Transcriptomic profiling and immuno-histological characterization of synovial biopsies in juvenile idiopathic arthritis (JIA) suggest two broad categories, with significant overlap with rheumatoid arthritis (RA).

OBJECTIVES: To characterize transcriptomic profiles and immune cell composition and distribution in Juvenile Idiopathic Arthritis (JIA) synovial biopsies, assess for associations of these features with clinical parameters, and compare JIA and Rheumatoid Arthritis (RA) synovial features. METHODS: RNASeq was performed on 24 samples, with pathway analysis and inference of relative abundance of immune cell subsets based on gene expression data. Two multiplex fluorescence immunohistochemistry (IHC) panels were performed on 28 samples (including 13 on which RNASeq was performed), staining for CD206- classical and CD206+ non-classical macrophages, CD8+ and CD4+ T and B lymphocytes. Data were compared to a published series of early RA synovial biopsies. RESULTS: Pathway analysis of the (n=339) most variably expressed genes identified a B and plasma cell signature as the main driver of heterogeneity in JIA synovia, with strong overlap between JIA and RA synovitis. Multiplex IHC confirmed heterogeneity of immune cell infiltration. M1-like macrophage rich synovial lining was associated with greater lining hypertrophy and higher pan (CD45+) immune and CD8+ T cell infiltration. CONCLUSION: Our study indicates significant similarities between JIA and RA synovitis. Similar to RA, JIA synovia may be broadly categorized into two groups: (i) those with an inflammatory/adaptive immune transcriptomic signature, M1-like macrophage and CD8+ T cell infiltration and thicker, M1-like macrophage rich synovial lining, and (ii) those with an M2-like macrophage transcriptomic signature, greater M2/M1-like macrophage ratios and thinner, M2-like macrophage rich synovial lining. Synovial features were not significantly associated with clinical parameters, likely due to group size and heterogeneity.

Compound heterozygous mutations in the kinase domain of IKKα lead to immunodeficiency and immune dysregulation.

IKKα, encoded by CHUK , is crucial in the non-canonical NF-κB pathway and part of the IKK complex activating the canonical pathway alongside IKKß. Absence of IKKα cause fetal encasement syndrome in human, fatal in utero, while an impaired IKKα-NIK interaction was reported in a single patient and cause combined immunodeficiency. Here, we describe compound heterozygous variants in the kinase domain of IKKα in a female patient with hypogammaglobulinemia, recurrent lung infections, and Hay-Wells syndrome-like features. We showed that both variants were loss-of-function. Non-canonical NF-κB activation was profoundly diminished in stromal and immune cells while the canonical pathway was partially impaired. Reintroducing wild-type CHUK restored non-canonical NF-κB activation. The patient had neutralizing autoantibodies against type I IFN, akin to non-canonical NF-κB pathway deficiencies. Thus, this is the first case of bi-allelic CHUK mutations disrupting IKKα kinase function, broadening non-canonical NF-κB defect understanding and suggesting IKKα's role in canonical NF-κB target gene expression in human.

Atrial fibrillation in a pediatric patient caused by an unusual malignant etiology: A case report.

This case report describes a 15-year-old patient with a known congenital malformation syndrome and immune deficiency, presenting with new-onset atrial fibrillation (AF) after a recent diagnosis of an intrathoracic mass. Transthoracic echocardiography showed a structurally and functionally normal heart and workup confirmed a primary diffuse large B-cell lymphoma, with pericardial and left atrial involvement on cardiac magnetic resonance imaging. Electrical cardioversion was successfully performed to convert the AF and chemotherapy was promptly started. Antiarrhythmic treatment was continued for 6 weeks, without recurrent AF. We discuss the pathogenesis of AF in the setting of malignancies as well as the management strategies of AF, mainly based on adult guidelines.

Successful use of empagliflozin to treat neutropenia in two G6PC3-deficient children: Impact of a mutation in SGLT5.

Neutropenia and neutrophil dysfunction found in deficiencies in G6PC3 and in the glucose-6-phosphate transporter (G6PT/SLC37A4) are due to accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), an inhibitor of hexokinase made from 1,5-anhydroglucitol (1,5-AG), an abundant polyol present in blood. Lowering blood 1,5-AG with an SGLT2 inhibitor greatly improved neutrophil counts and function in G6PC3-deficient mice and in patients with G6PT-deficiency. We evaluate this treatment in two G6PC3-deficient children. While neutropenia was severe in one child (PT1), which was dependent on granulocyte cololony-stimulating factor (GCSF), it was significantly milder in the other one (PT2), which had low blood 1,5-AG levels and only required GCSF during severe infections. Treatment with the SGLT2-inhibitor empagliflozin decreased 1,5-AG in blood and 1,5-AG6P in neutrophils and improved (PT1) or normalized (PT2) neutrophil counts, allowing to stop GCSF. On empagliflozin, both children remained infection-free (>1 year - PT2; >2 years - PT1) and no side effects were reported. Remarkably, sequencing of SGLT5, the gene encoding the putative renal transporter for 1,5-AG, disclosed a rare heterozygous missense mutation in PT2, replacing the extremely conserved Arg401 by a histidine. The higher urinary clearance of 1,5-AG explains the more benign neutropenia and the outstanding response to empagliflozin treatment found in this child. Our data shows that SGLT2 inhibitors are an excellent alternative to treat the neutropenia present in G6PC3-deficiency.

Safety of reducing antibiotic use in children with febrile neutropenia: A systematic review.

Febrile neutropenia is the most frequent complication in children treated with chemotherapy. Nevertheless, neutropenic children are a very heterogeneous group and invasive bacterial infections concern a minority of patients. Reducing antibiotics would bring many benefits. Yet, we can only explore this strategy if the safety of children is preserved. The main aims of this review were to study the safety and effectiveness of reducing antibiotic use in children with febrile neutropenia in terms of duration, route of administration (oral versus intravenous) and narrowing of antimicrobial spectrum. Cochrane Library, Pubmed and Embase were searched for relevant articles until February 2020. We have included all articles describing controlled trials written in French or in English. The risk of bias was assessed with ROB-2 (Cochrane Handbook for Systematic Reviews of Interventions Version 6.0. 2019, Chap. 8) or ROBINS-1 (Cochrane Handbook for Systematic Reviews of Interventions Version 6.0. 2019, Chap. 25). On 2351 articles, the systematic research retained 13 studies. Nine were used for a meta-analysis comparing oral versus intravenous treatment. We found no pediatric studies concerning de-escalation of empiric broad-spectrum antibiotics. No publication biases were found and almost all of the selected studies were at low risk or with some concern for bias. In comparing oral versus intravenous treatment and early cessation versus continuing antibiotics when no infection is proven, we found no difference in terms of safety (mortality and admission in intensive care unit) and efficacy (need of readmission/antibiotic modification/recurrence of fever). It seems safe and effective to provide oral treatment in low-risk febrile neutropenia and to stop antibiotics when no bacterial infection is proven. Spectrum reduction remains an important topic in pediatric research.Supplemental data for this article is available online at https://doi.org/10.1080/08880018.2022.2055245.

Characterization and risk factors of hyperglycaemia during treatment of childhood hematologic malignancies.

BACKGROUND: Secondary forms of diabetes are often understudied and underdiagnosed in children and adolescents with cancer. The objectives of our cohort study were to study the incidence and risk factors for hyperglycaemia in leukaemia and lymphoma patients. METHODS: We retrospectively collected 15 years of data from paediatric patients treated for acute lymphoblastic leukaemia (ALL), Hodgkin's lymphoma (HL), and non-Hodgkin's lymphoma (NHL) immediately at cancer diagnosis. We studied risk factors for hyperglycaemia in univariate and multivariate analyses. RESULTS: Our study cohort included 267 patients corresponding to 179 patients with ALL, 48 with NHL and 40 with HL. Eighteen per cent of ALL patients (32/179) and 17% of NHL patients (8/48) developed hyperglycaemia, with more than 61% developing hyperglycaemia within the first month of treatment. No hyperglycaemia was observed in HL patients. Multivariate analysis showed the following hyperglycaemia risk factors for ALL patients: overweight or obesity (OR 3.793) and pubertal onset (OR 4.269) at cancer diagnosis, steroid-resistant disease (OR 3.445) and hematopoietic stem cell transplant (HSCT) (OR 4.754). CONCLUSION: In our cohort, 18% of patients with ALL or NHL developed early-onset hyperglycaemia after chemotherapy/radiotherapy. Patients with ALL with increased hyperglycaemia risk can be readily identified by measuring BMI and puberty stage at cancer diagnosis. Also, glucose monitoring should be reinforced when patients show steroid-resistant disease and/or require HSCT.

Hemiplegic Migraine Associated With PRRT2 Variations: A Clinical and Genetic Study.

BACKGROUND AND OBJECTIVE: PRRT2 variants have been reported in a few cases of patients with hemiplegic migraine. To clarify the role of PRRT2 in familial hemiplegic migraine, we studied this gene in a large cohort of affected probands. METHODS: PRRT2 was analyzed in 860 probands with hemiplegic migraine, and PRRT2 variations were identified in 30 probands. Genotyping of relatives identified a total of 49 persons with variations whose clinical manifestations were detailed. RESULTS: PRRT2 variations were found in 12 of 163 probands who previously tested negative for CACNA1A, ATP1A2, and SCN1A variations and in 18 of 697 consecutive probands screened simultaneously on the 4 genes. In this second group, pathogenic variants were found in 105 individuals, mostly in ATP1A2 (42%), followed by CACNA1A (26%), PRRT2 (17%), and SCN1A (15%). The PRRT2 variations included 7 distinct variants, 5 of which have already been described in persons with paroxysmal kinesigenic dyskinesia and 2 new variants. Eight probands had a deletion of the whole PRRT2 gene. Among the 49 patients with variations in PRRT2, 26 had pure hemiplegic migraine and 16 had hemiplegic migraine associated with another manifestation: epilepsy (8), learning disabilities (5), hypersomnia (4), or abnormal movement (3). Three patients had epilepsy without migraine: 2 had paroxysmal kinesigenic dyskinesia without migraine, and 1 was asymptomatic. DISCUSSION: PRRT2 should be regarded as the fourth autosomal dominant gene for hemiplegic migraine and screened in any affected patient, together with the 3 other main genes. Further studies are needed to understand how the same loss-of-function PRRT2 variations can lead to a wide range of neurologic phenotypes, including paroxysmal movement disorder, epilepsy, learning disabilities, sleep disorder, and hemiplegic migraine.

High-dose chemotherapy followed by autologous stem cell rescue in Wilms tumors: French report on toxicity and efficacy.

BACKGROUND: Heterogeneous data have been reported on high-dose chemotherapy (HDCT) with autologous stem cell rescue (ASCR) in Wilms tumors (WTs). We aimed to define its safety and efficacy in the French cohort, and to compare this management to current international recommendations. METHODS: Data prospectively collected from children, adolescents, and young adults with WT treated with HDCT/ASCR between 2000 and 2016 in French centers were retrospectively analyzed. Toxicity was reported according to CTCAE v4.03. RESULTS: Fifty-four patients received HDCT/ASCR (first line, n = 13; recurrence, n = 41). Their median age at the time of ASCR was 5.3 years (range 2.2-21.6). Main nonhematological acute grades 3-4 toxicities were digestive and renal. No significant difference of toxicity rate was observed among HDCT regimens and schedules. Two patients died shortly after ASCR (renal and multiorgan failure), and one heavily pretreated patient died of late respiratory failure. The selection criteria applied to define those patients eligible for HDCT/ASCR retrospectively matched to those currently used in the International Society of Pediatric Oncology (SIOP) UMBRELLA protocol for 38 patients, with encouraging survival rates compared to published data. The objective response rate to HDCT was 21%, with a disease control rate after HDCT of 85%. After a median follow-up of 7 years, the 5-year event-free survival (EFS) and overall survival (OS) were 54% (95% CI: 32%-76%) and 62% (95% CI: 31%-82%) for frontline patients, and 57% (95% CI: 39%-71%) and 69% (95% CI: 52%-81%) at recurrence. CONCLUSION: HDCT was feasible and showed encouraging results in well-defined settings. Data from the current prospective protocol will help to better evaluate HDCT impact on survival.

Serum calprotectin (S100A8/A9): a promising biomarker in diagnosis and follow-up in different subgroups of juvenile idiopathic arthritis.

INTRODUCTION: In the management of juvenile idiopathic arthritis (JIA), there is a lack of diagnostic and prognostic biomarkers. This study assesses the use of serum calprotectin (sCal) as a marker to monitor disease activity, and as a classification and prognosis tool of response to treatment or risk of flares in patients with JIA. METHODS: Eighty-one patients with JIA from the CAP48 multicentric cohort were included in this study, as well as 11 non-paediatric healthy controls. An ELISA method was used to quantify sCal with a commercial kit. RESULTS: Patients with an active disease compared with healthy controls and with patients with inactive disease showed an eightfold and a twofold increased level of sCal, respectively. sCal was found to be correlated with the C-reactive protein (CRP) and even more strongly with the erythrocyte sedimentation rate. Evolution of DAS28 scores correlated well with evolution of sCal, as opposed to evolution of CRP. With regard to CRP, sCal could differentiate forms with active oligoarthritis from polyarthritis and systemic forms. However, sCal brought an added value compared with the CRP as a prognosis marker. Indeed, patients with active disease and reaching minimal disease activity (according to Juvenile Arthritis Disease Activity Score) at 6 months following the test had higher sCal levels, while patients with inactive disease had higher sCal levels if a flare was observed up to 3-9 months following the test. CONCLUSIONS: This study confirms the potential uses of sCal as a biomarker in the diagnosis and follow-up of JIA.

Detection of alternative lengthening of telomeres mechanism on tumor sections.

The vast majority of adult cancer cells achieve cellular immortality by activating a telomere maintenance mechanism (TMM). While this is mostly achieved by the de-silencing of hTERT telomerase gene expression, an alternative homologous recombination-based and telomerase-independent mechanism, known as ALT (Alternative Lengthening of Telomeres), is frequently activated in a subset of tumors, including paediatric cancers. Being absent from normal cells, the ALT mechanism offers interesting perspectives for new targeted cancer therapies. To date, however, the development of better translationally applicable tools for ALT detection in tumor sections is still needed. Here, using a newly derived ALT-positive cancer cell mouse xenograft model, we extensively examined how the previously known ALT markers could be used as reliable tools for ALT diagnosis in tumor sections. We found that, together with the detection of ultra-bright telomeric signals (UBS), an ALT hallmark, native telomeric FISH, that detects single-stranded C-rich telomeric DNA, provides a very sensitive and robust tool for ALT diagnosis in tissues. We applied these assays to paediatric tumor samples and readily identified three ALT-positive tumors for which the TMM was confirmed by the gold-standard C-circle amplification assay. Although the latter offers a robust assay for ALT detection in the context of research laboratories, it is more difficult to set up in histopathological laboratories and could therefore be conveniently replaced by the combination of UBS detection and native telomeric FISH.

Clinical Spectrum of Ras-Associated Autoimmune Leukoproliferative Disorder (RALD).

Ras-associated autoimmune leukoproliferative disorder (RALD) is a clinical entity initially identified in patients evaluated for an autoimmune lymphoproliferative syndrome (ALPS)-like phenotype. It remains a matter of debate whether RALD is a chronic and benign lymphoproliferative disorder or a pre-malignant condition. We report the case of a 7-year-old girl diagnosed with RALD due to somatic KRAS mutation who progressed to a juvenile myelomonocytic leukemia phenotype and finally evolved into acute myeloid leukemia. The case report prompted a literature review by a search for all RALD cases published in PubMed and Embase. We identified 27 patients with RALD. The male-to-female ratio was 1:1 and median age at disease onset was 2 years (range 3 months-36 years). Sixteen patients (59%) harbored somatic mutations in KRAS and 11 patients (41%) somatic mutations in NRAS. The most common features were splenomegaly (26/27 patients), autoimmune cytopenia (15/16 patients), monocytosis (18/24 patients), pericarditis (6 patients), and skin involvement (4 patients). Two patients went on to develop a hematopoietic malignancy. In summary, the current case documents an additional warning about the long-term risk of malignancy in RALD.

B-acute Lymphoblastic Leukemia With Hypereosinophilia Associated With Severe Cardiac Complications: A Clinical Case.

Hypereosinophilia (HE) is rare but often secondary to a nonhematologic disease such as allergic disorders and parasitic infections. HE can also be associated with hematologic malignancies and be the result of a clonal proliferation or reactive to another hematologic condition. Association of HE with acute lymphoblastic leukemia (ALL) is rare in children. We reported a case of a teenager presented with HE secondary to B-ALL who experienced severe cardiac complications with severe absolute eosinophil count. We compared his clinical evolution with other published cases and we reported 2 mutations linked to B-ALL never described before in this context.

Rapid identification and characterization of infected cells in blood during chronic active Epstein-Barr virus infection.

Epstein-Barr virus (EBV) preferentially infects epithelial cells and B lymphocytes and sometimes T and NK lymphocytes. Persistence of EBV-infected cells results in severe lymphoproliferative disorders (LPDs). Diagnosis of EBV-driven T or NK cell LPD and chronic active EBV diseases (CAEBV) is difficult, often requiring biopsies. Herein, we report a flow-FISH cytometry assay that detects cells expressing EBV-encoded small RNAs (EBERs), allowing rapid identification of EBV-infected cells among PBMCs. EBV-infected B, T, and/or NK cells were detectable in various LPD conditions. Diagnosis of CAEBV in 22 patients of Caucasian and African origins was established. All exhibited circulating EBV-infected T and/or NK cells, highlighting that CAEBV is not restricted to native American and Asian populations. Proportions of EBV-infected cells correlated with blood EBV loads. We showed that EBV-infected T cells had an effector memory activated phenotype, whereas EBV-infected B cells expressed plasma cell differentiation markers. Thus, this method achieves accurate and unambiguous diagnoses of different forms of EBV-driven LPD and represents a powerful tool to study their pathophysiological mechanisms.

Rhabdomyosarcoma associated with germline TP53 alteration in children and adolescents: The French experience.

OBJECTIVE: To describe the clinical characteristics and outcome of patients with Li-Fraumeni-associated rhabdomyosarcoma (RMS). METHOD: Retrospective analysis of data from 31 French patients with RMS diagnosed before the age of 20 years associated with a TP53 pathogenic germline variant. Cases were identified through the French Li-Fraumeni database. Central histologic review was performed in 16 cases. RESULTS: The median age at diagnosis was 2.3 years, and the median follow-up was 9.1 years (0.3-34.8). The main tumor sites were head and neck (n = 13), extremities (n = 8), and trunk (n = 8). The local pathology report classified the 31 tumors in embryonal (n = 26), alveolar (n = 1), pleomorphic (n = 1), and spindle-cell (n = 1) RMS (missing = 2). After histological review, anaplasia (diffuse or focal) was reported in 12/16 patients. Twenty-five patients had localized disease, three had lymph node involvement, and three distant metastases. First-line therapy combined surgery (n = 27), chemotherapy (n = 30), and radiotherapy (n = 14) and led to RMS control in all, but one patient. Eleven patients relapsed, and 18 patients had second malignancies. The 10-year event-free, progression-free, and overall survival rates were 36% (95% CI: 20-56), 62% (95% CI: 43-77) and 76% (95% CI: 56-88), respectively. The 10-year cumulative risk of second malignancies was 40% (95% CI: 22-60). CONCLUSION: The high incidence of multiple primary tumors strongly influences the long-term prognosis of RMS associated with TP53 pathogenic germline variants. Anaplastic RMS in childhood, independently of the familial history, should lead to TP53 analysis at treatment initiation to reduce, whenever possible, the burden of genotoxic drugs and radiotherapy in carriers and to ensure the early detection of second malignancies.

Environmental exposures related to parental habits in the perinatal period and the risk of Wilms' tumor in children.

INTRODUCTION: Wilms' tumor is the most frequently diagnosed renal tumor in children. Little is known about its etiology. The aim of this study was to investigate the potential role of specific exposures related to parental habits such as parental smoking, maternal alcohol consumption and the use of household pesticides during pregnancy. METHODS: The ESTELLE study was a nationwide case-control study that included 117 Wilms' tumor cases and 1100 control children from the general French population, frequency-matched by age and gender. Unconditional logistic regression was used to estimate odds ratios and 95 % confidence intervals. RESULTS: After controlling for matching variables and potential confounders, the maternal use of any type of pesticide during pregnancy was associated with the risk of Wilms' tumor in children (OR 1.6 [95 % CI 1.1-2.3]). Insecticides were the most commonly reported type of pesticide and there was a positive association with their use (OR 1.7 [95 % CI 1.1-2.6]. The association was stronger when they were used more often than once a month (OR 1.9 [95 % CI 1.2-3.0]. Neither maternal smoking during pregnancy nor paternal smoking during preconception/pregnancy was associated with a risk of Wilms' tumor (ORs 1.1[95 % CI 0.7-1.8] and 1.1 [95 % CI 0.7-1.7], respectively). No association was observed with maternal alcohol intake during pregnancy (OR 1.2 [95 % CI 0.8-2.0]). CONCLUSION: Our findings suggest an association between the maternal use of household pesticides during pregnancy and the risk of Wilms' tumor.

Liver metastasis at diagnosis in children with nephroblastoma enrolled in SIOP2001 protocol: A French multicentric study.

BACKGROUND: Liver metastases are rare in children with Wilms tumor (WT), and their impact on the outcome is unclear. PATIENTS AND METHODS: The French cohort of patients with WT presenting liver metastases at diagnosis and enrolled in the International Society of Pediatric Oncology (SIOP) 2001 study was reviewed. RESULTS: From 2002 to 2012, 906 French patients were enrolled in the SIOP2001 trial. Among them, 131 (14%) presented with stage IV WT and 18 (1.9%) had liver metastases at diagnosis. Isolated liver metastases were displayed in four of them. After preoperative chemotherapy, persistent liver disease was reported in 14/18 patients, and 13 of them underwent metastasectomy after nephrectomy. In resected liver lesions, the same histology of the primary tumor was reported for three patients, blastemal cells without anaplasia were identified in one patient with DA-WT, and post-chemotherapy necrosis/fibrosis was identified for the other 10 patients. For the four patients who had liver and lung surgery, both sites had nonviable cells with post-chemotherapy necrosis/fibrosis. Six patients had hepatic radiotherapy. Sixteen patients achieved primary complete remission and were alive at the last follow-up (median follow-up: 6.4 years). The only two deceased patients presented diffuse anaplasia histology. The five-year EFS and OS were 83% (60%-94%) and 88% (66%-97%), respectively. CONCLUSION: Liver involvement does not appear to be an adverse prognostic factor in metastatic WT. The role of hepatic surgery and radiotherapy remains unclear, and should be carefully considered in case of persistent liver metastases, according to histology and radiological response to other metastatic sites.

DNAJB1-PRKACA-positive metastatic fibrolamellar carcinoma with unknown primary in a pediatric patient.

Fibrolamellar carcinoma (FLC) is a rare variant of hepatocellular carcinoma, occurring in children and young adults without underlying liver disease. The diagnosis is based on morphological characteristics of the tumor, supplemented by immunohistochemistry and/or genetic testing. Recently, the presence of a characteristic DNAJB1-PRKACA fusion gene has been associated with FLC. Herein, we report a case of FLC presenting as peritoneal carcinomatosis in a 14-year-old female. Interestingly, no liver tumor was seen on imaging, and an alternative possibility is that the tumor arose outside the liver as a hepatoid carcinoma with fibrolamellar features.

Total en bloc spondylectomy of T11 and spine shortening performed on a 17-month-old patient: art of the possible.

STUDY DESIGN: Case report. PURPOSE: The authors used spine shortening as an alternative strategy to intercalary graft fixation to restore permanent spine stability for a 17-month-old infant who received total en bloc spondylectomy (TES) of T11 to treat an embryonic rhabdomyosarcoma. TES involves complete removal of vertebra, compensated by spine reconstruction using intercalary allografts and permanent posterior instrumentation, which is not possible for skeletally immature patients with high growth potential and non-ossified vertebrae. METHODS: Surgery was performed over two consecutive days. During the first day, the tumor was released from its dorsal attachments through the posterior approach. During the second day, the tumor was dissected and excised through the anterior approach, leaving a gap between T10 and T12. The two vertebrae were then drawn toward each other until the gap was bridged. The dural sac slipped into the canal under T10 and T12 with no observable kinking. RESULTS: Fifteen weeks after surgery, thoraco-abdominal CT confirmed fusion of the T10 and T12 vertebral bodies. Three years later, the patient lives a normal life with no major neurological deficits or recurrence of sarcoma. CONCLUSIONS: This case report is the first to demonstrate the feasibility of TES with spine shortening of an entire thoracic segment without spine kinking or damage in an infant. This unprecedented surgical technique allowed complete removal of an embryonic rhabdomyosarcoma, while granting rapid stability and growth potential. LEVEL OF EVIDENCE: IV.