Development In Pediatric Patients Research Articles

Assessment of non-myelotoxic agents as a preparatory regimen for hematopoietic stem cell gene therapy.

RAG2 deficiency is characterized by a lack of B and T lymphocytes, causing severe lethal infections. Currently, RAG2 deficiency is treated with a Hematopoietic Stem Cell transplantation (HSCT). Most conditioning regimens used before HSCT consist of alkylating myelotoxic agents with or without irradiation and affect growth and development of pediatric patients. Here, we developed a non-myelotoxic regimen using G-CSF, VLA-4I or AMD3100. These agents are known HSC mobilizers or affect bone marrow (BM) permeability and may support the homing of HSCs to the BM, without inducing major side effects. Female Rag2-/- mice were pre-treated with Busulfan (BU), G-CSF, VLA-4I or AMD3100 and transplanted with male BM cells transduced with a lentiviral vector carrying codon optimized human RAG2 (RAG2co). Peripheral blood cell counts increased significantly after G-CSF, VLA-4I and AMD3100 treatment, but not after BU. Reconstitution of PB lymphocytes was comparable for all groups with full immune reconstitution at 6months post transplantation, despite different methods of conditioning. Survival of mice pre-treated with non-myelotoxic agents was significantly higher than after BU treatment. Here, we show that the non-myelotoxic agents G-CSF, VLA-4I, and AMD3100 are highly effective as conditioning regimen before HSC gene therapy and can be used as an alternative to BU.

Пути оптимизации антропометрических параметров у детей с фармакорезистентной эпилепсией, получающих кетогенную диетотерапию

Ketogenic diet (KD) whilst being an effective method of diet therapy for drug-resistant epilepsy (DRE) is nevertheless accompanied by a significant number of side effects that include the possibility for the delayed physical development in pediatric patients. The problem is multifactorial and is primarily associated with the non-physiological nature of the ketogenic diet itself. Foreign studies on the KD effect on the physical development in children are contradictory and there are none domestic ones. The purpose of this research was to study the dynamics of anthropometric parameters in children with DRE against the background of KD and to assess the possibilities of the alimentary factor in its improvement. Materials and methods used: single-center retrospective cohort study had been carried out on the basis of the Russian Federal Research Centre for Nutrition, Biotechnology and Food Safety (Moscow, Russia) in 2016-2024. The study included patients with an established diagnosis of DRE against the background of KD aged 1 to 18 y/o. Patients were monitored for 24 months as follows: quarterly during the first year and semiannually during the second year of observation, using anthropometric, clinical-laboratory and clinical-instrumental research methods. Results: by the 3rd month of KD, out of 174 pediatric patients, the diet was effective in 105 (60%); by 12th month, 100% control over attacks was achieved in 11 (6%). Analysis of anthropometric parameters made it possible to establish that at the initial point of observation, in accordance with the z-score of the body mass index (BMI), 108 (64%) had normal nutritional status, 22 (13%) had malnutrition and 40 (24%) were overweight/obese. When studying the dynamics of weight and height indicators of children who were on KD throughout the observation period, it was found that the median BMI z-score statistically significantly changed upward (p=0.047), which was largely due to growth retardation, with a decrease in the height/age z-score throughout the observation period (p<0.001). It was found that the protein component of the diet, as well as the level of ketonemia, have a significant impact on the dynamics of the BMI z-score in KD patients. The amount of protein in the diet at 6% to 7% of the energy value contributed to the maintenance of optimal growth parameters in children within this research. Conclusion: the significance of the BMI indicator in assessing the nutritional status over KD decreases against the background of growth retardation. Taking into account the value of the protein/energy indicator when calculating nutrition helps in maintaining of the physical development rate in such patients.

Transcriptional activation of PINK1 by MyoD1 mediates mitochondrial homeostasis to induce renal calcification in pediatric nephrolithiasis

This study aims to uncover the molecular mechanisms underlying pediatric kidney stone formation induced by renal calcium deposition by utilizing high-throughput sequencing data to reveal the regulation of PINK1 by MyoD1. We performed transcriptome sequencing on peripheral blood samples from healthy children and children with kidney stones to obtain differentially expressed genes (DEGs). Genes related to mitochondrial oxidative stress were obtained from the Genecards website and intersected with DEGs to obtain candidate target genes. Additionally, we conducted protein-protein interaction (PPI) analysis using the STRING database to identify core genes involved in pediatric kidney stone disease (KSD) and predicted their transcription factors using the hTFtarget database. We assessed the impact of MyoD1 on the activity of the PINK1 promoter using dual-luciferase reporter assays and investigated the enrichment of MyoD1 on the PINK1 promoter through chromatin immunoprecipitation (ChIP) experiments. To validate our hypothesis, we selected HK-2 cells and established an in vitro kidney stone model induced by calcium oxalate monohydrate (COM). We evaluated the expression levels of various genes, cell viability, volume of adherent crystals in each group, as well as mitochondrial oxidative stress in cells by measuring mitochondrial membrane potential (Δψm), superoxide dismutase (SOD) activity, reactive oxygen species (ROS), and malondialdehyde (MDA) content. Mitochondrial autophagy was assessed using mtDNA fluorescence staining and Western blot analysis of PINK1-related proteins. Apoptosis-related proteins were evaluated using Western blot analysis, and cell apoptosis was measured using flow cytometry. Furthermore, we developed a rat model of KSD and assessed the expression levels of various genes, as well as the pathologic changes in rat renal tissues using H&E and von Kossa staining, transmission electron microscopy (TEM), and the expression of creatinine, blood urea nitrogen, neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1) to evaluate the mitochondrial oxidative stress in vivo (through measurement of Δψm, SOD activity, ROS, and MDA content). Mitochondrial autophagy was evaluated by Western blot analysis of PINK1-associated proteins. Apoptosis-related proteins were detected using Western blot analysis, and cellular apoptosis was examined using cell flow cytometry and TUNEL staining. Bioinformatics analysis revealed that the PINK1 gene is upregulated and vital in pediatric kidney stone patients. Our in vitro and in vivo experiments demonstrated that silencing PINK1 could inhibit kidney stone formation by suppressing mitochondrial oxidative stress both in vitro and in vivo. We identified MyoD1 as an upstream transcription factor of PINK1 that contributes to the occurrence of pediatric kidney stones through the activation of PINK1. Our in vivo and in vitro experiments collectively confirmed that silencing MyoD1 could inhibit mitochondrial oxidative stress, mitochondrial autophagy, and cellular apoptosis in a rat model of kidney stones by downregulating PINK1 expression, consequently suppressing the formation of kidney stones. In this study, we discovered that MyoD1 may promote kidney stone formation and development in pediatric patients by transcriptionally activating PINK1 to induce mitochondrial oxidative stress.

Lung Ultrasound Efficacy in Monitoring Post-SARS-CoV-2 Pneumonia and Inflammatory Biomarkers in Pediatric Patients.

Background and Objectives: Recognizing the crucial gaps in our understanding of pediatric pneumonia post-SARS-CoV-2 infection, this study aimed to assess the relationship between Pediatric Pneumonia Ultrasound Scores (PedPne) and inflammatory biomarkers. The primary objective of this study is to evaluate the predictive value of PedPne in comparison with inflammatory biomarkers (IL-6 and dNLR) for the development of pneumonia in pediatric patients following SARS-CoV-2 infection. Materials and Methods: This longitudinal observational study collected data from pediatric patients diagnosed with pneumonia after an acute SARS-CoV2 infection. The study focused on analyzing changes in PedPne scores and inflammatory markers such as IL-6 and dNLR from initial admission to follow-up at 7 days. Statistical analysis involved calculating the sensitivity, specificity, and Area Under the Curve (AUC) for each biomarker, alongside regression analysis to determine their hazard ratios for predicting pneumonia development. Results: The analysis identified significant cutoff values for dNLR at 1.88 (sensitivity 77.0%, specificity 85.7%, AUC 0.802, p < 0.001), IL-6 at 6.1 pg/mL (sensitivity 70.3%, specificity 92.9%, AUC 0.869, p < 0.001), and PedPne score at 3.3 (sensitivity 75.7%, specificity 78.6%, AUC 0.794, p < 0.001). Conversely, NLR showed lower diagnostic performance (AUC 0.485, p = 0.327). Regression analysis further highlighted the strong predictive power of these markers, with IL-6 showing a fourfold increase in pneumonia risk (HR = 4.25, CI: 2.07-9.53, p < 0.001), dNLR indicating more than a twofold increase (HR = 2.53, CI: 1.19-6.97, p = 0.006), and PedPne score associated with more than a doubling of the risk (HR = 2.60, CI: 1.33-5.18, p < 0.001). Conclusions: The study conclusively demonstrated that both PedPne ultrasound scores and specific inflammatory biomarkers such as dNLR and IL-6 are significant predictors of pneumonia development in pediatric patients post-COVID-19 infection. These findings advocate for the integration of these biomarkers in routine clinical assessments to enhance the diagnostic accuracy and management of pneumonia in children following SARS-CoV-2 infection.

Effect of endoscopic endonasal skull base approaches on olfactory function and facial development in children.

Endoscopic approaches for skull base pathologies are increasingly being performed, and the subsequent complications, especially in the long term, have also been partially clarified. However, there is no information on the effects of endoscopic endonasal skull base surgeries (EESBS) in children on odor and facial development in parallel with long-term development. We conducted this study to investigate postoperative olfactory function and facial development in pediatric patients who underwent skull base surgery using the endoscopic endonasal method. We evaluated the smell test, sinonasal symptoms, and facial development of pediatric patients who underwent endoscopic endonasal skull base surgery after long-term follow-up. Odor was evaluated using the "Sniffin' Sticks" test kit, which assessed the T (odor threshold), D (odor discrimination), and I (odor identification) parameters. Sinonasal symptoms were evaluated using the SNOT-22 (sinus-nose outcome test) questionnaire. SNA (sella-nasion-A point), SNB (sella-nasion-B point), and ANB (A point-nasion-B point) angles were calculated from maxillofacial tomography and magnetic resonance imaging) to evaluate facial development. Data were compared with those of the healthy control group. We included 30 patients comprising 19 (63.3%) boys and 11 (36.7%) girls, with no age difference between case and control groups.The mean follow-up period was 7 years. Odor test data, cephalometric measurements, and SNOT-22 analysis results showed no statistically significant differences between the two groups. To our knowledge, this is a comprehensive study with the longest follow-up period in terms of evaluation of facial development after EESBS in children to analyze odor using the Sniffin' Sticks test kit and the quality of life using SNOT-22. Olfactory function, facial development, and quality of life remained unaffected after long-term follow-up after EESBS in children. Although this surgical approach is minimally invasive, we recommend considering the possibility of complications, and the procedure should be performed by an experienced surgical team with adequate equipment.

Phase 1 Open-Label Study of Omigapil in Patients With LAMA2- or COL6-Related Dystrophy.

Omigapil is a small molecule which inhibits the GAPDH-Siah1-mediated apoptosis pathway. Apoptosis is a pathomechanism underlying the congenital muscular dystrophy subtypes LAMA2-related dystrophy (LAMA2-RD) and COL6-related dystrophy (COL6-RD). Studies of omigapil in the (dyw/dyw) LAMA2-RD mouse model demonstrated improved survival, and studies in the (dy2J/dy2J) LAMA2-RD mouse model and the (Col6a1-/-) COL6-RD mouse model demonstrated decreased apoptosis. A phase 1 open-label, sequential group, ascending oral dose, cohort study of omigapil in patients with LAMA2-RD or COL6-RD ages 5-16 years was performed (1) to establish the pharmacokinetic (PK) profile of omigapil at a range of doses, (2) to evaluate the safety and tolerability of omigapil at a range of doses, and (3) to establish the feasibility of conducting disease-relevant clinical assessments. Patients were enrolled in cohorts of size 4, with each patient receiving 4 weeks of vehicle run-in and 12 weeks of study drug (at daily doses ranging from 0.02 to 0.08 mg/kg). PK data from each cohort were analyzed before each subsequent dosing cohort was enrolled. A novel, adaptive dose-finding method (stochastic approximation with virtual observation recursion) was used to allow for dose escalation/reduction between cohorts based on PK data. Twenty patients were enrolled at the NIH (LAMA2-RD: N = 10; COL6-RD: N = 10). Slightly greater than dose-proportional increases in systemic exposure to omigapil were seen at doses 0.02-0.08 mg/kg/d. The dose which achieved patient exposure within the pre-established target area under the plasma concentration-vs-time curve (AUC0-24h) range was 0.06 mg/kg/d. In general, omigapil was safe and well tolerated. No consistent changes were seen in the disease-relevant clinical assessments during the duration of the study. This study represents the thus far only clinical trial of a therapeutic small molecule for LAMA2-RD and COL6-RD, completed with an adaptive trial design to arrive at dose adjustments. The trial met its primary end point and established that the PK profile of omigapil is suitable for further development in pediatric patients with LAMA2-RD or COL6-RD, the most common forms of congenital muscular dystrophy. While within the short duration of the study disease-relevant clinical assessments did not demonstrate significant changes, this study establishes the feasibility of performing interventional clinical trials in these rare disease patient populations. This study provides Class IV evidence of omigapil in a dose-finding phase 1 study. Clinical Trials NCT01805024.

Analysis of the effect on costochondral graft for TMJ ankylosis with jaw deformities in pediatrics.

To evaluate the effects of costochondral grafting (CCG) used for temporomandibular joint ankylosis (TMJA) in growing patients. Pediatric patients with TMJA treated by CCG from 2010.5 to 2021.7 were included in the study. CT scans were performed before and after operations with at least 1 year follow-up. The height of the mandibular ramus, menton deviation or retraction, osteotomy gap, etc. were measured by ProPlan CMF1.4 software. CCG growth, resorption, and relapse were evaluated and analyzed with influencing factors such as age, ostectomy gap, etc. by generalized estimating equation. There were 24 patients (29 joints) with an average age of 6.30 ± 3.13 years in the study. After operation, the mandibular ramus was elongated by 5.97 ± 3.53mm. Mandibular deviation or retrusion was corrected by 4.82 ± 2.84mm and 3.76 ± 2.97mm respectively. After a mean follow-up of 38.91 ± 29.20 months, 58.62% CCG grew (4.18 ± 7.70mm), 20.69% absorbed (2.23 ± 1.16mm), and 20.69% re-ankylosed. The re-ankylosis was negatively correlated with the osteotomy gap (OR:0.348,0.172-0.702 95%CI, critical value = 6.10mm). CCG resorption was positively correlated with the distance of CCG ramus elongation (OR:3.353,1.173-9.586 95%CI, critical value = 7.40mm). An adequate osteotomy gap and CCG ramus elongation distance are the key factors for successful treatment of TMJA with jaw deformities in growing patients. TMJA affects mouth opening and jaw development in pediatric patients. The most common autogenous bone graft for pediatric patients is CCG due to its growth potential, convenient access and easy contouring. Also, it can simultaneously reconstruct the TMJ and improve jaw deformity by lengthening the mandibular ramus. But the growth of CCG is unpredictable. In this study, we explored several factors that may affect the absorption and re-ankylosis of CCG, expecting to provide several suggestions to improve future CCG treatment.

Diagnostic Challenges and Emerging Pathogeneses of Selected Glomerulopathies.

Recent progress in glomerular immune complex and complement-mediated diseases have refined diagnostic categories and informed mechanistic understanding of disease development in pediatric patients. Herein, we discuss selected advances in 3 categories. First, membranous nephropathy antigens are increasingly utilized to characterize disease in pediatric patients and include phospholipase A2 receptor (PLA2R), Semaphorin 3B (Sema3B), neural epidermal growth factor-like 1 (NELL1), and protocadherin FAT1, as well as the lupus membranous-associated antigens exostosin 1/2 (EXT1/2), neural cell adhesion molecule 1 (NCAM1), and transforming growth factor beta receptor 3 (TGFBR3). Second, we examine advances in techniques for paraffin and light chain immunofluorescence (IF), including the former's function as a salvage technique and their necessity for diagnosis in adolescent cases of membranous-like glomerulopathy with masked IgG kappa deposits (MGMID) and proliferative glomerulonephritis with monotypic Ig deposits (PGNMID), respectively. Finally, progress in understanding the roles of complement in pediatric glomerular disease is reviewed, with specific attention to overlapping clinical, histologic, and genetic or functional alternative complement pathway (AP) abnormalities among C3 glomerulopathy (C3G), infection-related and post-infectious GN, "atypical" post-infectious GN, immune complex mediated membranoproliferative glomerulonephritis (IC-MPGN), and atypical hemolytic uremic syndrome (aHUS).

Evaluation of overuse of Head Computerized Tomography scan on traumatic brain injury pediatric patients

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality among pediatric patients. Head Computerized Tomography (CT) scan has the undoubtedly benefit of diagnosing TBI lesions but is also associated with increased risk of cancer due to radiation. This study was composed of 190 patients evaluated in the emergency setting of a pediatric Brazilian hospital from January 2019 to December 2021. The results of the study demonstrated an increased amount of CT scans in patients with mild TBI during this period. Besides, we noticed that many of these CT scans showed normal results or clinically insignificant findings such as subgaleal hematomas. Knowing the risks related to radiation exposure at such a young age makes us question the validity of the hospital protocol we are following. Also, we believe that a future solution to this issue would be to implement radiation-free complimentary exams such as Magnetic Resonance Imaging (MRI) to our hospital protocol. Emphasizing the importance of justification of procedures and optimization of radiation doses are also crucial to prevent cancer development in pediatric patients.

Predictive factors of hydrocephalus development in pediatric patients undergoing hemispherectomy for intractable epilepsy.

Hemispherectomy surgery is an effective procedure for pediatric patients with intractable hemispheric epilepsy. Hydrocephalus is a well-documented complication of hemispherectomy contributing substantially to patient morbidity. Despite some clinical and operative factors demonstrating an association with hydrocephalus development, the true mechanism of disease is incompletely understood. The aim of this study was to investigate a range of clinical and surgical factors that may contribute to hydrocephalus to enhance understanding of the development of this complication and to aid the clinician in optimizing peri- and postoperative surgical management. A retrospective chart review was conducted on all pediatric patients younger than 21 years who underwent hemispherectomy surgery at the Cleveland Clinic between 2002 and 2016. Data collected for each patient included general demographic information, neurological and surgical history, surgical technique, pathological analysis, presence and duration of perioperative CSF diversion, CSF laboratory values obtained while an external ventricular drain (EVD) was in place, length of hospital stay, postoperative aseptic meningitis, and in-hospital surgical complications (including perioperative stroke, hematoma formation, wound breakdown, and/or infection). Outcomes data included hemispherectomy revision and Engel grade at last follow-up (based on the Engel Epilepsy Surgery Outcome Scale). Data were collected for 204 pediatric patients who underwent hemispherectomy at the authors' institution. Twenty-eight patients (14%) developed hydrocephalus requiring CSF diversion. Of these 28 patients, 13 patients (46%) presented with hydrocephalus during the postoperative period (within 90 days), while the remaining 15 patients (54%) presented later (beyond 90 days after surgery). Multivariate analysis revealed postoperative aseptic meningitis (OR 7.0, p = 0.001), anatomical hemispherectomy surgical technique (OR 16.3 for functional/disconnective hemispherectomy and OR 7.6 for modified anatomical, p = 0.004), male sex (OR 4.2, p = 0.012), and surgical complications (OR 3.8, p = 0.031) were associated with an increased risk of hydrocephalus development, while seizure freedom (OR 0.3, p = 0.038) was associated with a decreased risk of hydrocephalus. Hydrocephalus remains a prominent complication following hemispherectomy, presenting both in the postoperative period and months to years after surgery. Aseptic meningitis, anatomical hemispherectomy surgical technique, male sex, and surgical complications show an association with an increased rate of hydrocephalus development while seizure freedom postsurgery is associated with a decreased risk of subsequent hydrocephalus. These findings speak to the multifactorial nature of hydrocephalus development and should be considered in the management of pediatric patients undergoing hemispherectomy for medically intractable epilepsy.

Potential Predictive Biomarkers for the Development and Outcomes of Inhibitors in Hemophilia A Patients

Introduction Inhibitor development poses a significant challenge in the treatment of hemophilia A (HA). Approximately 30% of HA patients develop inhibitors in response to FVIII infusion therapy. While the risk is highest early in treatment days, patients are at risk throughout their lifetime. Regardless of certain known risk factors, the lack of biomarkers for inhibitor development hampers efforts to prevent their occurrence. Since inflammation is a well-known risk factor, one of our goals is to identify potential biomarkers among inflammatory cytokines. Another focus is glycosylation-related biomarkers, which has drawn great attention in biomarker discovery of various diseases including cancers. By analyzing the association of cytokines and plasma glycosylation with inhibitor formation, this research aims to provide valuable references for clinical care. Methods Plasma samples from 60 HA patients, and 23 healthy donors were analyzed to detect the levels of G-CSF, IFN-γ, IL-1β, IL-2, IL-6, IL-8, IL-10, IL12p70, IP-10 and TNF. The HA samples were divided into inhibitor negative (InhNeg, BU &amp;lt; 0.6, n = 26) and inhibitor positive (InhPos, BU ≥ 0.6, n = 34) groups. A predictive model of inhibitor development was established using logistic regression analysis. To investigate the correlation between cytokine levels and high inhibitor titers, the inhibitor-positive samples were further categorized into good risk (&amp;lt; 10 BU, n = 14) and poor risk (≥ 10 BU, n = 20) groups based on immune tolerance induction therapy prognosis. Total plasma N-glycans were released, methylated, and analyzed by using MALDI-TOF MS/MS. A synthesized N-glycan was spiked in to quantify each glycoform. The study evaluated the correlation between HA sample groups and various glycosylation ratios, including for sialylation, core-fucosylation, galactosylation and galactose. The cut-off value of each glycosylation ratio was based on the median of the inhibitor-negative group. Results The adjusted odds ratio of inhibitor development for elevated G-CSF, IL-6 and decreased IL-10 were 2.84 (95% CI: 1.45-8.48; p = 0.021), 1.50 (95% CI: 1.14-2.42; p = 0.069), and 0.28 (95% CI: 0.10-0.61; p = 0.006), respectively in HA patients. Among InhPos HA patients, the levels of G-CSF, IL-2, IL-6, IL-8, and IL-10 in poor risk group were significantly higher than in good risk group (p-value &amp;lt; 0.05, ANOVA). Since aging also causes glycosylation changes, we analyzed adult (≥ 18 years old, n = 31) and pediatric (&amp;lt; 18 years old, n = 17) HA patients separately. Among analyzed glycan ratios, 80% of adult HA patients with inhibitors had a higher core-fucosylation ratio. All pediatric patients with inhibitors had significant lower sialylation and higher galactosylation ratios. Strikingly, pediatric patients with inhibitors exhibited around 2-fold higher core-fucosylation than those without inhibitor. Conclusion Our finding of elevated levels of G-CSF and IL-6 along with decreased levels of IL-10 associated with the presence of inhibitors, suggests the potential for prediction of inhibitor development. Moreover, high levels of G-CSF, IL-2, IL-6, IL-8 and IL-10 in patients with high inhibitor titers (≥ 10 BU, poor risk group) but not in good risk group imply they could be explored in future studies as prognostic factors in immune tolerance therapy. Glycan ratios can also hold promise as biomarkers including higher core-fucosylation in adult patients. Additionally, significant lower sialyation, higher galactosylation and core-fucosylation ratios indicate higher possibility of inhibitor development in pediatric patients.

Expert consensus on the management of deep partial-thickness burn wounds in pediatric patients (2023 version)

Burns are the leading cause of accidental injuries among Chinese children. Due to the strong wound repair ability and the demand for growth and development in pediatric patients, there are many options for the treatment of deep partial-thickness burn wounds in pediatric patients, while many controversies about the strategies for treatment of this kind of wounds also exist. This article assembled the consensus reached by experts in burns and relevant fields in China and abroad on the management of thermal-induced deep partial-thickness burn wounds in pediatric patients aged 1-6 years, including definition and diagnosis, surgical treatment, non-surgical treatment, wound dressings, application of growth factors, treatment of infectious wounds, prevention and treatment of scar, to provide guiding recommendations for the diagnosis and treatment of deep partial-thickness burn wounds in pediatric patients in China.

The Utility of Responsive Neurostimulation for the Treatment of Pediatric Drug-Resistant Epilepsy.

Drug-resistant epilepsy (DRE) has a strongly negative impact on quality of life, as well as the development of pediatric patients. Surgical treatments have evolved over time, including more invasive craniotomies for resection or disconnection. More recently, neuromodulation techniques have been employed as a less invasive option for patients. Responsive neurostimulation (RNS) is the first closed-loop technology that allows for both treatment and device data collection, which allows for an internal assessment of the efficacy of treatment. This novel technology has been approved in adults and has been used off label in pediatrics. This review seeks to describe this technology, its history, and future directions.

Outcomes and Risk Factor Analysis of Plastic Bronchitis Among 321 Children with Influenza Pneumonia After Bronchoscopy Examination.

Plastic bronchitis (PB) is a rare and severe lung disease. It can be triggered by influenza virus infection, which is a common respiratory infection in children. Bronchoscopy can aid in the early detection and treatment of PB. However, the outcomes and risk for PB development in pediatric patients with influenza virus infection are not fully understood. Data from 321 children diagnosed with influenza virus pneumonia who underwent bronchoscopy examinations between 1st January, 2009 and 31st December, 2020 were retrospectively analyzed to assess the outcomes and risk factors associated with PB development. This study included 97 girls and 224 boys with influenza virus pneumonia with a median age of 42 months. Among them, 36 patients (11.2%) were categorized as having PB based on bronchoscopy findings. PB patients had significantly longer fever durations (p=0.010) and higher risks of developing severe conditions including respiratory failure (p<0.001), acute respiratory distress syndrome (p<0.001), and air-leak syndrome (p<0.001) compared to non-PB patients. Conventional treatment including the use of neuraminidase inhibitors and antibiotics did not differ between the PB and non-PB patients, but PB patients required more anti-inflammatory treatment (p=0.019) and ventilator support (p<0.001). Combined univariate and multivariate analyses suggested that radiographic findings, including mediastinal emphysema (p=0.012) and lung consolidation (p=0.012), as well as increased levels of neutrophils (p=0.026), aspartate aminotransferase (p=0.004), and lactate dehydrogenase (p<0.001), were identified as risk factors for PB development in patients with influenza virus pneumonia. Although PB patients required more intensive care and had longer hospital stays, they all recovered well after treatment. Influenza virus infection is linked to PB development in children. Identifying risk factors and early intervention such as bronchoscopy can improve the prognosis of children with PB.

Comparison between the modified Blalock-Taussig shunt and right ventricular outflow tract stent in the palliative treatment for tetralogy of Fallot.

For patients with tetralogy of Fallot (TOF) who are not suitable candidates for primary corrective surgery or have a high surgical risk, transcatheter right ventricular outflow tract (RVOT) stent implantation is considered a safe and effective palliative intervention. This study aims to investigate the therapeutic outcomes of RVOT stent implantation in neonates and infants with TOF in comparison with the modified Blalock-Taussig shunt (mBTS) and to compare the impact of the 2 palliative interventions on arterial oxygen saturation and pulmonary artery development in pediatric patients. Clinical data of 32 patients with TOF admitted to the Second Xiangya Hospital of Central South University from March 2011 to March 2021 were retrospectively collected. The patients were divided into an mBTS group (undergoing mBTS, n=15) and a stent implantation group (undergoing RVOT stenting, n=17) according to the surgical procedures. The 2 groups were assessed and compared in the surgical-related arterial oxygen saturation, postoperative complication rate, mortality rate, and re-intervention rate. The development of the patients' main pulmonary artery, right pulmonary artery, and left pulmonary artery was assessed by z-scores according to echocardiographic results. The children in the stent implantation group were younger and less weighed compared with the mBTS group (both P<0.05). Compared with the preoperative period, children in the stent implantation group had significantly higher arterial oxygen saturation [(75±17)% vs (96±3)%, P=0.026]; z-scores of pulmonary trunk [(-2.82±1.27) points vs (0.86±0.77) points, P=0.014], right pulmonary artery [(-1.88±0.59) points vs (-0.28±0.71) points, P=0.011], and left pulmonary artery [(-2.34±0.36) points vs (-1.67±0.36) points, P=0.036] were significantly increased. However, there were no significant differences in arterial oxygen saturation and pulmonary artery z-scores between pre- and post-mBTS procedures (all P>0.05). RVOT stent would have good surgical outcomes used in TOF patients with low weight and severe comorbidities. It also leads to an higher postoperative oxygen saturation and better promotion of pulmonary artery growth with RVOT stent compared to mBTS.

Imaging of the Pediatric Breast: Review of Normal Development and Spectrum of Disease.

HomeRadioGraphicsVol. 43, No. 1 PreviousNext Breast ImagingRadiographics FundamentalsImaging of the Pediatric Breast: Review of Normal Development and Spectrum of DiseaseSonia Phadke , Julie Sogani, Ashishkumar K. Parikh, Christabell C. Ndibe, Adina L. Alazraki, Leann E. Linam, Erica L. RiedeselSonia Phadke , Julie Sogani, Ashishkumar K. Parikh, Christabell C. Ndibe, Adina L. Alazraki, Leann E. Linam, Erica L. RiedeselAuthor AffiliationsFrom the Department of Radiology and Imaging Sciences, Divisions of Diagnostic Radiology (S.P.), Breast Imaging (J.S.), and Pediatric Imaging (A.K.P., C.C.N., A.L.A., L.E.L., E.L.R.), and Department of Pediatrics (A.K.P., C.C.N., A.L.A., L.E.L., E.L.R.), Emory University School of Medicine, 1364 Clifton Rd NE, Suite D112, Atlanta, GA 30322; and Division of Pediatric Radiology, Children’s Healthcare of Atlanta Pediatric Institute, Atlanta, Ga (A.K.P., C.C.N., A.L.A., L.E.L., E.L.R.).Address correspondence to S.P. (email: [email protected]).Sonia Phadke Julie SoganiAshishkumar K. ParikhChristabell C. NdibeAdina L. AlazrakiLeann E. LinamErica L. RiedeselPublished Online:Nov 25 2022https://doi.org/10.1148/rg.220047MoreSectionsFull textPDF ToolsImage ViewerAdd to favoritesCiteTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinked In AbstractKnowledge of normal pediatric breast development and the spectrum of common and uncommon benign and malignant masses is essential to accurately recognize disease and guide managementSuggested ReadingsBorders H, Mychaliska G, Gebarski KS. Sonographic features of neonatal mastitis and breast abscess. Pediatr Radiol 2009;39(9):955–958. Crossref, Medline, Google ScholarChung EM, Cube R, Hall GJ, González C, Stocker JT, Glassman LM. From the archives of the AFIP: breast masses in children and adolescents: radiologic-pathologic correlation. RadioGraphics 2009;29(3):907–931. Link, Google ScholarGao Y, Saksena MA, Brachtel EF, terMeulen DC, Rafferty EA. How to approach breast lesions in children and adolescents. Eur J Radiol 2015;84(7):1350–1364. Crossref, Medline, Google ScholarJaved A, Lteif A. Development of the human breast. Semin Plast Surg 2013;27(1):5–12. Crossref, Medline, Google ScholarKaneda HJ, Mack J, Kasales CJ, Schetter S. Pediatric and adolescent breast masses: a review of pathophysiology, imaging, diagnosis, and treatment. AJR Am J Roentgenol 2013;200(2):W204–W212. Crossref, Medline, Google ScholarKennedy RD, Boughey JC. Management of pediatric and adolescent breast masses. Semin Plast Surg 2013;27(1):19–22. Crossref, Medline, Google ScholarRestrepo R, Cervantes LF, Swirsky AM, Diaz A. Breast development in pediatric patients from birth to puberty: physiology, pathology and imaging correlation. Pediatr Radiol 2021;51(11):1959–1969. Crossref, Medline, Google ScholarSanchez R, Ladino-Torres MF, Bernat JA, Joe A, DiPietro MA. Breast fibroadenomas in the pediatric population: common and uncommon sonographic findings. Pediatr Radiol 2010;40(10):1681–1689. Crossref, Medline, Google ScholarSimmons PS, Jayasinghe YL, Wold LE, Melton LJ 3rd. Breast carcinoma in young women. Obstet Gynecol 2011;118(3):529–536 [Published correction appears in Obstet Gynecol 2012;119(6):1277.]. Crossref, Medline, Google ScholarValeur NS, Rahbar H, Chapman T. Ultrasound of pediatric breast masses: what to do with lumps and bumps. Pediatr Radiol 2015;45(11):1584–1599; quiz 1581–1583. Crossref, Medline, Google ScholarWright AG, Hayward JH, Price ER, Ray KM, Joe BN, Lee AY. Primum non nocere: Utility and outcomes of pediatric breast ultrasound. Clin Imaging 2020;68:131–135. Crossref, Medline, Google ScholarArticle HistoryReceived: Mar 14 2022Revision requested: Apr 12 2022Revision received: Apr 26 2022Accepted: May 2 2022Published online: Nov 25 2022 FiguresReferencesRelatedDetailsAccompanying This ArticleImaging of the Pediatric Breast: Review of Normal Development and Spectrum of DiseaseNov 25 2022Default Digital Object SeriesRecommended Articles RSNA Education Exhibits RSNA Case Collection Vol. 43, No. 1 Slide PresentationMetrics Altmetric Score PDF download

Survival and epidemiological, social, economic and clinical aspects of pediatric peritoneal dialysis: An integrative review

Introduction: The kidneys are fundamental organs for survival and the progressive loss of their functions causes the loss of regulatory, excretory and endocrine functions, essentially affecting the entire balance of the organism. Chronic Kidney Disease (CKD) is considered a complex disease and a worldwide public health problem with the number of patients continuously increasing, even in the pediatric population. CKD often progresses to end-stage requiring Renal Replacement Therapy (RRT). Kidney transplantation is the treatment of choice to maximize the survival, growth, and development of pediatric patients, however, if dialysis is necessary, Peritoneal Dialysis (PD) is a high-quality and low-cost RRT modality preferred therapy for children and adolescents with End-Stage Kidney Disease (ESKD). In this scope, this study aimed to carry out an integrative review of the survival and the epidemiological, clinical, social and economic profile of children and adolescents with PD. Methods: It is an integrative review whose data collection was carried out between January 2019 and January 2021 following the methodology suggested by the literature, using a validated data collection instrument. The following health science descriptors (DECs) from the VHL portal (virtual health library) were used: children, adolescents, chronic peritoneal dialysis, survival and epidemiology. Results: Thirty-five studies were selected and evaluated using the Critical Appraisal Skills Program (CASP). The level of evidence of the articles was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) scale. Survival and epidemiological, social, economic and clinical aspects of pediatric PD in Brazil and worldwide have been described and reviewed. Conclusions: The complexity and costs involved in the care of pediatric patients in RRT impact their survival. Mortality and morbidity are higher than in healthy children and life expectancy is considerably lower. ESKD is more severe in the pediatric population and interferes with general development, weight and height gain, regulation of mineral metabolism and causes definitive cardiovascular calcifications. Kidney transplantation is the treatment of choice to maximize the survival, growth and development of pediatric patients. However, if dialysis is necessary PD is the first-choice modality in this population. Unfortunately, data are scarce in the literature on its survival and its epidemiological, social, economic and clinical aspects.

11.4 Extrapolation of Atypical Antipsychotics for the Treatment of Schizophrenia From Adults to Adolescents

Antipsychotic drug development in pediatric patients is often challenged by disease heterogeneity, patient recruitment, clinical trial attrition, and ethical concerns. Regulatory agencies have explored various pathways to expedite pediatric drug development over the last decade. Extrapolation-based drug development strategies rely on leveraging prior data to reduce evidentiary requirements for newer data in establishing drug efficacy. On January 13, 2020, the FDA released a general advice letter to sponsors highlighting the acceptance of extrapolating the efficacy of atypical antipsychotics to pediatric patients.

Tanner Stages and Pubertal Development

Abstract Puberty typically follows a predictable pattern that can be assessed using the Tanner stages or Sexual Maturity Rating scale. Clinicians can use this tool to evaluate and monitor progress in female and male puberty. The timing and sequence of puberty are important indicators of the growth and development of pediatric patients. Stages of puberty and normal findings must be known before variations can be identified. Pubertal changes that fall outside the normal timeline or trajectory are considered abnormal and must be investigated. Treatments for abnormal variations are based on pathologic versus idiopathic causes. Nurses, as members of the interprofessional collaborative team, serve an important role by obtaining data, monitoring progress, providing health education, performing ongoing assessment/evaluation, and ensuring continuity of care when needed.

Overview of Physical, Neurocognitive, and Psychosocial Outcomes in Pediatric Intestinal Failure and Transplantation.

Intestinal failure and transplantation may significantly impact physical, neurocognitive, and psychosocial development in pediatric patients. Currently, there is a paucity of literature on the effects of intestinal failure and transplantation on these aspects of development. This article will review the current literature and discuss the short and long-term impacts as well as interventions to improve clinical outcomes in children with intestinal failure or those undergoing transplantation. Psychological disorders, neurodevelopmental delay, and social maladaptation are frequently encountered in this patient population. While the main focus is often on medical management, equal emphasis should be placed on other aspects of development such as increasing social support and improving school performance. The transition to adulthood also presents many obstacles for patients and healthcare providers should anticipate challenges such as childbirth, employment, and raising a family. The pre-operative, perioperative, and post-operative periods all represent opportunities for medical intervention. Frequent monitoring of physical, psychosocial, and neurocognitive status helps to improve clinical outcomes and long-term quality of life. Future research should emphasize continued development of multidisciplinary programs and specialized services to help address the physical and psychosocial needs of children with intestinal failure as well as transplant recipients.