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1.
J Invest Dermatol ; 144(3): 563-572.e9, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37742913

RESUMO

Sclerotic-type cutaneous chronic graft-versus-host disease is a severe complication of allogeneic hematopoietic stem cell transplantation, with profound morbidity. A dearth of effective, targeted treatment options necessitates further investigation into the molecular mechanisms underlying this T-cell-mediated disease. In this study, we compared the transcriptome in skin biopsies from pediatric and young adult (aged <25 years) patients with sclerotic-type cutaneous chronic graft-versus-host disease (n = 7) with that in demographically matched healthy controls (n = 8) and patients with atopic dermatitis (n = 10) using RNA sequencing with RT-PCR and immunohistochemistry validation. Differential expression was defined as fold change > 1.5 and false discovery rate < 0.05. Sclerotic-type cutaneous chronic graft-versus-host disease exhibited strong and significant T helper (Th)1 skewing through key related cytokines and chemokines (CXCL9/10/11, IFNG/IFN-γ, STAT1/signal transducer and activator of transcription 1). Several markers related to the TSLP-OX40 axis were significantly upregulated relative to those in both controls and lesional atopic dermatitis, including TNFSF4/OX40L, TSLP, and IL33, as well as fibroinflammatory signatures characterized in a prior study in systemic sclerosis. Gene set variation analysis reflected marker-level findings, showing the greatest enrichment of the Th1 and fibroinflammatory pathways, with no global activation identified in Th2 or Th17/Th22. Cell-type deconvolution revealed a significant representation of macrophages and vascular endothelial cells. Sclerotic-type cutaneous chronic graft-versus-host disease in young patients may therefore be characterized by strong Th1-related upregulation with a unique TSLP-OX40 signature, suggesting new therapeutic avenues for this devastating disease.


Assuntos
Síndrome de Bronquiolite Obliterante , Dermatite Atópica , Doença Enxerto-Hospedeiro , Dermatopatias , Adulto Jovem , Humanos , Criança , Citocinas/metabolismo , Dermatite Atópica/genética , Dermatite Atópica/patologia , Células Endoteliais/metabolismo , Células Th2/metabolismo , Doença Enxerto-Hospedeiro/genética , Ligante OX40
2.
Isr Med Assoc J ; 22(5): 310-314, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32378824

RESUMO

BACKGROUND: There is a lack of information regarding acute pancreatitis in Israel. However, the most prevalent worldwide etiologic causes of acute pancreatitis are biliary stones and alcohol abuse. OBJECTIVES: To delineate the prevalence, main causes, rate of recurrence, mortality, and complications of acute pancreatitis in southern Israel. METHODS: In this retrospective study medical files of all hospitalized patients diagnosed with acute pancreatitis during a 13-year period were reviewed. RESULTS: The study comprised 602 patients with acute pancreatitis (120/100,000 patients or 1.2/1000 admissions). The main causes were: biliary stones (41.5%), alcohol (8.8%), and drugs (8.3%). Disothiazide was the most common drug associated with acute pancreatitis followed by sitagliptin, angiotensin converting enzyme (ACE) inhibitors, and simvastatin. Undetermined etiology made up 33.6% of the cases. Recurrence rate was 33.8% (alcohol 3.7%, hypertriglyceridemia 1.8%). This finding had no implications on mortality rate, which was stable at 4.3%. Bilateral pleural effusion, advanced computed tomography severity index (CTSI) grading, older age, and being single were found to be poor prognostic predictive factors. CONCLUSIONS: Biliary pancreatitis is the main cause of acute pancreatitis in southern Israel, similar to the rest of the world, and constitutes a much more common etiology than alcohol. Furthermore, drug-induced pancreatitis is a common etiology, with disothiazide being the most common drug associated with pancreatitis followed by ACE-Inhibitors, sitagliptin, and simvastatin. Recurrence of pancreatitis is common in this geographic area, and older age, advanced CTSI grading, bilateral pleural effusion, and being single are all poor prognostic predictive factors.


Assuntos
Pancreatite/epidemiologia , Doença Aguda , Adulto , Idoso , Feminino , Humanos , Israel/epidemiologia , Masculino , Pessoa de Meia-Idade , Pancreatite/complicações , Pancreatite/etiologia , Prevalência , Recidiva , Estudos Retrospectivos
4.
Am J Trop Med Hyg ; 93(4): 770-3, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26283744

RESUMO

Cutaneous leishmaniasis (CL) is diverse in its clinical presentation but usually demonstrates an erythematous, infiltrated, ulcerated, and crusted papule or nodule in exposed areas of the body. Rare clinical features have been reported including lymphatic dissemination, usually with subcutaneous nodules along lymphatic channels. Herein, we present six patients suffering from Old World CL with lymphatic dissemination characterized by sporotrichoid subcutaneous nodules along the lymphatic channels draining the primary lesion. Patients' history, clinical and laboratory findings were collected and summarized. Lymphatic dissemination of CL in our patients manifested as subcutaneous nodules without epidermal involvement within the axis of lymphatic drainage toward the regional lymph node, at times accompanied by regional lymphadenopathy. In all patients, the lymphatic dissemination was not present at initial diagnosis of CL, appearing only after local (topical or intralesional) treatment was initiated. In three patients, the subcutaneous nodules resolved without systemic treatment. Lymphatic dissemination of Old World CL is not uncommon and may possibly be triggered by local treatment. It should be recognized by dermatologists, especially those working in endemic areas. Systemic treatment may be not necessary since spontaneous resolution may occur.


Assuntos
Leishmaniose Cutânea/patologia , Doenças Linfáticas/parasitologia , Administração Tópica , Adolescente , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Criança , Feminino , Humanos , Lactente , Leishmaniose Cutânea/complicações , Leishmaniose Cutânea/tratamento farmacológico , Linfonodos/parasitologia , Linfonodos/patologia , Doenças Linfáticas/etiologia , Masculino
7.
Eur J Intern Med ; 17(1): 20-3, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16378880

RESUMO

INTRODUCTION: Hospital readmission within a short time of discharge is a common phenomenon in internal medicine. Although there are a few reports of intensive care and surgical readmission rates there is almost no information available on the readmission rates of internal medicine patients. AIMS: To explore the medical patient readmission rate within 30 days of discharge from a medical center in southern Israel, and determine how it may be related to age, gender, diagnoses and other factors. METHODS: Chart review of all 2469 patients admitted to the departments of internal medicine of Barzilai Health Center between May 1st and July 15th 2002. A randomized control group of 87 patients was gathered from patients admitted to hospital during the study period but who were not readmitted within 30 days of discharge. RESULTS: 124 patients (5%) were readmitted. They were significantly older than controls (mean age 68.7+/-14.8 vs. 59.3+/-16.3 years), (p<0.0003), 21% being over 80 years of age (compared with 9% of controls, p<0.05) and had a lower average Functional Independence Measure (FIM). The index hospitalization of readmitted patients was significantly longer than the hospitalization of control patients (6.1+/-5.5 vs. 4.1+/-3.8 days), (p<0.04). Most patients (85%) were readmitted for the same medical reason that prompted the original hospitalization. The 15% readmitted for other reasons were older (74.9+/-12.4 vs. 67.6+/-15.0 years) (p<0.001) and had a lower Functional Independence Measure (mean FIM 4.6+/-2.2 vs. 5.7+/-1.9), (p<0.05). New immigrants (mean age 71.1+/- 12.9 years) had significantly lower readmission rate compared to the general population (3.2% vs. 4.98%), (p<0.05). Veteran Israelis, on the other hand, had a higher readmission rate than the general population (6.8% vs. 4.98%) (p<0.001). CONCLUSION: Only 5% of patients required readmission. The original hospitalization period of readmitted patients was significantly longer than controls and most readmissions were for the original medical problem for which they were readmitted originally or because of a low functional status. Hospitalized new immigrants although being older in age are less likely to require readmission, while veteran Israelis are more likely to be readmitted.

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