Recombinant Methioninase Is Selectively Synergistic With Doxorubicin Against Wild-type Fibrosarcoma Cells Compared to Normal Cells and Overcomes Highly-Doxorubicin-resistant Fibrosarcoma.

BACKGROUND/AIM: Doxorubicin is first-line therapy for soft-tissue sarcoma, but patients can develop resistance which is usually fatal. As a novel therapeutic strategy, the present study aimed to determine the synergy of recombinant methioninase (rMETase) and doxorubicin against HT1080 fibrosarcoma cells compared to Hs27 normal fibroblasts, and rMETase efficacy against doxorubicin-resistant HT1080 cells in vitro. MATERIALS AND METHODS: The 50% inhibitory concentrations (IC50) of doxorubicin and rMETase, as well as their combination efficacy, against HT1080 human fibrosarcoma cells, Hs27 normal human fibroblasts and doxorubicin-resistant HT1080 (DR-HT1080) cells were determined. Dual-color HT1080 cells which expressed red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nuclei were used to visualize nuclear fragmentation during treatment. Nuclear fragmentation was observed with an IX71 fluorescence microscope. RESULTS: The IC50 for doxorubicin was 3.3 µM for HT1080 cells, 12.4 µM for DR-HT1080 cells, and 7.25 µM for Hs27 cells. The IC50 for rMETase was 0.75 U/ml for HT1080 cells, 0.42 U/ml for DR-HT1080 cells, and 0.93 U/ml for Hs27 cells. The combination of rMETase and doxorubicin was synergistic against fibrosarcoma cells but not against normal fibroblasts. The combination of doxorubicin plus rMETase also caused more fragmented nuclei than either treatment alone in HT1080 cells. rMETase alone was highly effective against the DR-HT1080 cells as well as the parental HT1080 cells. CONCLUSION: The present results indicate the future clinical potential of rMETase in combination with doxorubicin for fibrosarcoma, including doxorubicin-resistant fibrosarcoma.

Enhancing Pathogen Detection in Implant-Related Infections through Chemical Antibiofilm Strategies: A Comprehensive Review.

Implant-related infections (IRIs) represent a significant challenge to modern surgery. The occurrence of these infections is due to the ability of pathogens to aggregate and form biofilms, which presents a challenge to both the diagnosis and subsequent treatment of the infection. Biofilms provide pathogens with protection from the host immune response and antibiotics, making detection difficult and complicating both single-stage and two-stage revision procedures. This narrative review examines advanced chemical antibiofilm techniques with the aim of improving the detection and identification of pathogens in IRIs. The articles included in this review were selected from databases such as PubMed, Scopus, MDPI and SpringerLink, which focus on recent studies evaluating the efficacy and enhanced accuracy of microbiological sampling and culture following the use of chemical antibiofilm. Although promising results have been achieved with the successful application of some antibiofilm chemical pre-treatment methods, mainly in orthopedics and in cardiovascular surgery, further research is required to optimize and expand their routine use in the clinical setting. This is necessary to ensure their safety, efficacy and integration into diagnostic protocols. Future studies should focus on standardizing these techniques and evaluating their effectiveness in large-scale clinical trials. This review emphasizes the importance of interdisciplinary collaboration in developing reliable diagnostic tools and highlights the need for innovative approaches to improve outcomes for patients undergoing both single-stage and two-stage revision surgery for implant-related infections.

Membrane Formed Around Liquid Nitrogen-treated Bone Promotes Osteogenesis and Revitalization in a Rat Model.

BACKGROUND/AIM: This study aimed to investigate the structure and functions of the membrane formed around liquid nitrogen-treated bones in the osteogenesis and revitalization of frozen bone using a rat model. MATERIALS AND METHODS: Segmental defects were created in femurs of rats, and resected bones treated with liquid nitrogen [frozen bone (FB) group, n=20] or polymethylmethacrylate (PMMA group; n=20) were implanted as spacers. Histological analysis and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) of the membrane around each spacer were performed for bone morphogenetic protein 2 (BMP2), transforming growth factor (TGF)-ß1, and vascular endothelial growth factor (VEGF). Furthermore, in week 2, spacers were removed from both groups (n=5 each), and autologous cancellous bone (ACB) harvested from the ilium was grafted into the defect. Radiological analysis was performed until bone union was observed. RESULTS: In week 2, similar two-layered membrane structures were observed in both groups; these matured into fibrous tissues over time. At each evaluation point, qRT-PCR showed higher expression of all factors in the FB than in the PMMA group. In the ACB graft model, the mean period to bone union and new bone volume were significantly shorter and greater, respectively, in the FB. Chondrocytes invaded the osteotomy site from the membrane in the FB, suggesting that endochondral ossification may occur and be related to osteogenesis. Additionally, fibroblasts and capillaries in the membrane invaded the surface of treated bone in week 2, and osteocytes were observed around them in weeks 6 and 8. CONCLUSION: Fibrous membranous tissue formed around liquid nitrogen-treated bones may be vital for osteogenesis and revitalization of frozen bones.

Combination therapy with immune checkpoint inhibitors and denosumab improves clinical outcomes in non-small cell lung cancer with bone metastases.

BACKGROUND: The concomitant use of denosumab and immune checkpoint inhibitor (ICI) treatment may have synergistic effects and enhance antitumor activity; however, this has not been fully evaluated. This study aimed to evaluate the clinical outcomes of non-small cell lung cancer (NSCLC) patients with bone metastases receiving combination therapy and to identify the best combination regimen. METHODS: Eighty-six NSCLC patients with bone metastases who received ICI treatment were enrolled in this study. The patients were divided into two groups; a denosumab combination group (D + ICI group; n = 47) and a non-combination group (non-D + ICI group; n = 39). The response rate (RR) for bone metastases, disease control rate (DCR), overall survival (OS), real world progression-free survival (rwPFS), and the incidence of immune-related adverse events (irAEs) were evaluated. Additionally, the time when denosumab treatment should commence and concomitant treatment duration were evaluated. RESULTS: The D + ICI group showed significantly better RR (40.4 % vs. 20.5 %, p = 0.01), DCR (67.3 % vs. 38.7 %, p = 0.02), OS (14.2 vs. 8.6 months, p = 0.02), and rwPFS (7.4 vs. 3.6 months, p < 0.01) than the non-D + ICI group; however, incidence of irAEs showed no difference (29.7 % vs. 12.8 %, p = 0.07). Although clinical outcomes did not differ regardless of whether denosumab was initiated before or after ICI treatment, the group that received concomitant denosumab for more than four months had significantly better RR (46.2 % vs. 17.4 %, p = 0.03), OS (20.3 vs. 3.8 months, p < 0.01), and rwPFS (10.9 vs. 2.8 months, p < 0.01) than the group that received concomitant denosumab for less than four months. However, the landmark analysis showed no significant differences in OS (20.4 vs. 12.7 months, p = 0.11) and rwPFS (22.8 vs. 11.2 months, p = 0.21), and the results of denosumab duration were influenced by long-term survivors. CONCLUSION: Denosumab showed favorable synergistic effects with ICI treatment and may significantly improve the response to bone metastasis and prognosis without increasing the incidence of irAEs.

Clinical features of patients with carcinoma soft tissue metastases as surgical indications: a retrospective cohort study.

BACKGROUND: Soft-tissue metastasis of carcinoma is rare. In the present study, we investigated the surgical indications and clinical features of patients with soft tissue metastases of carcinoma. METHODS: In this retrospective cohort study, we enrolled 26 patients with soft tissue carcinoma metastasis referred to our department for treatment. Sex, age, location, size, depth, pain due to the tumor, primary origin, serum C-reactive protein (CRP) level, MRI examinations, diagnosis by a previous physician, carcinoma markers from blood, history of carcinoma, other metastases, performance status (PS), and surgical procedures were documented. Associations between variables and surgery were statistically analyzed. RESULTS: The primary cancer origin was found to be the lung (n = 10), kidney (n = 7), esophagus (n = 2), stomach (n = 1), breast (n = 1), liver (n = 1), ureter (n = 1), anus (n = 1), and unknown (n = 2). The mean CRP level of all patients was 2.3 mg/dL. Seven tumors (26.9%) were originally suspected to be soft tissue metastases of carcinoma, while 19 tumors (73.1%) were considered soft tissue sarcomas or inflammatory lesions by the previous treating physician. Twenty patients (76.9%) had other metastases. The PS of the 12 patients (46.2%) was zero. Eleven patients (42.3%) underwent surgery for soft tissue metastases. Diagnosis of soft tissue metastasis by a previous physician and good PS (p < 0.05) were significantly associated with surgery. CONCLUSION: Overall, the present results show that surgical indications for soft tissue metastasis of carcinoma include diagnosis by the referring physician or good PS of the patients.

DNA-Binding Agent Trabectedin Combined With Recombinant Methioninase Is Synergistic to Decrease Fibrosarcoma Cell Viability and Induce Nuclear Fragmentation But Not Synergistic on Normal Fibroblasts.

BACKGROUND/AIM: The alkylating agent trabectedin, which binds the minor groove of DNA, is second-line therapy for soft-tissue sarcoma but has only moderate efficacy. The aim of the present study was to determine the synergistic efficacy of recombinant methioninase (rMETase) and trabectedin on fibrosarcoma cells in vitro, compared with normal fibroblasts. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells expressing green fluorescent protein (GFP) in the nucleus and red fluorescent protein (RFP) in the cytoplasm and Hs27 normal human fibroblasts, were used. Each cell line was cultured in vitro and divided into four groups: no-treatment control; trabectedin treated; rMETase treated; and trabectedin plus rMETase treated. The dual-color HT1080 cells were used to quantitate nuclear fragmentation in each treatment group. RESULTS: The combination of rMETase and trabectedin was highly synergistic to decrease HT1080 cell viability. In contrast, there was no synergy on Hs27 cells. Moreover, nuclear fragmentation occurred synergistically with the combination of trabectedin and rMETase on dual-color HT1080 cells. CONCLUSION: The combination treatment of trabectedin plus rMETase was highly synergistic on fibrosarcoma cells in vitro suggesting that the combination can improve the outcome of trabectedin alone in future clinical studies. The lack of synergy of rMETase and trabectedin on normal fibroblasts suggests the combination is not toxic to normal cells. Synergy of the two drugs may be due to the high rate of nuclear fragmentation on treated HT1080 cells, and the late-S/G2 cell-cycle block of cancer cells by rMETase, which is a target for trabectedin. The results of the present study suggest the future clinical potential of the combination of rMETase and trabectedin for soft-tissue sarcoma.

Effect of Enoxaparin and Daikenchuto Coadministration on Hepatic Disorder Markers in Gynecological Cancer Patients after Abdominal Surgery.

Enoxaparin and daikenchuto are commonly administered to prevent venous thromboembolism and intestinal obstruction after gynecological malignancy surgery. However, the effects of their combined use on hepatic function are not well studied. This study aimed to clarify the effects of the coadministration of enoxaparin and daikenchuto on hepatic function. First, Japanese Adverse Drug Event Report (JADER) data were analyzed to identify signals of hepatic disorders. Second, a retrospective observational study of patients who underwent surgery for gynecological malignancies was conducted. This study defined hepatic disorders as an increase in aspartate aminotransferase (AST) or alanine aminotransaminase (ALT) levels above the reference values, using 1-h postoperative values as the baseline. The analysis of JADER data revealed an increased risk for hepatic disorders with the coadministration of enoxaparin and daikenchuto. An observational study also showed higher odds ratios (95% confidence intervals) for the occurrence of hepatic disorders in the coadministration group (4.27; 2.11-8.64) and enoxaparin alone group (2.48; 1.31-4.69) than in the daikenchuto alone group. The median increase in the ALT level was also higher in the coadministration group (34; 15-59) than in the enoxaparin alone (19; 6-38) and daikenchuto alone groups (8; 3-33). In conclusion, our study suggests that compared with the use of enoxaparin or daikenchuto alone, enoxaparin and daikenchuto coadministration increases the risk of hepatic disorders, with more significant increases in AST and ALT levels. Healthcare workers need to be aware of these potential side effects when combining these drugs after surgery for gynecological malignancies.

Intraoperative Fracture during the Insertion of Advanced Locking Screws (T2 Alpha Femur Retrograde Intramedullary Nailing System): Report of Two Cases and Identifying Causes and Prevention.

Background: Recently, the T2 alpha nailing system (Stryker, Inc.), which has advanced locking screws that can attach a screw to a rod, has been used worldwide and is expected to improve fracture fixation. We analyzed two cases of supracondylar femoral fractures in older adult patients, in which intraoperative fractures occurred during the insertion of advanced locking screws of the T2 alpha femur retrograde intramedullary nail. Case presentation: A 93-year-old and an 82-year-old woman each underwent T2 alpha femur retrograde nail fixation for supracondylar femur fractures at separate hospitals, and advanced locking screws were used as the proximal transverse locking screws. In both patients, a fracture line was observed at the proximal screw postoperatively, and the fractures were refixed with distal cable wiring and/or femoral distal plates. The patients were subsequently discharged from the same facility with no remarkable pain. Conclusions: When inserting advanced locking screws, it is necessary to enlarge the screw hole in the near-bone cortex with a counterbore drill, which might add torque to the bone cortex that could result in fractures. If the sleeve is distant from the bone, the counterbore drill will not reach the bone, the screw hole will not expand, and the insertion of advanced locking screws will apply a strong torque to the bone cortex and may result in fracture. Moreover, it is important to confirm that the counterbore drill is securely inserted under fluoroscopy and to carefully enlarge the bony foramen manually to prevent fractures during screw insertion.

Development and validation of a nomogram to predict surgical site infection after soft-tissue sarcoma resection.

Aims: Surgical site infection (SSI) after soft-tissue sarcoma (STS) resection is a serious complication. The purpose of this retrospective study was to investigate the risk factors for SSI after STS resection, and to develop a nomogram that allows patient-specific risk assessment. Methods: A total of 547 patients with STS who underwent tumour resection between 2005 and 2021 were divided into a development cohort and a validation cohort. In the development cohort of 402 patients, the least absolute shrinkage and selection operator (LASSO) regression model was used to screen possible risk factors of SSI. To select risk factors and construct the prediction nomogram, multivariate logistic regression was used. The predictive power of the nomogram was evaluated by receiver operating curve (ROC) analysis in the validation cohort of 145 patients. Results: LASSO regression analysis selected possible risk factors for SSI, including age, diabetes, operating time, skin graft or flap, resected tumour size, smoking, and radiation therapy. Multivariate analysis revealed that age, diabetes, smoking during the previous year, operating time, and radiation therapy were independent risk factors for SSI. A nomogram was developed based on the results of multivariate logistic regression analysis. In the development cohort, the incidence of SSI was 4.5% in the low-risk group (risk score < 6.89) and 26.6% in the high-risk group (risk score ≥ 6.89; p < 0.001). In the validation cohort, the incidence of SSI was 2.0% in the low-risk group and 15.9% in the high-risk group (p = 0.004). Conclusion: Our nomogram will enable surgeons to assess the risk of SSI in patients with STS. In patients with high risk of SSI, frequent monitoring and aggressive interventions should be considered to prevent this.

Conjoined lumbosacral nerve root: a case report.

BACKGROUND: In patients with conjoined nerve roots, hemilaminectomy with sufficient exposure of the intervertebral foramen or lateral recess is required to prevent destabilization and ensure correct mobility of the lumbosacral spine. To the best of our knowledge, no case reports have detailed the long-term course of conjoined nerve roots after surgery. CASE PRESENTATION: We report the case of a 51-year-old Japanese man with a conjoined nerve root. The main symptoms were acute low back pain, radiating pain, and right leg muscle weakness. Partial laminectomy was performed with adequate exposure to the conjoined nerve root. The symptoms completely resolved immediately after surgery. However, the same symptoms recurred 7 years postoperatively. The nerve root was compressed because of foraminal stenosis resulting from L5-S disc degeneration. L5-S transforaminal lumbar interbody fusion was performed on the contralateral side because of an immobile conjoined nerve root. At 44 months after the second surgery, the patient had no low back pain or radiating pain, and the muscle weakness in the right leg had improved. CONCLUSIONS: This is the first report of the long-term course of conjoined nerve root after partial laminectomy. When foraminal stenosis occurs after partial laminectomy, transforaminal lumbar interbody fusion from the contralateral side may be required because of an immobile conjoined nerve root.

Soft Tissue Sarcomas: Treatment and Management.

Due to the rarity and heterogeneity of soft tissue sarcoma (STS), investigating new treatments for this condition has been challenging [...].

Evaluation of Conditions for the Development of Cryogenic Spinal Cord Injury Using a Canine Model: An Experimental Study on the Safety of Cryoablation for Metastatic Spinal Tumors.

BACKGROUND AND PURPOSE: Although the application of cryoablation to metastatic spinal tumors has been attempted, spinal cryoablation has the unique complication of cryogenic spinal cord injury. This study aimed to elucidate the conditions for the development of cryogenic spinal cord injury. MATERIALS AND METHODS: Fifteen canines were used in this study. A metal probe was inserted into the 13th thoracic vertebral body. Cryoablation was performed for 10 minutes by freezing the probe in liquid nitrogen. The control canine underwent probe insertion only. Spinal cord monitoring, epidural temperature measurement, motor function assessment, and pathologic examination of the spinal cord were performed. RESULTS: During the 10 minutes of cryoablation, the epidural temperature decreased and reached the lowest epidural temperature (LET) at the end of cryoablation. The LETs (degrees celsius [°C]) of each canine were -37, -30, -27, -8, -3, -2, 0, 1, 4, 8, 16, 18, 20, and 25, respectively. As the epidural temperature decreased, waveform amplitudes also decreased. At the end of cryoablation (10 minutes after the start of cryoablation), abnormal waves were observed in 92.9% (13/14) of canines. With epidural rewarming, the amplitude of the waveforms tended to recover. After epidural rewarming (2 hours after the start of cryoablation), abnormal waves were observed in 28.6% (4/14) of canines. The LETs (°C) of the canines with abnormal waves after epidural rewarming were -37, -30, -27, and -8. None of the canines with normal waves after epidural rewarming had any motor impairment. In contrast, all canines with remaining abnormal waves after epidural rewarming had motor impairment. In the pathologic assessment, cryogenic changes were found in canines with LETs (°C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (°C) of -37, -30, -27, -8, 0, and 1 caused cryogenic spinal cord injury. There was no evidence of cryogenic spinal cord injury in canines with LET of ≥4°C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4°C, suggesting that the epidural temperature should be maintained above at least 4°C to prevent cryogenic spinal cord injury.

Tumor-induced Osteomalacia Successfully Treated by En Bloc Tumor Excision and Reconstruction Using a Tumor-bearing Frozen Autograft: A Case Report.

BACKGROUND/AIM: Tumor-induced osteomalacia (TIO) is a rare pathology caused by overproduction of fibroblast growth factor 23 (FGF23). Its common clinical features include generalized muscle weakness, bone pain, and fractures. Complete resection of the offending tumor is the mainstay treatment. In this report, we present the first case of TIO by an FGF23 producing tumor treated using a tumor-bearing autograft treated with liquid nitrogen. CASE REPORT: A 63-year old female presented with generalized body pain, particularly in the left arm. The patient was diagnosed with a FGF23 producing tumor of the left humerus. Wide resection of the involved tumor was performed using a tumor-bearing autograft that was treated with liquid nitrogen. Postoperatively, the FGF23 and alkaline phosphatase (ALP) levels significantly decreased and inorganic phosphate normalized. There was also subsequent relief of generalized body pain. Immediately after the operation, range of motion of the left shoulder and elbow was initiated. The patient was instructed to perform forward flexion and abduction up to 90° with a rotational restraint. Almost complete bone union was observed at 12 months post procedure. Postoperative functional results were as follows: Musculoskeletal Tumor Society (MSTS) score of 27/30, 90% and International Society of Limb Salvage (ISOLS) score of 26/30, 87%. Ten years after the surgery, osteotomy line was completely obscured based on radiographs. The patient was disease free and without activity limitation. CONCLUSION: This is the first case report of wide excision of a FGF23 producing tumor and reconstruction using a tumor-bearing frozen autograft performed with excellent outcomes.

Extensive Synergy Between Recombinant Methioninase and Eribulin Against Fibrosarcoma Cells But Not Normal Fibroblasts.

BACKGROUND/AIM: The aim of the present study was to determine the synergy of recombinant methioninase (rMETase) and the anti-tubulin agent eribulin on fibrosarcoma cells, in comparison to normal fibroblasts, in vitro. MATERIALS AND METHODS: HT1080 human fibrosarcoma cells and HS27 human fibroblasts were used for in vitro experiments. Four groups were analyzed in vitro: No-treatment control; eribulin; rMETase; eribulin plus rMETase. Dual-color HT1080 cells which express red fluorescent protein (RFP) in the cytoplasm and green fluorescent protein (GFP) in the nuclei were used to visualize cytoplasmic and nuclear dynamics during treatment. RESULTS: Eribulin combined with rMETase greatly decreased the viability of HT 1080 cells. In contrast, eribulin combined with rMETase did not show synergy on Hs27 normal fibroblasts. Eribulin combined with rMETase also caused more fragmentation of the nucleus than all other treatments. CONCLUSION: The combination treatment of eribulin plus rMETase demonstrated efficacy on fibrosarcoma cells in vitro. In contrast, normal fibroblasts were resistant to this combination, indicating the potential clinical applicability of the treatment.

Seasonal variation of surgically treated distal radius fracture in Japan using inpatient database: cross-sectional study.

INTRODUCTION: The purpose of this study was to clarify the relationship between seasonal variation and distal radius fractures using diagnosis procedure combination data in Japan. MATERIALS AND METHODS: The participants were hospitalized patients who underwent surgical treatment for distal radius fracture as the primary injury at hospitals that introduced the diagnosis procedure combination system between April 2011 and March 2016. We obtained a summary table of the month of admission, region of residence, age at admission, and sex of the patients from the Ministry of Health, Labour and Welfare and evaluated it by month, region, age group, and sex. RESULTS: The total number of patients for the 5 years from 2011 to 2016 was 105,025. There were 29,224 male and 75,801 female participants, with a female-to-male ratio of 2.6. The mean age was 60.2 (standard deviation, 20.8) years. Distal radius fractures occurred more frequently in the winter, especially among female individuals in eastern Japan. Female participants aged ≥ 50 years tended to have a higher incidence of distal radius fracture in winter. The incidence of distal radius fracture among male participants aged 0-19 years was higher from spring to autumn. CONCLUSION: Surgically treated distal radius fractures occur frequently during the winter months among female individuals in eastern Japan or those aged ≥ 50 years and increase from school age to adolescence, especially in male individuals from spring to autumn. We should be aware of the high incidence of distal radius fractures in winter, especially in regions with snowfall and cold temperatures.

The use of ultrasonography as an effective screening tool for chronic posterior cruciate ligament injuries.

PURPOSE: We aimed to explore the applicability and validity of ultrasonography for diagnosing chronic posterior cruciate ligament (PCL) injuries. METHODS: PCL thickness was measured at 2 cm proximal to the tibia insertion site. Using the same ultrasonography image, the angle tangent to the PCL from the tibia insertion site was also measured. These data were analyzed by plotting the receiver operating curve (ROC), and the sensitivity and specificity were calculated according to the optimal cut-off point. Ultrasonography data from the PCLinjured knee were compared with those from the contralateral uninjured knee of the same patient. RESULTS: Twelve men and six women, with a mean age of 28.8 ± 14.0 years, were included in this study. The mean time from injury to medical examination was 10.0 ± 6.7 months. The mean thickness of the PCL was 8.1 ± 1.9 mm on the affected side and 5.8 ± 1.2 mm on the uninjured side, with the affected side being significantly thicker. ROC analysis revealed that the optimal cut-off value for the thickness of chronic PCL injuries was 6.5 mm (sensitivity 83.3%, specificity 77.8%, area under the curve [AUC] = 0.87). The optimal cut-off value for the angle was 20° (sensitivity 88.9%, specificity 94.4%, AUC = 0.96). CONCLUSION: Ultrasonography is useful as a screening tool for chronic PCL injuries. The optimal cut-off point was 6.5 mm for thickness and 20° for angle. LEVEL OF EVIDENCE: IV.

Characteristics of Scoliosis in Mice Induced by Chondrocyte-specific Inactivation of L-type Amino Acid Transporter 1.

STUDY DESIGN: A mouse study of the Slc7a5 gene using conditional knockout to assess the effects of its inactivation on spinal deformity. OBJECTIVES: This study aimed to investigate whether the mice with scoliosis [induced by chondrocyte-specific inactivation of L-type amino acid transporter 1 (LAT1)] show a developmental process similar to that of pediatric scoliosis and to examine the relationship between reduced bone mineral density (BMD) and scoliosis. Furthermore, we aimed to obtain insights into elucidating the etiology and pathophysiology of scoliosis. SUMMARY OF BACKGROUND DATA: The etiology and pathogenesis of scoliosis are not fully understood despite substantial investigative efforts. LAT1 is an amino acid transporter that mediates the cellular uptake of large neutral amino acids. A recent study revealed that chondrocyte-specific inactivation of LAT1 in mice results in scoliosis (Col2a1-Cre;Slc7a5fl/fl mice: "Sko mice"). MATERIALS AND METHODS: Body length, body weight, Cobb angle, vertebral body rotation angle, and BMD at 1, 2, 4, 6, and 8 weeks of age were examined and statistically compared with those of normal control mice. Pathologic and morphologic evaluation was performed on specimens from 10-week-old euthanized mice. RESULTS: The Sko mice developed thoracic scoliosis in infancy without congenital malformations. This spinal deformity progressed rapidly during growth, with diverse curve patterns and hypoplastic vertebral bodies. Pathologic examination revealed thickening of the growth plates and decreased osteoblasts, suggesting that impaired endochondral ossification was the cause of the scoliosis. Sko mice were also observed to have decreased BMD and degraded bone microstructure. Reduced BMD and bone quality may not be the causes of the onset and progression of scoliosis in the Sko mice. CONCLUSIONS: In Sko mice, the characteristics of scoliosis and vertebral pathology showed many similarities with syndromic scoliosis in humans. Endochondral ossification defects may impair growth, leading to scoliosis and decreased BMD.

Ultrasonographic diagnosis of medial meniscus posterior root tear in early knee osteoarthritis: a comparative study.

INTRODUCTION: This study aimed to detect medial meniscal posterior root tear (MMPRT) diagnostic methods with high sensitivity and specificity using dynamic ultrasonographic evaluation in patients with early knee osteoarthritis (OA) and demonstrate the usefulness of dynamic ultrasonographic medial meniscal extrusion (MME) evaluation in MMPRT diagnosis using a cutoff value. MATERIALS AND METHODS: Between 2018 and 2020, a total of 120 patients were diagnosed with early knee OA using clinical and radiographic findings. Dynamic ultrasonographic evaluations and magnetic resonance imaging were performed in all patients, and 47 patients who had and 73 patients who did not have MMPRT were classified into the MMPRT and non-MMPRT groups, respectively. Age, sex, femorotibial angle, MME of knee extension and flexion, and MME at weight-bearing were compared between the two groups. Additionally, the sensitivity and specificity of significant ultrasonographic findings were calculated using a receiver operating characteristic (ROC) curve. RESULTS: The MMEs under knee extension-flexion and weight-loading in the MMPRT group were significantly larger than those in the non-MMPRT group. ROC curve analysis for each ultrasonographic evaluation condition to diagnose MMPRT indicated that the sensitivity was 72-88% and the specificity was 66-85% when the cutoff values of MME under knee flexion at 0°, 90°, and weight-loading were set at 2.55 mm, 2.00 mm, and 3.55 mm, respectively. The highest sensitivity (88%) and specificity (85%) were exhibited upon > 2 mm MME at a knee flexion of 90° and were the most useful indicators for MME diagnosis. CONCLUSIONS: Ultrasonographic MME evaluations for MMPRT diagnosis showed relatively high sensitivity and specificity in patients with early knee OA. Dynamic ultrasonographic MME evaluation may lead to appropriate additional examinations, early diagnosis, and intervention for MMPRT in patients with early knee OA.

Medium-term Outcomes of Excision Using Surgical Microscope of Tenosynovial Giant Cell Tumors of the Hand.

BACKGROUND/AIM: The recurrence rate following the excision of tenosynovial giant cell tumors (TSGCT) of the hand is very high. Intraoperative application of a surgical microscope has been reported. However, to date, there are no reports of medium-term outcomes related to this technique. This study aimed to evaluate the medium-term outcomes of tumor excision using surgical microscope for TSGCT of the hand. PATIENTS AND METHODS: A total of 27 patients, who underwent an initial surgery for histologically-confirmed TSGCT of the hand, between 2008 and 2020, were included and evaluated. The mean follow-up time postoperatively was 6.8 years. Tumor recurrence and preoperative tumor characteristics were assessed. RESULTS: All tumors were adherent to tendons, tendon sheaths, neurovascular structures or periarticular ligaments and capsules. Bony lesions were observed in 11 tumors. The surgical microscope was used in 13 tumors. Recurrences were observed in three tumors (overall recurrence rate: 11%). Tumor characteristics were similar in both groups, but the recurrence rate in the group treated using the surgical microscope was 0%, whereas the recurrence rate in the group treated without the surgical microscope was 21%. Re-operations using the surgical microscope for recurrent tumors were performed, without recurrence postoperatively. CONCLUSION: Among patients with TSGCT of the hand treated with tumor excision using the surgical microscope, the postoperative recurrence rate was 0%. Based on the results of this study, the surgical microscope might be used for excision of TSGCTs of the hand.