Risk In Pediatric Patients Research Articles

Prognostic Model to Predict Postoperative Adverse Events in Pediatric Patients With Aortic Coarctation.

Background: Postoperative adverse events remain excessively high in surgical patients with coarctation of aorta (CoA). Currently, there is no generally accepted strategy to predict these patients' individual outcomes.Objective: This study aimed to develop a risk model for the prediction of postoperative risk in pediatric patients with CoA.Methods: In total, 514 patients with CoA at two centers were enrolled. Using daily clinical practice data, we developed a model to predict 30-day or in-hospital adverse events after the operation. The least absolute shrinkage and selection operator approach was applied to select predictor variables and logistic regression was used to develop the model. Model performance was estimated using the receiver-operating characteristic curve, the Hosmer–Lemeshow test and the calibration plot. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) compared with existing risk strategies were assessed.Results: Postoperative adverse events occurred in 195 (37.9%) patients in the overall population. Nine predictive variables were identified, including incision of left thoracotomy, preoperative ventilation, concomitant ventricular septal defect, preoperative cardiac dysfunction, severe pulmonary hypertension, height, weight-for-age z-score, left ventricular ejection fraction and left ventricular posterior wall thickness. A multivariable logistic model [area under the curve = 0.8195 (95% CI: 0.7514–0.8876)] with adequate calibration was developed. Model performance was significantly improved compared with the existing Aristotle Basic Complexity (ABC) score (NRI = 47.3%, IDI = 11.5%) and the Risk Adjustment for Congenital Heart Surgery (RACHS-1) (NRI = 75.0%, IDI = 14.9%) in the validation set.Conclusion: Using daily clinical variables, we generated and validated an easy-to-apply postoperative risk model for patients with CoA. This model exhibited a remarkable improvement over the ABC score and the RACHS-1 method.

Factors associated with acyclovir nephrotoxicity in children: data from 472 pediatric patients from the last 10 years.

Acyclovir may cause acute kidney injury (AKI) due to the accumulation of relatively insoluble acyclovir crystals in renal tubules. The aim of this study was to evaluate risk factors associated with acyclovir-related AKI in children. Between January 2010 and December 2019, pediatric recipients of intravenous (IV) acyclovir were evaluated retrospectively. There were a total of 472 patients [249 (52.7%) boys] of which 32 (6.8%) had AKI [15 (46.8%) boys]. Patients with AKI had greater mean age, baseline creatinine level, and duration of treatment compared to patients without AKI (p<0.001). In the AKI group, concomitant nephrotoxic drug use was more frequent (p=0.032), and the percentage of patients treated with 1500 mg/m2/day dosage was higher (p<0.001). AKI was diagnosedat a meanof 4.3 ± 2.5 days after acyclovir initiation and creatinine levels returned to normal at ameanof 7.3 ± 3.6 days after AKIdiagnosis. Only eight patients (25%) had vomiting which led to suspicion of AKI. Being older than 100.5 months (HR: 4.501, 95% CI: 1.802-11.241; p=0.001), use of 1500 mg/m2/day acyclovir (HR: 9.536, 95% CI: 2.157-42.158; p=0.003) and use of concomitant nephrotoxic drugs (HR: 5.043, 95% CI: 2.289-11.109; p<0.001) were the factors that independently increased the likelihood of nephrotoxicity.Conclusion: Most patients were asymptomatic when they were diagnosed with AKI. Clinicians should be aware of AKI risk in pediatricpatients with risk factors (age >100.5 months, 1500 mg/m2/day dosage, concomitant use of nephrotoxic drugs). Acyclovir dosing should be evaluated in prospective, multicenter studies in order to identify the lowest possible therapeutic doses that do not increase AKI risk. What is Known: • Although acyclovir is mostly well tolerated, nephrotoxicity may be seen due to the accumulation of acyclovir crystals in renal tubules. • Older age, obesity, and concomitant use of other nephrotoxic drugs are reported to be risk factors for acyclovir-induced AKI in children. What is New: • In this study, pediatric patients with acyclovir-induced AKI were older, received treatment longer, received concomitant nephrotoxic drugs more commonly, and had higher acyclovir dosage and baseline creatinine levels compared to those without AKI. • Being older than 100.5 months of age, use of 1500 mg/m2/day dosage and use of nephrotoxic drugs concomitantly appear to be the prominent risk factors for AKI development in children treated with acyclovir.

Rituximab-induced hypogammaglobulinemia and infection risk in pediatric patients

Rituximab is a B-cell depleting agent used in B-cell malignancies and autoimmune diseases. A subset of adult patients may develop prolonged and symptomatic hypogammaglobulinemia following rituximab treatment. However, this phenomenon has not been well delineated in the pediatric population. This study sought to determine the prevalence, risk factors, and clinical significance of hypogammaglobulinemia following rituximab therapy in children. This was a multicenter, retrospective cohort study that extracted clinical and immunological data from pediatric patients who received rituximab. The cohort comprised 207 patients (median age, 12.0 years). Compared to baseline values, there was a significant increase in hypogammaglobulinemia post-rituximab therapy, with an increase in prevalence of hypo-IgG (28.7%-42.6%; P= .009), hypo-IgA (11.1%-20.4%; P= .02), and hypo-IgM (20.0%-62.0%; P< .0001). Additionally, low IgG levels at any time post-rituximab therapy were associated with a higher risk of serious infections (34.4% vs 18.9%; odds ratio, 2.3; 95% CI, 1.1-4.8; P= .03). Persistent IgG hypogammaglobulinemia was observed in 27 of 101 evaluable patients (26.7%). Significant risk factors for persistent IgG hypogammaglobulinemia included low IgG and IgA levels pre-rituximab therapy. Nine patients (4.3%) within the study were subsequently diagnosed with a primary immunodeficiency, 7 of which received rituximab for autoimmune cytopenias. Hypogammaglobulinemia post-rituximab treatment is frequently diagnosed within the pediatric population. Low IgG levels are associated with a significant increase in serious infections, and underlying primary immunodeficiencies are relatively common in children receiving rituximab, thus highlighting the importance of immunologic monitoring both before and after rituximab therapy.

Veno-occlusive disease risk in pediatric patients with acute myeloid leukemia treated with gemtuzumab ozogamicin before allogeneic hematopoietic cell transplantation.

Gemtuzumab ozogamicin (GO) administered before allogeneic hematopoietic cell transplantation (alloHCT) has been linked to an increased risk of hepatic veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS). This retrospective analysis examined VOD/SOS risk and clinical outcomes in pediatric patients with acute myeloid leukemia who received myeloablative alloHCT in 2008-2011 with (n=148) and without (n=348; controls) prior GO exposure and were reported to the Center for International Blood and Marrow Transplant Research. Cumulative incidences (95% confidence interval [CI]) of VOD/SOS and severe VOD/SOS, respectively, at 100days were 16% (11-23%) and 8% (4-13%) for GO-exposed patients and 10% (7-13%) and 3% (2-5%) for controls. With a median follow-up of approximately 7years, the 5-year adjusted overall survival probability (95% CI) after alloHCT was 51% (43-58%) and 55% (50-60%) for GO-exposed patients and controls, respectively; three (4%) and one (<1%) deaths were attributed to VOD/SOS. In multivariate analyses, GO exposure was observed to be associated with an increased risk of VOD/SOS at 100days, but was not associated with overall survival, disease-free survival, relapse, or nonrelapse mortality. Results suggest that GO treatment prior to alloHCT in pediatric patients may increase the risk of VOD/SOS but not death.

Hearing Loss Risk in Pediatric Patients Treated with Cranial Irradiation and Cisplatin-Based Chemotherapy.

Cranial radiation therapy (RT) and cisplatin-based chemotherapy are essential to treating many pediatric cancers but cause significant ototoxicity. The objective of this study is to determine the relationship between the RT dose and the risk of subsequent hearing loss in pediatric patients treated with cisplatin. This retrospective study of cisplatin-treated pediatric patients examined ototoxicity from cranial RT. Ototoxicity was graded for each ear according to the International Society of Pediatric Oncology (SIOP) consensus ototoxicity scale. The RT dose to the cochlea was calculated using the mean, median, maximum, and minimum dose received to determine the most predictive parameter for hearing loss. Multivariable logistic regression models then examined risk factors for hearing loss. In 96 children (161 ears) treated with RT + cisplatin, the minimum cochlear RT dose was most predictive of hearing loss. A higher cochlear RT dose was associated with increased hearing loss (odds ratio per 10 Gy dose increase = 1.64; P = .043), with an added risk in those receiving an autologous bone marrow transplantation (hazard ratio = 10.47; P < .001). This research supports further testing of the minimum cochlear RT dose as a more predictive dose parameter for risk of ototoxicity. The cochlear RT dose was additive to the risk of hearing loss from underlying cisplatin-based chemotherapy. Exposure to autologous bone marrow transplantation was the strongest predictor of developing hearing loss, placing these children at particularly high risk for hearing loss across all cochlear doses. Future prospective studies are crucial to further inform RT dose thresholds and minimize the risk of hearing loss in childhood cancer survivors.

Association of genetic polymorphisms NCF4 rs1883112, CBR3 rs1056892, and ABCC1 rs3743527 with the cardiotoxic effects of doxorubicin in children with acute lymphoblastic leukemia.

Cardiotoxicity is a frequent complication secondary to the use of anthracyclines for cancer chemotherapy. Evidence suggests that certain polymorphic genetic variants modify the risk for anthracycline-related cardiotoxicity. Reports documenting the impact of genetic polymorphisms on anthracycline-cardiotoxicity risk in pediatric patients with cancers from Latin American countries are scarce. The objective of this study was to evaluate associations between NCF4 rs1883112, CBR3 rs1056892 and ABCC1 rs3743527 genotype status and echocardiographic parameters indicative of anthracycline-cardiotoxicity in a group of Mexican children with acute lymphoblastic leukemia (ALL). Sixty-seven children (2-18 years old) with ALL were treated at the State Cancer Center in Durango, Mexico. NCF4, CBR3, and ABCC1 genotypes were examined by real-time PCR. Left ventricular ejection fraction and diastolic filling ratio were examined as markers of systolic and diastolic anthracycline-toxicity. NCF4 rs1883112 genotype status was significantly associated with the risk of doxorubicin cardiotoxicity [odds ratio (OR) = 10.80, 95% confidence interval (CI) 1.69-68.98, P = 0.01]. There was a significant association between heterozygous CBR3 rs1056892 genotype status and anthracycline-cardiotoxicity risk (OR = 9.91, 95% CI 1.07-91.47, P = 0.04). Heterozygosis for the ABCC1 rs3743527 allele was associated with protection from anthracycline-cardiotoxicity (OR = 0.30, 95% CI 0.09-0.91, P = 0.03). This pilot study suggests that selected polymorphic variants may impact the risk for anthracycline-cardiotoxicity in pediatric patients with ALL treated with a contemporary chemotherapeutic regimen in Mexico.

Hospitalization risk in pediatric patients with bipolar disorder treated with lurasidone vs. other oral atypical antipsychotics: a real-world retrospective claims database study

Background Real-world evidence on atypical antipsychotic (AAP) use in pediatric bipolar disorder is limited. Objective To assess the risk of all-cause and psychiatric hospitalization among pediatric patients with bipolar disorder when treated with lurasidone versus other atypical antipsychotics (AAPs). Methods This retrospective cohort study used commercial claims data (January 1, 2011 to June 30, 2017) to identify pediatric patients (age ≤17 years) with bipolar disorder treated with oral atypical antipsychotics (N = 16,201). The date of the first claim for an AAP defined the index date, with pre- and post-index periods of 180 days. Each month of the post-index period was categorized as monotherapy treatment with lurasidone, aripiprazole, olanzapine, quetiapine, or risperidone, no/minimal treatment, or other. The risk of all-cause and psychiatric hospitalizations (defined by a psychiatric diagnosis on the facility claim) was analyzed based on treatment in the current month, time-varying covariates (prior treatment-month classification, hospitalization in the prior month, emergency room visit in the prior month), and fixed covariates (age, gender, pervasive development disorder/mental retardation, disruptive behavior/conduct disorder, attention deficit hyperactivity disorder, depression, anxiety, adjustment disorder, obesity, diabetes, antidepressants, anxiolytics, other co-medication) using a marginal structural model. Results Treatment with aripiprazole (OR = 1.60, 95% CI: 1.08–2.36) and olanzapine (OR = 1.68, CI: 1.03–2.71) was associated with significantly higher odds of all-cause hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.03, CI: 0.69–1.54) or risperidone (OR = 1.02, CI: 0.68–1.53) was not. Similarly, treatment with aripiprazole (OR = 1.61, 95% CI: 1.08–2.38) and olanzapine (OR = 1.73, CI: 1.06–2.80) was associated with significantly higher odds of psychiatric hospitalizations compared to lurasidone, but treatment with quetiapine (OR = 1.02, CI: 0.68–1.54) or risperidone (OR = 1.01, CI: 0.67–1.51) was not. Conclusion In usual clinical care, pediatric patients with bipolar disorder treated with lurasidone had a significantly lower risk of all-cause and psychiatric hospitalizations when compared to aripiprazole and olanzapine, but not quetiapine or risperidone.

906. Surgical Site Infections in Children with Beta-Lactam Allergy: A Matched Cohort Study

BackgroundSurgical site infections (SSIs) are a significant cause of morbidity and mortality. The administration of appropriate pre-operative antimicrobial prophylaxis (AMP) reduces SSI risk and beta-lactam antibiotics are considered the most effective agents. Studies in adult patients found increased SSI risk in patients with documented beta-lactam allergy (BLA) due to use of second line AMP agents. The SSI risk in BLA pediatric patients is not well-described.MethodsWe conducted a retrospective matched cohort study of patients (1-19 years-old) who underwent a surgical procedure at a quaternary pediatric hospital during 2010-2017. Patients with documented BLA at the time of surgery were matched 1:1 to patients with no BLA by age at surgery, National Surgical Quality Improvement Program (NSQIP) category, surgical calendar year, and presence of complex chronic conditions (CCC). AMP by BLA status was considered appropriate if recommended by the 2013 American Society of Health-System Pharmacists (ASHP) guidelines, antibiotic class appropriate, or recommended by an infectious disease physician. McNemar’s test was used to assess differences in SSI rates and antibiotic regimen appropriate for BLA status between BLA and no BLA groups.ResultsOf the 11878 surgical procedures among 9781 patients during the study period, 1021(9%) of patients had a reported BLA and we matched 972. SSI was rare in both groups and there was no significant difference in rates (18 (1.9%) in no BLA, 17 (1.8%) in BLA, p=1.0). BLA were more likely to receive an antibiotic regimen considered inappropriate for BLA status (22%) compared to no BLA (3%) with 89% receiving a beta-lactam-containing AMP regimen (p< 0.01).ConclusionBLA was not associated with increased SSI risk in the pediatric patients studied. Interestingly, a significant proportion of children with a documented allergy received a beta-lactam for AMP. This suggests some providers recognize that allergy labels are inaccurate and may be comfortable administering beta-lactam AMP regardless of allergy status.Disclosures All Authors: No reported disclosures

Broad-Spectrum Antibiotics and Risk of Graft-versus-Host Disease in Pediatric Patients Undergoing Transplantation for Acute Leukemia: Association of Carbapenem Use with the Risk of Acute Graft-versus-Host Disease

Variation in the gastrointestinal (GI) microbiota after hematopoietic cell transplantation (HCT) has been associated with acute graft-versus-host disease (aGVHD). Because antibiotics induce dysbiosis, we examined the association of broad-spectrum antibiotics with subsequent aGVHD risk in pediatric patients undergoing HCT for acute leukemia. We performed a retrospective analysis in a dataset merged from 2 sources: (1) the Center for International Blood and Marrow Transplant Research, an observational transplantation registry, and (2) the Pediatric Health Information Services, an administrative database from freestanding children's hospitals. We captured exposure to 3 classes of antibiotics used for empiric treatment of febrile neutropenia: (1) broad-spectrum cephalosporins, (2) antipseudomonal penicillins, and (3) carbapenems. The primary outcome was grade II-IV aGVHD; secondary outcomes were grade III-IV aGVHD and lower GI GVHD. The adjusted logistic regression model (full cohort) and time-to-event analysis (subcohort) included transplantation characteristics, GVHD risk factors, and adjunctive antibiotic exposures as covariates. The full cohort included 2550 patients at 36 centers; the subcohort included 1174 patients. In adjusted models, carbapenems were associated with an increased risk of grade II-IV aGVHD in the full cohort (adjusted odds ratio [aOR], 1.24; 95% confidence interval [CI], 1.02 to 1.51) and subcohort (sub hazard ratio [HR], 1.31; 95% CI, 0.99 to 1.72), as well as with an increased risk of grade III-IV aGVHD (subHR, 1.77; 95% CI, 1.25 to 2.52). Early carbapenem exposure (before day 0) especially impacted aGVHD risk. For antipseudomonal penicillins, the associations with aGVHD were in the direction of increased risk but were not statistically significant. There was no identified association between broad-spectrum cephalosporins and aGVHD. Carbapenems, more than other broad-spectrum antibiotics, should be used judiciously in pediatric HCT recipients to minimize aGVHD risk. Further research is needed to clarify the mechanism underlying this association.

Venous Thromboembolism Prophylaxis in Adolescent Patients with Sickle Cell Disease: A Multicenter Cohort Study

Background: Evolving pediatric data, including case reports, case series, and combined adult and adolescent cohort studies, suggest an increased prevalence of venous thromboembolism (VTE) in children with Sickle Cell Disease (SCD) who undergo central venous catheter (CVC) placement (Ko RH and Thornburg C, Front Pediatr, 2017). Additionally, VTE has been shown to affect patients with SCD at a younger age compared to African-American controls (Stein PD, et al, Am J Med, 2006). Anecdotally, pediatric hematologists acknowledge the VTE risk in pediatric patients with SCD and have been using thromboprophylaxis in their patients despite the lack of standardized guidelines. The goal of this retrospective cohort study is to assess the utilization of pharmacologic and non-pharmacologic thromboprophylaxis in adolescent patients with SCD using a large pediatric database. Methods: The data source for this multicenter cohort study was the Pediatric Health Information Systems (PHIS), an administrative database that contains clinical and resource utilization data for inpatient, ambulatory surgery, emergency department, and observation unit patient encounters for 49 freestanding children's hospitals in the US. ICD-9-CM and ICD-10-CM codes were used to identify subjects, including SCD genotype (SS, SC and SB0 thal) and other comorbidities (acute chest syndrome, vaso-occlusive crisis, osteomyelitis, and bacteremia). We included subjects, aged 13-21 years, admitted to any PHIS hospital between 01/01/2010 - 12/31/2019. Subjects with a history of VTE were excluded. Supply billing codes were used to identify CVC placement and mechanical prophylaxis. Pharmaceutical billing codes were used to identify anticoagulant use. Results: 6,903 unique patients (3,147 male) met inclusion criteria with a median age of 17.2 years (13.0-21.9 years). These patients comprised a total of 33,298 admissions, with 2,434 (7.3%) admissions identified as receiving pharmacologic or mechanical prophylaxis (Table 1). 4.3% of the total admissions received mechanical prophylaxis and 3.3% received pharmacologic prophylaxis. Enoxaparin was the most commonly used anticoagulant, utilized in 91.3% of admissions in which pharmacologic anticoagulation was prescribed. The use of thromboprophylaxis was noted to increase over the study period, with significant increases observed in both pharmacologic and mechanical prophylaxis(p&amp;lt;.0001; Figure 1). The percentage of unique patients receiving thromboprophylaxis at each participating institution is shown in Figure 2. WConclusions: Use of both pharmacologic and mechanical thromboprophylaxis in hospitalized adolescent patients with SCD has increased in the last decade. However, there is variability amongst pediatric hospitals regarding the use and preferred method of thromboprophylaxis. Prospective cohort studies are needed to determine VTE risk factors in adolescents and children with SCD and the efficacy of prophylaxis regimens. These studies will help guide the development of VTE prophylaxis regimens. Disclosures Davila: ATHN: Other: Grant Funding; Spire Learning: Speakers Bureau. O'Brien:Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: The use of Direct Oral Anticoagulants and Enoxaparin in children

Testing of Braden QD Scale for predicting pressure ulcer risk in the Pediatric Intensive Care Unit.

Children admitted to the Pediatric Intensive Care Unit (PICU) are at risk for pressure injury due to immobility and the challenge of positioning medical devices. However, a comprehensive instrument to assess pressure injury risk is still finite. This study aimed to test the validity and reliability of the Braden QD Scale. The design used was a Pearson correlation coefficients and Cronbach’s alpha (α). Fifty-one pediatric patients below age 18 who had been bedridden for at least 24 hours were engaged through a consecutive sampling method. The results showed assessments made by using the Braden QD Scale revealed that 88.2% of patients were at risk for a pressure injury. The validity test results of the Braden QD Scale ranged between 0.532 and 0.833. The reliability test results of the Braden QD Scale ranged between 0.756 and 0.834. The sensitivity value is 100%, specificity value is 40%. In general, the study finding suggests that the Braden QD Scale is a valid and reliable instrument for predicting pressure injury risk. Nurses may employ this tool to assess pressure injury risk in pediatric patients.

Risk of seizures associated with antipsychotic treatment in pediatrics with psychiatric disorders: a nested case-control study in Korea.

Antipsychotic drugs raise seizure risk in adults, and antipsychotic drug use is increasing among pediatric psychiatric disorder patients. However, few studies have examined seizure risk in this younger patient population. To evaluate seizure risk in pediatric patients on antipsychotics, we conducted a nested case-control study using a nationwide database. Patient information was retrieved from the Korean Health Insurance Review and Assessment (HIRA) database from 2008-2018. Antipsychotic use among newly diagnosed psychiatric patients was gathered starting 1 year before the index date and categorized as recent, past, consistent, or none. Seizure cases among these patients were defined based on (1) prescription of antiepileptic drugs or (2) an electroencephalography (EEG) examination among patients with seizure diagnostic code. A conditional logistic regression model was constructed to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for seizure risk due to antipsychotic use. In total, 1523 seizure cases and 6092 seizure-free controls aged 8-19years with newly diagnosed psychiatric disorders were included for analysis. Logistic regression revealed a significant association between antipsychotic use and seizure development (recent users OR = 4.03, 95% CI 3.4-4.79; consistent users: OR = 2.84, 95% CI 2.44-3.3). Seizure risk enhanced further with an increase in the number of antipsychotic drugs used. Risperidone, aripiprazole, quetiapine, olanzapine, paliperidone, and blonanserin were independently associated with greater seizure risk. Pediatric patients receiving antipsychotics, especially new or multiple antipsychotic users, should be carefully monitored for seizure development.

Perioperative Bleeding Risk Assessment in a Cohort of Children with Low Levels of Von Willebrand Factor

Background: Identifying perioperative bleeding risk in pediatric patients undergoing major surgery is challenging because personal history is often not sufficiently informative and laboratory tests are also more susceptible to pre-analytical variables. Children with low Willebrand add further uncertainty in the treatment options. The aim of this study was to evaluate practices to assess hemorrhagic risk and manage bleeding prophylaxis in children with low von Willebrand factor levels (30 and 50 IU/dL; low VWF), known von Willebrand disease (VWD) or healthy controls undergoing ear, nose and throat (ENT) surgery. Methods: In this retrospective observational study, data from consecutive paediatric patients undergoing ENT surgery between January 1, 2010 and December 31, 2017 at the Turin Paediatric Hospital were analysed. All statistical analyses were performed using STATA (StataCorp. 2013. Been Statistical Software: Release 13. College Station, TX: StataCorp LP). Demographic and clinical characteristics of patients were assessed using the absolute frequencies and percentages for qualitative variables and percentiles for quantitative variables. The risk of bleeding was estimated from the number of patients who experienced bleeding within 21 days as a proportion of the number of patients subjected to surgery. 90% confidence intervals (90% CIs) were estimated for the evaluation of bleeding risk, using the Jeffreys method and any differences in the risk of bleeding between patient groups were tested using a proportions test. To investigate any factors associated with the therapeutic strategy used, multinomial logistic regression models were conducted. Results: Major perioperative bleeding was seen in 6.3% (5/79) of low VWF patients, 3.0% (35/1152) of healthy controls and 20.0% (5/25) of patients with VWD. In low VWF patients, perioperative bleeding prophylaxis was given to 59.5% and included subcutaneously desmopressin (n=21) and VWF-containing concentrate (n=26). Oral or intravenous tranexamic acid was administered to all low VWF patients. Of these patients, one major hemorrhagic event occurred in patients who did not receive prophylaxis and the remaining events occurred in patients treated with VWF-containing concentrate. In patients who received a VWF-containing concentrate, lower VWF ristocetin cofactor levels were observed compared with patients who received desmopressin or were untreated during surgery. No differences in clinical and laboratory features were observed between patients with low VWF treated with desmopressin and those who were untreated. Conclusions: Patients with low VWF have a higher risk of perioperative bleeding compared with healthy controls but a significantly lower risk compared with patients with VWD. The perioperative management of these patients is complex with a high risk of overtreatment. In our experience the caution of keeping the VWF-containing concentrate in the operating room available for use in case of bleeding appears to be a balanced approach. Prospective randomized studies to identify accurate methods of assessing bleeding risk and evaluate the most effective perioperative bleeding prevention are warranted. Essential bibliography: Ruchika Sharma and Veronica H. Flood. Advances in the diagnosis and treatment of Von Willebrand disease. Hematology American Society of Hematology Education Program 2017:379-384 Sadler JE. Low von Willebrand factor: sometimes a risk factor and sometimes a disease. Hematology American Society of Hematology Education Program 2009:106-112 Rodeghiero F, Tosetto A, Abshire T, et al. ISTH/SSC bleeding assessment tool: a standardized questionnaire and a proposal for a new bleeding score for inherited bleeding disorders. J Thromb Haemost. 2010;8(9):2063-2065. Casey LJ, Tuttle A, Grabell J, et al. Generation and optimization of the self-administered pediatric bleeding questionnaire and its validation as a screening tool for von Willebrand disease. Pediatr Blood Cancer. 2017;64(10) Mannuccio Mannucci P, Kyrle PA, Schulman S, Di Paola J, Schneppenheim R, Cox Gill J. Prophylactic efficacy and pharmacokinetically guided dosing of a von Willebrand factor/factor VIII concentrate in adults and children with von Willebrand's disease undergoing elective surgery: a pooled and comparative analysis of data from USA and European Union clinical trials. Blood Transfus. 2013;11(4):533-540 Disclosures No relevant conflicts of interest to declare.

Feasibility of fast non local means filter in pediatric chest x-ray for increasing of pulmonary nodule detectability with 3D printed lung nodule phantom

General x-ray images have a lower probability of nodule detection than other modalities. Especially in children, the probability of nodule detection can likely drop due to poor image quality from using low radiation dose. To demonstrate the effectiveness of fast non-local means (FNLM) filter to increase the probability of nodule detection in pediatric chest x-ray images and reduce radiation dose while maintaining image quality. Quantitative assessment of normalised noise power spectrum (NNPS), coefficient of variation (COV) and contrast to noise ratio (CNR) were performed after applying four filters (median, Wiener, total variation and FNLM) on a 1-year-old child phantom. A 3D-printed patient nodule phantom was inserted into the phantom. Assessment was performed on AP and LAT view images acquired with the tube voltage reduced to 38 and 27%, and tube current reduced to 84 and 61%, respectively. The results showed the lowest NNPS and COV values and the highest CNR value when the FNLM filter applied. Moreover, the AP view results showed 37% decrease in COV and 30% increase in CNR in images with the FNLM filter applied (images exposed with the tube voltage and current reduced to 29% and 50%, respectively). The LAT view results showed 5% decrease in COV and 36% increase in CNR in images with the FNLM filter applied (images exposed with the tube current reduced by 27%). By applying the FNLM filter, the probability of nodule detection could be increased by denoising and contrast enhancement. Moreover, using the FNLM filter could reduce cancer risk in pediatric patients by reducing radiation dose about 30% to 44%.

Lipoprotein particles in patients with pediatric Cushing disease and possible cardiovascular risks.

Background:Cardiovascular (CV) complications are the most significant cause of mortality in adults with Cushing disease (CD); little is known about CV risk factors in children with CD. Measurement of lipoprotein particles by nuclear magnetic resonance (NMR) spectroscopy is a novel technology to assess CV risk. The objective of the current study is to analyze the NMR lipid profile in pediatric CD patients before and 1 year after remission.Methods:NMR lipid profile was obtained via the Vantera NMR analyzer, using frozen serum samples from 33 CD patients (mean age 13.8 ± 4.0 years) evaluated between 1997 and 2017 at the National Institutes of Health (NIH) Clinical Center (CC).Results:GlycA, triglyceride-rich particles (TRLP medium and very small sizes), LDL particles (LDLP total and large size), HDL particles (HDLP total, medium and small sizes), total cholesterol, LDL cholesterol, HDL cholesterol, GlycA inflammatory biomarker, Apolipoprotein B and Apolipoprotein A1 concentrations showed statistically significant changes after remission of CD (p<0.05).Conclusion:In our study population, most of the lipid variables improved post-CDremission, with the exception of HDL and apoA1, indicating that NMR lipoprotein profile may be a helpful tool in assessing the cardiovascular risk in pediatric patients with CD.

Halo Gravity Traction Can Mitigate Preoperative Risk Factors and Early Surgical Complications in Complex Spine Deformity.

Retrospective review of prospective cohort. We sought to examine the role of halo gravity traction (HGT) in reducing preoperative surgical risk. The impact of HGT on procedure choice, preoperative risk factors, and surgical complications has not been previously described. Patients treated with HGT before primary surgery were included. The FOCOS Score (FS) was used to quantify operative risk. FS was calculated using patient-factors (ASIA, body mass index, etiology), procedure-factors (PcF; osteotomy planned, number of levels fused, etc.), and curve magnitude (CM). Scores ranged from 0 to 100 with higher scores indicating increased risk. FS was calculated before and after HGT to see how changes in FS affected complication rates. A total of 96 patients were included. Halo-related complications occurred in 34% of patients but revision was required in only 8.3%. Average FS improved by 18 points after HGT. CM, PcF, and patient-factors all improved (P < 0.05). The greatest changes were in CM and PcF. The planned rate of three-column osteotomies dropped from 91% to 38% after HGT. FS (area under the curve [AUC]: 0.68, P = 0.023) and change in FS (AUC: 0.781, P < 0.001) was successfully able to predict the rate of surgical complications. A preoperative FS of 74 was identified as a cut-off for a higher rate of surgical complications (sensitivity 58.8%, specificity 74.7%). Patients with a reduction in FS < = 10pts were five times more likely to have a complication (relative risk 5.2, 95% confidence interval: 1.9-14.6, P < 0.001). A multivariate regression showed that change in FS was an independent predictor of complication rates (P < 0.05). FS can successfully predict surgical risk in pediatric patients with complex spinal deformity. Preoperative HGT can reduce FS and surgical risk by improving CM, lowering three-column osteotomies use, and improving body mass index. A reduction in FS after HGT predicts a lower rate of surgical complications. 3.

Association of Proton Pump Inhibitors With Hospitalization Risk in Children With Oropharyngeal Dysphagia

Proton pump inhibitors (PPI) are commonly prescribed to children with oropharyngeal dysphagia and resultant aspiration based on the assumption that these patients are at greater risk for reflux-related lung disease. There is little data to support this approach and the potential risk for increased infections in children treated with PPI may outweigh any potential benefit. The aim of this study was to determine if there is an association between hospitalization risk in pediatric patients with oropharyngeal dysphagia and treatment with PPI. We performed a retrospective cohort study to compare the frequency and length of hospitalizations for children who had abnormal results on videofluoroscopic swallow studies that were performed between January 1, 2015, and December 31, 2015, and who were or were not treated with PPI, with follow-up through December 31, 2016. Records were reviewed for children who presented for care at Boston Children's Hospital, a tertiary referral center. Participants included 293 children 2 years and younger with evidence of aspiration or penetration on videofluoroscopic swallow study. Groups were compared based on their exposure to PPI treatment. The primary outcomes were hospital admission rate and hospital admission nights and these were measured as incident rates. Multivariable analyses were performed to determine predictors of hospitalization risk after adjusting for comorbidities. Kaplan-Meier curves were created to determine the association of PPI prescribing with time until first hospitalization. A total of 293 patients with a mean (SD) age of 8.8 (0.4) months and a mean (SD) follow-up time of 18.15 (0.20) months were included in the analysis. Patients treated with PPI had higher admission rates (Incidence rate ratio [IRR], 1.77; 95% CI, 1.16-2.68) and admission nights (IRR, 2.51; 95% CI, 1.36-4.62) even after adjustment for comorbidities. Patients with enteral tubes who were prescribed PPIs were at the highest risk for admission (hazard ratio [HR], 2.31; 95% CI, 1.24-4.31). Children with aspiration who are treated with PPI have increased risk of hospitalization compared with untreated patients. These results support growing concern about the risks of PPI use in children.

Regional oxygen extraction predicts border zone vulnerability to stroke in sickle cell disease.

To determine mechanisms underlying regional vulnerability to infarction in sickle cell disease (SCD) by measuring voxel-wise cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen utilization (CMRO2) in children with SCD. Participants underwent brain MRIs to measure voxel-based CBF, OEF, and CMRO2. An infarct heat map was created from an independent pediatric SCD cohort with silent infarcts and compared to prospectively obtained OEF maps. Fifty-six participants, 36 children with SCD and 20 controls, completed the study evaluation. Whole-brain CBF (99.2 vs 66.3 mL/100 g/min, p < 0.001), OEF (42.7% vs 28.8%, p < 0.001), and CMRO2 (3.7 vs 2.5 mL/100 g/min, p < 0.001) were higher in the SCD cohort compared to controls. A region of peak OEF was identified in the deep white matter in the SCD cohort, delineated by a ratio map of average SCD to control OEF voxels. CMRO2 in this region, which encompassed the CBF nadir, was low relative to all white matter (p < 0.001). Furthermore, this peak OEF region colocalized with regions of greatest infarct density derived from an independent SCD cohort. Elevated OEF in the deep white matter identifies a signature of metabolically stressed brain tissue at increased stroke risk in pediatric patients with SCD. We propose that border zone physiology, exacerbated by chronic anemic hypoxia, explains the high risk in this region.

Association of interleukin (IL)-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms with susceptibility to pediatric autoimmune hepatitis type 1

ObjectiveAutoimmune hepatitis (AIH) is a chronic inflammatory liver disease mediated by an autoimmune reaction to hepatocytes, the present study aimed to assess the possible associations between interleukin-4 (IL-4) variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms and susceptibility to autoimmune hepatitis type 1 in children. Subjects and methodsThe study was performed on 101 children diagnosed with AIH and 104 apparently healthy, age and sex-matched control children, diagnosis of AIH was based on the simplified score for the diagnosis of AIH. Genotyping for the IL-4 VNTR and IL-4-590 were performed using PCR-RFLP. ResultsThe distribution of genotype frequencies of IL-4 gene intron 3 VNTR polymorphism were not significantly different between AIH patients and controls for 3R/2R and 2R/2R genotypes, while the 2R allele distribution was significantly higher among AIH patients than the control group. The frequency of IL-4-590 single nucleotide polymorphism (SNP) CT and TT genotypes was statistically higher among AIH patients than controls. ConclusionThis study revealed the presence of an association between IL-4 -590 TT genotype and T alleles with increased AIH risk in pediatric patients, also assess its severity as they were detected with Child Plugh scores B and C.

Predicting Pressure Injury Risk in Pediatric Patients: The Braden QD Scale

To describe the development and initial testing of the Braden QD Scale to predict both immobility-related and medical device-related pressure injury risk in pediatric patients. This was a multicenter, prospective cohort study enrolling hospitalized patients, preterm to 21 years of age, on bedrest for at least 24 hours with a medical device in place. Receiver operating characteristic curves using scores from the first observation day were used to characterize Braden QD Scale performance, including areas under the curve (AUC) with 95% CIs. Eight centers enrolled 625 patients. A total of 86 hospital-acquired pressure injures were observed in 49 (8%) patients: 22 immobility-related pressure injuries in 14 (2%) patients and 64 medical device-related pressure injuries in 42 (7%) patients. The Braden QD Scale performed well in predicting immobility-related and medical device-related pressure injuries in the overall sample, with an AUC of 0.78 (95% CI 0.73-0.84). At a cutoff score of 13, the AUC was 0.72 (95% CI 0.67-0.78), providing a sensitivity of 0.86 (95% CI 0.76-0.92), specificity of 0.59 (95% CI 0.55-0.63), positive predictive value of 0.15 (95% CI 0.11-0.19), negative predictive value of 0.98 (95% CI 0.97-0.99), and a positive likelihood ratio of 2.09 (95% CI 0.95-4.58). The Braden QD Scale reliably predicts both immobility-related and device-related pressure injuries in the pediatric acute care environment and will be helpful in monitoring care and in guiding resource use in the prevention of hospital-acquired pressure injuries.