Expert consensus on the monitoring and treatment of sepsis-induced immunosuppression

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

Clinical significance of peripheral blood immune cells in patients with gastric cancer after surgery

BACKGROUND Gastric cancer is one of the most common malignant tumors worldwide,and surgical resection is one of the main ways to treat gastric cancer.However,the immune status of postoperative patients is crucial for prognosis and survival,and immune cells play an important role in this process.Therefore,it is helpful to understand the immune status of postoperative patients by evaluating the levels of peripheral blood immune cells,especially total T cells(CD3+),helper T cells(CD3+CD4+),and suppressor T cells(CD3+CD8+),and its relationship to sur-vival.AIM To analyzed the immune cells in peripheral blood of patients with gastric cancer after surgery,detect the levels of total T cells,helper T cells and suppressor T cells.METHODS A total of 58 patients with gastric cancer who received surgical treatment were included in the retrospective study.Flow cytometry was used to detect the level of peripheral blood immune cells and analyze the correlation between total T cells,helper T cells and inhibitory T cells.To explore the relationship between these immune markers and patient survival.RESULTS The results showed that the levels of total T cells,helper T cells,and suppressor T cells changed in patients after gastric cancer surgery.There was a significant positive correlation between total T cells,helper T cells and suppressor T cells(r=0.35,P<0.01;r=0.56,P<0.01).However,there was a negative correlation between helper T cells and suppressor T cells(r=-0.63,P<0.01).Follow-up showed that the survival rate of patients in the high-level total T cell group was significantly higher than that in the low-level group(28.87±24.98 months vs 18.42±16.21 months).The survival curve shows that the curve of patients in the high-level group is shifted to the upper right,and that of the low-level group is shifted downward.There was no significant difference between the levels of helper T cells and suppressor T cells and patient survival time.CONCLUSION By detecting peripheral blood immune cells with flow cytometry,we can initially evaluate the immune status of patients after gastric cancer surgery and initially explore its relationship with patient survival.

Role of the clinical immunology laboratory in disease monitoring

Immunological investigations provide useful informa-tion to guide diagnosis of several disorders. Many such tests are also commonly repeated at intervals, in an effort to facilitate disease monitoring. In general how-ever, immunology test results are often slow to alter. Furthermore, audit activity has indicated that repeated testing accounts for a substantial workload in many immunology services, which may waste resources and compromise the effcient completion of necessary tests. Consequently, the need and appropriate mini-mum interval between repeated testing requires critical evaluation. In this review, the clinical utility of repeat-ed performance of several common immunology inves-tigations has been evaluated, based upon published evidence. In some cases （ e.g. , paraprotein quantifca-tion, or measurement of anti-glomerular basement membrane antibodies）, repeated testing provides vital clinical information and can be justifed on a frequent and individualized basis. However, many other investi-gations provided by immunology services provide less valuable information when used to aid disease moni-toring rather than diagnosis. It is hoped that the data summarized here will facilitate a more evidence-based approach to repeated testing. Such information may also assist with the local implementation of demand management strategies based upon setting of mini-mum retesting intervals for these investigations.

Sepsis-induced immunosuppression:mechanisms,diagnosis and current treatment options

Sepsis is a common complication of combat injuries and trauma,and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.It is also one of the significant causes of death and increased health care costs in modern intensive care units.The use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with sepsis.Although its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic death.Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis.It is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune checkpoints.By targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance.Here,we comprehensively discuss recent findings on the mechanisms,regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

Delayed introduction of immunosuppressive regimens in critically ill patients after liver transplantation

BACKGROUND: The manipulation of immunosuppression therapy remains challenging in patients who develop infectious diseases or multiple organ dysfunction after liver transplantation. We evaluated the outcomes of delayed introduction of immunosuppression in the patients after liver transplantation under immune monitoring with ImmuKnow assay. METHODS: From March 2009 to February 2014, 225 consecutive liver recipients in our institute were included. The delayed administration of immunosuppressive regimens was attempted in 11 liver recipients with multiple severe comorbidities. RESULTS: The median duration of non-immunosuppression was 12 days (range 5-58). Due to the infectious complications, the serial ImmuKnow assay showed a significantly low ATP level of 64 +/- 35 ng/mL in the early period after transplantation. With the development of comorbidities, the ImmuKnow value significantly increased. However, the acute allograft rejection developed when a continuous distinct elevation of both ATP and glutamyltranspeptidase levels was detected. The average ATP level measured just before the development of acute rejection was 271 +/- 115 ng/mL. CONCLUSIONS: The delayed introduction of immunosuppressive regimens is safe and effective in management of critically ill patients after liver transplantation. The serial ImmuKnow assay could provide a reliable depiction of the dynamics of functional immunity throughout the clinical course of a given patient.

Construction of regulatory network for alopecia areata progression and identification of immune monitoring genes based on multiple machine-learning algorithms

Objectives Alopecia areata(AA)is an autoimmune-related non-cicatricial alopecia,with complete alopecia(AT)or generalized alopecia(AU)as severe forms of AA.However,there are limitations in early identification of AA,and intervention of AA patients who may progress to severe AA will help to improve the incidence rate and prognosis of severe AA.Methods We obtained two AA-related datasets from the gene expression omnibus database,identified the differentially expressed genes(DEGs),and identified the module genes most related to severe AA through weighted gene co-expression network analysis.Functional enrichment analysis,construction of a protein–protein interaction network and competing endogenous RNA network,and immune cell infiltration analysis were performed to clarify the underlying biological mechanisms of severe AA.Subsequently,pivotal immune monitoring genes(IMGs)were screened through multiple machine-learning algorithms,and the diagnostic effectiveness of the pivotal IMGs was validated by receiver operating characteristic.Results A total of 150 severe AA-related DEGs were identified;the upregulated DEGs were mainly enriched in immune response,while the downregulated DEGs were mainly enriched in pathways related to hair cycle and skin development.Four IMGs(LGR5,SHISA2,HOXC13,and S100A3)with good diagnostic efficiency were obtained.As an important gene of hair follicle stem cells stemness,we verified in vivo that LGR5 downregulation may be an important link leading to severe AA.Conclusion Our findings provide a comprehensive understanding of the pathogenesis and underlying biological processes in patients with AA,and identification of four potential IMGs,which is helpful for the early diagnosis of severe AA.