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The Turkish Journal of Pediatrics 2024Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We...
BACKGROUND
Intensive multimodal treatment can improve survival in patients with high-risk neuroblastoma, and consolidative radiation therapy has contributed to local control. We examined the clinical outcomes of patients who underwent consolidative radiation therapy at our institution.
METHODS
We retrospectively reviewed the records of patients with high-risk neuroblastoma who underwent consolidative radiation therapy from March 2001 to March 2021 at Asan Medical Center. Patients underwent multimodal treatment including high-dose chemotherapy, surgery, stem cell transplantation, and maintenance therapy. Radiation (median, 21.0 Gy; range, 14-36) was administered to the primary site and surrounding lymph nodes.
RESULTS
This study included 37 patients, and the median age at diagnosis was 2.8 years (range, 1.3-10.0). Four patients exhibited local failure, and 5-year free-from locoregional failure rate was 88.7%, with a median followup period of 5.7 years. The 5-year disease-free survival (DFS) and overall survival (OS) rates were 59.1% and 83.6%, respectively. Univariate analysis revealed that patients with neuron-specific enolase levels > 100 ng/mL had significantly worse DFS and OS (P = 0.036, 0.048), and patients with no residual disease before radiation therapy showed superior OS (P = 0.029). Furthermore, patients with 11q deletion or 17q gain exhibited poor DFS and OS, respectively (P = 0.021, 0.011). Six patients experienced grade 1 acute toxicity. Late toxicity was confirmed in children with long-term survival, predominantly hypothyroidism and hypogonadism, typically < grade 3, possibly attributed to combination treatment. Four patients experienced late toxicity ≥ grade 3 with chronic kidney disease, growth hormone abnormality, ileus, premature epiphyseal closure, and secondary tumor, and recovered by hospitalization or surgical treatment.
CONCLUSIONS
In patients with high-risk neuroblastoma, consolidative radiotherapy to the primary tumor site resulted in excellent local control and a tolerable safety profile.
Topics: Child; Humans; Infant; Child, Preschool; Retrospective Studies; Neuroblastoma; Disease-Free Survival; Combined Modality Therapy
PubMed: 38523384
DOI: 10.24953/turkjped.2023.575 -
The Journal of Investigative Dermatology Mar 2024The read-through therapy suppresses premature termination codons and induces read-through activity consequently restoring missing proteins. Aminoglycosides are widely...
The read-through therapy suppresses premature termination codons and induces read-through activity consequently restoring missing proteins. Aminoglycosides are widely studied as read-through drugs in different human genetic disorders including hereditary skin diseases. Our previous work revealed that aminoglycosides have effect on COL17A1 nonsense mutations and represent a therapeutic option to alleviate disease severity. However, the amount of restored type XVII collagen (C17) in C17 deficient junctional epidermolysis bullosa (JEB-C17) keratinocytes was less than 1% relative to normal keratinocytes and was achieved only after high dose gentamicin treatment, which induced deep transcriptional changes. Therefore, in this study, we designed a strategy for the read-through therapy to challenge with aminoglycosides limitation factors in clinical use and the chronic inflammation in JEB-C17 patients. We developed TRID-C5 containing low dosage of aminoglycosides, CC-90009, NMDI-14, melatonin and apocynin that was able to induce about 20% of missing C17 without cell toxicity and effect on in vitro wound closure. TRID-C5 significantly induced COL17A1 expression and reverted the proinflammatory phenotype of JEB-C17 keratinocytes. Evaluation of this drug cocktail regarding its stability, penetration and efficacy as a topical treatment remains to be determined. TRID-C5 might represent an improved therapeutic strategy for JEB and for other genetic skin disorders.
PubMed: 38522573
DOI: 10.1016/j.jid.2024.02.027 -
Frontiers in Pediatrics 2024Interventions using ultrasound-guided closed reduction and percutaneous pinning (UG-CRPP) of humeral lateral condylar fractures (HLCFs) have been increasingly applied;...
BACKGROUND
Interventions using ultrasound-guided closed reduction and percutaneous pinning (UG-CRPP) of humeral lateral condylar fractures (HLCFs) have been increasingly applied; however, their effectiveness for unstable HLCFs and the criteria for ultrasound outcomes remain unclear. This study assessed the outcomes of UG-CRPP for HLCFs and evaluated the success criteria in children.
METHODS
Data were retrospectively collected from 106 patients with unstable HLCFs admitted to three hospitals between January 2021 and August 2022. Fifty-five cases were left-sided and 51 cases were right-sided: 74 male patients and 32 female patients were included. Perioperative data, elbow function, complications, and criteria for UG-CRPP were analyzed.
RESULTS
The mean rate of UG-CRPP was 88%. The mean surgical time was 54.56 ± 21.07 min, and the mean fluoroscopy frequency was 9.25 ± 2.93 times. At the last follow-up, there were significant differences in elbow flexion between the affected side (135.82° ± 6.92°) and the unaffected side (140.58° ± 5.85°) ( = 0.01). The Mayo score of the affected side was 90.28° ± 4.97°, the Baumann angle was 71.4° ± 5.4°, condylar shaft angle was 39.9° ± 6.4°, and the carrying angle was 8.4° ± 3.6°. Seventy patients presented mild lateral spurs and 16 patients exhibited moderate spurs. Fourteen patients presented with pin infection, and one patient exhibited postoperative re-displacement. There was no premature physeal closure, varus, or valgus elbow deformity, delayed union, or non-union. Successful ultrasound-based outcome criteria for UG-CRPP were defined as follows: (i) absent or less than a cartilage thickness step on the cartilage hinge on coronal plane parallel articular surface scanning, (ii) no lateral displacement and intact distal end of the condylar and capitellum on coronal plane vertical articular surface scanning, (iii) no anteroposterior displacement and absent or less than a cartilage thickness step on sagittal plane vertical articular surface scanning, and (iv) intact posterior fracture line or less than a cortex step on posterolateral sagittal plane vertical articular surface scanning.
CONCLUSION
UG-CRPP is a procedure with minimal blood loss, less invasive, cosmetic, and no radiation exposure. It yielded good outcomes in unstable HLCFs. The successful criteria make it suitable for clinical application.
PubMed: 38510077
DOI: 10.3389/fped.2024.1373913 -
JAMA Network Open Mar 2024Platform trials have become increasingly common, and evidence is needed to determine how this trial design is actually applied in current research practice.
IMPORTANCE
Platform trials have become increasingly common, and evidence is needed to determine how this trial design is actually applied in current research practice.
OBJECTIVE
To determine the characteristics, progression, and output of randomized platform trials.
EVIDENCE REVIEW
In this systematic review of randomized platform trials, Medline, Embase, Scopus, trial registries, gray literature, and preprint servers were searched, and citation tracking was performed in July 2022. Investigators were contacted in February 2023 to confirm data accuracy and to provide updated information on the status of platform trial arms. Randomized platform trials were eligible if they explicitly planned to add or drop arms. Data were extracted in duplicate from protocols, publications, websites, and registry entries. For each platform trial, design features such as the use of a common control arm, use of nonconcurrent control data, statistical framework, adjustment for multiplicity, and use of additional adaptive design features were collected. Progression and output of each platform trial were determined by the recruitment status of individual arms, the number of arms added or dropped, and the availability of results for each intervention arm.
FINDINGS
The search identified 127 randomized platform trials with a total of 823 arms; most trials were conducted in the field of oncology (57 [44.9%]) and COVID-19 (45 [35.4%]). After a more than twofold increase in the initiation of new platform trials at the beginning of the COVID-19 pandemic, the number of platform trials has since declined. Platform trial features were often not reported (not reported: nonconcurrent control, 61 of 127 [48.0%]; multiplicity adjustment for arms, 98 of 127 [77.2%]; statistical framework, 37 of 127 [29.1%]). Adaptive design features were only used by half the studies (63 of 127 [49.6%]). Results were available for 65.2% of closed arms (230 of 353). Premature closure of platform trial arms due to recruitment problems was infrequent (5 of 353 [1.4%]).
CONCLUSIONS AND RELEVANCE
This systematic review found that platform trials were initiated most frequently during the COVID-19 pandemic and declined thereafter. The reporting of platform features and the availability of results were insufficient. Premature arm closure for poor recruitment was rare.
Topics: Humans; Pandemics; COVID-19; Cognition; Data Accuracy; Medical Oncology
PubMed: 38506807
DOI: 10.1001/jamanetworkopen.2024.3109 -
International Journal of Burns and... 2024The primary objective of this study was to juxtapose the union rate and incidence of complications in paediatric patients presenting early (≤ 7 days) following injury...
The primary objective of this study was to juxtapose the union rate and incidence of complications in paediatric patients presenting early (≤ 7 days) following injury with children presenting later (> 7 days) with femoral neck fractures. This critical appraisal evaluated 15 patients according to their timing of presentation and surgery from the initial day of injury (Group A: operated ≤ 7 days or Group B: > 7 days of injury). Patients with traumatic femoral neck fractures with Delbet 1 to 4 subtypes who were skeletally immature (age ≤ 16 years) were included in the study. Pathological fractures and post-infective fractures were not included. Each patient's secondary loss of reduction was calculated by measuring the Neck shaft angle (NSA) on the immediate post-operative radiograph and at the union. A change in NSA of ≥ 5 degrees was considered a significant loss of reduction. Ratliff's Criteria was used to analyze the final result, and a thorough record of complications was kept. There were no significant variations in the two groups' with respect to distributions of age, sex, injury mechanism, or fracture pattern. The most frequent injury culprit in both groups was falling from a height. Type II fracture pattern (54.54%) was more common in group A, while Type III and Type II fracture pattern was equally distributed in group B. In group A, the mean operation time was 55 ± 8.25 minutes, whereas in group B, it was 65 ± 15 minutes (-value > 0.05). In group A, 90.9% of patients underwent CCS fixation, and in group B, 75% underwent fixation by CCS. The quality of reduction in post-operative radiographs was anatomical in 10 (90.9%) patients and unacceptable in 1 (9.1%) patient. In group B, 2 (50%) patients had an anatomical reduction, while 2 (50%) patients had an unacceptable reduction. Timing of reduction and its association with complications showed that early stable reduction and fixation decrease the occurrence of complications in femoral neck fractures (-value = 0.033). Fracture union was seen in all our patients in both groups and none of our patients underwent non-union. The mean union time was 11.11 ± 7.06 weeks in group A and 16.5 ± 2.59 weeks in group B (-value = 0.0189). In group A, only 1 (9.1%) patient developed coxa vara. In group B, out of 4 patients, the femoral head of one patient underwent avascular necrosis, one patient exhibited coxa vara, and 1 patient developed premature physeal closure with limb length inequality. Management of femoral neck fractures in children is challenging because of the paediatric bone's peculiar anatomic and physiological considerations. In our study, patients operated within 7 days developed fewer complications as compared to patients who were operated after 7 days, which was statistically significant. Although AVN is a frequent adverse consequence of pediatric femoral neck fractures, early reduction and stable fixation lowers AVN rates, as observed in our study. Our short-term functional and radiological results using the Ratliff scoring system were comparable to previous studies owing to stable anatomic reduction. Based on our findings and the existing literature, we emphasize long-term follow-up and recommend an early stable anatomic reduction in the treatment of paediatric femoral neck fractures.
PubMed: 38505344
DOI: 10.62347/ZQKE1542 -
Early Human Development Apr 2024Patent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited...
Active versus restrictive ligation strategy for patent ductus arteriosus - A retrospective two-center study of extremely preterm infants born between 22 + 0 and 25 + 6 weeks of gestational age.
BACKGROUND
Patent ductus arteriosus (PDA) in premature infants is associated with adverse clinical outcomes. Mode and timing of treatment are still controversial. Data are limited in the most extremely premature infants <26 weeks of gestational age (GA), where clinical problems are most significant and patients are most vulnerable.
AIMS
To investigate whether different approaches to surgical closure of PDA in two large Swedish centers has an impact on clinical outcomes including mortality in extremely preterm infants born <26 weeks GA.
STUDY DESIGN
Retrospective, two-center, cohort study.
SUBJECTS
Infants born at 22-25 weeks GA between 2010 and 2016 at Uppsala University Children's Hospital (UUCH; n = 228) and Queen Silvia Children's Hospital Gothenburg (QSCHG; n = 220).
MAIN OUTCOME MEASURES
Survival, bronchopulmonary dysplasia (BPD), and retinopathy of prematurity (ROP).
RESULTS
Surgical closure of PDA was more common and performed earlier at QSCHG (50 % vs 16 %; median age 11 vs 44 days; p < 0.01). Survival was similar in both centres. There was a higher incidence of severe BPD and longer duration of mechanical ventilation at UUCH (p < 0.01). There was a higher incidence of ROP, IVH and sepsis at QSCH (p < 0.05, p < 0.01 and p < 0.01). A sub-group analysis matching all surgically treated infants at QSCHG with infants at UUCH with the same GA showed similar results as the total cohort.
CONCLUSION
Earlier and higher rate of surgical PDA closure in this cohort of extremely preterms born <26 weeks GA did not impact mortality but was associated with lower rates of severe BPD and higher rates of severe ROP.
Topics: Infant; Female; Child; Infant, Newborn; Humans; Infant, Extremely Premature; Ductus Arteriosus, Patent; Gestational Age; Retrospective Studies; Cohort Studies; Bronchopulmonary Dysplasia; Retinopathy of Prematurity
PubMed: 38452632
DOI: 10.1016/j.earlhumdev.2024.105976 -
Journal of Neurosurgery. Case Lessons Mar 2024Myelomeningocele (MMC) is the most serious form of spina bifida, a congenital defect in neural tube development. Defect closure in a patient with an extremely low birth...
BACKGROUND
Myelomeningocele (MMC) is the most serious form of spina bifida, a congenital defect in neural tube development. Defect closure in a patient with an extremely low birth weight presents unique challenges and risks; lower birth weight is associated with multiple organ system concerns, homeostasis is difficult, and local tissue is underdeveloped. To the authors' knowledge, the present case is the lowest reported weight (490 g) for a neonate with postnatal MMC repair.
OBSERVATIONS
A preterm male with a prenatally diagnosed lumbosacral MMC and associated Chiari malformation type II was born at 23 weeks 1 day to a 29-year-old mother, gravidity 6 parity 4. The patient was medically stabilized and underwent MMC closure on day of life 5. His weight was 490 g at the time of this repair, and he did not have any surgical complications. At age 16 months, he underwent endoscopic third ventriculostomy with choroid plexus cauterization; he has not required any further hydrocephalus treatments since the last follow-up at 30 months of age.
LESSONS
To the authors' knowledge, this case is the lowest birth weight ex utero MMC closure reported in the literature. Challenges of prematurity and size required appropriate preoperative stabilization, careful hemostasis and temperature regulation, and meticulous surgical technique.
PubMed: 38437685
DOI: 10.3171/CASE23556 -
Journal of Orthopaedic Case Reports Feb 2024Distal tibia fractures are a common cause of physeal injuries that can subsequently cause deformity in pediatric populations. Limited literature exists supporting...
INTRODUCTION
Distal tibia fractures are a common cause of physeal injuries that can subsequently cause deformity in pediatric populations. Limited literature exists supporting treatment strategies for varus deformities. In this study, we illustrate a unique case of premature physeal closure complicated by development of a varus ankle deformity treated with navigation guided physeal bar resection that spontaneously resolved without the requirement for guided growth.
CASE REPORT
A 6-year-old female presented to our clinic after development of a right ankle varus deformity measuring 14°. She had sustained a right Salter Harris type 3 distal tibia fracture 10 months prior and underwent fixation at an external facility. After undergoing navigation guided physeal bar resection, resolution of her deformity occurred without the use of guided growth.
CONCLUSION
Spontaneous resolution of an ankle deformity is possible after a physeal bar resection. However, in these technically demanding procedures, it is important to optimize accuracy and results using preoperative bar mapping and intraoperative three-dimensional navigation.
PubMed: 38420249
DOI: 10.13107/jocr.2024.v14.i02.4212 -
Advances in Medical Education and... 2024Literature suggest that physicians' high level of confidence has a negative impact on medical decisions, and this may lead to medical errors. Experimental research is...
BACKGROUND
Literature suggest that physicians' high level of confidence has a negative impact on medical decisions, and this may lead to medical errors. Experimental research is lacking; however, this study investigated the effects of high confidence on diagnostic accuracy.
METHODS
Forty internal medicine residents from different hospitals in Saudi Arabia were divided randomly into two groups: A high-confidence group as an experimental and a low-confidence group acting as a control. Both groups solved each of eight written complex clinical vignettes. Before diagnosing these cases, the high-confidence group was led to believe that the task was easy, while the low-confidence group was presented with information from which it could deduce that the diagnostic task was difficult. Level of confidence, response time, and diagnostic accuracy were recorded.
RESULTS
The participants in the high-confidence group had a significantly higher confidence level than those in the control group: 0.75 compared to 0.61 (maximum 1.00). However, neither time on task nor diagnostic accuracy significantly differed between the two groups.
CONCLUSION
In the literature, high confidence as one of common cognitive biases has a strong association with medical error. Even though the high-confidence group spent somewhat less time on the cases, suggesting potential premature decision-making, we failed to find differences in diagnostic accuracy. It is suggested that overconfidence should be studied as a personality trait rather than as a malleable characteristic.
PubMed: 38410282
DOI: 10.2147/AMEP.S442689 -
European Heart Journal. Case Reports Feb 2024Previously, ablation at the outflow tract was considered to be safe and rarely affected the His-Purkinje system due to their spatial distance. However, we have reported...
BACKGROUND
Previously, ablation at the outflow tract was considered to be safe and rarely affected the His-Purkinje system due to their spatial distance. However, we have reported a case of right bundle branch block (RBBB) and junctional beats that were recorded during radiofrequency catheter ablation in a patient who had a history of peri-membranous ventricular septal defect (pmVSD) closure and the implantation of a metallic occluder.
CASE SUMMARY
A 16-year-old girl with a metallic occluder for peri-membranous ventricular septum defect underwent an ablation procedure for premature ventricular complexes. During the ablation at the right ventricular outflow tract (RVOT), RBBB and junctional beats were recorded. His bundle potentials and the high-frequency potential generated by electrical interference were observed when mapping the margin of the occluder. To ensure safety, we attempted ablation at the right coronary cusp in the left ventricular outflow tract, which eventually proved to be successful, presenting an alternative ablation strategy.
CONCLUSION
This is a rare report of RBBB and junctional beats observed during ablation at RVOT in a patient with pmVSD and a metallic occluder. The observed damage to the His-Purkinje system may be attributed to uncontrolled radiofrequency energy heating up caused by the metallic device. This case emphasizes the importance of thorough electroanatomic and activation mapping prior to starting the ablation procedure, especially in complicated cases. Furthermore, it suggests that ablation at a relatively remote position is both feasible and relatively safe for patients with occluder devices.
PubMed: 38362062
DOI: 10.1093/ehjcr/ytae054