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mRNA vaccines are a novelty in the medical world. The researchers created these vaccines in a short time, which led to many question marks. In this article, we have analyzed the perception of the world's countries on these vaccines.

Background It has been established that the level of some inflammatory cytokines increases in celiac disease (CD) and non-celiac gluten sensitivity (NCGS) in comparison with healthy subjects. Therefore, the primary interest in our research was proposing an accurate tool to diagnose patients with CD and NCGS from healthy individuals in an Iranian population. Methods The serum samples were examined in 171 participants, including 110 CD patients, 46 healthy individuals, and 15 NCGS. The commercial ELISA kits were used to detect the level of the following cytokines: IL-1, IL-6, IL-8, IL-15, and IFN-γ. The receiver operating characteristic (ROC) curve analysis was applied to determine the optimal thresholds for high sensitivity, specificity, positive and negative predictive values of cytokines, as the indicators of CD, NCGS, and healthy control groups. Results In NCGS group, the values of area under the ROC curve for IL-1, IL-8, and IFN-γ were 71%, 78%, and 70%, respectively. To differentiate the CD and NCGS groups from the control group, IL-15 had the highest sensitivity (82.70%), specificity (56.50%), positive predictive value (81.98%), and negative predictive value (57.78%), followed by IL-8 with the highest sensitivity of 74.50%, specificity of 73.30%, and positive and negative predictive values of 95.35% and 30.21%, respectively. Conclusion The obtained results demonstrate that IL-15 and IL-8 could be proposed as potential markers in their optimal cut-off points for distinguishing CD from the NCGS and the healthy control. Based on our findings, the evaluation of cytokine levels can be recommended as a useful tool for the diagnosis of CD and NCGS in a clinical practice.

The pathology of Dravet syndrome is of particular importance in children. In this article we analyze the involvement of the SCN1A gene in Dravet syndrome, we approach the new treatment strategies in Dravet syndrome.

Patients with Kawasaki disease (KD) may develop cardiovascular complications in the presence of predictive factors, including young age6 months, male gender, unfavorable response to intravenous immunoglobulin (IVIG), low albuminemia, thrombocytosis, fever over 8 days, increased C-reactive protein (CRP), elevated levels of 25 OH vitamin D3, elevated levels of fibroblast growth factor 23 (FGF23), elevated D-dimers, elevated ferritin. The objectives of this study were to determine the laboratory negative predictive factors for the occurrence of cardiac complications in children with KD. Studies in the literature that dealt with these predictive factors were analyzed.We followed the studies published in PubMed over a 10-year period. Seventy articles were reviewed and, after applying the inclusion and exclusion criteria, 20 articles were selected.We evaluated the population studies which showed factors can predict the occurrence of heart complications. These factors were different depending on age and depending on resistance to IVIG treatment.Some biological parameters such as low albumin, thrombocytosis, increased CRP, elevated levels of 25 OH vitamin D3, elevated levels of FGF23, elevated D-dimers, and elevated ferritin could be considered as laboratory negative predictive factors for CAL.

Food allergy (FA) is a condition with a growing incidence and is a constant concern for the medical world and healthcare providers. With potential symptoms including anaphylaxis, in the event of an allergic reaction the patient’s life may well be endangered. The diagnosis of FA is a continuous challenge because mild cases tend to be ignored or diagnosed late and young children with allergies are cared for by parents, who are not always able to accurately interpret symptoms. It is very important to be able to differentiate FAs from food intolerance and toxic reactions to food. An accurate diagnosis is required to provide personalized management of an FA. More sophisticated and accurate diagnostic tests, including component diagnosis and epitope reactivity, allow the provision of a directed diagnosis, a more accurate therapeutic approach, and a useful prognostic evaluation. Tests used in current practice include the specific search for serum IgE, elimination diets, oral food challenges, single, blind, and double-blind (DBPCFC) tests, as well as skin tests. The risk of anaphylaxis can be assessed by molecular diagnostics/component-resolved diagnosis (CRD) and by conducting a basophilic activation test (BAT). These tests allow a planned, personalized treatment based on molecular and clinical profiles. CRD can determine the individual profile of allergic molecular reactivity and enable the formulation of a prognostic judgment. Our article highlights the importance of knowing the immune mechanisms, diagnostics, and immunotherapies in FAs. Starting from observing exposure to food allergens, to identifying allergic reactions, analysing the severity of clinical manifestations, noting the possibilities of diagnosis, and illustrating adequate management strategies.

Background This study aimed to investigate the implications of antinuclear antibodies (ANAs) in juvenile idiopathic arthritis (JIA), the association with uveitis and the favorable evolution of the disease. Methods We followed 45 pediatric patients suffering from JIA, according to the International League of Associations for Rheumatology (ILAR), for a period of 2 years. ANAs were followed through immunofluorescence methods using a high-performance immunofluorescence automatic Helios device. Results A total of 15 of the ANA-positive patients presented an oligoarticular form of the disease, eight of them presented a polyarticular form of the disease and two of them presented a systemic form. The most severe forms have associated iridocyclitis. ANA-positive patients presented an earlier onset of disease in comparison with ANA-negative ones. ANA-positive patients from different ILAR categories had similar characteristics of the disease such as onset age (earlier), higher prevalence in females and the presence of asymmetric arthritis or iridocyclitis. Conclusions ANA may be an important marker for JIA and association with iridocyclitis. Following ANA titer in evolution might be a criterion for assessing the evolution of the disease. The association between positive ANA, oligoarticular JIA, iridocyclitis and a 2- to 4-year-old onset is common.

Background: Colorectal cancer (CRC) represents a major public health problem owing to the fact that many patients are diagnosed in locally advanced or metastatic stage when chemotherapy is the only remaining option. However, treatment response is still unpredictable and depends upon a diversity of factors such as tumor inherited or acquired drug resistance and the host immune response to the malignant cells. The aim of this study was to evaluate the serum levels of interleukin 6, 8, 10 (IL-6, 8, 10) as possible predictive factors for response to chemotherapy and the correlation between the cytokines and the psychological distress.Methods: Forty-nine patients undergoing chemotherapy for locally advanced or metastatic CRC were included, for each patient IL-6, 8 and 10 were assessed through ELISA. Depression and anxiety were quantified through questionnaires. Statistical data were performed with GraphPad.Results: Patients with CRC had high serum levels of IL-8 and IL-6 compared to the healthy control group. High levels of IL-8 before treatment were correlated with progressive disease. There was a high incidence of psychological complication in CRC patients, especially in young male patients, from an urban area, with a positive correlation between serum levels of IL-8 and depression.Conclusions: These results indicate that high serum levels of IL-8 are predictive factors in CRC patients that undergo chemotherapy, but also could be useful in identifying psychological distress associated with this pathology.

Colorectal cancer is an important global health burden marked by a high mortality rate. Medical attention is drawn more often by the new targeted therapies, but also by the concept of liquid biopsy. Tumor's genetic profile is the major indicator of the response to targeted therapies and the risk for metastatic relapse. Therefore, analysis of tumor-linked genetic alterations holds a great importance, both for diagnostic and prognostic purposes. Areas covered: The present paper highlights the molecular basis of the liquid biopsy concept and its major clinical applications in colorectal cancer. This consists in circulating tumor cells (CTC) and cell-free tumor DNA (cfDNA) and is described in manuscripts as an alternative to tissue samples, providing more information about tumor heterogeneity and tumor evolution in dynamic. Expert opinion: Liquid biopsy is an innovative, minimally invasive method which enables real-time monitoring of tumor's genetic heterogeneity, being an important step towards personalized medicine. However, despite the large number of detection methods available, it is necessary to standardize them regarding the blood collection processing and sample storage, analysis in order to be implemented in clinical guidelines.

The following was emphasised in an informative, educational issued on the American College of Rheumatology website in April 2017: "About one child in every 1000 develops some type of chronic arthritis. These disorders can affect children at any age, although rarely in the first six months of life. It is estimated that around 300,000 children in the United States have been diagnosed with the condition". Therefore, knowledge of immunological investigations in patients with juvenile idiopathic arthritis is important for finding new treatment pathways. Our aim was to assess the immunological investigations and immune system implications in juvenile idiopathic arthritis. We will discuss: a) the specifically targeted proteins - the citrullinated peptide antibodies; b) non-specifically targeted proteins - heat-shock proteins (anti-HSP60, -65, and -70 antibodies), CLEC16A, inflammasomes, and phagocyte-derived S100; c) interleukins - IL-1, IL-6, IL-10, IL-17, and IL-18; d) innate immunity - macrophage activation syndrome, natural killer cells, complement activity, and immune complexes; and e) therapeutic targets - monoclonal antibodies, JAK inhibitors, and intravenous immune globulin.

BACKGROUND Our study was undertaken to detect the prevalence of serum specific antibodies to TORCH agents in children by establishing the presence of the specific IgM antibodies with DiaSorin "Flash" chemiluminescence technology. MATERIALS AND METHODS A total of 804 blood samples were collected for the detection of the Toxoplasma IgM; 2,048 cases were collected for CMV IgM, and 337 cases were collected for HSV-1/2 IgM, over a period of 9 months (from January 2019 to September 2019). RESULTS In our cohort, a total of 103 samples (12.8%) were found to be seropositive for Toxoplasma, 1,551 samples (75.7%) were positive for CMV and 174 samples (51.6%) were positive for the HSV-1/2 infections. The perinatal CMV infection was observed in 11.9% of the patients with positive serology for CMV. CONCLUSIONS The routine antenatal screening with chemiluminescence technology should be recommended in general population to avoid congenital malformations, as long as the prevalence of serum specific antibodies to TORCH agents is high and seropositivity rate increases with age.

Even though there are various types of cancer, this pathology as a whole is considered the principal cause of death worldwide. Lung cancer is known as a heterogeneous condition, and it is apparent that genome modification presents a significant role in the occurrence of this disorder. There are conventional procedures that can be utilized against diverse cancer types, such as chemotherapy or radiotherapy, but they are hampered by the numerous side effects. Owing to the many adverse events observed in these therapies, it is imperative to continuously develop new and improved strategies for managing individuals with cancer. Nanomedicine plays an important role in establishing new methods for detecting chromosomal rearrangements and mutations for targeted chemotherapeutics or the local delivery of drugs via different types of nano-particle carriers to the lungs or other organs or areas of interest. Because of the complex signaling pathways involved in developing different types of cancer, the need to discover new methods for prevention and detection is crucial in producing gene delivery materials that exhibit the desired roles. Scientists have confirmed that nanotechnology-based procedures are more effective than conventional chemotherapy or radiotherapy, with minor side effects. Several nanoparticles, nanomaterials, and nanosystems have been studied, including liposomes, dendrimers, polymers, micelles, inorganic nanoparticles, such as gold nanoparticles or carbon nanotubes, and even siRNA delivery systems. The cytotoxicity of such nanosystems is a debatable concern, and nanotechnology-based delivery systems must be improved to increase the bioavailability, biocompatibility, and safety profiles, since these nanosystems boast a remarkable potential in many biomedical applications, including anti-tumor activity or gene therapy. In this review, the nanosystems involved in treating lung cancer and its associated challenges are discussed.

Juvenile idiopathic arthritis (JIA) represents a significant challenge for pediatricians who intend to diagnose and treat this pathology. The classification criteria for JIA subtypes are rigid and often do not fully satisfy the possibilities of classification in the subtype. The objective of this study was to identify clearer criteria for classifying JIA subtypes. The 2019 expert committee meeting (PRINTO) shows the difficulties of this classification and proposes new research directions for the identification of disease subtypes. Four different chronic disorders are used to define JIA in a concise and easy to follow classification system. However, dates from the literature suggest that at least 10% of cases are still difficult to classify. Possibly in the future, different classifications of JIA based on pathophysiological and genetic criteria would be necessary.

In this report, we present the case of a one-year-old female patient with a history of febrile seizures, which was characterized by multiple seizures during hot baths and more than one episode of status epilepticus. Dravet syndrome was suspected due to the clinical context of the seizures and was confirmed by genetic testing. The brain MRI was found to be normal. Throughout the course of disease progression, the patient showed no signs of neurological degradation. The patient was found to have a mutation in the SCN1A gene with a peculiar course, which had not been reported previously. The normal psychomotor development, as seen in this case, highlights the different possibilities related to disease progression in Dravet syndrome.

Background The COVID-19 pandemic has had an impact on global health. Design The impact of the COVID-19 pandemic on patients with coeliac disease was assessed in the present review. Results The incidence of coeliac disease and the problems associated with coeliac disease increased during the COVID-19 pandemic. Adherence to the diet is crucial for the patient's health and quality of life since the only approved therapy for coeliac disease is a gluten withdrawal. Conclusions A gluten-free diet should be promoted by the therapeutic team and implemented among these categories of patients.

This study aimed to analyse vitamin d-binding protein (Gc-globulin) serum levels in acute liver failure (ALF) in children in relation to disease outcomes and correlations with other known markers used to evaluate the severity of ALF. Our study included 34 children (mean age 4.87 &plusmn, 5.30 years) with ALF of different causes (metabolic, 26.47%, autoimmune, 23.53%, toxic, 20.59%, infection, 17.65%, unknown, 11.76%) and 30 children without any liver injury (mean age 6.11 &plusmn, 4.26 years). The outcome was poor in 14 patients (41.18%), including one child with liver transplantation (2.94%). Serum Gc-globulin levels were significantly lower in ALF patients compared to the control group (151.57 &plusmn, 171.8 mg/L vs. 498.63 &plusmn, 252.50 mg/L, p &lt, 0.000001), with an optimum cut-off of 163.5 mg/L (Area Under the Curve, AUC, 0.8921, sensitivity, 76.50%, specificity, 100%). Levels were also lower in patients with poor outcomes compared to survivors (59.34 &plusmn, 33.73 mg/L vs. 216.12 &plusmn, 199.69 mg/L, 0.0001), with an optimum cut-off 115 mg/L (AUC, 0.7642, sensitivity, 100%, specificity, 50%). Gc-globulin serum levels were variable according to ALF aetiology, i.e., lower in metabolic, infectious, or unknown causes compared to autoimmune and toxic causes. Gc-globulin serum levels were decreased in children with ALF and lower in those with poor outcomes compared with survivors. Gc-globulin serum levels were correlated with other known parameters used to evaluate the severity of ALF and could help to identify patients at high risk for poor outcomes.

Colorectal cancer remains a frequent disease to which screening and target therapy exist, but despite this is still marked by a high mortality rate. Even though radical surgery may be performed in many cases, patients relapse with metastatic disease. Circulating tumor cells were incriminated for tumor recurrence, that's why vigorous research started on their field. Owning prognostic and predictive value, it was revealed their usefulness in disease monitoring. Moreover, they may serve as liquid biopsies for genetic tests in cases where tissue biopsy is contraindicated or cannot be performed. In spite of these advantages, they were not included in clinical guidelines, despite CellSearch and many other detection methods were developed to ease the identification of circulating tumor cells. This review highlights the implication of circulating tumor cells in metastasis cascade, intrinsic tumor cells mechanisms and correlations with clinical parameters along with their utility for medical practice and detection techniques.

Guillain-Barré Syndrome (GBS) is currently the most frequent cause of acute flaccid paralysis on a global scale, being an autoimmune disorder wherein demyelination of the peripheral nerves occurs. Its main clinical features are a symmetrical ascending muscle weakness with reduced osteotendinous reflexes and variable sensory involvement. GBS most commonly occurs after an infection, especially viral (including COVID-19), but may also transpire after immunization with certain vaccines or in the development of specific malignancies. Immunoglobulins, plasmapheresis, and glucocorticoids represent the principal treatment modalities, however patients with severe disease progression may require supportive therapy in an intensive care unit. Due to its symptomology, which overlaps with numerous neurological and infectious illnesses, the diagnosis of GBS may often be misattributed to pathologies that are essentially different from this syndrome. Moreover, many of these require specific treatment methods distinct to those recommended for GBS, in lack of which the prognosis of the patient is drastically affected. Such diseases include exposure to toxins either environmental or foodborne, central nervous system infections, metabolic or serum ion alterations, demyelinating pathologies, or even conditions amenable to neurosurgical intervention. This extensive narrative review aims to systematically and comprehensively tackle the most notable and challenging differential diagnoses of GBS, emphasizing on the clinical discrepancies between the diseases, the appropriate paraclinical investigations, and suitable management indications.

Chimeric antigen receptor (CAR) T-cell therapy represents a new genetically engineered method of immunotherapy for cancer. The patient’s T-cells are modified to express a specific receptor that sticks to the tumor antigen. This modified cell is then reintroduced into the patient’s body to fight the resilient cancer cells. After exhibiting positive results in hematological malignancies, this therapy is being proposed for solid tumors like colorectal cancer. The clinical data of CAR T-cell therapy in colorectal cancer is rather scarce. In this review, we summarize the current state of knowledge, challenges, and future perspectives of CAR T-cell therapy in colorectal cancer. A total of 22 articles were included in this review. Eligible studies were selected and reviewed by two researchers from 49 articles found on Pubmed, Web of Science, and clinicaltrials.gov. This therapy, at the moment, provides modest benefits in solid tumors. Not taking into consideration the high manufacturing and retail prices, there are still limitations like increased toxicities, relapses, and unfavorable tumor microenvironment for CAR T-cell therapy in colorectal cancer.

Introduction: The liver is the main location for metastasization in stage IV colorectal cancers. Areas covered: This review intends to comprehensively present the most important studies conducted in the past few years concerning the role of miRNAs in colorectal cancer liver metastases, trying to clarify some aspects regarding tumor biology and favorite liver metastasization site. Expert commentary: Recent advances in tissue and serum RNA extraction has considerably improved the field of microRNAs studies. These molecules known to play a crucial role in the metastatic stage indicate a starting point in the development of clinical biomarkers with a possible role in the stratification of high-risk patients for adequate treatment.

Pancreatic cancer has attracted a great deal of attention owing to the poor outcome, increasing prevalence in the last years and delay diagnosis. Known as a complex disease, it involves genetic mutations, changes in tumour microenvironment and inflammatory component dominated by interleukin-6 and its activated pathways, like Janus Kinase-Signal Transducer and Activator of Translation3, Mitogen Activated Protein Kinase and Androgen receptor. The pro-inflammatory cytokine, plays a central role in oncogenesis, cancer progression, invasiveness, microenvironment changes, treatment resistance, prognosis and associated co morbidities like cachexia and depression. Fulfilling these roles IL-6 requires special attention to understand its complexity in PC development.

Evolution of celiac disease is continuously changing. Celiac disease has become a public health problem in some countries. Knowledge of the disease evolution is important to find current problems of disease. In this article, we wanted to discuss the recent medical and diagnostic discoveries from Romania.

Background and Aims. Two-dimensional (2D) and Doppler echocardiography are the main methods for the non-invasive evaluation of ventricular function in children. Our study monitored the evaluation of systolic and diastolic function in pediatric patients, using classical echocardiographic parameters and pulsed tissue Doppler parameters, as well as the correlation between these. Methods. The study included 18 healthy children and 9 children diagnosed with congestive heart failure secondary to congenital heart malformations. The parameters of systolic and diastolic function were measured by 2D echocardiography, 2D guided M mode, color and pulsed Doppler, as well as by pulsed tissue Doppler at the level of the mitral and tricuspid annulus. Results. A relaxation alteration pattern or a pseudonormal pattern of E diastolic velocity compared to the A wave was found (E = A; E > A) in the group of subjects with heart failure. E wave deceleration time had significantly increased values in the case of patients with CHF, being correlated with diastolic dysfunction. Left ventricular flow propagation velocity Vp was decreased in patients with heart failure, the E/Vp ratio being maintained relatively constant in subjects with congestive heart failure and healthy subjects, most probably on account of the concomitant change in the E wave. Associations between the severity of systolic dysfunction and the diastolic dysfunction were found in pediatric patients diagnosed with congestive heart failure (Student test, p < 0.05). Conclusions. Tissue Doppler measurements proved to be useful for the evaluation of pediatric patients with altered ventricular geometry secondary to congenital heart disease, systolic-diastolic dysfunction and heart failure.

Our immunological system is every day under threat from different bacteria, viruses and disease. One of those many diseases is celiac disease. Once this disease affects the metabolism, it produces an imbalance of the electrolyte in blood. Therefore diagnostic tests are very important.

A new entity was included in the gluten diseases: the non-celiac gluten sensitivity. But the non-celiac gluten sensitivity is not yet clearly defined and its diagnosis is difficult. These lead us to implement a national register for the patients with non-celiac gluten sensitivity.

The prevalence of coeliac disease (CD) in systemic lupus erythematosus (SLE) is unclear since evidence of this co -association is scarce. Furthermore, CD -specific antibodies have been described in patients with SLE without biopsy -confirmed CD. Here we describe the diagnostic challenges of CD in a patient suffering from SLE and secondary antiphospholipid syndrome, with transient positive serum levels of CD -specific antibodies, with an increased genetic risk for CD, demonstrated by HLA-DQ2 positivity. Guidance is still needed for the CD diagnosis in some atypical conditions.

Celiac disease is a disease where both children and adults are affected. It symptoms were previously described in Galen times. Today we recognize its starter, pathological mechanism, and also its atypical behaviour. There is only one causal therapeutic model in terms of compliance with the principles of lifelong strict gluten-free diet. It is an under-diagnosed disease. Further steps should be associated with the improvement of diagnosis and detection of all global forms of disease followed by proper care for patients, including prevention. The second part of the task is to support basic and applicable research with outcomes for further practice and therapeutic outcomes. It is an interdisciplinary issue with lack of its own publishing space. Given these facts, collaboration with the broader but highly professional Editorial Board found a new journal was: International Journal of Celiac Disease, which aims to address the issue at a high professional level, so the results could be applied in practice and science as well.

Diagnosis of adult celiac disease is often a problematic part of clinical medicine. High risk groups for adult celiac disease deserve an intense search, even if atypical extra-intestinal symptoms suggest some other underlying cause. In part, diagnosis may occur over a long time period during adult years, and even then, could potentially remain undiagnosed until very late, even in very elderly stages of life. The objective of this work was to record our clinical experience with the diagnosis of adult forms of the celiac disease, in spite of their atypical presentations with extra-intestinal symptoms alone, and consider the role of serological testing for case-finding in these patients. We chose 9 adult patients with celiac disease diagnosed over a long period during an outpatient medical care by various physician specialists. Examination of autoantibodies for tissue transglutaminase, antiendomysium antibodies and autoantibodies against gliadin as well as cow's milk were done. To confirm positive autoantibodies as an indicator of adult celiac disease, samples of duodenal mucosa were taken and histopathologically examined.

Celiac disease is a chronic, Th1- type immune-mediated disorder, characterized by small intestinal inflammation and villous atrophy, which leads to malabsorption of nutrients,after the ingestion of gluten or related proteins from rye and barley by genetically susceptible individuals. Exclusion of offending food antigens results in disease remission and reexposure leads to recurrence. Extraintestinal manifestations have been associated with celiac disease in children and adults. Eosinophilic esophagitis is a chronic, Th2- type immune-mediated disorder, isolated to the esophagus, which is most often triggered by exposure to food antigens in children and aeroallergens in adults. During the last decade, the increasing prevalence of celiac disease and eosinophilic esophagitis has been recognized in pediatric and adult populations all over the world. Case series have suggested an association between eosinophilic esophagitis and celiac disease. The prevalence of eosinophilic esophagitis in subjects with celiac disease was about 10-times that of the general population. The aim of this review is to analyse the similarity between these two frequent associated conditions. Coexistent eosinophilic esophagitis should be considered in children with celiac disease who have persistent esophageal symptoms.

Background The detection of sideroblastic anemia in a newborn may suggest developing Pearson syndrome. The prognosis of these patients is severe and death occurs in the first 3 years of life, so it is important to find new ways of diagnosis. Case Presentation: In the case of our patient the diagnosis was supported only at the age of 5 months, highlighting the difficulties of diagnosis at this age. Conclusions The diagnosis of Pearson syndrome with neonatal onset is difficult to sustain or even impossible at that age. This diagnosis can be confirmed and supported during disease progression.

Autoimmune diseases have become a major medical problem of recent years. Celiac disease is an autoimmune disease model. The aim of our study was to follow the changes in the clinical autoimmunity picture of the celiac disease from recent years. The study of autoimmunity in celiac disease has focused on associated diseases with the aforementioned disease: type 1 diabetes mellitus, thyroid autoimmunity disease, Graves’ disease, Hashimoto's disease, systemic lupus erythematosus, systemic sclerosis, spondyloarthritis, hyperprolactinemia, Turner syndrome, Addison's disease, sensory neuronopathies. Immune reactivity to tissue transglutaminase targeted autoantibodies and other autoantigens, including transglutaminase 3, actin, ganglioside, collagen, calreticulin or zonulin which have been reported in the celiac disease. New research directions given by celiac disease autoimmunity, interleukin 1, interleukin 2, protein tyrosine phosphatase non-receptor type 22, CD4+CD25+ T lymphocytes, cytotoxic T-lymphocyte antigen 4, infection with Necator americanus and definitive identification of pathogenic T cell epitopes, seem to provide a solution in celiac disease treatment.

Aims. Pill-induced esophagitis has been recognized in adults, but rarely in children. The aim of this article is to discuss endoscopic features, drugs implicated, prevention and treatment in pill-induced esophagitis in children. Patients and methods. Over a period of 4 years, 26 patients presented at our clinic with drug-induced esophageal ulcerations. All patients were diagnosed by means of endoscopy and treated with proton-pump inhibitors and prokinetics. The mean age of the children was 10.76 years. Results. The ulcers were frequently located at the mid-esophagus. Odynophagea, retrosternal pain and dysphagia were the most common presenting symptoms. All children took pills (non- steroidal anti-inflammatory drugs, antibiotics – Doxycycline and ferrous sulfate) with little water and at bed time. The mean elapse between the drug intake and endoscopy was 4.96 days. The symptoms resolved within a maximum of one week of antireflux therapy. Conclusions. In pediatric cases treated by tablets or capsules, the possibility of medication-induced esophagitis should always be considered. The drug-induced esophagitis should be suspected in all patients presenting with chest pain and dysphagia. Physicians must warn the patients to take the pills and capsules with enough water and in the upright position.

Celiac disease remains one of the most challenging pathologies of the small intestine. It involves multiple pathogenic pathways and there are no disease-changing pharmacological agents available against it yet. The term microbiota refers to the community of microorganisms that inhabit a particular region of the body. Normal gut microbiota has a vital role in maintaining the intestinal homeostasis and promoting health. Celiac disease is associated with microbiota alteration, especially with an increase in the number of Gram-negative bacteria and a decrease in the number of Gram-positive bacteria. There is a strong relationship between intestinal dysbiosis and celiac disease, and recent studies are aimed at determining whether the celiac disease is a risk factor for dysbiosis or dysbiosis is for celiac disease. Therefore, the aim of this review was to assess the latest findings regarding the gut microbiota and its impact on the celiac disease, including therapeutic aspects.

Many recent studies discredit breastfeeding protection against coeliac disease. We will try to answer the question: “Is the evidence of breast feeding protection against coeliac disease real?”

Background New treatments in coeliac disease are being vigorously pursued to either replace or facilitate the difficult-tofollow gluten-free diet. Design The present review intends to summarise the challenges in gluten-free diet adherence during the transitional period, as reflected in the last Prague consensus, published in 2016. Results The honourable panel members recommended that dietary adherence and the consequences of nonadherence represent key components for discussion in the transitional period setting. Conclusions There are numerous difficulties in adhering to gluten withdrawal, but the transition period from adolescence to young adulthood is considered a fragile and high-risk period for intentional and unintentional gluten intake.

CD163, a membrane glycoprotein restricted to monocyte-macrophage cell lineage, is released in the terminal phase of acute inflammation and during chronic inflammation, with anti-inflammatory and antiangiogenic role. The proteolytically detached ectodomain of CD163 is the soluble component sCD163. A few studies were performed regarding circulating sCD163 in human diseases. Only two were accomplished in patients with rheumatoid arthritis (RA). Our concern was (1) to evaluate sCD163 serum concentrations in active RA patients with long-standing evolution, (2) to correlate them with clinical parameters, laboratory markers, disease activity, and (3) to search possible relationships with some cytokines (IL-12, IL-17) and chemokine (CXCL10), involved in RA pathogenesis. First and third topics were not achieved until now, and the second one points out discordant findings and unspecified aspects. It was achieved immunoassay of serum sCD163, IL-12, IL-17, CXCL10 and traditional methods for RA laboratory markers. The mean sCD163 level of 33 patients was significantly higher than in 20 normal controls (p = 0.0001), 59.3 % of them with concentrations above normal cut-off value. sCD163 levels were weakly correlated with CRP and RF but not with ERS and disease activity. IL-12 and CXCL10 serum levels strongly correlated with sCD163 concentrations, while IL-17 positively but insignificantly correlated. In conclusion, serum sCD163 levels are significantly elevated in long-standing RA patients, but sCD163 has no role as a biomarker of disease activity. High correlation of sCD163 with IL-12 and CXCL10 suggests the association of their well-known anti-inflammatory function in long-standing RA patients.

With all the advancements of science, genetic tests are important for the diagnosis of celiac disease but a lack of standardization is evidenced.

Objective: We serologically monitored the evolution of patients with celiac disease under a gluten-free diet, in correlation with the family’s level of education. Methods: Our study was performed in a representative sample of 50 children with celiac disease, in whom we monitored the evolution of immunoglobulin A (IgA) anti-tissue transglutaminase antibodies (TGA) during 2008–2009. Results: In the children of parents with a primary education (38%), the evolution of IgA anti-tissue TGA was intermittent; in the children of parents with a secondary education (44%), the evolution of IgA anti-tissue TGA was decreased but with many intermittences; and in the children of parents with a higher education (18%), the evolution of IgA anti-tissue TGA was decreasing, without intermittences. Conclusions: The role of a gluten-free diet is not completely understood in the families of children with celiac disease, particularly in those with primary education. * IgA : immunoglobulin A ACDA : American Celiac Disease Alliance TGA : transglutaminase antibodies AGA : American Gastroenterological Association ELISA : enzyme-linked immunosorbent assay IVD : in vitro diagnostic

The aim of this study was to evaluate the clinical importance of autoantibodies in pemphigus vulgaris patients who developed steroid-induced diabetes mellitus (SID) because of the glucocorticoid therapy of pemphigus.A total of 137 patients with pemphigus vulgaris were studied. Patients with SID and pemphigus were compared with those that had only pemphigus. The variables recorded were: age at diagnosis, sex, body mass index, presence of diabetes mellitus (DM), cumulative cortisone dose, treatment duration, value of anti-desmoglein 1 and 3, and anti-glutamic acid decarboxylase autoantibodies.A total of 31 patients (22.62%) that developed steroid-induced DM were identified. Anti-glutamic acid decarboxylase autoantibodies were positive in 20.75% of patients with pemphigus vulgaris and in 25.75% of patients with pemphigus vulgaris and SID.The overall anti-glutamic acid decarboxylase autoantibodies prevalence in pemphigus patients was high, and the risk of developing DM in patients with pemphigus remains a serious problem, being associated with increased risk of mortality.

Background and aims. The aim of this study was t o investigate the value of serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) correlated with some tissue molecules as predictive markers for recurrence in colon cancer. Methods . A total of 30 patients diagnosed with colon cancer stage II or III who underwent optimal surgery were enrolled in study. Tumor markers CEA and CA 19-9 were determined before surgery. Tumor samples were prepared using tissue microarray kit (TMA) then stained for different cellular markers (Ki 67, HER2, BCL2, CD56, CD4, CD8) and analyzed using Inforatio programme for quantitative determination. All patients received standard adjuvant treatment, which consisted of eight cycles chemotherapy type XELOX. The patients were followed up for 3 years. Results . Upon 3 years follow-up, 67% of patients developed tumor relapse, the most common site of metastasis being the liver. No correlations were observed between either serum or tissue tumor markers and the risk of tumor relapse. Conclusion . Over 50% of patients with colon cancer who had optimal treatment developed metastasis. No statistically significant predictive value for investigated molecules was found. Future studies are needed to confirm the use of molecular markers in monitoring patients with colorectal cancer

The prevalence of gluten-related diseases is increasing in an alarming rate. The studies regarding wheat allergy in the Southeastern and Central Europe are few. The aim of our study was to discuss the effectiveness of serological tests in detecting the prevalence of specific allergens.

Old age seems to be the greatest risk factor for celiac disease. Strict adherence to a gluten-free diet is difficult for these patients. We present the clinical reassessment in the case of a third age patient, with celiac disease under gluten-free diet and multiple related diseases.

The “four out of five rule” has not been officially endorsed by official guidelines. However, HLA-associated genes that predispose to CD are found in as much as 30–40% of healthy people. Thus, their presence seems too indecisive for the occurrence of CD.

BACKGROUND Several associations between HLA polymorphisms and JIA subtypes have been reported in multiple populations, but with significant variations across different ethnic groups. The aim of our study was to search specific HLA-DRB1, -DQA1 and -DQB1 polymorphisms that are associated with JIA and different disease phenotypes in Romanian patients compared with other ethnic groups. METHODS HLA genotyping was performed in 61 JIA patients and 30 ethnicity-matched controls using molecular biology methods, PCR-SSOP. RESULTS A protective effect across the whole cohort was observed for HLA-DRB1*15 (OR = 0.179, 95% CI: 0.054 -0.58) and HLA-DQB1*06 (OR = 0.285, 95% CI: 0.11-0.72). Each ILAR subgroup had a characteristic pattern of HLA associations. Unlike other populations, we found a positive association of HLA-DQA1*03 with chronic uveitis (OR = 14.67, 95% CI: 1.5-143) and a negative association of HLA-DQA1*01 with early disease onset (OR = 0.175, 95% CI: 0.036- 0.862), suggesting that the HLA-DR/DQ profile can affect the clinical expression of the disease. CONCLUSIONS The study reveals multiple HLA-DR/DQ associations with JIA, not only similar with those found in other populations, but also some distinctive associations. However, some of the previously established associations were not replicated in Romanian patients. These results might be due to the small size of our cohort or to true population differences.

Background The presence of autoantibodies is frequent in chronic viral hepatitis evolution. Defining the role of autoimmunity in disease evolution or response to interferon treatment is still in debate, both in children and in adults. There are few studies about the influence of autoimmunity in children with chronic viral hepatitis. The aim of our study was to establish the clinical significance of antinuclear autoantibodies (ANA) in chronic hepatitis B in children. Methods We have studied 80 children with chronic hepatitis B (30 female; mean age 12.31 +/- 4.13 years). For each patient we performed haematological and biochemical tests and in 41 patients we analyzed the liver histology. The immunological parameters analyzed were: circulating immune complexes (CIC), complement, and the serum levels of immunoglobulin G, A, and M. We analysed by indirect fluorescence the presence of ANA and other autoantibodies. The response to treatment (hepatoprotectors, interferon and Lamivudine) was established depending on seroconversion to HBeAb and HBsAb. Results Positive ANA were found at baseline in 15% of the patients and during follow-up in 21.25%. In ANA-positive patients compared to those without autoantibodies we found lower levels of haemoglobin and platelet numbers (p = 0.0245, p = 0.0236, respectively), higher gamma-glutamyl-transferase level (p = 0.040) and higher CIC level (p = 0.0155). During interferon treatment 13.79% of those who initially tested ANA-negative presented ANA, compared to 2.56% in those without interferon (p = 0.042). There was no difference in response to interferon treatment according to the presence of ANA (p = 0.4201). Conclusions Searching for ANA in children with chronic hepatitis B is a key element in describing the evolution of these patients, especially when considering interferon therapy. Interferon treatment stimulates the development of ANA, but their presence does not influence the response to this particular treatment. The role of autoimmune processes in the evolution and response to treatment of chronic hepatitis B patients remains controversial.

BACKGROUND Oxidative stress and inflammatory reactions are known to hold an important role in the etiopathogeny and persistence of acute or chronic clinical entities. Isoprostanes--a group of prostaglandin-like compounds, active products of arachidonic acid--have proved to be representative biomarkers of lipid peroxidation. The aim of this study was to determine the activity of serum 8-iso-prostaglandin F2alpha, (8iPGF2alpha), as an in vivo oxidative stress marker, in paediatric patients with diabetes mellitus type 1 (DM1) and in a control group. The main goals of this study were the following: establishing a possible correlation between the activity of 8iPGF2alpha and the presence of an autoimmune disease associated with DM1 and identifying a possible correlation between 8iPGF2alpha, the value of glycosylated hemoglobin (HbA1c) and the pancreatic autoimmune markers GAD65, IA2, IA in the group of patients with DM1 and other associated autoimmune diseases. METHODS Fifty-one children and adolescents (31 males) aged 11.65 +/- 4.1 years with DM1 were enrolled in the study. Twenty-seven healthy children, age- and gender-matched, were enrolled as controls. Patients and controls underwent the 8iPGFzalpha assessment through an ELISA serum method. RESULTS The mean 8iPGF2alpha value was 2090.6 +/- 3536.5 in the DM1 patient group and 509.9 +/- 493.5 in controls (p = 0.03). The mean 8iPGF2alpha value was 2178.19 +/- 4017.05 in patients with DM1 who did not suffer from other associated autoimmune diseases (n = 38) vs. 1834.95 +/- 1504.73 in patients with DM1 and other associated autoimmune diseases (n = 13) (p = 0.76). The correlation between the 8iPGF2alpha and the HbA1c values was determined by obtaining a correlation coefficient r = 0.38 and p = 0.0057. No correlation was observed between GAD65 and 8iPGF2alpha (r = 0.3; p = 0.29), IA2 and 8iPGF2alpha (r = -0.02; p = 0.92), IAA and 8iPGF2alpha (r = 0.4; p = 0.12). CONCLUSIONS Oxidative stress reactions are more intense in patients with diabetes mellitus type 1 than in healthy patients. Similar results were obtained in patients associating other autoimmune diseases. 8iPGF2alpha can be an ideal marker for determining oxidative reactions in vivo.

Lately, many hospital laboratories are using for antinuclear antibody (ANA) screening the solid-phase immunoassays (ELISA-ANA) instead of the traditional immunofluorescence ANA test (IF-ANA). Results of previous studies that compare the two technologies show poor correlation between them in both juvenile idiopathic arthritis (JIA) and childhood lupus erythematous (SLE) patients. In this study, we investigated whether ELISA-ANA and traditional IF-ANA results are comparable in pediatric patients with different rheumatic diseases. A total of 156 consecutive patients were included in the study—90 children with JIA, 33 with reactive arthritis, 19 with SLE, 4 with idiopathic chronic uveitis, and 10 with other systemic rheumatic diseases. ANA determination was performed using both assays. The higher rate of discrepancies between the two methods of ANA screening appeared in the JIA population (19/90, p < 0.001). All JIA patients with false-negative results by ELISA had significant or high IF-ANA titres. The prevalence of JIA-associated uveitis was higher in the group of false-negative ELISA-ANA children than in the ELISA-positive patients but without statistical significance (p = 0.62). On the contrary, in SLE group, the consistency rate of the two assays was 100 %, and the reactivity levels of ELISA-ANA were significantly higher than in ELISA-positive JIA patients (p < 0.001). ELISA seems to be a reliable method for screening ANA in childhood SLE, but not in JIA. Limited by the few SLE patients, our findings need further consideration.

Celiac disease has become extensively studied. What could be the cause? Increasing the accuracy of diagnostic tests for celiac disease has led to more discovered cases. Serological diagnosis of celiac disease has undergone important changes in recent years. Application of serological tests has reflected the diagnostic performance of tissue transglutaminase antibody and endomysial antibody as screening tests for celiac disease but also the progress of new serological tests as the antibodies against synthetic deamidated gliadin peptides. Serological tests are largely responsible for the recognition that celiac disease is not a rare disease. The Consensus in celiac disease from 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition which agreed that "Celiac disease is an immune-mediated enteropathy that can affect any system or organ and that can present itself with a wide range of clinical manifestations of variable severity" was confirmed. But increasing prevalence of this disease has led to the need for new methods of treatment among patients with celiac disease. Studies on quality of life of patients with celiac disease have questioned the gluten-free diet. As such new therapies, like TG2 inhibitors, the copolymer P (HEMA-co-SS) and other new experimental therapies, have emerged in celiac disease. The new therapies in celiac disease are based on new investigations in gluten toxicity screening, like K562(S)-cell agglutination, A1 and G12 monoclonal antibodies and proteomics. In this paper we want to present the investigative developments in celiac disease. We also want to find whether a new treatment in celiac disease is necessary.