Wash, Rinse, Repeat: Which Patients Undergo Serial Joint Irrigation in Pediatric Septic Hip Arthritis?

BACKGROUND: The purpose of this study is to identify risk factors associated with repeat surgical irrigation in pediatric septic hip arthritis. METHODS: A single center retrospective case-control study was performed. Patients who underwent ≥2 washouts (cases) were compared with those who had only 1 washout (controls). Demographic, clinical, laboratory, microbial, and magnetic resonance imaging data were compared between cases and controls and a prediction model was developed using logistic regression. A risk score was then constructed by counting the number of risk factors from the model that were present in each patient. RESULTS: We identified 26 patients between 1994 and 2015 who underwent ≥2 washouts for septic hip arthritis, and 63 control patients who had only a single washout. Twenty-two patients had 2 washouts, 3 had 4 washouts, 1 had 5 washouts. Median number of days between first and second washout was 5 (interquartile range, 4 to 8). The most common reason for repeat washout was persistent fever (N=21), followed by persistently elevated laboratory values (N=13), abnormal magnetic resonance imaging findings (N=12), and continued pain (N=12). Repeat washout cases demonstrated higher temperature preoperatively (P<0.001), had more frequent initial misdiagnosis (P=0.002), and had a longer time from symptom onset to surgery (P=0.02). Laboratory values in these cases showed higher C-reactive protein (P=0.003), and more frequent left shift (P=0.03) at presentation, with a greater proportion of positive cultures (P<0.001). Postoperatively, repeat washout cases had higher temperatures (P<0.001), more frequent wound drainage (P=0.02), and complications (P=0.001). A risk score for predicting the likelihood of undergoing repeat washout was constructed by counting the number of the following factors present: presence of left shift in CBC, positive blood or synovial fluid cultures, and postoperative temperature over 39°C. Seventy percent of cases had ≥2 of these risk factors and 80% of controls had ≤1 risk factor. CONCLUSIONS: Cases of pediatric septic arthritis which undergo repeat washout are associated with left shift, high postoperative temperatures, and positive cultures. They have more frequent misdiagnosis leading to delayed treatment and subsequent medical complications. LEVEL OF EVIDENCE: Level III.

Role of Genetic Susceptibility in the Development of Bronchopulmonary Dysplasia.

OBJECTIVE: To assess heritable contributions to bronchopulmonary dysplasia (BPD) risk in a twin cohort restricted to gestational age at birth <29 weeks. STUDY DESIGN: A total of 250 twin pairs (192 dichorionic, 58 monochorionic) born <29 weeks gestational age with known BPD status were identified. Three statistical methods applicable to twin cohorts (χ2 test, intraclass correlations [ICCs], and ACE modeling [additive genetic or A, common environmental or C, and unique environmental or E components]) were applied. Heritability was estimated as percent variability from A. Identical methods were applied to a subcohort defined by zygosity and to an independent validation cohort. RESULTS: χ2 analyses comparing whether neither, 1, or both of monochorionic (23, 19, 16) and dichorionic (88, 56, 48) twin pairs developed BPD revealed no difference. Although there was similarity in BPD outcome within both monochorionic and dichorionic twin pairs by ICC (monochorionic ICC = 0.34, 95% CI [0.08, 0.55]; dichorionic ICC = 0.39, 95% CI [0.25, 0.51]), monochorionic twins were not more likely than dichorionic twins to have the same outcome (P = .70). ACE modeling revealed no contribution of heritability to BPD risk (% A = 0.0%, 95% CI [0.0%, 43.1%]). Validation and zygosity based cohort results were similar. CONCLUSIONS: Our analysis suggests that heritability is not a major contributor to BPD risk in preterm infants <29 weeks gestational age.

Planar dGEMRIC Maps May Aid Imaging Assessment of Cartilage Damage in Femoroacetabular Impingement.

BACKGROUND: Three-dimensional (3-D) delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) helps quantify biochemical changes in articular cartilage that correlate with early-stage osteoarthritis. However, dGEMRIC analysis is performed slice by slice, limiting the potential of 3-D data to give an overall impression of cartilage biochemistry. We previously developed a computational algorithm to produce unfolded, or "planar," dGEMRIC maps of acetabular cartilage, but have neither assessed their application nor determined whether MRI-based grading of cartilage damage or dGEMRIC measurements predict intraoperative findings in hips with symptomatic femoroacetabular impingement (FAI). QUESTIONS/PURPOSES: (1) Does imaging-based assessment of acetabular cartilage damage correlate with intraoperative findings in hips with symptomatic FAI? (2) Does the planar dGEMRIC map improve this correlation? (3) Does the planar map improve the correlation between the dGEMRIC index and MRI-based grading of cartilage damage in hips with symptomatic FAI? (4) Does the planar map improve imaging-based evaluation time for hips with symptomatic FAI? METHODS: We retrospectively studied 47 hips of 45 patients with symptomatic FAI who underwent hip surgery between 2009 and 2013 and had a 1.5-T 3-D dGEMRIC scan within 6 months preoperatively. Our cohort included 25 males and 20 females with a mean ± SD age at surgery of 29 ± 11 years. Planar dGEMRIC maps were generated from isotropic, sagittal oblique TrueFISP and T1 sequences. A pediatric musculoskeletal radiologist with experience in hip MRI evaluated studies using radially reformatted sequences. For six acetabular subregions (anterior-peripheral [AP]; anterior-central [AC]; superior-peripheral [SP]; superior-central [SC]; posterior-peripheral [PP]; posterior-central [PC]), modified Outerbridge cartilage damage grades were recorded and region-of-interest T1 averages (the dGEMRIC index) were measured. Beck's intraoperative cartilage damage grades were compared with the Outerbridge grades and dGEMRIC indices. For a subset of 26 hips, 13 were reevaluated with the map and 13 without the map, and total evaluation times were recorded. RESULTS: There were no meaningful differences in the correlations obtained with versus without referencing the planar maps. Planar map-independent Outerbridge grades had a notable (p < 0.05) Spearman's rank correlation (ρ) with Beck's grades that was moderate in AP, SC, and PC (0.3 < ρ < 0.5) and strong in SP (ρ > 0.5). For map-dependent Outerbridge grades, ρ was moderate in AP, AC, and SC and strong in SP. Map-independent dGEMRIC indices had a ρ with Beck's grades that was moderate in AP and SC (-0.3 > ρ > -0.5) and strong in SP (ρ < -0.5). For map-dependent dGEMRIC indices, ρ was moderate in SC and strong in SP. Similarly, there were no meaningful, map-dependent differences in the correlations. When comparing Outerbridge grades and dGEMRIC indices, there were notable correlations across all subregions. Without the planar map, ρ was moderate in AC and PC and strong in AP, SP, SC, and PP. With the map, ρ was strong in all six subregions. In AC, there was a notable map-dependent improvement in this correlation (p < 0.001). Finally, referencing the planar dGEMRIC map during evaluation was associated with a decrease in mean evaluation time, from 207 ± 32 seconds to 152 ± 33 seconds (p = 0.001). CONCLUSIONS: Our work challenges the weak correlation between dGEMRIC and intraoperative findings of cartilage damage that was previously reported in hips with symptomatic FAI, suggesting that dGEMRIC has potential diagnostic use for this patient population. The planar dGEMRIC maps did not meaningfully alter the correlation of imaging-based evaluation of cartilage damage with intraoperative findings; however, they notably improved the correlation of dGEMRIC and MRI-based grading in AC, and their use incurred no additional time cost to imaging-based evaluation. Therefore, the planar maps may improve dGEMRIC's use as a continuous proxy for an otherwise discrete and simplified MRI-based grade of cartilage damage in hips with symptomatic FAI. LEVEL OF EVIDENCE: Level III, diagnostic study.

Radiographic Criteria for Undergoing an Ulnar Shortening Osteotomy in Madelung Deformity: A Long-term Experience From a Single Institution.

BACKGROUND: There are no established guidelines on the age or the severity of deformity for which an ulna shortening osteotomy or ulna epiphysiodesis should be performed in children and adolescents with Madelung deformity. The purpose of this study was to identify radiographic criteria associated with the eventual performance for an ulna shortening procedure in this patient population. METHODS: We retrospectively identified 41 wrists in 31 Madelung patients (mean±SD age 13.8±3.2 y) subjected to surgical correction of their deformity between 1999 and 2013. We assessed established radiographic criteria (ulnar tilt, lunate subsidence, palmar carpal displacement, ulnar variance) at preoperative and postoperative visits. Univariate and multivariate analyses were carried out to determine which radiographic criteria were associated with the performance of an "ulnar shortening procedure" at the first (index) surgical procedure. RESULTS: Eleven wrists were subjected to an ulna shortening osteotomy at the index and 5 at subsequent procedures; 10 cases received an ulnar epiphysiodesis (mean age 13.4±1.5 y). Ulnar shortening at the index procedure was associated with significantly higher preoperative lunate subsidence, ulnar variance, and palmar carpal displacement. Ulnar variance of >5 mm and lunate subsidence >4 mm resulted in a respective 67% and a 53% likelihood of undergoing ulnar shortening osteotomy; palmar carpal displacement over 22 mm resulted in a 50% likelihood for ulnar shortening. Patients who required a subsequent procedure (n=8) showed a significant increase in palmar displacement between surgeries. None of the 10 cases with a primary ulnar epiphysiodesis received a subsequent ulnar shortening; none of those undergoing late ulnar shortenings had an ulna epiphysiodesis at their index procedure (at 10.3±4.3 y). CONCLUSIONS: Lunate subsidence, ulnar variance, and palmar carpal displacement were significant radiographic criteria for undergoing an ulnar shortening osteotomy at our institution. A shortening osteotomy may be prevented by early ulna epiphysiodesis in skeletally immature children older than 10 years of age. LEVEL OF EVIDENCE: Therapeutic level IV-case series.

Reducing Cost and Radiation Exposure During the Treatment of Pediatric Greenstick Fractures of the Forearm.

BACKGROUND: We hypothesize that after successful closed reduction of pediatric greenstick fractures of the forearm, there is a low rate of lost reduction requiring intervention. By reducing the frequency of clinical and radiographic follow-up, we can reduce costs and radiation exposure. METHODS: A retrospective analysis was performed on patients aged 2 to 16 years treated with closed reduction and cast immobilization for greenstick fractures of the forearm at our institution between 2003 and 2013. The primary endpoint was a healed fracture with acceptable alignment at the final radiographic evaluation. Time-derived activity-based costing was used for cost analysis. We estimated radiation exposure in consultation with our hospital's radiation safety office. RESULTS: One hundred and nine patients with an average age of 6.9 years (range, 2 to 15 y) met the inclusion criteria. The initial maximal fracture angulation of the affected radius and/or ulna averaged 19.3 (SD=±8.7) degrees (range, 2 to 55 degrees). Patients were followed for an average of 60 days (range, 19 to 635 d). On average, patients received 3.6 follow-up clinical visits and 3.5 sets of radiographs following immediate emergency department care. Ninety-four percent of patients met criteria for acceptable radiographic alignment. Only 1 patient (0.9%; 95% confidence interval, 0.2%-5.0%) underwent rereduction, as determined by the treating physician. If clinical follow-up were limited to 2 visits and 3 sets of radiographs total, there would be a 14.3% reduction in total cost of fracture care and a 41% reduction in radiation exposure. CONCLUSIONS: This retrospective study suggests that pediatric greenstick fractures of the forearm rarely require intervention after initial closed reduction. We propose that 2 clinical follow-up visits and 3 sets of radiographs would reduce overall care costs and radiation exposure without compromising clinical results. LEVEL OF EVIDENCE: Level IV-economic and decision analyses.

Is acetabular osteoplasty always required in mixed impingement?

BACKGROUND: Mixed femoroacetabular impingement (FAI) is typically managed with both femoral and acetabular rim osteoplasties, but it has not been reported if the rim osteoplasty is always required. HYPOTHESIS/PURPOSE: We hypothesized that mixed FAI managed by femoral or combined femoral and acetabular osteoplasties will both attain satisfactory clinical results, provided intraoperative impingement-free functional motion is attained. METHODS: We retrospectively reviewed 30 hips (23 patients, mean age at surgery 24.3 years, mean follow-up time 1.6 years) with mixed FAI who underwent surgical dislocation of the hip and had femoral osteochondroplasty with rim trim (RT, n = 21) or no rim trim (NRT, n = 9). Physical examination results and Western Ontario and McMaster Universities Osteoarthritis (WOMAC) scores were evaluated. RESULTS: Mean (± SD) WOMAC pain scores improved from 6.56 (± 2.96) to 2.33 (± 3.64) in the NRT group (p = .002) and from 6.86 (± 4.15) to 3.86 (± 3.95) in the RT group (p = .014). Function improved in both groups, but the difference was significant only for the NRT group (p < .001). Over 50 % of patients in both groups had resolution of impingement sign. Internal rotation increased from 8.6° (± 11.8) to 20.0° (± 10.4) in the NRT group (p = .043) and from 4.0° (± 12.1) to 18.6° (± 14.0) in the RT group (p < .001). Both groups had increased flexion post-operatively to normal range, but the change was only significant for the RT group (p = .02). Both groups had insignificant decreases in external rotation. CONCLUSION: Satisfactory clinical outcomes were seen in hips with mixed impingement, regardless of whether RT was performed, provided impingement-free functional motion was attained and no severe cartilage damage was seen.

PedsQL correlates to PODCI in pediatric orthopaedic outpatient clinic.

PURPOSE: Quality-of-life (QOL) measures can be a valuable tool to assess the general welfare across a spectrum of patients in a pediatric orthopaedic outpatient clinic and can be a simple way to assess patient-based outcomes particularly for quality initiatives. The Pediatric Outcomes Data Collection Instrument (PODCI) is validated for many orthopaedic conditions but typically takes around 20 minutes to complete (86 questions). The Pediatric Quality of Life Inventory (PedsQL) takes <4 minutes to complete (23 questions) but has not been assessed in an orthopaedic setting. We initiated this study to find the best method for assessing QOL in our outpatient clinic. A short pediatric QOL measure that is correlated to an established orthopaedic-specific QOL measure is needed; therefore, we compared the PedsQL to the PODCI in the outpatient orthopaedic clinic. METHODS: This was a quality initiative project and as such did not require a priori IRB approval. Families of patients 2 to 18 years old who presented for follow-up after upper or lower extremity fractures or brachial plexus injuries in the orthopaedic clinic from October 2010 through August 2011 were asked to fill out both the PODCI and the PedsQL. Patients aged 5 years and older filled out a patient-report PedsQL; patients aged 11 years and older filled out the patient-report PODCI. Parents/guardians completed questionnaires for children of all ages. Most fracture patients (and/or their parent/guardian) repeated the questionnaires after 6 to 12 weeks. Data were then assessed for correlation between the PODCI and PedsQL. RESULTS: A total of 428 parent/guardian reports for 283 patients and 172 self-reports for 104 patients were included. The correlation between the PODCI Global score and the PedsQL Total score for the parent/guardian-reported questionnaires for all injuries was 0.77 (95% confidence interval, 0.72-0.82). When categorized within domains and injuries, parent/guardian-reported correlations ranged from 0.23 to 0.79. In patients aged 11 years and older, the correlation between the PODCI and PedsQL for the patient-reported questionnaire for all injuries was 0.85 (95% confidence interval, 0.80-0.89). When categorized within domains and injuries, patient-reported correlations ranged from 0.30 to 0.99. CONCLUSIONS: Utilizing the substantially shorter PedsQL in a high volume orthopaedic clinic as a substitute for the PODCI for quality improvement measures seems reasonable. Correlation between the PedsQL Global score and the PODCI Total score for orthopaedic patients is strong. Utilizing the patient-reported questionnaires when age appropriate is best. In this era of increased outcome reporting, PedsQL may be a valuable tool.

Is the damage of cartilage a global or localized phenomenon in hip dysplasia, measured by dGEMRIC?

BACKGROUND: The mechanism of damage in osteoarthritis is believed to be multifactorial where mechanical and biological factors are important in its initiation and progression. Hip dysplasia is a classic model of increased mechanical loading on cartilage attributable to insufficient acetabular coverage that leads to osteoarthritis. If the damage is all attributable to direct mechanical damage then one initially would expect only local, not global changes. QUESTIONS/PURPOSES: We hypothesize that in hip dysplasia although the elevated cumulative contact stresses are localized, the damage to cartilage is biologically mediated, therefore, biochemical changes will be global. METHODS: Thirty-two patients with symptomatic hip dysplasia were scanned using a 1.5-T MRI scanner. We used a high-resolution three-dimensional dGEMRIC technique to characterize the distribution of cartilage damage in dysplastic hips. High-resolution isotropic acquisition was reformatted around the femoral neck axis and the dGEMRIC index was calculated separately for femoral and acetabular cartilages. Joint space widths also were evaluated in each reformatted slice. Each hip was characterized by the presence or absence of joint migration and by Tönnis grade. RESULTS: The global dGEMRIC index correlated with the dGEMRIC indices of individual regions with the highest correlations occurring in the anterosuperior to posterosuperior regions. The corresponding correlations for joint space width were uniformly lower, suggesting that tissue loss is a more local phenomenon. Higher Tönnis grades and hips with joint migration were associated with lower dGEMRIC indices. CONCLUSIONS: The dGEMRIC index shows a global decrease, whereas tissue loss is more localized. This suggests that hip osteoarthritis in acetabular dysplasia is a biologically mediated event that affects the entire joint.

Shoulder motion, strength, and functional outcomes in children with established malunion of the clavicle.

BACKGROUND: Recent investigations of displaced clavicle fractures in adults have demonstrated a higher prevalence of nonunion, symptomatic malunion, diminished functional outcome, and decreased strength with nonoperative treatment. Although these data have led to increased surgical management of displaced fractures, little published information is available regarding the consequences of malunion in the pediatric population. The purpose of this investigation was to assess pain, functional outcome, range of motion, and strength in children with displaced clavicle fractures treated nonoperatively. METHODS: Clinical evaluation of 16 patients with mid-diaphyseal clavicle fractures and >2 cm of initial displacement was performed; all had undergone nonoperative treatment and went on to radiographic malunion. The mean age at the time of injury was 12.2±3.3 years. Pain, aesthetic appearance, and satisfaction with treatment were rated by patients on a visual analog scale (VAS) (range 0 to 10 with 10 indicating the worst score). Patient-based outcomes were assessed with the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and the Pediatric Outcomes Data Collection Instrument (PODCI). Bilateral shoulder motion was measured by a physical therapist. Isokinetic strength testing of the bilateral shoulders was performed with a Biodex dynometer. Range of motion and strength were analyzed with a multivariable regression, controlling for hand dominance. The mean follow-up was 27.2 months after injury. RESULTS: All displaced fractures treated nonoperatively achieved union. Overall, there was reduced forward flexion and abduction on the injured side compared with the contralateral sides of 7.3 and 6.5 degrees, respectively, adjusted for hand dominance (P<0.05). Biodex testing did not detect any significant difference in abduction or adduction torque or power between affected and unaffected shoulders. The mean VAS score for pain was 1.6, with 4 patients reporting pain ≥to 3. The mean VAS scores for satisfaction with aesthetic appearance was 2.7, with 4 patients reporting scores >5. The mean VAS scores for satisfaction with treatment was 2.0, with only 1 patient scoring >5. The mean DASH score was 4.9±7.5, with 3 patients scoring ≥10. The mean scores on the DASH sports and performing arts module was 1.9±4.2, with only 1 patient scoring ≥10. The mean global PODCI score was 94.5±6.0. The mean PODCI scores for upper extremity function, sports, and pain were 97.9±5.5, 95.4±5.3, and 84.6±20.5, respectively. Only 1 patient was symptomatic enough to require corrective osteotomy. CONCLUSIONS: Skeletally immature patients with established clavicle fracture malunions do not develop clinically meaningful loss of shoulder motion or abduction/adduction strength. Routine surgical fixation for displaced, nonsegmental clavicle fractures may not be justified based upon concerns regarding shoulder motion and strength alone. Further investigation is required to determine the risk factors and causes of pain and functional compromise in the minority of pediatric patients with symptomatic malunions. LEVEL OF EVIDENCE: Level IV.

Prospective evaluation of a prenatal sonographic clubfoot classification system.

BACKGROUND: The purpose of this study was to prospectively evaluate our recently described fetal sonographic classification system for prenatal diagnosis of clubfoot. METHODS: Over 18 months, we prospectively enrolled consecutive pregnant patients evaluated for a prenatally diagnosed clubfoot. Prenatal sonographic scores assigned by a radiologist were compared to final clinical diagnosis and severity given by a pediatric orthopedic surgeon. Pearson's χ(2) test and logistic regression were used in statistical analyses on the subject level. Generalized estimating equations were used in analyses on the foot level to account for intrasubject correlation. RESULTS: There were 50 subjects, with 26 unilateral and 24 bilateral clubfeet, according to the prenatal ultrasound (US). A total of 51 (69%) of 74 feet and 36 (72%) of 50 subjects had a postnatal diagnosis of clubfoot. The accuracy of diagnosis in cases of a severe, moderate, and mild US score was 94, 70, and 25%, respectively (p = 0.003 comparing moderate-severe vs. mild). US severity correlated with the Dimeglio classification scoring system (Spearman's correlation 0.30). CONCLUSION: The fetal sonographic scoring system is predictive of clinical severity after birth, and improves the ability to counsel families with a prenatal diagnosis of clubfoot.

Trends in anti-D immune globulin for childhood immune thrombocytopenia: usage, response rates, and adverse effects.

In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D. Anti-D was the second most commonly prescribed drug for ITP from 2003 to 2010 overall and was given first most frequently (41%). Sixty-four percent of patients responded to anti-D, but 36% had adverse effects, including five patients requiring hospitalization. From 2003 to 2010, the use of anti-D as an initial therapy for ITP significantly decreased (P < 0.001). This trend preceded the 2010 FDA black box warning. In our experience, anti-D was associated with a significant number of adverse effects when used as a treatment for ITP, although none were life-threatening. Despite recent guidelines suggesting anti-D therapy for initial treatment for ITP, anti-D therapy for ITP has significantly decreased over the past 7 years.

Applicability of 2009 international consensus terminology and criteria for immune thrombocytopenia to a clinical pediatric population.

BACKGROUND: Since pediatric immune thrombocytopenia (ITP) is relatively infrequent, comparisons among clinical studies are critical but have previously been limited by differences in terminology. In 2009, an international working group (IWG) developed consensus criteria to enhance comparability in future studies in adults and children. METHODS: We performed a retrospective medical record review of all pediatric ITP patients seen at a single children's hospital with a first visit between 2003 and 2010 and applied both historical (criteria(Hist) ) and IWG (criteria(IWG) ) ITP criteria to available clinical data. RESULTS: Among the 505 patients seen for ITP over 7 years, 98% could be classified as "acute" or "chronic" ITP using the criteria(Hist) , while only 90.7% could be classified as "newly diagnosed," "persistent," or "chronic" ITP using the criteria(IWG) (P < 0.01). Only 33.7% met criteria(IWG) for severe ITP, whereas 77.4% met criteria(Hist) for severe ITP. A striking difference was that overall response to therapies was lower if the criteria(IWG) were used rather than the criteria(Hist) , particularly for IVIG (55.4% vs. 70%, P = 0.02) and rituximab (35.3% vs. 83.3% P = 0.05). Only 2 subjects (0.4%) met the criteria(IWG) for refractory ITP. CONCLUSIONS: Most ITP patients could easily be classified using the 2009 criteria(IWG) . Limitations to applying the criteria(IWG) included absence of treatment response durations, incomplete definition of pediatric "refractory ITP," and exclusion of secondary ITP. Nevertheless, the criteria(IWG) were more clinically relevant given the reliance on definitions based on bleeding and their ability to be applied prospectively. The utility of using the criteria(IWG) within prospective trials remains to be determined.

Response to steroids predicts response to rituximab in pediatric chronic immune thrombocytopenia.

BACKGROUND: Treatment choice in pediatric immune thrombocytopenia (ITP) is arbitrary, because few studies are powered to identify predictors of therapy response. Increasingly, rituximab is becoming a treatment of choice in those refractory to other therapies. METHODS: The objective of this study was to evaluate univariate and multivariable predictors of platelet count response to rituximab. After local IRB approval, 565 patients with chronic ITP enrolled and met criteria for this study in the longitudinal, North American Chronic ITP Registry (NACIR) between January 2004 and October 2010. Treatment response was defined as a post-treatment platelet count ≥ 50,000/µl within 16 weeks of rituximab and 14 days of steroids. Treatment response data were captured both retrospectively at enrollment and then prospectively. RESULTS: Eighty (14.2%) patients were treated with rituximab with an overall response rate of 63.8% (51/80). Univariate correlates of response to rituximab included the presence of secondary ITP and a positive response to steroids. In multivariable analysis, response to steroids remained a strong correlate of response to rituximab, OR 6.8 (95% CI 2.0-23.0, P = 0.002). Secondary ITP also remained a strong predictor of response to rituximab, OR 5.6 (95% CI 1.1-28.6, P = 0.04). Although 87.5% of patients who responded to steroids responded to rituximab, 48% with a negative response to steroids did respond to rituximab. CONCLUSION: In the NACIR, response to steroids and presence of secondary ITP were strong correlates of response to rituximab, a finding not previously reported in children or adults.

Design and validation of a high-throughput matrix-assisted laser desorption ionization time-of-flight mass spectrometry method for quantification of hepcidin in human plasma.

Disorders of iron metabolism affect over a billion people worldwide. The circulating peptide hormone hepcidin, the central regulator of iron distribution in mammals, holds great diagnostic potential for an array of iron-associated disorders, including iron loading (ß-thalassemia), iron overload (hereditary hemochromatosis), and iron deficiency diseases. We describe a novel high-throughput matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry assay for quantification of hepcidin in human plasma. This assay involves enrichment using a functionalized MALDI chip, a novel solvent-detergent precipitation buffer, and quantification using a stable isotope labeled internal standard. The linear range of hepcidin in plasma was 1-120 nM, with a low limit of quantification (LOQ) (1 nM), high accuracy (<15% relative error (RE)), and high precision (intraday average 5.52-18.48% coefficient of variation (CV) and interday 9.32-14.83% CV). The assay showed strong correlation with an established hepcidin immunoassay (Spearman; R(2) = 0.839 n = 93 ethylenediaminetetraacetic acid (EDTA) plasma). A collection of normal healthy pediatric samples (range 3.8-32.5 ng/mL; mean 12.9 ng/mL; n = 119) showed significant differences from an adult collection (range 1.8-48.7 ng/mL; mean 16.1 ng/mL; n = 95; P = 0.0096). We discuss these preliminary reference ranges and correlations with additional parameters in light of the utility and limitations of hepcidin measurements as a stand-alone diagnostic and as a tool for therapeutic intervention.

Risk factors for parenteral nutrition­associated liver disease following surgical therapy for necrotizing enterocolitis: A Glaser Pediatric Research Network Study [corrected].

OBJECTIVE: The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children. PATIENTS AND METHODS: : From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥ 2 mg/dL or ALT ≥ 2 × the upper limit of normal in the absence of sepsis after ≥ 14 days of exposure to PN. RESULTS: Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97-12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56-3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5-4.7; P = 0.001) times greater in patients with ≥ 4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD. CONCLUSIONS: The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.

The Effect of Casting Simulation on Maintenance of Fracture Alignment Following Closed Reduction of Pediatric Distal Radius Fractures: Does More Simulation Matter?

BACKGROUND: The purpose of this study was to evaluate the effectiveness of a simulation curriculum on performance of closed reduction (CR) and casting of distal radius and distal both-bone forearm fractures by orthopaedic surgery residents. The secondary aim was to identify if repeated simulation training during the clinical rotation provided additional benefit. METHODS: Orthopaedic surgery residents performed simulated distal radius fracture (DRF) reduction and cast application near the beginning and end of their 6-month pediatric orthopaedic clinical rotation at a tertiary care children's hospital. A subgroup of trainees were randomly assigned additional simulation training halfway through their rotation. Clinically, 28 residents treated 159 distal radius and/or distal both-bone forearm fractures with CR and casting during the study period. Radiographic evaluations were performed comparing postreduction fracture angulation, displacement, cast index, and loss of reduction (LOR) rates at the beginning of a resident's rotation (presimulation cases) and at the end of the resident's rotation (postsimulation cases). Comparisons were also made between residents who had and did not have additional simulation training exposure during their rotation. RESULTS: Overall, postreduction radius angulation, maximal angulation, and cast index were lower in the postsimulation group than in the presimulation group with means 1.8°, 2.6°, and 0.75 vs 4.0°, 4.4° and 0.77, respectively. LOR rate was also lower (14% vs 30%). No significant differences were demonstrated for postreduction ulna angulation as well as for radius, ulna, or maximal displacement between these 2 groups. No significant differences were observed in radiographic parameters, cast indices, or LOR rates between residents who underwent additional mid-rotation training vs those who did not. CONCLUSIONS: The incorporation of a simulation training curriculum for CR and casting of pediatric distal forearm fractures resulted in statistically significant, however, marginally improved postreduction radiographic parameters and LOR rates among orthopaedic residents. The utility of repeated additional simulation training during the course of a clinical rotation remains unclear in the short term.

Tibial tubercle fractures in children and adolescents: a large retrospective case series.

To report patient characteristics, fracture types, treatment methods, early clinical outcomes and complications of children and adolescents treated for tibial tubercle fractures. Retrospective case series of patients 18 years old and younger treated for tibial tubercle fractures at a single institution from 1995 to 2015. Clinical and radiographic outcomes were reported at minimum six-month follow-up. In 228 patients, 236 tibial tubercle fractures were identified, of whom, 198 (87%) were males. Mean age and BMI was 14.3 years and 25.0, respectively. Pre-existing Osgood-Schlatter disease was identified in 31% cases and was most commonly associated with type I fractures (P < 0.001). Most fractures occurred while participating in athletics (86%). Initial treatment was surgical for 67% fractures. Type III fractures were most common (41%), followed by type I (29%). Type I fractures were most commonly treated nonoperatively (91%) and types II-V fractures were most commonly treated surgically (89%, P < 0.001). Compartment syndrome was identified in 4 (2%) patients, 3 of which had type IV fractures. Most patients returned to sports (88%). Tibial tubercle fractures are sports-related injuries and occur most commonly in adolescent males. They can be associated with pre-existing Osgood-Schlatter disease, a higher than average BMI, and a small but relevant risk of compartment syndrome. Following treatment, most patients return to sports participation.

PerR confers phagocytic killing resistance and allows pharyngeal colonization by group A Streptococcus.

The peroxide response transcriptional regulator, PerR, is thought to contribute to virulence of group A Streptococcus (GAS); however, the specific mechanism through which it enhances adaptation for survival in the human host remains unknown. Here, we identify a critical role of PerR-regulated gene expression in GAS phagocytosis resistance and in virulence during pharyngeal infection. Deletion of perR in M-type 3 strain 003Sm was associated with reduced resistance to phagocytic killing in human blood and by murine macrophages in vitro. The increased phagocytic killing of the perR mutant was abrogated in the presence of the general oxidative burst inhibitor diphenyleneiodonium chloride (DPI), a result that suggests PerR-dependent gene expression counteracts the phagocyte oxidative burst. Moreover, an isogenic perR mutant was severely attenuated in a baboon model of GAS pharyngitis. In competitive infection experiments, the perR mutant was cleared from two animals at 24 h and from four of five animals by day 14, in sharp contrast to wild-type bacteria that persisted in the same five animals for 28 to 42 d. GAS genomic microarrays were used to compare wild-type and perR mutant transcriptomes in order to characterize the PerR regulon of GAS. These studies identified 42 PerR-dependent loci, the majority of which had not been previously recognized. Surprisingly, a large proportion of these loci are involved in sugar utilization and transport, in addition to oxidative stress adaptive responses and virulence. This finding suggests a novel role for PerR in mediating sugar uptake and utilization that, together with phagocytic killing resistance, may contribute to GAS fitness in the infected host. We conclude that PerR controls expression of a diverse regulon that enhances GAS resistance to phagocytic killing and allows adaptation for survival in the pharynx.

Risk factors for intestinal failure in infants with necrotizing enterocolitis: a Glaser Pediatric Research Network study.

OBJECTIVE: To determine risk factors for intestinal failure (IF) in infants undergoing surgery for necrotizing enterocolitis (NEC). STUDY DESIGN: Infants were enrolled in a multicenter prospective cohort study. IF was defined as the requirement for parenteral nutrition for >or= 90 days. Logistic regression was used to identify predictors of IF. RESULTS: Among 473 patients enrolled, 129 had surgery and had adequate follow-up data, and of these patients, 54 (42%) developed IF. Of the 265 patients who did not require surgery, 6 (2%) developed IF (OR 31.1, 95% CI, 12.9 - 75.1, P < .001). Multivariate analysis identified the following risk factors for IF: use of parenteral antibiotics on the day of NEC diagnosis (OR = 16.61, P = .022); birth weight < 750 grams, (OR = 9.09, P < .001); requirement for mechanical ventilation on the day of NEC diagnosis (OR = 6.16, P = .009); exposure to enteral feeding before NEC diagnosis (OR=4.05, P = .048); and percentage of small bowel resected (OR = 1.85 per 10 percentage point greater resection, P = .031). CONCLUSION: The incidence of IF among infants undergoing surgical treatment for NEC is high. Variables characteristic of severe NEC (low birth weight, antibiotic use, ventilator use, and greater extent of bowel resection) were associated with the development of IF.

Assessment of psychological distress among children and adolescents with food allergy.

BACKGROUND: Youth with food allergy may experience psychosocial stressors including limitations in activities, differences from peers, and anxiety. Factors such as allergy-related medical history, children's attitudes toward their allergies, and parental anxiety may function as risk and resilience factors associated with psychological distress in this population. OBJECTIVE: To assess mean scores and rates of elevated scores on standardized measures of psychological distress among youth with food allergy and identify factors associated with distress. METHODS: A total of 141 mothers of children age 2 to 17 years with food allergy completed questionnaires about child medical history, child anxiety and depressive symptoms, and maternal anxiety symptoms. A total of 69 children age 8 to 17 years completed self-report measures of anxiety and depressive symptoms, social stress, and attitudes toward food allergy. RESULTS: Mean scores on self-report and parent-report measures of child anxiety symptoms, depressive symptoms, and social stress fell in the average range on standardized measures of child distress. Comparisons with normative scores generally indicated either no differences or lower rates of distress in our sample of youth with food allergy, with the exception of child-reported anxious coping and separation anxiety symptoms, which were significantly higher than normative scores. Maternal reports of child symptoms were significantly higher than child self-reports. Multiple regression analyses yielded models in which child attitudes toward food allergy and maternal anxiety were associated with child distress for children 8 to 17 years old. CONCLUSION: Results suggest targets for prevention of distress, including assessment of attitudes toward food allergy and support for parental anxiety management.