The neuroprotection conferred with CLN pre-treatment was reduced with the Fas ligand (FasL) binding antibody Nok1, suggesting that the effects of CLN may involve a Fas:soluble FasL interaction. These findings indicate that CLN could possibly play a role in the prevention of AD pathogenesis, though the inhibition of Fas-mediated apoptosis.

IntroductionChronic Obstructive Pulmonary Disease (COPD) is characterized by high morbidity and mortality. Lung computed tomography parameters, individually or as part of a composite index, may provide more prognostic information than pulmonary function tests alone.AimTo investigate the prognostic value of emphysema score and pulmonary artery measurements compared with lung function parameters in COPD and construct a prognostic index using a contingent staging approach.Material-MethodsPredictors of mortality were assessed in COPD outpatients whose lung computed tomography, spirometry, lung volumes and gas transfer data were collected prospectively in a clinical database. Univariate and multivariate Cox proportional hazard analysis models with bootstrap techniques were used.Results169 patients were included (59.8% male, 61.1 years old; Forced Expiratory Volume in 1 second % predicted: 40.5±19.2). 20.1% died; mean survival was 115.4 months. Age (HR = 1.098, 95% Cl = 1.04–1.252) and emphysema score (HR = 1.034, 95% CI = 1.007–1.07) were the only independent predictors of mortality. Pulmonary artery dimensions were not associated with survival. An emphysema score of 55% was chosen as the optimal threshold and 30% and 65% as suboptimals. Where emphysema score was between 30% and 65% (intermediate risk) the optimal lung volume threshold, a functional residual capacity of 210% predicted, was applied. This contingent staging approach separated patients with an intermediate risk based on emphysema score alone into high risk (Functional Residual Capacity ≥210% predicted) or low risk (Functional Residual Capacity <210% predicted). This approach was more discriminatory for survival (HR = 3.123; 95% CI = 1.094–10.412) than either individual component alone.ConclusionAlthough to an extent limited by the small sample size, this preliminary study indicates that the composite Emphysema score-Functional Residual Capacity index might provide a better separation of high and low risk patients with COPD, than other individual predictors alone.

No abstract

Metastatic uveal melanoma is a rare malignancy with a poor prognosis. To date, systemic therapy has been ineffective; however, there are few data on the benefits of anti-CTLA4 or anti-PD-1 antibodies in sequence with liver-directed therapy. A retrospective cohort analysis was carried out on 37 consecutive patients managed in a tertiary referral centre examining the safety and efficacy of treatment; patterns of care; and impact on survival. The sequential treatment with transarterial chemotherapy (TAC), systemic immunotherapy (IT) and systemic chemotherapy was reviewed. In all, 18 patients in the series received sequential therapy. The median overall survival (OS) was 17 months (n=37), which compared favourably with previously reported series. Patients treated with TAC first or second line had an overall progression-free survival (PFS) of 9 months (n=29) and IT PFS 7 months (n=26). The overall response rate (ORR) for TAC first line was 26% and the disease control rate (DCR) was 65% (n=23). ORR for IT first line was 7%, DCR 77% (n=14). Second-line (cross-over) IT ORR was 16%, DCR 58% (n=12). For second-line (cross-over) TAC, ORR was 50% and DCR was 66% (n=6). Toxicity was manageable. There were no cases of autoimmune hepatitis. In this retrospective small series analysis in uveal melanoma, liver-directed therapy and IT in sequence have shown to be active and reasonably well tolerated. Further prospective clinical trials should clarify the role of these treatments and their potential survival benefit.