Over-expression of programmed death-ligand 1 and programmed death-1 on antigen-presenting cells as a predictor of organ dysfunction and mortality during early sepsis: a prospective cohort study

BACKGROUND:This study aimed to explore the changes of programmed death-ligand 1(PDL1)and programmed death-1(PD-1)expression on antigen-presenting cells(APCs)and evaluate their association with organ failure and mortality during early sepsis.METHODS:In total,40 healthy controls and 198 patients with sepsis were included in this study.Peripheral blood was collected within the first 24 h after the diagnosis of sepsis.The expression of PDL1 and PD-1 was determined on APCs,such as B cells,monocytes,and dendritic cells(DCs),by flow cytometry.Cytokines in plasma,such as interferon-γ(IFN-γ),tumor necrosis factor-α(TNF-α),interleukin-4(IL-4),IL-6,IL-10,and IL-17A were determined by Luminex assay.RESULTS:PD-1 expression decreased significantly on B cells,monocytes,myeloid DCs(mDCs),and plasmacytoid DCs(pDCs)as the severity of sepsis increased.PD-1 expression was also markedly decreased in non-survivors compared with survivors.In contrast,PD-L1 expression was markedly higher on mDCs,pDCs,and monocytes in patients with sepsis than in healthy controls and in non-survivors than in survivors.The PD-L1 expression on APCs(monocytes and DCs)was weakly related to organ dysfunction and infl ammation.The area under the receiver operating characteristic curve(AUC)of the PD-1 percentage of monocytes(monocyte PD-1%)+APACHE II model(0.823)and monocyte PD-1%+SOFA model(0.816)had higher prognostic value than other parameters alone.Monocyte PD-1%was an independent risk factor for 28-day mortality.CONCLUSION:The severity of sepsis was correlated with PD-L1 or PD-1 over-expression on APCs.PD-L1 in monocytes and DCs was weakly correlated with infl ammation and organ dysfunction during early sepsis.The combination of SOFA or APACHE II scores with monocyte PD-1%could improve the prediction ability for mortality.

Changes in intestinal mucosal immune barrier in rats with endotoxemia

AIM:To investigate the dysfunction of the immunological barrier of the intestinal mucosa during endotox-emia and to elucidate the potential mechanism of this dysfunction.METHODS:Male Wistar rats were randomly distributed into two groups:control group and lipopolysaccharide(LPS)group.Endotoxemia was induced by a single caudal venous injection of LPS.Animals were sacrifi ced in batches 2,6,12 and 24 h after LPS infusion.The number of microfold(M)-cells,dendritic cells(DCs),CD4+ T cells,CD8+ T cells,regulatory T(Tr)cells and IgA+ B cells in the intestinal mucosa were counted after immunohistochemical staining.Apoptotic lympho-cytes were counted after TUNEL staining.The levels of interleukin(IL)-4,interferon(IFN)-γ and forkhead box P3(Foxp3)in mucosal homogenates were measured by ELISA.The secretory IgA(sIgA)content in the total protein of one milligram of small intestinal mucus was detected using a radioimmunological assay.RESULTS:This research demonstrated that LPS-induced endotoxemia results in small intestinal mucosa injury.The number of M-cells,DCs,CD8+ T cells,and IgA+ B cells were decreased while Tr cell and apoptotic lymphocyte numbers were increased signifi cantly.The number of CD4+ T cells increased in the early stages and then slightly decreased by 24 h.The level of IL-4 significantly increased in the early stages and then reversed by the end of the study period.The level of IFN-γ increased slightly in the early stages and then decreased markedly by the 24 h time point.Level of Foxp3 increased whereas sIgA level decreased.CONCLUSION:Mucosal immune dysfunction forms part of the intestinal barrier injury during endotoxemia.The increased number and function of Tr cells as well as lymphocyte apoptosis result in mucosal immunodefi ciency.

Japanese encephalitis following liver transplantation: A rare case report

BACKGROUND Japanese encephalitis(JE) is a serious public health concern with a high mortality rate in many Asian countries. For many years, JE virus(JEV) was considered the major cause of viral encephalitis in Asia. Although most JE cases are asymptomatic, the case fatality rate approaches 30%, and approximately 30%–50% of survivors have long-term neurological sequelae. To the best of our knowledge, JEV infection has never been reported following liver transplantation.CASE SUMMARY We report a case of a woman who underwent liver transplantation for autoimmune liver disease but presented with fever and neurological symptoms 13 d after transplantation. Magnetic resonance imaging revealed JEV infection,and positive immunoglobulin M antibody to JEV in blood and cerebrospinal fluid confirmed JE. The patient was treated with antiviral agents, immune regulation,and organ function support. No neurological sequelae were present after 1 year of follow-up.CONCLUSION Imaging and lumbar puncture examination should be performed as soon as possible in patients with fever and central nervous system symptoms after liver transplantation, and the possibility of atypical infection should be considered,which is helpful for early diagnosis and improved prognosis.

Successful treatment of gastrointestinal infection-induced septic shock using the oXiris■ hemofilter: A case report

BACKGROUND Septic shock leads to multiple organ failure,and bacterial endotoxins and endogenous cytokines play essential roles in the pathogenesis.The oXiris■hemofilter can efficiently adsorb endotoxins and cytokines.CASE SUMMARY We admitted a critically ill 59 year-old male patient with gastrointestinal septic shock due to infection by a Gram-negative bacterium and septic acute kidney injury(AKI).Prior to intensive care unit admission,the patient reported intermittent diarrhea and decreased urine output.His blood pressure was 70/40 mmHg,necessitating fluid resuscitation and large doses of noradrenaline.Based on the results of a blood culture and the presence of hypotension,oliguria,and hypoxemia,we diagnosed septic shock,AKI,and multiple organ dysfunction.We administered continuous renal replacement therapy(CRRT)with an oXiris■hemofilter for 72 h with intermittent continuous veno-venous hemodiafiltration(CVVHDF),and changed the filter every 12 h.After his hemodynamic parameters were stable,we used a traditional filter(AN69 hemofilter)with intermittent CVVHDF.The 72 h CRRT with the oXiris■hemofilter led to stabilization of his vital signs,marked reductions in disease severity scores,and decreased levels of procalcitonin,endotoxin,and inflammatory factors.After 8 d of CRRT,his kidney function had completely recovered.CONCLUSION We conclude that the oXiris■hemofilter combined with appropriate antibacterial therapy was an effective treatment for this patient with gastrointestinal septic shock.

Malaria-associated secondary hemophagocytic lymphohistiocytosis:A case report

BACKGROUND Malaria-associated secondary hemophagocytic lymphohistiocytosis(HLH)is rare.Moreover,the literature on malaria-associated HLH is sparse,and there are no similar cases reported in China.CASE SUMMARY We report the case of a 29-year-old woman with unexplained intermittent fever who was admitted to our hospital due to an unclear diagnosis.The patient concealed her history of travel to Nigeria before onset.We made a diagnosis of malaria-associated secondary HLH.The treatment strategy for this patient included treatment of the inciting factor(artemether for 9 d followed by artemisinin for 5 d),the use of immunosuppressants(steroids,intravenous immunoglobulin)and supportive care.The patient was discharged in normal physical condition after 25 d of intensive care.No relapses were documented on follow-up at six months and 1 year.CONCLUSION Early diagnosis of the primary disease along with timely intervention and a multidisciplinary approach can help patients achieve a satisfactory outcome.

Epidemiology of Sepsis-3 in a sub-district of Beijing: secondary analysis of a population-based database

Background: With the publication of Sepsis-3 definition, epidemiological data based on Sepsis-3 definition from middle-income countries including China are scarce, which prohibits understanding of the disease burden of this newly defined syndrome in these settings. The purpose of this study was to describe incidence and outcome of Sepsis-3 in Yuetan sub-district of Beijing and to estimate the incidence rate of Sepsis-3 in China. Methods: The medical records of all adult residents hospitalized from July 1, 2012 to June 30, 2014 in Yuetan sub-district of Beijing were reviewed. Patients with sepsis-3 and severe sepsis/septic shock were identified. The incidence rates and mortality rate of sepsis-3 and sepsis/septic shock were calculated, incidence rates and in-hospital mortality rates were normalized to the population distribution in the 2010 National Census. Population incidence rate and case fatality rate between sexes were compared with the Z test, as the data conformed to Poisson distribution. Results: Of the 21,191 hospitalized patients, 935 patients were diagnosed with Sepsis-3, and 498 cases met severe sepsis/septic shock criteria. The crude annual incidence rate of Sepsis-3 in Yuetan sub-district was 363 cases per 100,000 population, corresponding to standardized incidence rates of 236 cases per 100,000 population per year, respectively. The overall case fatality rate of Sepsis-3 was 32.0%, the crude population mortality rates of Sepsis-3 was 116 cases per 100,000 population per year, the standardized mortality rate was 67 cases per 100,000 population per year, corresponding to a speculative extrapolation of 700,437 deaths in China. The incidence rate and mortality rate of Sepsis-3 were significantly higher in males, elderly people, and patients with more comorbidities. The 62.1% of patients with Sepsis-3 had community-acquired infections, compared with 75.3% of infected patients without Sepsis-3 (P < 0.001). The most common infection in patients with Sepsis-3 was lower respiratory tract infection. When compared with patients with Sepsis-3, patients diagnosed as severe sepsis/septic shock were more likely to have higher case fatality rate (53.4% vs. 32.0%, P < 0.001) Conclusions: This study found the standardized incidence rate of 236 cases per 100,000 person-year for Sepsis-3, which was more common in males and elderly population. This corresponded to about 2.5 million new cases of Sepsis-3 per year, resulting in more than 700,000 deaths in China.

Lung-protective Ventilation in Patients with Brain Injury： A Multicenter Cross-sectional Study and Questionnaire Survey in China

Background： Over the years, the mechanical ventilation （MV） strategy has changed worldwide. The aim of the present study was to describe the ventilation practices, particularly lung-protective ventilation （LPV）, among brain-injured patients in China. Methods： This study was a multicenter, 1-day, cross-sectional study in 47 Intensive Care Units （ICUs） across China. Mechanically ventilated patients （18 years and older） with brain injury in a participating ICU during the time of the study, including traumatic brain injury, stroke, postoperation with intracranial tumor, hypoxic-ischemic encephalopathy, intracranial infection, and idiopathic epilepsy, were enrolled. Demographic data, primary diagnoses, indications for MV, MV modes and settings, and prognoses on the 60th day were collected. Multivariable logistic analysis was used to assess factors that might affect the use of LPV. Results： A total of 104 patients were enrolled in the present study, 87 （83.7%） of whom were identified with severe brain injury based on a Glasgow Coma Scale 〈8 points. Synchronized intermittent mandatory ventilation （SIMV） was the most frequent ventilator mode, accounting for 46.2% of the entire cohort. The median tidal volume was set to 8.0 ml/kg （interquartile range [IQR], 7.0-8.9 ml/kg） of the predicted body weight; 50 （48.1%） patients received LPV. The median positive end-expiratory pressure （PEEP） was set to 5 cmH20 （IQR, 5-5 cmH20）. No PEEP values were higher than 10 cmH20. Compared with partially mandatory ventilation, supportive and spontaneous ventilation practices were associated with LPV. There were no significant differences in mortality and MV duration between patients subjected to LPV and those were not. Conclusions： Among brain-injured patients in China, SIMV was the most frequent ventilation mode. Nearly one-half of the brain-injured patients received LPV. Patients under supportive and spontaneous ventilation were more likely to receive LPV.

Paeonol Improves Lipopolysaccharide-induced Microcirculatory Disturbance in Rat Mesentery

Objective: To investigate the effect of paeonol on lipopolysaccheride(LPS)-induced rat mesenteric microcirculatory dysfunctions.Methods: Male Wistar rats were randomly distributed into 5 groups(n=6 in each): Sham group, LPS group, paeonol group, paeonol+LPS group, and LPS+paeonol group. Endotoximia model was conducted by continuous LPS infusion. Changes in mesenteric microcirculatory variables, including diameter of venule, velocity of red blood cells in venule, leukocyte adhesion, free radicals produced in venule and albumin leakage from venule, were observed through an inverted intravital microscope. Meanwhile, the expression of myeloperoxidase(MPO), CD18,intercellular adhesion molecule-1(ICAM-1), toll-like receptor 4(TLR4), nuclear factor-kappa B p65 subunit(NF-κB p65), activator protein-1(AP-1), and Jun N-terminal kinase(JNK) was assessed by Western blot.Results: After infusion of LPS, the number of leukocytes adherent to venular wall, the intensity of dihydrorhodamine 123(DHR)fluorescence in the venular walls, and albumin leakage from venules were significantly increased, whereas the red blood cell velocity in venule was decreased. All the manifestations were significantly reduced by pre-treatment and post-treatment with paeonol. Moreover, paeonol significantly attenuated the expression of MPO, CD18, ICAM-1, TLR4, NF-κB p65, AP-1 and JNK in rat mesentery after LPS.Conclusions: The results demonstrated that paeonol could protect from and ameliorate the microcirculation disturbance induced by LPS.

Current status of China’s critical care medicine big data platform and future prospects

Overview The term“Big Data”originated at the 11th Electronic Materials Conference World Annual Conference,which originally referred to the large amount of data generated by the application of technology.[1]Medical big data includes not only the medical history and examination data accumulated during patient hospitalization,but also patient-related follow-up data,prognostic data from outpatient,emergency,and medical insurance settlement departments as well as clinical experiment centers.So far,it has profound applications in the various specialties of medicine.[2-4]However,intensive care medicine(ICU)is different from other medical fields.In comparison with clinical practice data,medical data in ICU have the following characteristics:large scale,rapid production,diverse dimensions,inaccuracies,heterogeneity,incompleteness,complexity,and privacy concerns.[5]In fact,in the process of constructing major ICU databases in China and worldwide,these databases have been optimized at great length.Taking heterogeneity as an example。