Bristol-Myers Squibb.

Exploratory CheckMate 040 analysis Advanced hepatocellular carcinoma Pre-and posttreatment blood samples Pretreatment tumour biopsies IHC analysis Gene expression profiling Inflammatory gene expression Inflammatory markers Higher PD-1 PD-L1 ≥1% PCR and serological testing Association with improved overall survival and response No association with survival Tumour microenvironment CD3 + /CD8 + T cells CD68 + /CD163 + macrophages Highlights Many inflammation-related markers are associated with response to nivolumab in HCC. Many inflammatory signature scores within tumour samples are associated with survival. Lower ratios of systemic inflammation markers are associated with clinical benefit. Patients with HCC demonstrated positive responses regardless of AFP and viral dynamics.

No abstract

Mistiming is not a unitary construct. Its extent is associated with maternal characteristics and behaviors. Future research on pregnancy intention should examine the extent of mistiming and consider alternatives to traditional definitions of intendedness.

Purpose:The purpose of this study was to compare performance metrics of postanalytical interpretive tools of the Region 4 Stork collaborative project to the actual outcome based on cutoff values for amino acids and acylcarnitines selected by the California newborn screening program.Methods:This study was a retrospective review of the outcome of 176,186 subjects born in California between 1 January and 30 June 2012. Raw data were uploaded to the Region 4 Stork Web portal as .csv files to calculate tool scores for 48 conditions simultaneously using a previously unpublished functionality, the tool runner. Scores for individual target conditions were deemed informative when equal or greater to the value representing the first percentile rank of known true-positive cases (17,099 cases in total).Results:In the study period, the actual false-positive rate and positive predictive value were 0.26 and 10%, respectively. Utilization of the Region 4 Stork tools, simple interpretation rules, and second-tier tests could have achieved a false-positive rate as low as 0.02% and a positive predictive value >50% by replacing the cutoff system with Region 4 Stork tools as the primary method for postanalytical interpretation.Conclusion:Region 4 Stork interpretive tools, second-tier tests, and other evidence-based interpretation rules could have reduced false-positive cases by up to 90% in California.

BackgroundInflammatory mediators, including acute phase reactants and cytokines, have been reported to be associated with clinical efficacy in patients with melanoma and other cancers receiving immune checkpoint inhibitors (ICI). Analyses of patient sera from three large phase II/III randomized ICI trials, one of which included a chemotherapy arm, were performed to assess whether baseline levels of C-reactive protein (CRP), interleukin-6 (IL-6) or neutrophil/lymphocyte (N/L) ratios were prognostic or predictive.Patients and methodsBaseline and on-treatment sera were analyzed by multiplex protein assays from immunotherapy-naïve patients with metastatic melanoma randomized 1:1 on the Checkmate-064 phase II trial of sequential administration of nivolumab followed by ipilimumab or the reverse sequence. Baseline sera, and peripheral blood mononuclear cells using automated cell counting, were analyzed from treatment-naïve patients who were BRAF wild-type and randomly allocated 1:1 to receive nivolumab or dacarbazine on the phase III Checkmate-066 trial, and from treatment-naïve patients allocated 1:1:1 to receive nivolumab, ipilimumab or both ipilimumab and nivolumab on the phase III Checkmate-067 trial.ResultsHigher baseline levels of IL-6 and the N/L ratio, and to a lesser degree, CRP were associated with shorter survival in patients receiving ICI or chemotherapy. Increased on-treatment levels of IL-6 in patients on the Checkmate-064 study were also associated with shorter survival. IL-6 levels from patients on Checkmate-064, Checkmate-066 and Checkmate-067 were highly correlated with levels of CRP and the N/L ratio.ConclusionIL-6, CRP and the N/L ratio are prognostic factors with higher levels associated with shorter overall survival in patients with metastatic melanoma receiving ICI or chemotherapy in large randomized trials. In a multi-variable analysis of the randomized phase III Checkmate-067 study, IL-6 was a significant prognostic factor for survival.

California bar patrons increasingly support and comply with the smoke-free bar law.

The authors documented California's tobacco control initiatives for Asian Ameri-