Mechanisms of redox balance and inflammatory response after the use of methylprednisolone in children with multisystem inflammatory syndrome associated with COVID-19.

Background: Multisystem inflammatory syndrome in children (MIS-C) associated with being infected with coronavirus-19 (COVID-19) is a life-threatening condition resulting from cytokine storm, increased synthesis of reactive oxygen species (ROSs), and hyperinflammation occurring in genetically predisposed children following an infection with SARS-CoV-2. Aim: The primary aims of our study were to identify changes in the activity of antioxidant enzymes in erythrocytes and total oxidative status in plasma after being treated with methylprednisolone (MP). Methods: A prospective cohort study of 67 children (56.7% male) under 18 with MIS-C being treated with MP was conducted at the Mother and Child Health Institute from January 2021 to April 2022. The impact of the therapy was assessed on the basis of the clinical condition, haematological and biochemical blood parameters, and echocardiographic findings. Results: 59.7% of patients presented cardiovascular (CV) manifestations, while myocardial dysfunction was observed in half of all patients (50.7%). A severe clinical course was observed in 22/67 patients. Children with CV involvement had a significantly higher relative concentration of B lymphocytes and lower relative concentration of NK cells than patients without CV issues (p < 0.001 and p = 0.004, respectively). Patients with severe MIS-C had a lower relative count of NK cells than those with moderate MIS-C (p = 0.015). Patients with myocardial dysfunction had a higher total oxidative plasma status (TOPS) than children without (p = 0.05), which implicates pronounced oxidative stress in the former cohort. In patients with shock, lower erythrocytes superoxide dismutase (SOD) activity was observed on admission compared to patients without shock (p = 0.04). After MP was administered, TOPS was significantly reduced, while catalase (CAT) and SOD activity increased significantly. Treatment failure (TF) was observed in 6 patients, only females (p=0.005). These patients were younger (p=0.05) and had lower CAT activity on admission (p=0.04) than patients with favorable treatment responses. In the group of patients with TF, TOPS increased after treatment (before 176.2 ± 10.3 mV, after 199.0 ± 36.7 mV). Conclusion: MP leads to rapid modulation of TOPS and increases the activity of antioxidant enzymes in erythrocytes resulting in clinical and echocardiographic improvement. Based on the observed changes in the activity of the antioxidant enzymes, we can conclude that s hydrogen peroxide is the dominant ROS in patients with MIS-C. Patients with TF showed reduced CAT activity, whereas the treatment with MP led to pronounced oxidation. This implies that low CAT activity may be a contraindication for using MP.

An Extensive Quality Control and Quality Assurance (QC/QA) Program Significantly Improves Inter-Laboratory Concordance Rates of Flow-Cytometric Minimal Residual Disease Assessment in Acute Lymphoblastic Leukemia: An I-BFM-FLOW-Network Report.

Monitoring of minimal residual disease (MRD) by flow cytometry (FCM) is a powerful prognostic tool for predicting outcomes in acute lymphoblastic leukemia (ALL). To apply FCM-MRD in large, collaborative trials, dedicated laboratory staff must be educated to concordantly high levels of expertise and their performance quality should be continuously monitored. We sought to install a unique and comprehensive training and quality control (QC) program involving a large number of reference laboratories within the international Berlin-Frankfurt-Münster (I-BFM) consortium, in order to complement the standardization of the methodology with an educational component and persistent quality control measures. Our QC and quality assurance (QA) program is based on four major cornerstones: (i) a twinning maturation program, (ii) obligatory participation in external QA programs (spiked sample send around, United Kingdom National External Quality Assessment Service (UK NEQAS)), (iii) regular participation in list-mode-data (LMD) file ring trials (FCM data file send arounds), and (iv) surveys of independent data derived from trial results. We demonstrate that the training of laboratories using experienced twinning partners, along with continuous educational feedback significantly improves the performance of laboratories in detecting and quantifying MRD in pediatric ALL patients. Overall, our extensive education and quality control program improved inter-laboratory concordance rates of FCM-MRD assessments and ultimately led to a very high conformity of risk estimates in independent patient cohorts.

Complex karyotype with cryptic FUS gene rearrangement and deletion of NR3C1 and VPREB1 genes in childhood B-cell acute lymphoblastic leukemia: A case report.

B-cell acute lymphoblastic leukemia (B-ALL) is a hematopoietic malignancy characterized by overproduction of immature B-lymphoblasts. B-ALL is the most common pediatric tumor and remains the leading cause of mortality in children and adolescents. Molecular and cytogenetic analyses of B-ALL revealed recurrent genetic and structural genomic alterations which are routinely applied for diagnosis, prognosis and choice of treatment regimen. The present case report describes a 4-year-old female diagnosed with B-ALL. GTG-banding at low resolution revealed an abnormal clone with 46,XX,?t(X;19)(q13;q13.3),der(9) besides normal cells. Molecular cytogenetics demonstrated a balanced translocation between chromosomes 16 and 19, and an unbalanced translocation involving chromosomes 5 and 9. A locus-specific probe additionally identified that the FUS gene in 16p11.2 was split and its 5' region was translocated to subband 19q13.33, whereas the 3' region of the FUS gene remained on the derivative chromosome 16. Overall, this complex karyotype included four different chromosomes and five break events. Further analyses, including array-comparative genomic hybridization, additionally revealed biallelic deletion of the tumor suppressor genes CDKN2A/B, and deletion of the NR3C1 and VPREB1 genes. The patient passed away under treatment due to sepsis.

Outcome differences between simple and complex gastroschisis.

BACKGROUND: We reviewed differences of the outcome of newborn with simple and complex gastroschisis treated at our institution over the past fifteen years. METHODS: A retrospective cohort study was performed on all infants with gastroschisis treated at the Institute for mother and child health care, Belgrade, between 2001 and 2015 (n=70). Premature infants (<34 weeks of gestation) and babies with birth weight less than 1500 g were excluded (n=5). We compared outcomes in infants with simple gastroschisis and those with complex gastroschisis. An outcome analysis was performed for birth weight, gestational age, gender, mode of defect closure, presence of intestinal necrosis or perforation, reoperation, duration of mechanical ventilation and total parenteral nutrition, presence of bowel pseudoopstraction, sepsis, total duration of hospital stay, mortality rates. RESULTS: Of 65 patients, 15 (23,07%) had complex gastroschisis, including atresia 5 patients (33,3%), ischemic complication 9 patients (60%) and one patient with closing gastroschisis (6,66%). Sixty eight percent underwent primary closure.There was difference between the simple and the complex gastroschisis in duration of mechanical ventilation (P= ,000003), total parenteral nutrition (P= ,000019), bowel pseudoobstruction (P= ,00067), reoperation (P= ,00122), sepsis (P= ,0043), hospital stay (P= ,000198). In the simple gastroschisis group 92% of patients survived to discharge. In the complex gastroschisis group 3 patients died in hospital (P= ,338). CONCLUSIONS: More research should be focused to predict complex gastroschisis and to improve prenatal diagnosis and postnatal management, without a significant increase in morbidity and mortality. KEY WORDS: Complex, Gastroschisis, Outcomes, Simple, Vanishing.

Aggressive human neuroblastomas show a massive increase in the numbers of autophagic vacuoles and damaged mitochondria.

Autophagy is activated in cancer cells in response to multiple stresses and has been demonstrated to promote tumor cell survival and drug resistance in neuroblastoma (NB). This study was conducted to analyze the ultrastructural features of peripheral neuroblastic tumors (pNTs) and identify the relation of the types of NTs, the proliferation rate, and MYCN gene amplification with a number of autophagic vacuoles. Our results indicate that aggressive human NBs show a massive increase in the number of autophagic vacuoles associated with proliferation rate and that alteration of the mitochondria might be an important factor for the induction of autophagy in NTs.

Gastroschisis with gastric perforation and jejunal stenosis A rare association of anomalies.

AIM: Gastroschisis with prenatal gastric perforation and intestinal stenosis is a rare and serious anomaly. although there are several case reports, no case series exists to suggest the prognosis for these infants. MATERIAL AND METHODS: In this report a case of gastroschisis with gastric perforation and jejunal stenosis in male newborn is presented with literature review. The stomach, small bowel and the part of the colon were herniated through the abdominal wall defect. A large perforation site at the anterior wall of fundus and a thin fibrous strip that causing stenosis of jejunum was found. RESULTS: Gastrorraphy was performed. Stenosis of jejunum was resected and t-t anastomosis was performed, followed by primary fascial closure. DISCUSSION: The prenatal sonographic finding of bowel or gastric perforation are variable. Antenatal bowel dilatation and in particular intraabdominal bowel dilatation is prognostically useful for detection of patients with worse outcome. The absence of bowel dilatation cannot fully exclude complex patients. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure are not associated with prolonged time for full enteral feeding and length of hospital stay. CONCLUSIONS: We have presented the first detailed report of surgical intervention and outcomes in case of gastroschisis with prenatal gastric perforation and congenital jejunal stenosis. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure is recommended here. More research should be focused to predict complex gastroschisis and to improve prenatal diagnosis and postnatal management, without a significant increase in morbidity and mortality. KEY WORDS: Gastroschisis, Gastric perforation, Stenosis of jejunum.

Gastroschisis with gastric perforation and jejunal stenosis. A rare association of anomalies.

AIM: Gastroschisis with prenatal gastric perforation and intestinal stenosis is a rare and serious anomaly. although there are several case reports, no case series exists to suggest the prognosis for these infants. MATERIAL AND METHODS: In this report a case of gastroschisis with gastric perforation and jejunal stenosis in male newborn is presented with literature review. The stomach, small bowel and the part of the colon were herniated through the abdominal wall defect. A large perforation site at the anterior wall of fundus and a thin fibrous strip that causing stenosis of jejunum was found. RESULTS: Gastrorraphy was performed. Stenosis of jejunum was resected and t-t anastomosis was performed, followed by primary fascial closure. DISCUSSION: The prenatal sonographic finding of bowel or gastric perforation are variable. Antenatal bowel dilatation and in particular intraabdominal bowel dilatation is prognostically useful for detection of patients with worse outcome. The absence of bowel dilatation cannot fully exclude complex patients. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure are not associated with prolonged time for full enteral feeding and length of hospital stay. CONCLUSIONS: We have presented the first detailed report of surgical intervention and outcomes in case of gastroschisis with prenatal gastric perforation and congenital jejunal stenosis. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure is recommended here. More research should be focused to predict complex gastroschisis and to improve prenatal diagnosis and postnatal management, without a significant increase in morbidity and mortality. KEY WORDS: Gastroschisis, Gastric perforation, Stenosis of jejunum.

Nasopharyngeal Capillary Arteriovenous Malformation with Ancient/Symplastic Change: A Simulator of Malignancy.

There are only 8 published cases of symplastic hemangioma (SH), a relatively recently described, distinct benign entity characterized by pleomorphic vascular smooth muscle and interstitial cells in a pre-existing, long-standing vascular lesion. Seven of these cases were of SH in cutaneous locations, and 1 case was described in the mediastinum. We report the case of the 12-year-old girl with a nasopharyngeal tumor mass with prominent symplastic changes arising in the background of a combined capillary arteriovenous malformation. After critical analysis of all published cases of SH, it is clear that these lesions commonly represent capillary arteriovenous malformations (CAVM) with ancient/symplastic changes according to current terminology proposed in the classification required by the International Society for the Study of Vascular Anomalies (ISSVA). This is the first such lesion reported in a mucosal location and presenting in the pediatric age group. CAVM with ancient/symplastic change follows a benign clinical course, but it can simulate a malignant vascular tumor.

Duplication cyst with esophageal mucosa at the floor of the mouth: a case report.

Intraoral localization of alimentary tract duplication is extremely rare. We report a duplication cyst at the floor of the mouth, lined by esophageal epithelium and treated successfully by surgical excision. To our knowledge, this is the third case of intraoral enteric duplication cysts lined with esophageal epithelium reported in the literature.