Abderrahman Mami Hospital

Ariana, Tunisia

Abderrahman Mami Hospital

Ariana, Tunisia

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PubMed | Rajavithi Hospital, University of Ulsan, Fahat Hached Hospital, National Cancer Institute and 10 more.
Type: Journal Article | Journal: PLoS medicine | Year: 2016

Inflammatory breast cancer (IBC) is a rare, aggressive form of breast cancer associated with HER2 amplification, with high risk of metastasis and an estimated median survival of 2.9 y. We performed an open-label, single-arm phase II clinical trial (ClinicalTrials.gov NCT01325428) to investigate the efficacy and safety of afatinib, an irreversible ErbB family inhibitor, alone and in combination with vinorelbine in patients with HER2-positive IBC. This trial included prospectively planned exome analysis before and after afatinib monotherapy.HER2-positive IBC patients received afatinib 40 mg daily until progression, and thereafter afatinib 40 mg daily and intravenous vinorelbine 25 mg/m2 weekly. The primary endpoint was clinical benefit; secondary endpoints were objective response (OR), duration of OR, and progression-free survival (PFS). Of 26 patients treated with afatinib monotherapy, clinical benefit was achieved in 9 patients (35%), 0 of 7 trastuzumab-treated patients and 9 of 19 trastuzumab-nave patients. Following disease progression, 10 patients received afatinib plus vinorelbine, and clinical benefit was achieved in 2 of 4 trastuzumab-treated and 0 of 6 trastuzumab-nave patients. All patients had treatment-related adverse events (AEs). Whole-exome sequencing of tumour biopsies taken before treatment and following disease progression on afatinib monotherapy was performed to assess the mutational landscape of IBC and evolutionary trajectories during therapy. Compared to a cohort of The Cancer Genome Atlas (TCGA) patients with HER2-positive non-IBC, HER2-positive IBC patients had significantly higher mutational and neoantigenic burden, more frequent gain-of-function TP53 mutations and a recurrent 11q13.5 amplification overlapping PAK1. Planned exploratory analysis revealed that trastuzumab-nave patients with tumours harbouring somatic activation of PI3K/Akt signalling had significantly shorter PFS compared to those without (p = 0.03). High genomic concordance between biopsies taken before and following afatinib resistance was observed with stable clonal structures in non-responding tumours, and evidence of branched evolution in 8 of 9 tumours analysed. Recruitment to the trial was terminated early following the LUX-Breast 1 trial, which showed that afatinib combined with vinorelbine had similar PFS and OR rates to trastuzumab plus vinorelbine but shorter overall survival (OS), and was less tolerable. The main limitations of this study are that the results should be interpreted with caution given the relatively small patient cohort and the potential for tumour sampling bias between pre- and post-treatment tumour biopsies.Afatinib, with or without vinorelbine, showed activity in trastuzumab-nave HER2-positive IBC patients in a planned subgroup analysis. HER2-positive IBC is characterized by frequent TP53 gain-of-function mutations and a high mutational burden. The high mutational load associated with HER2-positive IBC suggests a potential role for checkpoint inhibitor therapy in this disease.ClinicalTrials.gov NCT01325428.


Hamzaoui K.,University of Tunis | Hamzaoui K.,Tunis el Manar University | Bouali E.,Tunis el Manar University | Hamzaoui A.,University of Tunis | And 2 more authors.
Human Immunology | Year: 2015

Since the discovery of interleukin-33 (IL-33) ligand for the ST2 receptor, scarce studies have implicated this cytokine in the pathogenesis of Behçet's disease (BD). IL-33 is member of the IL-1 superfamily of cytokines that is expressed by epithelial cells, endothelial cells, inflammatory cells and central nervous tissue. Its expression is upregulated following pro-inflammatory situations making IL-33 essential to innate immunity. IL-33 can function both as a traditional cytokine and as a nuclear factor regulating gene transcription. It is thought to function as an "alarmin" which is released following cell necrosis to alert the immune system of tissue damage or stress. This short review highlights the emerging roles of IL-33 protein and raises many interrogations about its involvement in BD. © 2015 American Society for Histocompatibility and Immunogenetics.


Tizaoui K.,Tunis el Manar University | Kaabachi W.,Tunis el Manar University | Hamzaoui A.,Tunis el Manar University | Hamzaoui A.,Abderrahman Mami Hospital | Hamzaoui K.,Tunis el Manar University
Cellular and Molecular Immunology | Year: 2015

Vitamin D receptor (VDR) polymorphisms have been studied as potential contributors to multiple sclerosis (MS). However, published studies differ with respect to study design and the significance of the effects detected. The aim of this study was to quantify the magnitude of the risk associated with the TaqI, BsmI, ApaI and FokI VDR polymorphisms in MS using a meta-analysis approach. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we conducted a systematic search and meta-analysis of the literature. Subgroup analyses were performed to detect potential sources of heterogeneity from the selected study characteristics. The stability of the summary risk was evaluated using sensitivity analyses. The meta-analysis included a total of 3300 cases and 3194 controls from 13 case-control studies. There were no significant associations found between TaqI and BsmI polymorphisms and MS risk. The association between the ApaI polymorphism and MS risk was significant in the homozygous and codominant models (P=0.013 and P=0.031, respectively), suggesting that the AA ApaI genotype might be a significant MS risk factor. Publication year and age significantly affected the association between TaqI polymorphisms and MS (P=0.014 and P=0.010, respectively), which indicates a protective effect of the major T allele. The AA ApaI and FF FokI genotypes are significant risk factors for MS. The association between the TaqI polymorphism and MS risk is significantly affected by study characteristics.


Chouchane L.,Cornell College | Boussen H.,Abderrahman Mami Hospital | Sastry K.S.R.,Cornell College
The Lancet Oncology | Year: 2013

Breast cancer is a major health problem in both developing and developed countries. It is the most frequently diagnosed female malignant disease in Arab populations. The incidence of breast cancer is lower in Arab countries than in Europe and the USA but is rising fast. Breast cancers in women from Arab populations have different characteristics to those reported in individuals from Europe and the USA. For example, affected patients are at least a decade younger, they have a more advanced stage of disease at first presentation, and their tumour size is larger. Moreover, in some Arab populations, reports suggest increased axillary-lymph-node invasion, a larger proportion of negative hormone receptors, and a higher tumour grade. These disparities are not only confined to clinicopathological features but also exist at the molecular level, as shown by findings of genome-wide association studies and expression profiling. © 2013 Elsevier Ltd.


Charrad R.,Abderrahman Mami Hospital | Berraies A.,Abderrahman Mami Hospital | Hamdi B.,Abderrahman Mami Hospital | Ammar J.,Abderrahman Mami Hospital | And 2 more authors.
Immunobiology | Year: 2016

BACKGROUND: The aim of this study was to assess interleukin (IL)-37 production in asthmatic children in serum and induced sputum and to look to the impact of IL-37 on pro-inflammatory cytokines production (TNF-α, IL-6, IL-1β and IL-17).METHODS: Forty children with well-controlled asthma (20 moderate and 20 mild asthmatics) were studied. IL-37 was measured by ELISA in serum and induced sputum (IS) samples, and compared with 22 age- and sex-matched healthy controls. Real-time quantitative PCR was used to determine IL-37 mRNA expression in induced sputum cells. Induced sputum mononuclear cells from 10 moderate asthmatics and 10 healthy controls were stimulated either with lipopolysaccharides (LPS) or LPS plus recombinant IL-37 (rIL-37) comparing pro-inflammatory cytokines production. TNF-α, IL-1β, IL-6 and IL-17 were measured by RT-PCR and ELISA.FINDINGS: The expression of IL-37 mRNA in asthmatic patients was significantly lower than that observed in healthy controls (P=0.0001). IL37 mRNA expression depended on asthma severity. Serum and IS IL-37 levels were significantly lower in asthma patients compared to healthy controls. LPS-stimulated sputum cells from asthma patients produced higher levels of IL-1β, IL-6, and TNF-α than those from HC. Adding rIL-37 suppressed TNF-α, IL-1β and IL-6 production in IS cells. In the same way, stimulating IS CD4(+) T cells in the presence of rIL-37 inhibited IL-17 production both in asthma patients and HC. IL-37 effect on IL-17 was more pronounced in patients than controls.INTERPRETATION: The decrease in IL-37 level observed in IS was found to correlate with disease severity. The increased pro-inflammatory cytokines production from asthma IS cells was abrogated by the addition of rIL-37. IL-37 could be an important cytokine in the control of asthma by suppressing the production of inflammatory cytokines. Copyright © 2015 Elsevier GmbH. All rights reserved.


Hamzaoui A.,Abderrahman Mami Hospital | Hamzaoui A.,Tunis el Manar University | Berraies A.,Abderrahman Mami Hospital | Berraies A.,Tunis el Manar University | And 6 more authors.
Immunobiology | Year: 2014

Vitamin D [25(OH)D3] deficiency has been associated with asthma as in many inflammatory and autoimmune pathologies; however, there is still a lack of data about the effects of administration of vitamin D in immune regulation in young asthmatic patients. In this study, we investigated its inhibitory effect on the immune response in young asthmatic patients and the possible mechanisms involved.Peripheral blood CD4+ T cells from 10 asthmatic patients and 10 healthy controls were cultured under Th17 polarizing conditions in the presence or absence of [25(OH)D3], IL-17 cytokine production was determined by ELISA and flow cytometry. Messenger RNA (mRNA) expression of several factors related to Th17 cell function was determined by real-time PCR. The effect of [25(OH)D3]-treated dendritic cells (DCs) on CD4+ T cell response was determined by ELISA and flow cytometry.Stimulation of naive CD4+ T cells under Th17 polarizing conditions showed a higher Th17 cell differentiation in asthmatic patients than healthy controls. The addition of [25(OH)D3] significantly inhibited Th17 cell differentiation both in patients [P<0.001] and in normal controls [P=0.001] in a dose-dependent way. [25(OH)D3] was able to inhibit the gene expression of RORC, IL-17, IL-23R, and CCR6. [25(OH)D3]-treated DCs significantly inhibited IL-17 production [P=0.002] and decreased the percentage of CD4+IL-17+ [P=0.007] in young asthmatics.The findings suggest that the inhibitory effect of [25(OH)D3] on the Th17 response was mediated via both T cells and DCs. DCs pathway is involved in the direct inhibition of 25(OH)D3 on Th17 cell differentiation in young asthmatics. © 2014 Elsevier GmbH.


Tizaoui K.,Tunis el Manar University | Berraies A.,Tunis el Manar University | Berraies A.,Abderrahman Mami Hospital | Hamdi B.,Tunis el Manar University | And 5 more authors.
Lung | Year: 2014

Methods: Following the preferred reporting items for systematic reviews and meta-analyses guidelines, a systematic search and meta-analysis of the literature were conducted. Subgroup analyses were performed to detect potential sources of heterogeneity from selected study characteristics.Background: The association between vitamin D receptor (VDR) polymorphisms and asthma risk has been inconsistently investigated, but published studies demonstrated conflicting results. The aim of the current study was to investigate the impact of TaqI, BsmI, ApaI, and FokI VDR polymorphisms on asthma disease by using a meta-analysis approach.Results: A total of 2,097 cases and 1,968 controls in eight case–control studies were included in meta-analyses. A significant association was found between TaqI polymorphisms and asthma risk [OR 1.488 (95 % CI 1.019–2.174); P = 0.040] in a codominant model. In the same way, BsmI was significantly associated with asthma risk [OR 2.017 (95 % CI 1.236–3.851); P = 0.017] in the codominant model. The homozygote BB BsmI genotype was found to confer significant asthma risk. FokI polymorphism was marginally associated with asthma risk [OR 1.187 (95 % CI 0.975–1.446); P = 0.088] in the codominant model. In contrast, no significant association was found between ApaI polymorphism and asthma risk. Subgroup analyses revealed that gender and age modified significantly the association between FokI polymorphisms and asthma risk (P = 0.035 and 0.013, respectively). Publication year and serum 25(OH) D level tended, marginally, to moderate the association between FokI polymorphism and asthma risk.Conclusion: TaqI, BsmI, and FokI VDR polymorphisms contribute to asthma susceptibility. The association between FokI polymorphism and asthma risk is influenced by study characteristics. © 2014, Springer Science+Business Media New York.


PubMed | Abderrahman Mami Hospital
Type: Journal Article | Journal: Revue de pneumologie clinique | Year: 2016

Fibrous dysplasia of bone is a rare benign lesion characterized by the coexistence of a fibrous tissue and an immature osteogenesis. Costal localization is rare and may be monostotic or polyostotic. The diagnosis may be suspected based on clinical and radiological findings. Facing the development of radiological investigations, we tried to highlight the diagnostic role of the microscopic examination through the experience of our department.We describe a retrospective study about 12 costal fibrous dysplasias diagnosed over a 17-year-period. Clinical records were retrieved from the department of thoracic surgery of the same hospital.Costal fibrous dysplasia is equally observed in men and women with predominance in the third and fourth decades. Clinical symptoms consist mainly in chest pain. Physical examination was normal in almost all cases. Based on the radiological findings, the diagnosis was suspected in 33% of the cases. Microscopic examination highlighted the diagnosis in all cases but it was challenging in one case and necessitated a multi-disciplinary approach. The difficulties encountered were due to artifact decalcification.Costal fibrous dysplasia is a benign lesion which diagnosis is based on microscopic features. Radiologic investigations show nonspecific features but allow to rule out a malignant tumor. The outcome of the patients is generally good except in rare cases with a malignant transformation.


PubMed | Abderrahman Mami Hospital
Type: Journal Article | Journal: Journal of immunoassay & immunochemistry | Year: 2016

Multidisciplinary concertation is mandatory in order to assess interstitial pneumonias. The study of the bronchoalveolar lavage helps evoking a diagnosis according to the lavage profile. In lymphocytic alveolitis, immunocytochemistry, or in flux cytometry are necessary in order to identify the different clusters of lymphocytes implicated. Our objective was to evaluate the profile of 31 lymphocytic alveolitis using 2 different techniques which are the immunocytochemistry and the in flow cytometry in order to evaluate the efficacy of each technique and to compare the different results to the final diagnoses. We describe a retrospective study about 31 patients admitted to our hospital in order to explore an interstitial pneumonia between January and July 2014. Bronchial endoscopy and bronchoalveolar lavage were performed in all cases. The sensitivity of the in flow cytometry was estimated to 53% and its specificity reached 33%. On the other hand, the immunocytochemistry presented a specificity of 42.8% and a sensitivity of 42.8%. The final diagnoses retained consisted in sarcoidosis in 12 cases, infectious pneumonia in 10 cases, hypersensitivity pneumonia in 3 cases, cryptogenic pneumonia in 3 cases, idiopathic fibrosis in 2 cases, and adenocarcinoma in 1 case. The relevance of both techniques depends on many factors. They necessitate an available material, well-trained technicians, and experimented pathologists.


PubMed | Abderrahman Mami Hospital and Tunis el Manar University
Type: Journal Article | Journal: Asian cardiovascular & thoracic annals | Year: 2016

Thymic carcinomas are rare tumors with a challenging diagnosis. Our aim was to report our 17-year experience of these tumors and to highlight the challenges encountered and the main differential diagnoses ruled out.We studied 12 (92%) men and 1 (7.7%) woman with a mean age of 37 years (range 15-60 years). All patients were symptomatic, with chest pain representing the most frequent symptom. Radiology revealed anterior mediastinal masses in all cases, with either infiltration of the adjacent organs or pulmonary parenchymal metastases.The diagnosis was made on surgical biopsies in 12 cases and a lymph node biopsy in one. Microscopic examination revealed squamous carcinoma in 3 cases, synovial sarcoma in 1, mucinous adenocarcinoma in 1, undifferentiated carcinoma in 2, clear cell carcinoma in 1, lymphoepithelioma-like carcinoma in 2, atypical carcinoid tumor in 2, and sarcomatoid carcinoma in 1. Total surgical resection was possible in one patient after neoadjuvant chemotherapy and radiotherapy. Follow-up was possible in only 6 patients, and the mean survival reached 13 months.In spite of the lack of follow-up information, this study demonstrates the poor outcome associated with these tumors and the need for standardized treatment.

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