Search

Background Coronavirus disease 2019 (COVID-19) is the current pandemic disease without any vaccine or efficient treatment to rescue the patients. Underlying diseases predispose the patients to a more severe disease and to a higher mortality rate. However, little evidence exists about COVID-19 outcomes in the pediatric population with congenital heart disease (CHD). Here, we report nine children with COVID-19 and concomitant CHD. Methods Our study included nine children with COVID-19 and concomitant CHD who were admitted to Children Medical Center Hospital during March and April 2020. The patients were classified based on the final outcome (death), and their clinical sign and symptoms, type of CHD, and drugs administered were compared. Results Among the nine patients, two died and we compared different characteristics, laboratory results and clinical findings of these cases based on the mortality. The deceased patients had severe types of CHD, worse arterial blood gases, severe clinical symptoms, higher mean level of partial thromboplastin time and C-reactive protein, and required more medications. Conclusions The present study showed that the general consideration of mild COVID-19 in children does not include patients with CHD and that it is necessary to pay greater attention to children with CHD to determine guidelines for treatment of COVID-19 in these children. Owing to the scarcity of CHD and COVID-19, we reported only nine cases. However, further studies are highly required in this regard.

Context: Fluoride is a necessary element for bone growth and the prevention of dental caries. Diet and dentifrices are the most significant sources of fluoride exposure in children. The concentration of fluoride differs in various types of foods. Although at optimal levels, fluoride has beneficial effects on dental health, in high concentrations, it has some adverse effects, such as structural and functional defects in organs like the kidney and interference with thyroid function. High doses of fluoride can lead to fluoride toxicity, affecting different parts of the body like teeth. Our study aimed to review the previous studies on fluoride toxicity and provide relevant information to dentists and specialists about fluoride safety in children. Evidence Acquisition: The data we used in our review were found from articles published until 2019 and collected from official web pages and documents published from different international institutions. Topics discussed in this review were dietary intake of fluoride, fluoride metabolism, history of fluoride use, mechanism of fluoride action, overuse, and toxicity of fluoride. After the abstract screening, we reviewed relevant studies for full-text review. Results: Fluoride is generally found in the human daily diet. There are different sources of fluoride, such as fluoride supplements or fluoride dentifrices. Fluoride also has a topical protective effect against teeth decay. Ingestion of high doses of fluoride in a short time can lead to fluoride poisoning. Emergency treatment is needed when the toxic dose of 15 mg/kg has been exceeded. This problem usually happens in children while using products such as fluoridated toothpaste for oral hygiene; this illness can threaten their overall health. Conclusions: Fluoride can damage organs such as the liver and kidney as the principal organs susceptible to toxicity induced by fluoride. Although the intake of high doses of fluoride has some adverse health effects, its topical use is considered safe. Fluoride can improve children’s dental health in different ways and prevent caries.

Background Coronavirus Disease 2019 (COVID-19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality. The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID-19 patients. Information on the benefit/risk ratio of this approach is still lacking. Objective To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug. Methods Consecutive COVID-19 patients admitted between February and April 2020 were included in a retrospective analysis. Major bleedings (MB) and clinically relevant non-major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee. Results Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants. The rate of the composite endpoint of MB or CRNMB was 6.9 per 100-person/months in patients who had been given prophylactic doses, and 26.4 per 100-person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90-7.97). The corresponding rates for overall mortality were 12.2 and 20.1 per 100-person/months, respectively. Conclusions The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants. In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher. Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non-critically ill patients with COVID-19.

Accurate and early detection of anomalies in peripheral white blood cells plays a crucial role in the evaluation of well-being in individuals and the diagnosis and prognosis of hematologic diseases. For example, some blood disorders and immune system-related diseases are diagnosed by the differential count of white blood cells, which is one of the common laboratory tests. Data is one of the most important ingredients in the development and testing of many commercial and successful automatic or semi-automatic systems. To this end, this study introduces a free access dataset of normal peripheral white blood cells called Raabin-WBC containing about 40,000 images of white blood cells and color spots. For ensuring the validity of the data, a significant number of cells were labeled by two experts. Also, the ground truths of the nuclei and cytoplasm are extracted for 1145 selected cells. To provide the necessary diversity, various smears have been imaged, and two different cameras and two different microscopes were used. We did some preliminary deep learning experiments on Raabin-WBC to demonstrate how the generalization power of machine learning methods, especially deep neural networks, can be affected by the mentioned diversity. Raabin-WBC as a public data in the field of health can be used for the model development and testing in different machine learning tasks including classification, detection, segmentation, and localization.

Supplemental Material, sj-pdf-1-iji-10.1177_20587384211073232 for Comparative study of six SARS-CoV-2 serology assays: Diagnostic performance and antibody dynamics in a cohort of hospitalized patients for moderate to critical COVID-19 by Sameh Chamkhi, Tarak Dhaouadi, Imen Sfar, Salma Mokni, Alia Jebri, Dhouha Mansouri, Salma Ghedira, Emna Ben Jemia, Samia Ben Boujemaa, Mohamed Houissa, Hichem Aouina, Ta��eb Ben Abdallah and Yousr Gorgi in International Journal of Immunopathology and Pharmacology

PURPOSE: To evaluate the secondary and exploratory outcomes of the Laser Intervention in Early Stages of Age-Related Macular Degeneration (LEAD) study, a 36-month trial of a subthreshold nanosecond laser (SNL) treatment for slowing the progression to late age-related macular degeneration (AMD) in its early stages. DESIGN: Multicenter, randomized, sham-controlled trial. PARTICIPANTS: Two-hundred ninety-two patients with bilateral large drusen. METHODS: Participants were randomly assigned to receive SNL or sham treatment to the study eye at 6-month intervals. MAIN OUTCOME MEASURES: The secondary outcome measure of the LEAD study was the time to development of late AMD, defined by multimodal imaging in the non-study eye. The exploratory outcome measures were the rate of change in best-corrected visual acuity (BCVA), low-luminance visual acuity, microperimetric mean sensitivity, drusen volume in the study and non-study eyes, and participant-reported outcomes based on the Night Vision Questionnaire and Impact of Vision Impairment questionnaire. RESULTS: Progression to late AMD in the non-study eye was not significantly delayed with SNL treatment (hazard ratio, 0.83; 95% confidence interval, 0.40-1.71; P = 0.611). There was no evidence of effect modification based on the coexistence of reticular pseudodrusen; interaction P = 0.065). There was no significant difference between study groups in the rate of change of low-luminance visual acuity, microperimetric mean sensitivity, and drusen volume in the study or non-study eyes, and Night Vision Questionnaire and Impact of Vision Impairment questionnaire scores (all P ≥ 0.167). The rate of BCVA decline was slightly higher for participants in the SNL group compared with the sham treatment group in the study eye (-0.54 and 0.23 letters/year, respectively; P < 0.001) but not the non-study eye (-0.48 and -0.56 letters/year, respectively; P = 0.628). CONCLUSIONS: Subthreshold nanosecond laser treatment of one eye did not have an effect on delaying progression to late AMD in the fellow eye and did not, in general, have an impact on the exploratory structural, functional, and participant-reported outcomes.

With the popularity of deep neural networks (DNNs) in recent years, many researchers have proposed DNNs for the analysis of survival data (time-to-event data). These networks learn the distribution of survival times directly from the predictor variables without making strong assumptions on the underlying stochastic process. In survival analysis, it is common to observe several types of events, also called competing events. The occurrences of these competing events are usually not independent of one another and have to be incorporated in the modeling process in addition to censoring. In classical survival analysis, a popular method to incorporate competing events is the subdistribution hazard model, which is usually fitted using weighted Cox regression. In the DNN framework, only few architectures have been proposed to model the distribution of time to a specific event in a competing events situation. These architectures are characterized by a separate subnetwork/pathway per event, leading to large networks with huge amounts of parameters that may become difficult to train. In this work, we propose a novel imputation strategy for data preprocessing that incorporates the subdistribution weights derived from the classical model. With this, it is no longer necessary to add multiple subnetworks to the DNN to handle competing events. Our experiments on synthetic and real-world datasets show that DNNs with multiple subnetworks per event can simply be replaced by a DNN designed for a single-event analysis without loss in accuracy.

Convolutional neural networks (CNNs) represent the state of the art for fully automated medical image segmentation. However, few works have combined CNNs with interactive user feedback in order to verify and, where necessary, correct their results. We present an interactive visual system that achieves this for the specific use case of segmenting drusen, which serve as a biomarker of age related macular degeneration, from Optical Coherence Tomography. Our main idea is to exploit the probabilistic nature of CNN-based segmentation. First, we derive two uncertainty measures from it. We demonstrate that they indicate cases in which automated segmentation is likely to have failed, and that visualizing them makes manual verification and correction more efficient. Second, based on the probabilistic information, we design intelligent tools for segmentation correction, which automatically propose the most likely alternative segmentation in agreement with user-specified constraints. In a small user study, uncertainty visualization and intelligent interaction reduced the time required to correct retinal layer segmentation by around 53% and, for drusen segmentation, even by 73%. In the future, we plan to use our system not only for efficient segmentation correction, but also for rapid creation of larger training sets.

The main obstacles that lead to clinical failure in cancer treatment are the development of resistant to chemotherapy and a rise in invasive characteristics in cancer tumor cells due to prolonged chemotherapeutic processes. Recent studies have revealed some evidence about the existence of a direct relationship between development of drug resistance and triggering of invasive capability in tumor cells. Therefore, devising and application of chemotherapeutic procedures that are not prone to the development of chemotherapy resistance are necessary. Here, we focus on CD147, CD44, ANAX2, P-gp, MMPs, and UCH-L1 proteins involved in the crosstalk between metastasis and cancer treatment. We think that further structural and functional analysis of these proteins may direct scientists towards designing highly effective chemotherapy procedures.

Accurate and early detection of peripheral white blood cell anomalies plays a crucial role in the evaluation of an individual's well-being. The emergence of new technologies such as artificial intelligence can be very effective in achieving this. In this regard, most of the state-of-the-art methods use deep neural networks. Data can significantly influence the performance and generalization power of machine learning approaches, especially deep neural networks. To that end, we collected a large free available dataset of white blood cells from normal peripheral blood samples called Raabin-WBC. Our dataset contains about 40000 white blood cells and artifacts (color spots). To reassure correct data, a significant number of cells were labeled by two experts, and the ground truth of nucleus and cytoplasm were extracted by experts for some cells (about 1145), as well. To provide the necessary diversity, various smears have been imaged. Hence, two different cameras and two different microscopes were used. The Raabin-WBC dataset can be used for different machine learning tasks such as classification, detection, segmentation, and localization. We also did some primary deep learning experiments on Raabin-WBC, and we showed how the generalization power of machine learning methods, especially deep neural networks, was affected by the mentioned diversity.

Hemolytic uremic syndrome (HUS), characterized by the triad of micro-angiopathic hemolytic anemia, thrombocytopenia, and acute renal insufficiency, is a common cause of acute renal failure in children. It usually follows an episode of gastroenteritis with enterotoxigenic Escherichia coli and is termed typical HUS. However, HUS is also a complication of invasive pneumococcal infection. Reasons for not diagnosing this condition include the absence of a specific laboratory test, the lack of consistent case definitions, unfamiliarity, a misdiagnosis of disseminated intravascular coagulation (DIC) and cases with micro-angiopathic hemolytic anemia and only mild renal injury. The aim of our study is to describe the epidemiology, the treatment and the evolution of HUS after invasive pneumococcal infections in Tunisia. Cases were identified between 2008 and 2016. Infection with S. pneumoniae was confirmed with culture of cerebrospinal fluid, pleural fluid, or blood. Eight children fulfilled our criteria for inclusion in the study. Primary patterns were fever, respiratory signs, neurological signs and uncommon patterns. Pneumonia was a presenting feature in 6 of 8 cases (75%), two patients had confirmed pneumococcal meningitis. Pneumococcal invasive infection was confirmed by positive yield for S. pneumoniae by culture in pleural levy or drainage in two cases, cerebrospinal fluid in two cases and blood in four cases. The mean duration of hospitalization was 23.5 days. Antibiotic therapy was initiated in all patients. Six patients from eight required dialysis for a median 27.8 days. No patients received plasma exchange therapy. Two patients died and. One patient with pneumococcal pneumatocele and presented a sepsis complicated with a nosocomial infection following a prolonged stay in the intensive care unit. One patient had bronchiectasis leading to recurrent broncho-pulmonary infections. One patient who was dialysis dependent at discharge died 4 months later.

Background: Information about renal involvement in pediatric patients with COVID-19 is limited, and there is not enough data about renal and urinary tract involvement in children infected with this novel virus. Objectives: This study aimed to determine the spectrum of kidney diseases in pediatric patients with COVID-19, admitted to a tertiary children’s hospital. Methods: This cross-sectional study was conducted on 71 pediatric patients with COVID-19 infection. Diagnosis of COVID-19 was established based on the guidelines by the Iranian Ministry of Health. The patients’ demographic characteristics, clinical symptoms, laboratory results, and renal ultrasonography findings were extracted from the hospital medical records. Results: On admission, 10% of patients had oliguria, 7.7% had edema, and 3% had hypertension. The first urinalysis indicated proteinuria, leukocyturia, and hematuria in 46%, 24%, and 23% of the patients, respectively. Overall, 40.7% of the patients showed some degree of renal involvement. During hospitalization, acute kidney injury (AKI) occurred in 34.5% of the patients. Based on the pediatric risk, injury, failure, loss of kidney function, and end-stage kidney disease (pRIFLE) classification, stage I (risk group) was found in 20% of patients, stage II (injury group) in 25% of patients, and stage III (failure group) in 55% of patients with AKI. The total mortality rate was estimated at 12.67%, and the incidence of in-hospital death was 30% in pediatric patients with severe COVID-19 infection associated with AKI. Conclusions: The prevalence of AKI was high in patients with COVID-19 infection hospitalized in our tertiary hospital. We also found that a decrease in renal function was associated with a higher risk of mortality. Overall, early detection of AKI and effective treatment may help reduce mortality in patients with COVID-19.

Background and Aim. Lung ultrasound (LUS) is a convenient imaging modality in the setting of coronavirus disease-19 (COVID-19) because it is easily available, can be performed bedside and repeated over time. We herein examined LUS patterns in relation to disease severity and disease stage among patients with COVID-19 pneumonia. Methods. We performed a retrospective case series analysis of patients with confirmed SARS-CoV-2 infection who were admitted to the hospital because of pneumonia. We recorded history, clinical parameters and medications. LUS was performed and scored in a standardized fashion by experienced operators, with evaluation of up to 12 lung fields, reporting especially on B-lines and consolidations. Results. We included 96 patients, 58.3% men, with a mean age of 65.9 years. Patients with a high-risk quick COVID-19 severity index (qCSI) were older and had worse outcomes, especially for the need for high-flow oxygen. B-lines and consolidations were located mainly in the lower posterior lung fields. LUS patterns for B-lines and consolidations were significantly worse in all lung fields among patients with high versus low qCSI. B-lines and consolidations were worse in the intermediate disease stage, from day 7 to 13 after onset of symptoms. While consolidations correlated more with inflammatory biomarkers, B-lines correlated more with end-organ damage, including extrapulmonary involvement. Conclusions. LUS patterns provide a comprehensive evaluation of patients with COVID-19 pneumonia that correlated with severity and dynamically reflect disease stage. LUS patterns may reflect different pathophysiological processes related to inflammation or tissue damage, consolidations may represent a more specific sign of localized disease, whereas B-lines seem to be also dependent upon generalized illness due to SARS-CoV-2 infection.

The Acknowledgements section in the original version of this Article was incomplete. ""This research was supported by the Else Kröner-Fresenius Foundation/German Scholars Organization (EKFS/GSO 16) to RF, the BONFOR GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0028) to MW, the GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0026) to ST and the German Ministry of Education and Research (BMBF), FKZ 13N10349. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report."" now reads: ""This research was supported by the Else Kröner-Fresenius Foundation/German Scholars Organization (EKFS/GSO 16) to RF, the BONFOR GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0028) to MW, the GEROK Program, Faculty of Medicine, University of Bonn, (Grant No. O-137.0026) to ST and the German Ministry of Education and Research (BMBF), FKZ 13N10349. The work of Shekoufeh Gorgi Zadeh was supported by a grant from Deutsche Forschungsgemeinschaft (DFG), grant number SCHM 2966/2-1. The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report."" The original Article has been corrected.

Objectives To evaluate the serum dosage of the biomedicine (DBM) and the incidence of antidrug antibody (ADA) against antitumor necrosis factor (TNF) in spondyloarthritis, and to demonstrate the influence of these parameters on the clinical efficiency. Methods We conducted a cross-sectional multicentric study including patients with spondylarthritis (SpA) under antiTNF (infliximab [INF], etanercept [ETA] and adalimumab [ADL]) for at least 6 months. A dosage of the ADA and DBM were practiced by the immuno-enzymatic essay. Result Seventy one patients were recruited. Disease modifying antirheumatic drugs (DMARDs) were associated with anti-TNF in 30%. ADA was positive in 54% for INF, 33% for ADL and 0% for ETA with a significant difference(p Conclusion The ADA formation lowered the DBM and favored the therapeutic failure.

Background SARS-CoV2 infection are frequently associated with cardiovascular manifestations, in particular with symptomatic acute coronary syndromes, cardiac arrhythmias and acute heart failure. However, the elevation of serum troponin seems to be non specific, and a cardiologic diagnostic workup should be performed. We aimed to assess the clinical characteristic and the prevalence of left ventricular (LV) dyssynergy patterns in a cohort of hospitalized non-critically ill COVID-19 patientsMethods Consecutive patients with an objective diagnosis of COVID-19, from February to April 2020. Baseline characteristics and comorbidities was collected. In case of increased troponin levels or symptoms suggestive for a concomitant cardiac syndrome, patients undergo to serial electrocardiograms, serial Troponin tests and bedside transthoracic echocardiogram.Results 402 consecutive patients were enrolled: 55 patients underwent an echocardiographic exam because of an increase in troponin levels or a suspected myocardial injury. Segmental left ventricular abnormalities were found in 10 (median WMSI 2.03 IQR 1.38-2.75) with a median LV ejection fraction was 30.1 % IQR, median troponin level was 3083 ng/L, median BNP was 761 ng/L. Death for any cause occurred in 4 patients among patients with regional LV abnormalities and in 3 with normal regional function (p= 0,02).Discussion A single bedside transthoracic echocardiogram performed in non critically ill COVID-19 patients with suspected cardiac injury has the potential to better assist clinicians in their challenging decision process. As an isolated increase of troponin levels is common in COVID patients, a bed-side echocardiographic evaluation of cardiac function should be routinely implemented during their early evaluation.

Background It is generally assumed that there have been mixed results in the literature regarding the association between ambient particulate matter (PM) and myocardial infarction (MI). The aim of this meta-analysis was to explore the rate of short-term exposure PM with aerodynamic diameters ≤2.5 μm (PM2.5) and examine its potential effect(s) on the risk of MI. Methods A systematic search was conducted on databases like PubMed, Scopus, Web of Science, and Embase with components: “air pollution” and “myocardial infarction”. The summary relative risk (RR) and 95% confidence intervals (95%CI) were also calculated to assess the association between the PM2.5 and MI. Results Twenty-six published studies were ultimately identified as eligible candidates for the meta-analysis of MI until Jun 1, 2018. The results illustrated that a 10-μg/m 3 increase in PM2.5 was associated with the risk of MI (RR = 1.02; 95% CI 1.01–1.03; P ≤ 0.0001). The heterogeneity of the studies was assessed through a random-effects model with p 2 was 69.52%, indicating a moderate degree of heterogeneity. We also conducted subgroup analyses including study quality, study design, and study period. Accordingly, it was found that subgroups time series study design and high study period could substantially decrease heterogeneity (I2 = 41.61, 41.78). Conclusions This meta-analysis indicated that exposure – response between PM2.5 and MI. It is vital decision makers implement effective strategies to help improve air pollution, especially in developing countries or prevent exposure to PM2.5 to protect human health.

Scientific reports 10(1), 7395 (2020). doi:10.1038/s41598-020-63924-6, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

Scleredema adultorum of Buschke is a rare fibromucinous, scleroderma-like connective tissue disease most commonly found in a post-infectious setting or linked to hematological disorders or diabetes. Lichen sclerosus et atrophicus is an autoimmune condition only in 2.5% of cases localized exclusively at an extragenital site, occurring in up to 34% of patients in association with other autoimmune diseases such as vitiligo, thyroid disorders, alopecia areata, lichen planus, morphea, pernicious anemia and systemic lupus erythematosus. In particular, a stronger link with an autoimmune background in lichen sclerosus et atrophicus has been observed in women who showed higher prevalence for autoimmune conditions and circulating autoantibodies. Literature reveals a genetic susceptibility linked to specific HLA types. We report three patients who developed lichen sclerosus et atrophicus superimposed on skin involved by scleredema adultorum of Buschke. Although the association of lichen sclerosus et atrophicus with scleredema adultorum of Buschke could be coincidental, both diseases could be considered part of the spectrum of sclerodermoid disorders with common underlying pathogenetic mechanisms; which could explain the sequential or simultaneous occurrence of both lesions in our patients.

Background: Many patients with a self-reported penicillin allergy go on to tolerate beta-lactam antibiotics. Allergy specialists may be consulted to determine the nature and extent of the allergy. However, electronic allergy records must be appropriately updated such that recommendations are carried forward. Objective: To determine the percentage of patients who have their electronic allergy record updated after an allergy service consult (ASC). Methods: This was a retrospective study of patients with at least 1 documented beta-lactam allergy and had an ASC during (inpatient) or prior to (outpatient) hospital admission at Northwestern Memorial Hospital and Prentice Women’s Hospital in Chicago, Illinois. Results: Within the study period, a total of 26 526 patients were identified as having a documented antibiotic allergy, with 21 657 patients (81.6% of patients with allergies) having a listed beta-lactam allergy. Of these patients, 1689 (7.8%) patients were identified as having an ASC during or prior to admission, with 598 patients meeting inclusion criteria. Changes in the allergy record were recommended by the ASC for 62% (n = 371) of patients; however, the allergy record was updated after the ASC in 74.9% (n = 278) of patients. Conclusion: ASC recommendations to delabel a patient as beta-lactam allergic must result in updating the allergy record in order to optimize future treatment. Given the low proportion of allergy-labeled patients tested, programs outside formal ASCs should be considered.

BACKGROUND AND OBJECTIVES While dermatoscopy improves diagnostic accuracy for raised nonpigmented lesions, those with white surface keratin can be problematical. We investigated whether retention of povidone-iodine by surface keratin provides a clue to benignity. METHODS We performed a retrospective pilot study (n = 57) followed by a prospective study (n = 117) on raised nonpigmented lesions with white surface keratin. An initial dermatoscopic image was taken of each lesion, povidone-iodine was applied and another image taken. Following lavage with 70% ethanol, a third image was acquired. The percentage surface area of residual povidone-iodine staining after lavage was recorded, and the results analysed. RESULTS The optimal cut-off point of residual staining was 80%, where values of ≤80% pointed to malignancy. At this cut-off, the OR for lesions with values ≤80% to be truly malignant in the retrospective set was 4.03 (95% CI: 2.1-7.6) and the AUC was 0.7 (95% CI: 0.62-0.78). For the prospective set, the corresponding OR was 2.3 (95% CI: 1.4-3.7) and the AUC was 0.62 (95% CI: 0.55-0.68). CONCLUSIONS This study presents evidence that povidone-iodine retention may have a degree of efficacy in distinguishing benign from malignant keratotic lesions. Further study is warranted.

Th17 cell subset has been implicated in autoimmune diseases, tumor immunity and, transplant rejection. In order to investigate the role of IL-17/IL-23 pathway in allograft outcome, intragraft expression of IL-17 mRNA and single nucleotide polymorphisms (SNPs) of IL-17A, IL-17F, IL-17RC, and IL23R genes were evaluated with a quantification of IL-17A, IL-17F, and IL-23 plasma levels. This study revealed that recipients with acute rejection (AR) had a significant increase in IL-17A mRNA expression levels after transplantation compared to controls (P = 0.037). Moreover, IL-17A plasma levels were significantly higher in AR group; pretransplantation (Day–1 [D–1]): P = 0.00022 and posttransplantation (Day 7 [D7]): P < 10–14. IL-17F and IL-23 plasma levels were significantly higher in AR at D7 only (47.86 vs. 22.99 pg/ml; and 33.82 vs. 18.811 pg/ml; P = 0.015 and P < 10–17, respectively). Using receiver-operating characteristic curves, D7 IL-17A and IL-23 plasma levels exhibited excellent sensitivities and specificities for predicting AR. Genetic study revealed no association between IL-17A, IL-17F, IL-17RC, and IL23R studied SNPs and AR. Nevertheless, a significant improvement of graft survival was found in kidney transplant recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G, and *G/A genotypes. Besides, IL-17A mRNA levels were significantly higher in patients carrying the IL-23R*G/G genotype comparatively to those with *G/A genotype. Based on these findings, significant increase of IL-17A mRNA and protein levels in AR recipients that are genetically controlled highlights the role of this cytokine that can be a useful clinical biomarker to predict early acute renal allograft rejection. Study showing significant associations between Day 7 plasma IL-17A, IL-17F and IL-23 and AR with good performances for IL-17A and IL-23 in predicting acute rejection (AR) occurrence; significant increase of IL-17A expression in kidney graft in case of AR; a significant improvement of graft survival in recipients carrying IL-17F-rs763780*A/A, IL-17RC*G/G and *G/A genotypes.

Background: Self-medication can lead to the latency of the real severity of disease, delay in diagnosis, a complication of treatment, threatening side effects, and unexpected intoxication. The present research aimed to explore the prevalence of self-medication and its factors among students affiliated to Bandar Abbas universities in 2016. Materials and Methods: This Descriptive Analytic study was performed on 600 students affiliated to the universities in Bandar Abbas; Islamic Azad University, Payam-e-Noor University, and University of Medical Sciences. The sample was selected through a stratified sampling method, and the data were collected by a questionnaire comprised of two parts, demographic information (6 items), and risk factors of self-medication and self-medicated drugs (26 items). SPSS version 19 was used to analyze the data through the required tests. Result: The mean age of the students was 24.11±5.85 years. One hundred and ninety-one subjects (31.8%) were male, and 409 (68.2%) were female. The results revealed the prevalence of self-medication in the target population was 80.2%., the main reasons for self-medication were reported underestimating the disease 461(77.0%), previous experience of the disease 457(76.4%), repeated prescription 441(73.6%), and easy access to drug 423(70.6%). The most prevalent drugs self-medicated by students were acetaminophen, herbal medicines, antibiotics, other drugs, sedatives, and anti-acids, respectively. Conclusion: Considering the high prevalence of self-medication (80.2%) revealed in this research, there is a need for more attentive care for consistent education and drug consumption culture promotion. Specific approaches can help the provision of easy access to medical services in universities.

BACKGROUND: Tibial plateau fractures are complex lesions capable of causing severe consequences if not appropriately treated. They are often the result of high-energy trauma and, not rarely, are associated with significant soft-tissue and intra-articular injuries. Different therapeutic options can be managed in the treatment of these lesions. Minimally invasive surgery percutaneous technique-offers several advantages compared to other surgical techniques and allows, with less additional soft tissue damages, good reduction and stable fixation of the fracture. CASE PRESENTATION: In this study, we assessed the results of the combined arthroscopic and radioscopic assisted reduction and internal fixation of tibial plateau fractures in 7 patients with Schatzker type II and III. CONCLUSION: According to Hohl’s and Rasmussen’s grading system, all of the patients scored excellent and good results at 1 year follow up. We experienced no complications due to arthroscopy.

BACKGROUND: Treatment of acute and chronic acromioclavicular joint dislocations is still controversial. We aimed evaluation of surgical outcomes after using the combined technique with a hook plate and transposition of the coracoacromial ligament in the treatment of acromioclavicular dislocation. CASE PRESENTATION: During two years 4 patients (2 acute and 2 chronic cases) were operated with this technique. Three male and one female with an average 37 (26-43) years old were: three on the right and one of the left side. Rockwood classification was used. The evaluation was done according to Constant score - preoperatively, 3 months after the operation and 3 months after the titanium plate was removed. CONCLUSION: Evaluation of the effectiveness using this combined technique show excellent result in all four patients. No surgical site infection and the favourable cosmetic result were present.

Molar pregnancy is a gestational trophoblastic disease that belongs to the category of precancerous lesions. On the other end of the spectrum are gestational trophoblastic neoplasms such as invasive mole, choriocarcinoma, placental site trophoblastic tumor and epithelioid trophoblastic tumor, which are considered malignant tumors. Based on defined histopathological criteria, molar pregnancy is divided into partial and complete hydatidiform mole. Especially in the case of early complete mole, the diagnosis can be quite challenging and often necessitates additional molecular or immunohistochemical methods. The aim of this study was to assess the importance of additional molecular and immunohistochemical methods to accurately diagnose complete hydatidiform mole and to stress the importance of correct diagnosis and close follow-up of these patients. A total of 367 consecutive cases of spontaneous abortion were analyzed in a 3-year period. Eight cases with histopathological diagnosis of complete molar pregnancy were selected for further analysis. Apart from standard microscopic analysis, additional molecular and immunohistochemical analyses were performed in all eight cases. Most of the histopathological characteristics of complete molar pregnancy were present in all cases, together with complete absence of positivity for the p57 immunohistochemical marker in the cytotrophoblasts and villous stromal cells. The molecular analysis revealed androgenetic diploidy in seven cases and biparental diploidy in one case with more than three consecutive complete molar pregnancies. Additional immunohistochemical and molecular methods can considerably aid in the correct diagnosis of molar pregnancy.

Background and Objectives: Obesity has been increasing around the world and this phenomenon is creating many physical and psychological problems. Hence, this study considered the effectiveness of Buckroyd’s group-based therapeutic approach on increasing self-esteem and improving eating attitude of obese 20- to 30-year-old females in Esfahan. Materials and Methods: This study was semi-experimental, statistical society of which involved all obese females referred to Sepahan Salamat Clinic in Esfahan, during year 2014. Overall, 30 over-weight females, who had a Body Mass Index (BMI) between 25 and 35, a minimum education of diploma, and age of 20 to 30 years old were selected purposefully and divided randomly to two equal groups. Buckroyd’s therapy was performed in sixteen sessions and each session lasted two hours twice per week. Research measurements included body mass index, demographic form, self-esteem and eating attitude questionnaires. Variance analysis and frequency measurement were performed with the SPSS-20 software and were used for confirming the hypothesis. Results: Results showed that Buckroyd’s group therapy increased self-esteem (P 0.05). Conclusions: The findings showed that Buckroyd’s therapy approach can be used for increasing self-esteem but cannot be used for improving eating attitude of obese females.

We investigated human leukocyte antigen (HLA) profiles for Tunisians with nasopharyngeal carcinoma (NPC), their families, and a sample of unrelated healthy Tunisians in order to identify HLA specificities associated with familial NPC. HLA-A, -B, and -DRB1 typing was successful for 36 NPC patients, 72 unaffected family members, and 130 community controls, and the chi square or Fisher exact test was used to compare allele frequencies between cases and controls. We observed a consistent protective effect of HLA-DRB1*10 on NPC development. However, none of the NPC patients or their family members had a positive result for this HLA marker (0% vs 9.2% in controls, P = 0.047). In addition, HLA-A*26 was probably an induction marker, as its allelic frequency was significantly higher among NPC patients than among controls (P = 0.003) and among NPC patients than among at-risk family members (P = 0.067). Logistic regression analysis of the joint effect of selected HLA specificities showed that HLA-A*26 and HLA-A*30 were co-associated and have an important effect on NPC risk. Despite the small size of our cohort, we showed that HLA-A*26-A*30 and HLA-DRB1*10 might be predictive markers for NPC screening of Tunisian families with a high risk of NPC.

Background One of the most important epidemiologic indices for the assessment and measurement of dental caries is the Decayed, Missing, and Filled Teeth (DMFT) index which is used as an important criterion for the evaluation of the oral and dental health status of individuals. Therefore, the present study was conducted to determine DMFT6 (DMFT of the first permanent molar) index and the related factors with the caries free status in students of 12 years of age in Larestan, Iran, in 2014.Materials And Methods The present cross-sectional survey was conducted on 2436 students. Data were collected using the National Oral Health Promotion Plan Checklist. If the features of decayed, missing, and filled were observed in any of the first permanent molars, they received a score of 1. Data were analyzed using chi-square test, chi-squared test for trend, independent two-sample t-test, and multiple logistic regression model.Results The mean and standard deviation of DMFT6 in all students was 1.00 ± 1.36. It was 1.07 ± 1.39 and 0.93 ± 1.33 in girls and boys, respectively, and this difference was statistically significant (P = 0.0080). In addition, more than half of the students (51.5%) were caries free. The variables of gender (P = 0.0007), mothers’ education (P Conclusions It seems that the amount of the DMFT6 index in students of 12 years of age in Larestan was high compared to the World Health Organization (WHO) standards in 2010. Therefore, it is recommended that efficient plans be made to promote the oral and ýdental health of students.

Using a variety of molecular techniques, it has been established that loss of pregnancy occurs in one to two thirds of all fertilized embryosin the first trimester. In about 50% of the cases, chromosomal abnormalities are the cause of early spontaneous abortion. Several histological characteristicsof the placenta, such as presence of villous stromal cavitations, fetal erythro-cytes, umbilical cord, fetal tissue,etc. are suggested as predictive factors for aneuploidy.Two hundred and thirty one cases were analyzed in this prospective study, 50 cases were control artificial abortionsand 181 cases were early spontaneous abor-tionsanalyzed in the period from May 2012 to De-cember 2014. Standard histopathological analysis and molecular techniques based on polymerase chain reaction were usedto analyze the samples.Usingmolecular techniques, aneuploidy was detected in 53.1% of the samples. The most frequently detected aneuploidy was trisomy 16, followed by trisomy 22, 21, 14 and 18. The molecular analysis also enabled dis-tinctionof maternal and paternal origin of the alleles.In the histopathological sample analysis, binary logis-tic regression analysis indicated the presence of trophob-lasticproliferation (p=0.008) and the absence of fetal red bloodcells (p=0.001) as independent significant fac-tors in the prediction of aneuploidy in early sponta-neous abortion.In conclusion, our results show that clinically relevant andaccurate diagnosis of early spontaneous abortionwhich candetermine its causecan only be achieved bya controlled process of selection of the material,histo-pathological and molecular analysis, followed bya necessary correlation of these results.

Infliximab (IFX) is a chimeric monoclonal antibody which has proven its efficacy in the treatment of inflammatory diseases. However, its efficacy can be limited by the development of anti-IFX antibodies (ATI) resulting in a therapeutic failure of IFX. ATI plasmatic monitoring is then indicated to optimize IFX treatment. The aim of this study was to validate an ELISA (enzyme linked immuno sorbent assay) method of ATI plasmatic monitoring. Methods Assessment of performance was based on the study of correlation and concordance (Bland Altman method) of the absorbances measured by the two readers. ELISA kit validation was made by calculating the accuracy and the exactitude. Results We collected 23 samples. Their mean age was 46 years and sex ratio M/W was 0.92. In nine cases, plasmatic AIT were positive and in 14 cases, they were not detected. Correlation between the two readers showed a correlation coefficient r2 of 99.95%. Concordance limits of the confidence interval 95% were [-112.768%-41.425%] with a bias of -35.671%. Repeatability and reproductibility were checked by a positive control and coefficients of variation were respectively of 5.574% and 14.184%. Limits of detection and quantification were respectively of 0.046 and 0.086. The positive predictive value was 0.5 and the negative predictive value was 1. The sensitivity was 100% and the specificity was 83%. Conclusion The assessment of the performance of the tested microplate reader and the validation of the tested ELISA kit showed good results allowing ATI routine measurement to optimize therapeutic management of patients treated by IFX.

Background Fc gamma receptors (FcgR) type IIA IIIA and IIIB play an important role in the recognition of immune complexes (ICs) by binding their Ig-Fc portion. However, it has been demonstrated that FcgR single nucleotide polymorphisms (SNP) leads to low binding affinity alleles (FcgRIIA-131R, IIIA-158V and IIIB NA2). Therefore, we can make an assumption that the presence of these risk alleles could influence the outcome of immune mediated disease such as rheumatoid arthritis (RA). Objectives The aim of this study was to assess the relationship between functional SNP of FcgR IIA H13R, IIIA V158F and IIIB NA1/NA2 and disease severity scores in RA. Methods We assessed disease severity in RA patients based on the Health Assessment Questionnaire (HAQ) and Sharp/van der Heijde (mSharp) method. To reduce selection biais, all recruited patients were treated with conventional DMARDs.We considered patients with HAQ score ranged from 2 to 3 as having severe disability. For radiographic evaluation, since there is not validated threshold for joint damage severity, we took mSharp score median value of our population as a reference. Patients underwent FcgRIIA, FcgRIIIA and FcgRIIIB SNP study using PCR-SSP and direct sequencing process. Then, biallelic polymorphisms were examined for association with HAQ and mSharp score. Results Fifty-eight RA patients were enrolled. The mean duration of the disease was 11.77 years [0.5-24]. Among these patients, 34 (58.62%) had severe disability according to HAQ score. The mSharp median value was 43,5 [0-232] and 28 (48.28%) patients had a score above this value. Genotypic study showed that FcgR IIIB-NA2 was significantly associated with severe disability (p=0.021) (Table 1). Furthermore, FcgRIIIA-158F and IIA-131R carriers were more frequent in patients with severe disability but the association was not statistically significant. Finally, no correlation was found between radiographic evaluation and FcgR SNP study (table 2). Conclusion FcgR low affinity alleles seem to confer susceptibility to severe functional impairment in RA but not to structural damage. However further studies on larger population must be done to corroborate these findings. References [1] Brun JG, Madland TM, Vedeler CA. Immunoglobulin G Fc-receptor (FcgammaR) IIA, IIIA, and IIIB polymorphisms related to disease severity in rheumatoid arthritis. J Rheumatol. 2002;29:1135–40. [2] Kastbom A, Ahmadi A, Soderkvist P, Skogh T. The 158V polymorphism of Fc gamma receptor type IIIA in early rheumatoid arthritis: increased susceptibility and severity in male patients (the Swedish TIRA project) Rheumatology (Oxford)2005;44:1294–8. [3] Lee YH, Bae SC, Song GG. FCGR2A, FCGR3A, FCGR3B polymorphisms and susceptibility to rheumatoid arthritis: a meta-analysis.Clin Exp Rheumatol. 2015 Sep-Oct; 33 (5):647-54. Disclosure of Interests None declared

Background Rheumatoid arthritis (RA)’s prognosis drastically improved with the introduction of TNF-blockers. However, reasons behind therapeutic failure in some patients remain unclear. Several factors might influence pharmacokinetics of these drugs by reducing their half-life and, consequently, their effectiveness. Considering Fc-containing biologics like infliximab (IFX) and adalimumab (ADL), Fc gamma receptors (FcgRs) polymorphism would be an interesting genetic candidate to focus on. Objectives The aim of our study was to determine the influence of low affinity allele FcgRIIA-131R on ADL and IFX bioavailability. Methods We enrolled RA patients treated with IFX and ADL for over six months. Blood samples were collected for each patient immediately prior to drug administration. Quantitative measurements of the residual drug concentration (DC) was carried out by a commercial enzyme-linked immunosorbent assay (ELISA) kit (Promonitor®). Then, we identified patients with DC above therapeutic cut-off (DC+) for each biologic. EULAR criteria were considered to determine treatment outcome. FcgRIIA H131R polymorphism was genotyped using PCR-SSP. Results Twenty-nine patients were included (13 treated with ADL and 16 with IFX). We identified 31.3% and 23.1% non-responders among patients treated with IFX and ADL respectively. Patients with DC+ were more frequent in ADL group (76.9%) than IFX group (43.75%). For IFX, DC+ was significantly correlated with the presence of FcgRIIA 131-R (p=0.033). In fact, none of the HH-genotyped patients had DC+. Furthermore, an association between FcgRIIA 131-R allele and poor response to IFX was noted (p=0.059) while all HH-genotyped patients responded to IFX. For ADL, no correlation was found with both of residual DC and response to treatment. Conclusion The presence of FcgIIA-131 R allele might be a predictive factor of non-responsiveness to TNF-blockers. It also appears to be associated to a higher residual DC. That might be explained by a reduced biologic clearance due to a lower binding affinity to Fc portion compared to wild allele FcgRIIA-131H. Therefore, FcgR polymorphism assessment in RA patients would be a decision-making parameter to consider, as part of the personalized medicine approach. References [1] Montes A, Perez-Pampin E, Narvaez J, et al. Association of FCGR2A with the response to infliximab treatment of patients with rheumatoid arthritis. Pharmacogenet Genomics. 2014;24(5):238-245 [2] DavilaaFajardo CL, van der Straaten T, Baak-Pablo R, et al. FcGR genetic polymorphisms and the response to adalimumab in patients with rheumatoid arthritis. Pharmacogenomics. 2015;16(4):373-381 [3] Canete JD, Suarez B, Hernandez MV, et al. Influence of variants of Fc gamma receptors IIA and IIIA on the American College of Rheumatology and European League Against Rheumatism responses to anti-tumour necrosis factor alpha therapy in rheumatoid arthritis. Ann Rheum Dis. 2009;68(10):1547-1552. Disclosure of Interests None declared

Background Even though biologics have been used for several years in treatment of rheumatoid arthritis (RA), little is known about factors that modify their pharmacokinetics and therefore their efficacy. Polymorphisms (SNPs) in receptors for constant region Fc of IgG (FcgR) might influence the therapeutic outcome of molecules that incorporate an Fc fragment in their structure such as etanercept (ETA), adalimumab (ADL) infliximab (IFX) and rituximab (RTX). Objectives The aim of our study was to determine whether the presence of low affinity allele of FcgR (FcgRIIA-131R, FcgRIIIA-158F and FcgRIIIB-NA2) influences efficiency and immunogenicity of ETA, ADL, IFX and RTX in RA Tunisian patients. Methods We included RA patients treated with biologics for at least six months. Response to treatment was assessed according to EULAR criteria. Quantitative measurement of antidrug antibodies (ADAb) for each biologic agent was carried out by a commercial enzyme-linked immunosorbent assay (ELISA) kit (Promonitor®). To do so, blood samples were collected for each patient right before drug administration. FcgRIIA, FcgRIIIA and FcgRIIIB SNPs was genotyped for all patients using PCR-SSP and direct sequencing process. Results Seventy-nine RA patients treated with biologics were enrolled (18 with ETA,13 with ADL,16 with IFX and 32 with RTX). Regardless of biologic type, 61 patients (77.2%) responded to treatment and 14 patients (17.7%) developed ADAb. Genotypic study revealed a correlation between poor response to treatment and the presence of at least one FcgRIIA 131-R allele (94.7% for RH/RR genotypes versus 5.3% for H/H genotype). But, the difference was not statistically significant (p=0.25). Besides, this mutant allele was significantly associated to the presence of ADAb (71.4% of ADAb positivity for RH/RR genotypes versus 28.6% for H/H genotype: p=0.041). The haplotypic study shows that the risk allele combination of FcgR IIA-131R/IIIA-158F/IIIB-NA2 was more frequent in ADAb+ (27%) compared to ADAb- subjects (23%) and in non-responders (27%) versus good responders (23%). But, neither of these associations was statically significant. Conclusion Our study suggests that RA patients FcgRIIA-131R allele carriers are more susceptible to develop ADAb than those with HH wild genotype. That could be explained by a higher biologic clearance in H-carrier patients, resulting in a decreased half-life and ultimately a lower risk of ADAb formation. Thus, FcgR polymorphism genotyping may be a useful marker for predicting response to Fc-containing biologics in Tunisian RA patients. Further studies need to be done on larger population. References [1] Romero-Cara P, Torres-Moreno D, Pedregosa J, Vilchez JA, Garcia-Simon MS, Ruiz-Merino G, Moran-Sanchez S, Conesa-Zamora P. A FCGR3A Polymorphism Predicts Anti-drug Antibodies in Chronic Inflammatory Bowel Disease Patients Treated With Anti-TNF. Int J Med Sci2018; 15(1):10-15 [2] Lee YH, Bae SC. Associations between PTPRC rs10919563 A/G and FCGR2A R131H polymorphisms and responsiveness to TNF blockers in rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2016Jun;36(6):837-44. [3] Lee YH, Bae SC, Song GG,Functional FCGR3A 158 V/F and IL-6 -174 C/G polymorphisms predict response to biologic therapy in patients with rheumatoid arthritis: a meta-analysis. Rheumatol Int. 2014Oct;34(10):1409-15. Disclosure of Interests None declared

Despite the current availability of more potent drugs, hepatitis C virus (HCV) infection is still treated with a combination of IFN-α and ribavirin in many countries. Interferon/ribavirin ...

The effect of bariatric surgery on non-alcoholic fatty liver disease is still controversial. In most cases, bariatric surgery results in hepatic improvement, but sometimes it can lead to impairment. We systematically reviewed the English literature for reports of stunting or deterioration of hepatic histology following bariatric surgeries through sequential liver biopsies to show the possibility of this negative occurrence by gathering all the reports regarding this event until March 2018. Underlying mechanisms, patient characteristics, possible risk factors, preventative strategies, presenting signs and symptoms, and available management options are discussed. This paper concludes that although rare, hepatic decompensation following bariatric surgeries can occur. Therefore, bariatric surgeons should be aware of the ways to prevent, monitor, and manage hepatic impacts.

Background : Several automated systems had been developed in order to reduce inter-observer variability in indirect immunofluorescence (IIF) interpretation. We aimed to evaluate the performance of a processing system in antinuclear antibodies (ANA) screening on HEp-2 cells. Patients and Methods : This study included 64 ANA-positive sera and 107 ANA-negative sera that underwent IIF on two commercial kits of HEp-2 cells (BioSystems® and Euroimmun®). IIF results were compared with a novel automated interpretation system, the “ Cyclopus CADImmuno®” (CAD). Results : All ANA-positive sera images were recognized as positive by CAD (sensitivity = 100%), while 17 (15.9%) of the ANA-negative sera images were interpreted as positive (specificity = 84.1%), κ=0.799 (SD=0.045). Comparison of IIF pattern determination between human and CAD system revealed on HEp-2 (BioSystems®), a complete concordance in 6 (9.37%) sera, a partial concordance (sharing of at least 1 pattern) in 42 (65.6%) cases and in 16 (25%) sera the pattern interpretation was discordant. Similarly, on HEp-2 (Euroimmun®) the concordance in pattern interpretation was total in 5 (7.8%) sera, partial in 39 (60.9%) and absent in 20 (31.25%). For both tested HEp-2 cells kits agreement was enhanced for the most common patterns, homogenous, fine speckled and coarse speckled. While there was an issue in identification of nucleolar, dots and nuclear membranous patterns by CAD. Conclusion : Assessment of ANA by IIF on HEp-2 cells using the automated interpretation system, the “ Cyclopus CADImmuno®” is a reliable method for positive/negative differentiation. Continuous integration of IIF images would improve the pattern identification by the CAD.

We aimed to investigate the prevalence of the JAK2 V617F mutation in Tunisian patients with myeloproliferative neoplasms (MPN) and to look for possible associations with diseases’ presentation. In this context, JAK2 V617F polymorphism was detected by PCR-RFLP and direct sequencing in 213 MPN patients (109 with polycythemia vera (PV), 93 with essential thrombocythemia (ET) and 11 with primary myelofibrosis (PMF)), 77 unclassified patients with thrombosis (UPT) and 95 healthy control subjects. The JAK2 V617F mutant allele was present by either PCR-RFLP or direct sequencing in 158 (74.17%) MPN patients while all UPT and controls were negative. Besides, the JAK2 V617F mutation was significantly more frequent in patients with PV 98 (89.9%) than in ET 54 (58.1%) and PMF 6 (54.5%) groups, p

Background : The Tuberculin skin test (TST) has been used for years in the latent tuberculosis infection (LTBI) diagnosis, but it has, well-documented, low sensitivity and specificity. Interferon-γ release assays (IGRA) has been reported to be more sensitive and specific than TST. Therefore, this study aimed to evaluate the performance of a commercial IGRA, QuantiFERON ® -TB Gold In-Tube (QFT-GIT), comparatively to TST in LTBI diagnosis. Patients and Methods : This study included 238 patients who were candidate for an anti-TNF therapy. The screening for LTBI was performed by both TST and QFT-GIT test for all patients. In order to evaluate the strength of associations, the odds ratios (OR) together with 95% confidence intervals (CI) were calculated. The correlation between QFT-GIT and TST was evaluated using κ statistics. Results : Sixty-three (26.4%) sera were positive for QFT-GIT with a mean level of IFN-γ of about 1.18 IU/ml, while 81 (34%) patients were positive for TST. Agreement between QFT-GIT and TST was poor (37 QFT-GIT+/TST- and 55 QFT-GIT-/TST+), κ=0.09 (SD=0.065). The positivity of QFT-GIT was not influenced by BCG vaccination or by immunosuppression. Nevertheless, it was significantly associated to both history of an earlier tuberculosis disease (HETD) and its radiological sequel (RS), p =6E-7 and p =1E-8, respectively. Inversely, the TST results were not correlated to either HETD or RS, but the TST positivity was less frequent in immunosuppressed patients (45.5% vs. 73.9%), p =1E-5, OR (95% CI) = 0.29 [0.17-0.52]. Moreover, the extent of both the immunosuppression period and the time elapsed from the last BCG injection was significantly correlated to a lesser TST positivity, p =3E-12 and p =5E-7, respectively. Among the QFT-GIT-/TST+ patients (n=55) whom received an anti-TNF agent without any prophylactic treatment of LTBI, no tuberculosis was detected with a median follow-up of 78 weeks [56-109]. Conclusion : Our study suggests that the QFT-GIT has a higher performance comparatively to TST in the LTBI screening that is unaffected by either BCG vaccination or immunosuppression. Therefore, IGRAs has to replace TST especially in patients who are under consideration for an anti-TNF therapy.

BackgroundPrimary membranous nephritis (PMN) is an autoimmune disease induced by the deposit of antibodies (Ab) to the phospholipase receptor A2 receptor (PLA2R) on podocytes. In this context, we aimed to assess the relationships between anti-PLA2R Ab, PLA2R rs4664308 SNP, PLA2R mRNA levels and PMN susceptibility and outcome.MethodsSixty-eight PMN patients, 30 systemic lupus erythematosus (SLE) patients with secondary MN and 30 healthy control subjects served for anti-PLA2R Ab measurement by ELISA and PLA2R rs4664308 SNP genotyping by a commercial real-time PCR. Twenty patients with tubulo-interstitial nephritis (TIN) were used as controls for renal PLA2R mRNA quantification in PMN patients from kidney biopsies. PLA2R mRNA quantification was carried-out by real-time PCR after RNA extraction.ResultsForty-three (63.2%) PMN patients received initial therapy consisting of alternating monthly cycles of corticosteroids and cyclophosphamide. Twelve (17.6%) patients had resistant PMN to initial therapy and were consecutively treated by cyclosporine or tacrolimus. Anti-PLA2R Ab were positive in 54 (79.4%) PMN patients, while all SLE patients and controls were negative, pConclusionAnti-PLA2R Ab and renal PLA2R mRNA could be useful markers for PMN outcome predicting. The PLA2R rs6446308 SNP is associated with PMN susceptibility in Tunisians.

Background:Fc gamma receptors (FcγRs) play a major role in the regulation of humoral immune responses. Single-nucleotide polymorphisms (SNPs) of FCGR2A and FCGR3A and FCGR3B can impact the expression level, IgG affinity and function of the CD32 and CD16 FcγRs in response to their engagement by the Fc fragment of IgG. It was described in patient treated for rheumatoid arthritis (RA), that such a polymorphism may influence patients response to TNF-blockers.Objectives:In this study, we aimed to investigate whether the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms can be involved in the genesis of anti-drug-antibody ADAb to anti-TNF therapy in RA patients under etanercept (ETA), adalimumab (ADL) and infliximab (INF).Methods:We included 47 patients treated for RA under TNF-blockers. To assess the association between the FCGR2A H131R (rs1801274), FCGR3A F158V (rs396991), and FCGR3B NA1/NA2 polymorphisms and immunogenicity of TNF-blockers, we used allele contrast, the recessive model, the dominant model, and the homozygote contrast. Quantitative measurements of the ADAbs was carried out by a commercial enzyme-linked immunosorbent assay (ELISA) kit (Promonitor)®after 6 months of treatment.Results:We involved 18 patients treated with ETA, 13 patients with ADL and 16 under INF. None of the patients under ETA has developed ADAb and respectively 1 and 7 patients developed immunogenicity with ADL and INF. We excluded patients under ETA from statistical study since they didn’t develop ADAb.A significant association was revealed between FCGR2A H131R polymorphism and immunogenicity of INF and ADL (table 1).Table 1.Association between FCGR2A polymorphism and immunogenicity to INF and ADLFCGR2A association with ADAb (n=29, crude analysis)GenotypeADAb=0ADAb=1OR (95% CI)P-valueH/H1 (4.8%)3 (37.5%)1.000.031H/R-R/R20 (95.2%)5 (62.5%)0.08 (0.01-0.98)There weren’t significant associations between ADAb’s development and FCGR3A F158V and FCGR3B NA1/NA2 polymorphism.Conclusion:FCGR2A R allele carriers show less susceptibility to develop ADAb to ADL and INF with follow-up times of 6 months. Our results provide an explanation for controversies in the relationships between FCGR2A H131R polymorphism and TNF-blockers response. Further studies with larger population of RA patients should be undertaken to confirm this hypothesis.References:NoneDisclosure of Interests:None declared

Purpose To assess which visual function measures are most strongly associated with overall retinal drusen volume in age-related macular degeneration (AMD). Methods A total of 100 eyes (16 eyes with early AMD, 62 eyes with intermediate AMD, and 22 eyes from healthy controls) were recruited in this cross-sectional study. All subjects underwent several functional assessments: best-corrected visual acuity (BCVA), low-luminance visual acuity (LLVA), visual acuity (VA) measured with the Moorfields Acuity Chart (MAC-VA), contrast sensitivity with the Pelli–Robson test, reading speed using the International Reading Speed texts, and mesopic and dark-adapted microperimetry. Drusen volume was automatically determined based on optical coherence tomography using an approach based on convolutional neural networks. The relationship between drusen volume and visual function was assessed with linear regressions controlling for confounders. Results Mean drusen volume and MAC-VA differed significantly among all AMD stages and controls (P < 0.001). In univariate linear regression, LLVA, MAC-VA, contrast sensitivity, and mesopic and dark-adapted microperimetry were significantly negatively associated with the overall drusen volume (all P < 0.006). After controlling for AMD stage, age, and the presence of subretinal drusenoid deposits, MAC-VA and mesopic and dark-adapted microperimetry were still significantly associated with drusen volume (P = 0.008, P = 0.023, and P = 0.022, respectively). Conclusions Our results suggest that MAC-VA, as well as mesopic and dark-adapted microperimetry, might indicate structural changes related to drusen volume in early stages of AMD.

Background: Benign esophageal strictures are complications resulting from various causes. They can be structurally categorized in two groups: simple and complex. Treatment is similar in most cases that require dilatation and means use of three general types of dilators that are currently in use. However, despite the last guidelines on esophageal dilatation, the therapeutic response, optimal timing of treatment and interval between sessions may vary and there is no strong consensus in the literature regarding this fact. Aims: To analyzethe first 4 year experience of Digestive Endoscopy Unit at the University Clinic of Gastroenterohepatology of the Medical Faculty, Skopje, Republic of Macedonia in treating benign esophageal strictures, since the Savary-Gilliard technique of “bougienage” was introduced for the first time in Republic of Macedonia, at our Institution, in December 2013, by assessing etiology, length of stricture, number of dilations required to achieve satisfactory therapeutic response, as well as the relationship between the type, extent of stenosis and therapeutic response. Methods: One hundred and forty five dilations, during a period from 20th December 2013, until March 2017, have been analyzed in 31 patients Results: The caustic strictures were the most prevalent, occurring in 15 (48%) of patients, followed by peptic stenosis presenting 26% of patients. The long and corrosive strictures needed more sessions to the absence of dysphagia. Peptic and short stenoses best respondedon treatment and needed fewer dilatation sessions per patient. Conclusion: Caustic stricture is the most common type of benign esophageal stenosis and the most refractory to treatment, especially the long one. Peptic stenosis is the second cause of benign esophageal strictures and responded well to endoscopic therapy. The higher the extent of stenosis, the greater the number of sessions required. Short strictures have good prognoses in most cases. The number of dilations depended directly on the cause and extent of stenosis. Bouginage using Savary-Gilliard or American type of technique, irrespective of the type and the extent of esophageal stenosis, is safe and purposeful procedure.

Background:: Self - burning is known as an extremely violent means of suicide. Objectives:: This study aimed to investigate the epidemiology of self - burning in Iranian townships covered by Shiraz University of Medical Sciences during years 2009 to 2012. Patients and Methods: This cross - sectional research was performed on 250 self - burning cases and 181 self - burning attempts. Data was collected from the Comprehensive Suicide Prevention Program Checklist. To analyze the data, the chi - square test and logistic regression model were utilized. Results: Most self - burning cases were observed in females (70.4%), married individuals (60.4%), an age group of 15 to 24 years (38%), and rural residents (60.8%). Moreover, the highest and lowest self - burning cases had occurred during spring (31.2%) and fall (17.6%) (P = 0.736). Conclusions: The findings are indicative of a high occurrence of self - burning among young married females. Therefore, it is vital to provide this at risk group with the necessary prevention programs.