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IntroductionAntiresorptive agent-related osteonecrosis of the jaw (ARONJ) is a rare but serious complication in patients receiving antiresorprtive agents (AR). However, the incidence of ARONJ after tooth extraction in patients with autoimmune disease (AID) remains unclear. The present study aimed to clarify the high-risk population of ARONJ in patients with AID.Materials and methodsThe study population comprised 232 patients treated with AR, AID or non-AID, who had undergone dental extraction from January 2011 to September 2017. The incidence and risk factors of ARONJ were analysed retrospectively. Additionally, the relationship between ARONJ and osteoporotic fracture (OF) and AR discontinuation during dental procedures was investigated.ResultsOf 232 patients, 10 developed ARONJ within 1 year of dental extraction. The incidence of ARONJ in patients with AID was higher than that in non-AID patients (2.0/100 person-year vs 0.5/100 person-year; p = 0.03). Among the AID patients, RA patients had strikingly high incidence of ARONJ (3.6/100 person-year). The incidence of neither ARONJ nor OF significantly differed between patients who continued and discontinued AR in the perioperative period.ConclusionPatients with AID who undergo dental extraction are at high risk of ARONJ. Discontinuation of AR would not significantly contribute to reduce the incidence of ARONJ in those patients.

ObjectivesTo collect clinical information and NOD2 mutation data on patients with Blau syndrome and to evaluate their prognosis.MethodsFifty patients with NOD2 mutations were analysed. The activity of each NOD2 mutant was evaluated in HEK293 cells by reporter assay. Clinical information was collected from medical records through the attending physicians.ResultsThe study population comprised 26 males and 24 females aged 0–61 years. Thirty-two cases were sporadic, and 18 were familial from 9 unrelated families. Fifteen different mutations in NOD2 were identified, including 2 novel mutations (p.W490S and D512V); all showed spontaneous nuclear factor kappa B activation, and the most common mutation was p.R334W. Twenty-six patients had fever at relatively early timepoints in the disease course. Forty-three of 47 patients had a skin rash. The onset of disease in 9 patients was recognised after BCG vaccination. Forty-five of 49 patients had joint lesions. Thirty-eight of 50 patients had ocular symptoms, 7 of which resulted in blindness. After the diagnosis of Blau syndrome, 26 patients were treated with biologics; all were antitumour necrosis factor agents. Only 3 patients were treated with biologics alone; the others received a biologic in combination with methotrexate and/or prednisolone. None of the patients who became blind received biologic treatment.ConclusionsIn patients with Blau syndrome, severe joint contractures and blindness may occur if diagnosis and appropriate treatment are delayed. Early treatment with a biologic agent may improve the prognosis.

Introduction Xanthogranulomatous prostatitis is a very rare benign inflammatory lesion of the prostate that may be similar to prostatic carcinoma in clinical presentation and radiological characteristics. Case presentation A 77‐year‐old man was admitted to our hospital because of high prostate‐specific antigen level. Magnetic resonance imaging showed a 6.5 cm in diameter multifocal mass with hemorrhage at the base of the left lobe of the prostate. Biopsy was performed. Histopathological examination revealed no evidence of malignancy. After biopsy, he developed recurring fever, so the patient was treated with open suprapubic tumor resection to control infection. Pathological examination revealed xanthogranulomatous prostatitis. Conclusion It is necessary to diagnose xanthogranulomatous prostatitis by cooperation between urologists and pathologists, and consider xanthogranulomatous prostatitis as a differential diagnosis. Treatment should be conservative in principle; however, surgical intervention may be necessary.

Introduction Methotrexate‐associated lymphoproliferative disorders appear during treatment with methotrexate as an immunosuppressive drug. However, the mechanism and frequency are still unknown, and the treatment is undefined. Case presentation A 76‐year‐old woman was admitted to the hospital with back pain, and magnetic resonance imaging showed a tumor in the right adrenal region. She had received methotrexate for rheumatoid arthritis. Enhanced computed tomography showed a tumor of 90 mm in diameter on the dorsal side of the liver abutting to the inferior vena cava. The preoperative diagnosis was a hepatic invasion of right adrenocortical carcinoma and right adrenalectomy was performed. The histopathological diagnosis was diffuse large B‐cell lymphoma. The final diagnosis was methotrexate‐associated lymphoproliferative disorders. Conclusion It is important to consider methotrexate‐associated lymphoproliferative disorders before surgery when neoplastic lesions are found in patients taking methotrexate.

BackgroundIn Japan, nivolumab administration is the standard treatment for patients with unresectable advanced or recurrent esophageal squamous cell carcinoma (ESCC) who are refractory or intolerant to fluoropyrimidines and platinum-based chemotherapy. We determined if inflammatory prognostic factors are useful in patients with ESCC treated with nivolumab monotherapy.MethodsThe clinical data of patients with ESCC treated with nivolumab monotherapy as the second- or later-line treatment were retrospectively analyzed. Neutrophil/lymphocyte, platelet/lymphocyte, and C-reactive protein/albumin ratios (CAR); prognostic index; and prognostic nutritional index were investigated. Cut-off values for each factor were determined according to overall survival using time-dependent receiver operating characteristic curves.ResultsDuring January 2017–June 2021, 93 consecutive patients with ESCC were enrolled from five institutions (median age, 70 years; male, 77%). With a median follow-up period of 9.1 (range, 1.0–34.7) months, the median overall and progression-free survival were 12.8 (95% confidence interval [CI], 9.0–16.6) and 4.0 (95% CI, 2.6–5.4) months, respectively. Of five inflammatory prognostic factors, the cut-off value for CAR was 0.62; prognosis was significantly longer in those with CAR < 0.62 (hazard ratio, 0.39; 95% CI, 0.22–0.67; p = 0.001).ConclusionsInflammatory prognostic factors were useful in predicting prognosis for ESCC patients pretreated with nivolumab, especially for those with CAR < 0.62, suggesting that CAR adequately reflects prognosis.

Introduction Nivolumab is effective for advanced renal cell carcinoma; however, reports are limited wherein nivolumab is combined with sequential therapy of angiogenesis inhibitors and metastasectomy. Case presentation A 65‐year‐old man was diagnosed with left renal cell carcinoma of cT2aN0M1 with lung metastasis. The patient underwent nephrectomy and sequential therapy with interferon‐α and angiogenesis inhibitors. Lung metastasis decreased by angiogenesis inhibitors, but new right adrenal gland metastasis appeared. Nivolumab as the fifth systemic therapy remarkably shrank the metastasis. After discontinuing nivolumab therapy, the metastasis continued to shrink. The patient underwent adrenalectomy, and pathological analysis revealed no remnant cancer cells in the specimen, confirming a pathological complete response. Twenty months postoperatively, he remains in good health without recurrence. Conclusion We report a rare case with renal cell carcinoma of a pathological complete response by nivolumab after angiogenesis inhibitors.

Background Cardiovascular disease is a frequent cause of death in peritoneal dialysis patients. Biocompatible peritoneal dialysis solutions with neutral pH have been anticipated to reduce cardiovascular disease more than conventional peritoneal dialysis solutions with low pH, but it remains unclear which factors at peritoneal dialysis initiation increase cardiovascular risk in patients using biocompatible peritoneal dialysis solutions. This study was undertaken to investigate which clinical factors at peritoneal dialysis initiation, including peritoneal transport status, are associated with cardiovascular event in patients using biocompatible peritoneal dialysis solution. Methods This retrospective cohort study of peritoneal dialysis patients using biocompatible solutions with neutral pH assessed relations of clinical parameters at peritoneal dialysis initiation to cardiovascular event during the subsequent five years. Results Of 102 patients who started peritoneal dialysis, cardiovascular event occurred in 18. Age, history of cardiovascular disease before peritoneal dialysis initiation, hemoglobin, serum albumin, C-reactive protein, peritoneal permeability defined by the ratio of dialysate to plasma creatinine concentration at 4 hr (D/Pcre) in peritoneal equilibration test (PET), number of patients in each PET category defined by D/Pcre, and peritoneal protein clearance significantly differed between patients with and without cardiovascular event. For patients divided according to PET category using Kaplan–Meier method, the group of high average to high peritoneal transporters exhibited significantly high incidence of cardiovascular event and mortality compared with the groups of low and low-average peritoneal transporters (Log rank; p = 0.0003 and 0.005, respectively). A Cox proportional hazards model showed independent association of PET category classification with cardiovascular event. Conclusions Peritoneal permeability expressed as PET category at peritoneal dialysis initiation is an independent cardiovascular risk factor in peritoneal dialysis patients using biocompatible peritoneal dialysis solution with neutral pH. Greater peritoneal permeability at peritoneal dialysis initiation might reflect subclinical vascular disorders.

1 To determine the binding characteristics of a highly potent agonist for protease‐activated receptor‐2 (PAR2), 2‐furoyl‐Leu‐Ile‐Gly‐Arg‐Leu‐amide (2‐furoyl‐LIGRL‐NH2), whole‐cell binding assays were performed utilising a radioactive ligand, [3H]2‐furoyl‐LIGRL‐NH2. 2 Specific binding of [3H]2‐furoyl‐LIGRL‐NH2 was observed in NCTC2544 cells, dependent upon PAR2 expression, and competitively displaced by the addition of unlabeled PAR2 agonists. Scatchard analysis of specific saturation binding suggested a single binding site, with Kd of 122±26.1 nM and a corresponding Bmax of 180±6 f mol in 3.0 × 105 cells. 3 The relative binding affinities of a series of modified PAR2 agonist peptides obtained from competition studies paralleled their relative EC50 values for Ca2+ mobilisation assays, indicating improved binding affinities by substitution with 2‐furoyl at the N‐terminus serine. 4 Pretreatment of cells with trypsin reduced specific binding of [3H]2‐furoyl‐LIGRL‐NH2, demonstrating direct competition between the synthetic agonist peptide and the proteolytically revealed tethered ligand for the binding site of the receptor. 5 In HCT‐15 cells endogenously expressing PAR2, the binding of [3H]2‐furoyl‐LIGRL‐NH2 was displaced by addition of unlabeled ligands, Ser‐Leu‐Ile‐Gly‐Lys‐Val (SLIGKV‐OH) or 2‐furoyl‐LIGRL‐NH2. The relative binding affinity of 2‐furoyl‐LIGRL‐NH2 to SLIGKV‐OH was comparable to its relative EC50 value for Ca2+ mobilisation assays. 6 The binding assay was successfully performed in monolayers of PAR2 expressing NCTC2544 and human umbilical vein endothelial cells (HUVEC), in 96‐ and 24‐well plate formats, respectively. 7 These studies indicate that [3H]2‐furoyl‐LIGRL‐NH2 binds to human PAR2 at its ligand‐binding site. The use of this radioligand will be valuable for characterising chemicals that interact to PAR2. British Journal of Pharmacology (2005) 145, 255–263. doi:10.1038/sj.bjp.0706189