Pediatric Patients Research Articles

Dupilumab Safety and Efficacy up to 1 Year in Children Aged 6 Months to 5 Years with Atopic Dermatitis: Results from a Phase 3 Open-Label Extension Study.

Pediatric patients with moderate-to-severe atopic dermatitis (AD) often experience a high disease burden and have a high risk of persistent disease. Standard-of-care immunosuppressive systemic treatments have been used off-label for AD in pediatric patients despite concerns for suboptimal safety with continuous use and risk of relapse upon discontinuation. The biologic agent dupilumab is the first systemic treatment approved for moderate-to-severe AD in children as young as 6 months. Long-term safety and efficacy data in this patient population are needed to inform continuous AD management. The purpose of this work was to determine the long-term safety and efficacy of dupilumab treatment up to 1 year in an open-label extension (OLE) study [LIBERTY AD PED-OLE (NCT02612454)] in children aged 6 months to 5 years with moderate-to-severe AD who previously participated in the 16-week, double-blind, phase 3 LIBERTY AD PRESCHOOL trial (NCT03346434 part B; parent study) and were subsequently enrolled in PED-OLE. In PED-OLE, patients received dupilumab every 4 weeks according to a weight-tiered regimen (body weight ≥ 5 kg to < 15 kg: 200 mg; ≥ 15 kg to < 30 kg: 300 mg). Data for 142 patients were analyzed, 60 of whom had completed the 52-week visit at time of database lock. Mean age at baseline was 4.1 y [SD, 1.13; range, 1.0-5.9 years]. A majority (78.2%) of patients reported ≥ 1 treatment-emergent adverse event (TEAE), most of which were mild or moderate and transient. The most frequently reported TEAEs were nasopharyngitis (19.7%), cough (15.5%), and pyrexia (14.1%). One TEAE led to treatment discontinuation (severe urticaria, which resolved in 1 day). By week 52, 36.2% of patients had achieved an Investigator's Global Assessment score of 0/1 (clear/almost clear skin), and 96.6%, 79.3%, and 58.6% had at least 50%, 75%, or 90% improvement, respectively, in Eczema Area and Severity Index scores. Consistent with results seen in adults, adolescents, and older children (aged 6-11 years), treatment with dupilumab for up to 1 year in children aged 6 months to 5 years with inadequately controlled moderate-to-severe AD demonstrated an acceptable long-term safety profile and sustained efficacy. These results support the long-term continuous use of dupilumab in this patient population. ClinicalTrials.gov Identifiers: NCT02612454 and NCT03346434 (part B).

Can ERAS help reduce health disparities and overcome barriers to equitable surgical care in marginalized communities?

Health inequities persist in surgical outcomes between different races and ethnicities. Enhanced Recovery after Surgery (ERAS) protocols are innovative perioperative management strategies that have improved outcomes and reduced costs of delivering care. Quality improvement tools embedded in the protocols allow for sequential improvements in compliance and outcomes. Standardization of perioperative care may reduce healthcare inequities and improve outcomes in marginalized communities. In this review, we describe the benefits of ERAS in surgical outcomes, discuss how implementation of ERAS could potentially reduce health disparities in pediatric surgical patients, demonstrate the barriers present in ERAS implementation, propose solutions to these implementation barriers (Table 1).

Coronary Plaque Analysis In The Pediatric Transplant Patients Using Coronary Computed Tomography

Coronary Plaque Analysis In The Pediatric Transplant Patients Using Coronary Computed Tomography

Phototherapy for the treatment of atopic dermatitis in Singaporean children and adolescents.

Phototherapy has emerged as a safe yet effective form of treatment of atopic dermatitis (AD). Few studies have been done to evaluate the efficacy of phototherapy in Asian children. The aim of this study was to review the phototherapy experience in a cohort of Asian pediatric patients with AD at a tertiary dermatologic center in Singapore. A retrospective study of patients 18 years and below with AD who had undergone phototherapy at KK Women's and Children's Hospital, Singapore, over a 4-year period was performed. Sixty-two patients were identified, between ages 4 and 16 years (mean age 11 years) at the time of commencement of phototherapy. Thirty-five (60%) patients were males and 23 (40%) were females. Most patients had moderate to severe disease, with 60.3% of the patients with an initial body surface area (BSA) involvement of 31%-60% and 13.8% of the patients with an initial BSA involvement of 61%-90%. For patients who had undergone narrowband ultraviolet B (NBUVB) and combined ultraviolet A (UVA) and NBUVB phototherapy, the mean reduction of the Eczema Area and Severity Index (EASI) scores were 11.4 and 7.9, respectively. Common side effects experienced include xerosis, pruritus, erythema, and pain. Other reasons for cessation of therapy in the NBUVB group included time commitment difficulty (9.3%), hyperactivity (2.3%), and claustrophobia (2.3%). Two patients that had photochemotherapy (psoralen + UVA) [PUVA] suffered from post-UVA burns requiring cessation of treatment. More than half of the patients (56.9%) treated with phototherapy experienced treatment success with improvement in Investigator Global Assessment and EASI scores. 86.2% of the patients had good compliance to the treatment regime, 12% had poor-compliance, and 3.4% were lost to follow-up. Phototherapy is a useful treatment adjunct for moderate to severe AD in Asian children.

The Strange Case of the Traveling Munchausen’s Earring: A Swallowed Foreign Body that Wasn’t

Factitious Disorder Imposed on Another (FDIA), formerly called Munchausen Syndrome by Proxy, is a disorder characterized by the falsification of symptoms of illness and diagnostic testing by a perpetrator in another individual to satisfy a psychological need of the perpetrator. This case report describes the clinical course of a 14-month-old female who presented with a purported swallowed foreign body who was eventually found to be a victim of FDIA following multiple presentations to the emergency department and extensive diagnostic workup. This manuscript aims to shed light on the complexity and potential harm that FDIA can cause patients as well as the burden on the healthcare system and to discuss the challenges in diagnosing FDIA in pediatric patients

Brace based Mechanical axis deviation (MAD) of lower limb correction in a Pediatric patient with severe femoral and tibial bowing - A case based description

Brace based Mechanical axis deviation (MAD) of lower limb correction in a Pediatric patient with severe femoral and tibial bowing - A case based description

The registers of pediatric patients with home artificial nutrition. The Spanish experience

Background: the number of infants and children who receive artificial nutrition at home has been steadily increasing over the last decades, as better outcomes for children with chronic conditions have been achieved. In order to evaluate the need of resources to implement the technique it is necessary to know how many patients benefit from home artificial nutrition. This information can be estimated from the register of patients, when available. Methods: in this paper the characteristics of all registers were reviewed, especially those devoted to pediatric patients. Results: only two pediatric registers are active in 2023: the Canadian register and the Spanish one. NADYA register from the Spanish Society for Clinical Nutrition and Metabolism (SENPE) and the recent REPAFI, form the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition. The most valuable register from the British Society, BANS, stopped providing information in 2018. Conclusion: despite the fact of acknowledging the importance of having gathered information on the prevalence and incidence of home artificial nutrition, to fit resources to necessities, the number of active registers is quite short.

Dose rationale for the use of meropenem/vaborbactam combination in paediatric patients with Gram-negative bacterial infections.

Meropenem/vaborbactam combination is approved in adults by FDA and EMA for complicated urinary tract infections and by EMA also for other Gram-negative infections. We aimed to characterise the pharmacokinetics of both moieties in an ongoing study in children and use a model-based approach to inform adequate dosing regimens in paediatric patients. Over 4196 blood samples of meropenem and vaborbactam (n = 414 subjects) in adults, together with 114 blood samples (n = 39) in paediatric patients aged 3 months to 18 years were available for this analysis. Data were analysed using a population with prior information from a pharmacokinetic model in adults to inform parameter estimation in children. Simulations were performed to assess the suitability of different dosing regimens to achieve adequate probability of target attainment (PTA). Meropenem/vaborbactam PK was described with two-compartment models with first-order elimination. Body weight and CLcr were significant covariates on the disposition of both drugs. A maturation function was evaluated to explore changes in clearance in neonates. PTA ≥90% was derived for children aged ≥3 months after 3.5-h IV infusion of 40 mg/kg Q8h of both meropenem and vaborbactam and 2 g/2 g for those ≥50 kg. Extrapolation of disposition parameters suggest that adequate PTA is achieved after a 3.5-h IV infusion of 20 mg/kg for neonates and infants (3 months). An integrated analysis of adult and paediatric data allowed accurate description of sparsely sampled meropenem/vaborbactam PK in paediatric patients and provided recommendations for the dosing in neonates and infants (3 months).

Atraumatic Infected Septal Hematoma in a Pediatric Patient

Case Presentation: We present a case of a 10-year-old male who developed an atraumatic, nasal septal hematoma with abscess following several days of rhinorrhea and cough. His chief complaint to the emergency department was a two-day history of nasal swelling and discomfort, associated with difficulty breathing through his nose. The patient was well-appearing with swelling and tenderness along the external nasal ridge and nasal septal swelling that occluded both nares. Contrast-enhanced maxillofacial computed tomography revealed a rim-enhancing, fluid-filled collection to the anterior nasal septum. The patient underwent successful incision and drainage by otolaryngology. Discussion: Infected septal hematomas are rare but important to recognize as they can result in septal deformity and potentially life-threatening sequelae, such as intracranial infections. Most are secondary to nasal trauma in adult patients. This case highlights a unique presentation of atraumatic septal hematoma with abscess formation in an immunocompetent pediatric patient.

Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies.

Outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims at giving a comprehensive overview about clinical and molecular characteristics of pediatric FA MB patients. Clinical data including detailed information on treatment and toxicities of six previously unreported FA MB patients were supplemented with data of 16 published cases. We identified 22 cases of children with FA and MB with clinical data available. All MBs with subgroup reporting were SHH-activated (n=9), confirmed by methylation profiling in five patients. FA MB patients exclusively belonged to complementation groups FA-D1 (n=16) or FA-N (n=3). Patients were treated with postoperative chemotherapy only (50%) or radiotherapy (RT)±chemotherapy (27%). 23% did not receive adjuvant therapy. Excessive treatment-related toxicities were frequent. Severe hematological toxicity occurred in 91% of patients treated with alkylating chemotherapy, while non-alkylating agents and RT were less toxic. Median overall survival (OS) was 1 year (95%CI 0.3-1.8). 1-year-progression-free-survival (PFS) was 26.3±10.1% and 1-year-OS was 42.1±11.3%. Adjuvant therapy prolonged survival (1y-OS/1y-PFS 0%/0% without adjuvant therapy vs. 53.3±12.9%/33.3±12.2% with adjuvant therapy, p=0.006/p=0.086). MB in FA patients is strongly associated with SHH activation and FA-D1/FA-N. Despite the dismal prognosis, adjuvant therapy may prolong survival. Non-alkylating chemotherapy and RT are feasible in selected patients with careful monitoring of toxicities and dose adjustments. Curative therapy for FA MB-SHH remains an unmet medical need.

Is It Possible to Predict Systemic Adverse Effects in Subcutaneous Allergen Immunotherapy? Single-Center Experience.

Subcutaneous immunotherapy (SCIT) is the oldest and an efficient immunotherapy method that has been used for the treatment of allergic diseases. Systemic adverse effects (SAEs) may occur during the SCIT. For this reason, there may be problems in the continuing treatment. In this study, we primarily aimed to determine the frequency of SAEs, the risk factors that may be associated with SAEs, and clinical and laboratory parameters that can predict systemic reactions in the patients who underwent SCIT. Second, we aimed to evaluate the reasons for discontinuing SCIT and the conditions special to Turkey. The files of 295 patients who had received SCIT were evaluated retrospectively. SCIT was administered against house dust mites (HDM) in almost all patients (n: 291, 98.6%). A total of 14,357 injections were administered to 295 patients included in the study, and 47.8% (n: 141) of the patients discontinued treatment. The most common reason for discontinuing treatment was the supply problem in Turkey for immunotherapy preparations (n: 70, 49.6%). The second reason was that the injection visits were not continued regularly, even though there were no adverse effects related to the treatment (n: 44, 31.2%). SAEs were observed in 16.6% of the patients and 0.66% of the injections. SAEs were more frequent in girls, in asthmatic patients, and in moderate asthmatic patients (p = 0.005, p = 0.016, p = 0.043, respectively). Treatment was terminated in 13 patients (4.4%) due to SAEs. The most common SAE was bronchoconstriction (n: 40, 85.1%). None of our patients developed hypotension or loss of consciousness. Median blood eosinophil count and basophil count and the skin prick test diameter for Dermatophagoides farinae were observed to be significantly higher in the group with SAE (p = 0.024, p = 0.034, p = 0.045, respectively). Although SAE may develop in pediatric patients undergoing HDM-specific SCIT, severe reactions are rare. Girls, asthmatic patients, especially moderate asthmatic patients, and patients with high blood eosinophil and basophil levels should be monitored more carefully for the development of SAE.

Holter Electrocardiographic Approach to Predicting Outcomes of Pediatric Patients With Long QT Syndrome.

This study was performed to clarify the clinical findings of pediatric patients diagnosed with long QT syndrome (LQTS) through electrocardiographic screening programs and to predict their outcome using Holter electrocardiographic approaches.Methods and Results: This retrospective study included pediatric patients with a Schwartz score of ≥3.5 who visited the National Hospital Organization Kagoshima Medical Center between April 2005 and March 2019. Resting 12-lead and Holter electrocardiograms were recorded at every visit. The maximum resting QTc and maximum Holter QTc values among all recordings were used for statistical analyses. To test the prognostic value of QTc for the appearance of cardiac events after the first hospital visit, receiver operating characteristic curves were used to calculate the area under the curve (AUC). Among 207 patients, 181 (87%) were diagnosed through screening programs. The prevalence of cardiac events after the first hospital visit was 4% (8/207). Among QTc at diagnosis, maximum resting QTc, and maximum Holter QTc, only maximum Holter QTc value was a predictor (P=0.02) of cardiac events after the hospital visit in multivariate regression analysis. The AUC of the maximum Holter QTc was significantly superior to that of maximum resting QTc. The maximum Holter QTc value can be used to predict the appearance of symptoms in pediatric patients with LQTS.

Unusual tumor metastasis from neuroblastoma in a pediatric patient. Case report

Unusual tumor metastasis from neuroblastoma in a pediatric patient. Case report

Idiopathic intracranial hypertension in a pediatric patient with cystic fibrosis on ETI generic formulation treatment

Idiopathic intracranial hypertension in a pediatric patient with cystic fibrosis on ETI generic formulation treatment

Tissue Inhibitor of Metalloproteinases-2 (TIMP-2) as a Prognostic Biomarker in Acute Kidney Injury: A Narrative Review

Acute kidney damage (AKI) is a serious and common consequence among critically unwell individuals. Traditional biomarkers, such as serum creatinine, frequently fail to detect AKI in its early stages, necessitating the development of new accurate early biomarkers. Tissue inhibitor of metalloproteinases 2 (TIMP-2) has emerged as a promising biomarker for predicting early AKI. The present narrative review investigates the role of TIMP-2 in AKI prediction in a variety of clinical scenarios. In the NephroCheck® test, TIMP-2 exceeds established biomarkers for the early identification of AKI in terms of sensitivity and specificity when combined with insulin-like growth factor-binding protein 7 (IGFBP-7). Elevated levels of these biomarkers can provide a warning signal for AKI two to three days before clinical symptoms appear. TIMP-2 and IGFBP-7 have high predictive values, with an area under the curve (AUC) typically above 0.8, indicating good predictive capacity. For example, the [TIMP-2] × [IGFBP-7] product produced an AUC of 0.85 in surgical patients at high risk. In critically ill patients, a threshold of 0.3 (ng/mL)2/1000 demonstrated 92% sensitivity and 72% specificity. Elevated TIMP-2 levels have been correlated with higher mortality rates and the need for renal replacement therapy (RRT). In sepsis-associated AKI (SA-AKI), TIMP-2 levels combined with clinical prognostic models improved predictive accuracy (AUC: 0.822). Furthermore, elevated urine TIMP-2 levels were good predictors of AKI in pediatric patients after cardiac surgery, with AUC-ROC values of up to 0.848. Urine output and the presence of concomitant disorders may influence the prognostic accuracy of these biomarkers; therefore, more research is needed to fully understand their utility. The predictive value of TIMP-2 could be strengthened by combining it with other clinical parameters, reinforcing its role in the early detection and treatment of AKI.

Characterization of Herpesviridae Family Members, BK Virus, and Adenovirus in Children and Adolescents with Nephrotic Syndrome

Since the significance of viral infections in children and adolescents with nephrotic syndrome (NS) is yet to be defined, this study intended to estimate the occurrence, pattern, and outcomes of some DNA viral infections in children with NS. Methods: A prospective study was conducted to determine the genome identification of the viruses Epstein-Barr (EBV), human cytomegalovirus (HCMV), human herpesvirus 6 (HHV-6 type A and type B) and 7 (HHV-7), polyomavirus (BKV), and human adenovirus (HAdV) in plasma and urine samples of pediatric patients with NS. Results: A total of 35 patients aged 1 to 18 years with NS and under immunosuppressant drugs participated in the study. Plasma and urine samples were collected at regular intervals during a median follow-up of 266 days (range 133–595), and DNA was analyzed to detect the selected DNA viruses. Eleven patients (31.4%) had active virus infections, and patterns were classified as coinfection, recurrent, and consecutive. Of these, six patients (54.5%) presented viral coinfection, six (54.5%) viral recurrence, and seven patients (63.3%) had viral consecutive infection. Ten of the eleven patients with active infection had a proteinuria relapse (91%) and eight (72.7%) were hospitalized (p = 0.0022). Active HCMV infection was the most frequent infection and was observed in six patients (54.5%), three of the eleven patients (27.2%) had suspected HCMV disease in the gastrointestinal tract, and one had HHV-7 coinfection. The frequency of other infections was: 9% for HHV-6, 45.5% for BKV, 27.3% for HHV-7, 18.2% for EBV, and 18.2% for HAdV. Conclusion: viral infections, especially HCMV, can be an important cause of morbidity and nephrotic syndrome relapse in children.

Use of regional anesthesia within a pediatric interventional radiology suite reduced periprocedural opioid use without delaying the overall workflow: a retrospective study

BackgroundNerve block utility has been extensively described in the operating room, however, there is a paucity of evidence regarding blocks in the interventional radiology (IR) suite, with no studies examining...

Influence of donor age and donor-recipient age difference on intimal hyperplasia in pediatric patients with young and adult donors vs. adult patients after heart transplantation.

Optimal selection and allocation of donor hearts is a relevant aspect in transplantation medicine. Donor age and cardiac allograft vasculopathy (CAV) affect post-transplant mortality. To what extent donor age impacts intimal hyperplasia (CAVIH) in pediatric and adult patients after heart transplantation (HTx) is understudied. In a cohort of 98 HTx patients, 58 pediatric (24.1% with adult donors) and 40 adult patients, we assessed the effect of donor age and donor-recipient age difference (D-R) on the continuous parameter of maximal intima thickness (mIT) in optical coherence tomography. We evaluated their predictive value regarding higher mIT and the prevalence of CAVIH, defined as mIT > 0.3 mm, and compared it to established CAV risk factors. In the overall population, donor age correlated with mIT (p < 0.001), while in the pediatric subpopulation, both donor age and D-R correlated with mIT (p < 0.001 and p = 0.002, respectively). In the overall population, donor age was a main predictor of higher mIT and CAVIH (p = 0.001 and p = 0.01, respectively) in addition to post-transplant interval, arterial hypertension, and dyslipidemia. In the pediatric patients, dyslipidemia remained a main predictor of both higher mIT and CAVIH (p = 0.004 and p = 0.040, respectively), while donor age and D-R were not. While there was an effect of the non-modifiable parameter of donor age regarding maximal intimal thickness, a stronger association was seen between the modifiable risk factor dyslipidemia and higher maximal intimal thickness and CAVIH in both the overall population and the pediatric subpopulation.

Sleep disorders in pediatric patients with agenesis of the corpus callosum.

There is limited information about sleep in agenesis of the corpus callosum (ACC). We aim to describe the sleep architecture and respiratory parameters of children with ACC. We performed a retrospective study of 20 patients with ACC who had polysomnography (PSG) between 2000-2023. Demographic data, BMI or weight for length, associated conditions, and PSG findings were collected. National Sleep Foundation (NSF) sleep quality indicators as well as increased PSG arousal index ≥10/h were used in the analysis. Fisher's exact test or unpaired t-test was used to compare groups. Average age was 5.9 ± 5.4 years old; 12/20 patients were male. 6/20 were overweight/obese. 14/20 had complete ACC, and 6/20 had partial ACC. 8/20 had seizures. 15/20 had ≥1 NSF poor sleep quality indicator (decreased SE (45%), decreased REM (53%)) and 9/20 had increased arousals. Between complete and partial ACC, there was no difference in presence of ≥1 poor sleep quality indicator (p= 0.61), SE (p=0.34), REM (p=0.28), and arousals (p=1.0). 11/18 had obstructive sleep apnea (OSA); 5/11 had associated central sleep apnea. There was no difference in OSA between those with complete and partial ACC (p=1.0). OSA was associated with children <3 years old (p=0.01). Children with ACC have poor sleep quality, and many have OSA. There was no difference in sleep quality or presence of OSA between those with complete and partial ACC. OSA was seen more in younger children. Our study supports the need for screening of sleep-related disorders in patients with ACC.

Influence of computerized intraosseous anesthesia compared with traditional mandibular nerve block on children's behavior: A randomized clinical trial.

Effective pain management is crucial for the successful completion of dental procedures in children. Research has examined whether computerized intraosseous anesthesia (CIOA) could serve as a safe and viable substitute for the conventional inferior alveolar nerve block (IANB) technique in pediatric patients. This study investigates the efficacy of CIOA, aiming to determine its effectiveness as an alternative anesthesia method. This study compared the efficacy of local intraosseous anesthesia using a computerized device (QuickSleeper 5) to conventional IANB anesthesia on cooperation and pain perception in children, using a randomized controlled trial design. The study included 88 healthy children, aged between 6 and 9 years, who required pulpotomy for their mandibular second primary molars. The study was approved by the local research ethics committee and registered at clinicaltrials.gov (NCT05193487). The heart rate and Venham behavior rating scale were recorded and analyzed. Categorical data were analyzed using Fisher's exact test. Age and heart rate were compared using an independent t-test for intergroup comparison. The intragroup comparison was carried out using repeated measures ANOVA, followed by the Bonferroni post hoc test. The Mann-Whitney U-test was used to analyze the Venham scale scores. The significance level was set at p < .05 RESULTS: The mean Venham score was slightly higher in the IANB group than in the CIOA group, but was not statistically significant (p = .852). One minute after anesthesia administration, the heart rate (beats per minute [BPM]) was significantly higher in the IANB group (92.30 ± 13.45) than in the CIOA group (83.20 ± 10.40) (p < .001). Additionally, there was a significant difference in heart rate values measured at different intervals within the IANB group. The QuickSleeper 5 device was found to be a feasible alternative for IANB in children over 6 years old.