Impaired TGF-ß signaling in patients with active systemic lupus erythematosus is associated with an overexpression of IL-22.

The mechanisms leading to the disruption of self-tolerance in systemic lupus erythematosus (SLE) remain elusive. Herein, we aimed to decipher the molecular basis of the impaired response of mononuclear cells to TGF-ß1. The Smad3-pathway was explored on CD3+ lymphocytes in either active or non active SLE patients. An impaired transcription of TGF-ß1 target genes was demonstrated in the CD3+ lymphocytes of active SLE patients confirming that the defect involves T cells and pointing to its extrinsic nature. We further demonstrate that the defect did not result from an impaired TGF-ßRII expression or Smad2/3 phosphorylation suggesting that the mechanism lies downstream Smad2/3 translocation. Interestingly, the TGF-1 signaling defect did not correlate with an increased expression of soluble or membrane-bound IL-15. However, it was associated with an overexpression of IL-22. This suggests that an excessive activation of AhR pathway (through UV radiations, infections, etc.) could lead to the inhibition of immunosuppressive actions of TGF-ß thus disrupting immune homeostasis in SLE. Collectively, our data suggest that the impaired response to TGF-ß in SLE patients is associated with disease activity and provide new insights into the pathogenesis of SLE since it could establish the link between the environmental factors and the aberrancies of the immune system usually described in SLE.

Young ischemic stroke in Tunisia: a multicentric study.

PURPOSE: There is wanting data regarding young ischemic stroke in developing countries, especially in Tunisia. The purpose of this study was to investigate risk factors and etiologies of young ischemic stroke in Tunisian and make a comparison with previous reports. MATERIALS AND METHODS: A total of 102 young ischemic stroke patients (15-45 years old) were admitted, between January 1996 and August 2007, to 11 departments of internal medicine in different Tunisian hospitals. The risk factors for stroke were documented and assessed. Diagnosis workup consisted of anamnesis, complete physical examination and extensive laboratory, radiologic, immunologic, neurologic and cardiologic examination. Stroke etiologies were classified according the Trial of ORG 10172 in acute stroke treatment. RESULTS: There were 42 men (41.2%) and 60 women (58.89%) with a mean age at onset of 35.7 years. As regards stroke subtype, large-artery atherosclerosis was diagnosed in 6.9% of cases, cardioembolism in 11.8%, small-vessel occlusion in 8.8%, other determined etiology in 37.3% and undetermined etiology in 35.3%. Concerning the traditional risk factors, smoking (31.4%), hypertension and diabetes mellitus (12.7% for each one) and a family history of stroke (10.8%) were the most common. The mean follow-up period was 30.5 months. CONCLUSIONS: In our study, traditional risk factors were not-so-uncommon in young adults with ischemic stroke suggesting that prevention can go through controlling these factors. Stroke of other determined etiology was the most common among our patients, so that a broad and detailed diagnostic workup is crucial to puzzle out the etiology for more and better stroke prevention.

The incidence of serious adverse events in a tunisian hospital: a retrospective medical record review study.

AIM: To describe the epidemiology of serious adverse events (SAE) reported in the division of internal medicine at the Mongi Slim university hospital in Tunis, to analyze their causes and contributing factors and compare them to that reported in literature so as to establish prevention strategies when these events were deemed preventable. Methods This retrospective study collected the medical records of randomly selected 500 index hospitalizations. Records review was conducted in two stages: a primary review that aimed to detect hospitalizations where a SAE was likely to have occurred then a secondary review which purpose was to confirm the presence of the SAE, to determine its nature and its preventability. RESULTS: SAE were detected in 5.2% of hospitalizations with a preventability of 57.7%. These events were responsible for a prolongation in 27.0% of hospitalizations and disability in 15.4% of cases. They were the cause of admission in 42.9% of hospitalizations in which a SAE occurred. The SAE consisted in adverse drug events in 73.0% of cases, healthcare-associated infections in 19.0% of cases, non-surgical procedures in 4% of cases and pressure ulcers in 4.0% of cases. Age and number of comorbidities were identified as the main risk factors for the occurrence of SAE. CONCLUSION: Awareness of the extent and severity of the problem of iatrogenesis is necessary because it is a prerequisite to establishing a culture of patient safety among caregivers.

Aetiology of Vascular Purpura in a Single Centre Experience: Contribution of Clinical and Paraclinical Data.

Background: Vascular purpura can be the clinical expression of infectious, inflammatory, drug-related, neoplastic, and endocrine pathologies. To date, there is no consensus codifying the investigation of vascular purpura, especially when it is isolated. Patients and methods: We proposed to study through a retrospective study of 73 cases of vascular purpura, occurring during the period 2004-2019 in our internal medicine department, the contribution of various clinical and paraclinical data to the aetiological diagnosis of vascular purpura. Data were considered to be contributory only when they constituted a solid argument in favour of the aetiological diagnosis of vascular purpura. Results: Our series involved 73 patients including 41 women and 32 men (Gender ratio: 0.78). Mean age was 49 ± 17 years [16-80]. Vascular purpura was isolated in 3% of cases. For the remaining patients, it was associated with functional (91%) or physical (48%) manifestations. It was associated with other skin lesions in 45% of cases. The accepted aetiologies were primary vasculitis (26%), drug-related (15%), infectious (11%) and secondary to connectivitis (10%). No cause was found in a third of cases. Clinical data alone made it possible to suggest the aetiology in more than half of cases. Special investigations were contributory in 46% of cases. The course was contributory in 18% of patients for drug-related and paraneoplastic causes. Conclusion: vascular purpura's diverse clinical presentation presents diagnostic challenges. Aetiologies include vasculitis, drug reactions, infections, and connective tissue disorders. Comprehensive clinical assessment is essential.

[Neuroacanthocytosis: a diagnosis that should be considered]. / Neuroacantheocytoses: un diagnostic à ne pas méconnaître.

BACKGROUND: Neuroacanthocythosis regroup heterogeneous neurodegenerative diseases. These conditions share neurological, hematological and even systemic features. In spite of the genetic progress, their pathogenesis is still unknown. AIM: To report a new case of neuroacanthocythosis CASE REPORT: A 37-year-old woman was admitted for orofacial choreatic movement disorder. These movements were associated to dysarthria, lip and tongue mutilation, areflexia and raised plasma creatine kinase level. Examination of blood smear reveled 10% of acanthocytosis. Neuro-acanthocytosis diagnosis, precisely choreaacanthocytosis, was done. CONCLUSION: Neuro-acanthocytosis should be considered in any movement disorder in order to attempt a genetic counseling.

Downhill oesophageal variceal bleeding: A rare complication in Behçet's disease-related superior vena cava syndrome.

Behçet's disease (BD) is a multisystemic disorder that involves vessels of all sizes. Superior vena cava (SVC) thrombosis is a rare complication that can lead to the development of various collateral pathways. A 31-year-old man presented with SVC syndrome. He had a history of recurrent genital aphthosis. Computed tomography revealed extensive thrombosis of the right internal jugular, axillary, and subclavian veins with collateral circulation. The patient was diagnosed with BD, and he was started on anticoagulation and immunosuppressive therapy. One week later, he presented with haematemesis. Upper gastrointestinal endoscopy disclosed varices in the upper third of the oesophagus with stigmata of recent bleeding. Portal hypertension was ruled out. Anticoagulation therapy was discontinued. He was discharged on immunosuppressive therapy. Bleeding from downhill oesophageal varices should be suspected in any patient presenting with upper gastrointestinal bleeding and a history of SVC syndrome due to BD.

[Pericarditis in systemic lupus erythematosus: prevalence and clinical and immunologic characteristics]. / Péricardites lupiques : prévalence, caractéristiques cliniques et immunologiques.

PURPOSE: Our study sought to determine the frequency and clinical and immunologic characteristics of pericarditis in patients with systemic lupus erythematosus (SLE). METHODS: We retrospectively analyzed the files of all patients with SLE diagnosed between 1987 and 2005. The study included only those patients who had undergone echocardiography. They were divided in two groups according to whether or not they had pericarditis, and their clinical and immunologic characteristics and outcome were compared. RESULTS: Our records found 180 patients with SLE, 97 of whom had had echocardiography. The frequency of pericarditis was 39%. The average age of the 34 women and 4 men with pericarditis at its onset was 36.4 years. There were 59 SLE patients without pericarditis, 56 women and 3 men with an average age of 28.8 years. Pericarditis was frequently associated with pleural effusions. The prevalence of anticardiolipin antibodies was significantly lower in the group of patients with pericarditis. CONCLUSION: Pericarditis is the most common cardiac manifestation in SLE. Its frequency in this sample of Tunisian patients was similar to that described in different ethnic groups. The association between pericarditis and pleuritis is standard. Anticardiolipin antibodies, commonly positive in valve diseases, were less frequent in our patients with pericarditis.