injury. This editorial highlights these new advances and its future potential.

Acute gastrointestinal injury in critically ill patients with COVID-19 in Wuhan,China

BACKGROUND The coronavirus disease 2019(COVID-19)is spreading rapidly around the world.Most critically ill patients have organ injury,including acute respiratory distress syndrome,acute kidney injury,cardiac injury,or liver dysfunction.However,few studies on acute gastrointestinal injury(AGI)have been reported in critically ill patients with COVID-19.AIM To investigate the prevalence and outcomes of AGI in critically ill patients with COVID-19.METHODS In this retrospective study,demographic data,laboratory parameters,AGI grades,clinical severity and outcomes were collected.The primary endpoints were AGI incidence and 28-d mortality.RESULTS From February 10 to March 102020,83 critically ill patients out of 1314 patients with COVID-19 were enrolled.Seventy-two(86.7%)patients had AGI during hospital stay,of these patients,30 had AGI gradeⅠ,35 had AGI gradeⅡ,5 had AGI gradeⅢ,and 2 had AGI gradeⅣ.The incidence of AGI gradeⅡand above was 50.6%.Forty(48.2%)patients died within 28 days of admission.Multiple organ dysfunction syndrome developed in 58(69.9%)patients,and septic shock in 16(19.3%)patients.Patients with worse AGI grades had worse clinical variables,a higher incidence of septic shock and 28-d mortality.Sequential organ failure assessment(SOFA)scores(95%CI:1.374-2.860;P<0.001),white blood cell(WBC)counts(95%CI:1.037-1.379;P=0.014),and duration of mechanical ventilation(MV)(95%CI:1.020-1.340;P=0.025)were risk factors for the development of AGI gradeⅡand above.CONCLUSION The incidence of AGI was 86.7%,and hospital mortality was 48.2%in critically ill patients with COVID-19.SOFA scores,WBC counts,and duration of MV were risk factors for the development of AGI gradeⅡand above.Patients with worse AGI grades had a higher incidence of septic shock and 28-d mortality.

Poor awareness of preventing aspirin-induced gastrointestinal injury with combined protective medications

AIM:To investigate prescribing pattern in low-dose aspirin users and physician awareness of preventing aspirin-induced gastrointestinal(GI) injury with combined protective medications.METHODS:A retrospective drug utilization study was conducted in the 2nd Affiliated Hospital,School of Medicine,Zhejiang University.The hospital has 2300 beds and 2.5 million outpatient visits annually.Data mining was performed on all aspirin prescriptions for outpatients and emergency patients admitted in 2011.Concomitant use of proton-pump inhibitors(PPIs),histamine 2-receptor antagonists(H2RA) and mucoprotective drugs(MPs) were analyzed.A defined daily dose(DDD) methodology was applied to each MP.A further investigation was performed in aspirin users on combination use of GI injurious medicines [non-steoid anti-inflammatory drugs(NSAIDs),corticosteroids and clopidogrel and warfarin] or intestinal protective drugs(misoprostol,rebamipide,teprenone and gefarnate).Data of major bleeding episodes were derived from medical records and adverse drug reaction monitoring records.The annual incidence of major GI bleeding due to low-dose aspirin was estimated for outpatients.RESULTS:Prescriptions for aspirin users receiving PPIs,H2RA and MPs(n = 1039) accounted for only 3.46% of total aspirin prescriptions(n = 30 015).The ratios of coadministration of aspirin/PPI,aspirin/H2RA,aspirin/MP and aspirin/PPI/MP to the total aspirin prescriptions were 2.82%,0.12%,0.40% and 0.12%,respectively.No statistically significant difference was observed in age between patients not receiving any GI protective medications and patients receiving PPIs,H2RA or MPs.The combined medication of aspirin and PPI was used more frequently than that of aspirin and MPs(2.82% vs 0.40%,P < 0.05) and aspirin/H2RA(2.82% vs 0.12%,P < 0.05).The values of DDDs of MPs in descending order were as follows:gefarnate,hydrotalcite > teprenone > sucralfate oral suspension > L-glutamine and sodium gualenate granules > rebamipide > sucralfate chewable tablets.The ratio of MP plus aspirin prescriptions to the total MP prescriptions was as follows:rebamipide(0.47%),teprenone(0.91%),L-glutamine and sodium gualenate granules(0.92%),gefarnate(0.31%),hydrotalcite(1.00%) and sucralfate oral suspension(0.13%).Percentages of prescriptions containing aspirin and intestinal protective drugs among the total aspirin prescriptions were:rebamipide(0.010%),PPI/rebamipide(0.027%),teprenone(0.11%),PPI/teprenone(0.037%),gefarnate(0.017%),and PPI/gefarnate(0.013%).No prescriptions were found containing coadministration of aspirin and other NSAIDs.Among the 3196 prescriptions containing aspirin/clopidogrel,3088(96.6%) prescriptions did not contain any GI protective medicines.Of the 389 prescriptions containing aspirin/corticosteroids,236(60.7%) contained no GI protective medicines.None of the prescriptions using aspirin/warfarin(n = 22) contained GI protective medicines.Thirty-five patients were admitted to this hospital in 2011 because of acute hemorrhage of upper digestive tract induced by low-dose aspirin.The annual incidence rates of major GI bleeding were estimated at 0.25% for outpatients taking aspirin and 0.5% for outpatients taking aspirin/warfarin,respectively.CONCLUSION:The prescribing pattern of low-dose aspirin revealed a poor awareness of preventing GI injury with combined protective medications.Actions should be taken to address this issue.

Risk factors for postoperative sepsis in patients with gastrointestinal perforation

BACKGROUND Sepsis is fatal in patients with gastrointestinal perforation(GIP).However,few studies have focused on this issue.AIM To investigate the risk factors for postoperative sepsis in patients with GIP.METHODS This was a retrospective study performed at the Department of General Surgery in our treatment center.From January 2016 to December 2018,the medical records of patients with GIP who underwent emergency surgery were reviewed.Patients younger than 17 years or who did not undergo surgical treatment were excluded.The patients were divided into the postoperative sepsis group and the non-postoperative sepsis group.Clinical data for both groups were collected and compared,and the risk factors for postoperative sepsis were investigated.The institutional ethical committee of our hospital approved the study.RESULTS Two hundred twenty-six patients were admitted to our department with GIP.Fourteen patients were excluded:Four were under 17 years old,and 10 did not undergo emergency surgery due to high surgical risk and/or disagreement with the patients and their family members.Two hundred twelve patients were finally enrolled in the study;161 were men,and 51 were women.The average age was 62.98±15.65 years.Postoperative sepsis occurred in 48 cases.The prevalence of postoperative sepsis was 22.6%[95%confidence interval(CI):17.0%-28.3%].Twenty-eight patients(13.21%)died after emergency surgery.Multiple logistic regression analysis confirmed that the time interval from abdominal pain to emergency surgery[odds ratio(OR)=1.021,95%CI:1.005-1.038,P=0.006],colonic perforation(OR=2.761,CI:1.821–14.776,P=0.007),perforation diameter(OR=1.062,95%CI:1.007-1.121,P=0.027),and incidence of malignant tumorrelated perforation(OR=5.384,95%CI:1.762-32.844,P=0.021)were associated with postoperative sepsis.CONCLUSION The time interval from abdominal pain to surgery,colonic perforation,diameter of perforation,and the incidence of malignant tumor-related perforation were risk factors for postoperative sepsis in patients with GIP.

Endothelial cell injury with inflammatory cytokine and coagulation in patients with sepsis

BACKGROUND:Current studies on CD62 P have focused mainly on cardiovascular diseases,while only few studies have evaluated the effects of CD62 P on the development of sepsis and the association between endothelial cell injury with inflammation and coagulation.This study attended to explore the association between endothelial cell injury with inflammation and coagulation by evaluating the expression of soluble CD62P(s-CD62P) in plasma and its mechanism in patients with sepsis,thus to provide the evidence of effective treatment of sepsis with anti-adhesion therapy targeted CD62 P.METHODS:A total of 70 critically ill patients with systemic inflammatory response syndrome(SIRS) admitted to intensive care unit(ICU) between September 2009 and February 2010 were enrolled for a prospective and control study.According to the diagnostic criteria of sepsis/SIRS,the patients were divided into two groups:a sepsis group(n=38) and a SIRS group(n=32).Another 20 healthy volunteers served as a control group.Patients in the sepsis group and SIRS group were matched by clinical signs of high blood pressure,diabetes and its complications.The demographics of the patients including age,sex,body mass index(BMI),smoking and alcohol addict were compared among the groups.Six mL peripheral blood samples were collected within 24-hour admission in ICU for enzymelinked immunosorbent assay(ELISA) to detect the plasma levels of S-CD62 P,TNF-α,and hs-CRP.And variables of coagulation function such as platelet(PLT),prothrombin(PT),activated partial thromboplastin time(APTT),D-dimer and antithrombin-Ⅲ(AT-Ⅲ) were analyzed during 24 hours after admission to ICU.Meanwhile sequential organ failure assessment(SOFA) score of critically ill patients was evaluated.Data were expressed as meanistandard deviation and were statistically analyzed by using SPSS 17.0statistical software.The differences in plasma levels of S-CD62 P of patients in each group were analyzed by ANOVA and the Kruskal-Wallis test.The relations between S-CD62 P and inflammatory cytokines as well as with coagulation were determined by Pearson's product moment correlation coefficient analysis.Changes were considered as statistically significant if P value was less than 0.05.RESULTS:Compared with the control group and SIRS group,the sepsis group demonstrated significantly higher levels of S-CD62 P,TNF-a and highly sensitive C-reactive protein(hs-CRP)(PO.05).The plasma levels of D-dimer,PT,and APTT in the sepsis and SIRS groups were significantly higher than those in the control group,while the platelet count and the activity of AT-Ⅲ were obviously lower(P<0.05).In the sepsis group,the plasma levels of hs-CRP and TNF-a were positively correlated with PT,APTT,and D-dimer,and negatively correlated with AT-Ⅲ and PLT(P<0.05).The plasma levels of S-CD62 P were significantly correlated with the plasma levels of TNF-a,hs-CRP,D-dimer,PT,and APTT,whereas they were correlated negatively well with PLT and AT-Ⅲ(P<0.05).CONCLUSIONS:The concentration of plasma S-CD62 P is elevated as a early biomarker in patients with sepsis,and it serves as one of the pathogenic factors responsible for endothelial cell damage.Coagulation and mediators of inflammation promote each other,aggravating the severity of sepsis.Plasma S-CD62 P may be an important factor for the development of coagulation and inflammatory reaction.