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immunomodulatory therapies for acute pancreatitis

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World Journal of Gastroenterology 2014年第45期20卷 16935-16947页

作者： Jing Li Wen-Juan Yang Lu-Ming Huang Cheng-Wei Tang Department of Gastroenterology West China Hospital Sichuan University Division of Peptides Related with Human Diseases Key Laboratory of Biotherapy of Human Diseases Ministry of Education

It is currently difficult for conventional treatments of acute pancreatitis (AP), which primarily consist of anti-inflammatory therapies, to prevent the progression of AP or to improve its outcome. This may be because the occurrence and progression of AP, which involves various inflammatory cells and cytokines, includes a series of complex immune events. Considering the complex immune system alterations during the course of AP, it is necessary to monitor the indicators related to immune cells and inflammatory mediators and to develop more individualized interventions for AP patients using immunomodulatory therapy. This review discusses the recent advances in immunomodulatory therapies. It has been suggested that overactive inflammatory responses should be inhibited and excessive immunosuppression should be avoided in the early stages of AP. The optimal duration of anti-inflammatory therapy may be shorter than previously expected (therapy of anti-inflammatory and immune-stimulating drugs would hopefully constitute an alternative to anti-inflammatory drug monotherapy. Additionally, the detection of the genotypes of critical inflammatory mediators may be useful for screening populations of AP patients at high risk of severe infections to enable the administration of early interventions to improve their prognosis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

关键词： Pancreatitis immunomodulatory therapy Systemic inflammatory response syndrome Immunosuppression Immunostimulation

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

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Military Medical Research 2023年第3期10卷 281-298页

作者： Fei Pei Ren‑Qi Yao Chao Ren Soheyl Bahrami Timothy RBilliar Irshad HChaudry De‑Chang Chen Xu‑Lin Chen Na Cui Xiang‑Ming Fang Yan Kang Wei‑Qin Li Wen‑Xiong Li Hua‑Ping Liang Hong‑Yuan Lin Ke‑Xuan Liu Ben Lu Zhong‑Qiu Lu Marc Maegele Tian‑Qing Peng You Shang Lei Su Bing‑Wei Sun Chang‑Song Wang Jian Wang Jiang‑Huai Wang Ping Wang Jian‑Feng Xie Li‑Xin Xie Li‑Na Zhang Basilia Zingarelli Xiang‑Dong Guan Jian‑Feng Wu Yong‑Ming Yao Department of Critical Care Medicine the First Affiliated Hospital of Sun Yat-Sen University58 Zhongshan Er RoadYuexiu DistrictGuangzhou 510080GuangdongChina Translational Medicine Research Center Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital28 Fuxing RoadHaidian DistrictBeijing 100853China Department of Burn Surgery the First Affiliated Hospital of Naval Medical UniversityShanghai 200433China Ludwig-Boltzmann Institute for Experimental and Clinical Traumatology 1200 ViennaAustria Department of Surgery University of Pittsburgh Medical CenterPittsburghPA 15213USA Center for Surgical Research and Department of Surgery University of Alabama at BirminghamBirminghamAL 35294USA Department of Critical Care Medicine Ruijin HospitalShanghai Jiaotong UniversityShanghai 200025China Department of Burns the First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of Critical Care Medicine Peking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China Department of Anesthesiology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 31003China Department of Critical Care Medicine West China Hospital of Sichuan UniversityChengdu 610041China Department of Critical Care Medicine General Hospital of Eastern Theater Command of Chinese PLANanjing 210002China Department of Surgical Intensive Critical Unit Beijing Chao‑Yang HospitalCapital Medical UniversityBeijing 100020China State Key Laboratory of Trauma Burns and Combined InjuryResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China Department of Critical Care Medicine Fourth Medical Center of the Chinese PLA General HospitalBeijing 100048China Department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Critical Care Medicine and Hematology the Third Xiangya HospitalCentral South UniversityChangs

Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of *** provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was *** 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 ***,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus *** 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 *** summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were ***,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 *** summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.

关键词： Sepsis Immune function monitoring immunomodulatory therapy Immunosuppression

Antioxidant and immunomodulatory effects of Viusid in patients with chronic hepatitis C

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World Journal of Gastroenterology 2010年第21期16卷 2638-2647页

作者： Eduardo Vilar Gomez Yadina Martinez Perez Hector Vega Sanchez Gretel Riveron Forment Enrique Arus Soler Luis Calzadilla Bertot Ali Yasells Garcia Maria del Rosario Abreu Vazquez Licet Gonzalez Fabian Department of Hepatology National Institute of GastroenterologyHavana 10400Cuba Department of Gastroenterology National Institute of GastroenterologyHavana 10400Cuba Department of Immunology National Institute of GastroenterologyHavana 10400Cuba Department of Oxidative Stress National Genetic CenterHavana 10400Cuba Department of Biostatistics National Institute of GastroenterologyHavana 10400Cuba Department of Pathology Institute of GastroenterologyHavana 10400Cuba

AIM:To investigate the efficacy of Viusid,a nutritional supplement,as an antioxidant and an immunomodulator in patients with chronic hepatitis ***:Sixty patients with chronic hepatitis C who were non-responders to standard antiviral treatment were randomly assigned to receive Viusid(3 sachets daily,n=30) or placebo(n=30) for 24 *** primary outcome was the change in serum malondialdehyde and 4-hydroxyalkenals(lipid peroxidation products).Secondary outcomes were changes in serum tumor necrosis factor-α(TNF-α),interferon-γ(IFN-γ) and interleukin-10(IL-10).RESULTS:Statistically significant reductions in serum 4-hydroxyalkenals and malondialdehyde levels were observed in both groups in comparison with pretreatment values,but the patients who received Viusid showed a more marked reduction as compared with the control group(P=0.001).TNF-α levels significantly increased from 6.9 to 16.2 pg/mL(P< 0.01) in the patients who received placebo in comparison with almost unchanged levels,from 6.6 to 7.1 pg/mL(P=0.26),in the patients treated with Viusid(P=0.001).In addition,IL-10 levels were markedly increased in the patients treated with Viusid(from 2.6 to 8.3 pg/mL,P=0.04) in contrast to the patients assigned to placebo(from 2.8 to 4.1 pg/mL,P=0.09)(P=0.01).Likewise,the administration of Viusid markedly increased mean IFN-γ levels from 1.92 to 2.89 pg/mL(P< 0.001) in comparison with a reduction in mean levels from 1.80 to 1.68 pg/mL(P=0.70) in the placebo group(P< 0.0001).Viusid administration was well ***:Our results indicate that treatment with Viusid leads to a notable improvement of oxidative stress and immunological parameters in patients with chronic hepatitis C.

关键词： Antioxidant therapy Chronic hepatitis C Cytokines immunomodulatory therapy Nutritional supplement Oxidative stress

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

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Military Medical Research 2023年第2期10卷 242-261页

作者： Di Liu Si-Yuan Huang Jian-Hui Sun Hua-Cai Zhang Qing-Li Cai Chu Gao Li Li Ju Cao Fang Xu Yong Zhou Cha-Xiang Guan Sheng-Wei Jin Jin Deng Xiang-Ming Fang Jian-Xin Jiang Ling Zeng Department of Trauma Medical Center Daping HospitalState Key Laboratory of TraumaBurns and Combined InjuryArmy Medical UniversityChongqing 400042China Department of Respiratory Disease Daping HospitalArmy Medical UniversityChongqing 400042China Department of Laboratory Medicine the First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Critical Care Medicine the First Affiliated Hospital of Chongqing Medical University400016 ChongqingChina Department of Physiology School of Basic Medicine ScienceCentral South UniversityChangsha 410078China Department of Anesthesia and Critical Care the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical UniversityZhejiang 325027 WenzhouChina Department of Emergency the Affiliated Hospital of Guizhou Medical UniversityGuizhou Medical University550001 GuiyangChina Department of Anesthesiology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310052China.

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 *** is also one of the significant causes of death and increased health care costs in modern intensive care *** use of antibiotics,fluid resuscitation,and organ support therapy have limited prognostic impact in patients with *** its pathophysiology remains elusive,immunosuppression is now recognized as one of the major causes of septic ***-induced immunosuppression is resulted from disruption of immune *** is characterized by the release of antiinflammatory cytokines,abnormal death of immune effector cells,hyperproliferation of immune suppressor cells,and expression of immune *** targeting immunosuppression,especially with immune checkpoint inhibitors,preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host ***,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.

关键词： Sepsis Immunosuppression Immune monitoring immunomodulatory therapy

Inflammatory bowel disease in liver transplanted patients

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World Journal of Gastroenterology 2017年第18期23卷 3214-3227页

作者： Tajana Filipec Kanizaj Maja Mijic Department of Gastroenterology University Hospital MerkurSchool of MedicineUniversity of Zagreb University Hospital Merkur

Most common hepatobiliary manifestation of inflammatory bowel disease(IBD) are primary sclerosing cholangitis(PSC) and autoimmune hepatitis, ranking them as the main cause of liver transplantation(LT) in IBD setting. Course of pre-existing IBD after LT differs depending on many transplant related factors. Potential risk factors related to IBD deterioration after LT are tacrolimus-based immunosuppressive regimens, active IBD and cessation of 5-aminosalicylates at the time of LT. About 30% patients experience improvement of IBD after LT, while approximately the same percentage of patients worsens. Occurrence of de novo IBD may develop in 14%-30% of patients with PSC. Recommended IBD therapy after LT is equivalent to recommendations to overall IBD patients. Antitumor necrosis factor alpha appears to be efficient for refractory IBD. Due to potential side effects it needs to be applied with caution. In average 9% of patients require proctocolectomy due to medically refractory IBD or colorectal carcinoma. The most frequent complication in patients who undergo proctocolectomy with ileal-pouch anal anastomosis is pouchitis. It is still undeterminable if LT adds to risk of developing pouchitis in PSC patients. Annual colonoscopies are recommended as surveillance and precaution of colonic malignancies.

关键词： Inflammatory bowel disease Anti-TNF alpha therapy Liver transplantation immunomodulatory therapy Immunosuppression Proctoproctocolectomy Risk factors

Diagnosis and treatment of autoimmune retinopathy

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Annals of Eye Science 2020年第3期5卷 56-68页

作者： Henry Lin David Dao H.Nida Sen Laboratory of Immunology National Eye InstituteNational Institutes of HealthBethesdaMarylandUSA

Autoimmune retinopathy(AIR)refers to both paraneoplastic and non-paraneoplastic forms of a rare,acquired retinal degeneration thought to be mediated by the production of antiretinal ***,the mechanisms underlying AIR pathogenesis are incompletely understood,and it remains a diagnosis of exclusion given the lack of definitive testing as well as its protean clinical *** review summarizes the current literature on the epidemiology,diagnosis,and management of AIR,with a focus on non-paraneoplastic disease and the potential role of immunomodulatory therapy.A recent expert consensus statement on diagnosis and management of non-paraneoplastic AIR served as a framework for interpreting the limited data available,a process that was complicated by the small sample sizes,heterogeneity,and retrospective nature of these *** work is needed to characterize AIR patients on the basis of cytokine and immunogenetic profiling;to establish the pathogenicity of antiretinal antibodies;and to standardize treatment regimens as well as assessment of clinical outcomes.

关键词： Autoimmune retinopathy(AIR) cancer-associated retinopathy melanoma-associated retinopathy immunomodulatory therapy

Update on the diagnosis and treatment of Vogt-Koyanagi-Harada syndrome

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Annals of Eye Science 2020年第3期5卷 5-10页

作者： Ghazala A.Datoo O’Keefe Department of Ophthalmology Emory University School of MedicineSection of Vitreoretinal Surgery and DiseasesSection of Uveitis and VasculitisAtlantaGeorgiaUSA

Vogt-Koyanagi-Harada syndrome(VKH)is a bilateral granulomatous panuveitis associated with serous retinal detachments and vitritis,and can be associated with extraocular manifestations of meningismus,poliosis,vitiligo,hearing loss,and *** is mediated by CD4+T cells that target melanocytes in the eye,ear,meninges,and *** classically presents in 4 different phases:prodromal,uveitic,convalescent,and *** have been considerable advances in our understanding of the disease in recent years,and options for treatment have also expanded beyond systemic corticosteroids though these remain the mainstay of therapy in patients with *** brief review will focus on updates in the diagnosis and treatment of VKH,specifically advances in imaging techniques including the use of optical coherence tomography angiography(OCTA)and enhanced depth imaging(EDI)optical coherence tomography(OCT).OCT parameters that are diagnostically predictive of acute VKH compared to other exudative maculopathies include the presence of subretinal membranous structures,a high retinal detachment,subretinal hyperreflective dots,and RPE *** of choroidal thickness using EDI-OCT demonstrate predominant involvement of the outer choroid in the acute inflammatory phase of VKH,consistent with histopathological *** may emerge as an alternative to fluorescein angiography(FA)and indocyanine angiography(ICGA)but is limited at this time due to its small field of *** the mainstay of treatment of acute VKH continues to be systemic corticosteroids,biological response modifiers(BRMs)such as adalimumab and infliximab have been shown to be effective in the management of adult and pediatric VKH with one benefit being a faster onset of action compared to conventional *** Search:A literature search was done in PubMed using the words“Vogt Koyanagi Harada”“imaging”“diagnosis”“treatment”“therapy“posterior uveitis”.

关键词： Vogt-Koyanagi Harada posterior uveitis imaging immunomodulatory therapy optical coherence tomography

Treatment of patients with severe sepsis using Ulinastatin and Thymosin al： a prospective, randomized, controlled pilot study

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Chinese Medical Journal 2009年第8期122卷 883-888页

作者： CHEN Hao HE Ming-yan LI Yu-min The Key Laboratory of Organ Transplantation of Public Health Ministry First Affiliated Hospital College of Medicine Zhejiang University Hangzhou Zhejiang 310003 China Department of General Surgery First Hospital of Lanzhou University Lanzhou Gansu 730000 China Department of General Surgery Second Hospital of Lanzhou University Lanzhou Gansu 730000 China

Background Tradition treatment of sepsis and new therapies, including high dose corticosteroids and non-steroidal anti-inflammatory drugs, have proven unsuccessful in improving survival. This study aimed to evaluate the potential efficacy of immunomodulating therapy using Ulinastatin （UTI） plus Thymosin al （Tal） for improving organ function and reducing mortality in patients with severe sepsis. Methods A prospective study was carried out with randomized and controlled clinical analysis of 114 patients conforming to the enrollment standard. All patients had severe sepsis and received standard supportive care and antimicrobial therapy. Fifty-nine patients were also administered UTI plus Tal （defined as Group A）, 55 patients were given a placebo （defined as Group B）. Clinical parameters were determined by evaluation with the Acute Physiology and Chronic Health Evaluation II （APACHE II）, multiple organ failure （MOF） and the Glasgow Coma Scores （GCS） on entry and after therapy on the 3rd, 8th, and 28th day. By flow cytometery and ELISA lymphocyte subsets and cytokines were analyzed. Survival analysis was determined by the Kaplan-Meier method at 28, 60, and 90 days. Results Based on comparison of the two groups, patients in Group A exhibited a better performance in organ failure scores which was noticeable soon after initiation of treatment. Patients in Group A also demonstrated a better resolution of pre-existing organ failures during the observation period. After initiation of treatment, significant improvements in the CD4^＋/CD8^＋ ratio, a quicker balance between proinflammatory mediators such as tumor necrosis factor a, interleukin 6 and anti-inflammatory cytokines including interleukin 4 and interleukin 10 were found. This was followed by cumulative survival increases of 17.3% at 28 days, 28.9% at 60 days, and 31.4% at 90 days in Group A. The reduction in mortality was accompanied by a considerably shorter stay in the ICU and a shorter length of supportive ventilation

关键词： Ulinastatin Thymosinal severe sepsis immunomodulatory therapy

Non-paraneoplastic Anti-NMDAR Encephalitis： First Confirmed Adult Case Report in Latvia

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Journal of Pharmacy and Pharmacology 2018年第2期6卷 123-129页

作者： Dace Ziemele Marija Litvi,nenko Guntis Karelis Viktorij a Kenina Lana Vainsteine Marite Karlovska Post-graduate Faculty Riga Stradins University Riga L V-1007 Latvia Faculty of Medicine Riga Stradins University Riga L V-1007 Latvia Department of Neurology Riga East Clinical University Hospital Riga L V-1038 Latvia

Anti-NMDAR （Anti-N-Methyl-D-aspartic acid） encephalitis is a rare autoimmune condition mainly affecting young women. It is associated with an underlying tumor in about 50% of reported cases. Antibodies directed against the GIuN1 subunit of the NMDA receptor are responsible for the disease pathogenesis and their detection in the patient＇s serum and cerebrospinal fluid are required to make a definite diagnosis. Classical clinical presentation consists of flu-like symptoms, followed by psychiatric disturbances and impaired consciousness, epileptic seizures and movement disorders. During the past decade, it has become an emerging area of research and discussion as more than 1,000 cases have been reported since the first description of this specific disease entity in 2007. Despite a rather typical clinical course it is frequently diagnosed and treated with a delay up to many months. Overall prognosis tends to be favorable. However, it strongly depends on early diagnosis and rapid treatment initiation. While diagnostic criteria for probable and definite anti-NMDAR encephalitis have been proposed, there are no evidence based guidelines for specific treatment strategies. Glucocorticoids, plasma exchange and IVIG are generally used as 1 st line treatment, in patients who do not respond, 2nd line treatment with Cyclophosphamide or Rituximab is used. We report a case of a confirmed non-paraneoplastic anti-NMDAR encephalitis with a rather classical manifestation in a Latvian woman who is first hospitalized in a psychiatric clinic then transferred to an ICU （intensive care unit）, treated with glucocorticoids, plasma exchange and later Cyclophosphamide with a good outcome.

关键词： Anti-NMDAR encephalitis non-paraneoplastic psychosis immunomodulatory therapy Cyclophosphamide.