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We report the case of a 48-year-old man who presented with fatigue and weight loss. A local physician observed elevated alkaline phosphatase levels, anemia, thrombocytopenia, and renal dysfunction. Fever also appeared, and the patient was admitted to our hospital. Computed tomography revealed hepatosplenomegaly, pleural and ascitic fluid, and left axillary lymphadenopathy. Bone marrow biopsy indicated hyperplasia with increased megakaryocytes and reticulin fibrosis. Axillary lymph node biopsy showed Castleman's disease-like features. Liver biopsy revealed proliferation of reticulin fibrosis. Therefore, TAFRO syndrome was diagnosed and treatment with 1 mg/kg prednisolone was started. Anemia and thrombocytopenia improved, and after 24 weeks of treatment, serum hyaluronic acid and type IV collagen decreased to the normal range. Bone marrow biopsy after 18 weeks of treatment showed decreased reticular fibers. In TAFRO syndrome, improvement of liver and bone marrow fibrosis can be expected with adequate intervention, and serum hyaluronic acid and type IV collagen are useful for evaluating fibrosis.
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Prednisolona , Humanos , Masculino , Pessoa de Meia-Idade , Prednisolona/administração & dosagem , Hiperplasia do Linfonodo Gigante/tratamento farmacológico , Hiperplasia do Linfonodo Gigante/patologia , Fibrose , Resultado do Tratamento , SíndromeRESUMO
Purpose: To evaluate 10-year outcome of infliximab (IFX) treatment for uveitis in Behçet disease (BD) patients using a standardized follow-up protocol. Design: Retrospective longitudinal cohort study. Participants: 140 BD uveitis patients treated with IFX enrolled in our previous study. Methods: Medical records were reviewed for demographic information, duration of IFX treatment, number of ocular attacks before IFX initiation, best corrected visual acuity (VA) at baseline and 1, 2, 3, 4, 5, and 10 years after IFX initiation, uveitis recurrence after IFX initiation and main anatomical site, concomitant therapies, and adverse events (AEs). Main outcome measures: 10-year IFX continuation rate and change in LogMAR VA. Results: Of 140 BD patients, 106 (75.7%) continued IFX treatment for 10 years. LogMAR VA improved gradually after initiation of IFX, and the improvement reached statistical significance from 2 years of treatment. Thereafter, significant improvement compared with baseline was maintained until 10 years, despite a slight deterioration of logMAR VA from 5 years. However, eyes with worse baseline decimal VA < 0.1 showed no significant improvement from baseline to 10 years. Uveitis recurred after IFX initiation in 50 patients (recurrence group) and did not recur in 56 (non-recurrence group). Ocular attacks/year before IFX initiation was significantly higher in the recurrence group (2.82 ± 3.81) than in the non-recurrence group (1.84 ± 1.78). In the recurrence group, uveitis recurred within 1 year in 58% and within 2 years in 74%. Seventeen patients (34%) had recurrent anterior uveitis, 17 (34%) had posterior uveitis, and 16 (32%) had panuveitis, with no significant difference in VA outcome. In addition, logMAR VA at 10 years did not differ between the recurrence and non-recurrence groups. AEs occurred among 43 patients (30.7%), and 24 (17.1%) resulted in IFX discontinuation before 10 years. Conclusions: Among BD patients with uveitis who initiated IFX, approximately 75% continued treatment for 10 years, and their VA improved significantly and was maintained for 10 years. Uveitis recurred in one-half of the patients, but visual acuity did not differ significantly from the patients without recurrence.
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PURPOSE: To compare the efficacy and safety of a combination therapy of prednisolone and cyclosporine and corticosteroid pulse therapy in Vogt-Koyanagi-Harada (VKH) disease. STUDY DESIGN: A prospective, multicenter, randomized, non-inferiority trial. METHODS: Patients of new-onset acute VKH disease at 11 centers in Japan between 2014 and 2018 were randomized to a combination (oral prednisolone 60 mg daily with gradual taper-off to 35 mg/day and cyclosporine 3 mg/kg/day) and corticosteroid (methylprednisolone 1000 mg for 3 days followed by oral prednisolone) groups, and were followed for 1 year. RESULTS: Thirty-four were assigned to the combination and thirty-six patients to the corticosteroid group. Recurrence/worsening risk was 0.15 (95% confidence-interval [CI] 0.03-0.27) in the combination group and 0.25 (95% CI 0.11-0.39) in the corticosteroid group, with a risk difference of - 0.10 (90% CI - 0.27 to 0.06), demonstrating non-inferiority of the combination group with a non-inferiority margin of 0.20 (P = 0.0013). Serious adverse events occurred in three patients (two with hyponatremia and one with severe headaches) in the combination group and none in the corticosteroid group. Sunset glow fundus grades and cataract rates at 1 year were 0.57 (95% CI 0.42-71) and 4.3% in the combination group and 0.91 (95% CI 0.78-1.04) and 34.0% in the corticosteroid group, respectively. CONCLUSIONS: Combination therapy was noninferior to corticosteroid therapy with respect to recurrence/worsening risk. Notably, the recurrence/worsening risk, sunset glow fundus grade, and cataract rate were lower in the combination group than in the corticosteroid group.
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Ciclosporina/uso terapêutico , Metilprednisolona/uso terapêutico , Síndrome Uveomeningoencefálica , Humanos , Estudos Prospectivos , Síndrome Uveomeningoencefálica/diagnóstico , Síndrome Uveomeningoencefálica/tratamento farmacológicoRESUMO
The patient was a 69-year-old man diagnosed with stage â £B lung adenocarcinoma with 95% programmed death- ligand 1 expression, and pembrolizumab monotherapy was initiated. The patient exhibited fatigue from the 12th course(36 weeks after treatment initiation) of treatment. Chest computed tomography revealed scattered ground-glass opacities in the upper lobes of both lungs, and he was subsequently diagnosed with interstitial pneumonia. Fatigue persisted even after a drug holiday from pembrolizumab, and the patient was diagnosed with hypopituitarism based on the results of endocrinological examinations. Rashes appeared on both legs 40 weeks after treatment initiation, which led to the patient being diagnosed with a drug-induced skin disorder. All the adverse events resolved upon treatment with hydrocortisone. Immune- related adverse events due to pembrolizumab may occur in multiple organs simultaneously.
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Anticorpos Monoclonais Humanizados , Neoplasias Pulmonares , Idoso , Anticorpos Monoclonais Humanizados/efeitos adversos , Humanos , Pulmão , Neoplasias Pulmonares/tratamento farmacológico , Masculino , HipófiseRESUMO
Scleritis involves inflammation of the sclera, which constitutes 75% of the wall of the eye. This pathology is often seen as an ocular lesion associated with systemic inflammatory diseases. Severe types of scleritis such as posterior scleritis require urgent immunosuppressive treatments, including molecularly targeted therapies to avoid permanent visual impairment. Which molecules should be selected as targets has remained unclear. To clarify the pathogenesis of scleritis and propose appropriate target molecules for therapy, we have established novel animal model of scleritis by modifying the Collagen-II Induced Arthritis (CIA) model. Immunization twice with collagen II emulsified with complete Freund's adjuvant (CFA) caused arthritis and scleritis. The clinical appearance resembled human diffuse scleritis. Histopathological analysis suggested that macrophages, plasma cells, deposition of immune complexes, and growth of blood and lymphatic vessels are involved in the pathogenesis of CIA-associated scleritis. In addition, we analysed the background diseases of posterior scleritis and responses to molecularly targeted therapies as a case series study. We inferred from both the animal model and case series study that targets should not be T cells, but factors inhibiting macrophage activity such as tumor necrosis factor (TNF) and interleukin (IL)-6, and molecules suppressing antibody-producing cells such as CD20 on B cells should be targeted by molecularly targeted therapies.
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Artrite Experimental/complicações , Terapia de Alvo Molecular , Esclerite/imunologia , Esclerite/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/metabolismo , Bovinos , Modelos Animais de Doenças , Feminino , Humanos , Imunoglobulinas/metabolismo , Inflamação/patologia , Linfangiogênese , Masculino , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Esclerite/diagnóstico por imagem , Esclerite/tratamento farmacológicoRESUMO
Sarcoidosis is a genetically complex systemic inflammatory disease that affects multiple organs. We present a GWAS of a Japanese cohort (700 sarcoidosis cases and 886 controls) with replication in independent samples from Japan (931 cases and 1,042 controls) and the Czech Republic (265 cases and 264 controls). We identified three loci outside the HLA complex, CCL24, STYXL1-SRRM3, and C1orf141-IL23R, which showed genome-wide significant associations (P < 5.0 × 10-8) with sarcoidosis; CCL24 and STYXL1-SRRM3 were novel. The disease-risk alleles in CCL24 and IL23R were associated with reduced CCL24 and IL23R expression, respectively. The disease-risk allele in STYXL1-SRRM3 was associated with elevated POR expression. These results suggest that genetic control of CCL24, POR, and IL23R expression contribute to the pathogenesis of sarcoidosis. We speculate that the CCL24 risk allele might be involved in a polarized Th1 response in sarcoidosis, and that POR and IL23R risk alleles may lead to diminished host defense against sarcoidosis pathogens.
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Quimiocina CCL24/genética , Sistema Enzimático do Citocromo P-450/genética , Predisposição Genética para Doença , Receptores de Interleucina/genética , Sarcoidose/etiologia , Alelos , Quimiocina CCL24/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Feminino , Estudos de Associação Genética , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Japão , Masculino , Razão de Chances , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Receptores de Interleucina/metabolismo , Sarcoidose/diagnóstico , Sarcoidose/metabolismoRESUMO
The eye is provided with immune protection against pathogens in a manner that greatly reduces the threat of inflammation-induced vision loss. Immune-mediated inflammation and allograft rejection are greatly reduced in the eye, a phenomenon called 'immune privilege'. Corneal tissue has inherent immune privilege properties with underlying three mechanisms: (1) anatomical, cellular, and molecular barriers in the cornea; (2) an immunosuppressive microenvironment; and (3) tolerance related to regulatory T cells and anterior chamber-associated immune deviation. This review describes the molecular mechanisms of the immunosuppressive microenvironment and regulatory T cells in the cornea that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, it also provides an update on immune checkpoint molecules in corneal and systemic immune regulation, and its relevance for dry eye associated with checkpoint inhibitor therapy.
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Córnea/imunologia , Síndromes do Olho Seco/imunologia , Privilégio Imunológico/imunologia , Sistema Imunitário , Animais , Câmara Anterior/imunologia , Antígeno B7-H1/metabolismo , Transplante de Córnea , Proteína Ligante Fas/metabolismo , Rejeição de Enxerto/imunologia , Humanos , Tolerância Imunológica , Fatores Imunológicos , Imunossupressores/uso terapêutico , Inflamação , Ligantes , Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Receptor fas/metabolismoRESUMO
Purpose: V-domain immunoglobulin suppressor of T cell activation (VISTA) is a novel immune checkpoint receptor and ligand for regulating T cell proliferation and cytokine production. The purpose of the present study was to determine the role of VISTA in the immune privilege of corneal allografts. Methods: Expression of VISTA mRNA in mouse eyes was assessed with reverse-transcription PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of BALB/c wild-type recipients treated with anti-VISTA mAb, and graft survival was assessed. A separate set of BALB/c mice treated with anti-VISTA mAb or rat IgG received injection of C57BL/6 splenocytes into the anterior chamber, and induction of allospecific anterior chamber-associated immune deviation (ACAID) was assessed. CD4+ and CD8+ T cells in the spleen were assessed with flow cytometry. Results: VISTA mRNA was constitutively expressed in the cornea, and the expression of VISTA was localized to CD11b+ cells on the corneal stroma. Survival of allografts treated with anti-VISTA mAb was less than that of the control. ACAID was induced less efficiently in BALB/c mice treated with VISTA mAb. The proportions of CD8+ T cells and CD8+ CD103+ T cells (CD8+ T regulatory cells) in the spleen of BALB/c mice treated with anti-VISTA mAb were significantly lower than those of the control. Conclusions: VISTA may play an essential role in the acceptance of corneal allografts via involvement with allospecific ACAID, which suppresses T cell infiltration into the cornea.
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Transplante de Córnea/métodos , Endotélio Corneano/patologia , Regulação da Expressão Gênica , Rejeição de Enxerto/genética , Sobrevivência de Enxerto/imunologia , Privilégio Imunológico/genética , Proteínas de Membrana/genética , Aloenxertos , Animais , Modelos Animais de Doenças , Endotélio Corneano/imunologia , Citometria de Fluxo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Imuno-Histoquímica , Masculino , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Linfócitos T/imunologia , Linfócitos T/patologiaRESUMO
Corneal transplantation is the most successful solid organ transplantation performed in humans. The extraordinary success of orthotopic corneal allografts, in both humans and experimental animals, is related to the phenomenon of "immune privilege". Inflammation is self-regulated to preserve ocular functions because the eye has immune privilege. At present, three major mechanisms are considered to provide immune privilege in corneal transplantation: 1) anatomical, cellular, and molecular barriers in the cornea; 2) tolerance related to anterior chamber-associated immune deviation and regulatory T cells; and 3) an immunosuppressive intraocular microenvironment. This review describes the mechanisms of immune privilege that have been elucidated from animal models of ocular inflammation, especially those involving corneal transplantation, and its relevance for the clinic. An update on molecular, cellular, and neural interactions in local and systemic immune regulation is provided. Therapeutic strategies for restoring immune privilege are also discussed.
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Transplante de Córnea , Privilégio Imunológico/fisiologia , Sobrevivência de Enxerto/imunologia , Humanos , Tolerância Imunológica/fisiologia , Linfangiogênese/fisiologia , Linfócitos T Reguladores/imunologiaRESUMO
Purpose: Corneal endothelial cell density undergoes a progressive decrease for many years after transplantation, eventually threatening patients with late endothelial failure. The purpose of this study was to investigate the possibility of an immunologic response in successfully grafted corneal endothelium. Methods: The corneal endothelium of patients who had undergone corneal transplantation was evaluated by specular microscopy. Rabbit models were subjected to penetrating keratoplasty (PK) with either syngeneic or allogeneic corneal transplants and Descemet's stripping endothelial keratoplasty (DSEK) with allogeneic corneal transplants. The presence of immune cells and expression of proinflammatory cytokines were determined by immunostaining. The corneal endothelium and immune cells were also evaluated by scanning electron microscopy. Results: Scanning slit contact specular microscopy of patients with no features of graft rejection revealed cell-like white dots on the grafted corneal endothelium. The corneal endothelium of the allogeneic PK and DSEK rabbit models displayed the presence of immune cells, including CD4+ T-helper cells, CD8+ cytotoxic T cells, CD20+ B lymphocytes, CD68+ macrophages, and neutrophils, but these immune cells were rarely observed in the syngeneic PK model. These immune cells also produced proinflammatory cytokines. Notably, some of the corneal endothelial cells situated near these immune cells exhibited features of apoptosis. Conclusions: T lymphocytes, B lymphocytes, macrophages, and neutrophils are present on the grafted corneal endothelium in both PK and DSEK allogeneic rabbit models. The potential involvement of immune cells as an underlying pathophysiology for late endothelial failure deserves further examination.
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Ceratoplastia Endotelial com Remoção da Lâmina Limitante Posterior/métodos , Endotélio Corneano/imunologia , Rejeição de Enxerto/imunologia , Imunidade Celular , Linfócitos T/imunologia , Adulto , Idoso , Animais , Contagem de Células , Doenças da Córnea/cirurgia , Citocinas/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Endotélio Corneano/ultraestrutura , Feminino , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Macrófagos/imunologia , Macrófagos/ultraestrutura , Masculino , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Neutrófilos/imunologia , Neutrófilos/ultraestrutura , Coelhos , Transplante HomólogoRESUMO
Purpose: The interaction between the inducible costimulatory molecule (ICOS) and ICOS ligand (ICOSL) has been implicated in the differentiation and functions of T cells. The purpose of the present study was to determine the role of ICOS-ICOSL in the immune privilege of corneal allografts. Methods: Expression of ICOS and ICOSL mRNA from mouse eyes was assessed by RT-PCR. Corneas of C57BL/6 mice were orthotopically transplanted into the eyes of ICOS-/- BALB/c recipients and BALB/c wild-type (WT) recipients treated with anti-ICOSL mAb, and graft survival was assessed. A separate set of WT and ICOS-/- BALB/c mice received an anterior chamber injection of C57BL/6 splenocytes, and induction of allospecific anterior chamber-associated immune deviation (ACAID) was assessed. In vitro, cornea was incubated with T cells from WT and ICOS-/- BALB/c mice, and destruction of corneal endothelial cells (CECs) and the population of Foxp3+ CD25+ CD4+ T cells was assessed. Results: Inducible costimulatory molecule ligand mRNA was constitutively expressed in the cornea, iris-ciliary body, and retina. Allograft survival in ICOS-/- recipients and WT recipients treated with anti-ICOSL mAb was significantly shorter than in control recipients. Anterior chamber-associated immune deviation was induced less efficiently in ICOS-/- mice. Destruction of CECs by alloreactive ICOS-/- T cells was enhanced compared with WT T cells. After coincubation with allogeneic corneal tissue, the proportion of regulatory T cells was significantly greater among WT T cells than in ICOS-/- T cells. Conclusions: The expression of ICOSL in the cornea and the ICOS-mediated induction of Foxp3+ CD4+ regulatory T cells may contribute to successful corneal allograft survival.
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Córnea/metabolismo , Transplante de Córnea , Regulação da Expressão Gênica , Sobrevivência de Enxerto/imunologia , Imunidade Celular , Ligante Coestimulador de Linfócitos T Induzíveis/genética , Proteína Coestimuladora de Linfócitos T Induzíveis/genética , Animais , Córnea/imunologia , Córnea/patologia , Citometria de Fluxo , Rejeição de Enxerto/genética , Rejeição de Enxerto/imunologia , Ligante Coestimulador de Linfócitos T Induzíveis/biossíntese , Proteína Coestimuladora de Linfócitos T Induzíveis/biossíntese , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Linfócitos T Reguladores/imunologia , Transplante HomólogoRESUMO
OBJECTIVES: Behçet's disease (BD) is a systemic inflammatory disorder polarised to the Th1 and Th17 immune systems. Allergic diseases are polarised to the Th2 immune system. The aim of the present study is to investigate the prevalence of allergic diseases in patients who have BD. METHODS: The study involved a large-scale interview survey of Japanese patients with BD at 21 institutes of ophthalmology; 353 patients (255 males and 98 females) were recruited for this study. We analysed the history of allergic diseases such as atopic dermatitis (AD), allergic rhinitis (AR), bronchial asthma (BA) and drug/food allergies (FA). RESULTS: Oral aphthous ulcers, ocular lesions, skin lesions, genital ulcers, arthritis, neurological lesions, intestinal lesions, deep vein thrombosis and epididymitis were reported in 95.8%, 98.6%, 72.5%, 44.8%, 13.9%, 6.8%, 6.2%, 3.7% and 1.4% of the patients, respectively. It was also reported that 73 patients (20.7%) had histories of allergic diseases: AD (5 cases, 1.4%), AR (36 cases, 10.2%), BA (19 cases, 5.4%) and FA (30 cases, 8.5%). This percentage was significantly lower than in a survey that Japan's Ministry of Health, Labour and Welfare conducted for healthy population (47.6%) (odds ratio = 0.29, 95% confidence interval = 0.22-0.38, p=4.9×10-22). Frequencies of posterior/pan-uveitis, relatively severe ocular findings, and visual prognosis were not affected by a history of allergic diseases in BD. CONCLUSIONS: Patients with BD had fewer complications from allergic diseases than did the entire population of Japan.
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Síndrome de Behçet/epidemiologia , Oftalmopatias/epidemiologia , Hipersensibilidade/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Síndrome de Behçet/diagnóstico , Síndrome de Behçet/imunologia , Comorbidade , Oftalmopatias/diagnóstico , Oftalmopatias/imunologia , Feminino , Inquéritos Epidemiológicos , Humanos , Hipersensibilidade/diagnóstico , Hipersensibilidade/imunologia , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Adulto JovemRESUMO
PURPOSE: To report the clinical statistical analysis of patients with endogenous intraocular inflammation who visited Nippon Medical School Hospital during the 8 years from 2004 to 2012. SUBJECTS AND METHODS: This retrospective study involved 759 new patients with endogenous intraocular inflammation who visited Nippon Medical School Hospital during the 8 years from April 2004 to April 2012. RESULTS: The subjects comprised 357 men and 402 women. The ratio of men to women was 1 : 1.1. The age averaged 50.8 ± 16.6 years. Definitive diagnosis was made in 464 cases (61.1%). The most frequent clinical entity was sarcoidosis, followed by scleritis, Vogt-Koyanagi-Harada disease, herpetic iridocyclitis without acute retinal necrosis, acute anterior uveitis associated with human leukocyte antigen (HLA) -B27 and Behçet's disease. Anterior uveitis was the most frequent compared with intermediate, posterior, and pan-uveitis. The incidence of secondary glaucoma was 28.6%, and steroid responder was 28.6%. CONCLUSION: Sarcoidosis, scleritis and Vogt-Koyanagi-Harada disease were frequent intraocular inflammations in ophthalmologic patients at Nippon Medical School Hospital.
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Sarcoidose/epidemiologia , Esclerite/epidemiologia , Síndrome Uveomeningoencefálica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Inflamação/epidemiologia , Japão , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
A 73-year-old man visited our hospital for consultation regarding a pancreatic tumor. Abdominal computed tomography, magnetic resonance imaging, and endoscopic ultrasound scan (EUS) revealed tumor 2 cm in diameter located in the pancreatic tail. EUS-guided fine needle aspiration (EUS-FNA) suggested pancreatic mixed acinar-endocrine carcinoma, and he underwent distal pancreatectomy. Few reports exist where preoperative EUS-FNA suggested pancreatic mixed acinar-endocrine carcinoma; thus, we report this case.
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas/patologia , Idoso , Humanos , Masculino , Cuidados Pré-Operatórios , Neoplasias PancreáticasRESUMO
PURPOSE: To evaluate the long-term efficacy and safety of infliximab for the treatment of uveitis in Behçet's disease (BD). DESIGN: Retrospective multicenter study using a questionnaire. PARTICIPANTS: A total of 164 consecutive patients with BD treated with infliximab for more than 1 year were studied. The mean age at initiation of infliximab treatment was 42.6±11.7 years, and the mean treatment duration was 32.9±14.4 months. METHODS: Data before and at the last visit during infliximab treatment were analyzed in 4 groups divided by duration of treatment: group A (n = 43, 12-<24 months), group B (n = 62, 24-<36 months), group C (n = 42, 36-<48 months), and group D (n = 17, ≥48 months). MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA), relapse of ocular inflammation, numbers of ocular inflammatory attacks per year, and adverse effects of infliximab therapy. RESULTS: The frequency of ocular attacks decreased in all groups (from 5.3±3.0 to 1.0±0.3 in group A, 4.8±4.6 to 1.4±0.3 in group B, 4.1±2.9 to 0.9±0.3 in group C, and 9.5±5.8 to 1.6±0.5 in group D; all P < 0.05). The BCVA was improved in approximately 55% of the eyes after treatment. Mean BCVA converted to logarithm of the minimum angle of resolution was improved after treatment with infliximab in groups A to C (from 0.79±1.04 to 0.59±0.94 in group A, 0.59±1.07 to 0.41±1.04 in group B, and 1.15±1.77 to 0.92±1.73 in group C; all P < 0.05) but not in group D. Uveitis relapsed in 59.1% of all patients after infliximab treatment, and no difference in duration until relapse was observed between individual groups. Approximately 80% of relapses occurred within 1 year after the initiation of infliximab treatment in all groups, 90% of which were controlled by increasing doses of topical corticosteroids and shortening the interval of infliximab infusion. Adverse effects were observed in 65 cases or 35% of all subjects. Infliximab treatment was continued in 85% of the patients, but 15% of the patients discontinued infliximab treatment because of adverse effects or insufficient efficacy. CONCLUSIONS: Infliximab reduced the frequency of ocular attacks and improved visual acuity in patients with BD-related uveitis and was generally well tolerated with few serious adverse events.
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Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Síndrome de Behçet/tratamento farmacológico , Uveíte/tratamento farmacológico , Adolescente , Adulto , Idoso , Análise de Variância , Anti-Inflamatórios não Esteroides/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Síndrome de Behçet/complicações , Feminino , Humanos , Infliximab , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários , Uveíte/etiologia , Acuidade Visual , Adulto JovemRESUMO
The eye is an immune-privileged organ, and corneal transplantation is therefore one of the most successful organ transplantation. The immunosuppressive intraocular microenvironment is known as one of the mechanisms underlying immune privilege in the eye. T-cell immunoglobulin and mucin domain (Tim)-3 is a regulatory molecule for T-cell function, and galectin (Gal)-9 is a Tim-3 ligand. We investigated the role of this pathway in establishing the immune-privileged status of corneal allografts in mice. Gal-9 is constitutively expressed on the corneal epithelium, endothelium and iris-ciliary body in normal mouse eyes and eyes bearing surviving allografts, and Tim-3 was expressed on CD8 T cells infiltrating the allografts. Allograft survival in recipients treated with anti-Tim-3 monoclonal antibody (mAb) or anti-Gal-9 mAb was significantly shorter than that in control recipients. In vitro, destruction of corneal endothelial cells by allo-reactive T cells was enhanced when the cornea was pretreated with anti-Gal-9 mAb. Blockade of Tim-3 or Gal-9 did not abolish anterior chamber-associated immune deviation. We propose that constitutive expression of Gal-9 plays an immunosuppressive role in corneal allografts. Gal-9 expressed on corneal endothelial cells protects them from destruction by allo-reactive T cells within the cornea.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Transplante de Córnea , Galectinas/metabolismo , Sobrevivência de Enxerto/imunologia , Imunidade/imunologia , Animais , Câmara Anterior/imunologia , Câmara Anterior/patologia , Morte Celular , Citoproteção , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Endotélio Corneano/patologia , Galectinas/antagonistas & inibidores , Galectinas/genética , Rejeição de Enxerto/imunologia , Receptor Celular 2 do Vírus da Hepatite A , Tecido Linfoide/metabolismo , Masculino , Camundongos , Receptores Virais/antagonistas & inibidores , Receptores Virais/genética , Receptores Virais/metabolismo , Transplante HomólogoAssuntos
Asma/complicações , Cegueira Cortical/etiologia , Hipóxia/complicações , Idoso , Cegueira Cortical/diagnóstico , Cegueira Cortical/tratamento farmacológico , Eletrorretinografia , Feminino , Angiofluoresceinografia , Humanos , Hipóxia/diagnóstico , Hipóxia/tratamento farmacológico , Imageamento por Ressonância Magnética , Escotoma/diagnóstico , Escotoma/tratamento farmacológico , Escotoma/etiologia , Tomografia Computadorizada de Emissão de Fóton Único , Acuidade Visual , Campos Visuais , Vitamina B 12/administração & dosagem , Vitamina B 12/análogos & derivadosRESUMO
The original evidence for the existence of immunologically privileged sites in the body was based on the prolonged survival of genetically disparate transplanted tissue in the anterior chamber of the eye. The failure of the immune system to elicit an immune response in this and other such sites constitutes the hallmark of the immune privilege status. The remarkably successful field of corneal transplantation in clinical practice is undoubtedly associated with corneal immune privilege. Several investigations have addressed the regulatory mechanisms governing this phenomenon, which involves a complex interplay between multiple molecular and cellular pathways. Furthermore, the use of various transgenic mouse models has facilitated the identification of critical pathways, which upon disruption can modify the immune privileged status of the eye. Understanding these pathways not only reveals the mechanisms underlying various ocular inflammatory disease conditions, but also has clinical implications for the transplantation field and for the treatment of autoimmunity.