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.).

No abstract

Information on the size and shape of the neutron skin on (208)Pb is extracted from coherent pion photoproduction cross sections measured using the Crystal Ball detector together with the Glasgow tagger at the MAMI electron beam facility. On exploitation of an interpolated fit of a theoretical model to the measured cross sections, the half-height radius and diffuseness of the neutron distribution are found to be c(n)=6.70±0.03(stat.)  fm and a(n)=0.55±0.01(stat.)(-0.03)(+0.02)(sys.)  fm, respectively, corresponding to a neutron skin thickness Δr(np)=0.15±0.03(stat.)(-0.03)(+0.01)(sys.)  fm. The results give the first successful extraction of a neutron skin thickness with an electromagnetic probe and indicate that the skin of (208)Pb has a halo character. The measurement provides valuable new constraints on both the structure of nuclei and the equation of state for neutron-rich matter.

Factors contributing to hematopoietic recovery following chimeric antigen receptor (CAR) T-cell therapy have not been well studied. In an analysis of 83 patients with hematologic malignancies treated with CAR T-cell therapy, we describe patterns of hematopoietic recovery and evaluate potentially associated factors. We included patients who received axicabtagene ciloleucel (n = 30) or tisagenlecleucel (n = 10) for B-cell lymphoma, CD19-28z CAR T therapy for B-cell acute lymphoblastic leukemia (NCT01044069; n = 37), or B-cell maturation antigen targeting CAR T cells for multiple myeloma (NCT03070327; n = 6). Patients treated with CAR T cells who had not progressed, died, or received additional chemotherapy had “recovered” (per definition in Materials and methods section) hemoglobin, platelet, neutrophil, and white blood cell counts at rates of 61%, 51%, 33%, and 28% at month 1 postinfusion and 93%, 90%, 80%, and 59% at month 3 postinfusion, respectively. Univariate analysis showed that increasing grade of immune effector cell–associated neurological syndrome (ICANS), baseline cytopenias, CAR construct, and higher peak C-reactive protein or ferritin levels were statistically significantly associated with a lower likelihood of complete count recovery at 1 month; a similar trend was seen for cytokine release syndrome (CRS). After adjustment for baseline cytopenia and CAR construct, grade ≥3 CRS or ICANS remained significantly associated with the absence of complete count recovery at 1 month. Higher levels of vascular endothelial growth factor and macrophage-derived chemokines, although not statistically significant, were seen patients without complete count recovery at 1 month. This remains to be studied further in larger prospective studies.

To ensure an adequate clinical composite filling light source for photopolymerization is of great importance. In everyday clinical conditions commonly used unit for polymerization of composite material is halogen curing unit. The development of new blue superbright light emitting diodes (LED) of 470 nm wavelengths comes as an alternative to standard halogen curing unit of 450-470 nm wavelengths. The purpose of this study was to compare the degree of conversion (DC) and temperature rise of four hybrid composite materials: Tetric Ceram, Pertac II, Valux Plus and Degufill Mineral during 40 s illumination with standard halogen curing unit Heliolux GTE of 600 mW cm(-2) intensity, Elipar Highlight soft-start curing unit of 100 mW cm(-2) (10 s) and 700 mW cm(-2) (30 s) intensity and 16 blue superbright LED of minimal intensity of 12 mW cm(-2) on the surface and 1 mm depth. The results revealed only a little bit higher DC values in case of polymerization with even 66 times stronger halogen curing units which showed twice higher temperature than blue diodes. Temperature and DC obtained are higher on the surface than on 1 mm depth regardless on the light source used.

Importance Postnatal cytomegalovirus (CMV) infection can cause serious morbidity and mortality in very low birth weight (VLBW) infants. The primary sources of postnatal CMV infection in this population are breast milk and blood transfusion. The current risks attributable to these vectors, and the efficacy of approaches to prevent CMV transmission, are poorly characterized. Objectives To estimate the risk of postnatal CMV transmission from 2 sources: 1) transfusion of CMV-seronegative and leukoreduced blood and 2) maternal breast milk. Design Prospective, multicenter birth-cohort study conducted from January 2010 to June 2013. CMV serologic testing of enrolled mothers was performed to determine their status. CMV nucleic acid testing (NAT) of transfused blood components and breast milk was performed to identify sources of CMV transmission. Enrolled VLBW infants underwent serum and urine CMV NAT testing at birth, to evaluate congenital infection, and surveillance CMV NAT testing at 5 additional intervals between birth and 90 days, discharge or death. Setting Three neonatal intensive care units (2 academically-affiliated and 1 private) in Atlanta, Georgia. Participants 539 VLBW infants (birth weight ≤1500 grams) who had not received a blood transfusion were enrolled, with their mothers, within 5 days of birth. Exposure Blood transfusion and breast milk feeding Main Outcomes and Measures Cumulative incidence of postnatal CMV infection, detected by serum or urine NAT. Results CMV positive sero-prevalence among enrolled mothers was 76% (352/462). Among 539 enrolled VLBW infants, the cumulative incidence of postnatal CMV infection at 12 weeks was 6.9% (95% CI: 4.2%–9.2%); five infants with postnatal CMV infection developed symptomatic disease or died. Although 58% (310/539) of infants received 2061 transfusions, none of the CMV infections were linked to transfusion, resulting in a CMV infection incidence of 0.0% (95%CI: 0.0%–0.3%) per unit of CMV-seronegative and leukoreduced blood. Twenty-seven of 28 postnatal infections occurred among infants fed CMV-positive breast milk (12-week incidence: 15.3%; 95%CI: 9.3%–20.2%). Conclusions and Relevance Transfusion of CMV-seronegative and leukoreduced blood products effectively prevents transmission of CMV to VLBW infants. Among infants managed with this transfusion approach, maternal breast milk is the primary source of postnatal CMV infection. Trial Registration clinicaltrials.gov Identifier: NCT00907686

HIV infection is associated with high rates of osteopenia and osteoporosis, but the mechanisms involved are unclear. We recently reported that bone loss in the HIV transgenic rat model was associated with upregulation of B cell expression of the key osteoclastogenic cytokine receptor-activator of NF-κB ligand (RANKL), compounded by a simultaneous decline in expression of its physiological moderator, osteoprotegerin (OPG). To clinically translate these findings we performed cross-sectional immuno-skeletal profiling of HIV-uninfected and antiretroviral therapy-naïve HIV-infected individuals. Bone resorption and osteopenia were significantly higher in HIV-infected individuals. B cell expression of RANKL was significantly increased, while B cell expression of OPG was significantly diminished, conditions favoring osteoclastic bone resorption. The B cell RANKL/OPG ratio correlated significantly with total hip and femoral neck bone mineral density (BMD), T- and/or Z-scores in HIV infected subjects, but revealed no association at the lumbar spine. B cell subset analyses revealed significant HIV-related increases in RANKL-expressing naïve, resting memory and exhausted tissue-like memory B cells. By contrast, the net B cell OPG decrease in HIV-infected individuals resulted from a significant decline in resting memory B cells, a population containing a high frequency of OPG-expressing cells, concurrent with a significant increase in exhausted tissue-like memory B cells, a population with a lower frequency of OPG-expressing cells. These data validate our pre-clinical findings of an immuno-centric mechanism for accelerated HIV-induced bone loss, aligned with B cell dysfunction.

Of patients with non-clear cell RCC, more than 20% had a germline mutation, of which half had the potential to direct systemic therapy. Current referral criteria for genetic testing did not identify a substantial portion of patients with mutations, supporting the role of a more inclusive sequencing approach.