The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

Celiac disease - a pluripathological model in pediatric practice.

Being defined as an autoimmune, chronic pathology, frequently encountered in any age group, but especially in pediatrics, celiac disease (also called gluten enteropathy), is gaining more and more ground in terms of diagnosis, but also interest in research. The data from the literature of the last decades attest the chameleonic way of its presentation, there may be both classic onset symptoms and atypical symptoms. Given the impact played by celiac disease, especially in the optimal growth and development of children, the current narrative review aims to highlight the atypical presentation methods, intended to guide the clinician towards the inclusion of the pathology in the differential diagnosis scheme. To these we add the summary presentation of the general data and therapeutic lines regarding the underlying condition and the existing comorbidities. In order to place the related information up to date, we performed a literature review of the recent articles published in international databases. We bring forward the current theories and approaches regarding both classic celiac disease and its atypical manifestations. Among these we note mainly constitutional, skin or mucous, bone, neuro-psychic, renal, reproductive injuries, but also disorders of biological constants and association with multiple autoimmunities. Knowing and correlating them with celiac disease is the key to optimal management of patients, thus reducing the subsequent burden of the disease.

Cystic fibrosis management in pediatric population-from clinical features to personalized therapy.

Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations of the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). In 1949, it's been identified as a monogenic disease and was thought to primarily affect individuals of Northern European descent. It was the most prevalent autosomal recessive disease that shortens life. With the availability of multiple testing methodologies nowadays, there is a chance to create novel and enhanced treatment options. Even in the absence of a high sweat chloride test (SCT) result, the discovery of two causal mutations is diagnostic for cystic fibrosis (CF). For a CF diagnosis, however, at least two positive E sweat chloride tests are still required. In order to achieve early and active intervention to manage cystic fibrosis (CF) and its comorbidities, treatment regimens for pediatric patients should be evaluated, improved, and closely monitored. New developments in the treatment of cystic fibrosis (CF) have led to the development of medications derived from molecules that target the pathogenetic pathway of the illness. These options are very efficient and allow pediatric patients to receive individualized care. However, in order to better direct patient care and enhance patient outcomes, it is crucial to research uncommon CF mutations, which can provide crucial information about the prognosis of the disease and the relationships between genotype and phenotype. To ensure the success of creating novel, safer, and more efficient treatment approaches, a deeper understanding of the pathogeny of the illness is required. In the age of customized medicine, genetic research will be essential to improving patient care and quality of life for those with uncommon mutations.

Insights into the Management of Chronic Hepatitis in Children-From Oxidative Stress to Antioxidant Therapy.

Recent research has generated awareness of the existence of various pathophysiological pathways that contribute to the development of chronic diseases; thus, pro-oxidative factors have been accepted as significant contributors to the emergence of a wide range of diseases, from inflammatory to malignant. Redox homeostasis is especially crucial in liver pathology, as disturbances at this level have been linked to a variety of chronic diseases. Hepatitis is an umbrella term used to describe liver inflammation, which is the foundation of this disease regardless of its cause. Chronic hepatitis produces both oxidative stress generated by hepatocyte inflammation and viral inoculation. The majority of hepatitis in children is caused by a virus, and current studies reveal that 60-80% of cases become chronic, with many young patients still at risk of advancing liver damage. This review intends to emphasize the relevance of understanding these pathological redox pathways, as well as the need to update therapeutic strategies in chronic liver pathology, considering the beneficial effects of antioxidants.

Overcoming Drug Resistance in a Clinical C. albicans Strain Using Photoactivated Curcumin as an Adjuvant.

The limited antifungal drugs available and the rise of multidrug-resistant Candida species have made the efforts to improve antifungal therapies paramount. To this end, our research focused on the effect of a combined treatment between chemical and photodynamic therapy (PDT) towards a fluconazole-resistant clinical Candida albicans strain. The co-treatment of PDT and curcumin in various doses with fluconazole (FLC) had an inhibitory effect on the growth of the FLC-resistant hospital strain of C. albicans in both difusimetric and broth microdilution methods. The proliferation of the cells was inhibited in the presence of curcumin at 3.125 µM and FLC at 41 µM concentrations. The possible involvement of oxidative stress was analyzed by adding menadione and glutathione as a prooxidant and antioxidant, respectively. In addition, we examined the photoactivated curcumin effect on efflux pumps, a mechanism often linked to drug resistance. Nile Red accumulation assays were used to evaluate efflux pumps activity through fluorescence microscopy and spectrofluorometry. The results showed that photoactivated curcumin at 3.125 µM inhibited the transport of the fluorescent substrate that cells usually expel, indicating its potential in combating drug resistance. Overall, the findings suggest that curcumin, particularly when combined with PDT, can effectively inhibit the growth of FLC-resistant C. albicans, addressing the challenge of yeast resistance to azole antifungals through upregulating multidrug transporters.

The Disease with a Thousand Faces and the Human Microbiome-A Physiopathogenic Intercorrelation in Pediatric Practice.

Numerous interrelationships are known in the literature that have the final effect of unmasking or influencing various pathologies. Among these, the present article aims to discuss the connection between systemic lupus erythematosus (SLE) and the human microbiome. The main purpose of this work is to popularize information about the impact of dysbiosis on the pathogenesis and evolutionary course of pediatric patients with SLE. Added to this is the interest in knowledge and awareness of adjunctive therapeutic means that has the ultimate goal of increasing the quality of life. The means by which this can be achieved can be briefly divided into prophylactic or curative, depending on the phase of the condition in which the patient is. We thus reiterate the importance of the clinician acquiring an overview of SLE and the human microbiome, doubled by in-depth knowledge of the physio-pathogenic interactions between the two (in part achieved through the much-studied gut-target organ axes-brain, heart, lung, skin), with the target objective being that of obtaining individualized, multimodal and efficient management for each individual patient.

The Footprint of Microbiome in Pediatric Asthma-A Complex Puzzle for a Balanced Development.

Considered to be of greater complexity than the human genome itself, the microbiome, the structure of the body made up of trillions of bacteria, viruses, and fungi, has proven to play a crucial role in the context of the development of pathological processes in the body, starting from various infections, autoimmune diseases, atopies, and culminating in its involvement in the development of some forms of cancer, a diagnosis that is considered the most disabling for the patient from a psychological point of view. Therefore, being a cornerstone in the understanding and optimal treatment of a multitude of ailments, the body's microbiome has become an intensively studied subject in the scientific literature of the last decade. This review aims to bring the microbiome-asthma correlation up to date by classifying asthmatic patterns, emphasizing the development patterns of the microbiome starting from the perinatal period and the impact of pulmonary dysbiosis on asthmatic symptoms in children. Likewise, the effects of intestinal dysbiosis reflected at the level of homeostasis of the internal environment through the intestine-lung/vital organs axis, the circumstances in which it occurs, but also the main methods of studying bacterial variability used for diagnostic purposes and in research should not be omitted. In conclusion, we draw current and future therapeutic lines worthy of consideration both in obtaining and maintaining remission, as well as in delaying the development of primary acute episodes and preventing future relapses.

Pediatric COVID-19 and Diabetes: An Investigation into the Intersection of Two Pandemics.

Coronavirus disease 2019 (COVID-19) is a complex infectious disease caused by the SARS-CoV-2 virus, and it currently represents a worldwide public health emergency. The pediatric population is less prone to develop severe COVID-19 infection, but children presenting underlying medical conditions, such as diabetes mellitus, are thought to be at increased risk of developing more severe forms of COVID-19. Diabetic children face new challenges when infected with SARS-CoV-2. On one hand, the glycemic values become substantially more difficult to manage as COVID-19 is a predisposing factor for hyperglycemia. On the other hand, alongside other risk factors, high glycemic values are incriminated in modulating immune and inflammatory responses, leading to potentially severe COVID-19 cases in the pediatric population. Also, there are hypotheses of SARS-CoV-2 being diabetogenic itself, but this information is still to be confirmed. Furthermore, it is reported that there was a noticeable increase in the number of cases of new-onset type 2 diabetes among the pediatric population, and the complications in these patients with COVID-19 include the risk of developing autoimmune diseases under the influence of stress. Additionally, children with diabetes mellitus are confronted with lifestyle changes dictated by the pandemic, which can potentially lead to the onset or exacerbation of a potential underlying anxiety disorder or depression. Since the literature contains a series of unknowns related to the impact of COVID-19 in both types of diabetes in children, the purpose of our work is to bring together the data obtained so far and to identify potential knowledge gaps and areas for future investigation regarding COVID-19 and the onset of diabetes type 1 or type 2 among the pediatric population.

Advances in Understanding the Human Gut Microbiota and Its Implication in Pediatric Celiac Disease-A Narrative Review.

Celiac disease (CD) is a multifactorial disorder, defined by a complex interplay of genetic and environmental factors. Both genetic predisposition and dietary exposure to gluten are essential factors in triggering CD. However, there is proof that their presence is necessary, but not sufficient, for disease development. Through gut microbiota modulation, several additional environmental factors have shown their potential role as co-factors in CD pathogenesis. The aim of this review is to illustrate the possible mechanisms that stand behind the gut microbiota's involvement in CD pathogenesis. Furthermore, we discuss microbiota manipulation's potential role as both a preventative and therapeutic option. The available literature provides evidence that even before CD onset, factors including cesarean birth and formula feeding, as well as intestinal infection exposure, amplify the risk of CD in genetically predisposed individuals, due to their influence on the intestinal microbiome composition. Active CD was associated with elevated levels of several Gram-negative bacterial genera, including Bacteroides, Escherichia, and Prevotella, while beneficial bacteria such as lactobacilli and bifidobacteria were less abundant. Viral and fungal dysbiosis has also been described in CD, evidencing specific taxa alteration. A gluten-free diet (GFD) may improve the clinical symptoms and duodenal histopathology, but the persistence of intestinal dysbiosis in CD children under a GFD urges the need for additional therapy. Probiotics, prebiotics, and fecal microbial transplant have demonstrated their efficacy in restoring gut microbiota eubiosis in adult CD patients; however, their efficacy and safety as adjunctive therapies to a GFD in pediatric patients needs further investigation.

Connection between Celiac Disease and Systemic Lupus Erythematosus in Children-A Development Model of Autoimmune Diseases Starting from What We Inherit to What We Eat.

Celiac disease (CD) and systemic lupus erythematosus (SLE) are two diseases intensively studied in all age groups, with an increasing incidence at the global level, possibly due to the increased awareness of the diseases and their accurate diagnosis and as a consequence of the new research and innovation technologies that have appeared in medicine. The first is a controllable condition found in approximately 1% of the entire population in the form of a reaction to environmental stimuli affecting individuals with genetic susceptibility, causing gluten intolerance, gastrointestinal and extradigestive symptoms, starting from subclinical stages and culminating in severe malabsorption. On the other hand, lupus is an autoimmune disease with chameleon-like symptoms and found mainly in the female sex, which leaves its clinical mark on most organs, from the skin, eyes, and kidneys to the cardiovascular, pulmonary, neurological, osteoarticular, and hematological systems. Current studies focus on the correlation between celiac disease and other autoimmune pathologies such as autoimmune thyroiditis (Hashimoto and Graves-Basedow), type I diabetes, and systemic lupus erythematosus. The current review aims to present a summary of the data from the specialized literature regarding the intercurrents between celiac disease and lupus by analyzing the most recent studies published on PubMed.

Postoperative atrial fibrillation prediction following isolated surgical aortic valve replacement.

OBJECTIVE: Postoperative atrial fibrillation (POAF) is the most common complication following cardiac surgery, with increased risk of stroke and high mortality. Our aim was to identify patients at risk and to design a model that could predict POAF. METHODS: In this single center study, we evaluated 1191 patients requiring isolated surgical aortic valve replacement between January 2000 and June 2014. The patients were followed during the early postoperative period until discharge. RESULTS: AF occurred in 342 patients (28.71%). Six variables associated with high arrhythmic risk [advanced age, body mass index, tricuspid regurgitation, prolonged ventilation, longer intensive care unit stay, and dilated left atrium (LA; volume ≥35 ml/m2)] were selected to create a multivariate prediction model. This model predicted POAF in 64.7% of cases, with a moderate discriminative power (AUC=0.65; p=0.001; 95% CI, 0.571-0.771). We also developed the CHAID (Chi-square automatic interaction detection) model showing multilevel interactions among risk factors for POAF. Age had the greatest discriminative power, with patients aged >68 years at a higher risk for POAF. In low-risk patients, the subgroup with dilated LA (volume ≥40 ml) was more prone to develop POAF. For the intermediate-risk group, history of AF was the next deciding variable, whereas for the high-risk group, it was tricuspid regurgitation (at least moderate). CONCLUSION: The multivariate logistic model has an acceptable predictive value. CHAID-derived model is a new tool that could be easily applied to identify patients requiring prophylactic regimens.

Midkine, a heparin-binding growth factor, and its roles in atherogenesis and inflammatory kidney diseases.

The heparin-binding protein midkine is a potent growth factor with emerging roles in numerous inflammatory diseases. Beyond its characterization in embryogenesis and organ development, ample insights into its function have been collected from experimental disease models using knockout animals or knockdown intervention strategies. Here a comprehensive overview on midkine and its functions in atherogenesis and kidney diseases is provided. Molecular clues to key signalling pathways (Akt, ERK, HIF1α) and key events in atherosclerotic vessels link midkine expression with vascular smooth muscle proliferation and (neo)angiogenesis. In acute and chronic kidney diseases, midkine expression is upregulated in tubular as well as endothelial cells. Experimental disease models that mimic diabetic nephropathy and/or immunologic glomerular damage indicate dichotomous midkine activities, with cytoprotective as well as injurious effects. This review also pinpoints the commonalities of the disease models. An understanding of the underlying molecular events will be required in order to design a targeted intervention into cardiovascular or renal diseases as well as inflammatory processes.

Loss of heparin-binding protein prevents necrotizing glomerulonephritis: first clues hint at plasminogen activator inhibitor-1.

The orchestration of acute inflammatory kidney injury is subject to widespread influences and involves cytokines as well as chemokines released by resident as well as infiltrating cells. Although intense research efforts have been made in the field, it still unravels yet novel key molecules involved in the pathogenesis of this kidney disease. A heparin-binding growth factor denoted midkine is expressed by various cell types following stress of tissue damage. Specific functions relate to orchestration of reparative and inflammatory processes by promoting migration of leucocytes and release of chemokines with ensuing angiogenesis. Midkine appears as a double-edged sword with beneficial or harmful effects in injured tissues. Here, we discuss a recent publication that provides evidence for the beneficial role of midkine in progressive glomerulonephritis, most likely due to blockade of plasminogen activator inhibitor-1 release.

Lessons from the heart and ischemic limbs: midkine as anti-inflammatory mediator for kidney diseases?

Inflammatory responses ensuing ischemia involve the release of numerous mediators. Among these the heparin-binding growth factor midkine has been recognized as a potent inducer of neoangiogenesis. In a recent publication, the release of midkine has been studied in different in vitro models, and effects of abrogated midkine expression by means of genetic knockout has been analyzed in ischemia models of the limbs. The observed effects indicate a profound effect exerted by midkine under ischemia in the coordination of the inflammatory response and neoangiogenesis.