Pediatric Patients Research Articles

Identification of Prostaglandin I2 Synthase Rare Variants in Patients With Williams Syndrome and Severe Peripheral Pulmonary Stenosis.

Peripheral pulmonary stenosis (PPS) is a condition characterized by the narrowing of the pulmonary arteries, which impairs blood flow to the lung. The mechanisms underlying PPS pathogenesis remain unclear. Thus, the aim of this study was to investigate the genetic background of patients with severe PPS to elucidate the pathogenesis of this condition. We performed genetic testing and functional analyses on a pediatric patient with PPS and Williams syndrome (WS), followed by genetic testing on 12 patients with WS and mild-to-severe PPS, 50 patients with WS but not PPS, and 21 patients with severe PPS but not WS. Whole-exome sequencing identified a rare PTGIS nonsense variant (p.E314X) in a patient with WS and severe PPS. Prostaglandin I2 synthase (PTGIS) expression was significantly downregulated and cell proliferation and migration rates were significantly increased in cells transfected with the PTGIS p.E314X variant-encoding construct when compared with that in cells transfected with the wild-type PTGIS-encoding construct. p.E314X reduced the tube formation ability in human pulmonary artery endothelial cells and caspase 3/7 activity in both human pulmonary artery endothelial cells and human pulmonary artery smooth muscle cells. Compared with healthy controls, patients with PPS exhibited downregulated pulmonary artery endothelial prostaglandin I2 synthase levels and urinary prostaglandin I metabolite levels. We identified another PTGIS rare splice-site variant (c.1358+2T>C) in another pediatric patient with WS and severe PPS. In total, 2 rare nonsense/splice-site PTGIS variants were identified in 2 pediatric patients with WS and severe PPS. PTGIS variants may be involved in PPS pathogenesis, and PTGIS represents an effective therapeutic target.

Superficial erosions in a pediatric patient.

Superficial erosions in a pediatric patient.

The association of COVID-19 pandemic with the increase of sinogenic and otogenic intracranial infections in children: a 10-year retrospective comparative single-center study.

Otitis media and sinusitis are common childhood infections, typically mild with good outcomes. Recent studies show a rise in intracranial abscess cases in children, raising concerns about a link to COVID-19. This study compares a decade of data on these cases before and after the pandemic. This retrospective comparative analysis includes pediatric patients diagnosed with otitis media and sinusitis, who later developed intracranial abscesses over the past decade. We collected comprehensive data on the number of cases, patient demographics, symptoms, treatment, and outcomes. Between January 2013 and July 2023, our center identified 10 pediatric patients (median age 11.1years, range 2.2-18.0 years, 60% male) with intracranial abscesses from otitis media and sinusitis. Of these, 7 cases (70%, median age 9.7 years, range 2.2-18.0 years) occurred since the onset of the COVID-19 pandemic, while the remaining 3 cases (30%, median age 13.3 years, range 9.9-16.7 years) were treated before the pandemic. No significant differences were found in otolaryngological associations, surgical interventions, preoperative symptoms, lab findings, or postoperative antibiotics between the two groups. All patients showed positive long-term recovery. This study reveals 5-fold increase of pediatric otogenic and sinogenic intracranial abscess cases in the last three-years since the onset of the COVID-19 pandemic. While further investigation is needed, these findings raise important questions about potential connections between the pandemic and the severity of otitis media and sinusitis complications in children. Understanding these associations can improve pediatric healthcare management during infectious disease outbreaks.

Surgical management of lobar cerebral cavernous malformations in children: a single-center experience.

We aimed to determine the surgical indications and postoperative outcomes among pediatric patients with lobar cerebral cavernous malformations (CCMs). We retrospectively reviewed pediatric patients operated on for lobar CCM between March 2010 and August 2021. Indications for surgery included (1) intracranial hemorrhage, (2) symptomatic superficially located lesion, and (3) asymptomatic CCM in non-eloquent area in case of strong parental preferences. Patients presenting with seizures were assessed using Engel Epilepsy Surgery Outcome Scale. Twenty-one patients were included. The predominant symptoms were seizures (57.1%), headaches (33.3%), and focal neurological deficits (23.8%). Patients were qualified for surgery due to symptomatic intracranial hemorrhage (47.6%), drug-resistant epilepsy (28.6%), and focal neurological deficits (9.5%). Three patients (14.3%) were asymptomatic. A gross total resection of CCM with the surrounding hemosiderin rim was achieved in all patients. The mean follow-up was 52 months. No patient experienced surgery-related complications. In all individuals with a preoperative first episode of seizures or focal neurological deficits, the symptoms subsided. All six patients with drug-resistant epilepsy improved to Engel classes I (67%) and II (33%). Surgical removal of symptomatic lobar CCMs in properly selected candidates remains a safe option. Parental preferences may be considered a sole qualifying criterion for asymptomatic lobar CCM excision.

Pubertal retroareolar cysts presenting as bluish lumps: New cases and literature review.

Retroareolar cysts (RCs) are a benign self-resolving condition primarily affecting pubertal individuals. However, their presentation as asymptomatic bluish areolar lumps remains underreported in the literature, with only six cases previously documented. This lack of awareness may lead to the oversight of RCs during diagnosis. To address this, we conducted a comprehensive literature review using PUBMED, and we further added three more cases. The mean time for clinical resolution was found to be 2.3 years. In light of these findings, we proposed a diagnostic and management algorithm to guide clinicians in their approach to RCs in pediatric patients. The algorithm involves thorough clinical examination, medical history assessment, and echographic investigation with color Doppler analysis. Regular follow-up visits are recommended until resolution of the lesions. Notably, due to the consistently favorable outcome of RCs, aggressive diagnostic interventions can be avoided, providing reassurance to patients and their families. It is crucial for paediatricians to stay updated on this underreported condition to ensure timely recognition and appropriate management. Dermatologists should be the first specialists to be consulted in cases of suspected RCs. Increasing awareness among healthcare professionals will contribute to improved diagnosis and management of this benign condition. In conclusion, RCs are a benign self-resolving condition commonly observed during puberty. Their presentation as asymptomatic bluish areolar lumps may often be overlooked. Through this study, we highlighted the importance of early recognition, proposed a diagnostic and management algorithm, and emphasized the favorable prognosis of RCs, which allows for a conservative approach to their management.

Adjuvant immune checkpoint inhibitor therapy may benefit pediatric patients with stage III melanoma and sentinel lymph node positivity: a case series.

Melanoma is the most common skin cancer in children. While the current literature establishes treatment protocols for adult-type melanoma, very few pediatric-specific studies exist, and children are often excluded from melanoma clinical trials2. We report a case series of 23 pediatric patients aged 2-20 years old diagnosed with melanoma at the University of Rochester Medical Center between 1/1/2011 and 1/1/2022. 9/23 patients were Stage III; all patients underwent wide local excision and 9 received adjuvant therapies. 2/23 (8.7%) patients had recurrence of their malignancy after therapy while 21/23 (91.3%) remained without disease progression; 1 patient died from unknown cause, but the rest are alive and currently without disease. All patients whose initial therapy included nivolumab in addition to wide local excision did not have recurrence or progression of their disease. This case series highlights trends in the presentation, treatment, and outcomes of pediatric melanoma; however, additional multi-center studies are needed to establish the clinical utility of such features in pediatric melanoma.

The Safety of Pediatric Bedside Tracheostomy.

Traditionally, pediatric tracheostomy has been viewed as a technically demanding procedure with a high complication rate, requiring the routine use of a formal operating room. Pediatric bedside tracheostomy in an intensive care unit (ICU) setting has not been widely reported, in contrast to the widespread adult bedside ICU tracheostomy. Transport of these critically ill, multiple life support systems dependent patients can be technically difficult, labor intensive, and potentially risky for these patients. Our study aimed to demonstrate the safety and efficacy of bedside tracheostomy in the pediatric ICU. A retrospective analysis of all pediatric patients undergoing tracheostomy at a tertiary care center, between 1st of January 2013 and 31st of December 2019. During the study period, 117 pediatric patients underwent tracheostomy, 57 (48.7%) were performed bedside while 60 (51.3%) were performed in the operating room. Patients' ages ranged from 2 weeks to 17 years of age, with a median age of 16 months. No case of bedside tracheostomy necessitated a shift to the operating room. There was no difference in 30-day morbidity and mortality between the 2 groups. Our results suggest that pediatric open bedside tracheostomy in an ICU setting is a safe procedure, with similar complications and outcomes compared to tracheostomy performed in the operating room.

Treatment of Primary Cardiac Tumors in Children: A Single Center 18-Year Experience.

This study aimed to compare the clinical characteristics and courses of pediatric patients with cardiac tumors in nonoperative and operative groups to help guide treatment decisions. We reviewed the medical records of patients diagnosed with primary pediatric cardiac tumors at our institution between 2003 and 2020. Demographic data, clinical characteristics, and follow-up data between the operation and nonoperation groups were compared. A total of 56 patients were included in the study. Thirteen patients underwent surgery. The median age was 1.4 months (range, 1 to 18 years). The patients in the operation group had more frequent symptoms or signs, such as desaturation, respiratory difficulty, murmur, a higher mass area/chamber area (MC) ratio, decreased ventricular contractility, and significant ventricular outflow tract obstruction (VOTO). An MC ratio of 0.568 was the cutoff value for differentiating patients with symptoms or signs of heart failure and decreased ventricular contractility. At the last follow-up, all patients had good ventricular contractility except one patient in the operative group with fibroma. In the non-operative group, rhabdomyomas often regressed spontaneously, while fibromas often increased in size. Two patients in the nonoperative group died. In the operative group, there was no early or late mortality or tumor recurrence. In this study, patients had good outcomes with or without surgery, even when the tumor was large, or surgery was performed in early infancy.

Epigenetic Leukocyte Counts from Dried Blood Spots of Pediatric Patients.

Epigenetic Leukocyte Counts from Dried Blood Spots of Pediatric Patients.

Echocardiography to predict left ventricular filling pressure for long-term paediatric heart transplant patients.

Left ventricular diastolic dysfunction is a recognised sequela following transplantation in paediatric heart transplant patients. Traditional echocardiographic indices do not correlate well with left ventricular filling pressure immediately after transplantation. This study aimed to assess whether these indices have any long-term correlation after transplantation in paediatric patients. A retrospective chart review of 41 patients who had a heart transplant before the age of 24 years was performed. The median time since the transplantation was 11 years. Data obtained from surveillance cardiac catheterisation and echocardiographic examination were reviewed. Traditional echocardiographic indices of diastolic function were compared with the pulmonary capillary wedge pressure and left ventricular end-diastolic pressure obtained from cardiac catheterisation. The median age at transplant was 12.1 years, and the median time since transplant was 11 years. Eighteen patients (43%) had a history of at least one rejection episode and 12 patients (29%) had a history of cardiac allograft vasculopathy. There was no correlation between mitral inflow E velocity, mitral E/A ratio, tissue Doppler velocities, mitral E/e' (mitral inflow E velocity to mitral annular velocity), and elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. There was no correlation between mitral valve deceleration time or isovolumetric relaxation time with elevated pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure. Our findings suggest that traditional echocardiographic indices of diastolic function do not correlate well with elevated invasive pulmonary capillary wedge pressure or elevated left ventricular end-diastolic pressure in paediatric heart transplant patients' long-term post-transplantation.

Ocular surface complications in children undergoing general anaesthesia: A prospective observational study.

Ophthalmic complications frequently occur after procedures requiring general anaesthesia, but their incidence is widely variable and not well reported in the paediatric population. The aim was to identify the incidence and possible risk factors of postoperative ocular surface complications in a tertiary care centre. This is a prospective study for paediatric patients undergoing general anaesthesia. An ophthalmologist performed the ocular examination after surgery. Parameters assessed were tear breakup time, punctate epithelial erosions and corneal abrasions. Multivariate logistic regression model was used to assess risk factors. A total of 108 paediatric patients were recruited, 36.1% showed abnormal corneal finding: 32 (29.6%) had decreased tear breakup time, three (2.7%) had punctate epithelial erosions, three (2.7%) had both punctate epithelial erosions and decreased tear breakup time and one (0.9%) was found to have a unilateral corneal abrasion postoperatively. A higher rate of corneal complications was noted with younger age, prolonged surgery and surgery in the head and neck region. The rate of postoperative corneal abnormalities in children undergoing general anaesthesia was 36.1%, associated with younger age, prolonged surgery and surgery in the head and neck region.

A new mutation in the Parkinson's-related FBXO7 gene impairs mitochondrial and proteasomal function.

Around 10% of Parkinson's disease (PD) cases are associated with mutations in various genes, including FBXO7, which encodes the substrate-recognition component for the Skp1-Cullin-F-box (SCF) class of ubiquitin E3 ligases that target proteins for proteasomal degradation. In their recent study, Al Rawi etal. characterized a new mutation in FBXO7, L250P, in a pediatric patient. Their findings reveal that the L250P mutation abolishes Fbxo7 interaction with the proteasome regulator, proteasome inhibitor 31kD (PI31), affecting proteasomal activity and the ubiquitination of some of the ligase's targets. Furthermore, the authors show that this previously undescribed mutation impairs mitochondrial function and mitophagy, emphasizing the importance of mitochondrial and proteasomal dysfunction in PD pathogenesis.

Fecal calprotectin and platelet count predict histologic disease activity in pediatric ulcerative colitis: results from a projection-predictive feature selection.

Especially for pediatric patients, proxies of mucosal inflammation are needed. The Pediatric Ulcerative Colitis Activity Index (PUCAI) has been established to predict clinical and endoscopic disease activity. However, histologic inflammation might persist. We applied a special variable selection technique to predict histologic healing in pediatric ulcerative colitis (UC) as parsimoniously (but still as precisely) as possible. The retrospective analysis included data from two study cohorts, comprising 91 visits from 59 pediatric patients with UC. A Bayesian ordinal regression model was used in combination with a projection-predictive feature selection (PPFS) to identify a minimal subset of clinical and laboratory parameters sufficient for the prediction of histologic disease activity. Following the PPFS, CEDATA-GPGE patient registry data were analyzed to investigate the relevance of the selected predictors in relation to PUCAI and Physician Global Assessment (PGA) in up to 6697 patient visits. Fecal calprotectin (FC) and platelet count were identified as the minimal subset of predictors sufficient for prediction of histologic disease activity in pediatric UC. FC and platelet count also appeared to be associated with increasing disease activity as measured by PUCAI and PGA in the CEDATA-GPGE registry. Based on the selected model, predictions can be performed with a Shiny web app. Conclusion: Our statistical approach constitutes a reproducible and objective tool to select a minimal subset of the most informative parameters to predict histologic inflammation in pediatric UC. A Shiny app shows how physicians may predict the histologic activity in a user-friendly way using FC and platelet count. To generalize the findings, further prospective studies will be needed. What is Known: • Histologic healing is a major endpoint in the therapy of ulcerative colitis (UC). • The PUCAI score has been established to predict disease activity in pediatric UC but is not suitable for the prediction of histologic healing. What is New: • Our Bayesian ordinal regression model in combination with a projection-predictive feature selection is a reproducible and objective tool to select the minimal subset of clinical and laboratory parameters to predict histologic inflammation in pediatric UC. • Histologic inflammation in pediatric UC can be non-invasively predicted based on the combination of fecal calprotectin levels and platelet count.

Pediatric Canalicular Lacerations: Epidemiology and Surgical Outcomes.

The aim of this study was to report the epidemiology and surgical outcomes of canalicular lacerations in the pediatric age group. All pediatric patients who underwent repair of canalicular lacerations of any cause were included in this study. Age, sex, mechanism of trauma, and type of stent used were recorded. The study group consisted of 47 patients with a median age of 6.4 years (22mo-17y). Thirty of the patients were male (63.8%). The lower canaliculus was affected in 76.6% (n=36), the upper canaliculus in 40.4% (n=19), and both canaliculi in 17% (n=8). The most common cause of canalicular laceration was sharp objects (n=33, 70.2%). Canalicular laceration most commonly affects boys and especially involves the lower canaliculus. There was no difference in functional success between monocanalicular and bicanalicular stents. Prevention of canalicular lacerations should be the main focus.

Double Ventricular Response with Aberrant Conduction Leading to Ventricular Dysfunction.

Double ventricular response (DVR), where a single P wave results in two QRS complexes, is a rare presentation of dual AV node physiology. It has been associated with ventricular dysfunction in the setting of incessant tachycardia. We present the case of an otherwise healthy adolescent who had frequent DVR without tachycardia leading to left ventricular dysfunction. Slow pathway modification led to a significant reduction in ectopy and normalization of ventricular function. This highlights that DVR without tachycardia might lead to ventricular dysfunction in pediatric patients. Slow pathway modification with reduction of ectopy may be sufficient to restore ventricular function.

Musculoskeletal misdiagnoses in pediatric patients with spinal tumors.

Childhood spinal tumors often present with musculoskeletal symptoms, potentially causing a misdiagnosis and delays in diagnosis and treatment. This study aims to identify, characterize, and compare children with spinal tumors who had prior musculoskeletal misdiagnoses to those without, analyzing clinical presentation, diagnostic interval, and outcome. This retrospective cohort study evaluated all children aged 0-14years diagnosed with a spinal tumor in Denmark from 1996 to 2018. The cohort was identified through the Danish Childhood Cancer Registry, and the registry data were supplemented with data from medical records. The survival was compared using the Kaplan-Meier method. Among 58 patients, 57% (33/58) received musculoskeletal misdiagnoses before the spinal tumor diagnosis. Misdiagnoses were mostly nonspecific (64%, 21/33), involving pain and accidental lesions, while 36% (12/33) were rheumatologic diagnoses. The patients with prior misdiagnosis had less aggressive tumors, fewer neurological/general symptoms, and 5.5months median diagnostic interval versus 3months for those without a misdiagnosis. Those with prior misdiagnoses tended to have a higher 5-year survival of 83% (95% confidence interval [CI]: 63%-92%) compared to 66% (95% CI: 44%-82%) for those without (p=.15). Less aggressive spinal tumors may manifest as gradual skeletal abnormalities and musculoskeletal symptoms without neurological/general symptoms, leading to misdiagnoses and delays.

Clinical Profile of Pediatric Oncology Patients Treated by Radiotherapy: A Retrospective Audit from a Tertiary Cancer Care Center in South India

Clinical Profile of Pediatric Oncology Patients Treated by Radiotherapy: A Retrospective Audit from a Tertiary Cancer Care Center in South India

Adherence and Persistence Among Risdiplam-Treated Individuals with Spinal Muscular Atrophy: A Retrospective Claims Analysis.

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions and/or mutations in the survival of motor neuron1 (SMN1) gene. Risdiplam, the first and only oral SMN2 pre-mRNA splicing modifier, is US Food and Drug Administration-approved for the treatment of pediatric and adult patients with SMA. For patients with SMA, long-term adherence to and persistence with an SMA treatment may be important for achieving maximum clinical benefits. However, real-world evidence on patient adherence to and persistence with risdiplam is limited. This retrospective study examined real-worldadherence and persistence with risdiplamfrom a specialty pharmacy in patients with SMA over a 12-month period. Adherence was estimated by using proportion of days covered (PDC) and was calculated over variable (time between first and last fill) and fixed (time from first fill to study period end) intervals. Persistence was defined as no gap in supply ≥ 90days. Patients were included if the time between the index date and study observation period was ≥ 12months, if they initiated risdiplam between August 2020 and September 2022, received ≥ 2 risdiplam fills, and had an SMA diagnosis associated with a risdiplam fill. Subgroup analyses of risdiplam adherence and persistence were performed by age and primary payer type. The proportion of patients (N = 1636) adherent at 12months based on variable and fixed interval PDC was 93% and 79%, respectively. Adherence was high among patients on commercial insurance, Medicaid, or Medicare (range 86-96%). Mean persistence was 330.4days. The highest proportion of patients who were persistent were on Medicaid (81%). These findings demonstrate that patient adherence to and persistence with risdiplam treatment were high, including across all subgroups tested.

Combination immunotherapy with vaccine and oncolytic HSV virotherapy is time dependent.

Oncolytic virotherapy or immunovirotherapy is a strategy that utilizes viruses to selectively infect and kill tumor cells while also stimulating an immune response against the tumor. Early clinical trials in both pediatric and adult patients using oncolytic herpes simplex viruses (oHSVs) have demonstrated safety and promising efficacy; however, combinatorial strategies designed to enhance oncolysis while also promoting durable T cell responses for sustaining disease remission are likely required. We hypothesized that combining the direct tumor cell killing and innate immune stimulation by oHSV with a vaccine that promotes T cell mediated immunity may lead to more durable tumor regression. To this end, we investigated the preclinical efficacy and potential synergy of combining oHSV with a self-assembling nanoparticle vaccine co-delivering peptide antigens and Toll-like receptor-7 and -8 agonists (TLR-7/8a) (referred to as SNAPvax™), that induces robust tumor specific T cell immunity. We then assessed how timing of the treatments (i.e., vaccine before or after oHSV) impacts T cell responses, viral replication, and preclinical efficacy. The sequence of treatments was critical, as survival was significantly enhanced when the SNAPvax™ vaccine was given prior to oHSV. Increased clinical efficacy was associated with reduced tumour volume and increases in virus replication and tumor antigen specific CD8+ T cells. These findings substantiate the criticality of combination immunotherapy timing and provide preclinical support for combining SNAPvax with oHSV as a promising treatment approach for both pediatric and adult tumors.

Risk factors and survival outcomes in children with early cardiotoxicity after allogeneic hematopoietic stem cell transplantation.

Cardiotoxicity in children is a potentially fatal complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); therefore, early identification of risk factors can improve patient prognosis. However, there are few data on the clinical characteristics of early-stage cardiotoxicity in children after allo-HSCT. We conducted a retrospective single-center study of pediatric patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) between January 2016 and December 2022 at the Children's Hospital Affiliated with Chongqing Medical University to evaluate the clinical characteristics of early cardiac events (ECEs) after allo-HSCT and their impact on survival outcomes. We enrolled 444 patients who underwent allo-HSCT-304 males (68%) and 140 females (32%)-with a median age of 3.3years (1.8-6.5years) at transplantation. We found that 73 patients (16.4%) had ECEs after allo-HSCT. The ECEs included valvular disease (n = 46), pericardial effusion (n = 38), arrhythmia (n = 9), heart failure (n = 16), and dilated cardiomyopathy (n = 1). Female sex, age ≥ 6years, body mass index (BMI) < 16kg/m2 and HLA-type mismatches were risk factors for ECEs. We designed a stratified cardiac risk score that included these risk factors, and the higher the score was, the greater the cumulative incidence of ECEs. The occurrence of an ECE was closely associated with a lower overall survival (OS) rate and greater nonrelapse mortality (NRM). In addition, stratified analysis based on the number of combined ECEs showed that the greater the number of combined ECEs was, the more significant the negative impact on OS rates.