The Importance of Molecular Genetic Testing for Precision Diagnostics, Management, and Genetic Counseling in MODY Patients.

Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic ß-cells. The diagnosis of MODY still remains a challenge for clinicians, with many cases being misdiagnosed as type 1 or type 2 diabetes mellitus (T1DM/T2DM), and over 80% of cases remaining undiagnosed. With the introduction of modern technologies, important progress has been made in deciphering the molecular mechanisms and heterogeneous etiology of MD, including MODY. The aim of our study was to identify genetic variants associated with MODY in a group of patients with early-onset diabetes/prediabetes in whom a form of MD was clinically suspected. Genetic testing, based on next-generation sequencing (NGS) technology, was carried out either in a targeted manner, using gene panels for monogenic diabetes, or by analyzing the entire exome (whole-exome sequencing). GKC-MODY 2 was the most frequently detected variant, but rare forms of KCNJ11-MODY 13, specifically, HNF4A-MODY 1, were also identified. We have emphasized the importance of genetic testing for early diagnosis, MODY subtype differentiation, and genetic counseling. We presented the genotype-phenotype correlations, especially related to the clinical evolution and personalized therapy, also emphasizing the particularities of each patient in the family context.

Diagnosis and Management of Simple and Complicated Meconium Ileus in Cystic Fibrosis, a Systematic Review.

The early management of neonates with meconium ileus (MI) and cystic fibrosis (CF) is highly variable across countries and is not standardized. We conducted a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The protocol was registered in PROSPERO (CRD42024522838). Studies from three providers of academic search engines were checked for inclusion criteria, using the following search terms: meconium ileus AND cystic fibrosis OR mucoviscidosis. Regarding the patient population studied, the inclusion criteria were defined using our predefined PICOT framework: studies on neonates with simple or complicated meconium which were confirmed to have cystic fibrosis and were conservatively managed or surgically treated. Results: A total of 566 publications from the last 10 years were verified by the authors of this review to find the most recent and relevant data, and only 8 met the inclusion criteria. Prenatally diagnosed meconium pseudocysts, bowel dilation, and ascites on ultrasound are predictors of neonatal surgery and risk factor for negative 12-month clinical outcomes in MI-CF newborns. For simple MI, conservative treatment with hypertonic solutions enemas can be effective in more than 25% of cases. If repeated enemas fail to disimpact the bowels, the Bishop-Koop stoma is a safe option. No comprehensive research has been conducted so far to determine the ideal surgical protocol for complicated MI. We only found three studies that reported the types of stomas performed and another study comparing the outcomes of patients depending on the surgical management; the conclusions are contradictory especially since the number of cases analyzed in each study was small. Between 18% and 38% of patients with complicated MI will require reoperation for various complications and the mortality rate varies between 0% and 8%. Conclusion: This study reveals a lack of strong data to support management decisions, unequivocally shows that the care of infants with MI is not standardized, and suggests a great need for international collaborative studies.

Congenital Hyperinsulinism Caused by Mutations in ABCC8 Gene Associated with Early-Onset Neonatal Hypoglycemia: Genetic Heterogeneity Correlated with Phenotypic Variability.

Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset HH caused by ABCC8 gene mutations. In the first patient, who presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330-1)del] that correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C>T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of the focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) positron emission tomography/computed tomography (PET/CT) was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

Impact of COVID-19 on Pediatric Inflammatory Bowel Diseases-From Expectations to Reality.

Viral infections have always been considered a threat to global health, with numerous outbreaks across time. Despite the relative recent experience with coronavirus-associated diseases such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), severe acute respiratory syndrome-2's (SARS-CoV-2) continuous evolution displays a different behavior. With a tropism for both respiratory and digestive mucosa, coronavirus disease 2019 (COVID-19) and inflammatory bowel disease (IBD) seem to share a particular common background. Current literature offers evidence that viral alteration of the immune system, inflammatory intestinal tissue damage, increased intestinal permeability, incomplete viral clearance with viral antigen persistence, and intestinal dysbiosis, might explain SARS-CoV-2-IBD relationship in terms of etiopathogenesis and evolution. The hyperinflammatory state that both entities have in common explains the lack of success of current IBD therapy, raising the need for new personalized therapeutic options, with better outcomes for IBD and COVID-19 as well. This review aims to summarize the current available data on pediatric IBD evolution, management, and outcomes in the post-COVID period, with an emphasis on the particular aspects of the SARS-CoV-2-IBD relationship in children.

Modern Treatment of Valvulopathies in Patients with Congenital Hemophilia.

Hemophiliacs can develop cardiovascular diseases, including valvulopathies of various etiologies and severities. Some require surgical treatment. Performing cardiac surgery in hemophiliacs is a challenge because they maintain an increased risk of bleeding throughout their lives. Our review shows that with a multidisciplinary team and careful planning, cardiac surgery can be safely performed in these patients. Valve repair and bioprosthetic valves should be preferred over mechanical valves to avoid life-long anticoagulation. In patients who cannot receive a bioprosthetic valve, the use of the On-X mechanical valve might be considered because it requires less intensive anticoagulation after 3 months of treatment. Antithrombotic treatment is feasible in hemophiliacs only if the coagulation factor level is kept constantly above a specific trough limit. Our review is valuable because, for the first time, the available data on the modern surgical treatment of valvular disease in hemophiliacs have been synthesized and systematized.

The Role of Natural Extracts in the Management of Infantile Hemangiomas and Vascular Tumors.

Hemangiomas are vascular tumors resulting from the proliferation of endothelial-like cells; they are the most common childhood tumors, affecting approximately 5-10% of newborns and infants. Besides hemangiomas, which are definitely benign tumors despite their overgrowth potential, there are other vascular tumors like hemangioendotheliomas, which may display intermediate characteristics between benign hemangiomas and highly malignant angiosarcomas. Standard therapy may be constricted by serious adverse effects, high cost, or traumatic influence. Diet is a major resource for health preservation, disease prevention, and treatment. The therapeutic property of edible berries, marine products, or medicinal plants have long been known and used in traditional medicine; a plant-based nutrition can prevent the development and progression of diseases associated with extensive neo-vascularization. The purpose of our review is to highlight those natural treatments that hemangioma and vascular tumor patients can receive in the future, both for their benefit and that of their families. We performed the review according to the Preferred Reporting Items for Systematic Reviews and Metanalysis Statement. We used the Web of Science, PubMed, and EMBASE engines for the study, and searched for the association of hemangioma with naturopathic treatment/plant extract/plants in published articles. We found that natural extracts from plants and fruits are cost-effective and safe treatments for hemangiomas and vascular tumors, as well as for other forms of cancer. In any case, more in vitro and in vivo studies are needed to confirm the proposed signaling pathways in tumors and validate the improvement parameters after natural products administration. The era of molecularly targeted therapy and personalized medicine is approaching and naturally occurring substances are very useful tools for tumor treatment and prevention. Plant extract substances have strong specificity and pertinence, are non- toxic and have few side effects, and may become an emerging cancer treatment.

Arrhythmogenic Right Ventricular Cardiomyopathy in Children: A Systematic Review.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by the progressive replacement of the normal myocardium by fibroadipocytic tissue. The importance of an early diagnosis is supported by a higher risk of sudden cardiac death in the pediatric population. We reviewed the literature on diagnosis, risk stratification, and prognosis in the pediatric population with ARVC. In case reports which analyzed children with ARVC, the most common sign was ventricular tachycardia, frequently presenting as dizziness, syncope, or even cardiac arrest. Currently, there is no gold standard for diagnosing ARVC in children. Nevertheless, genetic analysis may provide a proper diagnosis tool for asymptomatic cases. Although risk stratification is recommended in patients with ARVC, a validated prediction model for risk stratification in children is still lacking; thus, it is a matter of further research. In consequence, even though ARVC is a relatively rare condition in children, it negatively impacts the survival and clinical outcomes of the patients. Therefore, appropriate and validated diagnostic and risk stratification tools are crucial for the early detection of children with ARVC, ensuring a prompt therapeutic intervention.

Nanotechnology Innovations in Pediatric Cardiology and Cardiovascular Medicine: A Comprehensive Review.

(1) Background: Nanomedicine, incorporating various nanoparticles and nanomaterials, offers significant potential in medical practice. Its clinical adoption, however, faces challenges like safety concerns, regulatory hurdles, and biocompatibility issues. Despite these, recent advancements have led to the approval of many nanotechnology-based products, including those for pediatric use. (2) Methods: Our approach included reviewing clinical, preclinical, and animal studies, as well as literature reviews from the past two decades and ongoing trials. (3) Results: Nanotechnology has introduced innovative solutions in cardiovascular care, particularly in managing myocardial ischemia. Key developments include drug-eluting stents, nitric oxide-releasing coatings, and the use of magnetic nanoparticles in cardiomyocyte transplantation. These advancements are pivotal for early detection and treatment. In cardiovascular imaging, nanotechnology enables noninvasive assessments. In pediatric cardiology, it holds promise in assisting the development of biological conduits, synthetic valves, and bioartificial grafts for congenital heart defects, and offers new treatments for conditions like dilated cardiomyopathy and pulmonary hypertension. (4) Conclusions: Nanomedicine presents groundbreaking solutions for cardiovascular diseases in both adults and children. It has the potential to transform cardiac care, from enhancing myocardial ischemia treatment and imaging techniques to addressing congenital heart issues. Further research and guideline development are crucial for optimizing its clinical application and revolutionizing patient care.

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.

Current Data and New Insights into the Genetic Factors of Atherogenic Dyslipidemia Associated with Metabolic Syndrome.

Atherogenic dyslipidemia plays a critical role in the development of metabolic syndrome (MetS), being one of its major components, along with central obesity, insulin resistance, and hypertension. In recent years, the development of molecular genetics techniques and extended analysis at the genome or exome level has led to important progress in the identification of genetic factors (heritability) involved in lipid metabolism disorders associated with MetS. In this review, we have proposed to present the current knowledge related to the genetic etiology of atherogenic dyslipidemia, but also possible challenges for future studies. Data from the literature provided by candidate gene-based association studies or extended studies, such as genome-wide association studies (GWAS) and whole exome sequencing (WES,) have revealed that atherogenic dyslipidemia presents a marked genetic heterogeneity (monogenic or complex, multifactorial). Despite sustained efforts, many of the genetic factors still remain unidentified (missing heritability). In the future, the identification of new genes and the molecular mechanisms by which they intervene in lipid disorders will allow the development of innovative therapies that act on specific targets. In addition, the use of polygenic risk scores (PRS) or specific biomarkers to identify individuals at increased risk of atherogenic dyslipidemia and/or other components of MetS will allow effective preventive measures and personalized therapy.

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.

The Early Initiation Advantages of Physical Therapy in Multiple Sclerosis-A Pilot Study.

(1) Background: Multiple sclerosis (MS), a chronic progressive neurological disorder which affects the central nervous system (CNS), can result in disorders of all the functions controlled by the CNS: motor, sensory, cognitive and emotional. Physical therapy (PT), conducted through proprioceptive neuromuscular facilitation (PNF) techniques, can be customized to the individual patient's needs and has the potential to improve the patient's evolution. This study aims to establish if PT based on PNF techniques has a beneficial role in MS treatment. (2) Methods: We performed a prospective study on 40 patients who were diagnosed with MS and previously treated only with MS drug treatment (DT). These patients have participated in a PT program throughout one year. At the beginning and at the end of our study, after one year, we have assessed the following parameters: timed walk for 25 feet (Timed 25-Foot Walk test- T25FW test), dexterity of the upper limbs (9-Hole Peg Test-9HPT), disability level (Expanded Disability Status Scale-EDSS) and cognitive function (Paced Auditory Serial Addition Test-PASAT. (3) Results: In subjects in the early stages of MS, lower limb mobility improved significantly, T25FW decreasing from 6.46 to 5.80 (p < 0.001) and upper limb ability increased significantly in the dominant hand, 9HPT decreasing from 17.73 to 16.97 (p = 0.006) and not significantly in the non-dominant hand, 9HPT decreasing from 17.73 to 17.50 (p = 0.255). Furthermore, among these subjects, cognitive performance improved; their PASAT increased from 52.14 to 54.14 (p = 0.036), while the level of disability of these subjects improved only slightly, the EDSS scale evolving from 3.08 to 2.91 (p = 0.650). (4) Conclusions: In patients with early forms of MS, combining DT with a PT program based on PNF techniques results in: regaining muscle strength in the lower limbs, improving coordination while walking, correcting dexterity in the upper limbs and increasing the ability to concentrate.

Advancing Cancer Research: Current Knowledge on Cutaneous Neoplasia.

Skin cancers require a multidisciplinary approach. The updated guidelines introduce new insights into the management of these diseases. Melanoma (MM), the third most common skin cancer, a malignant melanocytic tumor, which is classified into four major histological subtypes, continues to have the potential to be a lethal disease. The mortality-incidence ratio is higher in Eastern European countries compared to Western European countries, which shows the need for better prevention and early detection in Eastern European countries. Basal cell carcinoma (BCC) and squamous cell carcinoma (cSCC) remain the top two skin cancers, and their incidence continues to grow. The gold standard in establishing the diagnosis and establishing the histopathological subtype in BCC and SCC is a skin biopsy. Sebaceous carcinoma (SeC) is an uncommon and potentially aggressive cutaneous malignancy showing sebaceous differentiation. It accounts for 0.7% of skin cancers and 3-6.7% of cancer-related deaths. Due to the rapid extension to the regional lymph nodes, SeC requires early treatment. The main treatment for sebaceous carcinoma is surgical treatment, including Mohs micrographic surgery, which has the advantage of complete margin evaluation and low recurrence rates. Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative diseases, with no evidence of extracutaneous determination at the moment of the diagnosis. PCLs have usually a very different evolution, prognosis, and treatment compared to the lymphomas that may secondarily involve the skin. The aim of our review is to summarize the important changes in the approach to treating melanoma, non-melanoma skin, cutaneous T and B cell lymphomas, and other types of skin cancers. For all skin cancers, optimal patient management requires a multidisciplinary approach including dermatology, medical oncology, and radiation oncology.

Acute Myocardial Infarction in Patients with Hereditary Thrombophilia-A Focus on Factor V Leiden and Prothrombin G20210A.

Factor V (FV) Leiden and prothrombin G20210A are the most common hereditary thrombophilias. While their role in venous thromboembolism is well known, there are still uncertainties regarding their relationship with arterial thrombotic events, especially coronary ones. Our research, based on an in-depth analysis of the available literature, provides up-to-date information on the relationship between FV Leiden and prothrombin G20210A and acute myocardial infarction. FV Leiden and prothrombin G20210A screening should be implemented only in select cases, such as acute coronary syndrome in young individuals and/or in the absence of traditional cardiovascular risk factors and/or in the absence of significant coronary artery stenosis at angiography. Their identification should be followed by the implementation of optimal control of modifiable traditional cardiovascular risk factors to reduce the risk of recurrent events and genotyping and genetic counseling of all family members of affected cases for proper prophylaxis. An extended dual antiplatelet therapy (DAPT) may be considered, given the lower risk of bleeding under DAPT conferred by FV Leiden.

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.

Exome sequencing in a Romanian Bardet-Biedl syndrome cohort revealed an overabundance of causal BBS12 variants.

Bardet-Biedl syndrome (BBS), is an emblematic ciliopathy hallmarked by pleiotropy, phenotype variability, and extensive genetic heterogeneity. BBS is a rare (~1/140,000 to ~1/160,000 in Europe) autosomal recessive pediatric disorder characterized by retinal degeneration, truncal obesity, polydactyly, cognitive impairment, renal dysfunction, and hypogonadism. Twenty-eight genes involved in ciliary structure or function have been implicated in BBS, and explain the molecular basis for ~75%-80% of individuals. To investigate the mutational spectrum of BBS in Romania, we ascertained a cohort of 24 individuals in 23 families. Following informed consent, we performed proband exome sequencing (ES). We detected 17 different putative disease-causing single nucleotide variants or small insertion-deletions and two pathogenic exon disruptive copy number variants in known BBS genes in 17 pedigrees. The most frequently impacted genes were BBS12 (35%), followed by BBS4, BBS7, and BBS10 (9% each) and BBS1, BBS2, and BBS5 (4% each). Homozygous BBS12 p.Arg355* variants were present in seven pedigrees of both Eastern European and Romani origin. Our data show that although the diagnostic rate of BBS in Romania is likely consistent with other worldwide cohorts (74%), we observed a unique distribution of causal BBS genes, including overrepresentation of BBS12 due to a recurrent nonsense variant, that has implications for regional diagnostics.

Omphalocele and Cardiac Abnormalities-The Importance of the Association.

Omphalocele is the most common ventral abdominal wall defect. Omphalocele is associated with other significant anomalies in up to 80% of cases, among which the cardiac ones are the most frequent. The aim of our paper is to highlight, through a review of the literature, the importance and frequency of association between the two malformations and what impact this association has on the management and evolution of patients with these pathologies. We reviewed the titles, the available abstracts, and the full texts of 244 papers from the last 23 years, from three medical databases, to extract data for our review. Due to the frequent association of the two malformations and the unfavorable effect of the major cardiac anomaly on the prognosis of the newborn, the electrocardiogram and echocardiography must be included in the first postnatal investigations. The timing of surgery for abdominal wall defect closure is mostly dictated by the cardiac defect severity, and usually the cardiac defect takes priority. After the cardiac defect is medically stabilized or surgically repaired, the omphalocele reduction and closure of the abdominal defect are performed in a more controlled setting, with improved outcomes. Compared to omphalocele patients without cardiac defects, children with this association are more likely to experience prolonged hospitalizations, neurologic, and cognitive impairments. Major cardiac abnormalities such as structural defects that require surgical treatment or result in developmental delay will significantly increase the death rate of patients with omphalocele. In conclusion, the prenatal diagnosis of omphalocele and early detection of other associated structural or chromosomal anomalies are of overwhelming importance, contributing to the establishment of antenatal and postnatal prognosis.

Nosocomial Infections Affecting Newborns with Abdominal Wall Defects.

Abdominal wall defects are serious birth defects, with long periods of hospitalization and significant costs to the medical system. Nosocomial infection (NI) may be an additional risk factor that aggravates the evolution of newborns with such malformations. METHODS: in order to analyze the factors that may lead to the occurrence of NI, we performed a retrospective study over a period of thirty-two years (1990-2021), in a tertiary children's hospital; 302 neonates with omphalocele and gastroschisis were eligible for the study. RESULTS: a total of 33.7 % patients were infected with one or more of species of bacteria or fungi. These species were Enterobacteriaceae, Pseudomonas aeruginosa and Acinetobacter spp., Staphylococcus spp., Enterococcus spp. or Candida spp., but the rate of NI showed a significant decrease between the 1990-2010 and 2011-2021 period (p = 0.04). The increase in the number of surgeries was associated with the increase in the number of NI both for omphalocele and gastroschisis; in the case of gastroschisis, the age of over 6 h at the time of surgery increased the risk of infection (p = 0.052, marginal statistical significance). Additionally, for gastroschisis, the risk of NI was 4.56 times higher in the presence of anemia (p < 0.01) and 2.17 times higher for the patients developing acute renal failure (p = 0.02), and a hospitalization period longer than 14 days was found to increase the risk of NI 3.46-fold (p < 0.01); more than 4 days of TPN was found to increase the NI risk 2.37-fold (p = 0.015). Using a logistic regression model for patients with omphalocele, we found an increased risk of NI for those in blood group 0 (OR = 3.8, p = 0.02), in patients with a length of hospitalization (LH) of ≥14 days (OR = 6.7, p < 0.01) and in the presence of anemia (OR = 2.5, p = 0.04); all three independent variables in our model contributed 38.7% to the risk of NI. CONCLUSION: although in the past 32 years we have seen transformational improvements in the outcome of abdominal wall defects, there are still many factors that require special attention for corrections.

Total Anomalous Pulmonary Venous Return in the Time of SARS-CoV-2-Case Report.

The management of children with complex and life-threatening heart malformations became a clinical conundrum during the SARS-CoV-2 pandemic. The pathophysiological features of the new coronavirus infection have raised major dilemmas regarding the postoperative evolution of an infected patient, and the epidemiological limitations have tightened the criteria for selecting cases. We present the case of a newborn diagnosed with total anomalous pulmonary venous return (TAPVR) who underwent surgical repair of the defect with favorable outcome, despite a prior diagnosis of SARS-CoV-2 infection. We discuss the medical and surgical management of TAPVR, highlighting possible management difficulties brought by the SARS-CoV-2 pandemic.

Unusual Association of Diamond-Blackfan Anemia and Severe Sinus Bradycardia in a Six-Month-Old White Infant: A Case Report and Literature Review.

Diamond-Blackfan anemia is a rare (6-7 million live births), inherited condition manifesting as severe anemia due to the impaired bone marrow production of red blood cells. We present the unusual case of a six month old infant with a de novo mutation of the RPS19 gene causing Diamond-Blackfan anemia who additionally suffers from severe sinus bradycardia. The infant was diagnosed with this condition at the age of four months; at the age of 6 months, she presents with severe anemia causing hypoxia which, in turn, caused severe dyspnea and polypnea, which had mixed causes (hypoxic and infectious) as the child was febrile. After correction of the overlapping diarrhea, metabolic acidosis, and severe anemia (hemoglobin < 3 g/dL), she developed severe persistent sinus bradycardia immediately after mild sedation (before central venous catheter insertion), not attributable to any of the more frequent causes, with a heart rate as low as 49 beats/min on 24 h Holter monitoring, less than the first percentile for age, but with a regular QT interval and no arrhythmia. The echocardiogram was unremarkable, showing a small interatrial communication (patent foramen ovale with left-to-right shunting), mild left ventricular hypertrophy, normal systolic and diastolic function, and mild tricuspid regurgitation. After red cell transfusion and appropriate antibiotic and supportive treatment, the child's general condition improved dramatically but the sinus bradycardia persisted. We consider this a case of well-tolerated sinus bradycardia and foresee a good cardiologic prognosis, while the hematologic prognosis remains determined by future corticoid response, treatment-related complications and risk of leukemia.