CD43-positive, EWSR1::FLI1 -rearranged Soft Tissue Sarcoma in a Pediatric Patient With History of B-Cell Acute Lymphoblastic Leukemia.

Ewing sarcoma is a small round blue cell tumor typically characterized by an EWSR1 rearrangement and expression of CD99 and NKX2.2, without expression of hematopoietic markers such as CD45. CD43 is an alternative hematopoietic immunohistochemical marker often utilized in the workup of these tumors and its expression typically argues against Ewing sarcoma. We report a 10-year-old with history of B-cell acute lymphoblastic leukemia presenting with an unusual malignant shoulder mass with variable CD43 positivity, but with an EWSR1::FLI1 fusion detected by RNA sequencing. Her challenging workup highlights the utility of next-generation DNA-based and RNA-based sequencing methods in cases with unclear or conflicting immunohistochemical results.

Poor Outcomes of Pediatric Acute Compartment Syndrome in the Setting of Extracorporeal Membrane Oxygenation: A Multicenter Case Series.

BACKGROUND: Acute compartment syndrome (ACS) is a well-described condition that merits emergent surgical decompression. Peripheral arterial cannulation can increase the likelihood of ACS in patients requiring extracorporeal membranous oxygen (ECMO). Comorbidities in these critically ill patients may portend negative consequences of decompressive fasciotomy. This study investigated the clinical short-term and mid-term outcomes in pediatric patients with ECMO-associated ACS. METHODS: This is a retrospective case series at 3 pediatric hospitals from 2006 to 2019, including children ages 0 to 19 years who underwent peripheral arterial cannulation and developed ACS. RESULTS: Eighteen patients developed ACS after receiving peripheral cannulation ECMO. Mean time to diagnosis after cannulation was 63.1 hours. All patients were diagnosed clinically; the most common findings were tight compartments, swelling, and loss of peripheral pulses. Eight patients (44%) died due to underlying illness. Treating physicians decided against decompression for 5 patients due to their underlying illness, instability, and concern for infection. Thirteen patients (72%) underwent decompressive fasciotomies. Ten surgical patients required subsequent surgeries and 6 (33%) developed surgical site infections. Of the 7 surviving surgical patients, 4 (57%) required extremity amputations and 4 had lower extremity neurological deficits on follow-up. Two of 3 nonsurgical patients (66%) had functional lower extremity motor deficits on follow-up. No surviving nonoperative patients developed infections or required amputations. CONCLUSIONS: ACS on ECMO is associated with high rates of complications including neurologic deficits, infection, and amputation. Patients treated nonoperatively avoided complications such as infection and amputation, but had more functional neurological deficits than surgical patients. Orthopaedic surgeons should consider the high morbidity of compartment release in these critically ill patients and, with critical care teams, assess whether the potential benefits of surgery outweigh expected risks. LEVEL OF EVIDENCE: Level IV.

Pediatric Tumor Management: Current and Controversial.

Bone and soft-tissue tumors are common in the pediatric population. It is important to be familiar with the appropriate workup, principles of biopsy, differences between unicameral and aneurysmal bone cysts, and principles of managing pathologic fractures in children. The management approach to pediatric soft-tissue masses and some of the recent advances in the field warrant discussion.

Management of Pediatric Type I Open Fractures in the Emergency Department or Operating Room: A Multicenter Perspective.

BACKGROUND: The management of pediatric type I open fractures remains controversial. The aim of this study is to compare outcomes in type I open fractures managed with superficial wound debridement and antibiotics in the emergency department (ED) (nonoperative management) to patients managed with operative debridement and antibiotics (operative management). METHODS: A multicenter retrospective review was performed of all pediatric type I open forearm, wrist, and tibia fractures treated at 4 high volume pediatric centers between 2000 and 2015. Patients with multiple traumatic injuries, immunocompromised patients, or those without final radiographs indicating healing were excluded. RESULTS: In total, 219 patients met inclusion criteria. A total of 170 fractures were treated operatively (77.6%), 49 fractures were treated nonoperatively (22.4%). There was 1 infection in the nonoperative group (2.0% infection rate), and no infections in the operatively managed group (P=0.062). Cefazolin was the most commonly administered antibiotic (88.1% of patients). Duration of hospital-administered antibiotics was significantly different, with a mean of 10.9 hours in the nonoperative group and 41.6 hours in the operative group (P<0.001). Length of stay averaged 16.3 hours for nonoperative patients and 48.6 hours for the operatively treated patients (P<0.001). In the nonoperative group, 44/49 had documented superficial wound debridement in the ED utilizing, on an average, 1500 mL of irrigant. There were 10 other complications, 9 in the operative group (5.4%) and 2 in the nonoperative group (4.1%, P=0.107), including 2 compartment syndromes and 1 acute carpal tunnel syndrome all requiring immediate surgical release (1.8%) in the operative group. CONCLUSIONS: There was no significant difference in infection rate or complication rate in those managed with antibiotics and operative debridement versus those managed with superficial wound debridement and antibiotics in the ED. Consideration should be given to the similar safety profiles for these 2 treatment modalities when managing pediatric patients with type I open fractures. LEVEL OF EVIDENCE: Level III.

Systematic review and meta-analysis of objective and subjective quality of life among pediatric, adolescent, and young adult bone tumor survivors.

BACKGROUND: Pediatric, adolescent, and young adult survivors of bone sarcomas are at risk for poor quality of life (QOL). We conducted a systematic review and meta-analysis to summarize the literature describing QOL in this population and differences in QOL based on local control procedures. PROCEDURE: Included studies described ≥5 patients <25 years old who had completed local control treatment for bone sarcoma, defined QOL as a main outcome, and measured it with a validated instrument. Data extraction and quality assessments were conducted with standardized tools. Meta-analyses compared QOL based on surgical procedure (limb-sparing vs. amputation) and were stratified by assessment type (objective physical function, clinician-assessed disability, patient-reported disability, and patient-reported QOL). Effect sizes were reported as the standard mean difference when multiple instruments were used within a comparison and weighted mean difference otherwise. All were weighted by inverse variance and modeled with random effects. RESULTS: Twenty-two of 452 unique manuscripts were included in qualitative syntheses, eight of which were included in meta-analyses. Manuscripts were heterogeneous with respect to included patient populations (age, tumor type, time since treatment) and QOL instruments. Prospective studies suggested that QOL improves over time, and that female sex and older age at diagnosis are associated with poor QOL. Meta-analyses showed no differences in outcomes between patients who underwent limb-sparing versus amputation for local control. CONCLUSION: QOL studies among children and AYAs with bone sarcoma are remarkably diverse, making it difficult to detect trends in patient outcomes. Future research should focus on standardized QOL instruments and interpretations.

Increasing Cases of Chronic Nonbacterial Osteomyelitis in Children: A Series of 215 Cases From a Single Tertiary Referral Center.

OBJECTIVE: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disease that is gaining recognition from clinicians and researchers. We aim to publish data from our cohort of patients with CNO living in the northwestern United States to increase the awareness of specific demographics, characteristics, and presentation of this rare disease. METHODS: A retrospective chart review was performed of our electronic medical records. Patients with complete chart records who met criteria for a diagnosis of CNO from 2005 to 2019 were included. Extracted data including patient demographics, bone biopsy results, and lesion locations on advanced imaging were analyzed. King County census data were used to calculate the annual new case rate within our center. RESULTS: A total of 215 CNO cases were diagnosed at our large tertiary pediatric hospital. The majority of cases were of White race residing in Washington's most populous county, King County. Most cases were diagnosed in 2016 to 2019, showing a significant increase in the annual case rate from 8 to 23 per million children in King County, though there did not appear to be a seasonal predilection. Biopsy rate decreased from 75% to 52%. One hundred fifty-two (71%) children had family history of autoimmunity. With increasing use of whole-body magnetic resonance imaging (WB-MRI), results showed 68% had multiple lesions. CONCLUSION: CNO has been diagnosed at an increased rate in recent years. WB-MRI may assist in identifying other lesions that may be asymptomatic on presentation. Bone biopsy is still required in some children at the time of diagnosis.

Computational fluid dynamics modeling aiding surgical planning in a toddler with Parkes Weber syndrome.

Parkes Weber syndrome is a fast-flow and slow-flow vascular anomaly with limb overgrowth that can lead to congestive heart failure and limb ischemia. Current management strategies have focused on symptom management with focal embolization. A pediatric case with early onset heart failure is reported. We discuss the use of computational fluid dynamics (CFD) modeling to guide a surgical management strategy in a toddler with an MAP2K1 mutation.

Defining the volume of consultations for musculoskeletal infection encountered by pediatric orthopaedic services in the United States.

OBJECTIVE: Adequate resources are required to rapidly diagnose and treat pediatric musculoskeletal infection (MSKI). The workload MSKI consults contribute to pediatric orthopaedic services is unknown as prior epidemiologic studies are variable and negative work-ups are not included in national discharge databases. The hypothesis was tested that MSKI consults constitute a substantial volume of total consultations for pediatric orthopaedic services across the United States. STUDY DESIGN: Eighteen institutions from the Children's ORthopaedic Trauma and Infection Consortium for Evidence-based Study (CORTICES) group retrospectively reviewed a minimum of 1 year of hospital data, reporting the total number of surgeons, total consultations, and MSKI-related consultations. Consultations were classified by the location of consultation (emergency department or inpatient). Culture positivity rate and pathogens were also reported. RESULTS: 87,449 total orthopaedic consultations and 7,814 MSKI-related consultations performed by 229 pediatric orthopaedic surgeons were reviewed. There was an average of 13 orthopaedic surgeons per site each performing an average of 154 consultations per year. On average, 9% of consultations were MSKI related and 37% of these consults yielded positive cultures. Finally, a weak inverse monotonic relationship was noted between percent culture positivity and percent of total orthopedic consults for MSKI. CONCLUSION: At large, academic pediatric tertiary care centers, pediatric orthopaedic services consult on an average of ~3,000 'rule-out' MSKI cases annually. These patients account for nearly 1 in 10 orthopaedic consultations, of which 1 in 3 are culture positive. Considering that 2 in 3 consultations were culture negative, estimating resources required for pediatric orthopaedic consult services to work up and treat children based on culture positive administrative discharge data underestimates clinical need. Finally, ascertainment bias must be considered when comparing differences in culture rates from different institution's pediatric orthopaedics services, given the variability in when orthopaedic physicians become involved in a MSKI workup.

Soft Tissue Sarcoma Response to Two Cycles of Neoadjuvant Chemotherapy: A Multireader Analysis of MRI Findings and Agreement with RECIST Criteria and Change in SUVmax.

RATIONALE AND OBJECTIVES: When soft tissue sarcomas are treated with neoadjuvant chemotherapy, the number of cycles of chemotherapy is usually dependent on the tumor's initial response. Popular methods to assess tumor response include Response Evaluation Criteria in Solid Tumors (RECIST) criteria, which rely solely on tumor size, and maximum standardized uptake value (SUVmax) reduction in positron emission tomography (PET), which requires an expensive and high radiation test. We hypothesized that contrast-enhanced magnetic resonance imaging (MRI) may offer a good alternative by providing additional information beyond tumor size. MATERIALS AND METHODS: Following IRB approval, a retrospective review identified patients with soft tissue sarcomas who underwent both PET and MRI before and after two cycles of neoadjuvant chemotherapy. Five readers independently examined the MRI exams for: changes in size, T2 or T1 signal, necrosis and degree of enhancement. Readers then made a subjective binary assessment of tumor response to therapy. Each reader repeated the anonymized randomized reading at least 2 weeks apart. 18 F-FDG PET exams were interpreted by a nuclear medicine specialist. The maximum standardized uptake values (SUVmax) for pre and post-chemotherapy exams were compared. Intra- and inter-reader agreement was assessed using Cohen's kappa and Light's kappa, respectively. . RESULTS: Twenty cases were selected for this multireader study, of which 9 (45%) were responders and 11 were nonresponders by SUVmax. Using all MRI criteria, 43% were classified as responders based on MRI and 1.5% were classified as responders by RECIST criteria. Using PET as the reference, the sensitivity and the specificity of the MRI diagnosis for response using all findings were 50% and 63%, respectively. There was fair to moderate intrareader (kappa = 0.37) and inter-reader (kappa = 0.48) agreement for the MRI diagnosis of response. None of the individual MRI signal characteristics were significantly different between the PET responders and nonresponders. Additionally, no MRI findings were significantly different between those with and without good clinical responses. CONCLUSION: By our assessment, there is a poor correlation between tumor response by RECIST criteria and PET SUVmax. In addition, varying MR features did not help in diagnosing tumor response. Imaging of tumor response remains a challenging area that requires further research.

Combined glue embolization and excision for the treatment of venous malformations.

BACKGROUND: The purpose of this study was to evaluate safety, technical success, and clinical outcomes of treatment for venous malformations using n-BCA glue embolization immediately prior to excision. Sixty three patients (22 male, 41 female; mean age 12 years (range 1-25)) who underwent 70 procedures for extremity and trunk venous malformations were reviewed. Indications for treatment included pain (100%), swelling (22%), and diminished range of motion (16%). Thirty seven patients (59%) had undergone prior stand-alone interventional or surgical treatment but were persistently symptomatic. Safety, technical and clinical success were retrospectively assessed. RESULTS: Embolization was technically successful in 100% of patients. Mean lesion size was 3.0 × 2.9 × 5.7 cm. Three patients (5%) underwent planned, second stage procedures for lesions intentionally not treated at the first procedure. Four patients (6%) underwent an unplanned, second stage procedure for residual disease after the primary operation. Mean and median follow-up duration were 18 and 17 months, respectively (range 3 to 35 months). Symptomatic improvement was achieved in 58 patients (92%), of whom 41 (65%) reported complete elimination of pain. There were no recognized instances of nontarget embolization or other complications of the interventional procedure. One patient required additional surgery for wound dehiscence and one patient developed an abscess requiring incision and drainage. Minor surgical complications included surgical site skin infections (n = 5) and numbness (n = 1). Mean and median surgical blood loss volumes were 131 mL and 10 mL, respectively. One patient required perioperative blood transfusion. CONCLUSIONS: Extremity and truncal venous malformations can be safely and effectively treated in a single-stage fashion using glue embolization immediately preceding excision.