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Acute promyelocytic leukemia (APL) accounts for up to 10% of all childhood acute myeloid leukemia cases with a median age at presentation of 9–12 years and a higher incidence in Italy, China, and L...

Background COVID-19, the novel coronavirus, has caused a global pandemic affecting millions of people around the world. Risk factors for critical disease in adults are advanced age and underlying medical comorbidities, including cancer. Data are sparse on the effect of COVID-19 infection on pediatric patients with cancer during their active antineoplastic therapy. The optimal management of antineoplastic treatment during COVID-19 infection in this unique population is controversial. Aim To describe the severity and clinical course of COVID-19 infection in pediatric patients with cancer during active antineoplastic treatment and to study their course of treatment. Methods Clinical and laboratory data were collected from medical files of patients diagnosed with COVID-19, confirmed by polymerase chain reaction (PCR), who received active antineoplastic treatment between March 2020 and May 2021 in a large tertiary pediatric medical center. Results Eighteen patients with diverse pediatric cancers are described. They were infected with COVID-19 at different stages of their antineoplastic treatment regimen. Eight had an asymptomatic COVID-19 infection, nine had mild symptoms, and one had severe disease. All of them recovered from COVID-19 infection. Two patients experienced delays in their antineoplastic treatment; none of the other patients had delays or interruptions, including patients who were symptomatic for COVID-19. Conclusion In pediatric patients with cancer who test positive for COVID-19, yet are asymptomatic or have mild symptoms, the continuance of antineoplastic therapy may be considered.

Supplemental Digital Content is available in the text., Background: Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pneumonia. Methods: Noncompartmental pharmacokinetics and safety were analyzed from 2 recently completed pediatric studies, a single-dose, phase 1 study in neonates and infants up to 3 months of age (7.5 mg/kg) and a phase 3 study in patients 3 months to 17 years of age with pneumonia (10–20 mg/kg with a maximum of 500 mg per dose every 8 hours for up to 14 days). Results: Total ceftobiprole plasma concentrations peaked at the end of infusion. Half life (median ranging from 1.9 to 2.9 hours) and overall exposure (median AUC ranging from 66.6 to 173 μg•h/mL) were similar to those in adults (mean ± SD, 3.3 ± 0.3 hours and 102 ± 11.9 μg•h/mL, respectively). Calculated free-ceftobiprole concentrations in the single-dose study remained above a minimum inhibitory concentration (MIC) of 4 mg/L (fT > MIC of 4 mg/L) for a mean of 5.29 hours after dosing. In the pneumonia study, mean fT > MIC of 4 mg/L was ≥5.28 hours in all dose groups. Ceftobiprole was well tolerated in both studies. Conclusions: Pharmacokinetic parameters of ceftobiprole characterized in the pediatric population were within the range of those observed in adults. In the pneumonia study, the lowest percentage of the dosing interval with fT > MIC of 4 mg/L was 50.8%, which suggests that pharmacokinetic-pharmacodynamic target attainment can be sufficient in pediatric patients. Ceftobiprole was well tolerated.

Summary Aim The aim of this study was to evaluate the nutritional status, the nutritional effect on the risk of infection and the severity of the disease, and the contribution of nutrition to the course of the infection in pediatric patients diagnosed with coronavirus disease who required additional nutritional support after hospitalization. Methods The body weight, height, body mass index, upper arm circumference, and triceps skinfold thickness of 49 patients aged 1 month to 18 years and diagnosed with Covid-19 and then hospitalized at the Ankara City Hospital, Pediatric Health and Diseases Hospital, Pediatric Infection ward between 15 May and 15 June 2020 were measured. Total protein, albumin, prealbumin, selenium, zinc, ferritin, folate, and selenium, C, D, E, and B12 levels were studied from blood drawn simultaneously from the patients. Results A total of 49 patients aged 8–18 years were evaluated. The median age was 13 years (age range 8–18). The females made up 53% and the males 47% of the group. No patient needed intensive care admission. Only 3 patients received antibiotic treatment and the others were followed up without treatment. The weight was normal in 75% and the height was normal in 90%. Mid-arm circumference and triceps thickness were normal in 72% of the patients. Vitamin D deficiency was present in 82%, vitamin B12 deficiency in 18%, vitamin C deficiency in 17%, ferritin deficiency in 16%, folate deficiency in 15%, vitamin A deficiency in 13%, and vitamin E deficiency in 7%. Conclusion No patient required intensive care admission. Only 3 patients received antibiotic treatment and the others were followed up without treatment. Malnourishment was present in 3% of the patients while 9% were obese. Vitamin D deficiency was the most common vitamin deficiency while vitamin B12, vitamin C, Ferritin, vitamin A, vitamin E, and Folate deficiency were less common. Selenium and zinc levels were normal in all patients. There was no correlation between anthropometric values and susceptibility to childhood COVID-19 infection or the clinical course. It is possible that vitamin D deficiency increases susceptibility to the infection.

Objective: To evaluate the levels of N-terminal pro-B-type Natriuretic Peptide in infants and children with non-cardiac diseases especially respiratory diseases. Study Design: Cross-sectional study. Place and Duration of Study: Department of Chemical Pathology/Biochemistry Laboratory Services of Liaquat National Hospital Karachi Pakistan, from Dec 2018 to Nov 2019. Methodology: Infants and children admitted to the Pediatric department with non-cardiac diseases were included in the study. Non-probability consecutive sampling was done. Blood was taken and analyzed for N- terminal pro-B-type Natriuretic Peptide, Troponin I, urea, creatinine, Lactate dehydrogenase, Creatinine Kinase, lactate and sodium analysis. Results: Out of the 93 patients, 74 (80%) were diagnosed with respiratory disorders, with bronchopneumonia making up 54 (59%) Bronchiolitis 15 (17%) and 4% had miscellaneous respiratory diseases. Out of the remaining 20%, 8 (9%) patients were diagnosed with sepsis, and the remaining 11% were diagnosed with miscellaneous diseases. There was a positive correlation of N- terminal pro-B-type Natriuretic Peptide with Troponin I, urea, creatinine, Creatinine Kinase and Lactate dehydrogenase levels (p

This is the first published case report of a child with acute lymphatic leukemia developing a fatal mucormycosis during blinatumomab treatment. The patient showed multiple, systemic thromboembolic lesions with ischemia, bleeding and infarction in almost all organs. The child succumbed to increased brain pressure resulting in cerebral herniation. This case particularly illustrates the fulminant progression and huge challenges of diagnosing and treating mucormycosis in children with hemato-oncological diseases during treatment with targeted therapeutic antibodies (blinatumomab).

The diagnosis of vascular tumors and malformations is usually achieved with clinical history and physical examination. The imaging of these patients has been sufficiently refined to answer pertinent questions when trying to make an accurate differential diagnosis in order to establish an informed treatment plan. The imaging modalities at hand include ultrasound, doppler sonography, magnetic resonance imaging and contrast material enhanced magnetic resonance angiography. We present two cases of different vascular anomalies that were managed according to the clinical aspect, natural history and imaging performed. Moreover, with better understanding of the imaging features, the radiologist has become a key player in the diagnosis and management plan of the vascular anomalies. This is crucial in avoiding misdiagnosis and improper treatment.

Purpose COVID-19 pandemic has adversely affected the medical services offered for non-COVID related pathologies all over the world. This led to most of the elective services being postponed. In this study, we investigated the impact of the initial wave of COVID-19 pandemic on patients with esophageal strictures that were listed on the endoscopic dilatation program. Methods Medical records were reviewed from March–September 2020 (study group). The study period was divided into three intervals guided by the number of confirmed cases with COVID-19 and the measures taken during the lockdowns in the corresponding periods. Case burden, dilatation sessions, dysphagia score, and further interventions were reviewed. Case burden and dilatation sessions were compared to equivalent periods in 2019 (control group). Results The study group included 13 patients that had 19 dilatation sessions in contrast to 29 patients that had 98 sessions in the comparative group. In the study group, eight cases experienced deterioration in their dysphagia score, while further interventions were performed on four of them. Conclusion To avoid morbidities during the pandemic, high-risk patients should be precisely identified and actively followed. Parents and caregivers should be reassured and encouraged to seek medical advice as quickly as possible whenever the need arises.

Objective This report summarizes the clinical features and 1‐month follow‐up observations for pediatric patients who were hospitalized with coronavirus disease 2019 (COVID‐19) in Wuhan Women and Children's Hospital. Methods The 1‐month follow‐up data included clinical manifestations and results from serum severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) IgG and IgM tests, reverse‐transcription polymerase chain reaction (RT‐PCR) for SARS‐CoV‐2, lung computed tomography (CT) scans, and laboratory tests. Results Between January 20 and March 15, 2020, 127 patients aged 0–15 years were hospitalized for COVID‐19 treatment, including 3 severe cases and 124 mild or moderate cases. The main therapies included inhalation of aerosolized interferon‐α (122/127) and additional antiviral drugs (28/127). Among the 81 patients who had pneumonia at admission, 35 with right lobe pneumonia had the longest hospital stay (mean 14.5 ± 7 days); 17 with left lobe pneumonia had the highest creatine kinase (154 ± 106 U/L) and creatine kinase myocardial band (CK‐MB, 43 ± 48 U/L) levels; and 29 with bilateral pneumonia had the highest white blood cell counts (8.3 ± 4 × 109/L). Among the 46 patients who were successfully followed up 1 month after discharge, two notable findings were right lobe pneumonia in 22% (95% confidence interval [CI]: 11%–37%) of patients and persistently elevated serum creatine kinase and CK‐MB levels. The median duration of elevated CK‐MB was 45 days. The mean concentrations of serum SARS‐CoV‐2 IgG and IgM in 41 patients were 8.0 ± 7.5 and 98 ± 40 ng/ml, respectively. At follow‐up, four patients retested positive for SARS‐CoV‐2. Conclusions The involvement of different lung lobes in patients with COVID‐19 was associated with variations in the persistence of pneumonia and elevation of CK‐MB levels and body temperature.

Background. The purpose of this study is to evaluate functional and radiological outcomes of subtalar arthroereisis in the treatment of symptomatic pediatric flexible flatfeet. Methods. A total of 16 patients (26 feet) were treated with a Kalix II as subtalar motion blocker between 2009 and 2014. Calcaneal pitch (CP) and Meary’s angle (MA) were measured on radiographs preoperatively, directly postoperatively, and at follow-up 47 ± 17 (range 19-79) months. Patient satisfaction surveys were used to assess functional outcome and patient satisfaction. Results. Surgery was performed mostly for pain, walking problems, or a combination of both at a mean age of 12.5 ± 1.5 (range 10-15) years. Symptoms were relieved in 62.5% of patients in the postoperative phase and increased to 68.75% at follow-up. A statistically significant increase in CP of 2.8° and decrease in MA of 14.0° was observed directly postoperatively, which persisted during the follow-up period irrespective of Kalix removal. Revision surgery was necessary in 6 cases (23%) because of arthroereisis migration. Conclusion. Subtalar Kalix II arthroereisis significantly reduced clinical symptoms and improved the CP and MA directly postoperatively, which persisted during follow-up, irrespective of Kalix removal. Therefore, subtalar arthroereisis is a considerable intervention to reduce symptoms in children with symptomatic flexible flatfeet. Levels of Evidence: Level IV: Case series

Treatment for pediatric-onset multiple sclerosis (POMS) currently reflects treatment for adult-onset MS, despite some differences in its clinical course. First-choice treatment of POMS generally consists of interferon β-1a or glatiramer acetate, with therapies such as natalizumab or fingolimod reserved for second-choice treatment. In cases of severe disease, both fingolimod and natalizumab can be considered first-choice therapy. This paper presents three case histories of patients with POMS and highlights the different uses of fingolimod within the POMS treatment algorithm. The first and third cases are examples of escalation therapy, both in females aged 16 to 17 years, with fingolimod administering as second choice following disease progression. The second case is an example of using fingolimod as first-choice therapy, given to a 12-year-old male with severe disease. In all three cases, over a period of approximately 1 year after the initiation of fingolimod treatment, there was no further disease progression and no adverse events were recorded.

IntroductionVarious neurological complications may occur as a consequence of arterial ischemic stroke (AIS) and have an impact on daily activity of the patients, costs of their medical care and rehabilitation. The aim of this study was to analyze risk factors, stroke symptoms and post-stroke consequences in Polish pediatric patients depending on stroke subtype.Material and methodsWe retrospectively reviewed 77 children under the age of 18 years following their first AIS. Patients were white, Polish Caucasians, recruited in the Department of Pediatric Neurology at the Medical University of Silesia in Katowice (Poland). Statistical analysis was performed using Statistica 12.0.ResultsGender differed significantly between stroke subgroups (p = 0.030). The presence of focal cerebral arteriopathy (FCA) and chronic diseases was associated with type of AIS (p = 0.003 and p = 0.050, respectively). An outcome without neurological deterioration (normal outcome) was observed in 43% of children with lacunar anterior circulation infarct (LACI). Hemiparesis was present in almost all children with total anterior circulation infarct (TACI), in two thirds of children with partial anterior circulation infarct (PACI) and in almost 50% of children with LACI or posterior circulation infarct (POCI). In every child with hemiplegia the stroke symptom evolved into hemiparesis at follow-up. Additionally, patients with a normal outcome were older at the time of AIS than those with at least one neurological consequence (OR = 0.894, p = 0.034).ConclusionsThe presence and number of neurological outcomes depend on stroke subtypes. A relation between the presence of post-stroke deficits and age at onset was observed. The odds of deficit after ischemic stroke decreases by an average of 10.6% if the child is 1 year older at the time of AIS.

Background Leukemia can create a significant economic burden on the patients and their families. The objective of this study is to assess the medical expenditure and compensation of pediatric leukemia, and to explore the incidence and determinants of catastrophic health expenditure (CHE) among households with pediatric leukemia patients in China. Methods A cross‐sectional interview was conducted among households living with pediatric leukemia using a questionnaire in two tertiary hospitals. CHE was defined as out‐of‐pocket (OOP) payments that were greater than or equal to 40% of a household's capacity to pay (CTP). Chi‐square tests and logistic regression analysis were performed to identify the determinants of CHE. Results Among 242 households living with pediatric leukemia, the mean OOP payment for pediatric leukemia healthcare was $9860, which accounted for approximately 35.7% of the mean household's CTP. The overall incidence of CHE was 43.4% and showed a downward trend with the lowest income group at 69.0% to the highest income group at 16.1%. The logistic regression model found that medical insurance, frequency of hospital admissions, charity assistance, and income level were significant predictors of CHE. Conclusion The results revealed that pediatric leukemia had a significant catastrophic effect on families, especially those with lower economic status. The occurrence of CHE in households living with pediatric leukemia could be reduced by addressing income disparity. In addition, extending coverage and improving compensation from medical insurance could also alleviate CHE. Some other measures that can be implemented are to address the barriers of charity assistance for vulnerable groups., Leukemia had a significant catastrophic effect on families, especially those with lower economic status. The occurrence of catastrophic health expenditure (CHE) in households living with pediatric leukemia could be reduced by addressing income disparity. In addition, extending coverage and improving reimbursement from medical insurance could also alleviate CHE. Some other measures that can be implemented are to address the barriers of charity assistance for vulnerable groups.

Supplemental Digital Content is available in the text., Background: Given the lack of specific antiviral drugs and effective vaccine for dengue infection, factors such as host nutritional status that may alter disease progression require investigation. This study examined the relationship between baseline nutritional status and severity of dengue infection in pediatric patients. Methods: Data from dengue patients 1–14 years of age treated at four hospitals in southern Thailand (2017–2018) were reviewed. Dengue infection was classified as dengue fever, dengue hemorrhagic fever and dengue shock syndrome. Children’s nutritional status was assessed based on international and national growth charts. Binary logistic regression was used to identify factors associated with dengue severity and malnutrition. Results: Overall, 248, 281 and 43 patients had dengue fever, dengue hemorrhagic fever and dengue shock syndrome, respectively. Overweight was associated with increased risk of dengue severity [odds ratio (OR) = 1.76, 95% confidence interval (CI): 1.13–2.75, P = 0.012; OR = 1.84, 95% CI: 1.09–3.09, P = 0.022, per international and national growth criteria, respectively). Stunting was associated with decreased risk of dengue severity (OR = 0.54, 95% CI: 0.33–0.88, P = 0.013; OR = 0.61, 95% CI: 0.39–0.95, P = 0.030, per international and national growth criteria, respectively). Being overweight was significantly and positively associated with levels of hemoglobin >14 g/dL, hematocrit >42%, hemoconcentration ≥20% and platelet count ≤50,000/mm3, whereas being stunted was significantly and negatively associated with levels of hemoglobin >14 g/dL and hematocrit >42%. Conclusions: These findings support a hypothesis that malnutrition might influence the severity of dengue infection through host immune response. Overweight children with dengue infections should be closely observed for early signs of severe dengue infection.

Introduction and objectives: Cases of viral hepatitis reported in Mexico are typically identified as hepatitis A, B and C. However, unspecified cases are reported annually. Hepatitis E virus (HEV) is an emergent agent that causes a self-limiting infection that can evolve to chronic in immunosuppressed individuals. In Mexico, HEV genotype 2 is considered endemic, though it's the prevalence is not well known. Therefore, the present study was designed to determine the prevalence of HEV among patients at the “Hospital Infantil de Mexico Federico Gomez”. Materials and methods: The study included 99 patients, anti-HEV antibody (IgG and IgM) were detected by indirect ELISA and viral genome was identified using RT-PCR technique. Two PCR products of positive cases were sequenced. Results: ELISA results were positive in 3% and 6%, for IgG and IgM respectively, 54.5% prevalence was found by PCR. Low lymphocyte count (p

Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets. c-miRNA profile was determined in serum of HF children by NGS before and one month after VAD-implant. The c-miRNA differentially expressed were analyzed by real time-PCR, before and at 4 hrs,1,3,7,14,30 days after VAD-implant. A miRNA mimic transfection study in HepG2 cells was performed to validate putative miRNA targets selected through miRWalk database. Thirteen c-miRNAs were modified at 30 days after VAD-implant compared to pre-VAD at NSG, and, among them, six c-miRNAs were confirmed by Real-TimePCR. Putative targets of the validated c-miRNAs are involved in the hemostatic process. The in vitro study confirmed a down-regulatory effect of hsa-miR-409-3p towards coagulation factor 7 (F7) and F2. Of note, all patients had thrombotic events requiring pump change. In conclusion, in HF children, the level of six c-miRNAs involved in the regulation of hemostatic events changed after 30 days of VAD-treatment. In particular, the lowering of c-miR-409-3p regulating both F7 and F2 could reflect a pro-thrombotic state after VAD-implant.

Hyperglycemic hyperosmolar syndrome (HHS) is a rare complication of diabetes mellitus among pediatric patients. Since its treatment differs from diabetic ketoacidosis (DKA), hence, pediatricians should be aware of its diagnosis and management.

Ventricular Assist Device (VAD) therapy is considered as a part of standard care for end-stage Heart Failure (HF) children unresponsive to medical management, but the potential role of miRNAs in response to VAD therapy on molecular pathways underlying LV remodeling and cardiac function in HF is unknown. The aims of this study were to evaluate the effects of VAD on miRNA expression profile in cardiac tissue obtained from HF children, to determine the putative miRNA targets by an in-silico analysis as well as to verify the changes of predicated miRNA target in the same cardiac samples. The regulatory role of selected miRNAs on predicted targets was evaluated by a dedicated in vitro study. miRNA profile was determined in cardiac samples obtained from 13 HF children [median: 29 months, 19 LVEF%, 9 Kg] by NGS before VAD implant (pre-VAD) and at the moment of heart transplant (Post-VAD). Only hsa-miR-199b-5p, hsa-miR-19a-3p, hsa-miR-1246 were differentially expressed at post-VAD when compared to pre-VAD, and validated by real-time PCR. Putative targets of the selected miRNAs were involved in regulation of sarcomere genes, such as cardiac troponin (cTns) complex. The expression levels of fetal ad adult isoforms of cTns resulted significantly higher after VAD in cardiac tissue of HF pediatric patients when compared with HF adults. An in vitro study confirmed a down-regulatory effect of hsa-miR-19a-3p on cTnC expression. The effect of VAD on sarcomere organization through cTn isoform expression may be epigenetically regulated, suggesting for miRNAs a potential role as therapeutic targets to improve heart function in HF pediatric patients.

Genetic alterations in the RUNX1 gene are associated with benign and malignant blood disorders, particularly of megakaryocyte and myeloid lineages. The role of RUNX1 in acute lymphoblastic leukemia (ALL) is less clear, particularly how germline genetic variation influences the predisposition to this type of leukemia. Sequencing 4,836 children with B-ALL and 1,354 cases of T-ALL, we identified 31 and 18 germline RUNX1 variants, respectively. RUNX1 variants in B-ALL consistently showed minimal damaging effects. By contrast, 6 T-ALL-related variants result in drastic loss of RUNX1 activity as a transcription activator in vitro. Ectopic expression of dominant-negative RUNX1 variants in human CD34+ cells repressed differentiation into erythroid, megakaryocytes, and T cells, while promoting myeloid cell development. Chromatin immunoprecipitation sequencing of T-ALL models showed distinctive patterns of RUNX1 binding by variant proteins. Further whole genome sequencing identified JAK3 mutation as the most frequent somatic genomic abnormality in T-ALL with germline RUNX1 variants. Co-introduction of RUNX1 variant and JAK3 mutation in hematopoietic stem and progenitor cells in mice gave rise to T-ALL with early T-cell precursor phenotype. Taken together, these results indicated that RUNX1 is an important predisposition gene for T-ALL and pointed to novel biology of RUNX1-mediated leukemogenesis in the lymphoid lineages.

Genetic disorders are a frequent cause of hospitalization, morbidity and mortality in pediatric patients, especially in the neonatal or pediatric intensive care unit (NICU/PICU). In recent years, rapid genome-wide sequencing (exome or whole genome sequencing) has been applied in the NICU/PICU. However, mtDNA sequencing is not routinely available in rapid genetic diagnosis programs, which may fail to diagnose mtDNA mutation-associated diseases. Herein, we explored the clinical utility of rapid exome sequencing combined with mtDNA sequencing in critically ill pediatric patients with suspected genetic disorders. Rapid clinical exome sequencing (CES) was performed as a first-tier test in 40 critically ill pediatric patients (aged from 6 days to 15 years) with suspected genetic conditions. Blood samples were also collected from the parents for trio analysis. Twenty-six patients presented with neuromuscular abnormalities or other systemic abnormalities, suggestive of suspected mitochondrial diseases or the necessity for a differential diagnosis of other diseases, underwent rapid mtDNA sequencing concurrently. A diagnosis was made in 18 patients (45.0%, 18/40); three cases with de novo autosomal dominant variants, ten cases with homozygous or compound heterozygous variants, three cases with hemizygous variants inherited from mother, three cases with heterozygous variants inherited from either parent, and one case with a mtDNA mutation. The 18 patients were diagnosed with metabolic (n = 7), immunodeficiency (n = 4), cardiovascular (n = 2), neuromuscular (n = 2) disorders, and others. Genetic testing reports were generated with a median time of 5 days (range, 3–9 days). Thirteen patients that were diagnosed had an available medical treatment and resulted in a positive outcome. We propose that rapid exome sequencing combined with mitochondrial DNA sequencing should be available to patients with suspected mitochondrial diseases or undefined clinical features necessary for making a differential diagnosis of other diseases.

Background: In April 2015, ivabradine was approved by the Food and Drug Administration for the treatment of patients with coronary artery disease and heart failure (HF). The use of this medication has been linked with improved clinical outcomes and reduced rates of hospitalization in patients with symptomatic HF and a baseline heart rate of 70 bpm and above. Nonetheless, little is known about the use of ivabradine in pediatric patients with supraventricular tachycardia (SVT). This use is not well-studied and is only endorsed by a few case reports and case series.Aim: This study discusses the off-label utilization of ivabradine in pediatric patients with SVT, and highlights its efficacy in treating treatment-resistant (refractory) SVT.Methods: We conducted a retrospective single-center observational study involving pediatric patients with SVT treated at our center between January 2016 and October 2020. We identified the total number of patients with SVT, and the number of patients with refractory SVT treated with Ivabradine. Similarly, we performed a thorough review of the databases of PubMed, Medline and Google Scholar to compare the clinical course of our patients to those described in the literature.Results: Between January 2016 and October 2020, 79 pediatric patients with SVT were seen and treated at our center. A treatment-resistant SVT was noted only in three patients (4%). Ivabradine was used in these patients as a single or combined therapy. The rest (96%) were successfully treated with conventional anti-arrhythmics such as β-blockers, flecainide, and other approved medications. In the ivabradine group, successful reversal to sinus rhythm was achieved in two of the three patients (66%), one patient was treated with a combination therapy of amiodarone and ivabradine, and the other patient was treated only with ivabradine.Conclusion: Overall, promissory results are associated with the use of ivabradine in pediatric patients with refractory SVT. Ivabradine appears to be a safe and well-tolerated medication that can induce adequate suppression of SVT, complete reversal to sinus rhythm, and effective enhancement of left ventricular function.

Purpose: To evaluate extravascular findings on thoracic MDCT angiography in secondary pulmonary vein stenosis (PVS) due to total anomalous pulmonary venous connection (TAPVC) repair in children. Materials and Methods: All patients aged ≤18 years with a known diagnosis of secondary PVS after TAPVC repair, confirmed by echocardiography, conventional angiography, and/or surgery, who underwent thoracic MDCT angiography studies between July 2008 and April 2021 were included. Two pediatric radiologists independently examined MDCT angiography studies for the presence of extravascular thoracic abnormalities in the lung, pleura, and mediastinum. The location and distribution of each abnormality (in relation to the location of PVS) were also evaluated. Interobserver agreement between the two independent pediatric radiology reviewers was studied using kappa statistics. Results: The study group consisted of 20 consecutive pediatric patients (17 males, 3 females) with secondary PVS due to TAPVC repair. Age ranged from 2 months to 8 years (mean, 16.1 months). In children with secondary PVS due to TAPVC repair, the characteristic extravascular thoracic MDCT angiography findings were ground-glass opacity (19/20, 95%), septal thickening (7/20, 35%), pleural thickening (17/20, 85%), and a poorly defined, mildly heterogeneously enhancing, non-calcified soft tissue mass (17/20, 85%) which followed the contours of affected pulmonary veins outside the lung. There was excellent interobserver kappa agreement between two independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (k = 0.99). Conclusion: Our study characterizes the extravascular thoracic MDCT angiography findings in secondary pediatric PVS due to TAPVC repair. In the lungs and pleura, ground-glass opacity, interlobular septal thickening, and pleural thickening are common findings. Importantly, the presence of a mildly heterogeneously enhancing, non-calcified mediastinal soft tissue mass in the distribution of the PVS is a novel characteristic thoracic MDCT angiography finding seen in pediatric secondary PVS due to TAPVC repair.

Intraoperative trans-esophageal echocardiography (TEE) is an important monitoring and diagnostic tool used during surgery for the repair of congenital heart lesions. Its ability to be used intraoperatively before and after cardiac repair makes it a unique tool. Although it is generally a safe procedure, due to the relatively large size and rigid nature of TEE probes airway complications, inadvertent extubation and insertion failures have been reported to occur predominantly in smaller patients (mean weight

Introduction/Objective. The aim of this study was to report visual, refractive, and tomographic outcomes of corneal collagen cross-linking (CXL) in pediatric keratoconus. Methods. This retrospective study included 17 eyes of 12 patients with progressive keratoconus who underwent epithelium-off CXL at the age ? 18 years. Following data were analyzed at baseline and postoperatively at one, three, six, nine, 12 months for all the patients, and annually where available: uncorrected distant visual acuity (UDVA) and best spectacle-corrected distant visual acuity (CDVA), refraction and corneal tomography. Results. Mean UDVA improved significantly from 0.52 ? 0.38 at baseline to 0.24 ? 0.29 logarithm of minimum angle resolution (log MAR) at one year (p = 0.011) and remained stable at two-year follow-up (0.21 ? 0.34 log MAR). Mean CDVA was 0.15 ? 0.21 at baseline and 0.06 ? 0.13 log MAR at one year (p = 0.248). Maximum keratometry showed a significant flattening of 1.30 ? 1.99 D (p = 0.011) after a year and remained stable two years after CXL. Minimum keratometry significantly decreased with a mean change of 1.34 ? 1.37 (p = 0.001). Mean reduction of corneal thickness after CXL was 55.35 ? 64.42 ?m (P=0.003). After a year, seven (42%) eyes showed Kmax regression, nine (53%) stabilization, and one (5%) progression. Conclusion. In our study CXL effectively prevented progression of keratoconus in 95% of pediatric patients after a year, while improving UDVA and keratometry values. One patient with eye rubbing behavior showed signs of keratoconus progression after CXL treatment.

The aim of the study was to validate the impact of the single-nucleotide polymorphism rs2413739 (T > C) in the PACSIN2 gene on thiopurines pharmacological parameters and clinical response in an Italian cohort of pediatric patients with acute lymphoblastic leukemia (ALL) and inflammatory bowel disease (IBD). In ALL, PACSIN2 rs2413739 T allele was associated with a significant reduction of TPMT activity in erythrocytes (p = 0.0094, linear mixed-effect model, multivariate analysis considering TPMT genotype) and increased severe gastrointestinal toxicity during consolidation therapy (p = 0.049). A similar trend was present also for severe hematological toxicity during maintenance. In IBD, no significant effect of rs2413739 could be found on TPMT activity, howeverazathioprine effectiveness was reduced in patients carrying the T allele (linear mixed effect, p = 0.0058). In PBMC from healthy donors, a positive correlation between PACSIN2 and TPMT protein concentration could be detected (linear mixed effect, p = 0.045). These results support the role of PACSIN2 polymorphism on TPMT activity and mercaptopurine adverse effects in patients with ALL. Further evidence on PBMC and pediatric patients with IBD supports an association between PACSIN2 variants, TPMT activity, and thiopurines effects, even if more studies are needed since some of these effects may be tissue specific.

Purpose The aim of our study was to evaluate the efficacy and safety of epi-off conventional and accelerated corneal collagen cross-linking in the treatment of progressive keratoconus in pediatric patients up to 4 years after treatment. Patients and methods Conventional (standard) CXL epi-off technique was performed in 37 eyes (S-CXL group) and accelerated CXL in 27 eyes (A-CXL group). Refraction, keratometry, cylindrical equivalent, spherical equivalent, slit lamp examination, pachymetry, corneal tomography, anterior segment ocular coherence tomography and visual acuity were performed up to 4 years. Results In the S-CXL group: the flat K values decreased from 47.41±3.39 D to 45.36±3.62 D at 4 years (p=0.004); steep K decreased from 51.98±4.11 to 50.21±4.81 D at 4 years (p=0.0078); mean K decreased with 1.99 D at 4 years (p=0.009). In the A-CXL group: the flat K values decreased from 46.97±4.17 D to 44.97±4.24 D at 4 years (p=0.048); steep K decreased from 50.55±4.10 D to 48.75±4.17 D at 4 years (p=0.0287); mean K decreased from 48.79±3.86 D to 46.86±4.11 D at 4 years (p=0.0356). The preoperative mean UCVA in the S-CXL group was 0.8 ±0.23 logMar and improved during the follow-up reaching 0.65 ±0.24 logMar at 4 years (p=0.072). The baseline mean UCVA in A-CXL group was 0.77±0.25 logMar and increased during the follow-up to 0.63 ±0.25 logMar at 4 years (p=0.0039). A similar improvement of BCVA was observed during the follow-up. Conclusion Epi-off conventional and accelerated CXL are efficient procedures for progressive keratoconus in pediatric patients. Accelerated and conventional CXL were comparable at all time points and both represent viable options for the therapy of KC in these patients.

The safety and efficacy of OPA‐15406 (international non‐proprietary name, difamilast; also referred to as MM36), a new topical, selective phosphodiesterase type‐4 inhibitor, in Japanese pediatric patients with atopic dermatitis aged 2–14 years were evaluated in a phase 2, randomized, double‐blind, vehicle‐controlled, 4‐week study. Seventy‐three patients were randomized 1:1:1 to receive OPA‐15406 0.3%, OPA‐15406 1% or vehicle ointment twice daily for 4 weeks. The mean age of patients was similar across treatment groups. No deaths or serious treatment‐emergent adverse events were reported; all treatment‐emergent adverse events were mild or moderate in severity. The incidence of treatment‐emergent adverse events leading to treatment discontinuation was 4.2% (1/24) in the OPA‐15406 0.3% group, 4.0% (1/25) in the OPA‐15406 1% group and 16.7% (4/24) in the vehicle group, all of which were worsening of atopic dermatitis. Both OPA‐15406 groups demonstrated a higher incidence of success in the Investigator Global Assessment score compared with the vehicle group over the 4‐week study. The OPA‐15406 groups also showed greater improvements from baseline compared with the vehicle group in the Investigator Global Assessment score, Eczema Area and Severity Index overall score and subscale (erythema, induration/papulation, excoriation and lichenification) scores, Visual Analog Scale pruritus score, Patient‐Oriented Eczema Measure score, and percentage of affected body surface area over the 4‐week study. Topical OPA‐15406 twice daily for 4 weeks was considered a safe and effective treatment option in this phase 2 study in pediatric patients with atopic dermatitis, and phase 3 development is currently ongoing.

Background: Data on pediatric DBS is still limited because of small numbers in single center series and lack of systematic multi-center trials. Objectives: We evaluate short- and long-term adverse events (AEs) of patients undergoing deep brain stimulation (DBS) during childhood and adolescence. Methods: Data collected by the German registry on pediatric DBS (GEPESTIM) were analyzed according to reversible and irreversible AEs and time of occurrence with relation to DBS-surgery: Intraoperative, perioperative (6 months). Results: 72 patients with childhood-onset dystonia from 10 DBS-centers, who received 173 DBS electrodes and 141 implantable pulse generators (IPG), were included in the registry. Mean time of postoperative follow-up was 4.6 ± 4 years. In total, 184 AEs were documented in 53 patients (73.6%). 52 DBS-related AEs in 26 patients (36.1%) required 45 subsequent surgical interventions 4.7 ± 4.1 years (range 3 months–15 years) after initial implantation. The total risk of an AE requiring surgical intervention was 7.9% per electrode-year. Hardware-related AEs were the most common reason for surgery. There was a tendency of a higher rate of AEs in patients aged 7–9 years beyond 6 months after implantation. Discussion: The intraoperative risk of AEs in pediatric patients with dystonia undergoing DBS is very low, whereas the rate of postoperative hardware-related AEs is a prominent feature with a higher occurrence compared to adults, especially on long-term follow-up. Conclusion: Factors leading to such AEs must be identified and patient management has to be focused on risk minimization strategies in order to improve DBS therapy and maximize outcome in pediatric patients.

Background: Sevoflurane is generally the preferred anesthetic agent for general anesthesia in pediatric patients, due to its rapid induction and recovery characteristics. However, it has been recognized that a major complication is emergence agitation when awakening from general anesthesia. The aim of this study was to evaluate the occurrence rate of emergence agitation in the operating room and postoperative recovery area following intraoperative administration of midazolam to pediatric patients under general anesthesia. Patients and methods: One hundred and twenty pediatric patients undergoing dental treatment under sevoflurane anesthesia were enrolled in this study. The patients were divided into three groups (n=40 each in the 0.1 mg/kg midazolam, 0.05 mg/kg midazolam, and control with saline groups). Midazolam or saline was injected intravenously approximately 30 minutes before the end of the dental treatment. We used the Richmond Agitation and Sedation Scale (RASS) to assess the level of sedation and drowsiness at emergence phase in the operating room. We also used the Pediatric Anesthesia Emergence Delirium Scale (PAED) to assess the level of agitation and delirium at the full recovery phase from anesthesia in the recovery area. Results:At the emergence phase, the incidence of emergence agitation in the 0.1 mg/kg midazolam group was significantly lower than in the other groups (p=0.0010). At the recovery phase, there was no significant difference among the three groups. The odds ratio between PAED score and RASS score was 4.0 using logistic regression analysis. The odds ratio between PAED score and Disability was 2.5. Conclusion: Administration of a single dose of 0.1 mg/kg midazolam dose significantly decreases the incidence of severe emergence agitation at the emergence after sevoflurane anesthesia, but not at the recovery phase. Furthermore, the evaluation of sedative and agitation condition using RASS score at emergence from anesthesia is useful to predict occurrence of agitation in the recovery phase., Drug Design, Development and Therapy, 13, pp.1729-1737; 2019

Background Patients with hereditary angioedema with C1 inhibitor deficiency or dysfunction have burdensome recurrent angioedema attacks. The safety, efficacy, and health-related quality of life (HRQoL) outcomes of C1 inhibitor (C1-INH) prophylaxis (intravenously administered) in patients aged 6-11 years were investigated. Methods Eligible patients were enrolled in a randomized, single-blind, crossover, phase 3 trial. After a 12-week baseline observation period (BOP), patients received 500 or 1000 U C1-INH, twice weekly, for 12 weeks before crossing over to the alternate dose for 12 weeks. The primary efficacy end-point was the monthly normalized number of angioedema attacks (NNA). HRQoL was assessed using the EuroQoL 5-dimensional descriptive system youth version and visual analog scale (EQ-VAS). Results Twelve randomized patients had a median (range) age of 10.0 (7-11) years. Mean (SD) percentage reduction in monthly NNA from BOP was 71.1% (27.1%) with 500 U and 84.5% (20.0%) with 1000 U C1-INH. Mean (SD) within-patient difference (-0.4 [0.58]) for monthly NNA with both doses was significant (P = 0.035 [90% CI, -0.706 to -0.102]). Cumulative attack severity, cumulative daily severity, and number of acute attacks treated were reduced. No serious adverse events or discontinuations occurred. Mean EQ-VAS change from BOP to week 9 of treatment (500 U C1-INH, 10.4; 1000 U C1-INH, 21.6) was greater than the minimal important difference, indicating a meaningful HRQoL change. Conclusions C1-INH prophylaxis was effective, safe, and well tolerated in children aged 6-11 years experiencing recurrent angioedema attacks. A post hoc analysis indicated a meaningful improvement in HRQoL with C1-INH. Trial registration ClinicalTrials.gov identifier NCT02052141.

BACKGROUNDBenign vascular lesions of the skin, hemangiomas and pyogenic granulomas are quite common in pediatric patients, which are complicated with bleeding in 7.5% of cases.MATERIAL AND METHODSIn 2016–2018, 17 children with cavernous hemangiomas and pyogenic granulomas complicated with bleeding were operated on an emergency basis at the Research Institute of Emergency Children’s Surgery and Traumatology. Surgical intervention for all patients was performed using the method of interstitial selective laser photodestruction developed by the RIECST, which took out the utility patent. This method was implemented using two wave laser surgical device IPG “IRE-Polus” (Russia), generating two wavelengths of laser radiation of 0.97 μm and 1.56 μm.RESULTSThe analysis of the long-term results of treatment in 17 pediatric patients who were operated on an emergency basis for hemangioma and pyogenic granuloma complicated by bleeding showed that all 17 patients (100%) had a good clinical and aesthetic result. The method of interstitial selective laser photodestruction provided a radical removal with guaranteed hemostasis of the indicated benign vascular lesions of the skin complicated with bleeding illustrate the effectiveness of this method in clinical practice, as well as the possibility of its use in inpatient and outpatient conditions.CONCLUSIONTo prevent the large blood loss in hemangiomas complicated by bleeding and pyogenic granulomas of the skin in children, emergency surgical treatment has been performed using interstitial selective laser photodestruction. This method ensures the radical photodestruction of tissues of a pathological vascular formation and reliable hemostasis, which guarantees the achievement of a good clinical and aesthetic result of treatment in inpatient and outpatient conditions in all cases.

Background: Meniscal repair is desirable over resection to prevent postmeniscectomy arthritis, especially among young and active patients. However, long-term data are currently lacking following isolated meniscal repair, particularly in the pediatric population. Purpose/Hypothesis: To report long-term follow-up of isolated meniscal tears treated by meniscal repair in a pediatric and adolescent population and to compare those results with previous midterm follow-up data reported. The authors hypothesized that these patients would have satisfactory function and reoperation rates at long-term follow-up. Study Design: Case series; Level of evidence, 4. Methods: Forty-four patients aged ≤18 years undergoing repair of an isolated meniscal tear (without concomitant anterior cruciate ligament injury) between 1990 and 2005 were included. At the time of final follow-up, recurrent tear, reoperations, and International Knee Documentation Committee (IKDC) and Tegner scores were determined. With logistic regression, the overall failure among tear types was calculated. Wilcoxon rank sum analysis were performed to calculate the differences in clinical outcome for different time points, and Spearman coefficients were calculated for Tegner and IKDC with different variables. Results: At a mean follow-up of 17.6 years (range, 13.1-25.9 years), 32 patients with 33 isolated meniscal repairs (29 male, 3 female) with a mean age of 16.1 years (range, 9.9-18.7 years) at surgery were included in this study. At early follow-up, the overall failure rate was 14 of 33 (42%); complex tears (80%) and bucket-handle tears (47%) had higher overall failure rates when compared with simple tears (18.2%), although only complex tears had a significantly higher failure rate. However, no further failures occurred since midterm follow-up with any tear type. At final follow-up, the mean IKDC score was 92.3, which was significantly increased when compared with preoperative (65.3, P < .0001) and midterm (90.2, P = .01) scores. The mean Tegner score (6.5) was significantly lower than both preoperative (8.3, P < .0001) and midterm (8.4, P < .0001) scores. There was no difference in Tegner or IKDC score for patients with successful versus failed repair. Conclusion: In conclusion, while there was a high early failure rate, this study demonstrated overall good to excellent long-term clinical outcomes after isolated meniscal repair in an adolescent population, even for those requiring reoperation. Early failure and reoperation rates were variable, depending on tear type, with complex multiplanar tears having more failures at short-term follow-up. However, at long-term follow-up, IKDC and Tegner scores were not significantly different for those with complex tears as compared with other tear types.

Background: Acute kidney injury (AKI) after cardiac surgery contributes to adverse outcomes. We aimed to assess the incidence and identify the predictors for persistent AKI after total cavopulmonary connection (TCPC) surgery.Methods: A retrospective study, including 465 children undergoing TCPC surgery from 2010 to 2019, was conducted. We used pRIFLE criteria to define AKI and defined persistent AKI as AKIs occurring between post-operative day1 (POD1) and POD3 and sustaining at least on POD7. Univariate and multivariate logistic regressions were applied to analyze the predictors for persistent AKI.Results: A total of 35.3% patients developed AKI between POD1 to POD3 and 15.5% patents had persistent AKI after TCPC. Patients with persistent AKI had prolonged mechanical ventilation and ICU stay, and had higher rates of renal replacement treatment and reintubation, which was associated with higher hospitalization costs and in-hospital mortality. The independent predictors for persistent AKI were peripheral oxygen saturation (SpO2) upon admission, intraoperative fluid balance, POD0 maximal lactic acid, renal perfusion pressure (RPP), POD0 estimated glomerular filtration rate and POD0 total bilirubin. The areas under receiver operating characteristic curve (AUC) in the total cohort and the subgroup undergoing TCPC surgery after 2017 were 0.75 (95% CI, 0.66–0.82) and 0.87 (95% CI, 0.77–0.97), respectively. The acceptable AUCs (nearly 0.7) were achieved in other 5 subgroups and good calibration ability (p ≥ 0.05) were achieved in the total cohort and all six subgroups.Conclusions: Persistent AKI after TCPC was common and strongly associated with poorer in-hospital outcomes in Chinese pediatric patients. Six perioperative variables, including SpO2, intraoperative fluid balance, POD0 maximal lactic acid, RPP, POD0 moderate-to-severe kidney injury and POD0 total bilirubin, were identified as independent predictors for persistent AKI. Our findings may help to perform an early risk stratification for these vulnerable patients and improve their outcomes.

BackgroundThe pandemic of Coronavirus Disease 2019 (COVID-19) brings new challenges for pediatricians, especially in the differentiation with non-COVID-19 pneumonia in the peak season of pneumonia. We aimed to compare the clinical characteristics of pediatric patients with COVID-19 and other respiratory pathogens infected pneumonias.MethodsWe conducted a multi-center, cross-sectional study of pediatric inpatients in China. Based on pathogenic test results, pediatric patients were divided into three groups, including COVID-19 pneumonia group, Non-COVID-19 viral (NCV) pneumonia group and Non-viral (NV) pneumonia group. Their clinical characteristics were compared by Kruskal-Wallis H test or chi-square test.ResultsA total of 636 pediatric pneumonia inpatients, among which 87 in COVID-19 group, 194 in NCV group, and 355 in NV group, were included in analysis. Compared with NCV and NV patients, COVID-19 patients were older (median age 6.33, IQR 2.00-12.00 years), and relatively fewer COVID-19 patients presented fever (63.2%), cough (60.9%), shortness of breath (1.1%), and abnormal pulmonary auscultation (18.4%). The results were verified by the comparison of COVID-19, respiratory syncytial virus (RSV) and influenza A (IFA) pneumonia patients. Approximately 42.5%, 44.8%, and 12.6% of the COVID-19 patients presented simply ground-glass opacity (GGO), simply consolidation, and the both changes on computed tomography (CT) scans, respectively; the proportions were similar as those in NCV and NV group (p>0.05). Only 47.1% of COVID-19 patients had both lungs pneumonia, which was significantly lower than that proportion of nearly 80% in the other two groups. COVID-19 patients presented lower proportions of increased white blood cell count (16.5%) and abnormal procalcitonin (PCT) (10.7%), and a higher proportion of decreased lymphocyte count (44.0%) compared with the other two groups.ConclusionMajority clinical characteristics of pediatric COVID-19 pneumonia patients were milder than non-COVID-19 patients. However, lymphocytopenia remained a prominent feature of COVID-19 pediatric pneumonia.

Background A predictive model for risk of Mycoplasma pneumoniae (MP)-related hepatitis in MP pneumonia pediatric patients can improve treatment selection and therapeutic effect. However, currently, no predictive model is available. Methods Three hundred seventy-four pneumonia pediatric patients with/without serologically-confirmed MP infection and ninety-three health controls were enrolled. Logistic regressions were performed to identify the determinant variables and develop predictive model. Predictive performance and optimal diagnostic threshold were evaluated using area under the receiver operating characteristic curve (AUROC). Stratification analysis by age and MP-IgM titer was used to optimize model’s clinical utility. An external validation set, including 84 MP pneumonia pediatric patients, was used to verify the predictive efficiency. After univariate analysis to screen significant variables, monocyte count (MO), erythrocyte distribution width (RDW) and platelet count (PLT) were identified as independent predictors in multivariate analysis. Results We constructed MRP model: MO [^109/L] × 4 + RDW [%] – PLT [^109/L] × 0.01. MRP achieved an AUROC of 0.754 and the sensitivity and specificity at cut-off value 10.44 were 71.72 and 61.00 %, respectively in predicting MP-related hepatitis from MP pneumonia. These results were verified by the external validation set, whereas it merely achieved an AUROC of 0.540 in pneumonia without MP infection. The AUROC of MRP was 0.812 and 0.787 in infants and toddlers (0–36 months) and low MP-IgM titer subgroup (1:160–1:320), respectively. It can achieve an AUROC of 0.804 in infants and toddler with low MP-IgM titer subgroup. Conclusions MRP is an effective predictive model for risk of MP-related hepatitis in MP pneumonia pediatric patients, especially infants and toddlers with low MP-IgM titer.

To retrospectively investigate the extravascular thoracic MDCT angiography findings of pulmonary vein stenosis (PVS) in children with a cardiac septal defect. Materials and Methods: Pediatric patients (age ≤ 18 years) with cardiac septal defect and PVS, confirmed by echocardiogram and/or conventional angiography, who underwent thoracic MDCT angiography studies from April 2009 to April 2021 were included. Two pediatric radiologists independently evaluated thoracic MDCT angiography studies for the presence of extravascular thoracic abnormalities in: (1) lung and airway (ground-glass opacity (GGO), consolidation, pulmonary nodule, mass, cyst, septal thickening, fibrosis, and bronchiectasis), (2) pleura (pleural thickening, pleural effusion, and pneumothorax), and (3) mediastinum (mass and lymphadenopathy). Interobserver agreement between the two independent pediatric radiology reviewers was evaluated with kappa statistics. Results: The final study group consisted of 20 thoracic MDCT angiography studies from 20 consecutive individual pediatric patients (13 males (65%) and 7 females (35%), mean age: 7.5 months, SD: 12.7, range: 2 days to 7 months) with cardiac septal defect and PVS. The characteristic extravascular thoracic MDCT angiography findings were GGO (18/20, 90%), septal thickening (9/20, 45%), pleural thickening (16/20, 80%), and ill-defined, mildly heterogeneously enhancing, non-calcified soft tissue mass (9/20, 45%) following the contours of PVS in the mediastinum. There was a high interobserver kappa agreement between two independent reviewers for detecting extravascular abnormalities on thoracic MDCT angiography studies (k = 0.99). Conclusion: PVS in children with a cardiac septal defect has a characteristic extravascular thoracic MDCT angiography finding. In the lungs and pleura, GGO, septal thickening, and pleural thickening are frequently seen in children with cardiac septal defect and PVS. In the mediastinum, a mildly heterogeneously enhancing, non-calcified soft tissue mass in the distribution of PVS in the mediastinum is seen in close to half of the pediatric patients with cardiac septal defect and PVS.

Hepatitis E virus (HEV) infection is a polymorphic condition, present throughout the world and involving children and adults. Multiple studies over the last decade have contributed to a better understanding of the natural evolution of this infection in various population groups, several reservoirs and transmission routes being identified. To date, acute or chronic HEV-induced hepatitis has in some cases remained underdiagnosed due to the lower accuracy of serological tests and due to the evolutionary possibility with extrahepatic manifestations. Implementation of diagnostic tests based on nucleic acid analysis has increased the detection rate of this disease. The epidemiological and clinical features of HEV hepatitis differ depending on the geographical areas studied. HEV infection is usually a self-limiting condition in immunocompetent patients, but in certain categories of vulnerable patients it can induce a sudden evolution toward acute liver failure (pregnant women) or chronicity (immunosuppressed patients, post-transplant, hematological, or malignant diseases). In acute HEV infections in most cases supportive treatment is sufficient. In patients who develop chronic hepatitis with HEV, dose reduction of immunosuppressive medication should be the first therapeutic step, especially in patients with transplant. In case of unfavorable response, the initiation of antiviral therapy is recommended. In this review, the authors summarized the essential published data related to the epidemiological, clinical, paraclinical, and therapeutic aspects of HEV infection in adult and pediatric patients.

Background Prevalent symptoms that affect children and adolescents throughout the process of cancer diagnosis and treatment include nausea and vomiting, fatigue, pain, mucositis, and anxiety. Aim To examine the effect of a home‐based multimodal symptom‐management program for alleviation of nausea and vomiting, fatigue, pain, mucositis, and anxiety in children and adolescents undergoing chemotherapy for hematological malignancies or solid tumors. Methods In an exploratory pilot randomized study with qualitative interview, patients between 10 and 18 years of age were randomly assigned to either the symptom‐management program plus usual care (intervention group) or usual care (control group). The program consisted of multiple nonpharmacological interventional components. The targeted symptoms were measured at baseline (after diagnosis), at the first 2 weeks of each cycle of chemotherapy, and at 6 months after baseline, using the Memorial Symptom Assessment Scale 10‐18 and the State Anxiety Scale for Children. Results Fifty children (31 boys; mean age, 13.7 years) were randomized either to the intervention group or the control group (25 each) and underwent baseline assessment. A comparison between the groups showed that the intervention group had a significant less fatigue over time (P

We evaluated mycophenolic acid (MPA) limited sampling strategies (LSSs) established using multiple linear regression (MLR) in children with nephrotic syndrome treated with mycophenolate mofetil (MMF). MLR-LSS is an easy-to-determine approach of therapeutic drug monitoring (TDM). We assessed the practicability of different LSSs for the estimation of MPA exposure as well as the optimal time points for MPA TDM. The literature search returned 29 studies dated 1998–2020. We applied 53 LSSs (n = 48 for MPA, n = 5 for free MPA [fMPA]) to predict the area under the time-concentration curve (AUCpred) in 24 children with nephrotic syndrome, for whom we previously determined MPA and fMPA concentrations, and compare the results with the determined AUC (AUCtotal). Nine equations met the requirements for bias and precision ±15%. The MPA AUC in children with nephrotic syndrome was predicted the best by four time-point LSSs developed for renal transplant recipients. Out of five LSSs evaluated for fMPA, none fulfilled the ±15% criteria for bias and precision probably due to very high percentage of bound MPA (99.64%). MPA LSS for children with nephrotic syndrome should include blood samples collected 1 h, 2 h and near the second MPA maximum concentration. MPA concentrations determined with the high performance liquid chromatography after multiplying by 1.175 may be used in LSSs based on MPA concentrations determined with the immunoassay technique. MPA LSS may facilitate TDM in the case of MMF, however, more studies on fMPA LSS are required for children with nephrotic syndrome.

Background Although regional cerebral oxygen saturation (rScO2) monitoring has been widely used in clinical practice, the relationship between hemoglobin (dHB) content and rScO2 is incompletely understood. The aim of this study was to analyze the effect of hemoglobin content on rScO2 in pediatric patients undergoing general anesthesia for correction of scoliosis. Methods Ninety-two pediatric patients aged 3 to 14 years undergoing scoliosis correction surgery were enrolled. Continuous monitoring of bilateral regional cerebral oxygen saturation by near-infrared spectroscopy (NIRS, CASMED, USA) was performed after entering the operation room. rScO2 was recorded when the patients entered the operating room (T0, baseline), after anesthesia induced intubation (T1), and after radial artery puncture (T2). The lowest value of rScO2 during surgery was also recorded. The arterial blood pressure (ABP), heart rate (HR), pulse oxygen saturation (SpO2), end tidal carbon dioxide partial pressure (PetCO2) were continuously recorded. Patients were classified as low rScO2 or high rScO2 group according to whether the lowest intraoperative rScO2 was 15% lower than the baseline value. An analysis and comparison of differences in hemoglobin content in these two groups was carried out. Results The preoperative hemoglobin-postoperative hemoglobin of patients in the high rScO2 group was significantly lower than that in the low rScO2 group (t = − 7.86, p 2 group (t = − 6.05, p 2 group (t = 4.27, p Conclusions The decrease in hemoglobin level which occurs during surgery leads to a decrease in cerebral oxygen saturation. In order to ensure patient safety during surgery, it is necessary to carry out volume management and appropriate transfusion and fluid replacement in a timely manner. Trial registration Chinese Clinical Trial Registry, ChiCTR1800016359. Registered 28 May 2018.

Highlights • We investigated trends in ASM prescriptions with children in Japan during 2013–2019. • Valproic acid, carbamazepine, and levetiracetam were most commonly prescribed. • A decline in valproic acid and carbamazepine prescriptions was observed. • An increase in levetiracetam prescriptions was observed. • ASM prescription in Japan has shifted toward the use of recently available ASMs., Temporal trends in prescriptions of anti-seizure medicines (ASMs) for children, including newer ASMs, are unclear. We investigated ASM prescription trends for pediatric outpatients in Japan. The MDV analyzer® was used to analyze the MDV database containing de-identified hospital administrative data. Administrative data as of June 2021 including pediatric outpatients (0–17 years) with epilepsy, visiting 123 acute diagnostic procedure combination hospitals during 2013–2019, were used. Annual ASMs prescription trends were calculated, based on proportions. The Cochran–Armitage trend test evaluated the proportion of prescriptions for each ASM. ASMs most often prescribed were valproic acid, carbamazepine, and levetiracetam, regardless of sex. In girls, the proportion of valproic acid and carbamazepine prescriptions decreased from 37.93% to 26.84%, and from 24.80% to 15.78%, respectively (p

Background: Alagille syndrome (ALGS) is a highly variable multisystem disorder inherited in an autosomal dominant pattern with incomplete penetration. The disorder is caused by mutations in the JAG1 gene, only rarely in the NOTCH2 gene, which gives rise to malformations in multiple organs. Bile duct paucity is the main characteristic feature of the disease. Methods: Molecular-genetic examination of genes JAG1 and NOTCH2 in four probands of Czech origin who complied with the diagnostic criteria of ALGS was performed using targeted next-generation sequencing of genes JAG1 and NOTCH2. Segregation of variants in a family was assessed by Sanger sequencing of parental DNA. Results: Mutations in the JAG1 gene were confirmed in all four probands. We identified two novel mutations: c.3189dupG and c.1913delG. Only in one case, the identified JAG1 mutation was de novo. None of the parents carrying JAG1 pathogenic mutation was diagnosed with ALGS. Conclusion: Diagnosis of the ALGS is complicated due to the absence of clear genotype-phenotype correlations and the extreme phenotypic variability in the patients even within the same family. This fact is of particular importance in connection to genetic counselling and prenatal genetic testing.

Jin-qiao Liu, Wen-juan Chen, Meng-jie Zhou, Wen-feng Li, Ju Tang Department of Ultrasound, Hunan Children’s Hospital, Changsha City, Hunan Province, People’s Republic of ChinaCorrespondence: Wen-juan ChenDepartment of Ultrasound, Hunan Children’s Hospital, No. 86 Ziyuan Road, Changsha City, Hunan Province, 410007, People’s Republic of ChinaTel + 86-13707484196Email cwj299979@aliyun.comBackground: Ischemic-type biliary lesions (ITBL) are accepted as the most incomprehensible biliary complications after living-donor liver transplantation (LDLT). Early predicting the development of ITBL in pediatric patients permits more preventive strategies. However, few studies have focused on the early prediction of ITBL.Objective: This study aimed to establish a nomogram including ultrasound-based multimodal imaging to predict ITBL in children with biliary atresia (BA) within 2 years after receiving LDLT.Methods: The records of 94 BA children with at least one year of follow-up after LDLT were reviewed retrospectively. They were randomly divided into a training cohort for constructing a nomogram (n=64) and a validation cohort (n=30). In the training cohort, patients diagnosed as ITBL were included in the ITBL group and those without any vascular and biliary complication were included in the non-ITBL group. Multivariate Cox regression was used for the establishment of the nomogram in predicting the risk of ITBL within 2 years post-LDLT. The discrimination and calibration of the nomogram were internally and externally validated. The performances of the nomogram and the individual components were compared by the area under the curve (AUC) of receiver operating characteristic (ROC) curve.Results: In the training cohort, 18 BA children were included in the ITBL group and 46 were in the non-ITBL group. Last pediatric end-stage liver disease (PELD) score, gamma-glutamyl transpeptidase (GGT), resistive index (RI), and liver stiffness measurement (LSM) were the independent predictors for the development of ITBL within 2 years post-LDLT. The nomogram incorporating these independent predictors showed good discrimination and calibration by the internal and external validation. Its performance was better than any individual component in predicting the prognosis (P < 0.05).Conclusion: The established nomogram may be used to predict the risk of ITBL within 2 years post-LDLT in BA children.Keywords: ischemic-type biliary lesions, living-donor liver transplantation, pediatric patients, biliary atresia, color Doppler flow imaging, liver stiffness measurement

A high prevalence of multidrug-resistant (MDR) pathogens has been reported in adult and pediatric populations of Pakistan. However, data describing the effect of MDR microbes on the gut microbiota is scarce. We designed a cross-sectional pediatric study to investigate the effect of MDR microbes’ infection on the gut microbiome and its resistome of children using high-throughput next-generation sequencing (NGS). A cross-sectional study was conducted at a tertiary health care hospital in Peshawar Pakistan, between 5 September 2019 to 15 February 2020. Pediatric patients with acute gastroenteritis (n = 200) were enrolled. All the enrolled pediatric patients underwent initial antimicrobial resistance (AMR) screening using the disk diffusion method. Children with MDR infections were identified and selected for gut microbiome and its resistome profiling using NGS. Out of 200 enrolled pediatric patients, 80 (40%) were found infected with MDR diarrheagenic Enterobacteriaceae consisting of 50 (62.5%) infections caused by extended-spectrum beta-lactamase (ESBL) producing E. coli while 30 (37.5%) by MDR Enterobacter specie. A total of 63 and 17 antibiotic-resistant genes (ARGs) conferring resistance to 7 and 5 classes of antibiotics were identified in the resistomes of MDR diarrheagenic Enterobacteriaceae infected and healthy children, respectively. NGS-based gut microbial profiling of MDR Enterobacter spp., ESBL producing E. coli infected pediatric patients and healthy controls revealed the predominance of Proteobacteria and Actinobacteria, respectively. An increased abundance of several pathogenic gram-negative bacteria namely E. coli, Enterobacter cloacae, and Salmonella enterica was observed in the gut microbiota of children infected with MDR bacterial infections than that of the healthy controls. This work indicates that children with MDR infections have reduced microbial diversity and enriched ARGs than healthy controls. The emergence of MDR bacterial strains and their association with gut dysbiosis needs immediate attention to regulate antibiotics usage in Pakistani children.

Bloodstream infections (BSI) are a severe complication of antineoplastic chemotherapy or hematopoietic stem cell transplantation (HSCT), especially in the presence of antibiotic resistance (AR). A multinational, multicenter retrospective study in patients aged ≤ 18 years, treated with chemotherapy or HSCT from 2015 to 2017 was implemented to analyze AR among non-common skin commensals BSI. Risk factors associated with AR, intensive care unit (ICU) admission and mortality were analyzed by multilevel mixed effects or standard logistic regressions. A total of 1291 BSIs with 1379 strains were reported in 1031 patients. Among Gram-negatives more than 20% were resistant to ceftazidime, cefepime, piperacillin-tazobactam and ciprofloxacin while 9% was resistant to meropenem. Methicillin-resistance was observed in 17% of S. aureus and vancomycin resistance in 40% of E. faecium. Previous exposure to antibiotics, especially to carbapenems, was significantly associated with resistant Gram-negative BSI while previous colonization with methicillin-resistant S. aureus was associated with BSI due to this pathogen. Hematological malignancies, neutropenia and Gram-negatives resistant to &gt, 3 antibiotics were significantly associated with higher risk of ICU admission. Underlying disease in relapse/progression, previous exposure to antibiotics, and need of ICU admission were significantly associated with mortality. Center-level variation showed a greater impact on AR, while patient-level variation had more effect on ICU admission and mortality. Previous exposure to antibiotics or colonization by resistant pathogens can be the cause of AR BSI. Resistant Gram-negatives are significantly associated with ICU admission and mortality, with a significant role for the treating center too. The significant evidence of center-level variations on AR, ICU admission and mortality, stress the need for careful local antibiotic stewardship and infection control programs.

PurposeThis retrospective study aimed to investigate the relationships between the methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C and high-dose methotrexate (HD-MTX)-related toxicities in pediatric non-Hodgkin lymphoma (NHL) patients.Patients and MethodsWe reviewed the medical records of 93 NHL patients aged under 18 years who received HD-MTX therapy at the dose of 5 g/m2 with 24-h infusion at Sun Yat-sen University Cancer Center between 2014 and 2019.ResultsThere were 61 males and 32 females, with a median age of 8.8 years (0.9–15.8 years). The tumor types included lymphoblastic lymphoma (n = 38), Burkitt’s lymphoma (n = 31), anaplastic large cell lymphoma (n = 18), diffuse large B-cell lymphoma (n = 6). Overall, 355 courses of HD-MTX therapy were prescribed. All patients were rescued with calcium folinate 12 h after the end of MTX infusion. We found that plasma MTX levels > 0.2 μmol/L at 48 h post-infusion increased the risk of developing oral mucositis (2.4% VS. 9.5%, P = 0.018). Also, patients carrying the C677T and T677T genotypes had tendencies to be more susceptible to oral mucositis (P = 0.034). Patients harboring mutant 677T allele were more likely to develop leucopenia (38.5 vs. 50.3%, P = 0.025) and thrombocytopenia (22.0 vs. 32.4%, P = 0.028). For polymorphism A1298C, the mutant genotype played a protective role in vomiting (11.1 vs. 4.3%, P = 0.018) but increased the risk of anemia (23.8 vs. 41.7%, P < 0.001) and leucopenia (38.1 vs. 50.3%, P = 0.021).ConclusionChildhood NHL patients harboring C677T genotype were more vulnerable to oral mucositis, leucopenia, and thrombocytopenia, while those with A1298C genotype were at a decreased risk of vomiting and more likely to develop anemia and leucopenia.

Purpose First, to investigate the added diagnostic value of chest computed tomography (CT) for evaluating COVID‐19 in symptomatic children by comparing chest CT findings with chest radiographic findings, and second, to identify the imaging signs and patterns on CT associated with COVID‐19 pneumonia in children. Materials and Methods From March 2020 to December 2020, 56 consecutive children (33 males and 23 girls; mean age ± SD, 14.8 ± 5.0 years; range, 9 months–18 years) with mild to moderate symptom and laboratory confirmed COVID‐19 (based on Centers for Disease Control criteria) underwent both chest radiography and chest CT on the same day within the first 2 days of initial presentation to the hospital. Two experienced radiologists independently evaluated chest radiographs and chest CT studies for thoracic abnormalities. The findings from chest radiography and chest CT were compared to evaluate the added diagnostic value of chest CT for affecting patient management. Interobserver agreement was measured with Cohen's κ statistics. Results Eleven (19.6%) of 56 patients had abnormal chest radiographic findings, including ground‐glass opacity (GGO) in 5/11 (45.4%) and combined GGO and consolidation in 6/11 (54.5%). On chest CT, 26 (46.4%) of 56 patients had abnormal CT findings, including combined GGO and consolidation in 19/26 (73.1%), GGO in 6/26 (23.1%), and consolidation in 1/26 (3.8%). Chest CT detected all thoracic abnormalities seen on chest radiography in 11/26 (42.3%) cases. In 15/26 (57.7%), chest CT detected lung abnormalities that were not observed on chest radiography, which included GGO and consolidation in 9/15 (60%), GGO in 5/15 (33.3%), and consolidation in 1/15 (6.6%) cases. These additional CT findings did not affect patient management. In addition, chest CT detected radiological signs and patterns, including the halo sign, reversed halo sign, crazy paving pattern, and tree‐in‐bud pattern. There was almost perfect interobserver agreement between the two reviewers for detecting findings on both chest radiographs (κ, 0.89, p = .001) and chest CT (κ, 0.96, p = .001) studies. Conclusion Chest CT detected lung abnormalities, including GGO and/or consolidation, that were not observed on chest radiography in more than half of symptomatic pediatric patients with COVID‐19 pneumonia. However, these additional CT findings did not affect patient management. Therefore, CT is not clinically indicated for the initial evaluation of mild to moderately symptomatic pediatric patients with COVID‐19 pneumonia.

Background: Ventricular arrhythmias (VAs) are rare in pediatric patients, especially in absence of structural heart disease (SHD). Few data are available regarding the invasive VAs treatment with catheter ablation (CA) in pediatric patients and predictors of outcomes have not been fully investigated. Objective: To describe the clinical presentation, procedural characteristics, and outcomes in pediatric patients undergoing CA for VAs. Methods: Eighty-one consecutive pediatric patients (58 male [72%], 15.5 ± 2.2 years) treated by CA for ventricular tachycardia (VT) or premature ventricular beats (PVBs) were retrospectively evaluated. Study endpoints were VAs recurrence and mortality for any cause. Results: Ninety-five procedures were performed in 81 patients, 52 (55%) PVBs and 43 (45%) VT ablations. During a follow-up of 35.0 months (interquartile range = 13.0–71.0), 14 patients (14.7%) had a VA recurrence: 11 (33.3%) patients treated with CA for VT and 3 (6.2%) patients treated for PVBs (p

Background: Acute necrotizing encephalopathy of childhood (ANE) is a rare but rapidly progressing encephalopathy. Importantly, the exact pathogenesis and evidence-based treatment is scarce. Thus, we aimed to identify the clinical, imaging, and therapeutic characteristics that associated with prognosis of pediatric ANE patients.Methods: A retrospective study was conducted on pediatric patients with ANE who were admitted to Wuhan Children's Hospital between January 2014 and September 2019. All cases met the diagnostic criteria for ANE proposed by Mizuguchi in 1997. The clinical information and follow-up data were collected. The prognostic factors were analyzed by trend chi-square test and Goodman–Kruskal gamma test.Results: A total of 41 ANE patients ranging in age from 8.9 to 142 months were included in this study. Seven cases (17%) died, and the other 34 survivors had different degrees of neurological sequelae. Factors tested to be significantly correlated with the severity of neurological sequelae were the intervals from prodromal infection to acute encephalopathy (G = −0.553), conscious disturbance (r = 0.58), endotracheal intubation (r = 0.423), elevation of alanine aminotransferase (r = 0.345), aspartate aminotransferase (r = 0.393), and cerebrospinal fluid protein (r = 0.490). In addition, dynamic magnetic resonance imaging (MRI) evaluation on follow-up revealed that the total numbers of brain lesion location (χ2 = 6.29, P < 0.05), hemorrhage (r = 0.580), cavitation (r = 0.410), and atrophy (r = 0.602) status were significantly correlated with the severity of neurological sequelae, while early steroid therapy (r = −0.127 and 0.212, respectively) and intravenous immunoglobulin (IVIG) (r = 0.111 and −0.023, respectively) within 24 h or within 72 h after onset showed no association.Conclusions: Intervals from prodromal infection to acute encephalopathy (≤1 day), total numbers of brain lesion location (≥3), the recovery duration of hemorrhage and atrophy (>3 months), and the presence of cavitation predict severe neurological sequelae in pediatric patients with ANE. Early treatments, including steroid therapy and IVIG, had no correlation with better outcomes. Further studies are needed to establish a consensus guideline for the management of ANE.

Mycoplasma is one of the most common pathogens causing community-acquired pneumonia in pediatric patients. In recent years, the number of refractory or severe cases with drug resistance has been gradually increasing and cases that developed embolism after Mycoplasma pneumoniae (M. pneumoniae) infection have been reported. The present study retrospectively analyzed the clinical features, diagnosis and treatment of M. pneumoniae pneumonia (MPP) combined with pulmonary embolism (PE) in a series of 7 cases encountered between January 1st, 2016 to August 1st, 2019 at the Department of Pediatric Intensive Care Unit of The First Hospital of Jilin University (Changchun, China). Combined with relevant Chinese and international studies published during the last two decades, a comprehensive analysis was performed. All of the pediatric patients of the present study had fever, cough and dyspnea respiratory symptoms at onset and the disease progressed rapidly. Thereafter, PE was confirmed by a series of examinations. Pulmonary CT indicated patchy inflammations and significantly elevated D-dimer levels, accompanied by positive anticardiolipin antibodies. Furthermore, a filling defect in the pulmonary artery branch was observed on CT pulmonary angiography (CTPA) examination. In 2 cases, the condition was improved with anti-infection and anticoagulation treatment with low-molecular-weight heparin and warfarin, respectively, and the pulmonary embolism disappeared after 3-4 months. A total of 5 cases, who were not responsive to the drug treatment, underwent surgical resection. During the operation, the local tissues were determined to be infarcted and the pathological diagnosis was consistent with pulmonary infarction. Among the 5 cases, 2 died of Acute Respiratory Distress Syndrome at 3-8 days after the operation. The remaining patients underwent 6-12 months of follow-up and respiratory rehabilitation and their quality of life is now good. In conclusion, compared with healthy individuals, pediatric patients with critical MPP have an elevated risk of embolism. It is necessary to be vigilant regarding whether MMP is combined with PE and perform timely CTPA examination. Early detection, early treatment and surgical intervention (if necessary) may significantly reduce the risk of mortality and disability.