Database : MEDLINE
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[PMID]: 29499223
[Au] Autor:Le Coz C; Trofa M; Syrett CM; Martin A; Jyonouchi H; Jyonouchi S; Anguera MC; Romberg N
[Ad] Address:Division of Immunology and Allergy, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
[Ti] Title:CD40LG duplication-associated autoimmune disease is silenced by non-random X-chromosome inactivation.
[So] Source:J Allergy Clin Immunol;, 2018 Feb 27.
[Is] ISSN:1097-6825
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:An inherited syndrome of autoimmunity associated with CD40LG duplication is silenced by non-random X-chromosome inactivation and is treatable with CD40L directed therapy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:Publisher

  2 / 7645 MEDLINE  
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[PMID]: 29205338
[Au] Autor:Pelz A; Schaffert H; Diallo R; Hiepe F; Meisel A; Kohler S
[Ad] Address:Department of Experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
[Ti] Title:S1P receptor antagonists fingolimod and siponimod do not improve the outcome of experimental autoimmune myasthenia gravis mice after disease onset.
[So] Source:Eur J Immunol;48(3):498-508, 2018 Mar.
[Is] ISSN:1521-4141
[Cp] Country of publication:Germany
[La] Language:eng
[Ab] Abstract:Myasthenia gravis (MG) is an autoimmune disease characterized by muscle weakness and fatigue in the presence of circulating antibodies against components of the neuromuscular junction. Most patients have a good prognosis, but some are refractory to standard-of-care immunosuppressive treatment and suffer from recurrent myasthenic crises. Functional sphingosine-1-phosphate (S1P) antagonists like fingolimod and siponimod (BAF312) are successfully used for the treatment of multiple sclerosis, and fingolimod was shown to prevent the development of myasthenic symptoms in experimental autoimmune myasthenia gravis (EAMG), the standard model of MG. Here, we investigated whether fingolimod or siponimod improves outcome in EAMG mice when administered after disease onset, modeling the clinical setting in human MG. Both S1P antagonists inhibited lymphocyte egress, resulting in peripheral lymphopenia. After stimulation, there were differences in T-cell responses, but no change in either antibody titers or total or antigen-specific plasma cell populations after treatment. Most importantly, disease incidence and severity were not influenced by fingolimod or siponimod therapy. Although fingolimod and siponimod did lead to subtle changes in T-cell responses, they had no significant effect on antibody titers and disease severity. In conclusion, our data show no evidence of a therapeutic potential for S1P receptor antagonists in MG treatment.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180309
[Lr] Last revision date:180309
[St] Status:In-Data-Review
[do] DOI:10.1002/eji.201747187

  3 / 7645 MEDLINE  
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[PMID]: 29515037
[Au] Autor:Francois B; Jeannet R; Daix T; Walton AH; Shotwell MS; Unsinger J; Monneret G; Rimmelé T; Blood T; Morre M; Gregoire A; Mayo GA; Blood J; Durum SK; Sherwood ER; Hotchkiss RS
[Ad] Address:Intensive Care Unit, and.
[Ti] Title:Interleukin-7 restores lymphocytes in septic shock: the IRIS-7 randomized clinical trial.
[So] Source:JCI Insight;3(5), 2018 Mar 08.
[Is] ISSN:2379-3708
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:BACKGROUND: A defining pathophysiologic feature of sepsis is profound apoptosis-induced death and depletion of CD4+ and CD8+ T cells. Interleukin-7 (IL-7) is an antiapoptotic common γ-chain cytokine that is essential for lymphocyte proliferation and survival. Clinical trials of IL-7 in over 390 oncologic and lymphopenic patients showed that IL-7 was safe, invariably increased CD4+ and CD8+ lymphocyte counts, and improved immunity. METHODS: We conducted a prospective, randomized, double-blind, placebo-controlled trial of recombinant human IL-7 (CYT107) in patients with septic shock and severe lymphopenia. Twenty-seven patients at academic sites in France and the United States received CYT107 or placebo for 4 weeks. Primary aims were to determine the safety of CYT107 in sepsis and its ability to reverse lymphopenia. RESULTS: CYT107 was well tolerated without evidence of inducing cytokine storm or worsening inflammation or organ dysfunction. CYT107 caused a 3- to 4-fold increase in absolute lymphocyte counts and in circulating CD4+ and CD8+ T cells that persisted for weeks after drug administration. CYT107 also increased T cell proliferation and activation. CONCLUSIONS: This is the first trial of an immunoadjuvant therapy targeting defects in adaptive immunity in patients with sepsis. CYT107 reversed the marked loss of CD4+ and CD8+ immune effector cells, a hallmark of sepsis and a likely key mechanism in its morbidity and mortality. CYT107 represents a potential new way forward in the treatment of patients with sepsis by restoring adaptive immunity. Such immune-based therapy should be broadly protective against diverse pathogens including multidrug resistant bacteria that preferentially target patients with impaired immunity. TRIAL REGISTRATION: Trials registered at clinicaltrials.gov: NCT02640807 and NCT02797431. FUNDING: Revimmune, NIH National Institute of General Medical Sciences GM44118.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Cl] Clinical Trial:ClinicalTrial
[St] Status:Publisher

  4 / 7645 MEDLINE  
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[PMID]: 29346519
[Au] Autor:Awan MJ; Nedzi L; Wang D; Tumati V; Sumer B; Xie XJ; Smith I; Truelson J; Hughes R; Myers LL; Lavertu P; Wong S; Yao M
[Ad] Address:Department of Radiation Oncology.
[Ti] Title:Final Results of a Multi-institutional Phase II Trial of Re-Irradiation with Concurrent Weekly Cisplatin and Cetuximab for Recurrent or Second Primary Squamous Cell Carcinoma of the Head and Neck.
[So] Source:Ann Oncol;, 2018 Jan 15.
[Is] ISSN:1569-8041
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Background: The optimal regimen of chemotherapy and re-irradiation (re-XRT) for recurrent head and neck squamous cell carcinoma (HNSCC) is controversial. We report the final outcomes of a multi-center Phase II trial evaluating cetuximab and cisplatin-based chemotherapy concurrent with re-XRT for patients with recurrent HNSCC. Methods and Materials: Patients with unresectable recurrent disease or positive margins after salvage surgery arising within a previously irradiated field with KPS≥70 were eligible for this trial. Cetuximab 400mg/m2 was delivered as a loading dose in Week 1 followed by weekly cetuximab 250mg/m2 and cisplatin 30mg/m2 concurrent with 6 weeks of IMRT to a dose of 60-66 Gy in 30 daily fractions. Patients who previously received both concurrent cetuximab and cisplatin with radiation or who received radiotherapy less than 6 months prior were ineligible. Results: From 2009 to 2013, 48 patients enrolled on this trial. 2 did not receive any protocol treatment. Of the remaining 46 patients, 34 were male and 12 female, with a median age of 62 years (range 36-85). Treatment was feasible and only 1 patient did not complete the treatment course. Common Grade 3 or higher acute toxicities were lymphopenia (46%), pain (22%), dysphagia (13%), radiation dermatitis (13%), mucositis (11%) and anorexia (11%). There were no Grade 5 acute toxicities. Eight Grade 3 late toxicities were observed, 4 of which were swallowing-related. With a median follow-up of 1.38 years, the 1-year overall survival (OS) was 60.4% and 1-year recurrence-free survival was 34.1%. On univariate analysis, OS was significantly improved with young age (p=0.01). OS was not associated with radiation dose, surgery prior to re-XRT or interval from prior XRT. Conclusions: Concurrent cisplatin and cetuximab with re-XRT is feasible and offers good treatment outcomes for patients with high-risk features. Younger patients had significantly improved OS. ClinicalTrials.Gov Identifier: NCT00833261.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180308
[Lr] Last revision date:180308
[Cl] Clinical Trial:ClinicalTrial
[St] Status:Publisher
[do] DOI:10.1093/annonc/mdy018

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[PMID]: 29512868
[Au] Autor:Werbel WA; Ison MG; Angarone MP; Yang A; Stosor V
[Ad] Address:Division of Infectious Diseases, Johns Hopkins University, Baltimore, MD, USA.
[Ti] Title:Lymphopenia is associated with late-onset Pneumocystis jirovecii pneumonia in Solid Organ Transplantation.
[So] Source:Transpl Infect Dis;, 2018 Mar 07.
[Is] ISSN:1399-3062
[Cp] Country of publication:Denmark
[La] Language:eng
[Ab] Abstract:BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) affected 5-15% of solid organ transplant (SOT) recipients prior to universal prophylaxis, classically with trimethoprim-sulfamethoxazole (TMP-SMX). Guidelines generally recommend 6-12 months of prophylaxis post SOT, yet optimal duration and robust PJP risk stratification have not been established. METHODS: A retrospective, single-center, case-control study of PJP among SOT recipients from January 1998 to December 2013 was conducted. Cases had positive PJ direct fluorescent antibody (DFA) assay of respiratory specimens. Controls were matched 4:1 by nearest date of SOT. Univariate testing and multivariate logistic regressions were performed. RESULTS: Fifteen cases were identified among 5505 SOT recipients (0.27% rate) and analyzed versus 60 controls. PJP occurred on average 6.1 years (range 0.9-13.8) post SOT; no case was receiving PJP prophylaxis at diagnosis. Most were treated with reduced immunosuppression and TMP-SMX plus steroids (80%). Six patients (40%) required critical care; three (20%) died. There were no significant demographic differences, though cases tended to be older at SOT (54 vs. 48 years, p=0.1). In univariate analysis, prior viral infection was more common among cases (67% vs. 37%, p=0.08). Lower absolute lymphocyte count (ALC) at diagnosis date was strongly associated with PJP (400 vs. 1230 x 10 cells/ µl, p<0.001); odds of infection were high with ALC ≤ 500 x 10 cells (OR 18.7, p<0.01). CONCLUSION: PJP is a rare, late complication of SOT with significant morbidity and mortality. Severe lymphopenia may be useful in identifying SOT recipients who warrant continued or reinstated PJP prophylaxis. This article is protected by copyright. All rights reserved.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher
[do] DOI:10.1111/tid.12876

  6 / 7645 MEDLINE  
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[PMID]: 29512373
[Au] Autor:Tavakol M; Mahdaviani SA; Ghaemi MR; Vaezi M; Dorudinia A; Jamaati H; Velayati AA
[Ad] Address:Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran AND Department of Allergy and Clinical Immunology, Shahid Bahonar Hospital, Alborz University of Medical Sciences, Karaj, Iran.
[Ti] Title:Good's Syndrome-Association of the Late Onset Combined Immunodeficiency with Thymoma: Review of Literature and Case Report.
[So] Source:Iran J Allergy Asthma Immunol;17(1):85-93, 2018 Feb.
[Is] ISSN:1735-1502
[Cp] Country of publication:Iran
[La] Language:eng
[Ab] Abstract:Good's syndrome, the adult onset hypogammaglobulinemia associated with thymoma has been explained about six decades ago. It generally presents with recurrent infections and several paraneoplastic syndromes including myasthenia gravis, pure red cell aplasia, connective tissue disorders, superior vena cava, Horner's syndrome, lichen planus and inflammatory bowel disease. Lack of B cell, dysfunction of T cell, CD4+ T cell lymphopenia, reversed CD4/CD8+ T cell ratio, autoantibodies against Th17 related cytokines have been respected as the pathogenesis of the immune dysregulation this syndrome. A 57-year-old man was admitted to our hospital with a history of thymectomy due to thymoma (Type A) 6 years ago. He developed weight loss and recurrent persistent diarrhea caused by isospora belli. His chest CT scan revealed bilateral bronchiectasis. His laboratory data showed hypogammaglobulinemia and he was treated by monthly IVIG with the diagnosis of good's syndrome. Nevertheless he referred again with left sided loss of vision because of CMV retinitis and he also developed nail candidiasis. Good's syndrome should be considered in every patient with a history of thymoma and recurrent infection. Immunologic evaluation of these patients including measurement of the serum level of immunoglobulin as well as B cell and T cell subgroups should be performed. Physicians must be aware and think about this entity in patients with adult onset immunodeficiency.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Data-Review

  7 / 7645 MEDLINE  
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[PMID]: 29509845
[Au] Autor:Varughese T; Taur Y; Cohen N; Palomba ML; Seo SK; Hohl TM; Redelman-Sidi G
[Ad] Address:Infectious Diseases Service, Memorial Sloan Kettering Cancer Center, New York, NY.
[Ti] Title:Serious Infections in Patients Receiving Ibrutinib for Treatment of Lymphoid Malignancies.
[So] Source:Clin Infect Dis;, 2018 Mar 02.
[Is] ISSN:1537-6591
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background: Ibrutinib is a Bruton's tyrosine kinase inhibitor that is used for the treatment of lymphoid malignancies, including chronic lymphocytic leukemia (CLL), Waldenström's macroglobulinemia and mantle cell lymphoma (MCL). Several case series have described opportunistic infections among ibrutinib recipients, but the full extent of these infections is unknown. We sought to determine the spectrum of serious infections associated with ibrutinib treatment. Methods: We reviewed the electronic medical records of patients with lymphoid malignancies at Memorial Sloan Kettering Cancer Center who received ibrutinib during a five-year period from January 1, 2012 to December 31, 2016. Serious infections were identified by review of the relevant microbiology, clinical laboratory, and radiology data. Risk factors for infection were determined by univariate and multivariate analyses. Results: 378 patients with lymphoid malignancies who received ibrutinib were analyzed. The most common underlying malignancies were CLL and MCL. 84% of patients received ibrutinib as monotherapy. Serious infection developed in 43 patients (11.4%), primarily during the first year of ibrutinib treatment. Of these, 23 (53.5%) developed invasive bacterial infections, and 16 (37.2%) developed invasive fungal infections (IFI). The majority of those who developed IFI on ibrutinib therapy (62.5%) lacked classical clinical risk factors for fungal infection (i.e., neutropenia, lymphopenia, and receipt of corticosteroids). Infection resulted in death in six of the 43 patients (14%). Conclusions: Patients with lymphoid malignancies receiving ibrutinib treatment are at risk for serious infections, including IFI.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180306
[Lr] Last revision date:180306
[St] Status:Publisher
[do] DOI:10.1093/cid/ciy175

  8 / 7645 MEDLINE  
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[PMID]: 29505002
[Au] Autor:Cappell MS; Edhi A; Amin M
[Ad] Address:Division of Gastroenterology & Hepatology, Department of Medicine, William Beaumont Hospital.
[Ti] Title:Case report of primary intestinal lymphangiectasia diagnosed in an octogenarian by ileal intubation and by push enteroscopy after missed diagnosis by standard colonoscopy and EGD.
[So] Source:Medicine (Baltimore);97(3):e9649, 2018 Jan.
[Is] ISSN:1536-5964
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:RATIONALE: Primary intestinal lymphangiectasia (PIL) is a rare, presumably congenital lesion that is usually diagnosed in patients < 3 years old, is rarely first diagnosed in adulthood, and when first diagnosed in adulthood typically presents with symptoms for many years. Although PIL is often identified by endoscopic abnormalities, it must be emphasized that the jejunoileum/distal duodenum must be intubated for diagnosis because the lesions are present in these regions. This work demonstrates that 1)-PIL can occur in an octogenarian; 2)-shows that the characteristic endoscopic findings are not found at colonoscopy without terminal ileal intubation; and 3)-may be missed at standard EGD without distal duodenal intubation. DIAGNOSES: A patient initially presented at age 83 with symptoms of watery diarrhea, abdominal distention, 5-Kg-weight-gain, and weakness for one month, and had typical clinical findings of PIL including chylous ascites, pleural effusions, bilateral pitting leg edema, hypoalbuminemia, borderline lymphopenia, hypovitaminosis-D, and hypocalcemia. Protein-losing-enteropathy was demonstrated by positive stool tests for alpha-1-antitrypsin. Standard colonoscopy revealed no significant lesions, but terminal ileal intubation during colonoscopy demonstrated creamy-white, punctate, mucosal lesions in terminal ileum, characteristic of lymphangiectasia. EGD with intubation to mid-descending duodenum revealed no significant lesions, but subsequent enteroscopy demonstrated lesions in distal duodenum/proximal jejunum similar to those in terminal ileum characteristic of lymphangiectasia. Histopathologic analysis of lesions of terminal ileum/distal duodenum demonstrated dilated mucosal vessels, confirmed as lymphatic vessels by immunohistochemistry. PIL was diagnosed after excluding secondary causes of intestinal lymphangiectasia. INTERVENTIONS/OUTCOMES: Patient placed on standard PIL diet: oral supplements of medium-chain triglycerides, a high protein diet, supplements of fat-soluble vitamins, and avoiding long-chain fatty acids, with marked clinical improvement. LESSONS: This work shows that: 1)-standard EGD and colonoscopy may miss characteristic lesions of PIL, 2)-enteroscopy or terminal ileal intubation at colonoscopy may be required for the diagnosis because lesions are typically located in distal duodenum/jejunoileum; and 3)-PIL can first present in the very elderly even with symptoms of short duration.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process
[do] DOI:10.1097/MD.0000000000009649

  9 / 7645 MEDLINE  
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[PMID]: 29490633
[Au] Autor:Dovsak T; Ihan A; Didanovic V; Kansky A; Verdenik M; Hren NI
[Ad] Address:Clinical Department of Maxillofacial and Oral Surgery, |University Medical Center, Ljubljana, Slovenia. tadej.dovsak@gmail.com.
[Ti] Title:Effect of surgery and radiotherapy on complete blood count, lymphocyte subsets and inflammatory response in patients with advanced oral cancer.
[So] Source:BMC Cancer;18(1):235, 2018 03 01.
[Is] ISSN:1471-2407
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The immune system has a known role in the aetiology, progression and final treatment outcome of oral squamous cell cancers. The aim of this study was to evaluate the influence of radical surgery and radiotherapy on advanced oral squamous cell carcinoma blood counts, lymphocyte subsets and levels of acute inflammatory response markers. METHODS: Blood samples were obtained from 56 patients 5 days before and 10 days after surgery, 30 days and 1 year after radiotherapy. The whole blood count, lymphocyte subsets and inflammatory response markers (C-reactive protein, erythrocyte sedimentation rate, leukocyte count, expression of index CD64 and index CD163 on neutrophils and monocytes) were measured, statistically analysed and correlated with clinical treatment outcomes. RESULTS: The post-operative period was characterised by the onset of anaemia, thrombocytosis, lymphopenia with reduced B lymphocyte, T helper cell and NK cell counts, and a rise in acute phase reactants. Immediately after radiotherapy, the anaemia improved, the lymphopenia worsened, and thrombocyte levels returned to pre-treatment values. There was a drop in counts across the T and B cell lines, including a reduction in B lymphocytes, naïve and memory T cells with reduced CD4+ and CD8+ counts and a decreased CD4/CD8 ratio. One year after radiotherapy all the lymphocyte subsets remained depressed, the only exception being NK cells, whose levels returned to pre-treatment values. CONCLUSIONS: We concluded that surgery resulted in a stronger acute phase response than radiotherapy, while radiotherapy caused a long-lasting reduction in lymphocyte counts. There was no correlation between any of the pre-treatment parameters and the clinical outcome.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:In-Process
[do] DOI:10.1186/s12885-018-4136-9

  10 / 7645 MEDLINE  
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[PMID]: 29427804
[Au] Autor:Redelman-Sidi G; Michielin O; Cervera C; Ribi C; Aguado JM; Fernández-Ruiz M; Manuel O
[Ad] Address:Service of Infectious Disease, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, USA. Electronic address: redelmansidi@hotmail.com.
[Ti] Title:ESCMID Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies: an infectious diseases perspective-immune checkpoint inhibitors, cell adhesion inhibitors, sphingosine 1-phosphate receptor modulators and proteasome inhibitors.
[So] Source:Clin Microbiol Infect;, 2018 Feb 07.
[Is] ISSN:1469-0691
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:BACKGROUND: The present review is part of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) Study Group for Infections in Compromised Hosts (ESGICH) consensus document on the safety of targeted and biological therapies. AIMS: To review, from an infectious diseases perspective, the safety profile of immune checkpoint inhibitors, LFA-3-targeted agents, cell adhesion inhibitors, sphingosine 1-phosphate receptor modulators and proteasome inhibitors, and to suggest preventive recommendations. SOURCES: Computer-based Medline searches with MeSH terms pertaining to each agent or therapeutic family. CONTENT: T-lymphocyte-associated antigen 4 (CTLA-4) and programmed death (PD)-1/PD-1 ligand 1 (PD-L1)-targeted agents do not appear to intrinsically increase the risk of infection but can induce immune-related adverse effects requiring additional immunosuppression. Although CD4 T-cell lymphopenia is associated with alefacept, no opportunistic infections have been observed. Progressive multifocal leukoencephalopathy (PML) may occur during therapy with natalizumab (anti-α4-integrin monoclonal antibody (mAb)) and efalizumab (anti-CD11a mAb), but no cases have been reported to date with vedolizumab (anti-α4ß7 mAb). In patients at high risk for PML (positive anti-JC polyomavirus serology with serum antibody index >1.5 and duration of therapy ≥48 months), the benefit-risk ratio of continuing natalizumab should be carefully considered. Fingolimod induces profound peripheral blood lymphopenia and increases the risk of varicella zoster virus (VZV) infection. Prophylaxis with (val)acyclovir and VZV vaccination should be considered. Proteasome inhibitors also increase the risk of VZV infection, and antiviral prophylaxis with (val)acyclovir is recommended. Anti-Pneumocystis prophylaxis may be considered in myeloma multiple patients with additional risk factors (i.e. high-dose corticosteroids). IMPLICATIONS: Clinicians should be aware of the risk of immune-related adverse effects and PML in patients receiving immune checkpoint and cell adhesion inhibitors respectively.
[Pt] Publication type:JOURNAL ARTICLE; REVIEW
[Em] Entry month:1802
[Cu] Class update date: 180307
[Lr] Last revision date:180307
[St] Status:Publisher


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