Citations

BACKGROUND Maroteaux-Lamy syndrome is a lysosomal storage disease of mucopolysaccharide metabolism (MPS type VI) that may involve the mitral and aortic valves. Affected patients have other skeletal and oropharyngeal malformations that complicate anesthetic and surgical management. METHODS AND RESULTS The present report describes the clinical, echocardiographic, and pathological findings in four patients with Maroteaux-Lamy syndrome. Two of three siblings underwent successful double-valve replacement for aortic and mitral valve stenoses. The third sibling, whose aortic and mitral valves were thick and fibrotic, died from septicemia after hip surgery. A fourth, unrelated patient also had successful double-valve replacement. CONCLUSIONS Our experience emphasizes the potential difficulties in preoperative assessment and surgical treatment as well as the unique problems related to airway management in patients with this syndrome.

GH deficiency has been found in subjects with amyotrophic lateral sclerosis (ALS). Disrupted endocrine function could contribute to the progressive muscle loss and hypermetabolism seen in ALS. It is not possible to study all the elements of the GH-IGF-I axis in ALS patients. Consequently, it remains unclear whether dysfunctional GH secretion contributes to disease pathogenesis and why GH and IGF-I directed treatment strategies are ineffective in human ALS. The hSOD1G93A transgenic mouse model is useful for the detailed investigation of the pathogenesis of ALS. We report that symptomatic male hSOD1G93A transgenic mice exhibit a deficiency in GH secretion similar to that seen in human ALS. Further characterization of the GH-IGF-I axis in hSOD1G93A mice reveals central and peripheral abnormalities that are not found in wild-type age-matched controls. Specifically, we observe aberrant endogenous pulsatile GH secretion, reduced pituitary GH content, and decreased circulating levels of IGF-I, indicating global GH deficiency in hSOD1G93A mice. Furthermore, a reduction in the expression of the IGF-I receptor α-subunit in skeletal muscle and lumbar spinal cords of hSOD1G93A mice suggests impaired IGF-I signaling within these tissues. This is the first account of disrupted GH secretion in a transgenic mouse model of ALS. These observations are essential for the development of effective GH and IGF-I targeted therapies in ALS.

Background— Measurement of hospital quality has traditionally focused on processes of care and postprocedure outcomes. Appropriateness measures for percutaneous coronary intervention (PCI) assess quality as it relates to patient selection and the decision to perform PCI. The association between patient selection for PCI and processes of care and postprocedural outcomes is unknown. Methods and Results— We included 203 531 patients undergoing nonacute (elective) PCI from 779 hospitals participating in the National Cardiovascular Data Registry (NCDR) CathPCI Registry between July 2009 and April 2011. We examined the association between a hospital's proportion of nonacute PCIs categorized as inappropriate by the 2009 Appropriate Use Criteria (AUC) for Coronary Revascularization and in-hospital mortality, bleeding complications, and use of optimal guideline-directed medical therapy at discharge (ie, aspirin, thienopyridines, and statins). When categorized as hospital tertiles, the range of inappropriate PCI was 0.0% to 8.1% in the lowest tertile, 8.1% to 15.2% in the middle tertile, and 15.2% to 58.6% in the highest tertile. Compared with lowest-tertile hospitals, mortality was not significantly different at middle-tertile (adjusted odds ratio [OR], 0.93; 95% confidence interval [CI], 0.73–1.19) or highest-tertile hospitals (OR, 1.12; 95% CI, 0.88–1.43; P =0.35 for differences between tertiles). Similarly, risk-adjusted bleeding did not vary significantly (middle-tertile OR, 1.13; 95% CI, 1.02–1.16; highest-tertile OR, 1.02; 95% CI, 0.91–1.16; P =0.07 for differences between tertiles) nor did use of optimal medical therapy at discharge (85.3% versus 85.7% versus 85.2%; P =0.58). Conclusions— In a national cohort of nonacute PCIs, a hospital's proportion of inappropriate PCIs was not associated with in-hospital mortality, bleeding, or medical therapy at discharge. This suggests PCI appropriateness measures aspects of hospital PCI quality that are independent of how well the procedure is performed. Therefore, PCI appropriateness and postprocedural outcomes are both important metrics to inform PCI quality.

Abstract B24 Purpose Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States for which no recommended screening guidelines are available. An estimated 34,290 deaths related to PC is expected to occur in 2008 and the 5-year relative survival rate for this cancer is 5% for all stages combined. A person's chance of developing this cancer increases three-fold if a first-degree relative has pancreatic cancer. The purpose of this study was to assess attitudes of unaffected family members in the Mayo Clinic Pancreas Cancer Family study toward PC cancer risk and future screening options. This is the first study to report such attitudes of PC family members. Subjects and Methods At-risk family members with two or more relatives affected with pancreas cancer in the kindred and primary care controls completed a survey asking about: perceived PC risk, degree of PC worry/concern, attitude toward cancer screening in general, and intentions regarding PC screening if it were a blood test or endoscopic ultrasound. Results 386 family members in 109 PC kindreds and 1058 controls completed surveys. Forty-six percent of PC family members reported that it was likely they would develop PC during their lifetime compared to 6% of controls. Forty-one percent of family members reported having thoughts regarding the possibility of getting pancreatic cancer during the past month versus 4.6% of controls. Similarly, 74% of family members reported concern about getting PC as compared to 40.6% of controls. 94% of family members reported they would be likely to undergo a blood-based PC screening test compared to 89.7% of controls. For endoscopic ultrasound, 71% of family members would be likely to undergo screening as compared to 55% of controls. All comparisons were statistically significant. Conclusion Compared to controls, PC family members perceive their personal PC risk to be high and report a higher rate of PC-related cancer worry/concern. A high percentage of family members and controls indicate receptivity to PC screening, especially if it were a blood test. If the screening is more invasive (i.e. EUS), interest declines, particularly among controls. This information can help investigators to understand and address potential motivators and barriers to recruitment for future PC studies and indicates that there is a need to develop educational interventions among these families to reduce their actual and perceived pancreatic cancer risk. Citation Information: Cancer Prev Res 2008;1(7 Suppl):B24.

Abstract Background: Increasing colorectal cancer screening (CRCS) is important for attaining the Healthy People 2020 goal of reducing CRC-related morbidity and mortality. Evaluating CRCS trends can help identify shifts in CRCS, and specific groups that might be targeted for CRCS. Methods: We utilized medical records to describe population-based adherence to average-risk CRCS guidelines from 1997 to 2008 in Olmsted County, MN. CRCS trends were analyzed overall and by gender, age, and adherence to screening mammography (women only). We also carried out an analysis to examine whether CRCS is being initiated at the recommended age of 50. Results: From 1997 to 2008, the size of the total eligible sample ranged from 20,585 to 21,468 people. CRCS increased from 22% to 65% for women and from 17% to 59% for men (P < 0.001 for both) between 1997 and 2008. CRCS among women current with mammography screening increased from 26% to 74%, and this group was more likely to be adherent to CRCS than all other subgroups analyzed (P < 0.001).The mean ages of screening initiation were stable throughout the study period, with a mean age of 55 years among both men and women in 2008. Conclusion: Although overall CRCS tripled during the study period, there is still room for improvement. Impact: Working to decrease the age at first screening, exploration of gender differences in screening behavior, and targeting women adherent to mammography but not to CRCS seem warranted. Cancer Epidemiol Biomarkers Prev; 21(2); 347–50. ©2011 AACR.

ABSTRACT Hepatitis C virus (HCV) protease inhibitors combined with pegylated alfa interferon-ribavirin have demonstrated improved efficacy compared with pegylated alfa interferon-ribavirin alone for the treatment of chronic hepatitis C. Asunaprevir (BMS-650032), a novel HCV NS3 protease inhibitor in clinical development, was evaluated for safety, antiviral activity, and resistance in four double-blind, placebo-controlled, sequential-panel, single- and multiple-ascending-dose (SAD and MAD) studies in healthy subjects or subjects with chronic HCV genotype 1 infection. In SAD studies, subjects (healthy or with chronic HCV infection) were randomized to receive asunaprevir in dose groups of 10 to 1,200 mg or a placebo. In MAD studies, healthy subjects were randomized to receive asunaprevir in dose groups of 10 to 600 mg twice daily or a placebo for 14 days; subjects with HCV infection received asunaprevir in dose groups of 200 to 600 mg twice daily, or a placebo, for 3 days. Across all four studies, headache and diarrhea were the most frequent adverse events in asunaprevir recipients. Asunaprevir at doses of 200 to 600 mg resulted in rapid HCV RNA decreases from the baseline; maximal mean changes in HCV RNA over time were 2.7 and 3.5 log 10 IU/ml in the SAD and MAD studies, respectively. No enrichment of signature asunaprevir-resistant viral variants was detected. In conclusion, the novel NS3 protease inhibitor asunaprevir, when administered at single or multiple doses of 200 to 600 mg twice daily, is generally well tolerated, achieving rapid and substantial decreases in HCV RNA levels in subjects chronically infected with genotype 1 HCV.