Pediatric Synovial Osteochondromatosis of the Knee with Leg Length Discrepancy: A Case Report.

Introduction: Synovial chondromatosis (SC) is very rare among children. We are aware of no reports of patients with SC accompanied by leg length discrepancy (LLD). Case Report: We describe a case of synovial osteochondromatosis of a 7-year-old boy complicated by LLD. We performed epiphysiodesis of the distal femur and arthroscopic resection of loose bodies and total synovectomy. Three years after surgery, LLD had been corrected and there was no sign of recurrence. Conclusion: Physicians should be aware of synovial osteochondromatosis complicated by LLD in childhood and take radiographs of the whole length of lower legs when this condition is suspected.

Revascularization of a Necrotic Femoral Head in Severely Slipped Capital Femoral Epiphysis With a Modified Dunn Procedure: A Case Report.

Avascular necrosis, a serious slipped capital femoral epiphysis (SCFE) complication, is difficult to treat. We report a rare case of revascularization of the necrotic femoral head in a 12-year-old male patient with a severe SCFE (posterior tilting angle, 87°). We performed the modified Dunn procedure (MDP), followed by long-term unloading therapy. Blood flow to the epiphysis had partially resumed 2.3 years postoperatively. At the final 4.5-year follow-up, blood flow had been restored, leading to epiphyseal closure without significant femoral head deformity or hip pain. The patient could walk unassisted, with a flexion range of 120°. These findings support the use of the MDP with long-term unloading therapy as a potential treatment option for severe SCFE.

Clinical outcomes in patients with adamantinoma: Report from the bone and soft tissue tumor registry in Japan.

BACKGROUND: Adamantinomas are rare malignant bone tumors. Due to their low incidence, there are few reports on the clinical results of adamantinoma. OBJECTIVES: This study aims to clarify outcomes in patients with adamantinoma using data from the National Bone and Soft Tissue Tumor Registry. METHODS: From 2006 to 2019, 38 cases of tibial origin were included. Twenty-four were male and 14 were female, with a mean age of 37 (6-87) years and a mean follow-up of 35 (1-128) months. RESULTS: Surgery was performed in 33 cases (87%) (curettage: 4 cases, wide resection: 27 cases, amputation: 2 cases). Reconstruction was performed in 27 patients who underwent wide resection. A total of 12 additional surgeries were performed in 11 patients. The main reason for the additional surgeries was nonunion of grafting bone in 6 cases. Oncologic outcomes were DOC (death from other causes) in one case and NED (no evidence of disease) in 37 cases. CONCLUSIONS: The results of treatment of adamantinomas in Japan have been extremely favorable. This may be due in part to the large number of cases with wide resection.

Coefficient of variation of T2-weighted MRI may predict the prognosis of malignant peripheral nerve sheath tumor.

BACKGROUND: We investigated whether non-enhancement MRI features, including measurement of the heterogeneity of the tumor with MR T2 imaging by calculating coefficient of variation (CV) values, were associated with the prognosis of non-metastatic malignant peripheral nerve sheath tumors (MPNST). METHODS: This retrospective study included 42 patients with MPNST who had undergone surgical resection (mean age, 50 years ± 21; 20 male participants). Non-enhancement MR images were evaluated for signal intensity heterogeneity on T1- and T2-weighted imaging, tumor margin definition on T1- and T2-weighted imaging, peritumoral edema on T2-weight imaging, and CV. We measured the signal intensities of MR T2-weighted images and calculated the corresponding CV values. CV is defined as the ratio of the standard deviation to the mean. The associations between factors and overall survival (OS) were investigated via the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: The mean CV value of MR T2 images was 0.2299 ± 0.1339 (standard deviation) (range, 0.0381-0.8053). Applying receiver operating characteristics analysis, the optimal cut-off level for CV value was 0.137. This cut-off CV value was used for its stratification into high and low CV values. At multivariate survival analysis, a high CV value (hazard ratio = 3.63; 95% confidence interval = 1.16-16.0; p = 0.047) was identified as an independent predictor of OS. CONCLUSION: The CV value of the signal intensity of heterogenous MPNSTs MR T2-weighted images is an independent predictor of patients' OS.

Adverse reactions in young children receiving the coronavirus disease 2019 vaccine.

BACKGROUND: We sought to investigate the occurrence of adverse reactions in Japanese children aged 6 months to 4 years who received the BNT162b2 coronavirus disease 2019 (COVID-19) vaccine, to examine parental considerations, and to evaluate potential risk factors associated with post-vaccination fever. METHODS: This cross-sectional survey study targeted 1617 children aged 6 months to 4 years who received their primary doses of BNT162b2 from November 10, 2022, to April 30, 2023, in Okayama Prefecture. We surveyed the occurrence of local and systemic reactions within 1 week after vaccination, and described the incidence proportions of adverse reactions for 515 participants overall and by age group. The study also examined the impact of previous COVID-19 infection and co-administration of the seasonal influenza vaccine on post-vaccination fever. A survey also assessed parents' reasons for vaccinating their children and the sources of information they used. RESULTS: Adverse reactions were infrequent (5.2%, with fever ≥37.5°C; no cases exceeded 39°C) and did not increase with vaccine doses administered. The risk of post-vaccination fever was not statistically associated with a history of COVID-19-the adjusted risk ratio (aRR) was 0.99, and the 95% confidence interval (CI) was 0.41-2.39-but was associated with co-administration of the seasonal influenza vaccine (aRR 3.24, 95% CI 1.14-9.18). Parental decisions regarding vaccination were influenced by official government guidelines and primary care physicians' opinion. CONCLUSION: This study provides valuable insight into the safety profile of the BNT162b2 vaccine in Japanese children aged 6 months to 4 years. Further research involving larger cohorts and appropriate control groups is needed.

Establishment and characterization of a novel dedifferentiated chondrosarcoma cell line, SMU-DDCS, harboring an IDH1 mutation.

Dedifferentiated chondrosarcoma (DDCS) is a high-grade subtype with a bi-morphic histological appearance of a conventional chondrosarcoma component and it can abruptly transition to a high-grade non-cartilaginous sarcoma. To better understand the biological features of DDCSs and to help develop new therapies, a novel DDCS cell line, SMU-DDCS, was established. Tissue from an open biopsy of a tumor resected from a 75-year-old patient was subjected to primary culture. The cell line was established and authenticated by assessing DNA microsatellite short tandem repeats. The cells maintained in monolayer cultures exhibited constant growth, spheroid formation, and high invasive capacity. Out of the four mice inoculated with SMU-DDCS cells, tumors developed in three mice after 2 weeks. R132C mutation was found in the IDH1 but not the IDH2 genomic DNA sequence of SMU-DDCS cells. SMU-DDCS cells exhibited low chemosensitivity to doxorubicin, methotrexate, and cisplatin. This SMU-DDCS cell line harboring an IDH1 mutation will be a useful tool for investigating DDCS development and for evaluating novel therapeutic agents against it.

Respiratory pathogen trends in patients with Kawasaki disease during the COVID-19 pandemic and respiratory syncytial virus epidemic in Japan.

BACKGROUND: Although the etiology of Kawasaki disease (KD) remains unknown, the most common view is that an infectious agent triggers the activation of the inflammatory cascade in predisposed children. The coronavirus disease 2019 (COVID-19) pandemic has led to the establishment of infection control measures, which reduced the overall incidence of respiratory infections; however, a resurgence of respiratory syncytial virus (RSV) infection occurred in the summer of 2021. This study aimed to examine the relationship between respiratory pathogens and KD during the COVID-19 pandemic and the RSV epidemic in Japan between 2020 and 2021. METHODS: We retrospectively reviewed the medical charts of pediatric patients with KD or respiratory tract infection (RTI) admitted to National Hospital Organization Okayama Medical Center between December 1, 2020, and August 31, 2021. All patients with KD and RTI underwent multiplex polymerase chain reaction testing upon admission. We classified patients with KD into the three subgroups-pathogen-negative, single pathogen-positive, and multi-pathogen-positive-and compared their laboratory data and clinical features. RESULTS: This study enrolled 48 patients with KD and 269 with RTI. Rhinovirus and enterovirus were the most prevalent pathogens in both patients with KD and RTI (13 [27.1%] and 132 patients [49.1%], respectively). The clinical characteristics of the pathogen-negative KD group and the pathogen-positive KD group at diagnosis were similar; however, the pathogen-negative group tended to receive additional treatment, such as multiple courses of intravenous immunoglobulin, intravenous methylprednisolone, infliximab, cyclosporine A, and plasmapheresis, more frequently. The number of patients with KD remained stable when RTI was not prevalent but increased following the surge in RTI with RSV. CONCLUSIONS: An epidemic of respiratory infections led to an increase in the incidence of KD. Patients with respiratory pathogen-negative KD could have greater recalcitrance to intravenous immunoglobulin than those with respiratory pathogen-positive KD.

Diagnostic utility of CSF1 immunohistochemistry in tenosynovial giant cell tumor for differentiating from giant cell-rich tumors and tumor-like lesions of bone and soft tissue.

BACKGROUND: Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT. METHODS: We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells. RESULTS: Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH. CONCLUSION: We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.

Risk Factors of Early Distant Metastasis After Primary Tumor Treatment in Soft Tissue Sarcoma.

BACKGROUND/AIM: Distant metastasis has a strong influence on prognosis in patients with soft tissue sarcoma (STS). While various risk factors have been reported for distant metastases, risk factors for distant metastases early after treatment of primary tumor have not been investigated. This study aimed to evaluate the factors of early distant metastasis after primary tumor resection in patients with STS. PATIENTS AND METHODS: We retrospectively identified patients with STS involving the extremities or trunk without any metastasis at the first visit. Data on clinical information and detailed assessment were collected. We evaluated clinical information as a risk factor for distant or lung metastases. Additionally, we evaluated risk factors for metastases in patients with distant metastases as early as 6 months after the initial resection of the primary tumor. RESULTS: A total of 337 patients were included in the study. Multivariate analysis revealed that the size of the primary tumor (p=0.0011 and p=0.0167), consultation in a short period after onset (p=0.0325 and p=0.0402), histological high grade (p=0.0006 and p=0.0002), and inadequate surgical margin (p=0.0151 and p=0.0055) were significant predictors for poor prognosis for all distant and lung metastases, respectively. However, the only risk factor for early metastases within 6 months was young age (p=0.0148). CONCLUSION: The only risk factor for early distant metastasis after primary tumor resection in patients with STS was young age, even though large tumor diameter and histological high grade were risk factors for distant metastasis.

Exercise-induced histone H3 trimethylation at lysine 27 facilitates the adaptation of skeletal muscle to exercise in mice.

Histone H3 trimethylation at lysine 27 (H3K27me3) is known to act as a transcriptionally repressive histone modification via heterochromatin formation. In skeletal muscle, it was also reported that H3K27me3 was enriched at the sites transcriptionally activated by exercise, although the role of H3K27me3 in adaptation to exercise is unknown. In this study, using mouse tibialis anterior muscle, we initially determined the genome-wide enrichment of RNA polymerase II and histone H3 trimethylation at lysine 4 (H3K4me3) and H3K27me3 using chromatin immunoprecipitation, followed by sequencing analysis. The loci that were transcriptionally upregulated by a single bout of running exercise were marked by both H3K27me3 and H3K4me3, which were also correlated with the distribution of RNA polymerase II. The genes that were not responsive to exercise exhibited high H3K4me3 occupancy, similar to the upregulated genes but with less H3K27me3. Next, we tested the effects of GSK343, a specific inhibitor of enhancer of zeste homologue 2 (EZH2). Unexpectedly, GSK343 administration enhanced the H3K27me3 occupancy at the target loci, leading to the upregulation of gene responses to acute exercise. Administration of GSK343 also facilitated the phenotypic transformation of type IIb to type IIa fibres and the upregulation of AMPK phosphorylation and levels of heat shock protein 70, pyruvate dehydrogenase kinase 4, peroxisome proliferator-activated receptor Î³ coactivator-1α and muscle RING finger 1. Furthermore, in contrast to the accelerated adaptation to exercise by GSK343, administration of the EZH1/2 dual inhibitor valemetostat prevented the changes in the aforementioned parameters after exercise training. These results indicate that exercise-induced H3K27me3 plays a key role in inducing exercise-related effects in the skeletal muscle. KEY POINTS: Exercise mediates histone H3 trimethylation at lysine 27 (H3K27me3) at transcriptionally upregulated loci in skeletal muscle, but the role of H3K27me3 in the adaptation of skeletal muscle to exercise training is unclear. Chromatin immunoprecipitation followed by sequencing analysis demonstrated that H3K27me3, in addition to H3K4me3 modifications, is the hallmark of sites showing higher responses to acute exercise. GSK343, a selective inhibitor of the enhancer of zeste homologue 2 (EZH2), enhanced the gene responses to a single bout of exercise and accelerated the adaptive changes during exercise training in association with myonuclear H3K27me3 accumulation. Administration of valemetostat, an EZH1/2 dual inhibitor, repressed myonuclear H3K27me3 accumulation during training and caused a failure of adaptive changes. Exercise-induced H3K27me3 might play a key role in inducing exercise-related effects in skeletal muscle.

Non-ossifying fibromas and fibrous cortical defects around the knee - an epidemiologic survey in a Japanese pediatric population.

BACKGROUND: The aim of the present study was to evaluate the prevalence of non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) in a Japanese pediatric population and the association between the lesion size and pain. METHODS: This retrospective study, conducted across 10 Japanese institutions, included patients aged 5-15 years who had undergone standard antero-posterior and lateral view radiography of the knee. Using these radiographs, we diagnosed the lesion as a NOF or FCD. Patient demographics, including age, sex, the size and location of the NOF, and chief complaint were recorded. The lesion size was determined using radiographs. Student's t-test was used to compare the associations between the lesion size and spontaneous pain. RESULTS: A total of 6222 subjects (3567 boys and 2455 girls) were included in this study. The number of NOF and FCD cases was 143 and 437, respectively, and the prevalence of NOF and FCD was 2.3% and 7.0%, respectively. The average size of NOF and FCD was 22.1 mm (range: 4-102 mm) and 13.2 mm (range: 5-21 mm), respectively. Three patients (2.1%) had pathological fractures due to NOF. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not associated with spontaneous pain in either lesion (p = 0.67 and p = 0.27, respectively). CONCLUSION: The prevalence of NOF and FCD around the knee was lower than that reported in previous studies. The prevalence of NOF increased and that of FCD decreased with advancing age. In both lesions, the lesion size may not be associated with pain.

Impact of Primary Tumor Resection on Metastasis to the Lung in Patients With Bone and Soft-tissue Sarcoma.

BACKGROUND: Few reports have investigated the effect of primary tumor resection on lung metastasis and prognosis in patients with bone and soft-tissue sarcoma, and we evaluated its effect on lung metastasis and prognosis. PATIENTS AND METHODS: We retrospectively identified patients with lung metastasis from bone and soft-tissue sarcoma. We examined the factors affecting prognosis and the rate of lung metastasis increase. RESULTS: A total of 48 patients were included. The multivariate analysis revealed that poor prognosis was significantly associated with a large maximum diameter of lung metastasis at the first visit and a rapid rate of increase (p=0.0400 and p=0.0003, respectively). The multivariate logistic regression analysis revealed that the rate of increase of size of lung metastases was only significantly associated with a large maximum diameter at the first visit (p=0.0245). CONCLUSION: Primary tumor resection of bone and soft-tissue sarcoma in patients with lung metastasis was not shown to affect their prognosis.

Infantile leukocytoclastic vasculitis caused by enterotoxin-producing methicillin-sensitive Staphylococcus aureus.

Staphylococcus aureus infections are known to cause leukocytoclastic vasculitis (LCV). Herein, we describe a case of an 18-month-old with LCV caused by enterotoxin-producing methicillin-sensitive Staphylococcus aureus (MSSA) emanating from an unrecognized pharyngeal abscess. It is critical to consider the possibility of extracutaneous sources of MSSA infection when investigating an infant with vasculitis. Prompt diagnosis and appropriate treatment are vital in preventing potentially life-threatening complications.

Oncological and prognostic analysis of soft tissue sarcoma of the elbow: report using the bone and soft tissue tumor registry in Japan.

OBJECTIVE: Soft tissue sarcomas in the elbow are extremely rare, and they have primarily been described in case series. Definitive concerning the prevalence and prognostic factors of elbow soft tissue sarcomas remain unknown. We examined the outcome of patients with elbow soft tissue sarcomas and identified the relevant prognostic factors. METHODS: In total, 219 patients with elbow soft tissue sarcomas were identified using data from the bone and soft tissue tumor registry in Japan. Differences in demographics, disease characteristics, treatment and survival were compared among the patients. Survival analyses including local recurrence-free survival, distant metastasis-free survival, and overall survival were performed using the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: Two hundred nineteen patients with elbow soft tissue sarcomas were identified, including 119 males (54.3%) and 100 females (45.7%). In total, 189 patients (86.3%) underwent surgery including re-excision. Of the surgically treated patients, 180 (95.2%) underwent limb salvage surgery, and nine patients (4.8%) underwent amputation. The 5-year overall survival, local recurrence-free survival, and distant metastasis-free survival rates for the entire patient cohort were 76.3, 70.1, and 69.3%, respectively. After adjusting for clinically relevant factors, overall survival was significantly worse among patients with tumors: >10 cm (hazard ratio = 4.34; 95% confidence interval = 1.03-18.2) and metastatic disease (hazard ratio = 6.94; 95% confidence interval = 1.55-31.0). CONCLUSIONS: Tumor size was identified as an independent risk factor for poor prognosis.

Reconstruction Using Free Vascularized Fibular Grafts after Wide Resection of Humerus Chondrosarcoma in a Patient with Cleidocranial Dysplasia.

Cleidocranial dysplasia is characterized by hypoplasia of the clavicles, unerupted teeth, narrow pelvis, short stature, and craniofacial malformations. A cause of this skeletal dysplasia is heterozygous mutations of the runt-related transcription factor 2 gene (Runx2), a master regulator for bone and cartilage development. Chondrosarcoma is a primary malignant bone tumor that is usually treated by wide resection surgery. This report shows a case of a 25-year-old female patient with cleidocranial dysplasia who was affected with chondrosarcoma of the left humerus. We performed wide resection of the tumor and reconstruction of the large bone defect of the humerus using free vascularized fibular grafts. The patient preserved the hand function and activity of daily life as the same level as preoperative condition more than five years after the surgery.

Bone marrow transplantation from a human leukocyte antigen-mismatched unrelated donor in a case with C1q deficiency associated with refractory systemic lupus erythematosus.

Human C1q deficiency is frequently associated with systemic lupus erythematosus (SLE), which requires long-term systemic corticosteroid administration. We report the case of a 12-year-old female patient with C1q deficiency presenting with intractable SLE who successfully underwent bone marrow transplantation from a human leukocyte antigen (HLA)-mismatched unrelated donor with an immunosuppressive conditioning regimen based on fludarabine, melphalan, and anti-thymocyte globulin. She developed Grade I graft-versus-host disease, but did not have any transplantation-related morbidity. Complete donor chimerism has been maintained for 2 years after transplantation, leading to the restoration of C1q levels and the resolution of SLE symptoms. Normal C1q mRNA expression was observed in CD14 + cells. Hematopoietic stem cell transplantation from an HLA-mismatched donor is a feasible treatment for patients with C1q deficiency with refractory SLE that is dependent on systemic corticosteroid treatment who do not have an HLA-matched donor.

Impact of Acridine Orange in Patients With Local Recurrent Soft Tissue Sarcoma.

BACKGROUND/AIM: Local recurrence in soft tissue sarcoma (STS) is a risk factor of worse prognosis. Although a few studies have shown that adjuvant therapy with acridine orange (AO) is effective for local control of primary STS, there have been no reports examining its effectiveness for local recurrence. PATIENTS AND METHODS: This retrospective study included 36 patients with first local recurrence of STS. Of them, 23 patients received wide excision without AO therapy (Wide group); the other 13 patients received marginal excision with AO therapy (AO group). We compared re-recurrence rates between these two groups. RESULTS: The total re-recurrence rate was 43.5% in the Wide group and 46.2% in the AO group. There was no significant difference in local re-recurrence-free survival and overall survival between the two groups. CONCLUSION: Adjuvant AO therapy combined with a marginal excision suppresses local re-recurrence rates of individuals with local STS recurrence.