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The activity of 6-phosphofructo-1-kinase is strictly controlled by fructose-2,6-bisphosphate, the level of which is regulated by another enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFK2/FBP2). PFK2/FBP2 is a bifunctional enzyme, having kinase and phosphatase activities, and regulates both glycolysis and gluconeogenesis. Here, we examined the hormonal regulation of the PFK2/FBP2 gene in vitro using the reporter assay, the electromobility shift assay (EMSA), and the chromatin immunoprecipitation (ChIP) assay in HuH7 cells and also using the mouse liver in vivo. We found that the transcriptional activity of the PFK2/FBP2 gene was stimulated by insulin and inhibited by cAMP and glucocorticoid. Liver X receptor (LXR) α showed a potent and specific stimulatory effect on PFK2/FBP2 gene transcription. Deletion and mutagenesis analyses identified the LXR response element (LXRE) in the 5'-promoter region of the PFK2/FBP2 gene. Binding of LXRα was confirmed by the EMSA and ChIP assay. Endogenous PFK2/FBP2 mRNA in the mouse liver was increased in the fasting/refeeding state compared with the fasting state. Altogether, PFK2/FBP2 gene transcription is found to be regulated in a way that is more similar to other glycolytic enzyme genes than to gluconeogenic genes. Furthermore, our data strongly suggest that LXRα is one of the key regulators of PFK2/FBP2 gene transcription. [ABSTRACT FROM AUTHOR]

Background/aim: Despite the well-publicized clinical outcomes after unplanned excision (UE) and re-excision (re-excision) in patients with soft-tissue sarcoma (STS), there is little information about the real-life referral patterns for UE, such as patient profile, details of procedures, and subsequent management after UE. We aimed to investigate the characteristics of patients with UE who were referred to sarcoma-specific centers., Patients and Methods: Between May 2022 and June 2023, we registered 97 patients who underwent UE and were referred to sarcoma-specific centers in Japan. We excluded those with well-differentiated liposarcomas and dermatofibrosarcoma protuberances. We investigated the details of UE and additional treatment after UE., Results: There were 49 men and 48 women, with a mean age of 62 years. A broad range of surgeons performed UE; 36 plastic surgeons, 22 orthopedic surgeons, 17 general surgeons, 17 dermatologists, and 5 others. The mean tumor size was 4.1 cm. Local anesthesia was administered to 58 patients. Forty-five patients underwent UE without prior magnetic resonance imaging. Inappropriate transverse skin incisions were performed in 42 patients. Of the 97 patients, 82 underwent re-excision after UE. The mean time between UE and date of initial presentation at the referral hospital was 46 days. The mean interval between UE and re-excision was 96 days. Of the 82 patients, 59 underwent soft-tissue reconstruction after re-excision., Conclusion: A broad range of surgeons performed UE. Continuous education about STS should be considered for all surgeons. UE should be avoided because residual tumors are common, and reconstructive surgery may be necessary., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Osteoid osteoma occasionally occur in the spine, but their malignant transformation is not common. We present an extremely rare case of the malignant transformation of an osteoid osteoma to high-grade osteosarcoma that formed in the pedicle and spread to the lateral mass of the cervical spine., Case Presentation: We report the case of an 18-year-old man who suffered from neck pain as an initial symptom. The size of the radiolucent lesion was 12 mm in diameter at the time of diagnosis. Intralesional tumour resection and autologous bone grafting were performed. The remaining tumour grew gradually for 40 months after the surgery; therefore, the tumour had grown rapidly till 51 months after the initial diagnosis. At this stage, the tumour size was approximately 6-fold larger than the initial size, and resulted in progressive paraplegia. A biopsy revealed that the tumour had transformed into a high-grade osteosarcoma. Heavy charged particle irradiation was performed to control tumour growth., Conclusions: There is a possibility of malignant transformation of osteoid osteoma. Patients with osteoid osteoma or osteoblastoma should be carefully observed, especially for recurrent tumours after an intralesional resection.

Case: A 76-year-old woman presented with a 2-month history of right shoulder pain with no apparent cause. Radiography revealed an ill-defined osteolytic lesion in the right scapular spine with a pathological fracture. Malignant bone tumor was suspected, and a biopsy was performed. Pathological examination with gold hydroxamic acid staining revealed phosphoglyceride crystal deposition. Lesion curettage was performed, and her symptoms improved. No recurrence was observed at the 3-year postoperative follow-up., Conclusion: Phosphoglyceride crystal deposition in the bone is an extremely rare disease. The gold hydroxamic acid staining method might be useful for the diagnosis of this condition., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C9)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Simultaneous administration of enteral formula and phenytoin in the clinical setting is known to reduce the plasma concentration of phenytoin. In this study, we examined the binding of phenytoin with enteral formulas and its components by quantifying the free phenytoin concentration. Furthermore, we investigated the effect of enteral formulas on gastrointestinal absorption of phenytoin in rats. The free phenytoin rate was reduced in vitro when phenytoin and enteral formula or pectin, a dietary fiber in enteral formulas, were co-administered. In vivo, when phenytoin and the enteral formula Mei Balance R ® were co-administered, the time to maximum plasma concentration (T max ) after oral administration was significantly increased. Moreover, the area under the phenytoin concentration-time curve from time zero to 6 h (AUC 0-6 h ) was significantly increased by co-administration of phenytoin with the enteral formula PG Soft EJ ® . These results showed the gastrointestinal absorption of phenytoin differs according to the type of enteral formula. In addition, we found the first time that plasma phenytoin levels increase when combined with enteral formula. Among the components of enteral formulas, in particular, milk protein delayed the absorption of phenytoin. Moreover, milk protein, casein and carrageenan tended to increase AUC 0-6 h . These results suggest the change in phenytoin concentration is due not only to the binding of enteral formula but also to the disintegration of components such as protein. Therefore, when co-administrated of phenytoin and enteral formula, phenytoin must be monitored frequently according to the enteral formula interaction.

Case: A 53-year-old man was referred to our institution for the treatment of sacral chordoma and underwent a wide resection. Multiple lung metastases were observed in both the lungs, a year after the surgery, and the diagnosis was confirmed by biopsy. The patient refused treatment, and the lesions continued to increase in size gradually. However, 3 years and 6 months after the surgery, computed tomography of both the lungs showed spontaneous regression of the lesions without any obvious causes. The metastatic lung lesions had disappeared at the final follow-up, 7 years and 5 months after the multiple pulmonary metastases were diagnosed., Conclusion: We report the first case of spontaneous regression of pathologically proven pulmonary metastases of a sacral chordoma., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B728)., (Copyright © 2021 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: To date, no standard treatments for primary bone sarcomas other than those for osteosarcoma, Ewing sarcoma and chondrosarcoma have been developed., Methods: The clinical characteristics and prognostic factors of 330 patients with primary bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma, listed in a nationwide tumour registry (Bone and Soft Tissue Tumor Registry in Japan) were investigated. The effects of adjuvant chemotherapy were determined by comparing the outcomes of patients with non-metastatic bone tumours who received surgery plus chemotherapy with those of patients who underwent surgery alone., Results: The most common diagnosis was undifferentiated high-grade pleomorphic sarcoma. Axial site tumours (47.8%) and distant metastases at presentation (24.5%) were frequent. The 5-year overall and progression-free survival rates were 44.9 and 39.9%, respectively. Prognostic factor analysis identified surgery as an independent predictor of overall survival, and distant metastases at presentation was significant and independent predictor of both overall and progression-free survival. No significant difference in outcome was observed between patients treated with surgery alone and those treated with surgery plus chemotherapy (P = 0.71)., Conclusions: Patients with bone sarcomas other than osteosarcoma, Ewing sarcoma and chondrosarcoma without metastasis at presentation have a relatively good prognosis with definitive surgery; however, the benefit of adjuvant chemotherapy is unclear., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The prevalence of quinolone- and macrolide-resistant Group B Streptococcus (GBS) is increasing worldwide, but the relationship between the resistance of GBS to these antibiotics and patient outcome remains unclear. Therefore, we evaluated whether blood stream infection caused by quinolone- or macrolide-resistant GBS is associated with high mortality. Our findings in 77 patients with GBS bacteremia demonstrate that quinolone and macrolide resistance may not be risk factors for 30-day mortality.

Macrophage recognition and phagocytosis of crystals is critical for the associated fibrosis and cancer. Of note, multi-walled carbon nanotubes (MWCNTs), the highly representative products of nanotechnology, induce macrophage NLRP3 inflammasome activation and cause asbestosis-like pathogenesis. However, it remains largely unknown how macrophages efficiently recognize MWCNTs on their cell surfaces. Here, we identify by a targeted screening of phagocyte receptors the phosphatidylserine receptors T cell immunoglobulin mucin 4 (Tim4) and Tim1 as the pattern-recognition receptors for carbon crystals. Docking simulation studies reveal spatiotemporally stable interfaces between aromatic residues in the extracellular IgV domain of Tim4 and one-dimensional carbon crystals. Further, CRISPR-Cas9-mediated deletion of Tim4 and Tim1 reveals that Tim4, but not Tim1, critically contributes to the recognition of MWCNTs by peritoneal macrophages and to granuloma development in a mouse model of direct mesothelium exposure to MWCNTs. These results suggest that Tim4 recognizes MWCNTs through aromatic interactions and mediates phagocytosis leading to granulomas., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)