Among patients with unstable angina or myocardial infarction without ST-segment elevation, prasugrel did not significantly reduce the frequency of the primary end point, as compared with clopidogrel, and similar risks of bleeding were observed. (Funded by Eli Lilly and Daiichi Sankyo; TRILOGY ACS ClinicalTrials.gov number, NCT00699998.).

On the basis of the data available, a combination of PEG and simethicone appears to be the best approach for small bowel preparation before VCE. However, large multicenter randomized-controlled trials are needed to validate this recommendation and to evaluate the ideal dose of PEG and timing of bowel preparation before VCE. Prokinetics administered before VCE do not improve the completion rate and should not be used.

BackgroundThe phase 3 CheckMate 214 trial demonstrated higher response rates and improved overall survival with nivolumab plus ipilimumab versus sunitinib in first-line therapy for advanced clear-cell renal cell carcinoma (RCC). An unmet need exists to identify patients with RCC who are most likely to benefit from treatment with nivolumab plus ipilimumab.MethodsIn exploratory analyses, pretreatment levels of programmed death ligand 1 were assessed by immunohistochemistry. Genomic and transcriptomic biomarkers (including tumor mutational burden and gene expression signatures) were also investigated.ResultsBiomarkers previously associated with benefit from immune checkpoint inhibitor-containing regimens in RCC were not predictive for survival in patients with RCC treated with nivolumab plus ipilimumab. Analysis of gene expression identified an association between an inflammatory response and progression-free survival with nivolumab plus ipilimumab.ConclusionsThe exploratory analyses reveal relationships between molecular biomarkers and provide supportive data on how the inflammation status of the tumor microenvironment may be important for identifying predictive biomarkers of response and survival with combination immunotherapy in patients with RCC. Further validation may help to provide biomarker-driven precision treatment for patients with RCC.

Background Host genetic factors are important determinants for risk of HIV-1 infection and disease progression. This study examined associations of host genetic variants and neurocognitive impairment in Chinese subjects infected through contaminated blood products. Methods 201 HIV-infected subjects from Anhui, China had neuropsychological (NP) tests at baseline and 12 months. DNA was genotyped for APOE ε2, ε3 and ε4 alleles, MBL2-A/O,CCR5-wt/Δ32, CCR5-59029-G/A, CCR2-180-G/A, SDF-1-G/A, IL4-589-C/T, MCP-1-2518-A/G, CX3CR1-745-G/A, -849-C/T polymorphisms and CCL3L1 copy number variants (CNVs) using real-time PCR. Univariate and multivariate analyses were performed. Results The cohort was 61% males, mean education: 5.5 years, AIDS diagnosis: 113(55%), on antiretrovirals: 114(56%), mean baseline CD4+ count: 349/mm3 and mean log10 RNA 4.09. At baseline, 37% had global NP impairment increasing to 44% after 12 months. Of 43 subjects with the APOE ε4 allele, 58% were cognitively impaired versus 31% without the ε4 allele (P=0.001, OR: 3.09; 95% CI: 1.54, 6.18). The mean GDS for ε4 positive participants on antiretrovirals for 12 months was 0.88 (0.55) versus 0.63 (.54) for ε4 negatives (P = 0.053, 95%CI: -0.004, 0.51). For MBL2, 52% of subjects with the O/O genotype declined in cognitive function over 12 months versus 23% with A/A (OR = 3.62. 95% CI: 1.46, 9.03; P=0.004). No associations were observed for the other genetic variants. Conclusions The APOE ε4 allele was associated with increased risk for cognitive deficits, while the MBL2 O/O genotype was associated with increased risk for progressive cognitive decline in Chinese subjects infected with HIV through contaminated blood products.

Objective-To quantify and characterize the nature of cognitive change over one year in a cohort of HIV+ former plasma donors in rural China. Design-Observational cohort studyMethods-192 HIV+ and 101 demographically comparable HIV− individuals, all former plasma donors, who lived in a rural part of China, received comprehensive medical and neuropsychological (NP) examinations. At study entry 56% of HIV+ group was on combination antiretroviral treatment (cART) and 60.9% at followup. Multiple regression change score approach was used with the HIV − sample to develop norms for change that would be then applied to the HIV+ participants. Followup test scores adjusted for the control group practice effect.Results-53 HIV+ individuals (27%) developed significant cognitive decline as compared to five (5%) of HIV− individuals. Cognitive decline was predicted at baseline by AIDS status, lower nadir CD4, and worse processing speed; at follow-up, it was associated with lower current CD4 and failure of viral suppression on cART. NP decline also was associated with decreased independence in activities of daily living. Using NP-impairment scores that were corrected for "practice" on repeated testing, we found that among the decliners, 41.5% (N=22) had incident impairment, while 38% (N=20) declined within the impaired range and another 20.7% (N=11) declined within the normal range.Conclusions-This study demonstrates that despite ongoing cART, cognitive decline in HIV+ people is common over a one year follow-up. Regression-based norms for change on Western NP tests can be used to detect disease-related cognitive decline in a developing country.