Relationship between interictal epileptiform discharges under medetomidine sedation and clinical seizures in canine idiopathic epilepsy.

BACKGROUND: Electroencephalography (EEG) is required for the diagnosis of canine idiopathic epilepsy as a highest confidence level of diagnosis by the International Veterinary Epilepsy Task Force; however, EEG is seldom used and a standardised assessment method has not been reported. METHODS: Interictal EEG was performed under medetomidine sedation in dogs with idiopathic epilepsy and in control dogs. Epileptiform discharge (ED) frequency was compared between dogs with more severe and less severe seizures during one month before EEG and control dogs. RESULTS: All 10 dogs with more severe seizures had ED, as had 7 of 11 with less severe seizures. All epileptic dogs without ED had good long-term outcomes. ED frequency (number of ED per five minutes) was significantly higher in dogs with more severe (median, 4.5) than with less severe seizure (median, 0.46) and in the control dogs (median, 0.15). An ED frequency greater than 0.8 was considered to indicate epilepsy. CONCLUSION: Interictal EEG in a light sleep state under medetomidine sedation had a high detection rate of ED, and ED frequency had a positive correlation with the recent severity of epileptic seizures. This allows interictal EEG recordings to be used as a simplified and objective test that may help to diagnose epilepsy and to assess the recent severity of the disease in dogs.

One-year maintenance with routine assessment of patient index data 3-based remission may inhibit radiographic progression in patients with rheumatoid arthritis treated with routine clinical therapy: A retrospective comparison of radiographic outcome and its prognostic factors between maintained remissions with patient-reported outcome index and physician-oriented disease activity indices.

OBJECTIVES: We investigated whether the maintenance of routine assessment of patient index data 3 (RAPID3) remission for one year (RAPID3-MR) may predict good radiographic outcomes. We also compared radiographic progression to prognostic factors among patients with RAPID3-MR, with the maintenance of clinical disease activity index remission for one year (CDAI-MR) or with the maintenance of 28 joint count disease activity score remission for one year (DAS28-MR). METHODS: Of 1220 patients with available clinical data, 92 with RAPID3-MR, 80 with RAPID3-NMR (not satisfying RAPID3-MR), 45 with CDAI-MR, and 75 with DAS28-MR were retrospectively investigated. CDAI and DAS28 for clinical outcomes and the modified total Sharp score (mTSS) for radiographic joint damage were investigated for at least one year. RESULTS: RAPID3, CDAI, DAS28, and their categories remained unchanged or significantly improved in RAPID3-MR patients but significantly deteriorated in RAPID3-NMR patients. The mean annual ΔmTSS was significantly lower in RAPID3-MR patients (0.12 ± 0.55) than in RAPID3-NMR patients (0.54 ± 1.27) (p = 0.025). There was no significant difference among RAPID3-MR patients, CDAI-MR patients (0.06 ± 0.85), and DAS28-MR patients (0.11 ± 0.89). The baseline mTSS (p = 0.038) and monotherapy with nonbiological disease-modifying antirheumatic drugs (p = 0.033) were good prognostic factors in RAPID3-MR patients. CONCLUSIONS: One-year RAPID3 remission maintenance may predict good radiographic outcomes.

Validation of major prognostic models for metastatic urothelial carcinoma using a multi-institutional cohort of the real world.

BACKGROUND: Several prognostic models predicting survival of patients with metastatic urothelial carcinoma (UC) have been developed; however, of them, the first model by Bajorin in 1999 is still the most representative and widely used, and validations of newer models are lacking. This study aimed to validate three major prognostic models for metastatic UC constructed based on clinical trials. METHODS: We reviewed 200 patients with metastatic UC who received first-line chemotherapy at our five affiliate institutions between 2003 and 2011. Using this multi-institutional cohort, we validated the following models: the "Bajorin model," a model consisting of visceral metastasis and performance status; the "Apolo model," a nomogram including visceral metastasis, performance status, albumin and hemoglobin; and the "Galsky model," a nomogram including leukocyte count, number of sites of visceral metastases, site of primary tumor, performance status and lymph node metastasis. Harrell's c-index was calculated for each model. Cox proportional hazards regression model was used for multivariate analysis. RESULTS: Among 200 patients, 171 (85.5%) died during the follow-up, with a median survival of 12.0 months. Multivariate analysis demonstrated ECOG performance status, visceral metastasis and leukocyte count to be independent predictors of overall survival. C-index results (95% confidence interval) were Bajorin: 0.86 (0.74-0.95); Apolo: 0.89 (0.78-0.98); and Galsky: 0.82 (0.69-0.93). CONCLUSIONS: All models were demonstrated to have high external validities in real-world patients, and of them, the "Apolo model" achieved the highest c-index in the present population. Further studies with larger populations are needed for establishment of the next standard model.

Intrapelvic Bulky Tumor as an Unusual Presentation of Erdheim-Chester Disease.

Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis, which is known to affect various organs; however, there have been no reports of its intrapelvic involvement. We herein describe the case of 69-year-old man who died of a rapidly-growing intrapelvic tumor, which was finally diagnosed as ECD at autopsy. Immunohistochemically, the tumor cells were positive for CD68 and BRAF V600E, and negative for CD1a. Since BRAF V600E has recently been reported to be specific to ECD, it can be a useful biomarker for diagnosis, especially in atypical cases.

Pretreatment neutrophil-to-lymphocyte ratio as an independent predictor of survival in patients with metastatic urothelial carcinoma: A multi-institutional study.

OBJECTIVES: To evaluate the prognostic significance of the pretreatment neutrophil-to-lymphocyte ratio in patients with metastatic urothelial carcinoma who underwent salvage chemotherapy. METHODS: We reviewed 200 metastatic urothelial carcinoma patients who received salvage chemotherapy at our five affiliate institutions between 2003 and 2011. The associations of pretreatment clinicopathological factors, including neutrophil-to-lymphocyte ratio, with cancer-specific survival and overall survival from the start of chemotherapy were assessed. Cox proportional hazards model was used for multivariate analysis. RESULTS: A total of 15 cases with missing data were excluded. Among the remaining 185 patients, 157 died during follow up, with a median survival of 13.0 months. Multivariate analysis showed that the pretreatment neutrophil-to-lymphocyte ratio ≥3, Eastern Cooperative Oncology Group performance status ≥2 and liver metastasis were independent poor prognostic factors, both for cancer-specific survival and overall survival. A prognostic model predicting overall survival was constructed based on the number of these three variables (0, 1 and ≥ 2). The classified patients showed significantly different overall survival (each P < 0.0001, log-rank test), with Harrell's concordance index as high as 0.81. CONCLUSIONS: Pretreatment neutrophil-to-lymphocyte ratio elevation was an independent poor prognostic factor for metastatic urothelial carcinoma undergoing salvage chemotherapy. Our newly constructed prognostic model including the pretreatment neutrophil-to-lymphocyte ratio proved to be an excellent discriminator of overall survival.

Inhibition of radiographic joint damage in rheumatoid arthritis patients in DAS28 remission using single- or combined with methotrexate non biological disease-modifying antirheumatic drug therapy in routine clinical practice.

OBJECTIVE: We retrospectively investigated the inhibitory effect on radiographic joint damage (RJD) for non-biological disease-modifying antirheumatic drug (non-bioDMARD) monotherapy or methotrexate (MTX) combination therapy for rheumatoid arthritis (RA) in the disease activity score with 28 joint counts with erythrocyte sedimentation rate (DAS28) remission. METHODS: Eighty-four patients (55 cases of monotherapy, 29 cases of MTX-combination therapy) in DAS28 remission (DAS28 ≤ 2.6) were investigated from 538 RA patients newly registered between February 2007 and August 2010. The patients were analyzed for radiological assessments using the modified total Sharp score/year (mTSS/y). RESULTS: The remission rates and ΔmTSS/y for each agent using monotherapy were 7.1% and 0.17 for sulfasalazine; 11.9% and 0.49 for bucillamine (BUC); and 23.9% and 2.06 for MTX. Those using combination therapy were 6.8% and 1.39 for MTX + BUC; 23.5% and -1.64 for MTX + leflunomide; and 8.0% and 0.31 for MTX + tacrolimus. The cumulative distribution in the single and combination therapy groups showed improvement of percentages in structural remission from baseline to 1-year treatment, 34.1% to 60.9% (P < 0.05) and from 0% to 56.7%(P < 0.0001), respectively. Baseline mTSS (r = 0.67, P < 0.0001), disease duration (r = 0.40, P < 0.01), swollen joint counts (r = 0.33, P < 0.05), and anti-cyclic citrullinated peptide antibody (r = 0.31, P < 0.05) were useful predictors of RJD for non-bioDMARD monotherapy, but not for combination therapy. CONCLUSION: Satisfactory inhibition of RJD was observed in the DAS28 remission cases of monotherapy or MTX combination therapy with a non-bioDMARD.

Silicate Urolithiasis during Long-Term Treatment with Zonisamide.

Silicate urinary calculi are rare in humans, with an incidence of 0.2% of all urinary calculi. Most cases were related to excess ingestion of silicate, typically by taking magnesium trisilicate as an antacid for peptic ulcers over a long period of time; however, there also existed unrelated cases, whose mechanism of development remains unclear. On the other hand, zonisamide, a newer antiepileptic drug, is one of the important causing agents of iatrogenic urinary stones in patients with epilepsy. The supposed mechanism is that zonisamide induces urine alkalinization and then promotes crystallization of urine components such as calcium phosphate by inhibition of carbonate dehydratase in renal tubular epithelial cells. Here, we report a case of silicate urolithiasis during long-term treatment with zonisamide without magnesium trisilicate intake and discuss the etiology of the disease by examining the silicate concentration in his urine.

Effect of reduced form of coenzyme Q10 on cyclosporine nephrotoxicity.

OBJECTIVES: Cyclosporine, a potent immunosuppressant, has nephrotoxic adverse effects that may be mediated by oxidative stress. The reduced form of coenzyme Q10 has antioxidant effects. The aim of the present study was to evaluate the effect of the reduced form of coenzyme Q10 on cyclosporine nephrotoxicity. MATERIALS AND METHODS: Six-week-old male Wistar rats were divided into 3 groups (10 animals each). Group 1 (control) received olive oil only. Group 2 received cyclosporine (30 mg/kg/d, which is an experimentally nephrotoxic dose). Group 3 received cyclosporine (30 mg/kg/d) and the reduced form of coenzyme Q10 (600 mg/kg/d). The cyclosporine and the reduced form of coenzyme Q10 were given orally for 4 weeks. Daily urinary albumin excretion, serum creatinine level, and urinary 8-hydroxydeoxyguanosine level were measured, and renal tissue was evaluated by immunohistochemistry. RESULTS: In rats treated with cyclosporine and the reduced form of coenzyme Q10 (group 3), there were significantly less abnormalities in mean urinary albumin excretion (group 1: 2.8 ± 0.5; group 2: 41 ± 7; group 3: 21 ± 4 µg/d), serum creatinine (group 1: 1.0 ± 0.2; group 2: 1.8 ± 0.4; group 3: 1.4 ± 0.3 mg/dL), and urine 8-hydroxydeoxyguanosine levels (group 1: 7 ± 3; group 2: 10 ± 3; group 3: 7 ± 1 mg/mL creatinine) than rats treated with cyclosporine alone (group 2). There were 8-hydroxydeoxyguanosine deposits seen in the proximal tubular cells of group 2 that were not present in rats treated with the reduced form of coenzyme Q10 (group 3). CONCLUSIONS: The reduced form of coenzyme Q10 may prevent or minimize cyclosporine nephrotoxicity by an antioxidant effect.