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Programmed cell death-1 inhibitor-related sclerosing cholangitis:A systematic review

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World Journal of Gastroenterology 2020年第3期26卷 353-365页

作者： Takumi Onoyama Yohei Takeda Taro Yamashita Wataru Hamamoto Yuri Sakamoto Hiroki Koda Soichiro Kawata Kazuya Matsumoto Hajime Isomoto Division of medicine and clinical Science Department of Multidisciplinary Internal MedicineFaculty of MedicineTottori UniversityTottori prefecture 683-8504Japan internal medicine Irisawa Medical ClinicShimane prefecture 690-0025Japan

BACKGROUND Programmed cell death-1(PD-1)inhibitor has been indicated for many types of ***,these inhibitors also cause immune-related adverse *** disorder is a phenotype of immune-related adverse event affecting 0%–4.5%of patients treated with PD-1 *** studies have reported PD-1 inhibitor-related sclerosing cholangitis(SC);however,the associated clinical and pathological features are *** To evaluate the clinical and pathological features of PD-1 inhibitor-related SC through a systematic review of the *** The review,conducted using electronic databases in PubMed,was restricted to the period from January 2014 to September 2019 and focused on case reports/series on PD-1 inhibitor-related SC published in *** scanned the references of the selected literature to identify any further relevant *** cases previously studied by us,including three that have not yet been published,were included in this *** Thirty-one PD-1 inhibitor-related SC cases were *** age of patients was 67 years(range,43–89),with a male to female ratio of 21:*** main disease requiring PD-1 inhibitor treatment was non-small cell lung *** that caused PD-1 inhibitor-related SC were nivolumab(19 cases),pembrolizumab(10 cases),avelumab(1 case),and durvalumab(1 case).The median number of cycles until PD-1 inhibitor-related SC onset was 5.5(range,1–27).Abdominal pain or discomfort(35.5%,11/31)was the most frequent *** serum tests identified liver dysfunction with a notable increase in biliary tract enzymes relative to hepatic enzymes,and a normal level of serum immunoglobulin *** dilation without obstruction(76.9%,20/26),diffuse hypertrophy of the extrahepatic biliary tract(90.5%,19/21),and multiple strictures of the intrahepatic biliary tract(30.4%,7/23)were *** 11/23(47.8%)cases,pathological examination indicated that CD8+T cells were the dominant inflammatory cells i

关键词： Nivolumab Pembrolizumab Avelumab Durvalumab Atezolizumab Programmed cell death-1 inhibitor Immune-related adverse events Cholangitis

Long-term esophageal and respiratory outcomes in children with esophageal atresia and tracheoesophageal fistula

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Gastroenterology Report 2016年第4期4卷 310-314,I0002页

作者： Richard H.Cartabuke Rocio Lopez Prashanthi N.Thota Department of internal medicine Cleveland ClinicClevelandOHUSA Department of Biostatistics Cleveland ClinicClevelandOHUSA Department of Gastroenterology and Hepatology Cleveland ClinicClevelandOHUSA

Objectives:Few studies have evaluated the long-term complications and outcomes of esophageal atresia with or without tracheoesophageal fistula(EA/TEF)beyond *** aim of our study was to characterize the esophageal and respiratory morbidity of EA/TEF through evaluation of clinical symptoms,diagnostic testing and therapeutic intervention at a tertiary care ***:Patients with congenital EA/TEF evaluated from 2011 to 2014 were *** characteristics,type and mode of repair of EA/TEF,clinical symptoms,radiographic,endoscopic,bronchoscopic and medication use data were ***:A total of 43 patients were *** median age of this predominantly Caucasian population was 8 years(interquartile range:3,20).Twenty(62.5%)had type C(EA with distal TEF)***-one(48.8%)patients had heartburn,19(44.1%)had acid regurgitation,and 31(72.1%)had dysphagia to *** swallow in 26 patients revealed strictures in 17(65.4%),dysmotility in 20(76.9%)and recurrent fistulas in four patients(15.4%).Thirty patients underwent upper endoscopy,of which 21(70.0%)had a stricture,and six(20.0%)had recurrent fistula requiring surgical ***(18.6%)patients underwent *** evaluation showed cough and choking in 31(72.1%)patients and dyspnea and wheezing in 32(53.4%)*** respiratory infections were reported in 19(44.2%).*** findings included tracheomalacia in 86.7% and restrictive lung disease in 54.5%of ***:There is a high burden of residual esophageal and pulmonary pathology in patients with EA/*** follow-up is required to monitor both the clinical symptoms and treatment responses.

关键词： esophageal atresia tracheoesophageal fistula gastroesophageal reflux disease(GERD) esophageal dysmotility aspiration pneumonia

Gaucher disease in Montenegro-genotype/phenotype correlations:Five cases report

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World Journal of clinical Cases 2019年第12期7卷 1475-1482页

作者： Snezana Vujosevic Sanja Medenica Vesko Vujicic Milena Dapcevic Nikola Bakic Ruhua Yang Jun Liu Pramod K Mistry Department of Endocrinology Internal Medicine Clinic Clinical Center of Montenegro Faculty of Medicine University of Montenegro Podgorica 81000 Montenegro Hematology Department Internal Medicine Clinic Clinical Center of Montenegro Faculty of Medicine University of Montenegro Podgorica 81000 Montenegro Yale Lysosomal Disease Center and Inherited Metabolic Liver Disease clinic Yale University School of Medicine New Haven CT 06510 United States

BACKGROUND The most common lysosomal storage disorder is Gaucher disease (GD). It is a deficiency of lysosomal glucocerebrosidase (GBA) due to biallelic mutations in the GBA gene, characterized by the deposition of glucocerebroside in macrophage-monocyte system cells. The report targets clinical phenotypes of GD in order to correlate them with GBA gene mutations, as well as to identify GBA gene mutation in patients in Montenegro that are diagnosed with GD. CASES SUMMARY Five patients (4 male, 1 female) of type 1 GD (GD1) are reported. The age at diagnosis ranged from 7 to 40. Patients experienced delays of 1-12 years in diagnosis after the original onset of symptoms. The most common mode of presentation was a variable degree of splenomegaly and thrombocytopenia, while other symptoms included bone pain, hepatomegaly, abdominal pain and fatigue. Osteopenia was present in a majority of the patients: 4/5. All patients were found to have an asymptomatic Erlenmeyer flask deformity of the distal femur. On enzyme replacement therapy (ERT), the hematological and visceral parameters showed significant improvement, but no significant progression in bone mineral density was noticed. GBA gene sequencing revealed homozygosity for the N370S mutation in one patient. The genotypes of the other patients were N370S/55bp deletion, N370S/D409H (2 patients), and H255Q/N370S (1 patient). CONCLUSION The phenotypes of the GD1 encountered in Montenegro were severe but all responded well to ERT.

关键词： Gaucher disease Lysosomal storage disorder Glucocerebrosidase GBA gene sequencing Genotype Case report

Efficacy and safety of sofosbuvir and ledipasvir in Japanese patients aged 75 years or over with hepatitis C genotype 1

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World Journal of Hepatology 2017年第36期9卷 1340-1345页

作者： Yoshinori Ozono Kenji Nagata Satoru Hasuike Hisayoshi Iwakiri Kenichi Nakamura Mai Tsuchimochi Yuri Yamada Yuka Takaishi Mitsue Sueta Tadashi Miike Yoshihiro Tahara Shojiro Yamamoto Kotaro Shide Tomonori Hidaka Yoko Kubuki Kazunori Kusumoto Toshimasa Ochiai Junya Kato Naoto Komada Shuichi Hirono Kazuo Kuroki Masafumi Shigehira Kazuya Shimoda Department of Gastoroenterology and Hematology Faculty of Medicine University of Miyazaki Department of Liver Disease University of Miyazaki Hospital Department of internal medicine Koga General Hospital Department of internal medicine National Hospital Organization Miyakonojo Medical Center Department of internal medicine Hirono Naika Clinic Department of internal medicine Kushima Municipal Hospital Department of internal medicine Shigehira Clinic

AIM To evaluate the efficacy and safety of a regimen containing sofosbuvir(SOF) and ledipasvir(LDV) in Japanese patients aged ≥ 75 years with hepatitis C genotype *** This multicenter, retrospective study consisted of 246 Japanese patients with HCV genotype 1 at nine centers in Miyazaki prefecture in Japan. Demographic, clinical, virological, and adverse effects(AE)-related data obtained during and after SOF/LDV therapy were collected from medical records. These patients were divided into two groups, younger(aged < 75 years) and elderly(aged ≥ 75 years). Virological data and AEs were analyzed by age *** The sustained virological response(SVR) rates at 12 wk after treatment were 99.2%, 99.4%, and 98.7% in the overall population and in patients aged < 75 and ≥ 75 years, respectively. Common AEs during therapy were headache, pruritus, constipation, and insomnia. These occurred in fewer than 10% of patients, and their incidence was not significantly different between the younger and elderly groups. Two patients discontinued treatment, one due to a skin eruption and the other due to cerebral bleeding. CONCLUSION Compared with younger patients, elderly patients had a similar virological response and tolerance to SOF/LDV therapy.

关键词： Chronic hepatitis C Sofosbuvir Ledipasvir Sustained virological response Direct acting antivirals

MicroRNA regulation of innate immune responses in epithelial cells

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Cellular & Molecular Immunology 2011年第5期8卷 371-379页

作者： Rui Zhou Steven P O’Hara Xian-Ming Chen Department of Microbiology and Immunology Creighton University School of MedicineOmahaNEUSA Division of Gastroenterology and Hepatology Department of Internal MedicineMayo Clinic College of MedicineRochesterMNUSA

Mucosal surface epithelial cells are equipped with several defense mechanisms that guard against *** studies indicate that microRNAs(miRNAs)mediate post-transcriptional gene suppression and may be a critical component of the complex regulatory networks in epithelial immune *** of miRNA genes in epithelial cells can be elaborately controlled through pathogen recognition receptors,such as Toll-like receptors(TLRs),and associated nuclear factor kappaB(NF-kB)and mitogen-activated protein kinase(MAPK)pathways,and ultimately nuclear transcription factor associated-transactivation and *** of these intracellular signaling pathways may also modulate the process of miRNA ***,miRNAs may modulate epithelial immune responses at every step of the innate immune network,including production and release of cytokines/chemokines,expression of adhesion and costimulatory molecules,shuttling of miRNAs through release of exosomes and feedback regulation of immune ***,miRNAs act as critical regulators to the fine-tuning of epithelial immune responses.

关键词： epithelial cells immune responses miRNAs posttranscriptional regulation TLRs

Effect of Foot Bath and Massage on Insomnia in Patients with Liver Cirrhosis and Investigation of Nursing Satisfaction

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Journal of Acupuncture and Tuina Science 2014年第2期12卷 105-108页

作者： Li Min-fen Huang Guo-qi clinic of Digestive internal medicine Tongde Hospital of Zhejiang Province

Objective: To observe the effect of foot bath and massage on insomnia in patients with liver cirrhosis. Methods: By control design of retrospective nonconcurrent cohort study, 100 insomnia patients with liver cirrhosis admitted and treated in our clinic between October 2011 and September 2012, were recruited in the control group and given routine nursing of internal medicine. A total of 105 insomnia patients with liver cirrhosis, admitted and treated between October 2012 and September 2013, were recruited in the intervention group and given foot bath and massage on the basis of routine nursing of internal medicine. After continuous intervention for 14 d, the clinical effects and the nursing satisfaction were evaluated. Results: There were statistically significant differences in clinical effects and sleeping quality between the two groups(Pclinical popularization and application.

关键词： Foot Bath Tuina Massage Liver Cirrhosis Complications Insomnia Nursing

Stem cell-derived exosomes-an emerging tool for myocardial regeneration

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World Journal of Stem Cells 2018年第8期10卷 106-115页

作者： Erzsebet Lazar Theodora Benedek Szilamer Korodi Nora Rat Jocelyn Lo Imre Benedek Department of internal medicine Clinic of Haematology and Bone Marrow Transplantation University of Medicine and Pharmacy Tirgu Mures Department of internal medicine Clinic of Cardiology University of Medicine and Pharmacy Tirgu Mures Department of Advanced Research in Multimodality Cardiac Imaging Cardio Med Medical Center Vagelos College of Physicians and Surgeons Columbia University

Cardiovascular diseases(CVDs) continue to represent the number one cause of death and disability in industrialized countries. The most severe form of CVD is acute myocardial infarction(AMI), a devastating disease associated with high mortality and disability. In a substantial proportion of patients who survive AMI, loss of functional cardiomyocytes as a result of ischaemic injury leads to ventricular failure, resulting in significant alteration to quality of life and increased mortality. Therefore, many attempts have been made in recent years to identify new tools for the regeneration of functional cardiomyocytes. Regenerative therapy currently represents the ultimate goal for restoring the function of damaged myocardium by stimulating the regeneration of the infarcted tissue or by providing cellsthat can generate new myocardial tissue to replace the damaged tissue. Stem cells(SCs) have been proposed as a viable therapy option in these cases. However, despite the great enthusiasm at the beginning of the SC era, justified by promising initial results, this therapy has failed to demonstrate a significant benefit in large clinical trials. One interesting finding of SC studies is that exosomes released by mesenchymal SCs(MSCs) are able to enhance the viability of cardiomyocytes after ischaemia/reperfusion injury, suggesting that the beneficial effects of MSCs in the recovery of functional myocardium could be related to their capacity to secrete exosomes. Ten years ago, it was discovered that exosomes have the unique property of transferring miRNA between cells, acting as miRNA nanocarriers. Therefore, exosomebased therapy has recently been proposed as an emerging tool for cardiac regeneration as an alternative to SC therapy in the post-infarction period. This review aims to discuss the emerging role of exosomes in developing innovative therapies for cardiac regeneration as well as their potential role as candidate biomarkers or for developing new diagnostic tools.

关键词： Acute myocardial infarction Exosome Stem cell Cardiac regeneration Cardiovascular diseases

Endoscopic ultrasound-guided fine-needle aspiration biopsy-Recent topics and technical tips

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World Journal of clinical Cases 2019年第14期7卷 1775-1783页

作者： Kazuya Matsumoto Yohei Takeda Takumi Onoyama Soichiro Kawata Hiroki Kurumi Hiroki Koda Taro Yamashita Hajime Isomoto Division of internal medicine Irisawa Medical ClinicMatsue 690-0025Japan Department of Multidisciplinary internal medicine Tottori UniversityYonago 683-8504Japan

Endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA) is a useful procedure that enables reliable pathological diagnoses of pancreatobiliary diseases, subepithelial lesions, and swollen lymph nodes. In recent years, a pathological diagnosis based on EUS-FNA has made it possible to provide accurate treatment methods not only in these fields, but also in respiratory organs and otorhinolaryngology. This review discusses the latest topics pertaining to EUS-FNA as well as procedural tips.

关键词： Endoscopic ultrasound-guided fine-needle aspiration biopsy Cytology Pathology Pancreatobiliary diseases Subepithelial lesions Lymph nodes

Persistent diarrhea with petechial rash-unusual pattern of light chain amyloidosis deposition on skin and gastrointestinal biopsies:A case report

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World Journal of clinical Cases 2022年第28期10卷 10252-10259页

作者： Shawna E Bilton Nikhil Shah Diana Dougherty Sarah Simpson Alex Holliday Farhad Sahebjam Douglas J Grider Department of Basic Science Education Virginia Tech Carilion School of MedicineRoanokeVA 24016United States Department of internal medicine Carilion ClinicRoanokeVA 24016United States Gastroenterology and Hepatology Section Department of Internal MedicineCarilion ClinicRoanokeVA 24016United States Dermatology Section Department of Internal MedicineCarilion ClinicRoanokeVA 24016United States Dominion Pathology Associates RoanokeVA 24018United States

BACKGROUND Amyloidosis is a rare disease characterized by extracellular deposition of misfolded protein aggregated into insoluble *** involvement in systemic amyloidosis is common,but is often subclinical or presents as vague and nonspecific *** is rare for gastrointestinal symptoms to be the main presenting symptom in patients with systemic amyloidosis,causing it to be undiagnosed until late-stage *** SUMMARY A 53 year-old man with diarrhea,hematochezia,and weight loss presented to a community *** with biopsy at that time was suspicious for Crohn *** to worsening symptoms including nausea,vomiting,and a new petechial rash,an abdominal fat pad biopsy was *** biopsy showed papillary and adnexal dermal amyloid deposition,in a pattern usually seen with cutaneous ***,Cytokeratin 5/6 was negative,excluding cutaneous *** patterns of nodular amyloidosis,subcutaneous amyloid deposits and perivascular amyloid were not *** Acid-Schiff stain was negative for lipoid proteinosis,Congo red was positive for apple green birefringence on polarization and amyloid typing confirmed amyloid light chain *** endoscopic biopsies of the gastrointestinal tract showed amyloid deposition from the esophagus to the rectum,in a pattern usually seen in serum amyloid A in the setting of chronic inflammatory diseases,including severe inflammatory bowel *** marrow biopsy showed kappa-restricted plasma cell *** Described is an unusual presentation of primary systemic amyloidosis,highlighting the risk of misdiagnosis with subsequent significant organ dysfunction and high mortality.

关键词： Light chain amyloidosis Diarrhea Endoscopy Petechial rash Plasma cell dyscrasia Case report