Inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in susceptible pediatric patients: a case series.

BACKGROUND: Pulmonary aspergillosis is a prevalent opportunistic fungal infection that can lead to mortality in pediatric patients with underlying immunosuppression. Appropriate and timely treatment of pulmonary aspergillosis can play a crucial role in reducing mortality among children admitted with suspected infections. CASE PRESENTATION: The present study reports three cases of inappropriate treatment of pulmonary aspergillosis caused by Aspergillus flavus in two Iranian pediatric patients under investigation and one Afghan patient. Unfortunately, two of them died. The cases involved patients aged 9, 1.5, and 3 years. They had been diagnosed with pulmonary disorders, presenting nonspecific clinical signs and radiographic images suggestive of pneumonia. The identification of A. flavus was confirmed through DNA sequencing of the calmodulin (CaM) region. CONCLUSION: A. flavus was the most prevalent cause of pulmonary aspergillosis in pediatric patients. Early diagnosis and accurate antifungal treatment of pulmonary aspergillosis could be crucial in reducing the mortality rate and also have significant potential for preventing other complications among children. Moreover, antifungal prophylaxis seems to be essential for enhancing survival in these patients.

Risk factors for chloral hydrate sedation failure in pediatric patients: a retrospective analysis.

Background: This study aimed to investigate the risk factors for chloral hydrate sedation failure and complications in a tertiary children's hospital in South Korea. Methods: A retrospective analysis of pediatric procedural sedation with chloral hydrate between January 1, 2021, and March 30, 2022, was performed. The collected data included patient characteristics, sedation history, and procedure. Multivariable regression analysis was performed to identify the risk factors for procedural sedation failure and complications. Results: A total of 6691 procedural sedation were included in the analysis; sedation failure following chloral hydrate (50 mg/kg) occurred in 1457 patients (21.8%) and was associated with a higher rate of overall complications compared to those with successful sedation (17.5% [225 / 1457] vs. 6.2% [322 / 5234]; P < 0.001; odds ratio, 3.236). In the multivariable regression analysis, the following factors were associated with increased risk of sedation failure: general ward or intensive care unit inpatient (compared with outpatient); congenital syndrome; oxygen dependency; history of sedation failure or complications with chloral hydrate; procedure more than 60 min; and magnetic resonance imaging, radiotherapy, or procedures with painful or intense stimuli (all P values < 0.05). Factors contributing to the complications included general ward inpatient, congenital syndromes, congenital heart disease, preterm birth, oxygen dependency, history of complications with chloral hydrate, and current sedation failure with chloral hydrate (all P values < 0.05). Conclusions: To achieve successful sedation with chloral hydrate, the patient's sedation history, risk factors, and the type and duration of the procedure should be considered.

Association between adeno-associated virus 2 and severe acute hepatitis of unknown etiology in Japanese children.

INTRODUCTION: Outbreaks of acute hepatitis of unknown etiology (AHUE) in children were reported in Western countries in 2022. Previous studies found that adeno-associated virus 2 (AAV2) and its helper viruses, such as human adenovirus (HAdV) and human herpesvirus-6 (HHV-6), are frequently detected in patients with AHUE. However, the existence of hepatitis associated with AAV2 prior to AHUE outbreaks in 2022 had not yet been investigated. We aimed to investigate the association between AAV2 and pediatric acute hepatitis in Japanese children, as well as the incidence of AAV2-related hepatitis prior to 2022. METHODS: Preserved blood samples obtained from 49 pediatric patients with acute hepatitis between 2017 and 2023 were retrospectively analyzed. Blood samples from 50 children with acute illnesses and 50 children with chronic conditions were used as controls. Viral DNA loads were quantitated using real-time PCR. RESULTS: AAV2 DNA was detected in 12 % (6/49) of acute hepatitis cases but in only one acute illness and none of the chronic-condition control cases. The concentration of AAV2 DNA in the six acute hepatitis cases was higher than that in the acute-illness control case. Co-infection with one or more helper viruses, including HAdV, HHV-6, cytomegalovirus, and Epstein-Barr virus, was observed in five AAV2-positive cases. CONCLUSIONS: Our results indicated the sporadic occurrence of pediatric severe hepatitis associated with AAV2 infection in Japan prior to the AHUE outbreaks in 2022. Our findings suggest that co-infection with AAV2 and helper viruses plays a role in developing severe hepatitis.

The PompeQoL questionnaire: Development and validation of a new measure for children and adolescents with Pompe disease.

Genetic disorders pose great challenges for affected individuals and their families, as they must cope with the irreversible nature of the disease and a life-long dependence on medical assistance and treatment. Children and adolescents dealing with Pompe disease (PD) often struggle to keep up with their peers in physical activities. To gain valuable insights into their subjective experiences and better understand their perception and coping related to daily challenges linked to their condition and treatment, the use of standardized questionnaires is crucial. This study introduces the novel PompeQoL 1.0 questionnaire for children and adolescents with PD, designed for comprehensive assessment of both disease-specific FDH and HRQoL through self- and proxy reports. Content validity was ensured through patients' and parents' involvement at the initial stages of development and in subsequent cognitive debriefing process. Participants found the questionnaire easy to understand, answerable, relevant, and comprehensive. Adjustments based on feedback from patients and their parents improved its utility as a patient- and observer-reported outcome measure. After careful item examination, 52 items were selected, demonstrating moderate to excellent test-retest reliability for most scales and initial evidence for satisfactory construct validity. The PompeQoL questionnaire stands as a valuable screening instrument for both clinical and research purposes. Future research should prioritize additional revisions and larger validation studies, focusing on testing the questionnaire in clinical practice and trials. Nevertheless, the PompeQoL 1.0 stands out as the first standardized measure providing insights into disease-specific FDH and HRQoL among children and adolescents with various forms of PD.

A novel approach to calculate the required volume of air for bronchial blockers in young children.

INTRODUCTION: Bronchial blocker balloons inflated with small volumes of air increase balloon pressure, involving a risk of airway injury especially in young children. However, there are no established guidelines regarding the appropriate volumes of air required to provide safe bronchial occlusion. METHODS: This study aimed to introduce a novel method for calculating the amount of air required for safe bronchial blocker balloon occlusion for one lung anesthesia in young children. We included 79 pediatric patients who underwent video-assisted thoracoscopic surgery at our hospital. Preoperatively, the balloon pressure and corresponding diameter of 5F bronchial blockers inflated with different volumes of air were measured. Intraoperatively, bronchial diameters measured by computerized tomographic scans were matched to the ex vivo measured balloon diameters. The quality of lung isolation, incidence of balloon repositioning, and airway injury were documented. Postoperatively, airway injury was evaluated through fiberoptic bronchoscopy. RESULTS: Balloon pressure and balloon diameter showed linear and nonlinear correlations with volume, respectively. The median lengths of the right and left mainstem bronchi were median (interquartile range) range: 5.3 mm (4.5-6.3) 2.7-8.15 and 21.8 (19.6-23.4) 14-29, respectively. Occluding the left mainstem bronchus required <1 mL of air, with a balloon pressure of 27 cm H2O. The isolation quality was high with no case of mucosal injury or displacement. Occluding the right mainstem bronchus required a median air volume of 1.3 mL, with a median balloon pressure of 44 cm H2O. One patient had poor lung isolation due to a tracheal bronchus and another developed mild and transient airway injury. CONCLUSION: The bronchial blocker cuff should be regarded as a high-pressure balloon. We introduced a new concept for safe bronchial blocker balloon occlusion for one-lung ventilation in small children.

ERCP-Related adverse events in pediatric patients: a 10-years single-site review.

PURPOSE: This retrospective analysis aimed to assess the feasibility and safety of endoscopic retrograde cholangiopancreatography (ERCP) in pediatric patients by examining ERCP-related adverse events (AEs) occurring over a decade at a single center. METHODS: Pediatric patients under 18 years old who underwent ERCP at the Second Hospital of Hebei Medical University from 1/2013 to 11/2023 were included. ERCP-related AEs were defined according to ERCP-related adverse events: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Clinical data of patients experiencing ERCP-related AEs were obtained from electronic medical records for analysis. RESULTS: Over the past decade, a total of 76 pediatric patients underwent 113 ERCP procedures, including 26 patients who underwent repeat ERCP, totaling 63 procedures. There were 32 males and 44 females, with a median age of 13 years (range 3 years and 5 months-17 years and 9 months). Among all ERCP procedures, 14 (12.4%) were diagnostic and 99 (87.6%) were therapeutic, with a 100% success rate. 16 cases (14.2%) of ERCP-related AEs, all post-ERCP pancreatitis (PEP), were observed, while no other AEs defined by ESGE such as bleeding, perforation, cholangitis, cholecystitis, or sedation-related events were noted. Additionally, 23 cases (20.4%) of ERCP-related AEs not included in the ESGE definition were observed, including post-ERCP abdominal pain in 20 cases (17.7%), post-ERCP nausea and vomiting in 2 cases (1.8%), and unplanned reoperation in 1 case (0.9%). In the 26 cases of pediatric patients who underwent repeat ERCP, we observed that AEs occurred in 15 cases (57.7%) during their initial ERCP, which was much higher than the overall average level. CONCLUSIONS: Post-ERCP abdominal pain and PEP are the most common ERCP-related AEs in pediatric patients, while severe AEs such as bleeding and perforation are rare. The incidence of AEs after initial ERCP in pediatric patients who received repeat ERCP is higher than the overall average level. Based on our center's experience, we believe that ERCP can be safely performed in children over 3 years old with biliary and pancreatic diseases and obtain reliable clinical benefits. However, active monitoring and management of ERCP-related AEs are essential to improve the clinical outcomes of pediatric ERCP.

Reconstructive Options for Pressure Ulcers in Pediatric Patients.

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.

Prevalence and Risk Factors of Healthcare-Associated Infections among Hospitalized Pediatric Patients: Point Prevalence Survey in Thailand 2021.

BACKGROUND: Healthcare-associated infections (HAIs) pose a grave threat to patient safety, morbidity, and mortality, contributing to antimicrobial resistance. Thus, we estimated the point prevalence, risk factors, types, and pathogens of HAIs in hospitalized pediatric patients. METHODS: A point prevalence survey (PPS) of HAIs in hospitalized pediatric patients < 18 years old was conducted from March to May 2021. Outcomes, risk factors, and types of HAIs associated with HAIs in 41 hospitals across Thailand were collected. RESULTS: The prevalence of HAIs was 3.9% (95% CI 2.9-5.0%) (56/1443). By ages < 1 month, 1 month-2 years, 2-12 years, and 12-18 years, the prevalence of HAIs was 4.2%, 3.3%, 4.1%, and 3.0%, respectively (p = 0.80). Significant independent risk factors were extended hospital length of stay (LOS) and central venous catheter (CVC) use. Compared to an LOS of <4 days, LOSs of 4-7 days, 8-14 days, and >14 days had adjusted odds ratios (aORs) of 2.65 (95% CI 1.05, 6.68), 5.19 (95% CI 2.00, 13.4), and 9.03 (95% CI 3.97, 20.5), respectively. The use of a CVC had an aOR of 2.45 (95% CI 1.06-5.66). Lower respiratory tract infection (LRTI) was the most common HAI type (46.4%: 26/56). The highest prevalence of HAIs was predominantly observed in LRTI diagnoses, with the highest among these in the <1 month age category at 2.3% (17/738). CONCLUSION: The prevalence of HAIs in hospitalized pediatric patients was 3.9%. Extended LOS and use of CVC were HAI risk factors. A strategy for reducing LOS and reviewing insertion indications or the early planned removal of a CVC was implemented. The surveillance of HAIs stands as a cornerstone and fundamental component of IPC, offering invaluable insights that enhance hospital IPC interventions aimed at preventing HAIs.

Unlocking Vitality: A Comprehensive Review of Vitamin D's Impact on Clinical Outcomes in Critically Ill Children.

This comprehensive review explores the multifaceted role of vitamin D (VD) in critically ill children, examining its implications for clinical outcomes. Although this substance has long been known for its function in maintaining bone health, it is now becoming more widely known for its extensive physiological effects, which include immune system and inflammation regulation. Observational research consistently associates VD levels with outcomes like duration of hospitalization, mortality, and illness severity in critically ill pediatric patients. Mechanistically, it exerts anti-inflammatory and endothelial protective effects while modulating the renin-angiotensin system. Increasing VD levels through supplementation presents promise as a therapeutic strategy; however, further research is necessary to elucidate optimal dosage regimens and safety profiles. This review emphasizes the significance of comprehending the intricate relationship between VD and critical illnesses among pediatric populations.

[Preventive and therapeutic strategies for relapse after hematopoietic stem cell transplant for pediatric AML (SFGM-TC)]. / Stratégies préventives et thérapeutiques de la rechute après allogreffe de cellules souches hématopoïétiques pour les LAM pédiatriques (SFGM-TC).

Treatment of pediatric high-risk acute myeloid leukemia (AML), defined either on molecular or cytogenetic features, relies on bone marrow transplant after cytologic remission. However, relapse remains the first post-transplant cause of mortality. In this 13th session of practice harmonization of the francophone society of bone marrow transplantation and cellular therapy (SFGM-TC), our group worked on recommendations regarding the management of post-transplant relapse in AML pediatric patients based on international literature, national survey and expert opinion. Overall, immunomodulation strategy relying on both measurable residual disease (MRD) and chimerism evaluation should be used for high-risk AML. In very high-risk (VHR) AML with a 5-year overall survival ≤30 %, a post-transplant maintenance should be proposed using either hypomethylating agents, combined with DLI whenever possible, or FLT3 tyrosine kinase inhibitors if this target is present on leukemia cells. In the pre-emptive or early relapse settings (< 6 months post-transplant), treatments combining DLI, Azacytidine and Venetoclax should be considered. Access to phase I/II trails for targeted therapies (menin, IDH or JAK inhibitors) should be discussed in each patient according to the underlying molecular abnormalities of the disease.

Cyclophosphamide exposure factors in family caregivers for pediatric cancer patients.

The exposure of family caregivers to anticancer drugs for pediatric patients with malignancy is a potential health risk that needs to be minimized. We monitored the amount of cyclophosphamide (CPM) that had adhered to the undershirts of patients and the personal protective equipment (PPE) of family caregivers as well as the caregivers' urine levels of CPM within the first three days after the first and second courses of high-dose CPM therapy. Liquid chromatography/mass spectrometry (LC/MS/MS) detected >0.03 ng/ml of CPM in 26% (23/88) of urine samples from 8 of 11 (72.7%) patients' family caregivers, with a peak of 0.7 ng/ml from 24 to 48 h after administration. Since urine CPM concentrations in family caregivers varied after the first and second courses, the exposure risk factors were analyzed by scoring the PPE-wearing time index (caring minutes × PPE points from wearing masks, gloves, and/or gowns) and CPM adhesion of PPE items with the caring patterns of diaper change, washing body care, oral care, eating assistance, emotional support, and co-sleeping. The closest association was observed for CPM adhesion between oral care gloves and undershirts (correlation coefficient 0.67, p = 0.001). The mixed-effect model analysis indicated only a significant correlation between the PPE-wearing time index and emotional care (playing, cuddling, and physical contact) (p = 0.016). These results suggest that prolonged emotional support results in poor PPE protection, which increases the risk of exposure in family caregivers. Strict PPE care within 48 h after high-dose CPM controls the exposure to high-risk anticancer drugs in caregivers of pediatric patients.

Remimazolam for anesthesia and sedation in pediatric patients: a scoping review.

Anesthetic management of pediatric patients poses several challenges and the optimal anesthetic agent for use in this population is still a matter of debate. We systematically searched PubMed/MEDLINE and Google Scholar from their inception for studies that investigated the role and potential applications of remimazolam, a novel ultra-short-acting benzodiazepine, in pediatric patients. Furthermore, in March 2024, an update of the literature search along with an additional post-hoc search on the EMBASE database were performed. A total of fourteen pertinent studies which spanned the 2021-2023 period explored remimazolam as either the primary or adjuvant hypnotic agent for inducing and/or maintaining general anesthesia or sedation. Preliminary evidence derived from these studies highlighted that remimazolam is a safe and effective option for both sedation and general anesthesia in pediatric patients, particularly those with concurrent mitochondrial disorders, myopathic diseases, or at risk for malignant hyperthermia. Moreover, the current evidence suggested that remimazolam may contribute to reducing preoperative anxiety and postoperative delirium in children. Its favorable pharmacodynamic and pharmacokinetic profile demonstrated potential safety, effectiveness, and ease-of-use in various perioperative pediatric contexts, making it suitable for integration into specific protocols, such as intraoperative monitoring of evoked potentials and management of difficult intubation. Notwithstanding these promising findings, further research is essential to determine optimal dosages, establish conclusive evidence of its superiority over other benzodiazepines, and elucidate the impact of genetic factors on drug metabolism.

Clinical application of voriconazole in pediatric patients: a systematic review.

The purpose of this study was to review the literature on the clinical use of voriconazole (VRC) in pediatric patients. MEDLINE, Embase, PubMed, Web of Science, and Cochrane Library were searched from January 1, 2000, to August 15, 2023 for relevant clinical studies on VRC use in pediatric patients. Data were collected based on inclusion and exclusion criteria, and a systematic review was performed on recent research related to the use of VRC in pediatric patients. This systematic review included a total of 35 observational studies among which there were 16 studies investigating factors influencing VRC plasma trough concentrations (Ctrough) in pediatric patients, 14 studies exploring VRC maintenance doses required to achieve target range of Ctrough, and 11 studies focusing on population pharmacokinetic (PPK) research of VRC in pediatric patients. Our study found that the Ctrough of VRC were influenced by both genetic and non-genetic factors. The optimal dosing of VRC was correlated with age in pediatric patients, and younger children usually required higher VRC doses to achieve target Ctrough compared to older children. Establishing a PPK model for VRC can assist in achieving more precise individualized dosing in children.

Optimizing vancomycin dosing in pediatrics: a machine learning approach to predict trough concentrations in children under four years of age.

BACKGROUND: Vancomycin trough concentration is closely associated with clinical efficacy and toxicity. Predicting vancomycin trough concentrations in pediatric patients is challenging due to significant inter-individual variability and rapid physiological changes during maturation. AIM: This study aimed to develop a machine learning model to predict vancomycin trough concentrations and determine optimal dosing regimens for pediatric patients < 4 years of age using ML algorithms. METHOD: A single-center retrospective observational study was conducted from January 2017 to March 2020. Pediatric patients who received intravenous vancomycin and underwent therapeutic drug monitoring were enrolled. Seven ML models [linear regression, gradient boosted decision trees, support vector machine, decision tree, random forest, Bagging, and extreme gradient boosting (XGBoost)] were developed using 31 variables. Performance metrics including R-squared (R2), mean square error (MSE), root mean square error (RMSE), and mean absolute error (MAE) were compared, and important features were ranked. RESULTS: The study included 120 eligible trough concentration measurements from 112 patients. Of these, 84 measurements were used for training and 36 for testing. Among the seven algorithms tested, XGBoost showed the best performance, with a low prediction error and high goodness of fit (MAE = 2.55, RMSE = 4.13, MSE = 17.12, and R2 = 0.59). Blood urea nitrogen, serum creatinine, and creatinine clearance rate were identified as the most important predictors of vancomycin trough concentration. CONCLUSION: An XGBoost ML model was developed to predict vancomycin trough concentrations and aid in drug treatment predictions as a decision-support technology.

Circulation pattern and genetic variation of rhinovirus infection among hospitalized children on Hainan Island, before and after the dynamic zero-COVID policy, from 2021 to 2023.

Throughout the COVID-19 pandemic, rhinovirus (RV) remained notable persistence, maintaining its presence while other seasonal respiratory viruses were largely suppressed by pandemic restrictions during national lockdowns. This research explores the epidemiological dynamics of RV infections among pediatric populations on Hainan Island, China, specifically focusing on the impact before and after the zero-COVID policy was lifted. From January 2021 to December 2023, 19 680 samples were collected from pediatric patients hospitalized with acute lower respiratory tract infections (ARTIs) at the Hainan Maternal and Child Health Hospital. The infection of RV was detected by tNGS. RV species and subtypes were identified in 32 RV-positive samples representing diverse time points by analyzing the VP4/VP2 partial regions. Among the 19 680 pediatric inpatients with ARTIs analyzed, 21.55% were found to be positive for RV infection, with notable peaks observed in April 2021 and November 2022. A gradual annual decline in RV infections was observed, alongside a seasonal pattern of higher prevalence during the colder months. The highest proportion of RV infections was observed in the 0-1-year age group. Phylogenetic analysis on 32 samples indicated a trend from RV-A to RV-C in 2022. This observation suggests potential evolving dynamics within the RV species although further studies are needed due to the limited sample size. The research emphasizes the necessity for ongoing surveillance and targeted management, particularly for populations highly susceptible to severe illnesses caused by RV infections.

Evaluation of novel Epstein-Barr virus-derived antigen formulations for monitoring virus-specific T cells in pediatric patients with infectious mononucleosis.

BACKGROUND: Infection with the Epstein-Barr virus (EBV) elicits a complex T-cell response against a broad range of viral proteins. Hence, identifying potential differences in the cellular immune response of patients with different EBV-associated diseases or different courses of the same disorder requires interrogation of a maximum number of EBV antigens. Here, we tested three novel EBV-derived antigen formulations for their ability to reactivate virus-specific T cells ex vivo in patients with EBV-associated infectious mononucleosis (IM). METHODS: We comparatively analyzed EBV-specific CD4+ and CD8+ T-cell responses to three EBV-derived antigen formulations in 20 pediatric patients during the early phase of IM: T-activated EBV proteins (BZLF1, EBNA3A) and EBV-like particles (EB-VLP), both able to induce CD4+ and CD8+ T-cell responses ex vivo, as well as an EBV-derived peptide pool (PP) covering 94 well-characterized CD8+ T-cell epitopes. We assessed the specificity, magnitude, kinetics, and functional characteristics of EBV-specific immune responses at two sequential time points (v1 and v2) within the first six weeks after IM symptom onset (Tonset). RESULTS: All three tested EBV-derived antigen formulations enabled the detection of EBV-reactive T cells during the early phase of IM without prior T-cell expansion in vitro. EBV-reactive CD4+ and CD8+ T cells were mainly mono-functional (CD4+: mean 64.92%, range 56.15-71.71%; CD8+: mean 58.55%, range 11.79-85.22%) within the first two weeks after symptom onset (v1) with IFN-γ and TNF-secreting cells representing the majority of mono-functional EBV-reactive T cells. By contrast, PP-reactive CD8+ T cells were primarily bi-functional (>60% at v1 and v2), produced IFN-γ and TNF and had more tri-functional than mono-functional components. We observed a moderate correlation between viral load and EBNA3A, EB-VLP, and PP-reactive CD8+ T cells (rs = 0.345, 0.418, and 0.356, respectively) within the first two weeks after Tonset, but no correlation with the number of detectable EBV-reactive CD4+ T cells. CONCLUSIONS: All three EBV-derived antigen formulations represent innovative and generic recall antigens suitable for monitoring EBV-specific T-cell responses ex vivo. Their combined use facilitates a thorough analysis of EBV-specific T-cell immunity and allows the identification of functional T-cell signatures linked to disease development and severity.

Clinical and Laboratory Profile, Management and Outcome of Pediatric SARS-CoV-2 Infection Admitted at the Philippine General Hospital.

Background: The Philippines has recorded over 470,000 COVID-19 cases in children, with over 1,500 deaths during the same period. Although a Philippine online pediatric COVID-19 registry exists, this only relies on passive surveillance. Objectives: This study determined the clinical and laboratory profile, risk factors for severe COVID-19, and mortality, management, and outcome of pediatric SARS-CoV-2 patients admitted at the Philippine General Hospital (PGH) from April 2020 to June 2022 to fill in knowledge gaps on the epidemiology of COVID-19 infection in children. Methods: This was a retrospective cohort study of pediatric COVID-19 cases admitted at the PGH, a designated COVID referral center during the study period. Demographic and clinical profile, risk factors, comorbidities, laboratory and radiologic findings, management, and outcomes across different disease severity states were gathered by chart review and the data were analyzed using STATA 17. Results: There were 448 pediatric patients admitted and diagnosed with COVID-19 during the study period. Most patients belonged to the 1-5-year age group (25.9%), had no known exposure to a COVID-19 case (65.4%), were mild cases (37.3%%), and did not receive any dose of the COVID-19 vaccine (96.7%). The most common presenting symptoms across all disease categories were fever (44.4%), cough (28.6%), and shortness of breath (26.6%). Multisystem inflammatory syndrome in children (MIS-C) presented with fever (100%) and rash (53.9%). The risk factors for severe disease were the presence of a congenital anomaly lung disease, and elevated procalcitonin. Most patients with MIS-C were previously well with no comorbidities. Laboratory findings which were markedly elevated among severe and critical cases were ESR, CRP, D-dimer, LDH, and IL-6. Ferritin, procalcitonin (PCT) and IL-6 were elevated only in severe to critical COVID-19 cases and remained within normal for the other disease categories. As to treatment, asymptomatic, mild, and moderate cases were given supportive medications (zinc, vitamin D, and vitamin C), while investigational drugs particularly corticosteroids, IVIG, and remdesivir, were used in severe cases.Antibiotics were given to 71.7% of patients at the outset. As to the outcomes, 89% recovered, while 8.9% died. The case fatality rate from COVID-19 infection was at 2.2%. Conclusion: Admitted pediatric COVID-19 cases are generally mild but admission is due to underlying illness or comorbidities. Those with severe to critical cases have underlying comorbidities and had either progression or complications due to COVID disease. D-dimer, LDH, IL-6, ferritin and procalcitonin were elevated among severe and critical cases which can be utilized as inflammatory markers.

In vitro activity of ceftolozane/tazobactam against Gram-negative bacilli isolated from pediatric patients: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART) 2017-2021, China.

OBJECTIVES: Ceftolozane-tazobactam (C/T) is a combination of a cephalosporin and a ß-lactamase inhibitor with activity against Gram-negative bacilli (GNB). The study aims were to evaluate the activity of C/T in vitro vs. comparators against clinical GNB isolated from Chinese pediatric patients. METHODS: From 2017-2021, 660 GNB isolates were collected from 20 hospitals across China. The minimum inhibitory concentrations were tested using a Trek Diagnostic System (Thermo Fisher Scientific). Susceptibility was determined by CLSI broth microdilution and the results were interpreted according to CLSI M100 (2021) breakpoints. RESULTS: GNB isolates were obtained from pediatric patients < 18 years old, mainly from the bloodstream (n=146), intraperitoneal cavity (n=138), lower respiratory (n=278) and urinary tract (n=96). Overall, C/T was active against 76.6% of 436 Enterobacterales, with a descending susceptibility rate of 100.0% to S. marcescens, 92.2% to E. coli, 83.3% to K. oxytoca, 66.7% to K. aerogenes, 66.7% to P. mirabilis, 58.6% to K. pneumoniae and 57.1% to E. cloacae. The susceptibility of P. aeruginosa to C/T was 89.4%, which was the highest among the ß-lactams and was second only to amikacin (92.9%). Isolates of respiratory tract infection (RTI) derived P. aeruginosa were highly susceptible (93.8%) to C/T, while < 75% of isolates of RTI derived P. aeruginosa were susceptible to the other ß-lactams tested, except for ceftazidime-avibactam (91.2%). CONCLUSION: GNBs collected from pediatric patients in China showed a high susceptibility to C/T making this drug combination an effective choice for treating the pediatric population, especially those infected with P. aeruginosa.

Enterovirus genotype diversity with emergence of coxsackievirus A2 circulating in pediatric patients with acute gastroenteritis in Thailand, 2019-2022.

Introduction: Enteroviruses (EVs) are recognized as potential causative agents of acute gastroenteritis (AGE) in children worldwide. This study aimed to investigate the epidemiology and molecular characteristics of EV infection in children admitted to hospitals with AGE in Chiang Mai, Thailand from 2019 to 2022. Methods: A total of 1,148 fecal samples collected from patients with AGE were screened for the presence of EV using RT-PCR. The prevalence, co-infection with common diarrheal viruses, and seasonal pattern of EV were examined. The genotypes of EV were identified based on the VP1 sequence and phylogenetic analysis. Results: The overall prevalence of EV in AGE patients was 8.8% (101/1,148). After the COVID-19 outbreak in 2019, a significant decrease in the EV infection rate and genotype diversity was observed (p < 0.05). EV infection alone was observed in 68.3% (69/101) of cases while co-infection with other enteric viruses was 31.7% (32/101). The seasonal pattern of EV infection showed a peak prevalence during the rainy season. EV species A was the most prevalent (37.5%), followed by species B (32.3%), species C (29.2%), and species D (1.0%). Twenty-five genotypes of EV were identified with the most predominant of the coxsackievirus A2 (CV-A2) (13.5%), CV-B2 (7.3%) and CV-A24 (5.2%). Conclusion: Our data demonstrate a significant decrease in the prevalence and diversity of EV circulating in AGE patients during the COVID-19 pandemic and highlight the emergence of CV-A2 during this study period. These findings contribute to a better understanding of the molecular epidemiology and diversity of EV in patients with AGE and provide useful information for further investigation into the potential association between specific EV genotypes and AGE in future studies.

CAFES: Chest X-ray Analysis using Federated Self-supervised Learning for Pediatric COVID-19 Detection.

Chest X-rays (CXRs) play a pivotal role in cost-effective clinical assessment of various heart and lung related conditions. The urgency of COVID-19 diagnosis prompted their use in identifying conditions like lung opacity, pneumonia, and acute respiratory distress syndrome in pediatric patients. We propose an AI-driven solution for binary COVID-19 versus non-COVID-19 classification in pediatric CXRs. We present a Federated Self-Supervised Learning (FSSL) framework to enhance Vision Transformer (ViT) performance for COVID-19 detection in pediatric CXRs. ViT's prowess in vision-related binary classification tasks, combined with self-supervised pre-training on adult CXR data, forms the basis of the FSSL approach. We implement our strategy on the Rhino Health Federated Computing Platform (FCP), which ensures privacy and scalability for distributed data. The chest X-ray analysis using the federated SSL (CAFES) model, utilizes the FSSL-pre-trained ViT weights and demonstrated gains in accurately detecting COVID-19 when compared with a fully supervised model. Our FSSL-pre-trained ViT showed an area under the precision-recall curve (AUPR) of 0.952, which is 0.231 points higher than the fully supervised model for COVID-19 diagnosis using pediatric data. Our contributions include leveraging vision transformers for effective COVID-19 diagnosis from pediatric CXRs, employing distributed federated learning-based self-supervised pre-training on adult data, and improving pediatric COVID-19 diagnosis performance. This privacy-conscious approach aligns with HIPAA guidelines, paving the way for broader medical imaging applications.