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Efficacy of 6-mercaptopurine treatment after azathioprine hypersensitivity in inflammatory bowel disease

World Journal of Gastroenterology 2008年第27期14卷 4342-4346页

作者： Ferenc Nagy Tamás Molnár Zoltán Szepes Klaudia Farkas Tibor Nyári János Lonovics First Department of Medicine University of Szeged Faculty of Medicine Institute of Medical Informatics University of Szeged Faculty of Medicine

AIM:To investigate the efficacy of 6-mercaptopurine (6-MP) in cases of azathioprine (AZA) hypersensitivity in patients with inflammatory bowel disease. METHODS: Twenty nine previously confirmed Crohn’s disease (CD) (n = 14) and ulcerative colitis (UC) (n = 15) patients with a known previous (AZA) hypersensitivity reaction were studied prospectively. The 6-MP doses were gradually increased from 0.5 up to 1.0-1.5 mg/kg per day. Clinical activity indicies (CDAI/CAI), laboratory variables and daily doses of oral 5-ASA, corticosteroids, and 6-MP were assessed before and in the first, sixth and twelfth months of treatment. RESULTS: In 9 patients, 6-MP was withdrawn in the first 2 wk due to an early hypersensitivity reaction. Medication was ineffective within 6 mo in 6 CD patients, and myelotoxic reaction was observed in two. Data were evaluated at the end of the sixth month in 12 (8 UC, 4 CD) patients, and after the first year in 9 (6 UC, 3 CD) patients. CDAI decreased transiently at the end of the sixth month, but no significant changes were observed in the CDAI or the CAI values at the end of the year. Leukocyte counts (P = 0.01), CRP (P = 0.02), and serum iron (P = 0.05) values indicated decreased inflammatory reactions, especially in the UC patients at the end of the year, making the possibility to taper oral steroid doses. CONCLUSION: About one-third of the previously AZA- intolerant patients showed adverse effects on taking 6MP. In our series, 20 patients tolerated 6MP, but it was ineffective in 8 CD cases, and valuable mainly in ulcerative colitis patients.

关键词： Inflammatory bowel disease Azathioprine 6-mercaptopurine side effects Efficacy

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Efficacy of one-day quadruple therapy for H pylori infection in Chinese patients

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World Journal of Gastroenterology 2006年第19期12卷 3105-3107页

作者： Xiao-Hui Huo Jian-Kun Chu Xiu-Fen Yang Jing Wang Li-Jing Zhang Jin-Cheng Ma Jun Yu Department of Gastroenterology First Affiliated Hospital of Hebei Medical University Shijiazhuang Hebei Province China Department of Medicine and Therapeutics Prince of Wales Hospital Chinese University of Hong Kong Hong Kong China

AIM： TO compare the efficacies of one-day quadruple therapy and seven-day triple therapy in Chinese patients. METHODS： Sixty consecutive patients with nonulcer dyspepsia and confirmed H pylori infection were randomized to receive either omeprazole 40 mg, amoxycillin 1 g, and furazolidone 100 mg, all twice a day for 7 d or omeprazole 20 mg （at breakfast and dinner）, amoxicillin 1 g, furazolidone 200 mg, and colloidal bismuth subcitrate 220 mg four times for only one day. H pylori status was determined before and at least 5 weeks after therapy by endoscopy with antral and corpus biopsies for rapid urease test and histology. RESULTS： Hpyloi eradication was successful in 66.67% （20/30） patients in the 7-d group and in 36.67% （11/30） patients in the 1-day group （P = 0.037）. side effects were induced by the treatment in 13.3% （4/30） patients of each group, but these were all self-limiting, shortlasting, and did not require any specific treatment. CONCLUSION： The one-day quadruple therapy is less effective than the one-week regimen in curing H pylori infection in Chinese patients.

关键词： H pylori Quadruple therapy Antibiotics Gastritis side effects

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Sirolimus-induced drug fever and ciclosporin-induced leukencephalopathia with seizures in one liver transplant recipient

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World Journal of Gastroenterology 2007年第45期13卷 6090-6093页

作者： Doris Schacherer Martina Zeitoun Roland Büttner Cornelia Gelbmann Aiman Obed Hans-Jürgen Schlitt Jürgen Schlmerich Gabi I Kirchner Department of Internal MedicineⅠ University of Regensburg Regensburg 93042 Germany Department of Surgery University of Regensburg Regensburg 93042 Germany

We describe the first case of sirolimus-induced drug fever in a female liver transplant recipient, with a history of hepatitis C-induced end-stage liver cirrhosis in 1999. In 2005, six years after transplantation, she developed calcineurin inhibitor-induced renal function impairment. Immunosuppression was switched from tacrolimus to sirolimus. Two days after the intake of sirolimus, she developed daily fever spikes, but no infectious focus was found. Antibiotic therapy had no influence on the fever. After fourteen days, sirolimus was switched back to tacrolimus and the fever disappeared. In history, the patient developed ciclosporin-induced generalized seizures eleven days after liver transplantation, followed by the development of a motoric speech disorder. Magnetic resonance imaging (MRI) findings were consistent with leucoencephalopathy, therefore immunosuppressive therapy was changed from ciclosporin to tacrolimus and the neurologic symptoms improved significantly. Our case is the first reported case of sirolimus-induced drug fever. In addition, the patient showed the rare occurrence of ciclosporin-induced leukencephalopathy with seizures.

关键词： Liver transplantation Immunosuppression side effects

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On tolerability and safety of a maintenance treatment with 6-thioguanine in azathioprineor 6-mercaptopurine intolerant IBD patients

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World Journal of Gastroenterology 2005年第35期11卷 5540-5544页

作者： Nanne KH de Boer Luc JJ Derijks Lennard PL Gilissen Daniel W Hommes Leopold GJB Engels Sybrand Y de Boer Gijsbertus den Hartog Piet M Hooymans Anja BU M(?)kelburg Barend D Westerveld Anton HJ Naber Chris JJ Mulder Dirk J de Jong Department of Gastroenterology and Hepatology VU University Medical Centre Amsterdam The Netherlands Department of Clinical Pharmacy Maxima Medical Centre Veldhoven The Netherlands Department of Gastroenterology and Hepatology Academic Hospital Maastricht The Netherlands Department of Gastroenterology and Hepatology Academic Medical Centre Amsterdam The Netherlands Department of Gastroenterology and Hepatology Maasland Hospital Sittard The Netherlands Department of Gastroenterology and Hepatology Rijnstate Hospital Arnhem The Netherlands Department of Clinical Pharmacy Maasland Hospital Sittard The Netherlands Department of Gastroenterology and Hepatology Isala Clinics Location Sophia Zwolle The Netherlands Department of Gastroenterology and Hepatology Radboud University Nijmegen Medical Centre The Netherlands

AIM: To determine the tolerability and safety profile of a low-dose maintenance therapy with 6-TG in azathioprine (AZA) or 6-mercaptopurine (6-MP) intolerant inflammatory bowel disease (IBD) patients over a treatment period of at least 1 ***: Database ***: Twenty out of ninety-five (21%) patients discontinued 6-TG (mean dose 24.6 mg; mean 6-TGN level 540 pmol/8×108 RBC) within 1 year. Reasons for discontinuation were GI complaints (31%), malaise (15%)and hepatotoxicity (15%). Hematological events occurred in three patients, one discontinued treatment. In the 6-TG-tolerant group, 9% (7/75) could be classified as hepatotoxicity. An abdominal ultrasound was performed in 54% of patients, one patient had ***: The majority of AZA or 6-MP-intolerant IBD patients (79%) is able to tolerate maintenance treatment with 6-TG (dosages between 0.3 and 0.4 mg/kg per d). 6-TG may still be considered as an escape maintenance immunosuppressant in this difficult to treat group of patients, taking into account potential toxicity and efficacy of other alternatives. The recently reported hepatotoxicity is worrisome and 6-TG should therefore be administered only in prospective trials.

关键词： 6-Thioguanine Azathioprine 6-Mercaptopurine Crohn's disease Ulcerative colitis side effects Tolerance Safety

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Steroid elimination within 24 hours after orthotopic liver transplantation:effectiveness and tolerability

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Hepatobiliary & Pancreatic Diseases International 2012年第2期11卷 137-142页

作者： Lin-Wei Wu,Zhi-Yong Guo,Qiang Tai,Wei-Qiang Ju,Dong-Ping Wang,An-Bin Hu,Xiao-Feng Zhu and Xiao-Shun He Organ Transplantation Center, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China Organ Transplantation Center First Affiliated Hospital Sun Yat-Sen University Guangzhou 510080 China Guangzhou China

BACKGROUND:Steroids have been the mainstay of immunosuppressive regimen in liver ***,the use of steroids is associated with various post-transplant *** study evaluated the efficacy and safety of reduced immunosuppressive regimen with steroids(steroid elimination within 24 hours post-transplant) in a cohort of Chinese liver transplant ***:Seventy-six patients in line with the selection criteria were enrolled in this prospective *** patients received anti-IL-2 receptor antibody induction and tacrolimusbased maintenance *** recipients were divided into two groups according to the duration of steroid use:40 transplant in a 3-month withdrawal group and the remaining 36 in a 24-hour elimination *** survival,postoperative infections,biopsy-proven acute rejection and steroidresistant acute rejection,non-healing wound,recurrence of hepatitis B virus(HBV) and hepatocellular carcinoma(HCC),de novo diabetes,hyperlipidemia and hypertension were assessed in the two ***:There was no significant difference in patient survival,incidence of acute rejection episodes and hyperlipidemia,and recurrence of HBV and HCC between the two ***,the incidence rates of post-transplant infection,non-healing wound,de novo diabetes and hypertension were significantly lower in the 24-hour elimination group than in the 3-month withdrawal group(all P values <0.05).CONCLUSION:Under anti-IL-2 receptor antibody induction and tacrolimus-based maintainance,steroid elimination within 24 hours post-transplant is associated with reduced steroidrelated complications without increasing the risk of rejection.

关键词： liver transplantation immunosuppression steroid side effects

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The development prospection of HDAC inhibitors as a potential therapeutic direction in Alzheimer’s disease

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Translational Neurodegeneration 2017年第1期6卷 181-186页

作者： Shuang-shuang Yang Rui Zhang Gang Wang Yong-fang Zhang Department of Pharmacology Institute of Medical SciencesSchool of MedicineShanghai Jiao Tong University280 South Chongqing RoadShanghai 200025China Department of Neurology Ruijin Hospital School of MedicineShanghai Jiao Tong UniversityRuijin 2nd Road 197Shanghai 200025China

Alzheimer’s disease(AD)is a chronic neurodegenerative disease,which is associated with learning and memory impairment in the *** studies have found that treating AD in the way of chromatin remodeling via histone acetylation is a promising therapeutic *** a number of recent studies,inhibitors of histone deacetylase(HDACs)have been found to be a novel promising therapeutic agents for neurological disorders,particularly for AD and other neurodegenerative *** HDAC inhibitors have the ability to ameliorate cognitive impairment,successful treatments in the classic AD animal model are rarely translated into clinical *** for the reduction of unwanted side effects,the development of HDAC inhibitors with increased isoform selectivity or seeking other directions is a key issue that needs to be *** review focused on literatures on epigenetic mechanisms in recent years,especially on histone acetylation in terms of the enhancement of specificity,efficacy and avoiding side effects for treating AD.

关键词： Histone deacetylase inhibitors Alzheimer’s disease side effects Specificity Efficacy

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Azathioprine monotherapy withdrawal in inflammatory bowel diseases: A retrospective mono-centric study

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World Journal of Gastroenterology 2023年第27期29卷 4334-4343页

作者： Martina Crepaldi Daria Maniero Alessandro Massano Margherita Pavanato Brigida Barberio Edoardo Vincenzo Savarino Fabiana Zingone Department of Surgery Oncologyand GastroenterologyUniversity of PaduaPadua 35128Italy

BACKGROUND There is no consensus on the recommended duration of and optimal time to stop azathioprine(AZA)therapy in inflammatory bowel disease(IBD).Determining the optimal duration and cessation time can help to balance the risks of long-term intake with the possibility of relapse after *** To describe the events following AZA *** Retrospective analysis was performed to examine data from adult patients affected by IBD who were followed at the University of Padua and had started but then discontinued AZA between 1995 and *** on therapy duration,reasons for cessation,and type of relapse after cessation were *** regression models were used to estimate the risk of relapse in different *** A total of 133 ulcerative colitis patients and 141 Crohn’s disease patients were *** with AZA was stopped in the 1st year in approximately 34%of patients but was continued for more than 10 years in approximately 10%of *** discontinuation was due to primary failure or disease relapse in 30%of patients and due to disease remission in 25.2%of *** of the remaining cases stopped AZA therapy due to side effects(primarily clinical intolerance,cytopenia,and pancreatic disease).Patients who stopped AZA for clinical remission had an 83%lower risk of relapse during the observation time than other groups,with a relapse-free rate of 89%after 1 year and 79%after 2 *** AZA administration is effective and safe,but it requires careful monitoring for potential minor and major side *** 10%of patients who achieved remission with AZA needed a new treatment within 1 year of drug interruption.

关键词： Azathioprine Inflammatory bowel diseases Ulcerative Colitis Crohn's Disease Relapse side effects

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Comparative risk of acute kidney injury among cancer patients treated with immune checkpoint inhibitors

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Cancer Communications 2023年第2期43卷 214-224页

作者： Fei Liu ZixianWang Xiaofan Li Zhen Zhang Yue Yang Junquan Chen Dinghua Chen Lingling Wu Xiangyu Liu Sujun Han Fangming Wang Wasilijiang Wahafu Yibo Gao Shancheng Ren Nianzeng Xing Guangyan Cai Xiangmei Chen Department of Urology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Laboratory of Translational Medicine National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Department of Medical Oncology Sun Yat-sen University Cancer CenterGuangzhouGuangdongP.R.China Department of Nephrology First Medical Center of Chinese PLA General HospitalNephrology Institute of the Chinese People’s Liberation ArmyState Key Laboratory of Kidney DiseasesNational Clinical Research Center for Kidney DiseasesBeijing Key Laboratory of Kidney Disease ResearchBeijingP.R.China Department of Plastic Surgery Plastic Surgery HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijingPR China State Key Laboratory of Molecular Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Central Laboratory National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenGuangdongP.R.China Department of Urology Shanghai Changzheng HospitalShanghaiP.R.China

With the development and introduction of immune checkpoint inhibitors(ICIs)in cancer patients,immune-related side effects have increasingly attracted ***,the risks of immune-related renal toxicity are poorly *** this study,we performed a network meta-analysis(NMA)of ICI-related randomized clinical trials(RCTs)to elucidate the comparative risk of acute kidney injury(AKI)in cancer patients receiving different *** also sought to identify other factors potentially affecting the risk of *** and EMBASE were searched for peer-reviewed trial reports published between January 2000 and May *** studies were RCTs studying ICIs in cancer patients and reporting AKI *** performed a frequentist NMA to evaluate the risk ratios for grade 1-5 and grade 3-5 AKI between the treatment *** also assessed the absolute incidence of AKI in the ICI-containing arm using traditional direct *** significant heterogeneity was detected in a traditional direct meta-analysis,multivariable meta-regression analysis was applied to identify factors that significantly affected the absolute incidence of AKI.A total of 85 RCTs were included in this *** the NMA for the risk of grade 1-5 and 3-5 AKI,ipilimumab showed a significantly higher risk than avelumab and durvalumab,whereas 1 mg/kg nivolumab plus 3 mg/kg ipilimumab(N1I3)showed a significantly higher risk than other *** terms of treatment ranking,durvalumab±low-dose tremelimumab and avelumab were consistently among the top three safest treatments for grade 1-5 or 3-5 AKI,whereas N1I3,ipilimumab and tremelimumab were consistently among the top three treatments with the highest risk for grade 1-5 or 3-5 *** with other cancers,renal cell carcinoma and urothelial carcinoma showed a significantly higher risk of *** incidence of AKI was significantly higher with ICI+chemotherapy than with ICI *** this NMA involving largescale up-to-date ICI trials,we dem

关键词： immune checkpoint inhibitors acute kidney injury cancer immune therapy side effects

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Neurological disorders and inflammatory bowel diseases

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World Journal of Gastroenterology 2014年第27期20卷 8764-8782页

作者： Giovanni Casella Gian Eugenio Tontini Gabrio Bassotti Luca Pastorelli Vincenzo Villanacci Luisa Spina Vittorio Baldini Maurizio Vecchi Medical Department Desio Hospital Gastroenterology and Gastrointestinal Endoscopy Unit IRCCS Policlinico San Donato 20097 San Donato Milanese Italy Gastroenterology Section Department of Medicine University of Perugia Medical School Department of Biomedical Sciences for the Health University of Milan Institute of Pathology Spedali Civili 25123 Brescia Italy

Extraintestinal manifestations occur in about one-third of patients living with inflammatory bowel disease(IBD) and may precede the onset of gastrointestinal symptoms by many years. Neurologic disorders associated with IBD are not frequent, being reported in 3% of patients, but they often represent an important cause of morbidity and a relevant diagnostic issue. In addition, the increasing use of immunosuppressant and biological therapies for IBD may also play a pivotal role in the development of neurological disorders of different type and pathogenesis. Hence, we provide a complete and profound review of the main features of neurological complications associated with IBD, with particular reference to those related to drugs and with a specific focus on their clinical presentation and possible pathophysiological mechanisms.

关键词： Inflammatory bowel diseases Crohn's disease Ulcerative colitis Extraintestinal manifestations Neurological disorders Multiple sclerosis Progressive multifocal encephalopathy Demyelinating neuropathies Cerebrovascular diseases side effects

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Second-generation direct-acting-antiviral hepatitis C virus treatment: Efficacy, safety, and predictors of SVR12

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World Journal of Gastroenterology 2016年第35期22卷 8050-8059页

作者： Christoph R Werner Julia M Schwarz Daniel P Egetemeyr Robert Beck Nisar P Malek Ulrich M Lauer Christoph P Berg Department of Gastroenterology Hepatology and Infectiology University Hospital Tübingen Institute of Medical Virology University Hospital Tübingen

AIM To gather data on the antiviral efficacy and safety of second generation direct acting antiviral(DAA) treatment with respect to sustained virological response(SVR) 12 wk after conclusion of treatment, and to determine predictors of SVR12 in this *** Two hundred and sixty patients treated with SOF combination partners PR(n = 51), R(n = 10), SMV(n = 30), DCV(n = 81), LDV(n = 73), or 3D(n = 15).144/260 were pre-treated, 89/260 had liver cirrhosis, 56/260 had portal hypertension with platelets side effects were mild. CONCLUSION Excellent SVR12 rates and the favorable side-effect profile of DAA-combination therapy can be well translated into "real-world". Patients with advanced liver disease, signs of portal hypertension, especially with platelets < 100/n L and patients with GT3 are in special need for further research efforts to overcome comparatively higher rates of virological failure.

关键词： Sofosbuvir Simeprevir Ledipasvir Hepatitis C Liver transplant Sustained virological response Liver cirrhosis side effects Resistance Daclatasvir

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