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Correlations between serum kidney injury molecule-1,cystatin C and immunosuppressants:A cross-sectional study of renal transplant patients in Bahrain

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Journal of Biomedical Research 2024年第3期38卷 269-277页

作者： Kannan Sridharan Shamik Shah Mona Al Hammad Fatima Ali Mohammed Sindhan Veeramuthu Mona Abdulla Taher Mustafa Mohamed Hammad Lamees Jawad Eman Farid Department of Pharmacology and Therapeutics College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain Department of Nephrology Salmaniya Medical ComplexManamaKingdom of Bahrain Department of Internal Medicine College of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain Salmaniya Medical Complex ManamaKingdom of Bahrain Department of Laboratory Medicine Salmaniya Medical ComplexManamaKingdom of Bahrain Department of Microbiology Immunologyand Infectious DiseasesCollege of Medicine and Medical SciencesArabian Gulf UniversityManamaKingdom of Bahrain

Renal transplant patients receive several immunosuppressive drug regimens that are potentially nephrotoxic for *** creatinine is the standard for monitoring kidney function;however,cystatin C(Cys C)and kidney injury molecule-1(KIM-1)have been found to indicate kidney injury earlier than serum creatinine and provide a better reflection of kidney ***,we assessed Cys C and KIM-1 serum levels in renal transplant patients receiving mycophenolate mofetil,tacrolimus,sirolimus,everolimus,or cyclosporine to evaluate kidney *** used both the Chronic Kidney Disease Epidemiology Collaboration(CKD-EPI)2021 equation,which is based on creatinine and combined creatinine with Cys C,and the CKD-EPI 2012 equation,which is based on Cys C alone,to estimate glomerular filtration rate(GFR).Then,we assessed the association between serum KIM-1 and GFR<90 mL per minute per 1.73 *** observed significantly higher serum Cys C levels in patients with the elevated serum creatinine,compared with those with normal serum *** estimated GFRs based on creatinine were significantly higher than those based on the other equations,while a significant positive correlation was observed among all *** KIM-1 levels were negatively correlated with the estimated GFRs by the CKD-EPI Cys C and the combined creatinine with Cys C equations.A serum KIM-1 level above 0.71 ng/mL is likely to indicate GFR<90 mL per minute per 1.73 *** observed a significant correlation between serum creatinine and Cys C in our renal transplant ***,serum KIM-1 may be used to monitor renal function when using potentially nephrotoxic drugs in renal transplants.

关键词： KIM-1 cystatin C mycophenolate mofetil tacrolimus everolimus sirolimus cyclosporine

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Twelve-month efficacy and safety of the conversion to everolimus in maintenance heart transplant recipients

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World Journal of Transplantation 2015年第4期5卷 310-319页

作者： Nicolás Manito Juan F Delgado María G Crespo-Leiro José María Arizón Javier Segovia Francisco González-Vílchez Sònia Mirabet Ernesto Lage Domingo Pascual-Figal Beatriz Díaz Jesús Palomo Gregorio Rábago Marisa Sanz Teresa Blasco Eulàlia Roig Heart Failure and Transplant Unit Department of CardiologyHospital de Bellvitge Heart Failure and Transplant Unit Department of CardiologyHospital 12 de Octubre Department of Cardiology Complejo Hospitalario Universitario A Coru?a Department of Cardiology Hospital Universitario Reina Sofía Heart Failure Transplant and Pulmonary Hypertension UnitHospital Universitario Puerta de Hierro Department of Cardiology Hospital Universitario Marqués de Valdecilla Department of Cardiology Hospital de la Santa Creu i Sant Pau Department of Cardiology Hospital Universitario Virgen del Rocío Department of Cardiology Hospital Virgen de la Arrixaca Department of Cardiology Hospital Universitario Central de Asturias Department of Cardiology Hospital General Universitario Gregorio Mara?ón Department of Cardiovascular Surgery Clínica Universitaria de Navarra Department of Cardiology Hospital Miguel Servet Department of Cardiology Hospital Clínic i Provincial

AIM: To determine the clinical reasons for conversion to everolimus(EVL) and long-term outcomes in heart transplant(HT) ***: A retrospective 12-mo study has been carried out in 14 Spanish centres to assess the efficacy and safety of conversion to EVL in maintenance HT ***: Two hundred and twenty-two patients were included(mean age: 53 ± 10.5 years; mean time from HT: 8.1 ± 4.5 years). The most common reasons for conversion were nephrotoxicity(30%), chronic allograft vasculopathy(20%) and neoplasms(17%). The doses and mean levels of EVL at baseline(conversion to EVL) and after one year were 1.3 ± 0.3 and 1.2 ± 0.6 mg/d and 6.4 ± 3.4 and 5.6 ± 2.5 ng/mL, respectively. The percentage of patients receiving calcineurin inhibitors(CNIs) at baseline and on the final visit was 95% and 65%, respectively. The doses and mean levels of CNIs decreased between baseline and month 12 from 142.2 ± 51.6 to 98.0 ± 39.4 mg/d(P < 0.001) and from 126.1 ± 50.9 to 89.2 ± 47.7 ng/mL(P < 0.001), respectively, for cyclosporine, and from 2.9 ± 1.8 to 2.6 ± 1.9 mg/d and from 8.3 ± 4.0 to 6.5 ± 2.7 ng/mL(P = 0.011) for tacrolimus. In the subgroup of patients converted because of nephrotoxicity, creatinine clearance increased from 34.9 ± 10.1 to 40.4 ± 14.4 mL/min(P < 0.001). There were 37 episodes of acute rejection in 24 patients(11%). The most frequent adverse events were oedemas(12%), infections(9%) and gastrointestinal problems(6%). EVL was suspended in 44 patients(20%). Since the database was closed at the end of the study, no further followup data is ***: Conversion to EVL in maintenance HT recipients allowed minimisation or suspension of the CNIs, with improved kidney function in the patients with nephrotoxicity, after 12 mo.

关键词： everolimus Mammalian target of rapamycin inhibitors Heart transplantation Nephrotoxicity Renal failure

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Combining cytochrome P-450 3A4 modulators and cyclosporine or everolimus in transplantation is successful

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World Journal of Transplantation 2015年第4期5卷 338-347页

作者： Fernando González Ricardo Valjalo Department of Nephrology Faculty of MedicineUniversidad de ChileHospital del Salvador

AIM: To describe the long term follow-up of kidney allograft recipients receiving ketoconazole with calcineurin inhibitors(CNI) alone or combined with everolimus. METHODS: This is an open-label, prospective observational clinical trial in low immunologic risk patients who, after signing an Institutional Review Board approved consent form, were included in one of two groups. The first one(n = 59) received everolimus(target blood level, 3-8 ng/m L) and the other(n = 114) azathioprine 2 mg/kg per day or mycophenolate mofetyl(MMF) 2 g/d. Both groups also received tapering steroids, the cytochrome P-450 3A4(CYP3A4) modulator, ketoconazole 50-100 mg/d, and cyclosporine with C0 targets in the everolimus group of 200-250 ng/mL in 1 mo, 100-125 ng/m L in 2 mo, and 50-65 ng/m L thereafter, and in the azathioprine or MMF group of 250-300 ng/mL in 1 mo, 200-250 ng/mL in 2 mo, 180-200 ng/m L until 3-6 mo, and 100-125 ng/mL thereafter. Clinical visits were performed monthly the first year and quarterly thereafter by treating physicians and all data was extracted by the ***: The clinical characteristics of these two cohorts were similar. During the follow up(66 + 31 mo), both groups showed comparable clinical courses, but the biopsy proven acute rejection rate during the full follow-up period seemed to be lower in the everolimus group(20% vs 36%; P = 0.04). The everolimus group did not show a higher surgical complication rate thanthe other group. By the end of the follow-up period, the everolimus group tended to show a higher glomerular filtration rate. Nevertheless, we found no evidence of a consistent negative slope of the temporal allograft function estimated by the modification of the diet in renal disease formula in any of both groups. At 6 years of follow-up, the uncensored and death-censored graft survivals were 91% and 93%, and 91% and 83% in the everolimus plus cyclosporine, and cyclosporine alone groups, respectively. The addition of ketoconazole saved

关键词： Kidney transplant Immunosuppressive Cyclosporine Ketoconazole everolimus Cytochrome P-450 Cytochrome P-450 3A4 modulator

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Multiple indications for everolimus after liver transplantation in current clinical practice

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World Journal of Transplantation 2014年第2期4卷 122-132页

作者： Itxarone Bilbao Cristina Dopazo Jose Lazaro Lluis Castells Mireia Caralt Gonzalo Sapisochin Ramon Charco Hepatobiliopancreatic Surgery and Liver Transplant Unit of the Department of General Surgery Hospital Vall HebrónUniversidad Autónoma Barcelona08035 BarcelonaSpain Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD o Ciberehd) Hospital Vall d'Hebron08035 BarcelonaSpain Hepatology Unit of the Department of Internal Medicine Hospital Vall HebrónUniversidad Autónoma Barcelona08035 BarcelonaSpain

AIM: To assess our experience with the use and management of everolimus-based regimens post-liver transplantation and to redefine the potential role of this drug in current clinical ***: From October 1988 to December 2012, 1023 liver transplantations were performed in 955 patients in our Unit. Seventy-four patients(7.74%) received immunosuppression with everolimus at some time post-transplantation. Demographic characteristics, everolimus indication, time elapsed from transplantation to the introduction of everolimus, doses and levels administered, efficacy, side effects, discontinuation andpost-conversion survival were analyzed. RESULTS: Mean age at the time of conversion to everolimus was 57.7 ± 10 years. Indications for conversion were: refractory rejection 31.1%, extended hepatocellular carcinoma in explanted liver 19%, post-transplant hepatocellular carcinoma recurrence 8.1%, de novo tumour 17.6%, renal insufficiency 8.1%, severe neurotoxicity 10.8%, and others 5.4%. Median time from transplantation to introduction of everolimus was 6 mo(range: 0.10-192). Mean follow-up post-conversion was 22 ± 19 mo(range: 0.50-74). The event for which the drug was indicated was resolved in 60.8% of patients, with the best results in cases of refractory rejection, renal insufficiency and neurotoxicity. Results in patients with cancer were similar to those of a historical cohort treated with other immunosuppressants. The main side effects were dyslipidemia and infections. Post-conversion acute rejection occurred in 14.9% of cases. The drug was discontinued in 28.4% of ***: everolimus at low doses in combination with tacrolimus is a safe immunosuppressant with multiple early and late indications post-liver transplantation.

关键词： everolimus Liver transplantation Indications Off-protocol Outcome

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Bone marrow metastatic neuroendocrine carcinoma with unknown primary site:A case report and review of the literature

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World Journal of Clinical Cases 2022年第30期10卷 11074-11081页

作者： Xue-Bing Shi Wen-Xia Deng Feng-Xiang Jin Department of Medical Oncology Tongling People’s HospitalTongling 244000Anhui ProvinceChina Department of Hematology Tongling People’s HospitalTongling 244000Anhui ProvinceChina

BACKGROUND Metastatic neuroendocrine carcinoma(NEC) of bone marrow is ***,we report a case of bone marrow metastatic NEC with an unknown primary *** SUMMARY A 73-year-old Chinese woman was admitted to our hospital because marked chest distress and asthma lasting 1 d on March 18,*** was initially diagnosed with pulmonary infection,cardiac insufficiency,thrombocytopenia and severe *** treatment with antibiotic therapy,diuresis and blood transfusion,the patient’s symptoms greatly *** bone marrow examinations,the patient was diagnosed with bone marrow metastatic NEC,bone marrow necrosis(BMN) and secondary myelofibrosis(MF).Further imaging workup did not show the primary tumor,we presumed that the primary site might regress spontaneously or merely be unexplored due to lack of positron emission tomography with gallium ***(10 mg/d) was added to the treatment and the best supportive and symptomatic therapies were also ***,the patient’s condition continued to deteriorate and she died on May 15,*** Bone marrow invasion of NEC is rare and our patient who suffered from bone marrow metastatic NEC as well as secondary BMN and MF had an extremely poor *** marrow biopsy plays an important role in the diagnosis of solid tumors invading bone marrow.

关键词： Neuroendocrine neoplasm Bone marrow metastasis Bone marrow necrosis Myelofibrosis everolimus Case report

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Pneumocystis jirovecii diagnosed by next-generation sequencing of bronchoscopic alveolar lavage fluid: A case report and review of literature

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World Journal of Clinical Cases 2023年第4期11卷 866-873页

作者： Qing-Wei Cheng Hong-Li Shen Zhi-Hui Dong Qian-Qian Zhang Ya-Fen Wang Jin Yan Yu-Sheng Wang Ning-Gang Zhang Department of Oncology The Sixth Division HospitalXinjiang Production and Construction CorpsWujiaqu 831300Xinjiang Uygur Autonomous RegionsChina Department of Gastrointestinal Oncology Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer HospitalChinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical UniversityTaiyuan 030013Shanxi ProvinceChina

BACKGROUND The advent of molecular targeted agents and immune checkpoint inhibitors has greatly improved the treatment of advanced renal cell carcinoma(RCC), thus significantly improving patient survival. The incidence of rare drug-related adverse events has gained increased *** SUMMARY We report a patient with advanced RCC treated with multiple lines of molecular targeted agents and immune checkpoint inhibitors, who developed a pulmonary infection after treatment with everolimus in combination with lenvatinib. Determining the pathogenic organism was difficult, but it was eventually identified as Pneumocystis jirovecii by next-generation sequencing(NGS) of bronchoscopic alveolar lavage fluid(BALF) and successfully treated with *** Rare pulmonary infections caused by molecular targeted agents are not uncommon in clinical practice, but their diagnosis is difficult. Evaluating BALF with NGS is a good method for rapid diagnosis of such infections.

关键词： Renal cell carcinoma everolimus Pneumocystis jirovecii pneumonia Next-generation sequencing Bronchoscopic alveolar lavage fluid Case report

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Influence of immunosuppressive drugs on natural killer cells in therapeutic drug exposure in liver transplantation

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Hepatobiliary Surgery and Nutrition 2023年第6期12卷 835-853,I0002-I0005页

作者： Rongrong Qin Jiwei Qin Xuefeng Li Zhijun Xu Peiqi He Xiaodong Yuan Cheng Sun Björn Nashan Department of Organ Transplantation The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiChina Organ Transplantation&Immunology Laboratory Division of Life Science and MedicineUniversity of Science and Technology of ChinaHefeiChina

Background:Natural killer(NK)cells are enriched in the liver and are the main regulators in liver transplantation regarding rejection or tolerance,viral infection,or tumor *** consists of a triple drug standard regimen comprising tacrolimus(TAC)and corticosteroids(CS)with either mycophenolate mofetil(MMF)or sirolimus(SIR)/everolimus(EVE).The aim of this study was to evaluate the impact of trough levels of these regimens under clinical conditions and exposure on human NK-cell activity and function in order to better understand the antiviral and anti-tumor effects of mammalian target of rapamycin inhibitor(mTORI).Methods:Peripheral blood mononuclear cells(PBMCs)were collected from liver transplant recipients and healthy *** and phenotypes of NK cells in vivo were analyzed by flow *** this study we simulated the immunosuppressive microenvironment in *** were cultured at the clinically effective plasma concentration of drugs for 3 d to detect the effect of immunosuppressants on NK *** type and concentration:single drug[EVE,5 ng/mL;SIR,5 ng/mL;TAC,5 ng/mL;cyclosporine A(CSA),125 ng/mL;MMF,15μg/mL;CS,0.5μg/mL]and combined immunosuppressants(Group 1:TAC,5 ng/mL+MMF,15μg/mL+CS,0.5μg/mL;Group 2:TAC,5 ng/mL+SIR,5 ng/mL+CS,0.5μg/mL;Group 3:TAC,5 ng/mL+EVE,5 ng/mL+CS,0.5μg/mL).In addition,NK cells were sorted from PBMCs and treated under the above conditions to detect NK cell killing function and RNA transcription ***:CS significantly impaired the cytolytic activity of NK cells,followed by MMF and SIR/*** and TAC/CSA significantly decreased the secretion of IFN-γand *** cell function in liver transplant recipients was most pronouncedly inhibited by a triple immunosuppressive regimen,with CS playing the most prominent role compared with the other *** MMF-containing regimen demonstrated a significant increase in the expression of suppressive genes,especially of the Siglec7/9 ***

关键词： Liver transplantation NK cells immunosuppressants calcineurin inhibitor(CNI) everolimus

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Current role of surgery for tuberous sclerosis complex-associated epilepsy

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Pediatric Investigation 2022年第1期6卷 16-22页

作者： Nicola Specchio Giusy Carfi Pavia Luca de Palma Alessandro De Benedictis Chiara Pepi Marta Conti Carlo Efisio Marras Federico Vigevano Paolo Curatolo Rare and Complex Epilepsy Unit Department of NeurosciencesBambino GesùChildren’s HospitalIRCCSRomeItaly Neurosurgery Unit Department of NeurosciencesBambino GesùChildren’s HospitalIRCCSRomeItaly Department of Neurosciences Bambino GesùChildren’s HospitalIRCCSRomeItaly Child Neurology and Psychiatry Unit Systems Medicine DepartmentTor Vergata UniversityRomeItaly

Tuberous sclerosis complex(TSC)is a rare multisystem,autosomal dominant neurocutaneous syndrome in which epilepsy is the most common of several neurological and psychiatric *** two thirds of patients develop drug-resistant epilepsy for whom surgical resection of epileptogenic foci is indicated when seizures remain inadequately controlled following trial of two antiseizure *** challenge with presurgical and surgical approaches with patients with TSC is overcoming the complexity from the number of tubers and the multiplex epileptogenic network forming the epileptogenic *** suggest that seizure freedom is achieved by 55%-60%of patients,but predictive factors for success have remained elusive,which makes for unconfident selection of surgical *** article presents three different cases as illustrations of the potential challenges faced when assessing the suitability of TSC patients for epilepsy surgery.

关键词： Epilepsy everolimus Imaging Prognostics Surgery Tuberous sclerosis complex(TSC)

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Current aspects of renal dysfunction after liver transplantation

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World Journal of Hepatology 2022年第1期14卷 45-61页

作者： Mariana P Pacheco Luiz Augusto Carneiro-D'Albuquerque Daniel F Mazo Division of Clinical Gastroenterology and Hepatology Department of GastroenterologyUniversity of São Paulo School of MedicineSao Paulo 05403-900Sao PauloBrazil Division of Digestive Organs Transplant Department of GastroenterologyUniversity of São Paulo School of MedicineSao Paulo 05403-900Sao PauloBrazil Division of Gastroenterology Department of Internal MedicineSchool of Medical Sciences of University of CampinasCampinas 13083-878Sao PauloBrazil

The development of chronic kidney disease(CKD)after liver transplantation(LT)exerts a severe effect on the survival of *** widespread adoption of the model for end-stage liver disease score strongly impacted CKD incidence after the procedure,as several patients are transplanted with previously deteriorated renal *** to its multifactorial nature,encompassing pre-transplantation conditions,perioperative events,and nephrotoxic immunosuppressor therapies,the accurate identification of patients under risk of renal disease,and the implementation of preventive approaches,are extremely *** for the evaluation of renal function in this setting range from formulas that estimate the glomerular filtration rate,to non-invasive markers,although no option has yet proved efficient in early detection of kidney *** the nephrotoxicity of calcineurin inhibitors(CNI)as a factor of utmost importance after LT,early nephroprotective strategies are highly *** are based mainly on delaying the application of CNI during the immediate postoperativeperiod,reducing their dosage,and associating them with other less nephrotoxic drugs,such as mycophenolate mofetil and *** review provides a critical assessment of the causes of renal dysfunction after LT,the methods of its evaluation,and the interventions aimed at preserving renal function early and belatedly after LT.

关键词： Liver transplantation Acute kidney injury Chronic kidney disease Calcineurin inhibitor Mycophenolic acid everolimus

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Safety and efficacy of a novel abluminal groove-filled biodegradablepolymer sirolimus-eluting stent for the treatment of de novo coronarylesions： 12-month results from the TARGET II trial

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Chinese Medical Journal 2014年第6期127卷 1027-1032页

作者： Xu Bo Zhao Yelin Yang Yuejin Zhang Ruiyan Li Hui Ma Changsheng Chen Shaoliang Department of Cardiology Fu Wai Hospital National Center for Cardiovascular Diseases Beijing 100037 China Department of Cardiology Ruijin Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200025 China Department of Cardiology Daqing Oil Field General HospitalDaqing Heilongjiang 163114 China Department of Cardiology Affiliated Anzhen Hospital of Capital Medical University Beijing 100029 China Department of Cardiology Nanjing First Hospital Nanjing Medical University Nanjing Jiangsu 210006 China

Background In the TARGET I randomized controlled trial, the novel abluminal groove-filled biodegradable polymersirolimus-eluting stent FIREHAWK proved non-inferior to the everolimus-eluting stent in nine-month in-stent late loss insingle de novo coronary lesions. This study was aimed at evaluating clinical safety and effectiveness of FIREHAWK in amoderately complex population （including patients with small vessels, long lesions and multi-vessels）, and at validatingthe ability of the SYNTAX score （SS） to predict clinical outcomes in patients treated with this latest generation drug-elutingstent.

关键词： 5-YEAR FOLLOW-UP ARTERY-DISEASE CLINICAL-EVALUATION RANDOMIZED-TRIALS VESSEL SIZE INTERVENTION everolimus OUTCOMES COHORT REVASCULARIZATION

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