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In the context of the near-global eradication of wild poliovirus, the significance of non-polio enteroviruses (NPEVs) in causing acute flaccid paralysis (AFP) and their impact on public health has gained increased attention. This research, conducted from 2001 to 2021, examined stool samples from 1597 children under 15 years in São Paulo, Brazil, through the AFP/Poliomyelitis Surveillance Program, detecting NPEVs in 6.9% of cases. Among the 100 NPEV-positive strains analyzed, 90 were genotyped through genomic sequencing of the partial VP1 region, revealing a predominance of EV-B species (58.9%), followed by EV-A (27.8%) and EV-C (13.3%). This study identified 31 unique NPEV types, including EV-A71, CVB2, and E11, as the most prevalent, along with the first documented occurrence of CVA19 in Brazil. These findings emphasize the importance of NPEV genotyping in distinguishing AFP from poliomyelitis, enhancing understanding of these viruses' epidemiology. Moreover, it ensures that AFP cases are correctly classified, contributing to the effective surveillance and eradication efforts for poliomyelitis. [ABSTRACT FROM AUTHOR]

Background: Food allergy (FA)-related bullying is a significant public health concern affecting pediatric patients. This systematic review investigates the prevalence, characteristics, and psychosocial impact of FA-related bullying, as well as current intervention strategies within educational and healthcare settings. Methods: A systematic literature search was conducted across the PubMed, Web of Science, and CINAHL databases, covering publications up to February 2024. The review followed PRISMA guidelines and included studies on children and adolescents (0–18 years) diagnosed with FAs. Studies were selected based on eligibility criteria and assessed for quality using the Newcastle–Ottawa Scale. Results: The initial search identified a total of 260 records (6 from scientific databases and 254 from registries). Twenty-six studies met the inclusion criteria. The findings of these studies reveal that FA-related bullying is prevalent, with rates varying between 17% and 60%, depending on the study population and methods. Bullying often involves verbal teasing, social exclusion, and physical threats using allergens, presenting both psychological and physical risks. Psychological consequences include increased anxiety, depression, and social withdrawal, which persist over time, significantly impacting quality of life for both children and their families. Notably, bullying often occurs in school settings, emphasizing the need for targeted interventions. Conclusion: FA-related bullying profoundly affects mental health and quality of life for affected children and their families. Interventions, such as school-based allergy education programs and policies promoting inclusivity and safety, have shown promise in reducing bullying incidents. A collaborative approach involving healthcare providers, educators, and policymakers is essential to mitigate the impact of FA-related bullying and improve outcomes for affected children. [ABSTRACT FROM AUTHOR]

Inherited retinal dystrophies (IRDs) are a common cause of blindness or severe visual impairment in children and may occur with or without systemic associations. The aim of the present study is to describe the phenotypic and genotypic spectrum of IRDs in a pediatric patient cohort in Retrospective single-center cross-sectional analysis. Presenting symptoms, clinical phenotype, and molecular genetic diagnosis were assessed in 309 pediatric patients with suspected IRD. Patients were grouped by age at genetic diagnosis (preschool: 0–6 years, n = 127; schoolchildren: 7–17 years, n = 182). Preschool children most frequently presented with nystagmus (34.5% isolated, 16.4% syndromic), no visual interest (20.9%; 14.5%), or nyctalopia (22.4%; 3.6%; p < 0.05); schoolchildren most frequently presented with declining visual acuity (31% isolated, 21.1% syndromic), nyctalopia (10.6%; 13.5%), or high myopia (5.3%; 13.2%). Pathogenic variants were identified in 96 different genes (n = 69 preschool, n = 73 schoolchildren). In the preschool group, 57.4% had isolated and 42.6% had syndromic IRDs, compared to 70.9% and 29.1% in schoolchildren. In the preschool group, 32.4% of the isolated IRDs were related to forms of Leber's congenital amaurosis (most frequent were RPE65 (11%) and CEP290 (8.2%)), 31.5% were related to stationary IRDs, 15.1% were related to macular dystrophies (ABCA4, BEST1, PRPH2, PROM1), and 8.2% to rod–cone dystrophies (RPGR, RPB3, RP2, PDE6A). All rod–cone dystrophies (RCDs) were subjectively asymptomatic at the time of genetic diagnosis. At schoolage, 41% were attributed to cone-dominated disease (34% ABCA4), 10.3% to BEST1, and 10.3% to RCDs (RP2, PRPF3, RPGR; IMPG2, PDE6B, CNGA1, MFRP, RP1). Ciliopathies were the most common syndromic IRDs (preschool 37%; schoolchildren 45.1%), with variants in USH2A, CEP290 (5.6% each), CDH23, BBS1, and BBS10 (3.7% each) being the most frequent in preschoolers, and USH2A (11.7%), BBS10 (7.8%), CEP290, CDHR23, CLRN1, and ICQB1 (3.9% each) being the most frequent in syndromic schoolkids. Vitreoretinal syndromic IRDs accounted for 29.6% (preschool: COL2A1, COL11A1, NDP (5.6% each)) and 23.5% (schoolage: COL2A1, KIF11 (9.8% each)), metabolic IRDs for 9.4% (OAT, HADHA, MMACHD, PMM2) and 3.9% (OAT, HADHA), mitochondriopathies for 3.7% and 7.8%, and syndromic albinism accounted for 5.6% and 3.9%, respectively. In conclusion we show here that the genotypic spectrum of IRDs and its quantitative distribution not only differs between children and adults but also between children of different age groups, with an almost equal proportion of syndromic and non-syndromic IRDs in early childhood. Ophthalmic screening visits at the preschool and school ages may aid even presymptomatic diagnosis and treatment of potential sight and life-threatening systemic sequelae. [ABSTRACT FROM AUTHOR]

Background and Objectives: This retrospective study aimed to evaluate the efficacy of preoperative blood transfusions in correcting anemia for pediatric patients with congenital malformations (CMs) versus those with acute abdomen (AA) conditions. The study hypothesized that the response to transfusions might vary significantly between these groups due to the differences in the underlying pathology and clinical status. Methods: The study included 107 pediatric patients admitted to Timisoara 'Louis Turcanu' Emergency Hospital for Children between January 2015 and May 2023, who required blood transfusions for preoperative anemia. Hemoglobin (HGB), hematocrit (HCT), and red blood cell counts (RBC) were assessed at admission, 48 h post-transfusion, and at discharge. Statistical analyses, including Student's t-test, Pearson correlation, and chi-square tests, were utilized to compare outcomes between the groups. The study population was divided into 53 children with CM and 54 with AA. Results: Initial analyses showed that children with CM had statistically significantly higher baseline HGB (8.54 ± 1.00 g/dL vs. 7.87 ± 1.02 g/dL, p = 0.001) and HCT (26.07 ± 3.98% vs. 23.95 ± 2.90%, p = 0.002) compared to those with AA. Post-transfusion, children with CM exhibited a greater increase in HGB, with the highest increases noted in patients with central nervous system defects (mean increase of 3.67 g/dL, p = 0.038). In contrast, the increases in HGB for children with AA were less pronounced, with the highest being 2.03 g/dL in those with peritonitis (p = 0.078). Conclusions: No significant gender differences were noted in response to transfusion. Children with congenital malformations respond more effectively to preoperative blood transfusions compared to those with acute abdomen conditions. These findings suggest that differential transfusion strategies may be required based on the underlying medical condition to optimize the management of preoperative anemia in pediatric patients. Tailoring transfusion approaches according to specific patient needs and conditions could enhance clinical outcomes and resource utilization in pediatric surgical settings. [ABSTRACT FROM AUTHOR]

Assessment of minimal residual disease (MRD) is the most powerful predictor of outcome in B-type acute lymphoblastic leukemia (B-ALL). MRD, defined as the presence of leukemic cells in the blood or bone marrow, is used for the evaluation of therapy efficacy. We report on a microfluidic-based MRD (MF-MRD) assay that allows for frequent evaluation of blood for the presence of circulating leukemia cells (CLCs). The microfluidic chip affinity selects B-lineage cells, including CLCs using anti-CD19 antibodies poised on the wall of the microfluidic chip. Affinity-selected cells are released from the capture surface and can be subjected to immunophenotyping to enumerate the CLCs, perform fluorescence in situ hybridization (FISH), and/or molecular analysis of the CLCs' mRNA/gDNA. During longitudinal testing of 20 patients throughout induction and consolidation therapy, the MF-MRD performed 116 tests, while only 41 were completed with multiparameter flow cytometry (MFC-MRD) using a bone marrow aspirate, as standard-of-care. Overall, 57% MF-MRD tests were MRD(+) as defined by CLC numbers exceeding a threshold of 5 × 10−4%, which was determined to be the limit of quantitation. Above a threshold of 0.01%, MFC-MRD was positive in 34% of patients. The MF offered the advantage of the opportunity for efficiently processing small volumes of blood (2 mL), which is important in the care of pediatric patients, especially infants. The minimally invasive means of blood collection are of high value when treating patients whose MRD is typically tested using an invasive bone marrow biopsy. MF-MRD detection can be useful for stratification of patients into risk groups and monitoring of patient well-being after completion of treatment for early recognition of potential impending disease recurrence. [ABSTRACT FROM AUTHOR]

Anemia diagnosis is crucial for pediatric patients due to its impact on growth and development. Traditional methods, like blood tests, are effective but pose challenges, such as discomfort, infection risk, and frequent monitoring difficulties, underscoring the need for non-intrusive diagnostic methods. In light of this, this study proposes a novel method that combines image processing with learning-driven data representation and model behavior for non-intrusive anemia diagnosis in pediatric patients. The contributions of this study are threefold. First, it uses an image-processing pipeline to extract 181 features from 13 categories, with a feature-selection process identifying the most crucial data for learning. Second, a deep multilayered network based on long short-term memory (LSTM) is utilized to train a model for classifying images into anemic and non-anemic cases, where hyperparameters are optimized using Bayesian approaches. Third, the trained LSTM model is integrated as a layer into a learning model developed based on recurrent expansion rules, forming a part of a new deep network called a recurrent expansion network (RexNet). RexNet is designed to learn data representations akin to traditional deep-learning methods while also understanding the interaction between dependent and independent variables. The proposed approach is applied to three public datasets, namely conjunctival eye images, palmar images, and fingernail images of children aged up to 6 years. RexNet achieves an overall evaluation of 99.83 ± 0.02% across all classification metrics, demonstrating significant improvements in diagnostic results and generalization compared to LSTM networks and existing methods. This highlights RexNet's potential as a promising alternative to traditional blood-based methods for non-intrusive anemia diagnosis. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) is a chronic inflammatory bowel condition with increasing global incidence. Diagnosing CD is challenging and requires close collaboration between clinicians and pathologists due to the lack of specific diagnostic criteria. Histologically, CD is characterized by transmural inflammation, crypt distortion, metaplasia, and granulomas, although granulomas are not always present. Schaumann bodies (SB), initially described in sarcoidosis, are rare in CD but have been reported in about 10% of cases. This case report presents a 4-year-old female with chronic hemorrhagic diarrhea, severe anemia, and elevated inflammatory markers. Endoscopic and histological evaluations suggested CD, with the presence of SB in the gastric mucosa. Further investigations ruled out sarcoidosis, confirming a diagnosis of multi-segmental, very early onset CD with atypical histological features. SB are inclusions composed of calcium carbonate crystals and conchoid bodies, typically found within giant cells. The presence of SB in the mucosa is rare, limiting their diagnostic significance in endoscopic biopsies. Differential diagnosis should exclude other granulomatous diseases such as intestinal tuberculosis and sarcoidosis. This case highlights the importance of considering SB in the diagnosis of CD, particularly in pediatric patients. [ABSTRACT FROM AUTHOR]

Background/Objectives: Risperidone-related metabolic side effects in children have been primarily linked to variations between guideline-recommended and clinical treatment procedures. We explored the metabolic effects of risperidone administration in pediatric patients diagnosed with neurological disorders, thus evaluating its influence on metabolic indicators. Methods: This prospective cohort study gathered data from electronic health records, medical databases, and clinical reports. These data included patient demographics (e.g., age, sex, and body mass index) and information on risperidone use, including dosage, dosing frequency, and treatment duration. Additionally, laboratory tests were conducted at baseline and during treatment, along with other pertinent clinical variables. Result: A total of 52 eligible children (male; 73.1%) with neurological disorders treated with risperidone were included. The mean age was 13.4 ± 2.2 years. Risperidone was administered to 32.7% of patients for <2 years, 40.4% for 2–5 years, and 26.9% for 6–9 years, with a mean duration of 3.6 years. Most (53.8%) of the children experienced at least one metabolic side effect, with hyperlipidemia being the most common (34.6%). The median prolactin level increased slightly from 448.5 ng/mL at baseline to 479 ng/mL after 6–8 weeks. No significant associations were found between age, sex, duration of treatment, dosage form, dosing frequency, and hemoglobin A1c levels. Conclusion: Monitoring metabolic and anthropometric parameters in children receiving risperidone for neurological disorders is cardinal. Clinicians should consider individualized treatment plans, closely monitor metabolic markers, and address potential risks associated with long-term risperidone use in this vulnerable population. [ABSTRACT FROM AUTHOR]

Aortic coarctation surgery in pediatric patients requires the placement of two arterial cannulas to monitor pressure gradients and surgical correction adequacy. Near-infrared spectroscopy (NIRS) monitoring provides insight into regional blood flow. This study aimed to investigate the correlation between NIRS values and invasive arterial pressures, exploring NIRS monitoring as a potential substitute for arterial cannulation. In a cohort of 21 consecutive pediatric patients undergoing aortic coarctation surgery, recordings of NIRS and invasive arterial pressure values were evaluated at various time intervals. Pearson correlation evaluated the relationship between NIRS values and invasively measured arterial pressures. Moderate to strong correlations were observed between the mean arterial pressure (MAP) of the upper and lower arteries and cerebral (rSO2-C) and somatic (rSO2-S) NIRS values 5 min after cross-clamp placement (r = 0.621, p = 0.003; r = 0.757, p < 0.001). Strong correlations were found 15 min after cross-clamp placement (r = 0.828, p = 0.002; r = 0.783, p = 0.004). Before transfer to the ICU, a strong correlation existed between the upper artery MAP and rSO2-C (r = 0.730, p < 0.001), but there was no correlation between the lower artery MAP and rSO2-S. These findings are promising, but further studies are required to validate it as a reliable substitute for invasive pressure monitoring in this patient population. [ABSTRACT FROM AUTHOR]

Human parainfluenza viruses (HPIVs) are the leading causes of acute respiratory tract infections (ARTIs), particularly in children. During the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) significantly influenced the epidemiology of respiratory viruses. This study analyzed 19,339 respiratory specimens from pediatric patients with ARTIs to detect HPIVs using PCR or tNGS, focusing on the period from 2021 to 2023. HPIVs were identified in 1395 patients (7.21%, 1395/19,339), with annual detection rates of 6.86% (303/4419) in 2021, 6.38% (331/5188) in 2022, and 7.82% (761/9732) in 2023. Notably, both the total number of tests and HPIV-positive cases increased in 2023 compared to 2021 and 2022. Seasonal analysis revealed a shift in HPIV prevalence from winter and spring in 2021–2022 to spring and summer in 2023. Most HPIV-positive cases were in children aged 0–7 years, with fewer infections among those aged 7–18 years. Since June 2022, HPIV-3 has been the most prevalent serotype (59.55%, 524/880), whereas HPIV-2 had the lowest proportion (0.80%, 7/880). The proportions of HPIV-1 (24.89%, 219/880) and HPIV-4 (15.45%, 136/880) were similar. Additionally, the incidence of co-infections with other common respiratory pathogens has increased since 2021. This study highlights rising HPIV detection rates post-COVID-19 and underscores the need for continuous surveillance of HPIVs to inform public health strategies for future epidemic seasons. [ABSTRACT FROM AUTHOR]

Intestinal anti-endomysium antibodies are a specific marker of celiac disease. The diagnostic accuracy of this marker seems high in pediatric patients and has not yet been investigated in adults, so the aim of this prospective multicentric study was to evaluate the specificity and sensitivity of this marker in childhood and adulthood. Pediatric and adult patients undergoing intestinal endoscopy for any intestinal condition were enrolled. Serological celiac disease markers and HLA type were evaluated in all patients. Intestinal biopsies were analyzed for standard histology and for intestinal anti-endomysium antibodies with biopsy culture assay. In this study, 291 patients (145 adults and 146 children) were included. In the adult population, 34 were diagnosed with celiac disease, 105 were controls, and, in 6, celiac disease was not confirmed. In the pediatric population, 77 were diagnosed with celiac disease, 57 were controls, and, in 12, celiac disease was not confirmed. High diagnostic sensitivity and specificity of intestinal anti-endomysium antibodies were confirmed in children and additionally proven in adults. To conclude, we can affirm that intestinal anti-endomysium antibodies can be detected with high diagnostic accuracy in both children and adults. The implementation of this marker in the diagnostic work-up would help clinicians to correctly identify celiac disease. [ABSTRACT FROM AUTHOR]

Background: Robotic-assisted surgery (RAS) holds many theoretical advantages, especially in pediatric surgical procedures. However, most robotic systems are dedicated to adult surgery and are less suitable for smaller children. The Senhance® Surgical System (SSS®), providing 3 mm and 5 mm instruments, focuses on making RAS technically feasible for smaller children. This prospective observational study aims to assess whether RAS in pediatric patients using the SSS® is safe and feasible. Methods and Results: A total of 42 children (aged 0–17 years, weight ≥ 10 kg) underwent a RAS procedure on the abdominal area using the SSS® between 2020 and 2023. The study group consisted of 20 male and 22 female individuals. The mean age was 10.7 years (range 0.8 to 17.8 years), with a mean body weight of 40.7 kg (range 10.1 to 117.3 kg). The 3-mm-sized instruments of the SSS® were used in 12 of the 42 children who underwent RAS. The RAS procedures were successfully completed in 90% of cases. The conversion rate to conventional laparoscopy was low (10%), and there were no conversions to open surgery. One of the 42 cases (2%) experienced intraoperative complications, whereas six children (14%) suffered from a postoperative complication. Overall, 86% of the patients had an uncomplicated postoperative course. Conclusions: The results of the current observational study demonstrate the safety and feasibility of utilizing the SSS® for abdominal pediatric RAS procedures. The study provides new fundamental information supporting the implementation of the SSS® in clinical practice in pediatric surgery. [ABSTRACT FROM AUTHOR]

Background and Objectives: Dentigerous cysts are one of the most frequent pathologies associated with unerupted or impacted teeth. Such cysts show a male predilection and a preference for the mandibular region. Also, they commonly occur in the second and third decades of life, with only 9% occurring in the first decade. The aim of this work is to apply and study the therapeutic algorithms developed for dentigerous cysts and their outcomes, from the early diagnostic stage to the complete healing phase of pediatric patients diagnosed with this medical condition. Materials and Methods: The study included 19 pediatric patients diagnosed with dentigerous cysts who underwent the enucleation and extraction or conservative attitude of the associated tooth. The bony healing was also followed-up 9 months after the surgery. Results: A higher incidence in the posterior area of the mandible and maxilla was observed, as well as a higher incidence in boys. The 9 months postoperative radiographic assessment showed that the bony defects were completely healed. Conclusions: A thorough understanding of the nature of the lesion backed by a good clinical history and by state-of-the-art radiographic and radiologic examinations can go a long way in helping the surgeon to choose the correct therapeutic approach and to ameliorate the medical condition in the best long-term interest of the young patient. The considered dentigerous cyst cases demonstrated that an early diagnosis and treatment of this pathology is followed by a responsive treatment. [ABSTRACT FROM AUTHOR]

Background: Pressure ulcers pose significant challenges in terms of treatment, often exhibiting a low success rate and a propensity for recurrence. Children with neurological impairments such as myelomeningocele and those with spinal injuries are particularly vulnerable to developing pressure ulcers. Despite advancements, achieving successful reconstruction remains a formidable task. Common sites prone to pressure ulcer formation include the sacral and ischial regions, as well as areas over bony prominences. Additionally, pressure ulcers attributable to medical devices facilitating ambulation are observed. While many pressure sores resolve spontaneously, conservative management may prove ineffective for some, especially in cases of stage 3 and 4 ulcers, necessitating surgical intervention. Various surgical techniques are employed for the treatment of decubitus ulcers, yet there exists no universally accepted gold standard for their management. This paper presents our institutional experience in this domain, highlighting differences in surgical approaches, treatment outcomes, complication rates, and long-term follow-up. Methods: This study involved a retrospective analysis of medical records from 11 children, ranging in age from 10 to 17 years, who presented with extensive pressure ulcers that were unresponsive to conservative treatment measures. Data collection spanned from February 2017 to June 2022. The pressure ulcers affected various anatomical regions, including the ischial area (5/11 patients), sacral region (3/11 patients), lower limb (1/11 patients), elbow (1/11 patients), and perineal area (1/11 patients). Surgical intervention was the chosen approach for all cases, employing techniques such as reconstructive surgery utilizing perforator, pediculated flaps, and locoregional flaps. Results: Eleven patients with sore ulcers (stage 3 and 4) were treated surgically. We present our experience of using surgical methods, including pedicled anterolateral flaps, pedicled gracilis musculocutaneous flaps, propeller flaps and locoregional flaps. In some cases, surgery was performed after 60 days of hospitalization or ten years after ulcer occurrence. We reviewed the length of hospital stay, surgical management and patient satisfaction. Patients were followed up to 5 years post-surgery. All flaps survived except for one flap where partial necrosis was observed. The recurrence rate was 9.01% (1/11). One patient underwent another surgery. The general outcome was satisfactory. Conclusions: Conclusions: Our findings underscore the efficacy of flap reconstruction surgical techniques in the management of pressure ulcers among pediatric patients. Based on our experience and the outcomes observed, we advocate for considering reconstructive surgery as a viable therapeutic option early in the treatment course, particularly for stage 3 and 4 ulcers. This approach not only addresses the immediate needs of patients but also holds promise for long-term wound healing and prevention of recurrence. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098–5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74–35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87–16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915–16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83–15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747–11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831–22.02, p = 0.004, HR = 9.571, 95% CI 2.856–32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669–16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411–13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST. [ABSTRACT FROM AUTHOR]

Acute mastoiditis, a complication of otitis media, poses significant challenges in diagnosis and treatment, particularly in pediatric populations. This study aims to comprehensively evaluate the demographic characteristics, clinical features, and prognostic factors associated with acute mastoiditis in pediatric patients in Saudi Arabia. Analysis of a multicenter dataset was conducted to assess demographic variables, symptomatology, disease course, and predictors of acute mastoiditis in pediatric patients. Significant associations were found between demographic variables (age group, gender, nationality) and acute mastoiditis risk. Symptomatology analysis revealed consistent frequencies of otalgia across age groups and genders. Disease course analysis highlighted a mean duration from symptom onset to diagnosis of 14.11 days, with frequent complications like mastoid abscess and meningitis. Predictor identification identified symptoms (otalgia, fever, otorrhea), duration of illness, and complications as significant predictors of disease severity. These findings contribute valuable insights into the epidemiology and clinical management of acute mastoiditis, informing targeted interventions to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Bepotastine, a second-generation antihistamine for allergic rhinitis and urticaria, is widely used in all age groups but lacks appropriate dosing guidelines for pediatric patients, leading to off-label prescriptions. We conducted this study to propose an optimal dosing regimen for pediatric patients based on population pharmacokinetic (popPK) and physiologically based pharmacokinetic (PBPK) models using data from two previous trials. A popPK model was built using NONMEM software. A one-compartment model with first-order absorption and absorption lag time described our data well, with body weight incorporated as the only covariate. A PBPK model was developed using PK-Sim software version 10, and the model well predicted the drug concentrations obtained from pediatric patients. Furthermore, the final PBPK model showed good concordance with the known properties of bepotastine. Appropriate pediatric doses for different weight and age groups were proposed based on the simulations. Discrepancies in recommended doses from the two models were likely due to the incorporation of age-dependent physiological factors in the PBPK model. In conclusion, our study is the first to suggest an optimal oral dosing regimen of bepotastine in pediatric patients using both approaches. This is expected to foster safer and more productive use of the drug. [ABSTRACT FROM AUTHOR]

This systematic review was conducted with the objective of understanding the efficacy and safety of proton pump inhibitors (PPIs) in the pediatric population. We used PubMed to identify randomized controlled trials (RCTs) published between 1 June 2010 and 30 June 2023, performed in patients from birth to 18 years old with gastroesophageal reflux disease (GERD) who received treatment with any PPI. This literature search yielded 76 articles and 13 of these met the inclusion criteria. For infants, PPIs were equal to placebos in reducing GERD symptoms in four articles. In one article, the numbers of GER episodes and esophageal acid exposures were lower in infants who received PPIs in the left lateral position, but there was generally no significant improvement in symptoms. In another publication, the combination of PPIs and feeding modifications (FMs) was not more effective than PPIs alone. For children and adolescents, PPIs were effective in improving symptoms and achieving endoscopic healing, which was subsequently maintained. To conclude, PPIs are not effective in reducing the symptoms related to GERD in infants but are effective in older children, where histological remission can be seen. Generally, PPIs are well tolerated, but it is important to remember the possible adverse events (AEs), especially if PPIs are used for an extended period. [ABSTRACT FROM AUTHOR]

Background: Polytherapy in neonatal and pediatric patients requiring parenteral nutrition (PN) administration is a challenging task. Due to limited intravenous access, the Y-site administration of medication with PN admixtures is sometimes inevitable. Aim: This review aims to summarize the evidence on the compatibility of the Y-site of intravenous medications and PN admixtures in neonatal and pediatric settings. Methods: A literature review of the PubMed database was conducted. Articles published between January 1995 and November 2023 concerning the compatibility of intravenous medications in pediatric-dose PN admixtures or with intravenous lipid emulsions only were included. Studies concerning the compatibility/stability of the ingredients of PN admixtures and those concerning unapproved medications were excluded. Based on the methodology used, the quality of the research was assessed. Results: A total of fifteen studies were explored. Among fifty-five different drug substances assessed in the research reviewed, 56% (31/55) were found to be compatible, 13% (7/55) were assigned as incompatible, and for 31% (17/55), the data were ambiguous. None of the studies demonstrated an "A" grade (very high quality), and the grades "B", "C", and "D" were assigned to four, six, and five studies, respectively. The compatibility data are presented in two tables, the first concerning the simultaneous administration of medications with 2-in-1 PN formulations (without lipids) and the second, with 3-in-1 formulations (with lipids) and lipid emulsions. Conclusions: This review presents data on compatibilities between intravenously administered medications and PN mixtures intended for neonates and pediatric patients found in the PubMed database. It should be highlighted, however, that this work has some limitations. The clinical decisions on the simultaneous administration of intravenous medication with PN admixtures should be based not only on this review (including assessment of the quality of evidence) but also on manufacturer data, available electronic databases, and incompatibility data for PN admixtures dedicated to adult patients. [ABSTRACT FROM AUTHOR]

Background: Nissen Fundoplication (NF) is a frequently performed procedure in children. Robotic-assisted Nissen Fundoplication (RNF), with the utilization of the Senhance® Surgical System (SSS®) (Asensus Surgical® Inc., Durham, NC, USA) featuring 3 mm instruments, aims to improve precision and safety in pediatric surgery. This matched cohort study assesses the safety and feasibility of RNF in children using the SSS®, comparing it with Laparoscopic Nissen Fundoplication (LNF). Methods and Results: Twenty children underwent RNF with the SSS® between 2020 to 2023 and were 1:1 matched with twenty LNF cases retrospectively selected from 2014 to 2023. Both groups were similar regarding male/female ratio, age, and weight. Two of the twenty RNF cases (10%) experienced intraoperative complications, whereas three in the LNF group of whom two required reinterventions. The observed percentage of postoperative complications was 5% in the RNF group compared to 15% in the LNF group (p = 0.625). The operative times in the RNF group significantly dropped towards the second study period (p = 0.024). Conclusions: Utilizing SSS® for NF procedures in children is safe and feasible. Observational results may tentatively suggest that growing experiences and continued development will lead to better outcomes based on more accurate and safe surgery for children. [ABSTRACT FROM AUTHOR]

The incidence of Inborn Error of Intermediary Metabolism (IEiM) diseases may be low, yet collectively, they impact approximately 6–10% of the global population, primarily affecting children. Precise treatment doses and strict adherence to prescribed diet and pharmacological treatment regimens are imperative to avert metabolic disturbances in patients. However, the existing dietary and pharmacological products suffer from poor palatability, posing challenges to patient adherence. Furthermore, frequent dose adjustments contingent on age and drug blood levels further complicate treatment. Semi-solid extrusion (SSE) 3D printing technology is currently under assessment as a pioneering method for crafting customized chewable dosage forms, surmounting the primary limitations prevalent in present therapies. This method offers a spectrum of advantages, including the flexibility to tailor patient-specific doses, excipients, and organoleptic properties. These elements are pivotal in ensuring the treatment's efficacy, safety, and adherence. This comprehensive review presents the current landscape of available dietary products, diagnostic methods, therapeutic monitoring, and the latest advancements in SSE technology. It highlights the rationale underpinning their adoption while addressing regulatory aspects imperative for their seamless integration into clinical practice. [ABSTRACT FROM AUTHOR]

Background: SPN-812 has been approved for attention-deficit/hyperactivity disorder (ADHD) treatment in children and adolescents. Objective: We aimed to analyze the efficacy and safety of different doses of SPN-812 for ADHD pediatric patients of different ages, verify its clinical efficacy, and evaluate its safety. Methods: Up until 30 August 2023, randomized controlled trials (RCTs) were searched in EMBASE, MEDLINE, the Cochrane Library, and clinicaltrials.gov to evaluate different doses of SPN-812 and a placebo. Results: We pooled 1619 patients from five RCTs with a duration of 6–8 weeks. Patients (6–17 years old) in SPN-812 (100, 200, and 400 mg/d) groups were superior to the control group in all efficacy outcomes with lower attention-deficit/hyperactivity disorder rating scale-5 (ADHD-RS-5), Conners 3-parent short form composite T score (Conners 3-PS), Weiss functional impairment rating scale-parent (WFIRS-P), and increased clinical global impression-improvement (CGI-I) score (both p < 0.05). At the same time, only SPN-812 300 mg/d did not show a significantly high risk of the adverse events (AEs) such as somnolence and decreased appetite (p = 0.09). There was no significant difference between placebo and SPN-812 groups (100, 200, and 400 mg/d) in serious adverse events (SAEs) such as syncope. The subgroup analyses showed that, both in children and adolescents subgroups, SPN-812 showed better efficacy than the placebo. The two age subgroups showed a significantly higher risk of AEs and an insignificant risk of SAEs than the placebo. Conclusion: At present, SPN-812 (100, 200, and 400 mg/d) is superior to the corresponding control in efficacy measures. However, the safety problem cannot be ignored. [ABSTRACT FROM AUTHOR]

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections cause outbreaks of severe disease in children ranging from bloody diarrhea to hemolytic uremic syndrome (HUS). The adherent factor intimin, encoded by eae, can facilitate the colonization process of strains and is frequently associated with severe disease. The purpose of this study was to examine and analyze the prevalence and polymorphisms of eae in clinical STEC strains from pediatric patients under 17 years old with and without HUS, and to assess the pathogenic risk of different eae subtypes. We studied 240 STEC strains isolated from pediatric patients in Finland with whole genome sequencing. The gene eae was present in 209 (87.1%) strains, among which 49 (23.4%) were from patients with HUS, and 160 (76.6%) were from patients without HUS. O157:H7 (126, 60.3%) was the most predominant serotype among eae-positive STEC strains. Twenty-three different eae genotypes were identified, which were categorized into five eae subtypes, i.e., γ1, β3, ε1, θ and ζ3. The subtype eae-γ1 was significantly overrepresented in strains from patients aged 5–17 years, while β3 and ε1 were more commonly found in strains from patients under 5 years. All O157:H7 strains carried eae-γ1; among non-O157 strains, strains of each serotype harbored one eae subtype. No association was observed between the presence of eae/its subtypes and HUS. However, the combination of eae-γ1+stx2a was significantly associated with HUS. In conclusion, this study demonstrated a high occurrence and genetic variety of eae in clinical STEC from pediatric patients under 17 years old in Finland, and that eae is not essential for STEC-associated HUS. However, the combination of certain eae subtypes with stx subtypes, i.e., eae-γ1+stx2a, may be used as risk predictors for the development of severe disease in children. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton therapy enables the delivery of a high radiation dose to tumors while sparing surrounding normal tissues. Inaccurate patient positioning may lead to underdosing of the targeted tumor and overdosing of nearby healthy tissues. Before a course of proton therapy, a CT scan is acquired for treatment planning with the patient in the treatment position, and this image dataset is used as a reference for patient localization at each treatment fraction. Radiation therapists perform daily cone-beam CT (CBCT) image guidance to align the patient to closely match the planning CT and minimize inaccuracies in radiation delivery. In this study, CBCT scans were systematically collected with clinical and treatment information to investigate questions related to image guidance, setup uncertainty, and patient motion during the treatment of pediatric brain tumors. Knowledge gained from this study provides a basis for designing safe and optimal proton treatments. This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1–1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients ( p = 0.0016 ). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort. [ABSTRACT FROM AUTHOR]

Non-Hodgkin lymphomas (NHL) are a group of cancers that originate in the lymphatic system, especially from progenitor or mature B-cells, T-cells, or natural killer (NK) cells. NHL is the most common hematological malignancy worldwide and also the fourth most frequent type of cancer among pediatric patients. This cancer can occur in children of any age, but it is quite rare under the age of 5 years. In recent decades, available medicines and therapies have significantly improved the prognosis of patients with this cancer. However, some cases of NHL are treatment resistant. For this reason, immunotherapy, as a more targeted and personalized treatment strategy, is becoming increasingly important in the treatment of NHL in pediatric patients. The objective of the following review is to gather the latest available research results, conducted among pediatric and/or adult patients with NHL, regarding one immunotherapy method, i.e., chimeric antigen receptor (CAR) T cell therapy. We focus on assessing the effectiveness of CAR-T cell therapy, which mainly targets B cell markers, CD19, CD20, and CD22, their connections with one another, sequential treatment, or connections with co-stimulatory molecules. In addition, we also evaluate the safety, aftermath (especially neurotoxicities) and limitations of CAR-T cell therapy. [ABSTRACT FROM AUTHOR]

Background: Percutaneous CT-guided cryoablation is an emerging technique for treating bone tumors. However, experience with using this procedure for osteoid osteomas in pediatric patients remains limited. Our study aims to assess its technical feasibility, clinical efficacy, and safety in children treated under conscious anesthesia. Methods: We conducted a retrospective study of consecutive pediatric patients who underwent CT-guided percutaneous cryoablation for osteoid osteomas at our institution between September 2017 and March 2021. All patients received conscious anesthesia. Data on peri-procedural VAS scores, post-procedural VAS scores, imaging findings, and nonsteroidal anti-inflammatory drug (NSAID) usage rates were collected for each patient. Technical success was defined as proper cryoprobe placement at the nidus center, while clinical success referred to pain relief without NSAID use. Intra- and post-operative complications were also evaluated. Results: Nine patients underwent CT-guided percutaneous cryoablation for osteoid osteomas under conscious sedation, with a 100% overall success rate with low peri-procedural and median VAS scores (p < 0.01). No complications were observed during or after the procedure. Conclusions: CT-guided percutaneous cryoablation of pediatric osteoid osteomas is an effective and safe minimally invasive procedure feasible under conscious anesthesia, holding promise as a valuable treatment option. [ABSTRACT FROM AUTHOR]

Oral chemotherapy (OC) has been increasingly used in pediatric patients diagnosed with cancer, which is primarily managed in the outpatient setting. Different from adults, pediatric patients face unique challenges in administering these hazardous medications at home. Because of the complexity of pediatric pharmaceutical care and the hazardous nature of chemotherapy agents, comprehensive patient education is imperative to mitigate the potential safety risks associated with OC administration at home. Pharmacists play a vital role in patient education and medication consultations. However, the lack of practice guidelines and limited resources supporting OC counseling are noted. Additional barriers include insufficient knowledge and training on OC, which can be improved by continuing education. In a regional children's hospital, a comprehensive OC education checklist was developed for pediatric patients and their caregivers to standardize consultations led by pharmacists. An infographic OC handout was also formulated to improve patient knowledge and awareness. Moreover, innovative approaches such as using telepharmacy, smartphone applications, and artificial intelligence have been increasingly integrated into patient care, which can help optimize OC consultations for children and adolescents. Further studies are warranted to enhance oral chemotherapy education specifically tailored for pediatric patients in outpatient settings. [ABSTRACT FROM AUTHOR]

Introduction: This retrospective study aimed to determine skeletal and dental changes after a growth spurt and shortly after treatment using a facemask in skeletal Class III malocclusion with maxillary deficiency. Methods: We retrospectively studied 50 patients (25 patients per group) with skeletal Class III malocclusion who underwent facemask treatment with tooth-anchored (T-A, mean age 7.92) and miniscrew-anchored (M-A, mean age 9.84) intraoral appliances. In both groups, the facemask applied a traction force of 350–400 g to each side, such that the traction was directed 30° forward and downward. Lateral cephalometric radiographs were obtained from all patients before (T1), immediately after (T2), and at an average of 37.11 months after maxillary protraction (T3). A total of 13 cephalometric measurements were analyzed to determine the skeletal and dental changes. A paired t-test was used to verify the effects before, after, and during follow-up periods in each group. Results: An anteroposterior relationship, the values of SNA and ANB, evident in both groups at T2, was significantly improved in the M-A group (p < 0.05). However, the values of ANB and MP–SN, which indicate the relapse of anteroposterior and vertical relation of maxilla and mandible, were significantly higher in the T-A group compared with the M-A group during follow-up period. The maxillary first molars were significantly more extruded and maxillary incisors were more protruded in the T-A group than the M-A group, and this persisted at T3 (p < 0.05). Conclusions: Miniscrew-anchored maxillary protraction increased the skeletal improvement of anteroposterior relationship and reduced the dental and skeletal relapses compared with tooth-anchored maxillary protraction in growing patients with a hyperdivergent patterns and skeletal Class III malocclusion. [ABSTRACT FROM AUTHOR]

Children with inflammatory bowel disease (IBD) have an increased susceptibility to Clostridium difficile infection (CDI), with a rising incidence over time. Differentiating between CDI and IBD exacerbation is challenging due to overlapping symptoms. In our cohort of 55 pediatric IBD patients, 6 were diagnosed with CDI. Upon conducting a thorough patient evaluation and subsequent data analysis, an exhaustive review of the existing literature was undertaken. CDI is more prevalent in ulcerative colitis (UC) than Crohn's disease (CD) patients, as seen in our patients and in the existing literature. The management of a pediatric patient with IBD is itself a challenge for a clinician because of the chronic, possibly relapsing course, and substantial long-term morbidity. When CDI is added, it becomes even more demanding, since CDI leads to more severe disease in children with IBD. A multidisciplinary approach and intensive treatment for possible sepsis, anemia, hypoalbuminemia, and hydro-electrolytic and acid-base imbalances are frequently mandatory in patients with CDI and IBD, which leads to a significant health care burden in hospitalized children with IBD. After the infection is treated with antibiotic therapy, important considerations regarding the future treatment for the underlying IBD are also necessary; in most cases, a treatment escalation is required, as also seen in our study group. [ABSTRACT FROM AUTHOR]

Simple Summary: Cryopreservation of ovarian tissue and transplantation are the only available fertility techniques to preserve fertility and endocrine function for prepubertal girls with cancer who require immediate cancer treatment. The primary objective of this systematic review was to identify and critically appraise the existing evidence regarding targeted minimal infiltrative disease detection in harvested ovarian tissues and identify markers that may be of value for assessment before autotransplantation, thereby facilitating fertility restoration in childhood cancer survivors. While the majority of malignancies were found to be at low risk of containing malignant cells in ovarian tissue, more studies are needed to ensure safe implementation of future fertility restoration in clinical practice. Background: Ovarian tissue cryopreservation and transplantation are the only available fertility techniques for prepubertal girls with cancer. Though autotransplantation carries a risk of reintroducing malignant cells, it can be avoided by identifying minimal infiltrative disease (MID) within ovarian tissue. Methods: A broad search for peer-reviewed articles in the PubMed database was conducted in accordance with PRISMA guidelines up to March 2023. Search terms included 'minimal residual disease', 'cryopreservation', 'ovarian', 'cancer' and synonyms. Results: Out of 542 identified records, 17 were included. Ovarian tissues of at least 115 girls were evaluated and categorized as: hematological malignancies (n = 56; 48.7%), solid tumors (n = 42; 36.5%) and tumors of the central nervous system (n = 17; 14.8%). In ovarian tissue of 25 patients (21.7%), MID was detected using RT-qPCR, FISH or multicolor flow cytometry: 16 of them (64%) being ALL (IgH rearrangements with/without TRG, BCL-ABL1, EA2-PBX1, TEL-AML1 fusion transcripts), 3 (12%) Ewing sarcoma (EWS-FLI1 fusion transcript, EWSR1 rearrangements), 3 (12%) CML (BCR-ABL1 fusion transcript, FLT3) and 3 (12%) AML (leukemia-associated immunophenotypes, BCR-ABL1 fusion transcript) patients. Conclusion: While the majority of malignancies were found to have a low risk of containing malignant cells in ovarian tissue, further studies are needed to ensure safe implementation of future fertility restoration in clinical practice. [ABSTRACT FROM AUTHOR]

Gender-based medicine is attracting increasing interest every day, but studies on pediatric populations are still limited. In this setting, sex differences among patients undergoing total parenteral nutrition (TPN) have not been previously reported. This study investigated the presence of sex differences in parenteral nutrition composition and outcomes among a cohort of pediatric patients admitted at the Oncohematology and Bone Marrow Transplant Unit of the Institute for Maternal and Child Health "Burlo Garofolo" of Trieste, Italy. For all 145 recruited patients (87 males, 58 females), the following data were collected: age, sex, volume and duration of TPN, macro- and micronutrient composition of TPN bags, electrolytic or blood gases imbalance, glycolipid alterations, liver damage during TPN, and the incidence of sepsis and thrombosis. The analysis showed that females required higher daily phosphate intake (p = 0.054) and essential amino acid supplementation (p = 0.07), while males had a higher incidence of hypertriglyceridemia (p < 0.05) and cholestasis. A higher incidence of sepsis was found in the non-transplanted male population (p < 0.05). No significant differences were appreciable in other analyzed variables. This study aims to create a basis for future gender-based nutritional recommendations in the pediatric field. [ABSTRACT FROM AUTHOR]

Atopic dermatitis (AD) is a chronic inflammatory skin disease affecting up to 20% of children. Methotrexate (MTX) is used off-label as a systemic treatment for AD patients unresponsive to topical therapies, but limited data exist regarding its safety and efficacy in children, especially in those < 4 years old. To further investigate MTX in younger patients, we screened the medical records of three referral centers between 2016 and 2022 and identified 28 infants and toddlers < 4 years old with AD treated with MTX. Mean age upon MTX initiation was 2.7 ± 1.2 years and mean investigator global assessment (IGA) score was 3.78 ± 0.4. Median duration of MTX treatment was five months. Following 12 and 24 weeks of MTX treatment, the response rate was 50% and IGA 0/1 was achieved in 14.2% and 21.4% of patients, respectively. Most treatment cessations were attributed to a lack of efficacy or parental concern. Although adverse events were reported in 57.1% of patients, MTX was discontinued due to such adverse events only in two patients (7.1%). Taken together, MTX demonstrated a high safety profile in AD patients <4 years old. MTX efficacy was moderate and presumably underestimated by parents who opted for premature treatment cessation due to concerns associated with an immunomodulatory drug. [ABSTRACT FROM AUTHOR]

Children who sustain major injuries are at risk of receiving insufficient pain relief and sedation, which can have physical and psychological repercussions. Heightened emotional distress can increase the likelihood of developing symptoms of post-traumatic stress. Providing sufficient analgesia and sedation for children with major trauma presents specific challenges, given the potential for drug-related adverse events, particularly in non-intubated patients. The current literature suggests that a relatively low percentage of pediatric patients receive adequate analgesia in pre-hospital and emergency department settings following major trauma. There are only sparse data on the safety of the provision of analgesia and sedation in children with major trauma in the pre-hospital and ED settings. The few studies that examined sedation protocols in this context highlight the importance of physician training and competency in managing pediatric airways. There is a pressing need for prospective studies that focus upon pediatric major trauma in the pre-hospital and emergency department setting to evaluate the benefits and risks of administering analgesia and sedation to these patients. The aim of this narrative review was to offer an updated overview of analgesia and sedation management in children with major trauma in pre-hospital and ED settings. [ABSTRACT FROM AUTHOR]

To date, the treatment for cysticercosis and neurocysticercosis consists of a single oral intake of praziquantel (5–10 mg/kg), which since it is only available as tablets, hinders its administration to pediatric patients. Praziquantel is a poorly water-soluble drug which represents a challenge for its formulation in solution, particularly for the pediatric population. Thus, this study aimed to develop a palatable solution for praziquantel using pharmaceutical-accepted co-solvent systems. A design of experiments approach was applied to identify the optimal conditions for achieving a suitable amount of praziquantel in solution using co-solvent mixtures. Thus, praziquantel solubility increased from 0.38 up to 43.50 mg/mL in the optimized system. A taste masking assay in healthy human volunteers confirmed a successful reduction of drug bitterness after the addition of selected flavors and a sweetener. Stability studies were also conducted at different temperatures (4, 25, and 40 °C) for 12 months Even though the presence of the three known impurities of praziquantel was observed, their amounts never exceeded the acceptance criteria of the USP. Thus, this novel approach should be considered a valuable alternative for further preclinical studies considering the high prevalence of this infection worldwide. [ABSTRACT FROM AUTHOR]

(1) Background: Extravasation injuries in pediatric patients can lead to significant harm if they are not promptly diagnosed and treated. However, evidence-based standardization on extravasation management remains limited, particularly for extensive wound necrosis. This case report presents the management of an 8-week-old premature patient with an extensive extravasation injury involving the right forearm and dorsum of the hand. (2) Methods: The patient was evaluated by a multidisciplinary team in our Neonatal Intensive Care Unit. Surgical intervention involved the debridement of necrotic tissues, followed by temporary coverage with an acellular dermal matrix. Definitive coverage was achieved through Meek micrografting after three weeks. Physical therapy was provided with pre- and post-rehabilitation range of motion assessed using goniometric measurements. Scar quality was evaluated using the Vancouver Scar Scale. (3) Results: The engraftment rate of the Meek micrografts was 93%, with 16 out of 226 micrografts lost. The patient achieved a Vancouver Scar Scale score of 6, indicating a moderate degree of scarring. Significant improvements in elbow, wrist, and finger joint range of motion were observed at a 1-year follow-up. (4) Conclusions: Close observation and heightened awareness of extravasation risks by trained personnel are crucial. Meek micrografting combined with dermal substitute coverage represents an innovative approach to managing extravasation wounds in pediatric patients. [ABSTRACT FROM AUTHOR]

Simple Summary: This review summarizes various unique aspects of managing APL in very elderly and pediatric patients, particularly treatment with ATO, toxicities, and dose modifications. Tailored treatment with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) has revolutionized the outcome of acute promyelocytic leukemia (APL) from a uniformly fatal disease to one of the most curable malignant diseases in humans. Due to its high efficacy, ATO/ATRA is the standard first-line therapy in younger adult, non-high-risk APL patients. However, early death is still a major issue in APL, particularly in older patients. Thus, rapid diagnostics, immediate access to ATRA-based therapy, and supportive care are of utmost importance. Nevertheless, challenging situations occur, particularly in patients excluded from controlled studies with clinical knowledge mainly based on case reports and registries. Besides the treatment of newly diagnosed patients, managing toxicities and complications remains challenging. This review discusses the approach to the treatment of APL in elderly and pediatric patients. [ABSTRACT FROM AUTHOR]

Anthracyclines are widely used in the treatment of many solid cancers, but their efficacy is limited by cardiotoxicity. As the number of pediatric cancer survivors continues to rise, there has been a concomitant increase in people living with anthracycline-induced cardiotoxicity. Accordingly, there is an ongoing need for new models to better understand the pathophysiological mechanisms of anthracycline-induced cardiac damage. Here we generated induced pluripotent stem cells (iPSCs) from two pediatric oncology patients with acute cardiotoxicity induced by anthracyclines and differentiated them to ventricular cardiomyocytes (hiPSC-CMs). Comparative analysis of these cells (CTX hiPSC-CMs) and control hiPSC-CMs revealed that the former were significantly more sensitive to cell injury and death from the anthracycline doxorubicin (DOX), as measured by viability analysis, cleaved caspase 3 expression, oxidative stress, genomic and mitochondrial damage and sarcomeric disorganization. The expression of several mRNAs involved in structural integrity and inflammatory response were also differentially affected by DOX. Functionally, optical mapping analysis revealed higher arrythmia complexity after DOX treatment in CTX iPSC-CMs. Finally, using a panel of previously identified microRNAs associated with cardioprotection, we identified lower levels of miR-22-3p, miR-30b-5p, miR-90b-3p and miR-4732-3p in CTX iPSC-CMs under basal conditions. Our study provides valuable phenotype information for cellular models of cardiotoxicity and highlights the significance of using patient-derived cardiomyocytes for studying the associated pathogenic mechanisms. [ABSTRACT FROM AUTHOR]

Lithiasis is a known side effect of ceftriaxone administration in children. Sex, age, weight, dosage, and duration of intake have been reported as risk factors for the formation of calcification or stones in the bile and urine excretory systems of children who received ceftriaxone. The purpose of this systematic review is to investigate the reported effects of ceftriaxone administration in pediatric patients who were admitted to a hospital due to infection, the likelihood of gallstones, nephroliths, or precipitations in both the biliary and urinary systems, as well as investigate the relationship with their mother's history during pregnancy. Original studies and literature reviews from the PubMed database were included in the study. No time limit related to research or publication was set for the articles. The results were evaluated, aiming to understand the outcomes and identify any predisposing factors relevant to this side effect. Of the 181 found articles, 33 were appropriate for inclusion in the systematic review. The administered dose of ceftriaxone presented variability. Symptoms, such as abdominal pain and vomiting, were associated with ceftriaxone-related lithiasis in many cases. It was noted that most of the results were the outcomes of retrospective observation and not of prospective randomized research. Definitively, more randomized control studies with long-term outcomes are needed to identify the exact association between ceftriaxone and lithiasis in children. [ABSTRACT FROM AUTHOR]

Background: This study describes the management protocol for capillary-venous malformations in pediatric patients and reports the epidemiology of diagnosed and treated cases at the Unit of Odontostomatology of the Aldo Moro University of Bari from 2014 to 2022. Methods: The authors classified the intraoral and perioral capillary-venous malformations by superficial diameter (<1 cm, 1–3 cm, >3 cm) and ultrasonographical depth extension (≤5 mm, >5 mm). All patients underwent pulsed-mode diode laser transmucosal photocoagulation (8–12 W/cm2); those with malformations that were wide (>3 cm) and deep (>5 mm) received intralesional photocoagulation, too (13 W/cm2). The children received general anesthesia based on their compliance and lesions' extension. The follow-up lasted six months. Results: A total of 22 females and 14 males (age range 4–18 years) presented 63 capillary-venous malformations. Five patients with Sturge–Weber syndrome, seven with hereditary hemorrhagic telangiectasia, and five with angiomatosis showed multiple malformations. The authors found no intraoperative or postoperative complications. Seventeen patients with lesions >1 cm and >5 mm deep required multiple laser sessions to heal. Conclusion: The results of the current study support diode laser photocoagulation as the gold standard for the treatment of intraoral and perioral capillary-venous malformations in pediatric patients. [ABSTRACT FROM AUTHOR]

Background: Secondary PTSD is defined as the natural, consequential behaviors and emotions that result from knowledge about a traumatic event experienced by a significant other deriving from working with suffering individuals. Pediatric health providers with symptoms of PTSD report problems with relationships and general life dissatisfaction as well as and anxiety, depression and burnout syndrome. Aim: The aim of this systematic review was to estimate the risk of developing secondary PTSD among pediatric health care providers as well as all additional contributing factors. In more detail, we investigated the PTSD symptomatology between pediatric health care providers and the extent to which parameters such as the job, gender, department and other factors had an impact on the mental health status of pediatric health care providers. Methodology: We searched all published English papers in PubMed, Google Scholar and the Cochrane Library from September to November 2022. We excluded reviews, systematic reviews and meta-analyses as well as letters to editors. From a total of 748 papers, we included only 12 research articles that met the admission criteria. Results: According to our results, the prevalence of secondary PTSD ranges from 13% to 94%. Burnout, nurses, the female gender, intensive care units, past traumatic life events and a psychiatric history identified as factors contributing to the development of secondary PTSD. Conclusions: Health policy-makers should take the specificity in the working environment of the pediatric sector seriously into consideration, especially emergency departments. [ABSTRACT FROM AUTHOR]

Background: The pandemic of coronavirus disease 2019 (COVID-19) was undoubtedly a stressful experience for everyone. General opinion believed that children with acute or chronic illness could experience additional burden, but this is not confirmed. The aim of this study is to understand how children and adolescents already suffering from acute or chronic illness (e.g., cancer, cystic fibrosis, neuropsychiatric disorders) feel about the COVID-19 pandemic, and if the experience is significantly different between these children and children without illness. Methods: Children and adolescents affected by acute or chronic illness (named the "fragile group") treated at the Regina Margherita Children Hospital in Italy, were enrolled in the study by filling a questionnaire about their pandemic experiences. Also, a group of children and adolescents without acute or chronic illness (named the "low-risk group") recruited in the emergency department of the hospital, participated in the study in order to compare experiences. Results: The study group was composed of 166 children and adolescents (Median age = 12 yrs; 78% fragile group, 22% low-risk group). Participants experienced a general state of fear of the virus and of a potential infection for both themselves and their families, while feelings and thoughts that interfere with daily functioning were less frequent. The fragile group seems to be more resilient towards the pandemic situation than low-risk group and some differences on the basis of the type of illness were found in the fragile group. Conclusions: Dedicated psychosocial intervention must be proposed in order to support fragile children and adolescents' well-being during the pandemic, also on the basis of their clinical and mental history. [ABSTRACT FROM AUTHOR]

B-cell precursor acute lyphoblastic leukemia (ALL) is a common pediatric malignancy and patients may have significant benefits from monoclonal antibodies therapy with increased survival rates. Positive CD20 expression is identified in about half of these patients and its presence may serve as a prognostic factor in disease evolution. We performed a retrospective study including 114 patients diagnosed with B-ALL and evaluated the expression of CD20 through flow cytometry at diagnosis and on day 15. Additional immunophenotypic analyses as well as cytogenetic and molecular genetic analyses were also performed. We observed an increase in the mean fluorescence intensity (MFI) of CD20 between diagnosis—1.9 (1.2–3.26) and day 15: 6.17 (2.14–27.4), (p < 0.0001). Furthermore, we assessed that both diagnosis and day 15 CD20 MFI had an impact on RFS and OS, respectively, for cut-off values of >8.08 at diagnosis and >28.65 at day 15. In conclusion, CD20 expression appears to be a poor prognostic feature of B-ALL in pediatric patients. In this study, stratification of the outcome by the intensity of CD20 has implications concerning the allocation to rituximab-based chemotherapy and may offer new, potentially useful information for pediatric patients with B-ALL. [ABSTRACT FROM AUTHOR]

Maple syrup urine disease (MSUD) is a metabolic disorder characterized by a difficulty to digest and process proteins necessary for growth. To monitor and maintain the ideal growth of children with MSUD, caregivers need to carefully control the consumption of harmful branched-chain amino acids (BCAAs). The dietary limits of amino acids for MSUD patients are recommended and controlled by pediatricians and metabolic dietitians according to age, height, weight, and the prevailing percentage of amino acids in the body. This study introduces an intelligent dietary tool called MSUD Baby Buddy for caregivers of MSUD patients that tracks the amino acids intake out of baby formulas for babies 0–6 months old. This tool aims to provide accurate recommendations of the appropriate daily intake of protein and BCAAs based on the patients' data, plasma BCAAs, and formula preferences. We use a knowledge-based system, including knowledge acquisition and verification, as well as knowledge management tool validation, and the ripple-down rules are employed for building the system. MSUD Baby Buddy can support the maintenance of adequate amino acid levels and increase awareness about the control of BCAAs. The average usability of MSUD Baby Buddy is 84.25, indicating that the tool is intuitive and may help caregivers to easily determine the recommended doses of formula based on patients' biometric data and preferred formula. On the other hand, interviews with metabolic dietitians revealed some drawbacks, which were addressed to further improve the tool. MSUD Baby Buddy is expected to help caregivers of MSUD patients to independently track nutrient intake and reduce the number of visits to the pediatrician and metabolic dietitian. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infections, as one of the most prevalent among humans, are generally acquired during childhood, and are one of the main causes of chronic gastritis and peptic ulcer disease. A bacterial culture from a gastric biopsy is the gold standard and is the only method that has 100% specificity. However, its sensitivity varies, depending on experience of the laboratory staff, applied culture media, specimen transport conditions, biopsy site, and quality of the sample. The same factors compromise all invasive methods and a culture-based H. pylori infection diagnostic, as well as a recent intake of antibiotics, bismuth-containing compounds, and proton pump inhibitors. Molecular methods have been used for clinical microbiology investigation since the beginning of the 21st century. However, their usefulness for H. pylori infections diagnosis remains unclear, especially in pediatric patients. The aim of the study was to assess the incidence of H. pylori infections in a group of 104 pediatric patients and to compare the results of the PCR test with the corresponding histopathological investigation effects. Among the biopsy samples collected from 104 children, 44 (42.3%) were positive in PCR, while 43 (41.3%) and 39 (37.5%) presented histologically-confirmed signs of inflammation and H. pylori colonization, respectively. Moreover, the mean grades of the parameters of the histopathological examination were higher in the group of PCR-positive samples. The compatibility of both research methods was confirmed, emphasizing the usefulness of molecular methods for detecting H. pylori infections in pediatric patients. Considering that the PCR-based method gives reliable results and is less time-consuming and costly, it is worth discussing this method as a new standard in the diagnosis of H. pylori infections, at least among pediatric patients, for which culture-based diagnostics is not sufficient or histopathological examination is negative, while inflammation signs are observed macroscopically. [ABSTRACT FROM AUTHOR]

Many cases of cellulitis in the head and neck region among hospitalized pediatric patients are related to odontogenic infections. C-reactive protein (CRP), white blood cell (WBC) count, neutrophils to lymphocytes ratio (NLR), D-dimer, and prealbumin can be used to assess the severity of odontogenic inflammation. The aim of the study is to evaluate the biochemical parameters as a predictor factor of the severity of odontogenic cellulitis in children. This study was conducted from 2020 to 2021 on patients admitted to the Department of Pediatric Otolaryngology and Pediatric Head and Neck Surgery of the Upper Silesian Children's Health Center in Katowice. We included 40 patients aged 2–16 in the study, who were divided into two groups: research (SS-Study subject) (n = 20) and control (CS-Control subject) (n = 20). The patients underwent an interview and physical examination to assess the presence of intraoral and extraoral swelling and the presence of trismus. The patients who qualified for the study had blood taken to determine the level of CRP, WBCs, NLR, D-dimers, and prealbumin. Differences in biochemical test results in the SS and CS were statistically significant (p < 0.05). In the SS group, the mean values of biochemical parameters exceeded the clinical norm. A statistically significant positive relationship was found between CRP and extraoral swelling. The NLR correlates significantly with extraoral swelling and the length of hospitalization. D-dimer statistically correlated with trismus, extraoral swelling, and the number of anatomical spaces involved. The NLR and CRP ratio can be considered a prognostic marker of the course of infection and hospitalization time. [ABSTRACT FROM AUTHOR]

Thiopurine drugs are part of the therapeutic armamentarium for pediatric patients suffering from inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL). The therapeutic drug monitoring of these drugs, consisting of measurements of the thiopurine metabolites thioguanine nucleotides (TGN) and methylmercaptopurine nucleotides (MMPN) are used to optimize the effectiveness of treatment and prevent adverse effects. In this context, we developed and validated a high-performance liquid chromatography—diode array detection (HPLC–DAD) method for the simultaneous quantification of thiopurine metabolites according to the most recent International Council for Harmonisation (ICH) guidelines. The calibration curves were built in the clinically relevant range of concentrations for TGN of 300–12,000 nM and for MMPN of 3000–60,000 nM. The limit of detection and the lower limit of quantification were 100 and 300 nM for TGN and 900 and 3000 nM for MMPN, respectively. The percentage of inter-day accuracy and precision (CV%) varied between 85 and 104% and 1.6 and 13.8%. Stability was demonstrated for both of the metabolites for at least 50 days at −20 °C. The proposed HPLC–DAD method showed an appropriate selectivity, specificity, linearity, accuracy, precision and good applicability to samples from patients with IBD and ALL undergoing thiopurine treatment. [ABSTRACT FROM AUTHOR]

Objective: Robot-assisted laparoscopic ureteral reimplantation (RALUR) and trans-umbilical multiport laparoscopic ureteral reimplantation (TMLUR) are both minimally invasive procedures for benign distal ureteral stricture (DUS). However, TMLUR has rarely been reported in published research, thus the difference in mid-term outcome of these two procedures warrants investigation. Methods: Patients who underwent RALUR or TMLUR for pediatric DUS from April 2017 to November 2020 at our institution were retrospectively analyzed and 56 patients were included in this retrospective comparison. Demographic characteristics, perioperative data and follow-up results were collected and analyzed in RALUR and TALUR groups. Results: RALUR and TMLUR were successfully performed in children aged from 12.0 to 142.0 months, without conversion to open ureteral reimplantation. RALUR took shorter operative time than TMLUR (p = 0.005) with less blood loss (p = 0.001). Meanwhile, patients receiving RALUR encountered a greater financial burden (p < 0.001) with less cosmetic satisfaction than TMLUR. The mean mid-term follow-up time for RALUR and TMLUR was 18.29 months and 24.64 months, respectively. Mid-term follow-up data showed that DUS was relieved with improved renal function after surgery in both groups, with no significant difference. Conclusions: RALUR and TMLUR are both safe and efficient for DUS treatment and achieve comparable mid-term outcomes in children. RALUR can reduce operative time and operative blood loss benefiting from its prominent technical superiority, but may currently bring about greater financial burden, with cosmetic satisfaction remaining to be improved. [ABSTRACT FROM AUTHOR]

Quinidine (QND) is an old antimalarial drug that was used in the early 20th century as an antiarrhythmic agent. Currently, QND is receiving attention for its use in epilepsy of infancy with migrating focal seizures (EIMFS) due to potassium sodium-activated channel subfamily T member 1 (KCNT1) genetic variants. Here, we report the application of Therapeutic Drug Monitoring (TDM) in pediatric patients carrying KCNT1 genetic variants and orally treated with QND for developmental and epileptic encephalopathies (DEE). We measured plasma levels of QND and its metabolite hydroquinidine (H-QND) by using a validated method based on liquid chromatography coupled with mass spectrometry (LC-MS/MS). Three pediatric patients (median age 4.125 years, IQR 2.375–4.125) received increasing doses of QND. Cardiac toxicity was monitored at every dose change. Reduction in seizure frequency ranged from 50 to 90%. Our results show that QND is a promising drug for pediatric patients with DEE due to KCNT1 genetic variants. Although QND blood levels were significantly lower than the therapeutic range as an anti-arrhythmic drug, patients showed a significant improvement in seizure burden. These data underlie the utility of TDM for QND not only to monitor its toxic effects but also to evaluate possible drug–drug interactions. [ABSTRACT FROM AUTHOR]

Pesticide poisoning in pediatric patients is still an important reason for presenting to the emergency department in Romania. In this context, the present study aims to raise awareness of the toxicological impact of pesticides on human health in pediatrics. For this purpose, the demographic characteristics, clinical assessment, and outcome of pediatric patients with acute pesticide poisoning admitted to the toxicology department of "Saint Mary" Emergency Children's Hospital from Iasi, were analyzed. This retrospective study focused on the clinical and laboratory data of patients aged under 18 years diagnosed with acute pesticide poisoning between 2010–2020. The statistical analysis was performed using the Statistica 10 package. A total of 49 patients presented with manifestations of acute pesticide poisoning, and the most common pesticide involved was diazinon. The most frequent exposure route was accidentally ingesting pesticide products (95%). The primary clinical manifestations were toxic encephalopathy, coma, depressive disorder, gastric disorders, and respiratory failure. Changes in the glycemic status, liver, and kidney damage were also present. Treatment included decontamination, administration of antidote, supportive care, and recommendations to be closely monitored to avoid a new incident. These results highlight the toxic potential of pesticides on human health and their biological consequences, which require an increase in consciousness of the precautions imposed on their use, especially when children are nearby. [ABSTRACT FROM AUTHOR]

Long-term preservation of kidney function after liver transplantation (LT) has not been well studied. We thus evaluated the rates of kidney function preservation and long-term survival after pediatric LT. We also investigated the risk factors associated with the progression of chronic kidney disease (CKD). We conducted a retrospective study of 184 pediatric patients who had undergone LT from 2003 to 2018 at a university hospital. We collected demographics, primary indications for LT, liver disease scores, renal function test results, immunosuppressive drug prescriptions, and diagnosis of post-LT complications. The 15-year survival rate was 90.8%. Furthermore, the rate of kidney function preservation at 14 years post-LT in patients at high risk of renal disease was 79.3%, and that in those with less risk of kidney diseases was 96.0%. Arterial hypertension was an independent risk factor associated with CKD progression. However, when arterial hypertension was excluded, the use of cyclosporine and liver disease with renal involvement were risk factors for CKD progression. We found that kidney function after pediatric LT was well preserved. We encourage the early detection of underlying kidney involvement, routine monitoring of renal function for high-risk patients, active control of hypertension, and appropriate immunosuppressive regimens for pediatric patients with LT. [ABSTRACT FROM AUTHOR]