The Use of Biomarkers in the Early Diagnosis of Septic Arthritis and Osteomyelitis-A Pilot Study.

BACKGROUND: The diagnosis of septic arthritis (SA) and osteomyelitis (OM) has remained challenging in the pediatric population, often accompanied by delays and requiring invasive interventions. The purpose of this pilot study is to identify a novel panel of biomarkers and cytokines that can accurately differentiate SA and OM at initial presentation using serum alone. METHODS: Twenty patients below 18 years old whose working diagnosis included SA (n=10) and OM (n=10) were identified. Serum was collected at initial evaluation. Each sample underwent seven ELISA [C1-C2, COMP, CS-846, hyaluronan, procalcitonin, PIIANP, C-terminal telopeptide of type II collagen (CTX-II)] and 65-plex cytokine panels. Principal component and Lasso regression analysis were performed to identify a limited set of predictive biomarkers. RESULTS: Mean age was 4.7 and 9.5 years in SA and OM patients, respectively (P=0.029). 50% of SA patients presented within 24 hours of symptom onset, compared with 0% of OM patients (P=0.033). 30% of SA patients were discharged home with an incorrect diagnosis and re-presented to the emergency department days later. At time of presentation: temperature ≥38.5°C was present in 10% of SA and 40% of OM patients (P=0.12), mean erythrocyte sedimentation rate (mm/h) was 51.6 in SA and 44.9 in OM patients (P=0.63), mean C-reactive protein (mg/dL) was 55.8 in SA and 71.8 in OM patients (P=0.53), and mean white blood cells (K/mm3) was 12.5 in SA and 10.4 in OM patients (P=0.34). 90% of SA patients presented with ≤2 of the Kocher criteria. 100% of SA and 40% of OM patients underwent surgery. 70% of SA cultures were culture negative, 10% MSSA, 10% Kingella, and 10% Strep pyogenes. 40% of OM cultures were culture negative, 50% MSSA, and 10% MRSA. Four biomarkers [CTx-II, transforming growth factor alpha (TGF-α), monocyte chemoattractant protein 1 (MCP-1), B cell-attracting chemokine 1] were identified that were able to classify and differentiate 18 of the 20 SA and OM cases correctly, with 90% sensitivity and 80% specificity. CONCLUSIONS: This pilot study identifies a panel of biomarkers that can differentiate between SA and OM at initial presentation using serum alone. LEVEL OF EVIDENCE: Level II-diagnostic study.

Pilot Study Analysis of Serum Cytokines to Differentiate Pediatric Septic Arthritis and Transient Synovitis.

BACKGROUND: In pediatric patients, the presentation of the nontraumatic acutely painful joint/limb poses a diagnostic dilemma due to the similarity of presentations of the most likely diagnoses [septic arthritis (SA), transient synovitis (TS), osteomyelitis]. Current tools employed to differentiate these diagnoses rely on nonspecific inflammatory markers, radiologic imaging, and arthrocentesis. Diagnostic algorithms utilizing these clinical, radiographic, and biochemical parameters have produced conflicting results. The purpose of this study was to identify a serum-based inflammatory signature which can differentiate SA from TS in pediatric patients. METHODS: Serum samples were collected from 22 pediatric patients presenting with joint/extremity pain whose working diagnosis included SA or TS. Each sample was analyzed for serum abundance of 72 distinct biomarkers and cytokines using enzyme linked immunosorbent assay based arrays. Linear discriminant analysis was performed to identify a combinatorial biomarker panel to predict a diagnosis of SA or TS. Efficacy of the biomarker panel was compared with definitive diagnoses as based on laboratory tests, arthrocentesis results, and clinical scenario. RESULTS: At the time of presentation: (1) mean erythrocyte sedimentation rate in the SA group was 56.6 mm/h and 12.4 mm/h in the TS group (P<0.001), (2) mean C-reactive protein was 55.9 mg/dL in the SA group and 13.7 mg/dL in the TS group (P=0.12), and (3) mean white blood cell was 10.9 k/mm3 in the SA group and 11.0 k/mm3 in the TS group (P=0.95). A combined panel of 72 biomarkers was examined using discriminant analysis to identify a limited set of predictors which could accurately predict whether a patient was diagnosed with SA or TS. A diagnostic algorithm consisting of transforming growth factor alpha, interleukin (IL)-7, IL-33, and IL-28A serum concentration correctly classified 20 of the 22 cases with a sensitivity and specificity of 90.9% (95% confidence interval: 73.9%-100.0%). CONCLUSION: This study identifies a novel serum-based 4-cytokine panel that accurately differentiates SA from TS in pediatric patients with joint/limb pain. LEVEL OF EVIDENCE: Level II-diagnostic study.

Organ System Anomalies Associated With Congenital Scoliosis: A Retrospective Study of 305 Patients.

DESIGN: Retrospective analyses of congenital scoliosis patients at 2 tertiary care pediatric hospitals. OBJECTIVE: This study objectives were (1) to report the rates of anomalies of 10 organ systems in congenital scoliosis patients and (2) to determine whether the presence of a single organ system anomaly increases the rate of nonspinal organ system defects. SUMMARY OF BACKGROUND DATA: Intraspinal, cardiac, renal, and gastrointestinal anomalies have been reported to occur at higher rates in congenital scoliosis than the normal population. It is unknown whether the presence of 1 organ system defect increases the risk of nonspinal organ system anomalies. METHODS: All patients diagnosed, evaluated in the outpatient setting, with congenital scoliosis who were below 18 years of age at time of presentation with available cardiac echo, renal ultrasound, or magnetic resonance imaging were included in this study. RESULTS: There were 305 patients (161 females, 53%) whose mean age was 7+3 years. In total, 84% of patients were observed to have at least 1 organ defect. Overall, 22% of patients had 1 organ defect, 19% had 2, 18% had 3, and 18% had ≥4 organ defects. There was an average of 2.2 anomalies per patient (range=0 to 8). Intraspinal anomalies were documented in 43% of patients; syrinx occurred most frequently. Urogenital anomalies were documented in 39% of patients; solitary kidney was most prevalent. Cardiac anomalies were documented in 54% of patients; ventricular septal defect was most common. In 12% of patients, the triad of spinal, urogenital, and cardiac defects was observed. Multiple organ systems were found to have significant associations (P<0.05) in anomaly development. CONCLUSIONS: Cardiac anomalies were the most common defect (54%), and occurred at a rate >2 times higher than previously reported. The high rate of intraspinal, cardiac, and urogenital defects makes magnetic resonance imaging, echocardiography, and renal ultrasound a critical part of evaluation for all congenital scoliosis patients. LEVEL OF EVIDENCE: Level II.

Ogden Type I to III tibial tubercle fractures in skeletally immature patients: is routine anterior compartment fasciotomy of the leg indicated?

PURPOSE: Determine the frequency of compartment syndrome of the leg after displaced, operatively treated modified Ogden I to III tibial tubercle fractures (TTFxs), evaluate the preoperative assessment and use of advanced imaging, and need for prophylactic fasciotomies. METHODS: Retrospective analysis of operatively treated, displaced modified Ogden I to III TTFxs, at our level 1 paediatric trauma centre between 2007 and 2019. Modified Ogden Type IV and V fracture patterns were excluded. Fracture patterns were determined by plain radiographs. RESULTS: There were 49 modified Ogden I to III TTFxs in 48 patients. None had signs nor symptoms of vascular compromise, compartment syndromes or impending compartment syndromes preoperatively. In all, 13 of the 49 fractures underwent anterior compartment fasciotomy at surgery; eight of the 13 had traumatic fascial disruptions, which were extended surgically. All incisions were primarily closed. There were no instances of postoperative compartment syndromes, growth arrest, leg-length discrepancy or recurvatum deformity postoperatively. All patients achieved radiographic union and achieved full range of movement. CONCLUSION: The potentially devastating complications of compartment syndrome or vascular compromise following TTFx did not occur in this consecutive series of patients over 12 years. The presence of an intact posterior proximal tibial physis and posterior metaphyseal cortex (Modified Ogden TTFx Type I to III) may mitigate the occurrence of vascular injury and compartment syndrome. Plain radiographs appear appropriate as the primary method of imaging TTFxs, with use of advanced imaging as the clinical scenario dictates. Routine, prophylactic fasciotomies do not appear necessary in Ogden I to III TTFxs, but should be performed for signs and symptoms of compartment syndrome. LEVEL OF EVIDENCE: Level IV.

Impact of Spinal Deformity Characteristics on Patient-reported Outcome Measurement Information System Scores in Patients With Idiopathic Scoliosis Undergoing Posterior Spinal Fusion.

INTRODUCTION: The impact of posterior spinal fusion (PSF) on physical function and pain and mental health in pediatric patients as quantified by the Patient-Reported Outcomes Measurement Information System (PROMIS), developed by the National Institute of Health, is largely unknown. The purpose of this study is to report the changes of PROMIS scores for upper extremity (UE), pain interference (PI), mobility (MOB), and peer relationships (PR) after PSF in patients with idiopathic scoliosis (IS), compare postoperative changes in PROMIS PI and Scoliosis Research Society-30 pain scores, and evaluate associations between curve characteristics and PROMIS scores. METHODS: A retrospective cohort of 122 patients (<18 years old) who underwent PSF for IS was identified through electronic medical record search. PROMIS scores were obtained preoperatively and 6 weeks, 6 months, 1 years, 2 years, and 3 years postoperatively. RESULTS: The mean age of the cohort was 14.2 ± 1.6 years, and the mean Cobb angle was 62.9 ± 13.8° at surgery. Eighty patients had preoperative PROMIS data. UE and MOB scores were statistically lower at 6 weeks and 6 months postoperatively and returned to baseline with a longer follow-up. PI scores were significantly lower at 1 and 2 years postoperatively. PR was unchanged up to 2 years postoperatively and then showed significant improvement. There was a statistically significant negative relationships between lowest instrumented vertebra and PROMIS UE and MOB scores at 6 weeks and 1 year postoperatively, but not at a longer follow-up. There were no significant differences noted in PI and PR PROMIS scores and lowest instrumented vertebra. PROMIS scores were not statistically associated with the Lenke Classification, number of vertebral levels fused, or percentage coronal correction. DISCUSSION: Changes in PROMIS functional domains (UE and MOB) postoperatively normalize at longer follow-ups. Changes in PI and PR demonstrated improvements over preoperative values at 1 to 2 years postoperatively. Preoperative coronal and sagittal measures, and the percentage correction did not correlate with any PROMIS scores.