Citations

We measured the financial consequences of new CRC treatment regimens. New regimens have increased cost directly through price and indirectly through nonstandard and second-line regimen use.

Pregnancy-associated plasma protein-A2 (PAPP-A2) is a novel homolog of PAPP-A in the metzincin superfamily. However, compared with the accumulating data on PAPP-A, very little is known about PAPP-A2. In this study, we determined the tissue expression pattern of PAPP-A2 mRNA in wild-type (WT) mice and characterized the phenotype of mice with global PAPP-A2 deficiency. Tissues expressing PAPP-A2 in WT mice were more limited than those expressing PAPP-A. The highest PAPP-A2 mRNA expression was found in the placenta, with abundant expression in fetal, skeletal, and reproductive tissues. Heterozygous breeding produced the expected Mendelian distribution for the pappa2 gene and viable homozygous PAPP-A2 knockout (KO) mice that were normal size at birth. The most striking phenotype of the PAPP-A2 KO mouse was postnatal growth retardation. Male and female PAPP-A2 KO mice had 10 and 25–30% lower body weight, respectively, than WT littermates. Adult femur and body length were also reduced in PAPP-A2 KO mice, but without significant effects on bone mineral density. PAPP-A2 KO mice were fertile, but with compromised fecundity. PAPP-A expression was not altered to compensate for the loss of PAPP-A2 expression, and proteolysis of PAPP-A2's primary substrate, IGF-binding protein-5, was not altered in fibroblasts from PAPP-A2 KO embryos. In conclusion, tissue expression patterns and biological consequences of gene KO indicate distinct physiological roles for PAPP-A2 and PAPP-A in mice.

AbstractPurposeThe purpose of this study is to determine whether the RetroScrew tibial fixation system offers a biomechanical advantage over the Delta screw for anterior cruciate ligament (ACL) reconstruction in cadaveric tibias with low bone mineral density (BMD).MethodsTen matched pairs of osteoporotic cadaveric tibiae underwent simulated ACL reconstruction using quadrupled hamstring grafts with one of the two tibial fixation constructs. Group 1 was fixed with the Delta screw (DS; 35‐mm antegrade biointerference screw), and group 2 was fixed with the RetroScrew system (RSS; 20‐mm retrograde and 17‐mm antegrade biointerference screws). Each construct was cyclically loaded (50–200 N, 1 Hz, 500 cycles) and subsequently loaded to failure (20 mm/s).ResultsAll specimens were osteoporotic without significant segmental (proximal, middle, and distal) BMD differences between groups by quantitative computed tomography (P = n.s.). A trend was noted for more construct failures due to graft slippage in the DS group (n = 3) over the RSS group (n = 1). There were no significant differences in cyclic displacement (P = n.s.), maximum cyclic stiffness (P = n.s.), maximum load at failure (P = n.s.), or pullout stiffness (P = n.s.) between groups.ConclusionsIn an osteoporotic cadaveric model, there was no significant biomechanical advantage of the RetroScrew system versus the Delta screw for tibial fixation in soft tissue graft ACL reconstruction. However, a trend toward lower graft fixation failure to cyclic loading was noted with the RetroScrew system.Level of evidenceBiomechanical comparative study, Level II.

Abstract Oncolytic viruses consist of a diverse range of DNA and RNA viruses traditionally thought to mediate their effects by exploiting aberrations in tumor pathways, allowing preferential viral replication in, and killing of, tumor cells. Clinical development has progressed to late-phase trials, potentially heralding their introduction into clinical practice. However, despite this promise, the activity of oncolytic viruses has yet to achieve the potential suggested in preclinical models. To address this disparity, we need to recognize the complex interaction among oncolytic viruses, tumor, chemotherapy, and host immune system, and appreciate that direct oncolysis may not be the only factor to play an important role in oncolytic virus-mediated antitumor efficacy. Although key in inactivating viruses, the host immune system can also act as an ally against tumors, interacting with oncolytic viruses under the right conditions to generate useful and long-lasting antitumor immunity. Preclinical data also suggest that oncolytic viruses show synergy with standard therapies, which may offer improved clinical response rates. Here, we explore clinical and preclinical data on clinically relevant oncolytic viruses, highlighting areas of progress, uncertainty, and translational opportunity, with respect to immune recruitment and therapeutic synergy. Clin Cancer Res; 17(13); 4214–24. ©2011 AACR.

Background— Although numerous studies have reported that cardiac rehabilitation (CR) is associated with reduced mortality after myocardial infarction, less is known about its association with mortality after percutaneous coronary intervention. Methods and Results— We performed a retrospective analysis of data from a prospectively collected registry of 2395 consecutive patients who underwent percutaneous coronary intervention in Olmsted County, Minnesota, from 1994 to 2008. The association of CR with all-cause mortality, cardiac mortality, myocardial infarction, or revascularization was assessed with 3 statistical techniques: propensity score–matched analysis (n=1438), propensity score stratification (n=2351), and regression adjustment with propensity score in a 3-month landmark analysis (n=2009). During a median follow-up of 6.3 years, 503 deaths (199 cardiac), 394 myocardial infarctions, and 755 revascularization procedures occurred in the study subjects. Participation in CR, noted in 40% (964 of 2395) of the cohort, was associated with a significant decrease in all-cause mortality by all 3 statistical techniques (hazard ratio, 0.53 to 0.55; P <0.001). A trend toward decreased cardiac mortality was also observed in CR participants; however, no effect was observed for subsequent myocardial infarction or revascularization. The association between CR participation and reduced mortality rates was similar for men and women, for older and younger patients, and for patients undergoing elective or nonelective percutaneous coronary intervention. Conclusions— We found that CR participation after percutaneous coronary intervention was associated with a significant reduction in mortality rates. These findings add support to published clinical practice guidelines, performance measures, and insurance coverage policies that recommend CR for patients after percutaneous coronary intervention.