Prostaglandin E2 receptor type 2-selective agonist prevents the degeneration of articular cartilage in rabbit knees with traumatic instability

[Introduction]Osteoarthritis (OA) is a common cause of disability in older adults. We have previously reported that an agonist for subtypes EP2 of the prostaglandin E2 receptor (an EP2 agonist) promotes the regeneration of chondral and osteochondral defects. The purpose of the current study is to analyze the effect of this agonist on articular cartilage in a model of traumatic degeneration. [Methods]The model of traumatic degeneration was established through transection of the anterior cruciate ligament and partial resection of the medial meniscus of the rabbits. Rabbits were divided into 5 groups; G-S (sham operation), G-C (no further treatment), G-0, G-80, and G-400 (single intra-articular administration of gelatin hydrogel containing 0, 80, and 400 μg of the specific EP2 agonist, ONO-8815Ly, respectively). Degeneration of the articular cartilage was evaluated at 2 or 12 weeks after the operation. [Results]ONO-8815Ly prevented cartilage degeneration at 2 weeks, which was associated with the inhibition of matrix metalloproteinase-13 (MMP-13) expression. The effect of ONO-8815Ly failed to last, and no effects were observed at 12 weeks after the operation. [Conclusions]Stimulation of prostaglandin E2 (PGE2) via EP2 prevents degeneration of the articular cartilage during the early stages. With a system to deliver it long term, the EP2 agonist could be a new therapeutic tool for OA

酸性尿酸アンモニウム結石の1例

32歳女.右肺部痛, 膿尿を主訴とした.plain radiograph, drip infusion pyelographyにて右腎結石症, 右水腎症と診断され, 体外衝撃波腎結石砕石術を施行した.結石の成分は, 酸性尿酸アンモニウム結石98%以上であった.症例は3年前より過度の拒食症に罹患し低栄養状態が続いていた時期があり, 本結石の原因として過度の拒食による低カロリー食と推測されたA 32-year-old woman complained of right back pain and pyuria. The plain radiograph (KUB) and drip infusion pyelography (DIP) demonstrated a right renal stone and hydronephrosis. The stone was successfully treated using extracorporeal shock wave lithotripsy. Infrared spectrophotometry revealed that the stone was composed of pure ammonium acid urate. The patient had a 3-year history of excessive anorexia. The low-caloric diet was considered to have caused the disease

Hip Arthroscopic Synovectomy and Labral Repair in a Patient With Rheumatoid Arthritis With a 2-Year Follow-up

The arthroscopic surgical procedures reported previously for a rheumatic hip joint have been primarily performed as diagnostic procedures. Only a few studies have reported the success of arthroscopic surgery in hip joint preservation. We encountered a special case in which joint remodeling was seen in a patient with rheumatoid arthritis treated with biological drugs after hip arthroscopic synovectomy and labral repair. We report the case of a 39-year-old woman with rheumatism, which was controlled with tocilizumab, prednisolone, and tacrolimus. The hip joint showed Larsen grade 3 destruction, and the Harris Hip Score was 55 points. Because of the patient's strong desire to undergo a hip preservation operation, we performed hip arthroscopic synovectomy and repair of a longitudinal labral tear. After 2.5 years, the joint space had undergone rebuilding with improvement to Larsen grade 2, and the Harris Hip Score had improved to 78 points; the patient was able to return to work with the use of 1 crutch. It is possible to perform hip arthroscopic surgery for rheumatoid arthritis with a hip preservation operation with biological drugs

Treatment of simple bone cysts using endoscopic curettage: a case series analysis

Abstract Background Endoscopic curettage is considered applicable for the treatment of simple bone cysts with the expectation that it might be less invasive than open curettage. In this study, we investigated the efficacy of endoscopic curettage for the treatment of simple bone cysts. The goal was to investigate the incidence of cyst recurrence and bone healing after endoscopic curettage. Moreover, complications and functionality at the final follow-up were evaluated. Methods From 2003 to 2014, 37 patients with simple bone cysts underwent endoscopic curettage. Twenty-four were male and 13 were female, with a mean age of 14.7 years. Endoscopic curettage was performed with the support of an arthroscope via 7–8 mm holes penetrated by cannulated drills with a small incision. The cysts underwent curettage using angled curettes, rongeurs, and an electrical shaver until the normal bone was observed in the medullary cavity. To investigate the bone healing after endoscopic curettage, we evaluated the consolidation of the cyst at the final evaluation (Modified Neer Classification) and the time to solid union after operation, which was defined as the sufficient thickness of the cortical bone to prevent fracture and allow physical activities. Results Recurrence occurred in seven patients (18.9%). A log-rank analysis revealed that contact with the physis was associated with recurrence (p = 0.006). Among 31 patients (83.7%), the consolidation of cyst was considered healed at the final X-ray follow-up period, and in these patients, the mean time taken for solid union of cortical bone thinning was 4.0 months (standard deviation, 2.4). With regard to major complications of endoscopic curettage, a transient radial nerve palsy and two postoperative fractures occurred. The former problem was managed conservatively and the latter problems by transient internal fixation; these problems were managed without any further complications. All patients had a good postoperative function. Conclusions Endoscopic curettage might be a useful alternative as it is a minimally invasive procedure for the treatment of simple bone cysts. Considering the relatively smaller size of this study, further investigation should be necessary for deducing the reliable conclusion

Predictive factors for hyperglycaemic progression in patients with schizophrenia or bipolar disorder

Background: Patients with schizophrenia or bipolar disorder have a high risk of developing type 2 diabetes. Aims: To identify predictive factors for hyperglycaemic progression in individuals with schizophrenia or bipolar disorder and to determine whether hyperglycaemic progression rates differ among antipsychotics in regular clinical practice. Method: We recruited 1166 patients who initially had normal or prediabetic glucose levels for a nationwide, multisite, l-year prospective cohort study to determine predictive factors for hyperglycaemic progression. We also examined whether hyperglycaemic progression varied among patients receiving monotherapy with the six most frequently used antipsychotics. Results: High baseline serum triglycerides and coexisting hypertension significantly predicted hyperglycaemic progression. The six most frequently used antipsychotics did not significantly differ in their associated hyperglycaemic progression rates over the 1-year observation period. Conclusions: Clinicians should carefully evaluate baseline serum triglycerides and coexisting hypertension and perform strict longitudinal monitoring irrespective of the antipsychotic used

Meningiomas in patients with neurofibromatosis type 2 predominantly comprise ‘immunogenic subtype’ tumours characterised by macrophage infiltration

Abstract Although recent molecular analyses revealed that sporadic meningiomas have various genetic, epigenetic, and transcriptomic profiles, meningioma in patients with neurofibromatosis type 2 (NF2) have not been fully elucidated. This study investigated meningiomas' clinical, histological, and molecular characteristics in NF2 patients. A long-term retrospective follow-up (13.5 ± 5.5 years) study involving total 159 meningiomas in 37 patients with NF2 was performed. Their characteristics were assessed using immunohistochemistry (IHC), bulk-RNA sequencing, and copy number analysis. All variables of meningiomas in patients with NF2 were compared with those in 189 sporadic NF2-altered meningiomas in 189 patients. Most meningiomas in NF2 patients were stable, and the mean annual growth rate was 1.0 ± 1.8 cm3/year. Twenty-eight meningiomas (17.6%) in 25 patients (43.1%) were resected during the follow-up period. WHO grade I meningiomas in patients with NF2 were more frequent than in sporadic NF2-altered meningiomas (92.9% vs. 80.9%). Transcriptomic analysis for patients with NF2/sporadic NF2-altered WHO grade I meningiomas (n = 14 vs. 15, respectively) showed that tumours in NF2 patients still had a higher immune response and immune cell infiltration than sporadic NF2-altered meningiomas. Furthermore, RNA-seq/IHC-derived immunophenotyping corroborated this enhanced immune response by identifying myeloid cell infiltration, particularly in macrophages. Clinical, histological, and transcriptomic analyses of meningiomas in patients with NF2 demonstrated that meningiomas in NF2 patients showed less aggressive behaviour than sporadic NF2-altered meningiomas and elicited a marked immune response by identifying myeloid cell infiltration, particularly of macrophages

Functional evaluation of PDGFB-variants in idiopathic basal ganglia calcification, using patient-derived iPS cells

Abstract Causative genes in patients with idiopathic basal ganglia calcification (IBGC) (also called primary familial brain calcification (PFBC)) have been reported in the past several years. In this study, we surveyed the clinical and neuroimaging data of 70 sporadic patients and 16 families (86 unrelated probands in total) in Japan, and studied variants of PDGFB gene in the patients. Variant analyses of PDGFB showed four novel pathogenic variants, namely, two splice site variants (c.160 + 2T > A and c.457−1G > T), one deletion variant (c.33_34delCT), and one insertion variant (c.342_343insG). Moreover, we developed iPS cells (iPSCs) from three patients with PDGFB variants (c.160 + 2T > A, c.457−1G > T, and c.33_34 delCT) and induced endothelial cells. Enzyme-linked immunoassay analysis showed that the levels of PDGF-BB, a homodimer of PDGF-B, in the blood sera of patients with PDGFB variants were significantly decreased to 34.0% of that of the control levels. Those in the culture media of the endothelial cells derived from iPSCs of patients also significantly decreased to 58.6% of the control levels. As the endothelial cells developed from iPSCs of the patients showed a phenotype of the disease, further studies using IBGC-specific iPSCs will give us more information on the pathophysiology and the therapy of IBGC in the future