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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.

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.

Introduction. Heart failure (HF) is characterized by neuroendocrine activation. The cardiac natriuretic hormones, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), together with their related pro-peptides (proANP and proBNP) represent a group of peptide hormones produced by the heart. A normal NT-proBNP level has a high negative predictive value for heart failure. The use of NT-proBNP testing is helpful in diagnosing acute HF in the emergency care setting, allowing an early and optimal treatment. The purpose of this study is to assess the prognostic value of NT-proBNP in heart failure in children younger than 3 years old and to establish whether it correlates with the NYHA/Ross functional class and left ventricle systolic function.

Înţelegerea relaţiei dintre agenţii infecţioşi şi autoimunitate pentru diagnosticarea precoce şi, de asemenea, prevenirea bolii celiace, precum şi a implicaţiilor clinice ale acesteia în cursul tratamentului cu interferon.

Background Supplementation of Lcarnitine is associated with improvement in some abnormalities present in hemodialysis (HD) patients. Objective. The study aim was to analyze the effect of oral L-carnitine supplementation on endothelial dysfunction (ED), oxidative stress (OS), inflammation and anemia in HD patients. Design. A prospective, longitudinal and observational study was performed in a single dialysis unit. Subjects and methods. We studied 31 HD patients: 21 patients formed the Lcarnitine supplementation group (group 1) and 10 entered the control group (group 2). At baseline and after 3 months of L-carnitine supplementation (500mg/day) we determined endothelial-dependent flow-mediated vasodilatation (FMD) and nitroglycerin induced endothelium independent vasodilatation, involving ultrasonographic brachial artery measurements, serum visfatin, malondialdehyde, body mass index, systolic blood pressure, diastolic blood pressure, interdialytic body weight gain, C-reactive protein, albumin, cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides, ferritin, transferrin saturation, hemoglobin, erythropoietin dose, calcium (Ca), phosphorus (P), parathormone and Kt/V . Results. In group 1, FMD (8.9 (4.5-12.5) to 10.6 (6.7-18), p=0.04) and Ca (8.4±0.6 to 8.8±0.5 mg/dL, p<0.001) significantly increased after L-carnitine supplementation, while visfatin (1.0 (0.2 1.3) to 0.4 (0-0.9) pg/mL, p=0.03), malondialdehyde (2.8 (2.4- 3.2) to 1.3 (1.2-1.5) nmol/mL, p<0.001) and P(5.6±1.3 to 5.0±1.2 mg/dL, p=0.005) significantly decreased. Albumin increased significantly in both groups (3.9±0.3 to 4.2±0.3mg/dL, p<0.001 in group 1 and 3.7±0.3 to 4.0±0.3 mg/dL, p=0.02 in group 2). There ere no other significant variations of the studied parameters. Conclusions. L-carnitine supplementation reduces ED, visfatin levels and markers of OS, but has no effect on inflammation, nutrition and anemia in HD patients. [ABSTRACT FROM AUTHOR]

Background. Metabolic syndrome is an important risk factor for cardiovascular diseases. Objective. To evaluate the prevalence of metabolic syndrome and serum profile of adipokines in children with overweight or obesity. Methods. Fifty two out of 62 referred children were included in the study, with a body mass index (BMI) that exceeded 85th percentile. Waist circumference and blood pressure (BP) were recorded, followed by the determination of: glucose, cholesterol, triglycerides, HDL cholesterol, insulin, adiponectin and leptin. The insulin resistance was then calculated by HOMA2 index. Results. Of the 52 children included, 28.8% have met the criteria for diagnosis of metabolic syndrome. BMI and BP values were higher in children with metabolic syndrome. The higher values of leptin (69.59 ± 50;89 vs. 58.44 ± 42.28 ng/ml) and insulin resistance (1.65 ± 0.74 vs. 1.41± 0.78) in the group with metabolic syndrome were without statistical significance. We found a positive correlation, statistically significant between BMI and serum leptin (r = 0.32, p =0.02), BMI and plasma insulin (r = 0.33, p =0.01), BMI and insulin resistance (r=0.33, p=0.01), respectively. This was not noticed for serum adiponectin. Conclusion. Metabolic syndrome has a high prevalence in childhood obesity. Serum leptin (but not adiponectin) seem to have a very good correlation with some clinical and bioumoral features of the metabolic syndrome. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) remains a significant public health concern because of its lethality, underscoring the need for deeper insights into its molecular mechanisms. Recent studies have increasingly highlighted the role of epigenetic modifications as critical players in cancer progression. Despite their importance, research specifically addressing epigenetic factors in GC is relatively scarce. This paper seeks to bridge that gap by examining recent literature that elucidates the epigenetic landscape associated with GC. The investigation of long noncoding RNAs (lncRNAs) has revealed their substantial involvement in gene dysregulation and epigenetic alterations within GC tumors. Notably, lncRNAs such as LINC00853 and LINC01266 have been identified as significant contributors to the epigenetic modulation of gene expression. Furthermore, the overexpression of KAT5 and GPX4 has been shown to mitigate the antiproliferative effects resulting from the depletion of circRHOT1, suggesting a complex interplay between these molecules in GC pathophysiology. Another pivotal aspect of epigenetic regulation in GC involves modifications in N6-methyladenosine (m6A), which play crucial roles in mRNA maturation processes such as splicing, export, degradation, and translation. m6A modifications are known for their influence on various cancer-related pathways, thus presenting a potential avenue for targeted interventions. Our findings indicate that the most pronounced instances of epigenetic dysregulation in GC can be traced back to the effects of long lncRNAs and alterations in m6A modification patterns. This underscores the urgent need for comprehensive investigations into these epigenetic factors, as a deeper understanding could lead to enhanced diagnostic markers and innovative therapeutic strategies. The integration of genetic and epigenetic considerations is essential for advancing the field of GC research. This synthesis of recent findings concerning epigenetic regulation offers valuable insights that could inform future studies and therapeutic developments. There is a critical need for ongoing research to elucidate the complexities of epigenetic modifications in GC, ultimately improving patient outcomes through tailored interventions.

Researchers have performed numerous studies on immunotherapy because of the high death rate associated with gastric cancer (GC). GC immunotherapy research has made tremendous progress, and we wanted to provide an update on this topic. On the basis of this update, we suggest performing a new medical evaluation before initiating immunotherapy in patients with GC to increase the success rate of immunotherapies. We propose that before patients start GC immunotherapy, they should be evaluated and given a score of one to two points for the following factors: immunopathological features, molecular and genomic features, potential consequences for bacterial pathogens, potential immunotherapeutic resistance and hyperprogressive illness, and the potential to use biomarkers to gauge their prognosis and immunotherapy responses to optimize immunotherapy following surgery. The proposed scoring system could also help in the diagnosis of GC. With all the advances in genetics, immunology, and microbiology, the diagnosis of GC could be improved, not changed. Currently, patients diagnosed with GC undergo surgical resection as the only permanent solution. Patients who meet the maximum score from the presented proposal could be eligible immediately after diagnosis for immunotherapy. Therefore, immunotherapy could be a first-line option for clinicians.

Physiological calcification occurs in bones and epiphyseal cartilage as they grow, whereas ectopic calcification occurs in blood vessels, cartilage, and soft tissues. Although it was formerly thought to be a passive and degenerative process associated with aging, ectopic calcification has been identified as an active cell-mediated process resembling osteogenesis, and an increasing number of studies have provided evidence for this paradigm shift. A significant association between vascular calcification and cardiovascular risk has been demonstrated by various studies, which have shown that arterial calcification has predictive value for future coronary events. With respect to cartilaginous calcification, calcium phosphate or hydroxyapatite crystals can form asymptomatic deposits in joints or periarticular tissues, contributing to the pathophysiology of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, tendinitis, and bursitis. The risk factors and sequence of events that initiate ectopic calcification, as well as the mechanisms that prevent the development of this pathology, are still topics of debate. Consequently, in this review, we focus on the nexus of the mechanisms underlying vascular and cartilaginous calcifications, trying to circumscribe the similarities and disparities between them to provide more clarity in this regard., Competing Interests: The authors declare no conflicts of interest.

Extracellular vesicles, or EVs, are membrane-bound nanocompartments produced by tumor cells. EVs carry proteins and nucleic acids from host cells to target cells, where they can transfer lipids, proteomes, and genetic material to change the function of target cells. EVs serve as reservoirs for mobile cellular signals. The collection of EVs using less invasive processes has piqued the interest of many researchers. Exosomes carry substances that can suppress the immune system. If the results of exosome screening are negative, immunotherapy will be beneficial for GC patients. In this study, we provide an update on EVs and GC based on ongoing review papers and clinical trials.

Many studies on gastric cancer treatment have identified predictors of immunotherapy benefits. This article provides an update on the major developments in research related to predictive factors of immunotherapy for gastric cancer. We used the search term "predictive factors, immunotherapy, gastric cancer" to find the most current publications in the PubMed database related to predictive factors of immunotherapy in gastric cancer. Programmed cell death, genetic, and immunological factors are the main study topics of immunotherapy's predictive factors in gastric cancer. Other preventive factors for immunotherapy in gastric cancer were also found, including clinical factors, tumor microenvironment factors, imaging factors, and extracellular factors. Since there is currently no effective treatment for gastric cancer, we strongly propose that these studies be prioritized.

Numerous studies have been performed on Helicobacter pylori infection because of the high death rate linked to this illness and gastric cancer. An update on the key developments in recent years in the investigation of Helicobacter pylori and gastric cancer is the goal of this review. Using the search term " Helicobacter pylori , gastric cancer", the PubMed database was searched. Only papers published in 2024 fulfilled the inclusion criteria. Because case report papers were not part of our investigation, they satisfied the exclusion criteria. Most of the research on the variable genes of Helicobacter pylori is guided by genetics to determine potential treatments. Studies on clinical treatments for the eradication of H. pylori with promising therapeutic options are needed. We found the fewest studies related to the immunopathology of H. pylori infection, which is still unknown. In conclusion, priority should be given to this kind of research.

Due to the high death rate associated with gastric cancer, a great deal of research has been conducted on this disease. The goal of this paper was to start a trimestral review of 2024 for the year that had just started. The scientific literature from 1 January 2024 was chosen with consideration of the the guidelines of the European Society of Medical Oncology (ESMO), which are updated with new findings but not systematically reviewed annually. We used the search term "gastric cancer" to find the most current publications in the PubMed database related to the prognosis and treatment of gastric cancer. As previously said, the only articles that satisfied the inclusion criteria were those from 2024. Articles with case reports were eliminated since they had nothing to do with our research. The treatment of gastric cancer is the focus of the majority of articles from 2024. The primary research axes include surgery and immunonutrition, immunotherapy and Helicobacter pylori , and therapeutic targets. Patients with GC may experience less psychological, social, and financial hardship if the recently identified markers discovered in circulation are better assessed and validated. This could be achieved by either including the markers in an artificial intelligence-based diagnostic score or by using them in conjunction with traditional diagnostic methods. Due to the rising death rate associated with GC, funding for research into diagnosis, prognosis, therapy, and therapeutic targets is essential.

Upper gastrointestinal bleeding (UGB) in children is a potentially life-threatening condition that represents a challenge for pediatricians and pediatric surgeons. It is defined as bleeding from any location within the upper esophagus to the ligament of Treitz. UGB can have many causes that vary with age. The impact on the child is often proportional to the amount of blood lost. This can range from mild bleeding that is unlikely to cause hemodynamic instability, to massive bleeding that requires admission to the intensive care unit. Proper and prompt management are very important factors in reducing morbidity and mortality. This article aims to summarize current research regarding the diagnosis and treatment of UGB. Most of the data used in the literature published on this subject is extrapolated from adulthood.

Introduction: The incidence of corrosive esophagitis, also known as caustic esophagitis in children, is still increasing in developing countries, according to different clinical reports. Acids and alkalis are, in the same manner, involved in the pathogenesis of corrosive esophagitis in children. The aim of our study was to determine the incidence and endoscopic grading of corrosive esophagitis in a cohort of children from a developing country., Materials and Methods: We performed a retrospective analysis of all pediatric patients who were admitted for corrosive ingestion at Pediatric Clinic II, Emergency Hospital for Children, Cluj-Napoca, over 10 years., Results: A total of 22 patients consisting of 13 (59.09%) girls and 9 boys (40.91%) were found in the present research. The majority of children lived in rural areas (69.2%). The results of laboratory tests were not well correlated with the degree of the injury. White blood cell counts over 20,000 cells/mm 3 , an increase in the C-reactive protein level and hypoalbuminemia were noticed only in three patients with strictures. The lesions were associated with increased levels of the pro - inflammatory cytokines , including interleukin (IL)-2, IL-5 and Interferon-gamma. Severe late complications such as strictures have been noticed in children with grade 3A injuries. The endoscopic dilation was done after the six months endoscopy. None of the patients treated with endoscopic dilation required surgical intervention for esophageal or pyloric perforation or dilation failure. The majority of complications (such as malnutrition) were noticed in children with grade 3A injuries. In consequence, prolonged hospitalization has been required. The second endoscopy (done six months after ingestion) revealed stricture as the most common late complication (n = 13, 60.60%: eight patients with grade 2B and five with grade 3A)., Conclusion: There is a low incidence of corrosive esophagitis in children in our geographic area. Endoscopic grading is a predictor of late complications such as strictures. Grade 2B and 3A corrosive esophagitis are likely to develop strictures. It is crucial to avoid strictures and to prevent malnutrition.

Suicides are one of the topics discussed around the world. This problem receives large space in scientific and professional literature, in order to eliminate its occurrence. Mechanisms of suicides are determined by whole spectrum of reasons determined by/depending on physical and psychological health. The objective of this work is to document the differences in mechanisms and realization of suicides by mentally sick people. Ten cases of suicides are reported in the article: three of which in people with a history of depression of the victim noted by family members, one with treated depression, three with anxiety-depressive disorder and three schizophrenic patients cases. There are five men and five women. Four of these women overdosed themselves by medicaments and one jumped out of a window. Two men shot themselves, two hanged themselves and one jumped out of a window. Persons without anamnestically proven psychiatric diseases end their lives mostly because of inconclusive situation or as a result of balancing their whole life (usually with good plan and preparation of the act). Persons with treatment of depression or anxiety-depressive disorder kill themselves mostly after several "unsuccessful" attempts. In case of victims with schizophrenia suicides follow a hardly predictable sequence of actions which sometimes do not seem to have any logic. Differences have been found between victims with and without mental disorders in ways of realization of suicides. Psychological predispositions in mood changes, long-term sadness and threatening suicide should be recognized by family members. Prevention of suicides in cases of people with a history of mental disorders is based on medical treatment and cooperation between the client and family members and a psychiatrist (Ref. 30). Keywords: forensic medicine, mental disorders, prevention, psychiatry, risk factors, suicides.

Atopic dermatitis (AD) is mainly considered an allergy, exacerbated by allergic factors. Is there evidence to suggest the existence of autoimmune components in the pathophysiology of the illness? Studies in the literature that dealt with the occurrence of autoimmunity in children with AD were analyzed. We followed the studies published in PubMed for 10 years, from 2001 to 2021. Clinical signs and symptoms were similar to other autoimmune diseases, having periods of remission and relapses. Other correlations between AD and autoimmune diseases have been described, and patients with AD can also present with a wide range of autoimmune comorbidities. Three major factors contribute to the pathogenesis of AD: damage of the skin barrier, disorders of the immune response, and imbalances of the skin microbiome-all based on genetic changes and influenced by environmental factors. Predominant activation of Th 2 cells, with the increase of Th 1, Th 17, and Th 22 subsets, promotes skin inflammation. All this evidence suggests that AD might be classified as an autoimmune disease, not just as an allergic reaction., Competing Interests: The authors declare no conflicts of interest.

Viral infections are a key issue in modern medicine. SARS-CoV-2 infection confirms that we are not sufficiently prepared for these unforeseen infections. The COVID-19 pandemic has cultivated a great sense of fear and distrust in patients. If viral infections, in this case, SARS-CoV-2, overlap with another infection, the symptoms are prolonged and worsened, and complications may occur. Starting from an objective clinical finding of a patient they had in follow-up and treatment, the authors present the problems of the diseases the patient suffered from. These are described as reviews so that readers can get an idea of the clinical methods of expression and the therapeutic possibilities. Therefore, this article describes Lyme disease and post-treatment Lyme disease syndrome, SARS-CoV-2 infection, and multisystem inflammatory syndrome in children (MISC-C), as the patient suffered from an incomplete form of Kawasaki disease. During the treatment for Lyme disease, the patient also contracted the influenza type A virus. Although any of these diseases could have the potential for serious evolution, our patient still went through these infections relatively well. This can be explained by the fact that the patient had a slow immune response to the aforementioned infections, which allowed him to survive these diseases relatively easily, unlike other individuals who have an exaggerated immune response or who suffer from serious immune involvement, e.g., hepatitis B with a fulminant response. The case was presented chronologically, but at the same time, all particular infection manifestations were accurately described. For these reasons, the article is presented in the form of a review, exemplified by the case itself. Of the 52 cases of MISC-C found in the Pediatrics Clinic II of Cluj-Napoca, we present the case of a male patient who presented with Lyme disease, post-treatment Lyme disease syndrome, Kawasaki disease, and MISC-C incomplete form.

Celiac disease (CD) is a disorder that affects both children and adults. Over the few last decades, several new atypical cases have been identified through improved diagnostic tools. On the other hand, the onset of CD at a later age, including atypical CD forms whose clinical picture overlaps with other autoimmune diseases, shows that currently there are several unknown gene mutations, which could be responsible for the disease development. Non-celiac gluten sensitivity (NCGS) is entity included by the ingestion of gluten leading to intestinal, or extraintestinal symptoms that improve once the gluten is removed from the nutrition. In this article relationships between genetically modified rodent animals with previously unknown multiple organ changes and CD, respectively NCGS are reviewed. Relationships between the small bowel histological changes and other organs pathology are discussed. Results of research document that changes have similar genetic background and can develop to serious autoimmune systematic diseases, including small bowel inflammation resembling atypical CD or NCGS. These may have extra-intestinal symptomatology but without a clear explanation of causes and differences in their manifestations. Research on animal models helps to discover links between several disorders associated with gastrointestinal damage. New methods based on individual gene mutations can help in atypical adult CD and NCGS recognitions in the future.

Mounting evidence shows that supplementation with vitamin D and K or their analogs induces beneficial effects in various diseases, e.g., osteoarticular, cardiovascular, or carcinogenesis. The use of drugs delivery systems via organic and inorganic nanocarriers increases the bioavailability of vitamins and analogs, enhancing their cellular delivery and effects. The nanotechnology-based dietary supplements and drugs produced by the food and pharmaceutical industries overcome the issues associated with vitamin administration, such as stability, absorption or low bioavailability. Consequently, there is a continuous interest in optimizing the carriers' systems in order to make them more efficient and specific for the targeted tissue. In this pioneer review, we try to circumscribe the most relevant aspects related to nanocarriers for drug delivery, compare different types of nanoparticles for vitamin D and K transportation, and critically address their benefits and disadvantages.

Kawasaki disease (KD) is a medium vessel systemic vasculitis that predominantly occurs in children below five years of age. It is an acute febrile condition in which coronary artery aneurysms and myocarditis are the most common cardiovascular complications. It is most often characterized by hypercytokinemia. The etiopathogenesis of KD is not fully understood. The present review synthesizes the recent advances in the pathophysiology and treatment options of KD. According to different studies, the genetic, infections and autoimmunity factors play a major role in pathogenesis. Several susceptibility genes (e.g. caspase 3) and cytokines (e.g. IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha) have been identified in KD. Patients with high cytokine levels are predisposed to KD shock syndrome. The importance of respiratory viruses in the pathogenesis of the disease is unclear. Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may induce in children and adults an abnormal systemic inflammatory response. This syndrome shares characteristics with KD. It has been called by many terms like MIS-C (Multisystem Inflammatory Syndrome in Children), PIMS-TS (pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2), hyperinflammatory shock syndrome, cytokine storm (cytokine release syndrome) or simply, Kawasaki-like syndrome. The cytokine's role in the development of KD or Kawasaki-like syndrome being triggered by COVID-19 is controversial. The presences of the antiendothelial cell autoantibodies (AECAs) together with the newly developed hypothesis of immunothrombosis are considered potential pathogenic mechanisms for KD. In consequence, the diagnosis and treatment of KD and Kawasaki-like syndrome, one of the most common causes of acquired heart disease in developed countries, are challenging without a clearly defined protocol.

Background: An early form of preeclampsia is rare. Abnormal placentation, placental perfusion disorders, and inflammatory cytokine release will have an effect on the fetus and newborn., Material and Methods: The study group consisted of preterm newborns whose mothers had a history of preeclampsia and a gestational age of between 30 weeks and 34 weeks + 6 days. The control group consists of neonates matched for gestational age with the case group, whose mothers had normal blood pressure. The incidence and severity of respiratory distress syndrome (RDS), intraventricular hemorrhage, hypoglycemia, pH gas changes, and hematological parameters were analyzed in the two groups., Results: The study group of preterm neonates had a lower birth weight than the control group ( p < 0.001). Most of the deliveries in the group of newborns exposed to preeclampsia were performed by cesarean section. Severe forms of RDS were two times more frequent in the group of newborns exposed to preeclampsia compared to those in the control group. Even though we expected to see a lower incidence, owing to the high number of deliveries by cesarean section, we still observed a higher rate of intraventricular hemorrhage in the preeclampsia group (16 cases in the study group vs. 7 in the control, p = 0.085). Neutropenia and thrombocytopenia were more frequent in preterm newborns exposed to preeclampsia., Conclusions: The study shows that early preeclampsia increases the risk of complications in preterm neonates. RDS was more frequent in the exposed group than in the control group. The severity of preeclampsia correlates with hematological changes.

Background: Vitamin K-dependent proteins (VKDPs) and the epidermal growth factor receptor (EGFR) are involved in lung cancer progression. Therefore, we aimed to study the serum concentration of Matrix Gla protein (MGP), Growth Arrest-specific 6 (Gas6), and EGFR before and after the first cycle of chemotherapy and to investigate how MGP, Gas6, and EGFR are modified after one cycle of chemotherapy., Methods: We performed an observational study on twenty patients diagnosed with lung cancer, by assessing the serum concentration of vitaminK 1 (VitK 1 ), MGP, Gas6, and EGFR using the ELISA technique before and after three weeks of the first cycle of chemotherapy. Patients were evaluated using RECIST 1.1 criteria., Results: Serum levels of MGP, Gas6, EGFR, and VK 1 before and after treatment were not changed significantly. Regarding the pre-treatment correlation of the MGP values, we found a strong positive relationship between MGP and VK 1 pre-treatment values (r = 0.821, 95%CI 0.523; 0.954, p < 0.001). Furthermore, there was a moderately negative correlation between VK 1 and EGFR pre-treatment values, with the relationship between them being marginally significant (r = -0.430, 95%CI -0.772; 0.001, p = 0.058). Post-treatment, we found a strong positive relationship between MGP and VK 1 post-treatment values (r = 0.758, 95%CI 0.436; 0.900, p < 0.001). We also found a moderate positive relationship between Gas6 and EGFR post-treatment values, but the correlation was only marginally significant (r = 0.442, p = 0.051).

The three types of neurofibromatosis, namely type 1, type 2, and schwannomatosis, are generally associated with various benign tumors affecting the skin and the nervous system. On rare occasions, especially in patients with neurofibromatosis type 1 (NF1), malignant neoplasms may also be present, several of them possessing a more aggressive course than in individuals without this syndrome. As such, a clear delineation between the three variants of neurofibromatosis is crucial to establish the correct diagnosis and management, as well as predict the neoplasm-related outcomes. Neurofibromin, the principal product of the NF1 gene, is a potent inhibitor of cellular proliferation, having been linked to several key signaling pathways involved in tumor growth. Therefore, it may provide a useful therapeutic target for tumor management in these patients. In this article, we want to present the association between deficiency of neurofibromin and the consequences of the lack of this protein leading to different kinds of malignant tumors. The therapy is still uncertain and most therapeutic options are in development or clinical trials.

Background: Itching is one of the major and mandatory signs of atopic dermatitis (AD) in children. Interleukin 31 (IL-31) is strongly involved in the genesis of pruritus. In our study, 68 patients aged 0-18 years with proven AD were followed clinically. The role of IL-31 in pruritus as clinical manifestation of AD is known but its etiopathogenetic mechanism is not well known., Methods: Serum was collected from 31 patients with moderate and severe forms of AD to determine IL-31 and its correlation with activity and severity of the disease. We also studied 30 healthy patients to compare the results of determinations. The IL-31 value was determined using the sandwich enzyme-linked-immunosorbent serologic assay (two antibodies assay). The IL-31 values were expressed as picograms per milliliter (pg/mL) and compared with activity and severity of the disease., Results: The IL-31 value was much higher in patients with AD compared to the control group. The mean value of findings was 1600 pg/mL compared to the control group with an average of 220 pg/mL. The IL-31 values were positively correlated with the severity and activity of the disease., Conclusions: The results of our pediatric study established the involvement of IL-31 in the pathophysiology of AD. IL-31 could be a marker of AD track.

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., (Copyright © 2021 Elsevier B.V. All rights reserved.)

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: Patients with Kawasaki disease (KD) may develop cardiovascular complications in the presence of predictive factors, including young age < 6 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., Methods: 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., Results: 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., Conclusions: 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.

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.

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.

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., (© 2021 Published by Elsevier B.V.)

A gluten-free diet is a special type of diet intended for people with celiac disease. The objective of this article is to report the past, present production, supply of gluten-free products as well as their future position in our market. In the past, there were only limited gluten-free products available and the awareness of the diet was limited to paediatric community. There were only few raw gluten-free materials and almost all the production was created in households. Later with the introduction of targeted screening into the practice, celiac diagnosis has improved, with an increase in newly diagnosed patients who have remained life-long dependents on a gluten-free diet. This was associated with an increased production of gluten-free products, referred to as weight loss diet, with their positive effects on health. Subsequently, the gluten-free diet has also been voluntarily adopted by both people with other diseases and healthy individuals. In the future, the gluten-free diet consumption is expected to increase, due to its increased popularity in populations. In this regard, gluten-free diets have been misinterpreted as a "miracle drug" that is effective on a variety of problems. The medical community will be confronting the future problems of people who are dependent on a gluten-free diet as well as the complications arising from the consumers of a gluten-free diet for no medical reasons. Compliance to the principles of a gluten-free diet should be maintained and should not be recommended to healthy individuals or those without relevant reasons., (©2020 RIGLD, Research Institute for Gastroenterology and Liver Diseases.)

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.

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 ± 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 ± 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 ± 171.8 mg/L vs. 498.63 ± 252.50 mg/L; p < 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 ± 33.73 mg/L vs. 216.12 ± 199.69 mg/L; p < 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.

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., Competing Interests: The authors declare no conflict of interest.

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.

Introduction: 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., Competing Interests: The authors declare no conflict of interest.

Purpose: Cytokines like IL-6, IL-10 and other factors like CRP are involved in the postoperative inflammatory-stress response. The association between IL-6, IL-10, CRP, albumin and early postoperative complications and deaths was analyzed on a cohort of cancer patient., Methods: The plasma levels of IL-6, IL-10 and serum levels of c-reactive protein (CRP) and albumin were measured in 85 patients undergoing surgical resection of pancreatic, hepatic and gastric tumors. The measurement of the studied biochemical parameters was made at three time points: before the operation, and on the 1st and 3rd day after the operation., Results: Of the 85 patients, 28 suffered early postoperative complications (14 gastric cancer patients; 11 pancreatic cancer patients; 3 liver cancer patients) and 9 patients died in the early postoperative period (5 gastric cancer patients; 4 pancreatic cancer patients; 0 liver cancer patients). Patients with elevated levels of serum CRP on the 3rd postoperative day had a significant increased risk of death. Also, patients with higher levels of IL-10 on the 3rd postoperative day demonstrated a significantly increased risk of early postoperative complications., Conclusion: This study demonstrates that plasma IL-10 concentration is positively associated with postoperative complications.