Pediatric Patients Research Articles

User-Centered Design and Usability of Voxe as a Pediatric Electronic Patient-Reported Outcome Measure Platform: Mixed Methods Evaluation Study

Background Electronic patient-reported outcome measures (ePROMs) are standardized digital instruments integrated into clinical care to collect subjective data regarding patients’ health-related quality of life, functional status, and symptoms. In documenting patient-reported progress, ePROMs can guide treatment decisions and encourage measurement-based care practices. Voxe is a pediatric and user-centered ePROM platform for patients with chronic health conditions. Objective We aimed to describe the user-centered design approach involving feedback from end users and usability testing of Voxe’s platform features to support implementation in a pediatric health care setting. Methods Purposive sampling was used to recruit patients aged 8-17 years from 2 chronic illness populations in 2 pediatric hospitals in Canada. Patients’ health care team members were also purposively recruited. One-on-one iterative testing sessions were conducted digitally by research team members with participants to obtain feedback on the appearance and functionalities of the Voxe platform prototype. Patients and health care providers (HCPs) completed Voxe-related task-based activities. International Organization for Standardization key performance indicators were tracked during HCP task-based activities. HCPs also completed the System Usability Scale. To test platform usability, the think-aloud technique was used by participants during the completion of structured tasks. After completing all task-based activities, patient participants selected 5 words from the Microsoft Desirability Toolkit to describe their overall impression and experience with the Voxe platform. Qualitative data about likes, dislikes, and ease of use were collected through semistructured interviews. Feedback testing sessions were conducted with patients and HCPs until Voxe was acceptable to participating end users, with no further refinements identified. Quantitative and qualitative data analysis were completed using descriptive statistics and content analysis. Results A total of 49 patients and 38 HCPs were recruited. Patients were positive about Voxe’s child-centered design characteristics and notification settings. HCPs rated Voxe as user-friendly and efficient, with the time to complete tasks decreasing over time. HCPs were satisfied with the Voxe platform functionalities and identified the value of Voxe’s system notifications, summarized display of ePROM results, and its capacity to integrate with electronic medical records. Patients’ and HCPs’ high satisfaction rates with the Voxe prototype highlight the importance of being responsive to user suggestions from the inception of eHealth platform developments to ensure their efficient and effective design. Conclusions This paper describes the user-centered creation and usability testing of Voxe as an ePROM platform for implementation into clinical care for pediatric patients with chronic health conditions. As a patient-facing platform that can be integrated into electronic medical records, Voxe aligns with measurement-based care practices to foster quality patient-centered approaches to care. End users’ positive feedback and evaluation of the platform’s user-friendliness and efficiency suggest that Voxe represents a valuable and promising solution to systematically integrate patient-related outcome (PRO) data into complex and dynamic clinical health care settings. International Registered Report Identifier (IRRID) RR2-10.1136/bmjopen-2021-053119

One and Done? An Evaluation of the Clinical Outcomes of Single- and Multi-Dose Dalbavancin Use in the Pediatric Population

Staphylococcus aureus is a leading cause of invasive bacterial infections in the pediatric population. In general, data surrounding the use of newly approved antimicrobials within children are lacking. Dalbavancin is a long-acting lipoglycopeptide that shows promise for off-label use in adults given its unique pharmacokinetics and in vitro potency against common Gram-positive isolates; however, evidence to supports its use in children is limited. We report the use of dalbavancin in three pediatric cases in patients aged 17 months of age, 3 years of age, and 11 years of age. All infections were caused by S. aureus (66.7% methicillin-resistant S. aureus) representing varied disease, including an osteoarticular infection and catheter-related bloodstream infection. Furthermore, all patients had pediatric infectious diseases involvement. Following the utilization of DAL, high clinical success and low rates of adverse effects were observed with high patients’ and parents’ satisfaction. While larger, confirmatory real-world studies are needed, our findings support safe off-label DAL use in select pediatric patients.

A rare cause of immune dysregulation, prolidase deficiency: a case report and review of the literature.

We report a pediatric patient with prolidase deficiency, caused by a mutation in the PEPD gene, which encodes the enzyme prolidase D, with a lupus-like clinic and marked dysmorphic features along with pulmonary, neurological, skeletal, and immune system involvement. In addition to being the first known case in the literature where Friedrich's ataxia and prolidase deficiency were observed together, we aimed to highlight that this diagnosis should be considered in patients with autoimmunity and additional systemic findings such as treatment-resistant skin lesions, intellectual disability, and pulmonary manifestations. Furthermore, we sought to compare this case with others documented in the literature.

Botulinum toxin-A in acute acquired comitant esotropia during COVID pandemic in children and young adolescents

Abstract Purpose: To study the effectiveness of botulinum toxin A (BTX-A) in the treatment of patients with acute acquired comitant esotropia (AACE) due to excessive use of mobile and laptops in the COVID era in the pediatric population and adolescents. Methods: This was a retrospective, interventional study of pediatric patients and young adults who presented with AACE and received unilateral or bilateral BTX-A. All the patients complained of binocular diplopia and sudden onset of esotropia with a history of mobile or laptop usage during the COVID era (2020–2023). Twenty-seven patients with acute-onset esotropia in 3 years (2020–2023) were included. All patients were administered 2.5–7.5 units of BTX-A (Botox, Allergan, India) into the unilateral or bilateral medial rectus muscle of the deviating eye under short general anesthesia or local anesthesia. The main outcome measures were pre- and post-injection angle of deviation, pre- and post-injection stereopsis, final level of stereopsis achieved, recurrence, and whether strabismus surgery was later required. Results: The mean age of patients was 12.85 ± 7.15 years (range: 4–25 years). The mean dosage of Botox was 6 U (2.5–7.5 U). The mean follow-up was 6 months (6 months–2 years). The mean preoperative angle of deviation (AOD) was 41.11 ± 10.9 prism diopters (PD) for distance and 41.67 ± 10.9 PD for near. The maximum effect of BTX-A was seen at 1 month; post-injection AOD was 13.65 ± 14.7 PD for distance and 14.87 ± 15.8 PD for near (P < 0.001). Over half of the patients achieved optimal outcomes, with improvements in stereopsis and sensory fusion. Early intervention (within 3 months of symptom onset) significantly correlated with treatment success. Conclusion: While BTX-A therapy for acute-onset esotropia demonstrates efficacy, patient-specific considerations are essential. This study highlights the evolving nature in the digital age and early administration of BTX-A along with close follow-up to monitor residual and recurrence of esotropia. The surgical intervention can increase the final success rate.

Assessment of central vein sign and paramagnetic rim lesions in pediatric multiple sclerosis.

The evaluation of white matter lesions (WMLs) showing the central vein sign (CVS) and paramagnetic rim lesions (PRLs) has been suggested to enhance the diagnostic work-up of adult multiple sclerosis (MS). We aimed to evaluate the fulfillment of different CVS criteria and the added value of PRLs in 22 pediatric MS patients. Eleven patients (50%) fulfilled the 40%-rule threshold. Nineteen (86%) patients had ≥3 CVS+ WMLs or ≥1 PRL, whereas 17 (77%) had ≥6 CVS+ WMLs or ≥1 PRL. A simplified CVS-based approach, with the combined evaluation of ≥1 PRL in patients with ≥6 CVS+ WMLs, may improve MS diagnosis in pediatric patients.

Effectiveness of Defocus Incorporated Multiple Segments in Slowing Myopia Progression in Pediatric Patients as a Function of Age: Three-Year Follow-Up

Background: The purpose of this study is to evaluate the effectiveness of Defocus Incorporated Multiple Segments (DIMSs) in slowing myopia progression in pediatric patients as a function of age. Methods: This was a non-randomized experimenter-masked retrospective controlled observational study of European individuals aged 6–16 years with progressive myopia but no ocular pathology. We retrospectively reviewed the charts of the participants allocated to receive DIMS spectacles (Hoya® MiyoSmart®) or single-vision spectacle lenses (control group). Cycloplegic spherical equivalent (SE) and axial length (AL) were measured at baseline and at 12-, 24-, and 36-month follow-ups. The results were stratified by age into four groups: patients wearing DIMS spectacles older or younger than 10 years of age (group A, 20 patients mean age 13.6 ± 2.2, and group C, 20 patients mean age 9.0 ± 1.2) and age-matched control groups (group B, 18 patients mean age 13.2 ± 2.5, and group D, 22 patients mean age 8.5 ± 0.9). Results: At 36 months, SE and AL increase were significantly reduced in groups A and C, respectively, compared to groups B and D (p < 0.05). Linear regression analysis showed a significant correlation (p < 0.05) between patient age and myopia progression for SE in groups A and C, but only in group A for AL. Groups B and D did not show any significant correlation (p > 0.05). Conclusions: DIMS spectacles seem to slow myopia progression in pediatric patients; however, their effectiveness shows the greatest results in children older than 10 years of age. Moreover, our findings suggest that AL may be the more reliable parameter for evaluating myopia progression.

Influenza A/H3N2 and Its Co-infection with Other Respiratory Pathogens: Higher Pneumonia Rates and Prolonged Hospital Stays in Pediatric Patients

Background: In pediatric populations, influenza viruses such as influenza B, influenza A/H1N1, and influenza A/H3N2 present unique clinical challenges due to their distinct characteristics. Co-infections with other respiratory pathogens can lead to more severe disease progression in children, although the specific impacts of these co-infections are not yet fully understood. Objectives: To explore the differences in clinical characteristics among children with single infections of influenza B, influenza A/H1N1, and influenza A/H3N2, and to assess the impact of co-infections with other respiratory pathogens on the severity of disease in children. Methods: This retrospective study evaluated the severity of pediatric influenza hospitalizations during 2022 - 2023 by correlating virus types/subtypes with clinical outcomes, including pneumonia incidence, mechanical ventilation requirements, PICU admissions, and duration of hospital stay. Results: The study included 1,380 pediatric patients with influenza: 343 with influenza A/H1N1, 678 with A/H3N2, and 359 with influenza B. In children aged six and older, influenza A/H3N2 infection resulted in higher pneumonia rates and longer hospital stays compared to influenza A/H1N1 and influenza B (P < 0.05). Laboratory result differences were also observed between single infections of influenza A and B in this age group. The co-infection rate for influenza A/H1N1 was 3.5%, significantly lower than that for H3N2 (11.9%) and influenza B (10.6%) (P < 0.05). Clinical differences were noted between single and co-infections of influenza A/H3N2 and B, with co-infections showing higher pneumonia rates and longer hospital stays compared to single infections (P < 0.05). Conclusions: In children aged six and older, influenza A/H3N2 is associated with higher rates of pneumonia and longer hospital stays. Co-infections involving Influenza B or A/H3N2 with additional respiratory pathogens further increase the risk of pneumonia and extend the duration of hospitalization.

ESKAPE pathogens in pediatric cardiac surgery patients: 5-year microbiological monitoring inatertiary hospital in Kazakhstan.

Hospital acquired infections greatly affect recovery and survival in pediatric surgical patients. We evaluated prevalence and antimicrobial resistance of ESKAPE pathogens in neonates and infants subjected to cardiac surgery in a tertiary hospital in Central Kazakhstan between 2019 and 2023 (2,278 patients) using routine methods of microbiological detection. ESKAPE pathogens were found in 1,899 out of 2,957 samples (Staphylococcus aureus - 35.3%, Klebsiella pneumoniae - 27.8%, Acinetobacter baumannii - 14.5%, Pseudomonas aeruginosa - 12.4%, Enterobacter sp. - 8.8%, Enterococcus faecium - 1.2%). The total prevalence of ESKAPE increased significantly from 45.1 to 76.9% (P = 0.005) during the study period. The resistance significantly increased in methicillin-resistant S. aureus (MRSA, from13.7 to 41.9%, P = 0.041) but decreased in carbapenem-resistant P. aeruginosa (from 64.3 to 37.7%, P = 0.037) and carbapenem-resistant A. baumannii (from 48.5 to 19.1%, P = 0.039). Gradual but non-significant changes were shown in third-generation cephalosporin resistant K. pneumoniae (from 63.6 to 45.2%) and carbapenem-resistant K. pneumoniae (from 0 to 8.3%). The relative prevalence of ESKAPE pathogens steadily increased in our pediatric cardiac surgery patients in 2019-2023. The most frequent were S. aureus, K. pneumoniae, and A. baumannii, with dramatically increasing tendencies for MRSA. Our results highlight the necessity for a well-designed infection control strategy and constant microbiological monitoring in pediatric cardiac surgery departments.

High parathyroid hormone rather than low vitamin D is associated with reduced event-free survival in childhood cancer.

Vitamin D deficiency is linked to poor cancer outcomes, but the impact of its consequence, elevated parathyroid hormone (PTH) remains understudied. PTH receptor activation influences cancer progression in vitro, yet the effect of elevated PTH on pediatric cancer survival is unexamined. This retrospective study examines associations between PTH, 25-OH vitamin D (25OHD), and event-free survival (EFS) and overall survival (OS) in pediatric cancer patients. Laboratory data from 4,349 patients (0-18 years) at a tertiary pediatric cancer unit were analyzed for the highest PTH and lowest 25OHD levels at diagnosis and the following five years. Data on relapse, secondary malignancies, and mortality were stratified by PTH levels above/below the cohort median (47 pg/ml) and 25OHD levels ≤ 30 nmol/L. EFS and OS were analyzed, and hazard ratios (HR) were calculated for the entire cohort and six cancer subgroups. PTH and 25OHD values were available for 1,286 patients (731 male). Higher PTH associated with inferior EFS in primary malignant brain tumors (HR 1.80 [1.19-2.72]), embryonal (HR 2.20 [1.1-4.43]), and lymphatic malignancies (HR 1.98 [1.05-3.72]). Vitamin D deficiency associated with inferior EFS in embryonal malignancies (HR 2.41 [1.24-4.68]). In a multivariate Cox model, only higher PTH remained significant for inferior EFS. Elevated PTH may indicate adverse outcomes in certain pediatric cancers. This study identifies elevated parathyroid hormone (PTH) as a potential marker for poor outcomes in pediatric cancer patients, emphasizing the need for adequate vitamin D and calcium management.

Effect of Whole Bowel Irrigation for Ingested Lead-Containing Foreign Bodies: A Pediatric Case Series

Background Foreign body (FB) ingestions cause lead toxicity in pediatric patients. These ingestions result in continued lead absorption until passage or removal from the gastrointestinal (GI) tract. Whole-bowel irrigation (WBI) is frequently recommended to aid in the removal of FBs, however effectiveness of this practice is not clear. Methods We performed a retrospective chart review of pediatric patients (<18 years old) admitted for treatment of lead toxicity at an academic pediatric medical center from 1 January 2017 through 31 October 2023. We abstracted patient age, identity of ingested FB, lead concentrations, duration of WBI, maximum flow rate of WBI, success or failure of FB passage, performance and results of endoscopy, and duration of hospital stay. Results Nine cases with radiopaque FB suspected to be lead were treated with WBI. Three cases resulted in the complete expulsion of the ingested FB. Four patients underwent endoscopic removal after WBI median duration of 47.5 h (range 27–80.5 h). One patient failed to clear despite 168.5 h of WBI. Conclusion WBI did not lead to the clearance of all FBs in this series. Practitioners should consider early endoscopic removal if WBI does not result in passage of the FB within the first 48 h.

Role of vesicoureteral reflux on pediatric kidney allograft function.

Vesicoureteral reflux (VUR) is a common urologic complication of pediatric kidney transplant, though there is little data on the effect of VUR on histologic graft changes or graft survival. All pediatric patients who received a kidney transplant from 2007 to 2020 were selected for retrospective chart review. All participants underwent a voiding cystourethrogram (VCUG) at a 6-month post-transplant. Patients were then categorized into two groups based on vesicoureteral reflux grade: no/low-grade VUR (grades 0-2) and high-grade VUR (grades 3-5). Outcomes collected included graft failure rates, graft function, urinary tract infections(UTIs), proteinuria, and Banff scores at 3- and 12-month post-transplant surveillance kidney biopsies. There were 74 pediatric patients who received a kidney transplant in the designated time-period, and of those 39 had no/low-grade VUR and 35 had high-grade VUR. There was no difference in graft failure among the two groups over time when stratified for age (p = 0.389, CI 0.53-5.08). Patients with high grade VUR had a higher risk of UTI development overall (RR 1.89, 95%CI 1-3.6, p = 0.041), mostly accounted for from increased development of febrile UTI (RR 1.66, 95%CI 1.1-2.6, p = 0.038). Unselected pediatric kidney transplant recipients with high-grade vesicoureteral reflux on VCUG at a 6-month post-kidney transplant are more likely to have febrile UTI compared to those in the low-grade VUR group. There is no difference in graft survival among the two groups.

Optimizing β-lactam-containing antibiotic combination therapy for the treatment of Buruli ulcer.

The current treatment for Buruli ulcer is based on empirical evidence of efficacy. However, there is an opportunity for shortening its duration and improving response rates. Evolving understanding of the pharmacokinetic-pharmacodynamic relationships provides the basis for a stronger dose rationale for antibiotics. In conjunction with modelling and simulation, it is possible to identify dosing regimens with the highest probability of target attainment (PTA). This investigation aims to: (i) assess the dose rationale for a new combination therapy including amoxicillin/clavulanic acid (AMX/CLV) currently in clinical trials; and (ii) compare its performance with alternative dosing regimens including rifampicin, clarithromycin and AMX/CLV. In vitro estimates of the minimum inhibitory (MIC) concentration were selected as a measure of the antibacterial activity of different drug combinations. Clinical trial simulations were used to characterize the concentration vs. time profiles of rifampicin, clarithromycin and amoxicillin in a virtual cohort of adult and paediatric patients, considering the effect of baseline covariates on disposition parameters and interindividual variability in exposure. The PTA of each regimen was then assessed using different thresholds of the time above MIC. A weight-banded dosing regimen including 150-600 mg rifampicin once daily, 250-1000 mg clarithromycin and AMX/CLV 22.5mg/kg /1000 mg twice daily ensures higher PTA than the standard of care with AMX/CLV 45 mg/kg/2000 mg once daily. The higher PTA values support the proposed 4-drug combination (rifampicin, clarithromycin, AMX/CLV) currently under clinical investigation. Our findings also suggest that higher rifampicin doses might contribute to enhanced treatment efficacy.

Pediatric RVOT reconstruction with ePTFE trileaflet valved conduits: a dual-center Chinese study

ObjectiveThis study aims to assess the early to mid-term clinical efficacy of expanded polytetrafluoroethylene (ePTFE) trileaflet valved conduits in pediatric right ventricular outflow tract reconstruction for congenital heart disease.MethodsWe conducted a retrospective analysis of pediatric patients who underwent right ventricular outflow tract (RVOT) reconstruction using ePTFE trileaflet valved conduits at two cardiac centers in China, between January 2017 and June 2023. The main assessment criterion was the functionality of the prosthetic pulmonary valve conduit.ResultsA total of 162 pediatric patients were included, with follow-up periods ranging from 0.1 to 5 years post-discharge, and a median follow-up duration of 1 year (interquartile range: 1, 2). Three patients (1.9%) required re-operation due to conduit obstruction. During follow-up, pulmonary valve flow velocities were recorded as &amp;lt;3 m/s in 134 patients (82.7%), between 3 and 4 m/s in 24 patients (14.8%), and &amp;gt;4 m/s in 4 patient (2.5%). Mild pulmonary valve regurgitation was noted in 148 patients (91.4%), and moderate pulmonary valve regurgitation was noted in 14 patients (8.6%), with no instances of more than moderate pulmonary valve regurgitation.ConclusionThe ePTFE trileaflet valved conduit, known for its accessibility and simplicity in manufacturing, demonstrates favorable early to mid-term clinical outcomes in pediatric RVOT reconstruction.

The enhanced recovery after surgery protocol in paediatric surgery: The analysis of the protocol principles based on a survey among Polish clinical centres

Introduction: The enhanced recovery after surgery (ERAS) protocol is a complex set of measures that improves patient outcomes in the adult population. The main goal of the protocol is to sustain homeostasis by mitigating the metabolic stress induced by surgical procedures. Hence, the search for similar solutions in paediatric patients since the benefits in the paediatric population are less well known. Material and methods: The principles of the ERAS protocol were presented. A questionnaire survey was prepared to assess the preparation for the implementation of ERAS in paediatric surgery departments. Heads of all 19 clinical centres from Poland providing colorectal surgery in children were invited to participate. Seven centres responded to the survey. The questionnaire included four general questions related to the familiarity with ERAS and specific questions about the implementation of the 23-item protocol. Results: Five centres confirmed familiarity with the principles of the protocol and two of them confirmed the use of ERAS. The lowest number of implemented procedures was six, while the highest number was 18 out of 23. No centre implemented the zero fluid balance strategy. However, as many as five of the seven centres avoided preoperative fasting, three centres avoided mechanical bowel preparation, and three respondents used early oral nutrition in the postoperative period. Conclusions: The ERAS protocol is commonly used and accepted worldwide. Other surgical teams may use the information contained in the manuscript to create or improve their ERAS protocol.

Molecular cytogenetic characterization of isolated recurrent 4q35.2 microduplication in Chinese population: a seven-year single-center retrospective study

BackgroundWith the extensive use of chromosomal microarray analysis (CMA), an increasing number of variants of uncertain significance (VOUS) have been detected. The objective of the present study was to elucidate the pathogenicity and clinical variability associated with isolated recurrent 4q35.2 microduplications within the Chinese population.MethodsThe present study involved 14 cases of isolated recurrent 4q35.2 microduplication (including 12 fetuses and 2 cases of pediatric patients) out of 5,188 subjects who sought genetic consultation at our hospital and received CMA detection. WES technology was subsequently utilized to identify additional sequence variants in a patient with multiple clinical anomalies.ResultsAll 14 cases exhibited isolated recurrent 4q35.2 microduplications spanning a 1.0-Mb region encompassing the ZFP42 gene. Among the 12 fetuses, 11 displayed normal clinical features, while one was born with renal duplication and hydronephrosis. Additionally, in the two pediatric patients, WES was performed for Case 1, who presented with congenital cataracts, severe intellectual disability, and seizures. This patient inherited the 4q35.2 microduplication from his phenotypically normal mother. WES identified a novel NM_000276:c.2042G > T (p.G681V) variant in the OCRL gene, which is associated with Lowe syndrome and may account for the observed phenotypic variability within this family.ConclusionA series of 14 cases with isolated recurrent 4q35.2 microduplications were investigated, highlighting a potential association with increased susceptibility to renal abnormalities. Further, the present findings may expand the mutation spectrum of the OCRL gene associated with Lowe syndrome and provide valuable insights for the genetic etiological diagnosis of patients with unexplained copy number variants.

Genetic and Functional Studies of Patients with Thyroid Dyshormonogenesis and Defects in the TSH Receptor (TSHR)

Genetic defects in the TSH receptor (TSHR) can cause poor thyroid differentiation (thyroid dysgenesis) and/or thyroid malfunction (thyroid dyshormonogenesis). The phenotype spectrum is wide: from severe congenital hypothyroidism to mild hyperthyrotropinemia. Over 250 TSHR variants have been published, many uncharacterized in vitro. We aimed to genetically characterize patients with thyroid dyshormonogenesis with TSHR defects and to study in vitro the effect of the genetic variants to establish the genotype–phenotype relationship. Pediatric patients with thyroid dyshormonogenesis (160 patients, Catalan CH neonatal screening program, confirmation TSH range: 18.4–100 mIU/L), were analyzed by a high-throughput gene panel. In vitro studies measuring the TSH-dependent cAMP–response–element activation were performed. Five patients with mild or severe thyroid dyshormonogenesis presented six TSHR variants, two unpublished. Each variant showed a different in vitro functional profile that was totally or partially deleterious. Depending on the genotype, some of the variants showed partial deficiency in both genotypes, whereas others presented a different effect. In conclusion, the percentage of patients with thyroid dyshormonogenesis and candidate variants in TSHR is 3.13%. Our in vitro studies contributed to the confirmation of the pathogenicity of the variants and highlighted the importance of studying the effect of the patient’s genotype for a correct diagnostic confirmation.

Insulin-induced copeptin response in children and adolescents to diagnose arginine vasopressin deficiency.

The diagnosis of arginine vasopressin deficiency (AVD, formerly central diabetes insipidus) remains a challenge. In recent years, stimulated copeptin has emerged as a promising tool to diagnose AVD. In this single centre retrospective study, we identified paediatric patients with suspected pituitary insufficiency who underwent standard insulin tolerance testing (ITT) previously. Patients with AVD and non-matched controls without polyuria-polydipsia syndrome were identified. Diagnosis of AVD was confirmed retrospectively using comprehensive clinical and diagnostic characteristics. Serum copeptin concentrations were measured using a commercially available automated immunofluorescence assay (B.R.A.H.M.S Copeptin-proAVP KRYPTOR®) in -20°C stored samples collected before and 30, 45 and 60 minutes after insulin injection. Cut-off analyses were performed using ROC curves. 25 patients with AVD and 43 non-matched controls were available for analysis. Median basal copeptin concentrations of 1.51 pmol/l (IQR: 0.91-1.95; serum osmolarity: 288.5 mmol/l (IQR: 282.3-293.5) increased at a median of 30 minutes to a maximum of 1.95 pmol/l (IQR: 1.31-2.39) in AVD patients (p=0.113), and from 4.41 pmol/l (IQR: 3.36-6.68; serum osmolarity: 281.0 mmol/l (IQR: 274.0-286.0, p&lt;0.001) to a maximum of 8.39 pmol/l (IQR: 4.95-19.72) (p&lt;0.001) in controls. ROC analysis resulted in a cut-off of 3.0 pmol/l for maximum copeptin (91.7 % sensitivity, 94.1 % specificity) for the diagnosis of AVD. Our results suggest that insulin-stimulated serum copeptin concentrations are a sensitive and specific diagnostic tool for AVD in paediatric patients, which allows us to test multiple pituitary hormone axes simultaneously in a single test.

Our Single Center Experience in Osteoid Osteoma Patients Treated with CT-Guided Percutaneous Radiofrequency Ablation Treatment and Follow-up.

Introduction Osteoid osteoma (OO) is a painful benign bone tumor. Typically, it causes pain that is most noticeable during the night, which is improved by nonsteroidal anti-inflammatory drugs. In the treatment of symptomatic lesions, open surgery for nidus removal is the gold standard. However, surgical technical difficulties and morbidities vary by location. Percutaneous radiofrequency ablation (RFA) therapy guided by computed tomography (CT) is now a popular treatment option for OO. This study aims to assess our single-center experience with the technique, complications, and procedure effectiveness. Materials and Methods The study included fifteen patients who were treated between 2017 and 2021. A retrospective analysis was carried out on archive images and file records. The lesions' location, nidus width, and affected area (cortical, medullary) were all recorded. The procedure and technical success, as well as postoperative complications and the need for repeat ablation, were all documented. Results A total of 20 patients, 18 men, and 2 women, were included in the study, and 12 of them were pediatric patients. The patients' mean age was 16.9±7.3 years old, and the mean nidus diameter was 7.1±8.7 mm. There were 13 cortical niduses, 2 intramedullary niduses, and 5 corticomedullary niduses. The lesions were in the femur (n=12), tibia (n=6), scapula (n=1), and vertebrae (n=1). Two recurrences (10%) were observed in our patients during the follow-up. Patient with a femoral OO, the pain started again 12 weeks after the procedure and we performed additional RFA. The patient with vertebral OO had fewer symptoms and full recovery was not achieved. Therefore, the vertebral OO was ablated again 4 months later, and clinical success was achieved. One patient had a minor burn at the entry site that went away on its own after a short period of time. Except for the patient who was scheduled for a repeat RFA, no recurrence has been observed so far. The primary and secondary success rates are, respectively, 90% (18/20) and 100% (20/20). Conclusion RFA has a high success rate in treating OO. The procedure failure and recurrence rates are low. There are possibilities for posttreatment pain relief, early discharge, and a quick return to daily life. For inappropriate lesion localization, the RFA process replaces surgical treatment. The procedure-related complication rate is low. On the other hand, the burn during the procedure can be a serious problem.

Short-term effectiveness and side effects of ketogenic diet for drug-resistant epilepsy in children with genetic epilepsy syndromes

BackgroundDrug-resistant epilepsy (DRE) impacts a significant portion, one-third, of individuals diagnosed with epilepsy. In such cases, exploring non-pharmacological interventions are crucial, with the ketogenic diet (KD) standing out as a valuable option. KD, a high-fat and low-carb dietary approach with roots dating back to the 1920s for managing DRE, triggers the formation of ketone bodies and modifies biochemistry to aid in seizure control. Recent studies have increasingly supported the efficacy of KD in addressing DRE, showcasing positive outcomes. Furthermore, while more research is needed, limited data suggests that KD May also be beneficial for specific genetic epilepsy syndromes (GESs).ObjectiveThis study aimed to assess the short-term efficacy of KD among pediatric patients diagnosed with GESs.Materials and methodsThis is a multi-center retrospective analysis of pediatric patients with GESs diagnosed using next-generation sequencing. The enrolled patients followed the keto-clinic protocol, and the KD efficacy was evaluated at 3, 6, and 12-month intervals based on seizure control and compliance. The collection instrument included demographic, baseline, and prognostic data. The collected data was coded and analyzed promptly.ResultsWe enrolled a cohort of 77 patients with a mean current age of 7.94 ± 3.83 years. The mean age of seizure onset was 15.5 months. Notably, patients experienced seizures at a younger age tended to have less positive response to diet. Overall, 55 patients responded favorably to the diet (71.4%) while 22 patients (28.6%) showed no improvement. Patients with genetic etiology showed a significantly more favorable responses to the dietary intervention. Patients with Lennox–Gastaut syndrome showed the most significant improvement (14/15) followed by patients with Dravet syndrome (6/8), and West syndrome (3/4). The number of used anti-seizure medications also played a significant role in determining their response to the diet. While some patients experienced mild adverse events, the most common being constipation, these occurrences were not serious enough to necessitate discontinuation of the diet.ConclusionThe study revealed a high improvement rate in seizure control, especially among younger patients and those with later seizure onset. The success of dietary treatment hinges greatly on early intervention and the patient’s age. Certain genetic mutations responded favorably to the KD, while efficacy varied among various genetic profiles.

Unraveling the Molecular Pathogenesis of Protein C Deficiency-Associated VTE: Insights from Protein C Mutations C238G and R189W in Thai Patients.

Protein C (PC) deficiency is a well-established risk factor for thromboembolism (TE), commonly manifesting in pediatric patients. This study aimed to elucidate the pathogenic mechanisms of two novel PC mutations, C238G and R189W, identified in Thai children with both venous and arterial TE. The effects of wild-type (WT), C238G, and R189W PC variants were investigated through transient transfection of HEK293T cells. PC secretion levels were measured, and immunofluorescence analysis was performed to assess intracellular localization. ER stress-related gene expression and UPR activation were evaluated. Structural analysis was conducted to explore the significance of the C238 and R189W residue in PC functionality. The C238G mutation led to a severe 95% reduction in PC secretion, while R189W showed a 30% decrease compared with WT. Immunofluorescence revealed that C238G-PC was predominantly retained in the ER, indicating protein misfolding. C238G-expressing cells exhibited significant upregulation of ER stress-related genes and UPR activation. In contrast, R189W resulted in only a modest increase in UPR gene expression, suggesting a less pronounced impact on protein folding and secretion. Structural analysis demonstrated the critical role of the C238 residue in maintaining PC's disulfide bond and overall conformation. This study reveals distinct molecular mechanisms by which the C238G and R189W mutations contribute to PC deficiency and increased thrombotic risk. The findings emphasize the essential role of the C238 residue in preserving PC structure and secretion, enhancing the understanding of PC deficiency-associated TE in pediatric patients.