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Cardamonin from a medicinal herb protects against LPS-induced Septic shock by suppressing NLRP3 inflammasome

Acta Pharmaceutica Sinica B 2019年第4期9卷 734-744页

作者： Zhilei Wang Guang Xu Yuan Gao Xiaoyan Zhan Nan Qin Shubin Fu Ruisheng Li Ming Niu Jiabo Wang Youping Liu Xiaohe Xiao Zhaofang Bai School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu 611137China China Military Institute of Chinese Materia the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing 100029China School of Pharmacy Jiangxi University of Traditional Chinese MedicineNanchang 330004China Research Center for Clinical and Translational Medicine the Fifth Medical CentreChinese PLA General HospitalBeijing 100500China Integrative Medical Center the Fifth Medical CentreChinese PLA General HospitalBeijing 100039China

Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin(CDN), the major active ingredient of the traditional Chinese medicinal herb Alpinia katsumadai, has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-κB-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner.Importantly, CDN improves the survival of mice suffering from lethal Septic shock and attenuates IL-1βproduction induced by LPS in vivo, which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.

关键词： Cardamonin NLRP3 inflammasome IL-1β Caspase-1 Septic shock

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Levosimendan does not reduce the mortality of critically ill adult patients with sepsis and Septic shock: a meta-analysis

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Chinese Medical Journal 2019年第10期132卷 1212-1217页

作者： Fang Feng Yu Chen Min Li Jiao-Jiao Yuan Xue-Ni Chang Chen-Ming Dong Department of Intensive Care Unit Lanzhou University Second Hospital Lanzhou University Lanzhou Gansu 730030 China

Background: Previous studies on whether or not levosimendan improved the prognosis of patients with sepsis and Septic shock been inconsistent. We aimed to provide an updated analysis of the therapeutic value of levosimendan in adult patients with sepsis and Septic shock, in order to provide evidence-based medical evidence for its use. Methods: PubMed, Embase, Cochrane Library, Wanfang Data, and CNKI were searched until August 2018 without language restriction. Randomized controlled studies of levosimendan with either inotropic drugs or placebo for the treatment of sepsis or Septic shock were enrolled. The primary outcome was mortality, and cardiac index and serum lactate levels were the secondary outcomes. Results: A total of 20 randomized controlled studies were included in this meta-analysis, including 1467 patients, with 738 patients in the experimental group (levosimendan group) and 729 patients in the control group (other inotropic drugs or placebo). There were no significant differences in mortality between the levosimendan and control groups (fixed-effect relative risk [RR]= 0.90, 95% confidence interval [CI][0.79, 1.03], P = 0.13). Levosimendan increased the cardiac index (VMD [weighted mean difference]= 0.51, 95% CI [0.06, 0.95], P = 0.02);and serum lactate levels were lower (VMD =—1.04, 95% CI [—1.47,—0.60], PSeptic shock. Physicians should use levosimendan with caution in patients with sepsis and Septic shock.

关键词： Levosimendan Sepsis Septic shock Meta-analysis

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Effect of Shen-Fu Injection(参附注射液)on Hemodynamics in Early Volume Resuscitation Treated Septic Shock Patients

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Chinese Journal of Integrative Medicine 2019年第1期25卷 59-63页

作者： FAN Kai-liang WANG Jun-hui KONG Li ZHANG Fei-hu HAO Hao ZHAO Hao TIAN Zheng-yun YIN Ming-xin FANG Hua YANG Hui-hui LIU Yang Department of Emergency the Affiliated Hospital of Shandong University of Traditional Chinese Medicine First Clinical College Shandong University of Traditional Chinese Medicine

Objective: To investigate the hemodynamic effect of Shen-Fu Injection(参附注射液, SFI) in early volume resuscitation treated Septic shock patients by monitoring pulse indicator continuous cardiac output(PICCO). Methods: All Septic shock patients admitted in the Intensive Care Unit of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine from January 1 st, 2014 to December 31 th, 2015, were reviewed, and totally 65 were enrolled in this study. They were assigned to SFI group(33 cases) and control group(32 cases). All 65 patients underwent conventional treatment mainly including volume resuscitation, antibiotics and vasoactive drugs therapy. The patients of the SFI group received additional 100 mL of SFI intravenously every 12 h. In all 65 patients, the PICCO arterial catheter and vein catheter were implanted within 1 h after the diagnosis of Septic shock. In the course of early volume resuscitation, hemodynamic data of patients were recorded by PICCO monitor at 0, 12, and 24 h after the catheter implantation. Results: The hemodynamic indices of the two groups showed no significant differences at the beginning of 0 h(P>0.05). At 12 and 24 h, the hemodynamic indices of SFI group were significantly improved in comparison with the control group(P0.05). Conclusion: SFI significantly improved hemodynamic indices such as CI, GEDI, MAP and HR in early volume resuscitation treated Septic shock patients.

关键词： Septic shock hemodynamic Shen-Fu Injection Chinese medicine pulse indicator continuous cardiac output

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Central venous pressure value can assist in adjusting norepinephrine dosage after the initial resuscitation of Septic shock

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Chinese Medical Journal 2019年第10期132卷 1159-1165页

作者： Dong-Kai Li Wei Du Department of Critical Care Medicine Peking Union Medical College Hospital Peking Union Medical College Chinese Academy of Medical Sciences Beijing 100730 China

Background: New definitions for sepsis and Septic shock (Sepsis-3) were published, but the strategy to adjust vasopressors a initial guidelines is still unclear. We conducted a retrospective observational study to explore dosing strategy of norepinephrine (NE). Methods: A retrospective observational study in the 15-bed mixed intensive care unit of a tertiary care university hospital. The study was performed on Septic shock patients after 30 mL/kg fluid resuscitation and mean arterial pressure (MAP) levels reached >65 mmHg requiring NE. We divided patients into NE dosage increase and decrease groups, and collected hemodynamic and tissue perfusion parameters before (Tl) and after (T2) adjusting NE dosage. Results: In both NE increase and decrease groups, central venous pressure (CVP) and pressure difference between usual MAP and MAP (dMAP) at the T1 time point were associated with lactate clearance. In groups LC HM (CVP 10 mmHg, dMAP > 0 mmHg), decrease in NE dosage decreased lactate level, while in group HC LM (CVP >10 mmHg, dMAP Septic shock (Sepsis-3) resuscitated to reach the initial recovery target goals, combination of CVP and MAP refer to usual levels can help doctors make the next decision to make the correct choice of increase NE dosage or decrease NE dosage.

关键词： Septic shock Vasopressors Central venous pressure Hemodynamics

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Polymyxin B hemoperfusion as a feasible therapy after source control in abdominal Septic shock

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World Journal of Gastrointestinal Surgery 2019年第12期11卷 422-432页

作者： Jin Joo Kim Young Jun Park Ki Yoon Moon Jin Hyeong Park Yong Ki Jeong Eun Young Kim Division of Trauma and Surgical Critical Care Department of Surgery Seoul St. Mary’s Hospital College of Medicine The Catholic University of Korea

BACKGROUND Polymyxin B hemoperfusion(PMX-HP)has been used as a treatment for intraabdominal Septic shock by absorbing and removing endotoxins of gram-negative bacilli.AIM To investigate the clinical efficacy of PMX-HP in patients with gram-negative Septic shock who underwent abdominal surgery.METHODS From January 2012 to December 2018,patients who had Septic shock secondary to peritonitis were enrolled.They were classified into PMX-HP treated and control groups based on postopreative intervention using PMX-HP.The clinical outcomes were compared using 1:1 propensity score matching methods to balance the overall distribution between the two groups.RESULTS After propensity score matching,40 patients were analyzed(20 patients in the PMX group and 20 patients in the control group).The scores of total Sequential Organ Failure Assessment(SOFA)score,renal SOFA and coagulation SOFA were significantly improved in the PMX group but not in the control group.(from 11.2±5.8 to 4.7±3.5 in PMX group vs 10.0±4.0 to 8.7±7.3 in control group,P=0.047 from 2.6±1.0 to 0.7±1.0 in PMX group vs 2.6±1.5 to 2.8±1.6 in control group,P=0.000,from 1.6±1.5 to 1.3±1.3 in PMX group vs 1.2±1.2 to 2.8±1.8 in control group,P=0.014,respectively).Further,the length of intensive care unit(ICU)stay was significantly shorter in PMX group.However,no statistically significant difference was found in ICU mortality(50%in PMX group vs 50%in control group).CONCLUSION PMX-HP is a feasible adjunct treatment for peritonitis in ICU patients with peritonitis for improved organ impairment and to stabilize hemodynamics.It would be helpful to enhance clinical outcomes especially in patients with complete elimination of the source of gram-negative bacilli infection by surgical procedure accompanied with conventional treatment of sepsis.

关键词： Intraabdominal Septic shock Panperitonitis Polymyxin B hemoperfusion Sepsis Toraymyxin

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Resuscitation of Septic Patients with Target-and-endpoint Protocol:A Retrospective Study from a Chinese Tertiary Hospital ICU

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Chinese Medical Sciences Journal 2018年第3期33卷 135-142页

作者： Hongmin Zhang Xiaoting Wang Qing Zhang Dawei Liu Department of Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100730China

Objective To investigate the effect of target-and-endpoint protocol on the resuscitation of Septic patients.Methods This is a retrospective study performed at the Peking Union Medical College Hospital Intensive Care Unit.We enrolled 545 Septic patients who needed vasopressors on at least the first day of ICU admission.The general characteristics,blood lactate level,mean arterial pressure(MAP),central venous pressure(CVP)and saturation of central venous oxygen(ScvO2)at admission and 6,24 hours after admission were collected.The parameters at different time points were compared.Lactate clearance rate and in-hospital mortality were analyzed.Results The 6-hour lactate clearance rate was 21.6%(IQR,8.6%-39.0%),and in-hospital mortality was 9.4%.For patients with low CVP values(Septic shock patients in the ICU,the target values did not need to be within the“normal range”recommended by early-goal directed therapy.The“target-and-end

关键词： sepsis Septic shock lactate central venous pressure

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Advanced Septic arthritis of the shoulder treated by a two-stage arthroplasty

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World Journal of Orthopedics 2019年第10期10卷 356-363页

作者： Patrick Goetti Nicolas Gallusser Alexander Antoniadis Diane Wernly Frédéric Vauclair Olivier Borens Department of orthopedic surgery and traumatology Lausanne University Hospital and University of Lausanne

BACKGROUND The usual treatment of Septic shoulder arthritis consists of arthroscopic or open lavage and debridement.However,in patients with advanced osteoarthritic changes and/or massive rotator cuff tendon tears,infection eradication can be challenging to achieve and the functional outcome is often not satisfying even after successful infection eradication.In such cases a two-stage approach with initial resection of the native infected articular surfaces,implantation of a cement spacer before final treatment with a total shoulder arthroplasty in a second stage is gaining popularity in recent years with the data in literature however being still limited.AIM To evaluate the results of a short interval two-stage arthroplasty approach for Septic arthritis with concomitant advanced degenerative changes of the shoulder joint.METHODS We retrospectively included five consecutive patients over a five-year period and evaluated the therapeutic management and the clinical outcome assessed by disability of the arm,shoulder and hand(DASH)score and subjective shoulder value(SSV).All procedures were performed through a deltopectoral approach and consisted in a debridement and synovectomy,articular surface resection and insertion of a custom made antibiotic enriched cement spacer.Shoulder arthroplasty was performed in a second stage.RESULTS Mean age was 61 years(range,47-70 years).Four patients had previous surgeries ahead of the Septic arthritis.All patients had a surgical debridement ahead of the index procedure.Mean follow-up was 13 mo(range,6-24 mo).Persistent microbiological infection was confirmed in all five cases at the time of the first stage of the procedure.The shoulder arthroplasties were performed 6 to 12 wk after insertion of the antibiotic-loaded spacer.There were two hemi and three reverse shoulder arthroplasties.Infection was successfully eradicated in all patients.The clinical outcome was satisfactory with a mean DASH score and SSV of 18.4 points and 70%respectively.CONCLUSION Short interval two-stage approach

关键词： Septic arthritis Shoulder Arthroplasty Spacer Antibiotic Enriched Infection Native joint

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Ulcerative colitis complicated with colonic necrosis, Septic shock and venous thromboembolism: A case report

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World Journal of Clinical Cases 2019年第16期7卷 2360-2366页

作者： Ming-Yu Zhu Li-Qun Sun Critical Care Unit the Second Affiliated Hospital of Nanjing Medical University

BACKGROUND Severe total colonic necrosis,Septic shock and venous thromboembolism secondary to ulcerative colitis (UC) are rare and life-threatening.No such severe complications have been reported in the literature.CASE SUMMARY We report a 36-year-old woman who developed total colonic necrosis and Septic shock secondary to UC.The patient was treated with emergency surgery because computed tomography showed suspicious perforations.Persistent massive ascites occurred after operation and computed tomography angiography demonstrated portal vein,mesenteric vein and splenic vein thrombosis.The patient was discharged from hospital after active treatment.CONCLUSION Clinicians should pay attention to venous thrombosis,colonic necrosis and Septic shock in UC patients.Close observation of surgical indications and timely surgical intervention are the key to reduce mortality and complications in UC.

关键词： Ulcerative colitis Total colonic necrosis Venous thromboembolism Sepsis Septic shock Case report

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Pilot study of a novel serum mRNA gene panel for diagnosis of acute Septic arthritis

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World Journal of Orthopedics 2019年第12期10卷 424-433页

作者： Blake J Schultz Timothy Sweeney Malcolm R DeBaun Melissa Remmel Uros Midic Purvesh Khatri Michael J Gardner Department of Orthopedic Surgery Stanford UniversityRedwood CityCA 94063United States Inflammatix Inc863 Mitten RoadSuite 104BurlingameCA 94010United States Institute for Immunity Transplantation and InfectionsCenter for Biomedical ResearchDepartment of MedicineStanford UniversityStanfordRedwood CityCA 94305United States

BACKGROUND Septic arthritis is an orthopedic emergency requiring immediate surgical intervention.Current diagnostic standard of care is an invasive joint aspiration.Aspirations provide information about the inflammatory cells in the sample within a few hours,but there is often ambiguity about whether the source is infectious(e.***.bacterial)or non-infectious(e.***.gout).Cultures can take days to result,so decisions about surgery are often made with incomplete data.Novel diagnostics are thus needed.The“Sepsis MetaScore”(SMS)is an 11-mRNA host immune blood signature that can distinguish between infectious and noninfectious acute inflammation.It has been validated in multiple cohorts across heterogeneous clinical settings.AIM To study whether the SMS holds diagnostic validity in determining the etiology of acute arthritis.METHODS We conducted a blinded,prospective,non-interventional clinical study of the SMS.All patients undergoing work-up for a Septic primary joint were enrolled.Patients proceeded through the normal standard-of-care pathway,including joint aspiration and inflammatory labs[white blood cell(WBC),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP)].Venous blood was also drawn into PAX gene RNA-stabilizing tubes and mRNAs were measured using Nano String nCounter?.SMS was calculated blinded to clinical results.RESULTS A total of 20 samples were included,of which 11 were infected based on aspiration or intra-operative cultures.The SMS had an area under the ROC curve(AUROC)of 0.87 for separating infectious from non-infectious conditions.For comparison,the AUROCs for ESR=0.58,CRP=0.6,and WBC=0.59.At 100%sensitivity for infection,the specificity of the SMS was 40%,meaning nearly half of non-Septic patients could have been ruled out for further intervention.CONCLUSION In this pilot study,SMS showed a high level of diagnostic accuracy in predicting Septic joints compared to other diagnostic biomarkers.This quick blood test could be an important tool for early,accurate identification of acute Septic joints

关键词： Biomarkers Bioinformatics Infection Septic arthritis Medical technology Diagnostics

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Recurrent Septic Pulmonary Embolism Related to an Implanted Central Venous Access Port Device

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Chinese Medical Journal 2018年第24期131卷 3009-3011页

作者： Goohyeon Hong Youn Seup Kim Department of Internal Medicine Division of Pulmonary and Critical Care MedicineDankook University HospitalDankook University College of Medicine Cheonan 31116Korea

To the Editor:Septic pulmonary embolism (SPE)is a rare type of nonthrombotic pulmonary embolism,in which, emboli-containing pathogens and purulent material admixed with fibrin thrombus embolize to the pulmonary artery, causing pulmonary embolism with focal lung infection. Embolization from this complex results in stenosis and/or obstruction of small pulmonary vessels,which frequently causes pulmonary infection.SPE is usually associated with the use of infected central venous catheters and with endocarditis, Septic thrombophlebitis (including Lemierre's syndrome),and oropharyngeal infection. The use of central venous access port devices (CVAPDs)has increased rapidly worldwide because of their convenience and safety for patients who need repeated blood sampling or long-term continuous intravenous therapy such as chemotherapy,transfusion of blood products,fluid hydration,or parenteral nutrition.

关键词： Septic Pulmonary Embolism SPE

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