Low-risk Pediatric Patients Research Articles

7685 Outcomes of Low-Risk Differentiated Thyroid Carcinomain a Predominantly Hispanic Pediatric Population

Abstract Disclosure: E.A. Delgado: None. A. Martinez: None. N. Solano: None. D. Baboun: None. F. Alkhoury: None. A. Carrillo-Iregui: None. C.L. Bustamante Escobar: None. Background: The American Thyroid Association (ATA) guidelines for the management of low-risk differentiated thyroid carcinoma (DTC) in children, recommend total thyroidectomy and central neck dissection without iodine ablation. Surveillance for recurrence in these patients includes serial TSH-suppressed thyroglobulin levels and thyroid ultrasounds. Iodine ablation is reserved for patients classified as ATA intermediate and high-risk given their risk of persistent cervical disease and distant metastasis, respectively. There is ongoing concern whether withholding Iodine-131 will result in higher rates of disease recurrence among ATA low-risk pediatric patients. To our knowledge this is the first study addressing a predominantly Hispanic pediatric population. Objective: Evaluate the recurrence rate of differentiated thyroid cancer (DTC) in ATA low risk patients since implementing the 2015 ATA pediatric guidelines in a predominantly Hispanic pediatric population. Methods: After obtaining Institutional Review Board approval, we performed a retrospective chart review of patients 19 years and younger, between 2012 and 2023, for DTC. We analyzed demographics, histopathological diagnoses, risk stratification, and post-diagnosis follow up. Results: From a cohort of 63 pediatric patients diagnosed with DTC, a significant majority (n=55, 87%) comprised Hispanic individuals, while non-Hispanic cases represented the minority (n= 8, 13%). The mean age at diagnosis was 14.7 ± 2.6 years. Papillary thyroid carcinoma emerged as the prevailing type in 58 (92%), while 5 (8%) were follicular carcinoma. Among the patients, 12 (20%) were categorized as low risk level and underwent surgery alone. Over a median follow-up period of 2.6 years (IQR 2.97, range 0.94-5.18), 2 out of the 12 (18%) in this low-risk group experienced disease recurrence, with an average time to recurrence of 1.6 ± 0.9 years. Notably, one of the patients had a history of autoimmune thyroiditis. Subsequently, these 2 patients underwent further evaluation and treatment with iodine ablation. Conclusion: In a free-standing hospital with a predominantly Hispanic population, we found a recurrence rate of 18% in patients with ATA low-risk DTC not treated with radioactive iodine. Our rates align closely with those observed in earlier studies, which featured a non-Hispanic population and reported a 24% recurrence rate during the surveillance period. This underscores the crucial role of surveillance in low-risk patients with DTC in a Hispanic pediatric population. Presentation: 6/1/2024

Skeletal survey yields in low vs. high risk pediatric patients with skull fractures

BackgroundTo assess for occult fractures, physicians often opt to obtain skeletal surveys (SS) in young, acutely head-injured patients who present with skull fractures. Data informing optimal decision management are lacking. ObjectiveTo determine the positive yields of radiologic SS in young patients with skull fractures presumed to be at low vs. high risk for abuse. Participants and setting476 acutely head injured, skull-fractured patients <3 years hospitalized for intensive care across 18 sites between February 2011 and March 2021. MethodsWe conducted a retrospective, secondary analysis of the combined, prospective Pediatric Brain Injury Research Network (PediBIRN) data set. Results204 (43 %) of 476 patients had simple, linear, parietal skull fractures. 272 (57 %) had more complex skull fracture(s). Only 315 (66 %) of 476 patients underwent SS, including 102 (32 %) patients presumed to be at low risk for abuse (patients who presented with a consistent history of accidental trauma; intracranial injuries no deeper than the cortical brain; and no respiratory compromise, alteration or loss of consciousness, seizures, or skin injuries suspicious for abuse). Only one of 102 low risk patients revealed findings indicative of abuse. In two other low risk patients, SS helped to confirm metabolic bone disease. ConclusionsLess than 1 % of low risk patients under three years of age who presented with simple or complex skull fracture(s) revealed other abusive fractures. Our results could inform efforts to reduce unnecessary skeletal surveys.

Universal COVID-19 pre-procedural swabs in children in a developing country: A comparison of findings over two transmission waves

AimThe Coronavirus disease (COVID-19) pandemic has strained healthcare systems worldwide. Some institutions have implemented additional precautionary measures such as pre-procedural swabbing (PPS) to reduce transmission in patients and healthcare workers. We evaluate our experience with universal pre-procedural screening for COVID-19 in low-risk pediatric patients.MethodsWe performed a retrospective review of patients aged 18 years and below who underwent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription-polymerase chain reaction (rRT-PCR) assay swabs in our center over two waves (1st May 2020 to 31st July 2020 and 1st April 2021 to 30th June 2021). We included patients who underwent rRT-PCR for SARS-CoV-2 prior to any procedures requiring general anesthesia and were deemed low risk for COVID-19 according to our institutional screening criteria. All study patients were followed up for 14 days post-procedure.ResultsOf 2065 swabs done for patients aged 18 years and below during the study period, 645 (31.2%) were pre-procedural swabs. Patients were aged 4.2 years (median, interquartile range: 1.6 years–9.8 years). Two patients (0.3%) tested positive for COVID-19 by PPS, detected during Period 2 – both had risk criteria which were overlooked by healthcare workers. Within 14 days post-procedure, 10 patients had unscheduled readmissions and 15 required repeat rRT-PCR, all of which were negative.ConclusionsIn patients deemed low risk for COVID-19 infection according to our screening criteria, routine pre-procedural swabbing returns a low positive rate. Our findings can guide screening protocols at institutions that provide surgical services during the COVID-19 pandemic.

Emergency Department Utilization and Serious Bacterial Infection Rates in Children With Renal Transplants.

Emergency department (ED) visits by children with solid organ transplants have increased significantly. Our objectives were to describe the common complaints, diagnosis, types, and rates of serious bacterial infection (SBI) in children with renal transplant (RT) who present to the hospital. We conducted a retrospective study from 2012 to 2016 of RT children up to 18 years who presented to the ED or were directly admitted. We excluded patients who presented for a procedure. We collected demographics, transplant type, immunosuppressive data, chief complaints, diagnostic testing with results, interventions performed, and final diagnosis. We analyzed 131 visits in 29 patients during the study period. Most common chief complaints were infectious (34.4%) and gastrointestinal (26%). Infection was proven in 42.0% of visits with only 3.1% being organ rejection. Serious bacterial infection was diagnosed in 34 visits (26.0%) with urinary tract infection (UTI) being the most common (20.6%). Of the 33 visits for fever, SBI occurred in 16 (48.5%) patients with the most common SBI being UTI 10 (30.3%). Bacteremia occurred in 1 patient and hypotension in 4 patients. Antibiotic administration was the most common intervention performed (78; 59.5%). Significant interventions were uncommon (2 patients). Logistic regression revealed no factors to be associated with SBI. Our cohort of children with RT presented most commonly with infections to the hospital with UTI being the most common SBI. Bacteremia and significant interventions were rare. Future studies are needed to identify subgroups of low-risk pediatric RT patients who can possibly be safely discharged home from the ED.

Standardizing the Diagnostic and Therapeutic Approach to Newly Diagnosed Children with ITP: An ITP Consortium of North America (ICON) Quality Improvement Initiative

BACKGROUNDPediatric immune thrombocytopenia (ITP) is an acquired disorder of platelet destruction that is associated with an increased risk of bleeding. Despite published guidelines for the management of ITP, the available evidence is of low grade, leading to practice variation in different settings. The use of validated bleeding scores to guide clinical decision making is inconsistent. In addition, many children are initially treated with medications despite the recommendation for observation in newly diagnosed children with ITP and no or mild bleeding symptoms. This approach leads to over-utilization of healthcare resources including hospitalizations, medication administration, and medical encounters for management-related side effects. In 2020, a quality improvement (QI) project of the Pediatric ITP Consortium of North America (ICON) was initiated to improve consistency in clinical practice at ICON sites using national ITP guidelines.DESIGN/METHODSWithin the ICON QI subcommittee, a standardized clinical care pathway (Figure 1) for newly diagnosed childhood ITP was developed based on the American Society of Hematology (ASH) 2019 guidelines. The goal was to unify approach to management, decrease practice variation, identify and learn from deviations in decision making, and decrease resource utilization by increasing observation rates in low-risk pediatric ITP patients. Site investigators shared the care pathway to update institutional providers on national guidelines. For Aim 1 of this project, sites completed a multi-center, retrospective analysis documenting the pre-QI pathway management of children, ages 1-16 years, diagnosed with ITP from January to December 2019. Statistical analysis was performed using R version 4.0.2. For Aim 2, after local dissemination and education of the clinical care pathway, clinicians at all participating sites will review the pathway at the time of managing newly diagnosed children and then complete a short survey documenting a bleeding score and management decisions.RESULTSCurrent data from the retrospective review is summarized in Figure 1. 98 patients across four ICON institutions are included in this analysis. The median age at diagnosis was 6 years (IQR 2.7, 9.2) with 61% being male. 43 (44%) patients had their first hematology encounter in the inpatient setting, 40 (41%) in the outpatient clinic, and 14 (14%) in the emergency room. Buchanan and Adix bleeding scores were obtained from only one patient (1%) at diagnosis. Treatment strategies varied including observation in 47 (48%) patients, IVIG in 40 (41%), corticosteroids in 9 (9%), and anti-D globulin in 3 (3%). 53 (54%) patients were admitted at the time of diagnosis. The prospective QI pathway is being utilized by six ICON institutions and 20 patients have been followed on the pathway since November 2020. An additional seven sites are in various phases of study activation.DISCUSSIONEvidence-based ITP guidelines and an expert consensus report have been recently published. For children with newly diagnosed ITP and a platelet count <20 x 10 9/L who have no or mild bleeding, ASH guidelines suggest against admission to the hospital and suggest observation rather than treatment with corticosteroids. Retrospective analysis of the management at four ICON centers demonstrates the variation in approach to treatment. However, although guidelines suggest initial management based on objective assessment of bleeding symptoms, only one patient (1%) had a documented bleeding score at presentation, suggesting a lack of a standard approach to management and practice variation. These data support the need for this quality initiative, which involves clinicians reviewing the pathway while managing patients and answering a survey at the time of clinical visits to report on bleeding symptoms and management. This initiative will be expanded to include a total of 13 institutions across the United States. Data will be analyzed every 1-2 years and changes will be made to the pathway with the goal of improving care. Further quality initiatives may help to standardize the management approach of pediatric ITP patients and optimize health outcomes in this patient population. [Display omitted] DisclosuresBadawy: Bluebird Bio Inc: Consultancy; Sanofi Genzyme: Consultancy; Vertex Pharmaceuticals Inc: Consultancy. Grace: Novartis: Research Funding; Dova: Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Research Funding; Principia: Membership on an entity's Board of Directors or advisory committees. Nakano: Novartis: Consultancy.

Early experience with universal preoperative and pre-procedural screening for COVID-19 in low-risk pediatric surgical patients requiring general anesthesia.

PurposeThe COVID-19 pandemic has placed extraordinary demands on healthcare services worldwide. Some have reported increased viral transmission to healthcare workers during aerosol-generating procedures such as intubation. We report our experience with universal preoperative and preprocedural screening for COVID-19 in children requiring general anaesthesia with low risk of having the infection.MethodsThis was a data review involving children aged < 18 years undergoing procedures under general anaesthesia in our institution from 18th March to 31st May 2020 and deemed low risk for COVID 19 infection, as defined by our institutional protocol. Confirmation of COVID-19 was by real time reverse-transcription polymerase chain reaction with confirmation by nucleic acid sequencing. All patients were followed up 14 days post-swab.ResultsOf the 66 children (median age 4.5 years, range 0–16.8) eligible for the study, 39 (60%) were male and infants (1–12 months) formed the largest group (n = 24, 36%). None were positive for COVID-19. On 14 day follow-up, none had symptoms related to COVID-19.ConclusionOur study shows that low risk asymptomatic children with no history of contact with COVID-19 patients test negative on universal screening. Larger studies are required to ascertain the role of screening prior to procedures done under general anaesthesia.

Risk of structural persistent disease in pediatric patients with low or intermediate risk differentiated thyroid cancer.

In pediatric patients with differentiated thyroid cancer (DTC), the risk of recurrence is high and the indication for postoperative 131I administration is still debated. The aim of this study was to assess the outcome in low and intermediate risk pediatric DTC patients. We retrospectively evaluated 45 pediatric patients with low or intermediate risk DTC, treated with surgery and 131I between 1992 and 2002 and with no detectable antithyroglobulin (Tg) antibodies. Follow-up was performed every 6-12 months with Tg blood level determination and imaging procedures. During follow-up (64 ± 53 months), 15 events occurred (33% cumulative event rate, with an annual event rate of 5% person years). Five of these patients were submitted to additional surgery and all these 15 patients underwent a second 131I treatment course. All patients were alive at the end of the follow-up. Structural persistent disease occurred more frequently in patients at intermediate risk (p < 0.01) and in those with Tg values after thyroid hormone withdrawal >10 ng/ml before 131I therapy (p < 0.01). At multivariate analysis, only a postoperative thyroid stimulating hormone-stimulated Tg level >10 ng/ml was an independent predictor of persistent disease. In pediatric patients with DTC, postoperative high stimulated Tg values (>10 ng/ml) should be taken into account for deciding the extent of both initial treatment and follow-up.

A003 DIRECT AMOXICILLIN CHALLENGE WITHOUT PRELIMINARY SKIN TESTING FOR PEDIATRIC PATIENTS WITH LOW-RISK PENICILLIN ALLERGY SYMPTOMS

In pediatric patients who report penicillin allergy, the majority are not at risk for IgE-mediated reaction with repeat exposure. The most common protocols for confirming penicillin allergy involve skin testing followed by oral challenge. However, there is increasing evidence suggesting the use of direct amoxicillin challenge without preliminary skin testing is safe and effective to rule out penicillin allergy in low risk individuals. This study aims to evaluate the safety and efficacy of direct oral amoxicillin challenge without preliminary skin testing in a population of low-risk pediatric patients with a penicillin allergy label.

Benign thyroid nodules in pediatric patients: determining best practices for repeat ultrasound evaluations.

Background The American Thyroid Association (ATA) recommendations for the follow-up of thyroid nodules with benign fine needle aspiration (FNA) cytology in children are largely based on adult data, despite well-characterized differences between thyroid nodules in adults and children. We aimed to determine the optimal time interval for repeat evaluation of an FNA-benign thyroid nodule in a pediatric patient. Methods This is a retrospective chart review of patients <19 years of age from 2003 to 2013 with a benign thyroid nodule by FNA cytology. Results We identified 43 patients with benign thyroid nodule cytology on FNA. The average age at diagnosis was 15.6 years, with female predominance (91%). Initial ultrasound (US) findings showed an average nodule size of 2.5 cm, 10% with calcifications, 37% hyperemia, 29% hypoechogenicity and 7% lymphadenopathy. Follow-up US was done in 42%. The first follow-up US occurred on average at 15 months after the initial US. Four patients had nodules with significant growth over time. One patient with papillary thyroid carcinoma (PTC) on final pathology initially had a decreasing nodule size, and then a subsequent increase in the nodule size after 4.5 years. Thyroid nodules were surgically removed in 33% with the final pathology showing a benign cytology in four patients, follicular adenoma in eight patients and PTC in two patients. Conclusions The majority of patients with benign thyroid nodules had no significant increase in nodule size in the first year of follow-up, including one patient who was subsequently found to have PTC. We recommend follow-up US at 1 year after initial presentation in low-risk pediatric patients with benign thyroid nodule cytology.

AXL Expression in Pediatric AML Is Associated with Putative LSC and Correlates with a Distinct Set of Proteins Associated with Cell Metabolism, Cell Cycle, and Unfolded Protein Response

Background: The receptor tyrosine kinase AXL is emerging as a critical regulator of survival signaling and cell cycle regulators in AML. Our previous work using AXL inhibitor ONO-7475 in treating AML cells demonstrated that the drug reduced proteins associated with cell cycle regulation such as CDK1 and PLK1 and PI3K/AKT/mTOR signaling (Ruvolo et al Haematologica 2017). PI3K/AKT/mTOR signaling supports cell survival from stress challenge including response to unfolded protein (UPR). CDK1 and PLK1 have also been implicated as having survival roles during UPR stress. At present an understanding of AXL expression in primary pediatric AML samples is unknown. Reverse phase protein analysis (RPPA) is a powerful proteomic tool that allows for the measurement of protein expression in clinical samples.Methods: ± the proteasome inhibitor bortezomib. Bioinformatic analysis was performed by calculating the Pearson correlation coefficients. Proteins were identified as significantly positively correlated with AXL or significantly negatively correlated with AXL based on p < 0.05 & r ≥ 0.25 or r ≤ -0.25, respectively. All p-values were Bonferroni corrected (0.05 / 291 = 0.0002). String analysis to determine protein: protein interactions was performed on sets associated with positive and negative correlation.Results: Expression of AXL appears to be lower in AML cells compared to healthy donor CD34+ cells (p < 0.001). The expression of AXL was not prognostic for clinical outcome . AXL expression was higher in AML patients with favorable cytogenetics category (p < 0.001) and in low risk pediatric patients (p = 0.002). AXL expression was significantly different in cytogenetic categories with AXL expression elevated in inv(16) and monosomy 7 and lower in 11q23 (p = 0.0014) . AXL expression is higher in putative leukemia stem cell (LSC) population (CD34+ CD38 -) compared to bulk AML (CD34+,CD38+)(p < 0.001). AXL expression in the pediatric AML cells was compared to 290 proteins by RPPA. Fifty-five protein displayed positive correlation with AXL including the immune checkpoint inhibitor protein PD-L1. Other proteins positively correlated with AXL included PLK1 and FOXM1. Our previous study using the ONO-7475 AXL inhibitor demonstrated reduction of PLK1 in cells treated with the inhibitor. Positive association of FOXM1 and PLK1 with AXL would be consistent with a regulatory network where AXL regulates PLK1 via FOXM1. Thirty-three proteins were negatively correlated with AXL expression including HNRNPK, STAT3, XPO1, and phosphorylated EIF2S1. Phosphorylation of EIF2S suppresses protein translation during stress events including unfolded protein response (UPR). String analysis to determine protein: protein interactions determined high interaction (p < 10 e-16) in both positively correlated and negatively correlated sets. KEGG pathways associated with proteins correlated with AXL include mTOR signaling (Pathway ID 4150), PI3K/AKT signaling (Pathway ID 4151), HIF signaling (Pathway ID 4066), and focal adhesion (Pathway ID 4510). Biological pathways associated with AXL networks included regulation of cellular metabolism (Pathway ID GO.0031325), regulation of gene expression (Pathway ID GO.0010604), and cellular response to unfolded protein (Pathway ID G0:0034620).Conclusions: These results suggest that AXL may be prominently expressed in putative LSC in pediatric AML. Though AXL expression appears to be associated with favorable risk cytogenetics, the correlation of AXL with PD-L1 suggests it may be involved in how the AML cell responds to immune surveillance. Finally, a distinct set of proteins are clearly associated with AXL expression and represent a number of different survival pathways including regulation of cell metabolism, cell cycle, and UPR that could contribute to AML cell survival. DisclosuresAndreeff:AstraZeneca: Research Funding.

Early conversion of pediatric kidney transplant patients to everolimus with reduced tacrolimus and steroid elimination: Results of a randomized trial.

In a 12-month, multicenter, open-label study, 106 children were randomized at 4 to 6 weeks after kidney transplantation to switch to everolimus with reduced TAC (EVR/rTAC) and steroid elimination from month 5 posttransplant or to continue standard tacrolimus with mycophenolate mofetil (sTAC/MMF) and steroids. The cumulative incidence of a co-primary efficacy end point (biopsy-proven acute rejection [BPAR], graft loss, or death from randomization to month 12) was 10.3% with EVR/rTAC and 5.8% with sTAC/MMF (difference 4.4%; P = .417). BPAR occurred in 9.6% and 5.6% of patients, respectively. Patient and renal allograft survival were 100%. The co-primary end point of mean estimated glomerular filtration rate at month 12 was 76.2 mL/min/1.73 m2 with EVR/rTAC and 72.5 mL/min/1.73 m2 for sTAC/MMF (difference 3.8 mL/min/1.73m2 ; P = .49). One EVR/rTAC patient developed posttransplant lymphoproliferative disease. Longitudinal growth and sexual maturation were equivalent between groups. The randomized drug regimen was discontinued in 34.6% and 13% of patients in the EVR/rTAC and sTAC/MMF groups, respectively (P = .024), and discontinued due to adverse events/infections in 25.0% and 11.1% of patients (P = .062). In conclusion, early conversion of pediatric kidney transplant patients from TAC, MMF, and steroids to EVR/rTAC and steroid withdrawal maintains immunosuppressive efficacy and preserves renal function.

Cell-Free Plasma Hemoglobin and Male Gender Are Risk Factors for Acute Kidney Injury in Low Risk Children Undergoing Cardiopulmonary Bypass.

To determine the relationship between the production of cell-free plasma hemoglobin and acute kidney injury in infants and children undergoing cardiopulmonary bypass for cardiac surgery. Prospective observational study. Twelve-bed cardiac ICU in a university-affiliated children's hospital. Children were prospectively enrolled during their preoperative outpatient appointment with the following criteria: greater than 1 month to less than 18 years old, procedures requiring cardiopulmonary bypass, no preexisting renal dysfunction. None. Plasma and urine were collected at baseline (in a subset), the beginning and end of cardiopulmonary bypass, and 2 hours and 24 hours after cardiopulmonary bypass in 60 subjects. Levels of plasma hemoglobin increased during cardiopulmonary bypass and were associated (p < 0.01) with cardiopulmonary bypass duration (R = 0.22), depletion of haptoglobin at end and 24 hours after cardiopulmonary bypass (R = 0.12 and 0.15, respectively), lactate dehydrogenase levels at end cardiopulmonary bypass (R = 0.27), and change in creatinine (R = 0.12). Forty-three percent of patients developed acute kidney injury. There was an association between plasma hemoglobin level and change in creatinine that varied by age (overall [R = 0.12; p < 0.01]; in age > 2 yr [R = 0.22; p < 0.01]; and in < 2 yr [R = 0.03; p = 0.42]). Change in plasma hemoglobin and male gender were found to be risk factors for acute kidney injury (odds ratio, 1.02 and 3.78, respectively; p < 0.05). Generation of plasma hemoglobin during cardiopulmonary bypass and male gender are associated with subsequent renal dysfunction in low-risk pediatric patients, especially in those older than 2 years. Further studies are needed to determine whether specific subgroups of pediatric patients undergoing cardiopulmonary bypass would benefit from potential treatments for hemolysis and plasma hemoglobin-associated renal dysfunction.

Clinical breast concerns in low-risk pediatric patients: practice review with proposed recommendations.

Fibroadenoma is overwhelmingly the most common pediatric breast lesion. Breast malignancy is quite uncommon in children, most frequently metastatic or hematological malignancy. Core biopsy has largely replaced excision for diagnosis of breast masses in adults. The purpose of this study is two-fold: (1) compare utilization at our institution of interventional procedures vs. surgery for breast mass diagnosis in patients ≤18years and (2) propose guidelines for breast imaging and biopsy in this population. We extracted data for all patients ≤18 who, between 2004 and 2016, underwent either (a) imaging and/or intervention procedure, or (b) breast surgery, from the Radiology Information System and Pathology Data System, respectively. We recorded age, gender, imaging, procedure, lesion size and histopathology. We found 1,050 pediatric patients ≤18years who underwent diagnostic breast ultrasound between 2004 and 2016. Of these, 168 patients underwent 199 interventional procedures. One hundred thirty patients underwent 160 core biopsies of solid lesions. Core biopsy pathology diagnosed benign lesions in 99%, of which 84.3% were fibroadenomas (n=135). One malignancy was diagnosed, B cell lymphoma. Two hundred three patients underwent surgical excision for 266 discrete lesions, and 89% were fibroadenomas. Seven benign phyllodes tumors were surgically diagnosed. No malignancies were diagnosed. Core biopsy in patients 18years and younger is well-tolerated, has few risks, and is preferable to surgery in developing breasts, but the goal is to avoid any breast procedure whenever possible. We propose guidelines for pediatric breast imaging, follow-up, core biopsy and excisions.

(174) - Impact of Induction Therapy Type in High and Low Risk Pediatric Patients After Heart Transplant: Analysis of the PHTS Database

(174) - Impact of Induction Therapy Type in High and Low Risk Pediatric Patients After Heart Transplant: Analysis of the PHTS Database

Anti-D treatment for pediatric immune thrombocytopenia: Is the bad reputation justified?

The purpose of this study was to assess the efficacy and side effect profile of the repeated use of anti-D for the treatment of pediatric immune thrombocytopenia (ITP) in a large pediatric hematology center. We performed a retrospective analysis of patient records for children (aged 4 months–18 years) treated for ITP at Schneider Children’s Medical Center of Israel from 1995–2015. Demographic and clinical data, reported adverse events, and therapy response were extracted from written and electronic files for all patients having received anti-D. Therapy response was defined as time to platelet count >30 x 109/L. Thirty-six patients received 170 treatments of anti-D at a dose of 75 μg/kg. The majority were previously treated with corticosteroids and/or intravenous immunoglobulin (IVIG). Minimal adverse events were recorded including fever (3.5%), vomiting (2.9%), and headaches (1.7%). Notably only 1/170 treatments required blood transfusion and no life-threatening events occurred. The average time to platelets >30 x 109/L was 2.3 days, with a median of 1 day, range 1–12 days. Despite the reported severe adverse events in mainly elderly patients, the use of anti-D can be safe and effective in carefully chosen, low-risk pediatric patients with ITP.

Clinical and Microbiologic Assessment of Cases of Pediatric Community-associated Clostridium difficile Infection Reveals Opportunities for Improved Testing Decisions.

Most children with Clostridium difficile infection (CDI) experience community onset of CDI symptoms. We retrospectively compared hospital-onset healthcare facility-associated CDI cases to community-associated (CA) CDI cases diagnosed by Cepheid Xpert tcdB polymerase chain reaction (PCR) at an academic children's hospital over a 1-year period. Saved stools from CDI cases additionally underwent anaerobic stool culture and multiplex gastrointestinal pathogen PCR testing. Compared with 25 hospital-onset healthcare facility-associated CDI cases, the 74 CA-CDI cases were more frequently <2 years old (18% vs. 0%, P = 0.034) and less frequently had antibiotic exposure in the past 30 days (26% vs. 88%, P < 0.0001), proton pump inhibitor exposure (16% vs. 36%, P = 0.036) or a gastrostomy tube (11% vs. 32%, P = 0.013). Among children diagnosed with CA-CDI, 19 (26%) had no identified CDI risk factors (immunocompromised; gastrostomy tube; recent antibiotic, proton pump inhibitor or inpatient/outpatient healthcare exposures). Clinical testing for viral pathogens was uncommon among children thought to have CA-CDI. Multiplex PCR testing of saved stool samples failed to identify C. difficile among 23% of cases diagnosed with CA-CDI by the Cepheid Xpert tcdB PCR assay. CDI antibiotic therapy was provided to nearly all patients testing positive by tcdB PCR irrespective of CDI risk factors. Many children diagnosed with CA-CDI by PCR lack CDI risk factors and have discordant results when additional CDI testing methods are performed, suggesting overdiagnosis of CDI in children with community-onset diarrhea. More selective CDI testing of low-risk pediatric patients is needed to more accurately diagnose CDI and limit unnecessary CDI antibiotic treatment in children.

Performance of a parallel diagnostic algorithm for HIV diagnosis in low risk pediatric and obstetric patient populations

BackgroundLittle is known about the clinical performance of the 2010 APHL/CDC Western-blot independent HIV testing algorithm in low risk pediatric and obstetric patients. ObjectiveTo evaluate the performance of an alternate Western-blot independent algorithm and the individual algorithm components in diagnosing HIV infections in low risk pediatric and obstetric patients. Study design6242 specimens from pediatric and obstetric patients were tested by the Bio-Rad Multispot HIV-1/HIV-2 (MS) and VITROS Anti HIV 1+2 (VITROS) assays. 913 specimens were also tested by the ARCHITECT HIV Ag/Ab Combo assay (ARCHITECT). Discordant specimens were tested by the APTIMA HIV-1 RNA qualitative assay (RNA Qual). ResultsTwenty-eight specimens tested positive for HIV-1 by both MS and VITROS, 4 of these 28 specimens were also tested by and positive by ARCHITECT; all 28 positives identified by the algorithm were positive by viral load analysis. MS identified 164 preliminary positives, which were not confirmed as true positives, representing a specificity of 97.4%. This specificity varied between patient populations (96.1% in the pediatric population and 99.1% in the obstetric population). The specificities of VITROS and ARCHITECT were 99.2% and 99.4% for pediatric patients; 99.7% and 99.8% for obstetric patients, respectively. ConclusionOur results highlight suboptimal specificity of MS in pediatric patients, and a lower specificity in both pediatric and obstetric patients relative to either VITROS or ARCHITECT. Additionally, parallel testing with both a third and fourth generation EIA in a low risk patient population provides a potential alternative to Western-blot dependent algorithms for confirmation.

Reatment of Febrile Neutropenia in Pediatric Cancer Patients. A Clinical Evaluation of Effectiveness of Emperical Oral Antibiotic Therapy

Introduction: Febrile neutropenia in cancer patients represents a common complication from chemotherapy that is potentially lethal. However in patient with fever and neutropenia during cancer chemotherapy who have a low risk of complications, oral antibiotic may be an acceptable alternative to intravenous antibiotics. Methods: We conducted a prospective hospital based study to the patients aged 2-14 years who had fever and neutropenia during cancer chemotherapy for both hematological and solid tumors. Only low risk patients i.e. neutropenia of less than seven days, who were hemodynamically stable and ANC >250/mm 3 were included in the study. All the patients followed Guidelines for pre-treatment assessments and investigations before they were hospitalized and given oral antibiotic ofloxacin and were closely observed until fever subsided for more than 48 hours and improved from neutropenia. Results: A total of 92 cases were enrolled in the study. Out of 92 patients 1 patient was lost to follow-up, 14 needed IV antibiotics for different reasons and 74 patients (80%) improved well with oral antibiotic only. The events that led to changing the treatment regimen were: grade III/IV vomiting (two cases), fever lasting for more than 72 hours (seven episodes), severe mucositis (one episode), anal cellulitis (one episode) and no obvious cause (three episodes). Conclusion: In hospitalized low risk patients who have fever and neutropenia, empirical therapy with oral ofloxacin may be a safe and effective alternative to IV antibiotics. Further study should be aimed at clarifying the definition of low risk pediatric patients.

Computed Tomography for Low-Risk Pediatric Patients: Impact of the 2009 Prediction Rule of the Pediatric Emergency Care Applied Research Network

Computed Tomography for Low-Risk Pediatric Patients: Impact of the 2009 Prediction Rule of the Pediatric Emergency Care Applied Research Network

The Clinical Impact of Humoral Immunity in Pediatric Renal Transplantation

The development of anti-donor humoral responses after transplantation associates with higher risks for acute rejection and 1-year graft survival in adults, but the influence of humoral immunity on transplant outcomes in children is not well understood. Here, we studied the evolution of humoral immunity in low-risk pediatric patients during the first 2 years after renal transplantation. Using data from 130 pediatric renal transplant patients randomized to steroid-free (SF) or steroid-based (SB) immunosuppression in the NIH-SNSO1 trial, we correlated the presence of serum anti-HLA antibodies to donor HLA antigens (donor-specific antibodies) and serum MHC class 1-related chain A (MICA) antibody with both clinical outcomes and histology identified on protocol biopsies at 0, 6, 12, and 24 months. We detected de novo antibodies after transplant in 24% (23% of SF group and 25% of SB group), most often after the first year. Overall, 22% developed anti-HLA antibodies, of which 6% were donor-specific antibodies, and 6% developed anti-MICA antibody. Presence of these antibodies de novo associated with significantly higher risks for acute rejection (P=0.02), chronic graft injury (P=0.02), and decline in graft function (P=0.02). In summary, antibodies to HLA and MICA antigens appear in approximately 25% of unsensitized pediatric patients, placing them at greater risk for acute and chronic rejection with accelerated loss of graft function. Avoiding steroids does not seem to modify this incidence. Whether serial assessments of these antibodies after transplant could guide individual tailoring of immunosuppression requires additional study.