Long term inhibition of hip joint damage under tumor necrosis factor-alpha inhibitors in spondyloarthritis.

The aim of this study was to assess the impact of long-term treatment with TNF blockers on the radiographic progression of hip disease in spondyloarthritis (SpA). This retrospective multicentric cohort study included 2 groups of patients with SpA and hip involvement. Patients of group 1 were treated with anti-TNF alpha for at least 2 years, whereas those of group 2 were anti-TNF-naïve patients. Clinical, laboratory and radiologic parameters were assessed at baseline and after at least 2 years. Groups 1 and 2 included respectively 48 and 46 patients. The radiological features of hip disease were comparable between the two groups at baseline. The second evaluation was performed after an average duration of 4.1 ± 2.9 years [2-10] in group 1 and 4.8 ± 2.1 years [2-14] in group 2 (p = 0.116). The absence of hip structural damage was more frequently found in group 1 (72 hips vs 52, p < 0.0001, odds ratio [OR] = 4.7, 95% confidence interval [CI] = 2.1-10.4). The better outcome in group 1 remained significant even after adjusting for BASDAI (p < 0.05, (adjusted odds ratio [aOR] = 3.3, 95% CI = 1.2-9.2), BASFI (p < 0.0001, aOR = 3.1, 95% CI = 1.1-8.9), and CRP (p < 0.01, aOR = 4.2, 95% CI = 1.8-9.8). Our finding suggests that anti-TNF therapy may inhibit hip joint damage in patients with SpA.

An Immunoscore System Based On CD3+ And CD8+ Infiltrating Lymphocytes Densities To Predict The Outcome Of Patients With Colorectal Adenocarcinoma.

PURPOSE: The aim of this study was to evaluate the Immunoscore (IS) methodology as a prognostic marker of colorectal adenocarcinoma in Tunisian population. Tumor blocks were retrospectively collected from 106 patients with sporadic colorectal cancer. METHODS: Immunohistochemical staining and images analysis software were used to quantify the density of CD3+ and CD8+ tumor-infiltrating lymphocytes in the center of the tumor and invasive margin. RESULTS: The density of CD3+ and CD8+ was significantly associated with 5-year overall survival (P=0.001 and P=0.00098, respectively) and 5-year disease-free survival (P=0.0006 and P=0.0056, respectively). The earlier stage and the absence of vascular emboli showed a significant association with IS analysis. Cox multivariate regression analysis revealed that Immunoscore (from I0 to I4) was more significantly correlated with overall survival (P=0.00011) and disease-free survival (P=0.0008) than Tumor-Node-Metastasis (TNM) staging (P=0.057 and P=0.039, respectively). Patients with low IS were associated with inferior disease-free survival and overall survival, contrary to patients with high IS. CONCLUSION: This is the first study which evaluated the prognostic value of IS methodology in colorectal cancer in African and Arabic population. The IS methodology carries out in this study allows to estimate the risk of relapse in patients with colorectal cancer. Overall, our results support the implementation of the consensus Immunoscore as a new component for the classification of cancer, designated TNM-Immune.

Parenteral Nutrition Complications in Children Undergoing Bone Marrow Transplantation.

BACKGROUND: Parenteral nutrition (PN) seems to be a practical solution to face the negative nutritional effects of bone marrow transplantation. OBJECTIVE: Report and describe all observed PN-related complications in children undergoing allogenic bone marrow transplantation in a tertiary center and determine the possible risk factors. MATERIALS AND METHODS: This was a retrospective and observational study including 51 allografted children 2 to 17 years of age. We collected from medical patient records any noticed PN-related complications using an assessment causality method. The independent risk factors for complications were investigated by multivariate analysis. RESULTS: A total of 92% of patients (n=47) developed a total of 136 complications attributable to PN. The incidence rate of complications was 5 for 100 patient days of PN. Infectious complications (32.3%) and electrolytic disorders (27.9%) were the most common conditions identified during our study. Multivariate analysis showed that the duration of PN exposure, age, and hyperglycemia were the risk factors for the onset of these complications. CONCLUSIONS: Although we have noticed multiple complications attributable to PN, a certain causal link is difficult to establish in this particular context. Emphasizing enteral nutrition in bone marrow graft protocols would be the best way to avoid these complications.

A cross sectional study of bone and cartilage biomarkers: correlation with structural damage in rheumatoid arthritis.

The aim of our study was to assess the relationship between bone and cartilage remodeling biomarkers and joint damage in Rheumatoid Arthritis (RA), and to detect whether they have the capacity to predict the progression of joint disease assessment by computed tomography (CT) erosion score. We analyzed 65 female patients with established RA in our Rheumatology Department. Serum levels of bone and cartilage markers were measured: osteocalcin (OC), N-propeptide of type I collagen (PINP), collagen type I and II, C-telopeptide (CTX I, CTX-II) and cartilage oligomeric matrix protein (COMP). Radiography of both wrist and MCP joints were available. Two expert-readers independently scored articular damage and progression using the High-resolution low dose CT scan in a blinded fashion. 65 female patients with established RA with a median age of 44 years were included. The median disease-duration was two years and the median (Disease activity score) DAS 28 score at 4.46 [2.65-7.36]. The percentage of patient with low disease activity was 13.8%, while 55.4 and 30.8% for those with moderate and high disease activity respectively. The resorption bone markers were high in active versus non-active RA. Wrist and MCP erosion scores were also associated with RA activity. Our study shows that biomarkers of bone and cartilage collagen breakdown were related to specific joint erosion in RA and could predict subsequent radiographic damage in RA. Further larger scale longitudinal studies maybe needed to confirm our data.

Filgrastim following HLA-Identical Allogeneic Bone Marrow Transplantation: Long-Term Outcomes of a Randomized Trial.

Human recombinant granulocyte colony stimulating factor reduces the duration of neutropenia following HLA-identical allogeneic bone marrow transplantation. However, its use remains controversial due to the risk of increasing the incidence of acute graft-versus-host disease (GVHD) and slower platelet recovery. To clarify these risks, we conducted a prospective randomized placebo-controlled trial of filgrastim 5 µg/kg/day i.v. from day 7 post-transplant until neutrophil recovery in 145 consecutive adults undergoing HLA-identical allogeneic bone marrow transplantation, with cyclosporine and methotrexate as GVHD prophylaxis. The primary endpoint was the incidence of acute GVHD; hematological recovery, nonrelapse mortality, and post-transplant complications were secondary endpoints. Filgrastim had no significant effect on the incidence of acute GVHD, platelet recovery, platelet transfusion requirements, chronic GVHD, or survival. Filgrastim accelerated granulocyte recovery significantly (with absolute neutrophil counts >.5 × 109/L achieved after a median of 16 days versus 23 days for placebo; P < .0001), and reduced both early nonrelapse mortality (2.9% versus 10.5%; P = .042) and the duration of i.v. antibiotic therapy (18 days versus 26 days; P = .001) and hospitalization (27 versus 34 days; P = .017). In conclusion, in this setting, filgrastim reduced significantly the duration of neutropenia, i.v. antibiotic therapy, hospitalization, and early nonrelapse mortality, without increasing the risk of acute and chronic GVHD or relapse, or delaying platelet recovery.

First site of recurrence after breast cancer adjuvant treatment in the era of multimodality therapy: which imaging for which patient during follow-up?

PURPOSE: We evaluated the relation between first site of recurrence of early breast cancer and disease profile at presentation and reported survival results, suggesting a personalized diagnostic imaging guidance during follow up. METHODS: Among 1400 early breast cancer treated from 2000 to 2010, 324 relapses were divided into 4 groups according to first site: A-locoregional, B-bone, C-Brain and D-visceral. We analyzed redictive factors of each group compared to a control group of 100 non relapsing patients and the remaining groups matched. RESULTS: In group A, patients were more likely to have histological tumor size above >2 cm, grade 1-2, HR positive and 0-3 involved lymph nodes. In group B, patients had more commonly grade 2-3, 1-3 positive lymph nodes and HR positive tumors. In group C, patients were more frequently young, with large tumor size, grade3, positive lymph nodes and HER2 positive tumors. In group D, patients were more likely to have tumors>2 cm in size, with nodal involvement, grade 3, HR negative and HER2 positive tumors. Annual recurrence rate in group A, was stable ranging between 15%-18%, within the first 3 years and peaked at 19.4% in the interval [1-2]year in group B. Median survival was 46 months in group A, 43 months in group B, with no significant difference. CONCLUSION: Outcome of loco-regional and bone relapses was good, suggesting that both systematic mammography and bone-scan/CT scan for high risk patients (N+, gradeIII) during the first 2-3 years may represent a tailored relevant follow-up protocol for breast cancer patients.

Late mitral restenosis after percutaneous commissurotomy: Predictive value of inflammation and extracellular matrix remodeling biomarkers.

BACKGROUND: The role of chronic inflammation in mitral restenosis after percutaneous mitral commissurotomy (PMC) is still controversial. AIMS: We sought to assess the predictive value of inflammation and extracellular matrix (ECM) remodeling biomarkers in late mitral restenosis after PMC. METHODS: We prospectively enrolled 155 patients (mean age 46.2±11 years) with at least 5 year follow up after primary PMC. Serum levels of high sensitive C-Reactive Protein (hs-CRP), matrix metalloproteinases MMPs, tissue-specific inhibitors of matrix metalloproteinases TIMPs, and tumor necrosis factor α (TNFα)] were measured. RESULTS: Late mitral restenosis occurred in 55 patients (35.5%). The independent predictors of late mitral stenosis were: age> 55 years [HR10.51 (95%CI 1.12-95.9); p=0.037]; no long acting penicillin therapy [HR 18.1 (95% CI 2.6-122.9); p=0.003]; TNFα > 80 ng/ml [HR 5.85 (95% CI 1.1-31.42); p=0.039]; and TIMP-2 > 289 ng/ml [HR 0.52 (95% CI 0.22-0.95); p=0.045]. CONCLUSION: Chronic inflammation and ECM remodeling are involved in late mitral restenosis after PMC.

Prognostic factors in children with extracranial malignant germ cell tumors: a monocentric pediatric Tunisian study.

Background Extracranial Germ cell tumors (GCT) are a rare and a heterogeneous group of pediatric cancers but highly curable. Aim We aimed to review management, outcome and prognostic factors that influence overall survival (OS) in a pediatric Tunisian oncologic unit. Methods We retrospectively evaluated between January 1998 and December 2012, 33 patients affected by extracranial germ cell tumors and treated according to TGM95 protocol established by the SFOPin a pediatric Tunisian oncologic unit. Results Patients had a mean age of 57 months (ranges: 1 day-13 years). There were 19 girls and 14 boys. Primary sites included 12 sacrococcygeal, 11 ovarian, 6 testicular, 3retro peritoneal and 1 mediastinal site. After a mean follow up of 26.1 months (ranges: 0-96 months), OSat 2 years and 5 years were respectively 82% and 75%. Event-free survival were respectively 79% at 2 years and 74% at 5 years. Various prognostic factors have been studied according to Kaplan-Meier. Univariate analyses identified significant factors which influence strongly OS: the stage (p=0.04), the completeness of surgery (p<0.001) and the relapse (p = 0, 0001). A multivariate study showed that only the quality of resection and the clinical stage remained strong significant prognostic factors (p=0,021) for 5-year OS. Conclusion Disease stage, completeness of surgery and relapse have been established as the most powerful prognostic parameter in our analysis. The improvement of survival of patients affected by extracranial germ cell tumors in Tunisia is a real achievement mainly due to the success of salvage treatments.

Development and validation of a food photography manual, as a tool for estimation of food portion size in epidemiological dietary surveys in Tunisia.

BACKGROUND: Estimation of food portion sizes has always been a challenge in dietary studies on free-living individuals. The aim of this work was to develop and validate a food photography manual to improve the accuracy of the estimated size of consumed food portions. METHODS: A manual was compiled from digital photos of foods commonly consumed by the Tunisian population. The food was cooked and weighed before taking digital photographs of three portion sizes. The manual was validated by comparing the method of 24-hour recall (using photos) to the reference method [food weighing (FW)]. In both the methods, the comparison focused on food intake amounts as well as nutritional issues. Validity was assessed by Bland-Altman limits of agreement. In total, 31 male and female volunteers aged 9-89 participated in the study. RESULTS: We focused on eight food categories and compared their estimated amounts (using the 24-hour recall method) to those actually consumed (using FW). Animal products and sweets were underestimated, whereas pasta, bread, vegetables, fruits, and dairy products were overestimated. However, the difference between the two methods is not statistically significant except for pasta (p<0.05) and dairy products (p<0.05). The coefficient of correlation between the two methods is highly significant, ranging from 0.876 for pasta to 0.989 for dairy products. Nutrient intake calculated for both methods showed insignificant differences except for fat (p<0.001) and dietary fiber (p<0.05). A highly significant correlation was observed between the two methods for all micronutrients. The test agreement highlights the lack of difference between the two methods. CONCLUSION: The difference between the 24-hour recall method using digital photos and the weighing method is acceptable. Our findings indicate that the food photography manual can be a useful tool for quantifying food portion sizes in epidemiological dietary surveys.

Comparative clinical trial: fluconazole alone or associated with topical ketoconazole in the treatment of pityriasis versicolor.

BACKGROUND: The efficacy of ketoconazole and fluconazole in pityriasis versicolor had been proved. AIM: To compare the efficacy and the safety of two doses of fluconazole given 1 week apart alone or associated to ketoconazole shampoo. METHODS: Our study included all patients with pityriasis versicolor who attended in dermatology department of Habib Thameur Hospital, Tunis (over a 21-month period). During the considered period, patients were randomly assigned in two study groups: G1 receiving fluconazole two doses 300mg given 1 week apart with G2 taken an association of fluconazole (two doses 300mg given 1 week apart) and ketoconazole shampoo the first day. RESULTS: Seventy one patients were enrolled in our study: 35 in the fluconazole group and 36 in the fluconazole associated to ketoconazole shampoo comparator group. The mean age was 29.1 years [16-70 years].  Concerning the clinical form, 27% had macular lesions, 24% had plaques and 49% had mixed form. Lesions werehyperchromic52%; hypochromic 15% and erythematous 6%. As for main location, 67% had lesions on the neck; 66% on the trunk, 60% on the shoulders. At the end of the study, there was no significant difference in clinical presentation and in improvement rate of pityriasis versicolor between fluconazole and association of fluconazole and ketoconazole shampoo ((p=0.13 at day 14, p=0.57 at day 28 and p=0.2 at day56). CONCLUSION: In this study, we have shown that the improvement rate of PV treated with two doses of 300 mg of fluconazole with one week interval was similar to those of an association of one application of ketoconazole shampoo and the same dose of fluconazole.

[High risk areas for echinococcosis-hydatidosis in Tunisia]. / Identification des zones à risque élevé pour l'échinococcose-hydatidose en Tunisie.

AIM: The study was conducted in order to identify high risk areas for hydatidosis in Tunisia witch would be eligible for a Hydatidosis control program initiation. METHODS: The most recent epidemiological investigation on surgical incidence of hydatidosis was used to classify governorates according to their incidence rate. A "global hydatidosis risk score" was calculated for each governorate, combining some parameters related to the hygiene conditions of the population, the literacy rate, the canine density and livestock census. Spearman correlation coefficient was used to compare scores and surgical incidences. Mapping analysis has been conducted. The surgical incidence rate of hydatidosis classifies each governorate regarding occurrence of human cases. The global hydatidosis risk score, by governorate, pointed out the most exposed areas to the disease. RESULTS: The mapping analysis showed a good agreement between the incidence rate of the disease and the global hydatidosis risk score and made it possible to identify the population of the center and the west of the country as a most exposed population for the diseases. CONCLUSION: In order to have a chance for implementation, hydatidosis control program should target the three jointed governorates of Kasserine, Siliana and Kef, which have the highest incidence rates and the worst scores.

Predictive score for positive upper endoscopies outcomes in children with upper gastrointestinal bleeding.

BACKGROUND: Upper gastrointestinal bleeding (UGIB) is a common pediatric emergency. Esophago-gastro-duodenoscopy (EGD) is the first line diagnostic procedure to identify the source of bleeding. However etiology of UGIB remains unknown in 20% of cases. Furthermore, emergency endoscopy is unavailable in many hospitals in our country. AIMS: Identify clinical predictors of positive upper endoscopy outcomes and develop a clinical prediction rule from these parameters. METHODS: Retrospective study of EGDs performed in children with first episode of UGIB, in the endoscopic unit of Children's Hospital of Tunis, during a period of six years. Statistical analysis used SPSS20. Univariate analysis was performed and multivariate logistic regression was then modelled to derive a clinical prediction rule. RESULTS: We collected 655 endoscopies (23.2% normal, 76.8% pathological). We found that time to EGD within 24 hours from the onset of bleeding (p=0.027; Adj OR: 3.30 [1.14 - 9.53]), rebleeding (p=0.009; Adj OR: 6.01 [1.57 - 23.02]), positive gastric lavage outcome (p=0.001; Adj OR: 4.79 [1.95 - 11.79]) and non steroidal anti-inflammatory drugs intake (p=0.035; Adj OR: 5.66 [1.13 - 28.31]) were predictors of positive upper endoscopy outcomes. By assigning each factor, the adjusted odds ratio (Adj OR), we developed a score with four items, ranging from 4 to 20. Using the receiver operating characteristic (ROC) curve the best cut off ≥ 9 was defined (sensitivity 88.2%, specificity 60.6%, positive predictive value 92.7% and negative predictive value 47.6%). The score discriminated well with a ROC curve area of 0.837 (95% confidence interval [0.769 - 0.905]). CONCLUSIONS: This clinical prediction rule is a simple measure that may identify children who needed emergency endoscopy. A prospective study is required to validate our results and evaluate other clinical features that were insufficient for this analysis.

Association of LRP5 genotypes with osteoporosis in Tunisian post-menopausal women.

BACKGROUND: Osteoporosis is a highly heritable trait. Among the genes associated with bone mineral density (BMD), the low-density lipoprotein receptor-related protein 5 gene (LRP5) has been consistently identified in Caucasians. However LRP5 contribution to osteoporosis in populations of other ethnicities remains poorly known. METHODS: To determine whether LRP5 polymorphisms Ala1330Val and Val667Met are associated with BMD in North Africans, these genotypes were analyzed in 566 post-menopausal Tunisian women with mean age of 59.5 ± 7 .7 years, of which 59.1% have low bone mass (T-score<-1 at spine or hip). RESULTS: In post-menopausal Tunisian women, 1330Val was weakly associated with reduced BMD T-score at lumbar spine (p=0.047) but not femur neck. Moreover, the TT/TC genotypes tended to be more frequent in women with osteopenia and osteoporosis than in women with normal BMD (p=0.066). Adjusting for body size and other potential confounders, LRP5 genotypes were no longer significantly associated with aBMD at any site. CONCLUSIONS: The less common Val667Met polymorphism showed no association with osteoporosis. The Ala1330Val polymorphism is weakly associated with lower lumbar spine bone density and osteopenia/osteoporosis in postmenopausal Tunisian women. These observations expand our knowledge about the contribution of LRP5 genetic variation to osteoporosis risk in populations of diverse ethnic origin.

A randomized, controlled trial of nebulized 5% hypertonic saline and mixed 5% hypertonic saline with epinephrine in bronchiolitis.

BACKGROUND: Bronchiolitis is a public health problem in the word and in Tunisia. Nebulized hypertonic saline seems to have some benefits in bronchiolitis. The aim of this study is to evaluate the efficacy of nebulized 5% hypertonic saline alone or mixed with epinephrine in bronchiolitis as measured by improvement in clinical score, oxygen saturation or reduction in duration of hospitalization. METHODS: This prospective, double blind, placebo controlled, randomized clinical trial was performed at Children's Hospital of Tunis from February 2012 to Mars 2012. A total of 94 patients less than 12 months of age with diagnosis of moderately severe bronchiolitis were enrolled and assigned to receive 5% nebulized hypertonic saline, mixed 5% hypertonic saline with standard epinephrine 0,1% or normal saline (placebo) at admission and every 4 hours during hospitalization. RESULTS: There were no significant difference between nebulized 5% hypertonic saline, mixed 5% hypertonic saline with epinephrine or normal saline at baseline, T30 min, T60 min, and T120 min after start study in Wang severity score, oxygen saturation in room air, rate respiratory and heart rate. There was no difference in duration of hospitalization. CONCLUSION: Nebulized 5% hypertonic saline or mixed 5% hypertonic saline with epinephrine are safety but does not appear effective in treating moderately ill infants with the first acute bronchiolitis.

Anomalies of intra-synovial citrullination: is there any interest in the diagnosis of early rheumatoid arthritis?

Autoantibodies to citrullinated proteins (ACPA) are specifically associated with rheumatoid arthritis (RA) and seem to play an important role in its pathogenesis. The specific immunological conflict between ACPA and citrullinated fibrin plays a major role in the self-maintenance of synovial inflammation by forming fibrin deposits in the synovial tissue. These deposits, secondarily citrullinated by a local peptidylarginine deiminase (PADI) enzyme activity, seem to maintain the immunological conflict and the inflammation. Our objective in this work is to study the anomalies of citrullination in a group of patients with early RA, in comparison with a control group of patients suffering from undetermined inflammatory arthritis, osteoarthritis and spondyloarthropathy. For this purpose, we used an enzyme-linked immunosorbent assay (ELISA) to determine the levels of ACPA in serum and synovial fluid. By immunohistochemistry, subtype 4 of PADI was also sought in the synovial biopsies taken from all our patients. We found that the ACPA levels in serum and synovial fluid were significantly higher in patients with RA. The enzyme PADI4 was found only in the group with RA and was statistically correlated with ACPA mean levels in sera and synovial fluid. The expression of PADI4 seems to correlate with intra-synovial deposits of fibrin in RA. However, determination of synovial ACPA levels and detection of intra-synovial PADI4 deposits are of no additional benefit compared with assessment of ACPA levels in serum for the diagnosis of early RA.

Health-related Quality of Life Assessment on 100 Tunisian Patients with Ankylosing Spondylitis using the SF-36 Survey.

OBJECTIVES: The main objective of the study was to examine the self reported health status in patients with ankylosing spondylitis (AS) compared with the general population and the secondary objective (in the AS group) was to study the association between health status, demographic parameters, and specific disease instruments in AS. METHODS: A cross sectional study of 100 AS patients recruited between 2006 and 2009 at the Department of Rheumatology. Health status was assessed by using the SF-36 health questionnaire in patients with AS. Demographic characteristics and disease-specific instruments were also examined by the questionnaire. A sample of 112 healthy individuals was also surveyed using the SF-36 health questionnaire. RESULTS: This study showed a great impairment in the quality of life of patients with AS involving all scales. All male patients with AS reported significantly impaired health-related quality of life on all items of the SF-36 compared with the general population whereas female patients reported poorer health on three items only, namely physical functioning, general health and bodily pain. Mental health was mostly affected than physical role. The physical role was significantly higher in patients with high education level than in patients with low education level (p=0.01). Physical functioning was better in employed patients. All scales of SF-36 were correlated with BASFI, BASDAI and BAS-G. Only physical functioning and general health were correlated with BASMI. CONCLUSION: Impairment in the quality of life can be significant when suffering from AS, affecting mental health more than physical health. Among disease parameters, functional impairment, disease activity, mobility limitation, and spinal pain were the most associated factors resulting to the deterioration of quality of life.

Comparison of C-reactive protein and high-sensitivity C-reactive protein levels in patients on hemodialysis.

Chronic inflammation is highly prevalent in patients on hemodialysis (HD), as evidenced by increased levels of C-reactive protein (CRP). We compared CRP to high-sensitivity C-reactive protein (hs-CRP) to determine whether it has any clinical implications and prognostic significance in terms of mortality. CRP was measured using a standard immunoturbidometric assay on the COBAS® INTEGRA system and hs-CRP was measured using the Dade Behring on the Konelab Nephelometer in 50 patients on HD. CRP (≥6 mg/L) and hs-CRP (≥3 mg/L) levels were elevated in 30% and 54% of the patients, respectively. A significant correlation was noted between hs-CRP and CRP levels (r = 0.98, P <0.001). Deming regression analysis showed that the slope was near one (r = 0.90; 0.83-0.94) and that the intercept was small. Multivariate regression confirmed that age above 40 years (RR = 3.69, P = 0.027) and duration on HD greater than five years (RR = 3.71, P = 0.028) remained significant independent predictors of serum hs-CRP. Thirteen patients died during follow-up (26%). Multivariate Cox regression demonstrated that hs-CRP (RR = 1.062, P = 0.03) and CRP levels (RR = 1.057, P = 0.009) and age (RR = 1.078, P = 0.001) were the most powerful predictors of mortality. The CRP standard assay presents a reasonable alternative to the hs-CRP assay in patients on HD. The advantages of the CRP standard assay are its online and real-time availability as well as lower costs, particularly in developing countries.