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Objectives: The efficacy of postexposure prophylaxis (PEP) after human immunodeficiency virus (HIV) contact relies on administering the treatment within 4 hours of contact with the virus. This study aimed to evaluate predictors of the time that elapses between HIV exposure and emergency department arrival., Material and Methods: Prospective observational study carried out at Hôpital Bichat, a university teaching hospital in Paris, France. All emergency visits for occupational or nonoccupational exposure to HIV in 2016 and 2017 were included., Results: A total of 1475 cases were studied; 598 patients responded to the follow-up survey. A delay of 4 hours or more between HIV exposure and the emergency department visit was associated with type of contact: health care occupational exposure, other occupational exposure, or sexual intercourse (P .001). We found significant differences between individuals exposed during sexual contact versus occupational exposure with respect to knowledge of the PEP program pathway (65.2% vs 46.9%, respectively), previous use of PEP (23.9% vs 13.1%), alcohol intake (36.2% vs 18.5%), drug use (34.6% vs 8.6%), and chemsex (sexualized drug use) (26.1% vs 0%) (P .001, all comparisons). Predictors of time until start of PEP among individuals exposed during sexual intercourse were knowledge and prior use of the PEP pathway (P .001), drug use (P = .03), and chemsex (P .001). Predictors among occupationally exposed individuals were prior knowledge of the PEP pathway and drug use (P .001)., Conclusion: Delay in seeking PEP after HIV exposure is greater among individuals exposed during sexual intercourse. Knowledge of the PEP program and prior use of it are associated with less delay. Exposure during sexual intercourse, alcohol and drug use, and chemsex are associated with longer delays, especially in men who have sex with men.

Background: High-density lipoproteins (HDLs), particles characterized by their reverse cholesterol transport function, display pleiotropic properties, including anti-inflammatory and antioxidant functions. Moreover, all lipoproteins (HDLs but also low-density lipoproteins (LDLs)) neutralize lipopolysaccharides, leading to increased bacterial clearance. These two lipoproteins decrease during sepsis, and an association between low lipoprotein levels and poor outcome was reported. The goals of this study were to characterize the lipid profile of septic patients hospitalized in our intensive care unit (ICU) and to determine the relationship with the outcome., Methods: A prospective observational study was conducted in a university hospital ICU. All consecutive patients admitted for septic shock or sepsis were included. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were assessed at admission (day 1), at day 3, and at ICU discharge. When available, a prehospitalization lipid profile collected prior to the patient's hospitalization was compiled. Short-term and 1-year prognostic outcomes were prospectively assessed., Results: A total of 205 patients were included. We found a decrease in HDL-C concentration between previous values and those at admission, followed by an additional decrease at day 3. At ICU discharge, the concentration was higher than that at day 3 but did not reach the concentration measured prior to hospitalization (prior HDL-C = 1.22 (1.04-1.57) mmol/l; day 1 HDL-C = 0.44 (0.29-0.70) mmol/l; day 3 HDL-C = 0.30 (0.25-0.48) mmol/l; and HDL-C at discharge = 0.65 (0.42-0.82) mmol/l). A similar trend was found for LDL-C (prior LDL-C = 2.7 (1.91-3.33) mmol/l; day 1 LDL-C = 1.0 (0.58-1.50) mmol/l; day 3 LDL-C = 1.04 (0.64-1.54) mmol/l; and LDL-C at discharge = 1.69 (1.26-2.21) mmol/l). Mixed models for repeated measures of lipoprotein concentrations showed a significant difference in HDL-C and LDL-C concentrations over time between survivors and nonsurvivors at day 28. An HDL-C concentration at admission of less than 0.4 mmol/l was associated with increased mortality at day 28 (log-rank test, p = 0.034) but not at 1 year (log-rank test, p = 0.24). An LDL-C concentration at admission of less than 0.72 mmol/l was associated with increased mortality at day 28 and at 1 year (log-rank test, p < 0.001 and p = 0.007, respectively). No link was found between prior lipid profile and mortality., Conclusions: We showed no relationship between the prehospitalization lipid profile and patient outcome, but low lipoprotein levels in the ICU were strongly associated with short-term mortality.

Background: Rapid identification of patients with high suspicion of COVID-19 will become a challenge with the co-circulation of multiple respiratory viruses (RVs). We have identified clinical or biological characteristics to help distinguish SARS-CoV-2 from other RVs., Methods: We used a prospective cohort including all consecutive patients admitted through the emergency department's (ED) and presenting respiratory symptoms from November 2019 to April 2020. Patients were tested for RV using multiplex polymerase chain reaction (mPCR) and SARS-CoV-2 RT-PCR., Results: 203/508 patients were positive for an RV during the non-SARS-CoV-2 epidemic period (November to February), and 268/596 patients were SARS-CoV-2 positive during the SARS-CoV-2 epidemic (March to April). Younger age, male gender, fever, absence of expectoration and absence of chronic lung disease were statistically associated with SARS-CoV-2 detection. Combining these variables allowed for the distinguishing of SARS-CoV-2 infections with 83, 65, 75 and 76% sensitivity, specificity, PPV and NPV, respectively., Conclusion: Patients' characteristics associated with a positive PCR are common between SARS-CoV-2 and other RVs, but a simple discrimination of strong SARS-CoV-2 suspicion with a limited set of clinical features seems possible. Such scoring could be useful but has to be prospectively evaluated and will not eliminate the need for rapid PCR assays., Competing Interests: DB and BV declare having received past personal fees and grant from Qiagen. All the others declare having no conflict of interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

ED-visits and through-ED admissions to medical/surgical wards (MSW) and intensive care unit (ICU) during influenza, COVID-19 and lockdown periods were evaluated in a four-hospital prospective observational study from November 2018 to March 2020. ED visit characteristics and main diagnostic categories were assessed. Analysis of 368,262 ED-visits highlighted a significantly increasing trend in ED-visits during influenza followed by a significantly decreasing trend after lockdown. For MSW-admissions, a pattern of growth during influenza was followed by a fall that began during COVID-19 pandemic and intensified during the lockdown. For ICU-admissions, a significant rise during the COVID-19 pandemic was followed by diminution during the lockdown period. During lockdown, significantly diminishing trends were shown for all diagnostic categories (between -40.8% and -73.6%), except influenza-like illness/COVID cases (+31.6%), Pulmonary embolism/deep vein thrombosis (+33.5%) and frequent users (+188.0%). The present study confirms an increase in demand during the influenza epidemic and during the initial phase of the COVID-19 epidemic, but a drop in activity during the lockdown, mainly related to non-COVID conditions. Syndromic surveillance of ILI cases in ED is a tool for monitoring influenza and COVID-19, and it can predict ED activity and the need for MSW and ICU beds.

Introduction: Severe acute respiratory syndrome coronavirus2 has caused a global pandemic of coronavirus disease 2019 (COVID-19). High-density lipoproteins (HDLs), particles chiefly known for their reverse cholesterol transport function, also display pleiotropic properties, including anti-inflammatory or antioxidant functions. HDLs and low-density lipoproteins (LDLs) can neutralize lipopolysaccharides and increase bacterial clearance. HDL cholesterol (HDL-C) and LDL cholesterol (LDL-C) decrease during bacterial sepsis, and an association has been reported between low lipoprotein levels and poor patient outcomes. The goal of this study was to characterize the lipoprotein profiles of severe ICU patients hospitalized for COVID-19 pneumonia and to assess their changes during bacterial ventilator-associated pneumonia (VAP) superinfection., Methods: A prospective study was conducted in a university hospital ICU. All consecutive patients admitted for COVID-19 pneumonia were included. Lipoprotein levels were assessed at admission and daily thereafter. The assessed outcomes were survival at 28 days and the incidence of VAP., Results: A total of 48 patients were included. Upon admission, lipoprotein concentrations were low, typically under the reference values ([HDL-C] = 0.7[0.5-0.9] mmol/L; [LDL-C] = 1.8[1.3-2.3] mmol/L). A statistically significant increase in HDL-C and LDL-C over time during the ICU stay was found. There was no relationship between HDL-C and LDL-C concentrations and mortality on day 28 (log-rank p = 0.554 and p = 0.083, respectively). A comparison of alive and dead patients on day 28 did not reveal any differences in HDL-C and LDL-C concentrations over time. Bacterial VAP was frequent (64%). An association was observed between HDL-C and LDL-C concentrations on the day of the first VAP diagnosis and mortality ([HDL-C] = 0.6[0.5-0.9] mmol/L in survivors vs. [HDL-C] = 0.5[0.3-0.6] mmol/L in nonsurvivors, p = 0.036; [LDL-C] = 2.2[1.9-3.0] mmol/L in survivors vs. [LDL-C] = 1.3[0.9-2.0] mmol/L in nonsurvivors, p = 0.006)., Conclusion: HDL-C and LDL-C concentrations upon ICU admission are low in severe COVID-19 pneumonia patients but are not associated with poor outcomes. However, low lipoprotein concentrations in the case of bacterial superinfection during ICU hospitalization are associated with mortality, which reinforces the potential role of these particles during bacterial sepsis., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Every winter, emergency departments (EDs) face overcrowding with patients presenting influenza-like symptoms, and organisational issues such as single room assignment and droplet precautions to avoid hospital-acquired influenza. Our main objective was to assess the impact of PCR results and patient's severity on single room assignment., Methods: All patients admitted to Bichat-Claude Bernard Hospital through the ED and tested for influenza by PCR (GenXpert, Cepheid) or (FilmArray, BioMérieux) on a nasopharyngeal swab were retrospectively included during three influenza seasons (2015-2018., Results: Of 1,330 included patients, 278 (20.9%) had a positive PCR for influenza. The median time to obtain a PCR result was 19 hours, and 238 (18.3%) patients were assigned a single room. Among patients with positive and negative influenza PCR, 22.3% and 16.7% were assigned a single room (p = 0.03). The multivariable analysis was performed on the two first epidemic periods, excluding the third epidemic because of the concomitant use of influenza immune-chromatic test. Only level 1 of the Emergency severity index (ESI) (aOR, 1.9; 95% CI, 1.3-2.8; p < 0.01) was associated with single-room assignment. PCR result was not statistically associated with the decision of single room assignment (aOR, 1.4; 95%CI, 1.0-1.4; p = 0.07)., Conclusion: A PCR positive for influenza was not significantly associated with single-room assignment. Less than one quarter of influenza patients were adequately assigned a single room, likely due to the long turnaround time of PCR result and other conflicting indications for single room-assignment. Accelerating biological diagnosis could improve single-room assignment., Competing Interests: The authors have declared that no competing interests exist.

Background: The use of efficient, reliable and sensitive PCR assays is a cornerstone in the race to contain the SARS-CoV-2 pandemic. In this work we performed an independent evaluation of the RealStar® SARS-CoV-2 RT-PCR Kit Researh Use Only (Altona) for SARS-CoV-2 detection., Methods: A comparative limit of detection (LoD) assessment was performed between RealStar® SARS-CoV-2 and the currently WHO recommended RT-PCR (WHO-PCR) workflow using a quantified clinical sample. Assessment of the RealStar® SARS-CoV-2 assay was also performed using 83 primary clinical samples in comparison with the WHO-PCR., Results: The RealStar® SARS-CoV-2 demonstrated a slightly higher sensitivity than the WHO recommended assay with a limit of detection at 625 copies/mL instead of 1250 copies/mL for the WHO-PCR in our conditions. The overall percent agreement between RealStar® SARS-CoV-2 and WHO-PCR on 83 clinical samples was 97.6 % (81/83) with a sensitivity at 97.8 % (45/46) and specificity at 97.3 % (36/37). No cross reaction was encountered for the other human coronaviruses (HKU1, OC43, NL63, 229E)., Conclusions: In this comparison of the RealStar® SARS-CoV-2 assay with the reference WHO assay, we observed a slightly better sensitivity of the RealStar® assay. It provides a robust option for all molecular biology laboratories, with a strong real-life LoD and is compatible with various real-time PCR platforms., Competing Interests: Declaration of Competing Interest BV received travel accommodations and personal fees from Qiagen and Biomérieux. The other authors have no conflict of interest to declare., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In the race to contain severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), efficient detection and triage of infected patients must rely on rapid and reliable testing. In this work, we performed the first evaluation of the QIAstat-Dx respiratory SARS-CoV-2 panel (QIAstat-SARS) for SARS-CoV-2 detection. This assay is the first rapid multiplex PCR (mPCR) assay, including SARS-CoV-2 detection, and is fully compatible with a non-PCR-trained laboratory or point-of-care (PoC) testing. This evaluation was performed using 69 primary clinical samples (66 nasopharyngeal swabs [NPS], 1 bronchoalveolar lavage fluid sample [BAL], 1 tracheal aspirate sample, and 1 bronchial aspirate sample) comparing SARS-CoV-2 detection with the currently WHO-recommended reverse transcription-PCR (RT-PCR) (WHO-RT-PCR) workflow. Additionally, a comparative limit of detection (LoD) assessment was performed for QIAstat-SARS and WHO-RT-PCR using a quantified clinical sample. Compatibility of sample pretreatment for viral neutralization or viscous samples with the QIAstat-SARS system were also tested. The QIAstat-Dx respiratory SARS-CoV-2 panel demonstrated a sensitivity comparable to that of the WHO-recommended assay with a limit of detection at 1,000 copies/ml. The overall percent agreement between QIAstat-Dx SARS and WHO-RT-PCR on 69 clinical samples was 97% with a sensitivity of 100% (40/40) and specificity at 93% (27/29). No cross-reaction was encountered for any other respiratory viruses or bacteria included in the panel. The QIAstat-SARS rapid multiplex PCR panel provides a highly sensitive, robust, and accurate assay for rapid detection of SARS-CoV-2. This assay allows rapid decisions even in non-PCR-trained laboratory or point-of-care testing, allowing innovative organization., (Copyright © 2020 Visseaux et al.)

Background: Health Education in the emergency department (ED) is one of the tasks that the HIV-exposure triage implementation needs to be considered. No triage training has been evaluated., Methods: A prospective 3-years pre- and post-intervention study in an urban academic ED was realized. The intervention was a simulation-based training on triage rules for triage nurses. Triage is based on time between HIV-exposure and ED arrival (≤48 h: level 2 (urgent); ≥48 h: level 5 (non-urgent))., Findings: A total of 2011 HIV-exposures were included; 15.1 per cent were well triaged in pre-intervention vs. 88 per cent in post-intervention period (P < 0.0001). Among well-triaged patients as level 2, the post-exposure prophylaxis prescription rate increased from 30.5 to 57.6 per cent (P < 0.0001). Time interval quality indicators (minutes) were: ED arrival-Triage Nurse 10.9 ± 9.6 vs. 9.1 ± 4.8 (P < 0.0001), ED arrival-Physician 56.3 ± 26.0 vs. 49.9 ± 36.0 (P = 0.0001), and ED arrival to Post-exposure prophylaxis first-dose 86.9 ± 30.0 vs. 65.2 ± 42.0 (P < 0.0001)., Conclusions: These results suggest that time interval HIV-exposure to ED arrival can be used as a triage criterion. A continuous quality improvement program for PEP after HIV-exposure based on a nurse triage training program achieved the objectives of optimizing the triage performance by reducing the time to access the post-exposure prophylaxis first-dose., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

To evaluate the impact of an influenza vaccination (IV) coverage (IVC) in a vaccination campaign of an Emergency Department (EDVC) and its impact on ED time interval quality indicators. We conducted a 4 year observational study, with an intervention during the 4th year. IVC was calculated during pre-and early-epidemic periods. During the final period, a 12 weeks EDVC was implemented. Physicians and nurses were trained and sensitized in the importance of vaccination, and their role in the prevention of severe forms of influenza was reinforced. The vaccine was proposed by physicians and nurses, and delivered by them. Repeated measures ANOVA is a validated method for related not independent groups ( https://statistics.laerd.com/statistical-guides/repeated-measures-anova-statistical-guide.php ). Overall, IVC was 987/3191 (30.9%) with an increasing trend from 28.8 to 33.2%. In the fourth period, out of 868 patients identified with IV indication, 288 had already been vaccinated (IVC 33.2%). After excluding patients presenting criteria of exclusion, IV was proposed to 475 patients: 317 (66.7%) accepted. The vaccination rate after patient's acceptance was 89.6% (288/317). At the end of the EDVC, influenza vaccination coverage was 572 (284 + 288)/868 (65.9%). The delay between arrival at the ED and seeing the triage nurse and physician as well as the overall ED length of stay were not modified during the study period and before and during EDVC. EDVC effectively doubled the influenza vaccination coverage, without modifying ED time interval quality indicators.

Objectives: Influenza vaccination (IV) coverage remains low in France. Objectives were to assess patient knowledge and behaviors and missed opportunities for vaccination (MO) and their impact on vaccine uptake., Methods: This is a prospective-observational study, including emergency department patients at risk for severe influenza. Patients were interviewed about their knowledge and behaviors. We evaluated the health-care voucher scheme (HCVS) and MO., Results: 868 patients were included. Vaccine uptake was 33.2%, 42% of patients knew about the possible severity of influenza, 23% thought that they were not at risk for severe influenza, 39% knew that they have an indication for the vaccine, and 4.3% to 11.5% expressed reservations concerning IV side effects and effectiveness. HCVS was used by 44.3% of patients, but only 14.8% had been vaccinated. MO were reported by 484 patients (69.4%) declaring 1104 consultations and 148 IV propositions (86.6%). Predictors of vaccine uptake (p<0.0001) were: knowledge of serious and fatal influenza forms [OR 0.36 (CI95% 0.25-0.5)]; confidence in influenza vaccine effectiveness [0.38 (0.2-0.7)]; opposition to vaccines [0.22 (0.1-0.48)]; visit to general practitioner [4.53 (2.9-7.1)]; general practitioner proposed IV [2.1 (1.2-3.4)]., Conclusion: Our results indicate that high rate of missed opportunities, some patient behaviors and general practitioner visits may explain low influenza vaccine uptake, and that HCVS use is a complex process. Of interest, we found that the patient's knowledge of the potential severity of influenza is not sufficient to promote vaccine, suggesting that the information strategy must be adapted to each patient behavior.

Background: New rapid influenza diagnostic tests (RIDT) are available but their clinical utility in adults has not been validated., Objectives: To evaluate the diagnostic performances of OSOM ® Ultra Flu A&B a RIDT on viral strains of influenza A/B from the last epidemic season, and its feasibility by Emergency Department (ED) physicians and nurses., Study Design: Of the 1099 patients admitted to the ED with suspected influenza, all having a nasopharyngeal swab tested by the Xpert ® Flu PCR and then stored at -20 °C; 500 were selected at random and their samples were tested using the RIDT. Two experts reviewed ED and hospital medical records and all virological data to define influenza cases. Intra- and inter-observer variability were calculated., Results: Of the 500 patients included 45% were ≥75 years, 122 (24.4%) presented with influenza based on clinical and virological criteria. PCR test performances (%) were Se 98.4 (95% CI 93.6-99.7), Spe 99.7 (98.3-100), PPV 99.2 (94.8-100) and NPV 99.5 (97.9-100); and RIDT performances were Se 95.1 (89.2-97.9), Spe 98.4 (96.4-99.4), PPV 95.1 (87.2-99.9) and NPV 98.4 (96.4-98). There was no difference in test performance between influenza A and B virus nor between the influenza A subtypes. Intra- and inter-observer variability of RIDT were 0.94 (0.89-0.99) and 0.96 (0.92-1)., Conclusion: Our results show that the Xpert ® Flu PCR and the OSOM ® Ultra Flu A&B Test perform very well in diagnosing strains of circulating virus in adults and elderly. Our results also confirm the feasibility of this RIDT at point-of-care by ED staff., (Copyright © 2017. Published by Elsevier B.V.)

Objective: The common association between NOD2/CARD15 and TLR4 gene variants with inflammatory bowel disease (IBD) has not been replicated in all studies. We studied the polymorphism of these two genes in Tunisian patients with IBD., Methods: Polymorphisms of NOD2 (R702W, G908R and L1007fs) and TLR4 (Asp299Gly and Thr399Ile) genes were analyzed in 106 patients with IBD (68 with ulcerative colitis [UC], 38 with Crohn's disease [CD]) and 160 healthy controls using polymerase chain reaction-restriction fragment length polymorphism. Genotypes and phenotypes were correlated., Results: The mutated allele of TLR4-Thr399Ile was strongly associated with IBD (9.4% in IBD, 7.4% in UC and 13.2% in CD vs 2.5% in controls; P = 0.0004, 0.014 and 0.00006, respectively). Heterozygous genotypes were significantly more frequent in patients with IBD (17.0%), UC (14.7%) and CD (21.1%) than in controls (5.0%) (P = 0.0012, 0.012 and 0.001, respectively). Interestingly, the wild genotype was found to be protective (odds ratio 0.24). The mutated allele of TLR4-Asp299Gly was more frequent in controls (6.8%) than in patients with IBD (2.9%). A phenotypic correlation of Asp299Gly-AG genotype with arthritis in UC patients was detected (P = 0.003). Regarding the NOD2 gene, the common variations studied were not polymorphic and there was no genetic association with IBD., Conclusion: The TLR4-Thr399Ile variant was strongly associated with susceptibility to IBD, whereas TLR4-Asp299Gly seems to play a role in the clinical expression of UC. The rarity and non-association of NOD2 mutations with IBD may reveal a genetic characteristic of the population in our region., (© 2017 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Unlabelled: Intraoperative radiotherapy (IORT) is continuously gaining ground in cancer treatment. However, there is currently no planning system associated with these devices, which precludes patient-specific dose delivery optimization. The objective of this study was the development and validation of a Monte Carlo simulation (MCS)-based dosimetry platform using the Intrabeam™ system., Methods: After surgical resection of the tumor this system delivers a single dose fraction at the surface of an applicator irradiating the tumor bed through a 50 kV x-ray beam. The GATE MCS platform was used in this study combining the phase space obtained by modeling the x-ray source and the detailed modeling of the additional parts of the Intrabeam™ system. The model was validated by comparing simulated versus experimental measurements of depth dose curves (DDC) and isotropy. A clinical validation study was also carried out using patient computed tomography images., Results: The mean deviation between measured and simulated DDC was 2.9% ± 4.4% and 5.9% ± 5.7% for the bare needle and the use of applicators, respectively. A good agreement with experimental measurements was also found in terms of dose isotropy with a maximum difference of 2.04% for the 40 mm diameter applicator. A patient study revealed a mean absolute deviation of 0.06 Gy between simulated and thermoluminescent dosimeters (TLD) measured skin doses., Conclusion: This study shows the potential of using the GATE MCS platform to model three-dimensional dose distributions of the Intrabeam™ system for use in IORT.

Autoimmune diseases (ADs) share several genetic factors resulting in similarity of disease mechanisms. For instance polymorphisms from the KIAA1109-interleukin 2 (IL2)-IL21 block in the 4q27 chromosome, has been associated with a number of autoimmune phenotypes. Here we performed a haplotype-based analysis of this AD related region in Tunisian patients. Ten single nucleotide polymorphisms (rs6534347, rs11575812, rs2069778, rs2069763, rs2069762, rs6852535, rs12642902, rs6822844, rs2221903, rs17005931) of the block were investigated in a cohort of 93 systemic lupus erythematosus (SLE), 68 ulcerative colitis (UC), 39 Crohn's disease (CD) patients and 162 healthy control subjects of Tunisian origin. In SLE population, haplotypes AGCAGGGTC, AGAAGAGTC, AGAAGGGTC and AGCCGAGTC provided significant evidence of association with SLE risk (p = 0.013, 0.028, 0.018 and 0.048, respectively). In the UC population, haplotype AGCCGGGTC provided a susceptibility effect for UC (p = 0.025). In the CD population, haplotype CAGGCC showed a protective effect against the development of CD (p = 0.038). Haplotype AAGGTT provided significant evidence to be associated with CD risk (p = 0.007). Our results support the existence of the associations found in the KIAA1109/IL2/IL21 gene region with ADs, thus confirms that the 4q27 locus may contribute to the genetic susceptibility of ADs in the Tunisian population.

Type 1 diabetes (T1D) is an autoimmune disease (AID) with both genetic and environmental components. We aimed to investigate the genetic association of polymorphisms in genes previously linked with other AIDs, namely BANK1, IL15 and IL2/IL21 region. A total of 76 T1D patients and 162 controls from Southern Tunisia were recruited for a case-control association study investigating the relationship between sixteen SNPs of the BANK1, IL15 and IL2/IL21 gene region and T1D. In the BANK1 gene, G allele and GG genotype of rs3733197 were significantly increased in the group of T1D patients compared to controls. In addition, in the IL15 gene, the minor allele A of rs10519613 polymorphism was significantly higher in patients than in controls. No significant association was found for SNPS in IL2/IL21 gene region. The analysis of the haplotype structure revealed the G-C-A-C-T haplotype of the IL15 gene as associated with a reduction in the risk of developing T1D, while A-T-A-C-T haplotype increased the risk of developing the disease. Furthermore, in the IL2/IL21 region, only one haplotype consisting of eight SNPs was markedly associated with T1D susceptibility. Moreover, G-C combination of the BANK1/IL15 was significantly increased in T1D patients, compared to controls. Our results establish BANK1 and IL15 as new T1D genetic susceptibility factors and replicate the association of the 4q27 region with T1D. Our data agree with the effect previously observed for other autoimmune conditions and delineate a shared underlying mechanism., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Type 1 diabetes (T1D) is caused by an immune-mediated destruction of the insulin-producing β-cells. Several studies support the involvement of T cell activation molecules. In order to underline the role of the genes involved in this pathway, we investigated, using the Sequenom MassARRAY platform, polymorphisms of sixteen single-nucleotide polymorphisms (SNPs) belonging to PTPN22, CD28, CTLA-4, and ZAP-70 genes in 76 T1D patients and 162 unrelated healthy controls from Southern Tunisia. We confirmed the association with PTPN22 (rs2476601, Corrected P (Pcorr)=0.002, OR=6.20) and CD28 gene (rs1879877, Pcorr=0.003; OR=4.27 and rs3181096, Pcorr=0.02; OR=1.73). We also identified an association with rs17695937 of ZAP-70 gene (Pcorr=0.02, OR=1.87). Our results suggest a significant effect on T1D susceptibility for A-C-A-G-C and T-C-C-T-A-C haplotypes, of ZAP-70 and CD28 genes, respectively. In addition, (A-G-C) combination of ZAP-70/CD28 gene was significantly increased in T1D patients as compared to controls, suggesting the possible interaction between these genes. These results confirm the involvement of PTPN22 and CD28 genes in the genetic susceptibility to T1D. Interestingly, ZAP-70 seems to contribute to the susceptibility to the disease in our population. However, this finding has to be confirmed in further studies., (© 2013.)

Associations with different autoimmune diseases of polymorphisms in genes encoding the IL2RA and IL2RB subunits (located in 10p15 and 22q13, respectively), were identified through genome-wide studies. Polymorphisms in these two genes were studied in 107 inflammatory bowel disease (IBD) patients (39 Crohn's disease [CD] and 68 ulcerative colitis [UC]) and in 162 ethnically healthy controls from Tunisia (Sfax). Two of the 15 IL2RA single-nucleotide polymorphisms (SNPs) genotyped (rs4749924 and rs706778) were significantly associated with UC (pcorr=0.018 and 0.048, respectively), but no evidence of association with CD was observed. The IL2RA GTCT haplotype was also more frequent in UC patients compared to controls (2.6% vs. 0%; p=0.002). One of the 6 IL2RB SNPs genotyped (rs743776) was significantly associated with CD (pcorr= 0.039), but no evidence of association with UC was observed. No significant association between IL2RB haplotypes was observed among investigated groups. Our study identified markers in the IL2RA and IL2RB genes that are significantly associated with UC and CD, respectively. Our results supporting IL2RA and IL2RB as promising candidate genes for IBD and suggesting a potential role of IL2R in the pathogenesis of IBD, likely involves regulatory T cells.

Background: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastro-intestinal tract with unknown etiology. Both environmental and genetic factors are involved in the pathogenesis of these inflammatory bowel diseases (IBD)., Aim: The purpose of the present study was to determine the association between the polymorphism of the transmembrane region of MICA (MICA-TM), and the genetic susceptibility in Tunisian patients with IBD., Patients and Methods: A total of 102 Tunisian patients (66 with UC, 36 with CD) and 123 healthy controls were enrolled in our study. MICA-TM was genotyped by a semiautomatic fluorescent-labelled PCR method, amplicons were analysed on an ABI Prism 310 genotyper. Comparisons of allele frequencies between patients and controls, and between patients' subgroups were performed using SPSS 13.0., Results: No MICA allele was significantly increased in both groups of IBD compared to controls. The MICA-A5.1 allele was significantly decreased in CD patients (p=0.006, pc=0.03). In UC, MICA-A6 was associated with the presence of extraintestinal manifestations (p=0.04, pc=0.2), whereas MICA-A5 was associated with late age of onset (p=0.04). In CD, MICA-A6 was significantly increased in active disease patients when compared to moderately active or inactive disease (p=0.03, pc=0.15)., Conclusion: Some clinical features of CD and UC may be influenced by specific MICA-TM alleles. In our South Tunisian population, MICA plays a disease modifying role, rather than being an important gene in the susceptibility for developing IBD.

Unlabelled: BACKGROUND / AIMS: Inflammatory bowel diseases (IBDs), Crohn's disease (CrD) and ulcerative colitis (UC), are chronic gastrointestinal inflammatory disorders. The precise etiology of IBD remains unclear, and it is thought that interactions among various factors, including, genetic factors, the host immune system and environmental factors, cause disruption of intestinal homeostasis, leading to dysregulated inflammatory responses of the gut. As inflammation is intimately related to formation of reactive intermediates, including, reactive oxygen species, oxidative stress has been proposed as a mechanism underlying the pathophysiology of IBD. The purpose of this study is to examine the lipid peroxidation, protein oxidation and anti-oxidative profile in Tunisian IBD., Materials and Methods: Malondialdehyde (MDA), conjugated dienes (CD), protein thiol levels, as well as the catalase (CAT) activity were evaluated in intestinal biopsies of 17 patients affected by IBD (12 CrD and 5 UC) and 12 healthy control individuals., Results: Oxidative stress was confirmed in these two types of disease biopsies as compared to controls. MDA and CD levels were significantly increased in both UC and CrD patients' biopsies as compared to controls' biopsies ( P < 0.001). CAT activity was similar in UC and CrD biopsies' and was not significantly increased in IBD patients' biopsies compared with controls' biopsies ( P > 0.05). Anon-significant decrease in thiol (SH) level was observed in both UC and CrD patients' biopsies compared with controls' biopsies ( P > 0.05)., Conclusion: Increased levels of MDA and CD in IBD patients' biopsies underline the implication of oxidative stress in the physiopathology of IBD.

Inflammatory bowel diseases (IBDs), consisting of ulcerative colitis (UC) and Crohn's disease (CD), are complex disorders with multiple genes contributing to disease pathogenesis. We aimed to identify the associations of genetic variations in the ZAP70, PTPN6, BANK1, and CLEC2D genes encoding for intracellular signaling molecules with IBDs. One hundred seven patients (39 CD and 68 UC) with IBD and 162 healthy control subjects from the Southern Tunisia were recruited. We genotyped 4 single-nucleotide polymorphisms (SNPs) in ZAP70 (rs1020396, rs11686881, rs13420683, and rs17695937), 2 SNPs in PTPN6 (rs7310161 and rs759052), 3 SNPs in BANK1 (rs10516487, rs17266594, and rs3733197), and 1 SNP in CLEC2D (rs3764021). ZAP70 displayed a strong genetic association with CD for rs13420683 [allele C, p=0.003, P(corr)=0.006, odds ratio (OR)=2.25 (1.32; 3.85); genotype CC, p=0.016, P(corr)=0.048, OR=2.57 (1.22; 5.41)]. However, in UC, a weak association with PTPN6 was observed [TT (p=0.01; P(corr)=0.03; OR=2.11 (1.18; 3.76)]. No significant association in the BANK1 and CLEC2D genes was observed. These results suggest the involvement of the ZAP70 and PTPN6 genes in the genetic component conferring a general susceptibility to CD and UC, respectively. This work provides motivation for studies aiming to replicate these findings in larger populations.

Autoimmune Polyglandular Syndrome Type II (APSII) is characterized by the co-occurrence of clinical insufficiency of at least two endocrine glands. Although, HLA determinants of APSII predisposition have been identified, little attention has been paid to non-HLA genes. Here, we used SNP genotyping in a Sequenom platform and genetic association tests to study a cohort of 60 APSII Tunisian patients presenting highly frequent co-occurrence of Autoimmune Thyroid Disease (AITD) and Type 1 Diabetes (T1D) and lower frequency of Addison's disease (AD). We tested the high a priori possibility that well-established non-HLA autoimmunity loci were involved in APSII and confirmed five association signals to APSII, namely: (1) two T1D-associated SNPs, in CTLA4 and IL2RA, suggest their involvement in T1D pathogenesis in this cohort; (2) two SNPs in STAT4 and IL15 not previously associated to endocrinopathies, are possibly involved in co-occurrence of organ autoimmunity in APSII, and; (3) one SNP in TNF alpha showed association to APSII irrespective of AD. While this work was performed in a relatively small cohort, these results support the notion that the non-HLA genetic component of APSII include genetic factors specific of particular autoimmune manifestations as well as genetic factors that promote the co-occurrence of multiple autoimmune endocrinopathies., (Copyright © 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

This study aimed to investigate the association between HLA DR/DQ and inflammatory bowel diseases (IBD) in Tunisian patients and to determine the relationship between HLA DR/DQ alleles with the clinical disease patterns. DNA typing of human leukocyte antigen (HLA) genes was performed in 70 ulcerative colitis (UC) patients, 40 Crohn's disease (CD) patients, and 123 healthy controls (HC) using a polymerase chain reaction sequence specific primer technique. Data were analyzed using Cochran-Mantel-Haenszel test and binary logistic regression. Compared with HC, IBD patients showed an increased frequency of the homozygous DRB1*07 genotype. This positive association was maintained when UC and CD were separately compared to HC. In UC patients, DQB1*03:02 was predictive of colonic extension whereas DRB1*13 and DQB1*03:01 were associated limited disease localization (left-sided colitis and proctitis). The DRB1*15 allele increased in patients with extraintestinal manifestations. In CD, female patients showed an increased frequency of DRB1*13, DRB1*15, and DQB1*06 alleles and DRB1*13-DQB1*06 haplotype, whereas a significant increase of DRB1*07, DQB1*02 alleles, and DRB1*07-DQB1*02 haplotype was noted in male patients. These results show a significant association of the homozygous HLA-DRB1*07 genotype with UC and CD and of several HLA DR/DQ alleles and haplotypes with the clinical phenotypes of these diseases in Tunisian patients. Because of limited statistical power, our study findings are subject to further investigation.

The identification of susceptibility genes for inflammatory bowel disease (IBD) is key to understanding pathogenic mechanisms. Recently, the results of genetic association studies have highlighted many loci that are shared among several autoimmune diseases. We aimed to study the genetic epidemiology of polymorphisms in specific genes previously associated with other autoimmune diseases, namely the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes. Twelve polymorphisms in the CREM, STAT4, STAT5a, Stat5b, and IRF5 genes were genotyped in a cohort of 107 IBD patients (39 Crohn's disease [CD] and 68 ulcerative colitis [UC]) and 162 controls from southern Tunisia. One CREM single nucleotide polymorphism (SNP) displayed evidence for genetic association with IBD (p=8.7×10(-4), odds ratio [OR]=2.84 [1.58; 5.09]). One STAT4 SNP (p=0.026; OR=1.65 [1.06; 2.58]) exhibited a marginal association with UC but not with CD. No significant association was observed with the SNPs in STAT5a, IRF5, and STAT5b. These results suggest that common variants of the CREM gene are involved in the genetic component conferring general susceptibility to IBD, whereas STAT4 appears to be more specifically associated with UC. This work provides motivation for studies aiming to replicate these findings in larger populations., (Copyright © 2011 American Society for Histocompatibility and Immunogenetics. All rights reserved.)

We evaluated the combined use of different fixatives for the identification of atypical perinuclear anti-neutrophil cytoplasmic antibodies (p-ANCA) in patients with inflammatory bowel diseases (IBD) by indirect immunofluorescence (IIF). Sera from 59 ulcerative colitis (UC) and 37 Crohn's disease (CD) patients, and from 64 healthy controls were studied. The IIF on ethanol-, formalin-, and methanol-fixed neutrophils was used for the detection of ANCA. Enzyme linked immunosorbant assay (ELISA) was performed to identify the antigens recognized by ANCA. ANCAs were present in 35 of 59 (59.3%) UC patients and in 10 of 37 (27.02%) CD patients. Atypical p-ANCA positivity was strongly associated with UC disease (44.1% in UC vs. 8.1% in CD; p = 0.0002). The combined application of different fixatives contributed to make easy the differentiation between typical p-ANCA and atypical p-ANCA. Atypical p-ANCA determination appears to be a useful parameter for the distinction between UC and CD.

Unlabelled: The aim of our study was to evaluate the sensitivity, specificity and predictive values of isolated and combined ASCA and NANA assays in Tunisian inflammatory bowel diseases patients and to assess whether their presence is associated with particular clinical features of the disease., Methods: 128 patients (39 with ulcerative colitis, 25 with Crohn disease, and 64 healthy subjects) were enrolled in the study. ASCA and NANA were performed by ELISA and indirect immuno-fluorescence, respectively. Sensitivity, specificity, PPV and NPV of NANA for UC was: 56.4%, 88%, 88% and 56.4%; and ASCA for CD were: 56%, 82.1%, 54.5% and 75.6%, respectively. The combined use of these two markers modified diagnostic accuracy: NANA+/ASCA- in UC 53.8%, 88%, 87.5% and 55% and for NANA-/ASCA+ in CD 52%, 94.9%, 86.7% and 75.5%. No significant association was found between the presence of a specific serological marker and patients' clinical features. In conclusion, the specificity of these combined markers tends to be higher than sensitivity, what made them more useful in the differentiation of the IBD subtypes rather than population screening.

Magnesium intake was assessed using six 24-h dietary records during a 1-year period in 5,448 subjects (3,111 women 35-60 yrs old and 2,337 men 45-60 yrs old) in the SU.VI.MAX cohort, selected at a national level in France. The overall mean dietary intake was estimated at 369 +/- 106 mg/day in men and 280 +/- 84 mg/day in women. 77 per cent of women and 72 per cent of men had dietary magnesium intakes lower than recommended dietary allowances; 23 per cent of women and 18 per cent of men consumed less than 2/3 of these RDA. A strong positive correlation existed between energy and magnesium intake (r = 0.79; p < 10(-4)). Slight variations were observed according to socio-professional and educational levels and place of residence. Cereal products represented the main contribution in both men (21 per cent) and women (19.8 per cent). In men, the second source was represented by alcoholic beverages (11.7 per cent), which were a lower source of magnesium in women (5.5 per cent). Dairy products, vegetables, meat and poultry were the other main sources of dietary magnesium intake.