Citations

Purpose Preoperative therapy for localized gastric cancer has considerable appeal. We hypothesized that, in a cooperative group setting, preoperative chemoradiotherapy would induce a 20% pathologic complete response (pathCR) rate. Combined-modality therapy quality, survival, and safety were secondary end points. Patients and Methods Patients with localized gastric adenocarcinoma were eligible. A negative laparoscopic evaluation was required. Patients received two cycles of induction fluorouracil, leucovorin, and cisplatin followed by concurrent radiation and chemotherapy (infusional fluorouracil and weekly paclitaxel). Resection was attempted 5 to 6 weeks after chemoradiotherapy was completed. Quality of therapy was assessed with other end points. Results Twenty institutions participated. Forty-nine patients were entered and 43 were assessable (12% stage IB; 37% stage II; and 52% stage III). The pathCR and R0 resection rates were 26% and 77%, respectively. At 1 year, more patients with pathCR (82%) are living than those with less than pathCR (69%). Grade 4 toxicity occurred in 21% of patients. Chemotherapy, radiotherapy, and surgery per protocol (including acceptable variations) occurred in 98%, 44%, and 63% of patients, respectively. A D2 dissection was performed in 50% of patients. Of 18 major radiotherapy variations, 17 were due to the lack of inclusion of the L3-4 vertebral interphase as prespecified. Conclusion For localized gastric cancer, preoperative chemoradiotherapy strategy achieved a pathCR rate of more than 20% in a cooperative group setting. The quality of surgery improved (50% with D2 dissection) possibly because surgery was part of this trial. With some refinements, this preoperative chemoradiotherapy strategy is poised for a randomized comparison with postoperative adjuvant chemoradiotherapy in patients with gastric cancer.

Purpose The purpose of this study was to assess the feasibility of a nurse-driven effort to improve hyperglycemia management in the intensive care unit (ICU) setting. Methods The setting was the ICU of a large urban hospital. The program was composed of 3 components: nurses as leaders, a clinical pathway to identify patients in need of hyperglycemia therapy, and implementation of a redesigned insulin infusion algorithm (the Columnar Insulin Dosing Chart). Time to reach a target glucose range of 80 to 110 mg/dL (4.4-6.1 mmol/L) was evaluated. Results One hundred sixteen ICU nurses were trained in the project. The Columnar Insulin Dosing Chart was applied to 20 patients. The average time required to reach the target blood glucose range was 12.8 hours. Below-target blood glucose levels were 6.9% of all blood glucose levels recorded, but only 0.9% were below 60 mg/dL (3.3 mmol/L). There was no sustained hypoglycemia, and no persistent clinical findings attributable to hypoglycemia were noted. Barriers to implementing the project included an increased nursing workload, the need for more finger-stick blood glucose monitors, and the need to acquire new finger-lancing devices that allowed for shallower skin puncture and increased patient comfort. Conclusions Tighter glycemic control goals can be attained in a busy ICU by a nurse-led team using a pathway for identifying and treating hyperglycemia, clear decision support tools, and adequate nurse education. The novel chart based insulin infusion algorithm chosen as the standard for this pilot was an effective tool for reducing the blood glucose to target range with no clinically significant hypoglycemia.

Background— Cardiac resynchronization therapy (CRT) is an effective therapy for patients with moderate to severe heart failure and prolonged QRS duration. The purpose of this study was to determine whether reverse left ventricular (LV) remodeling and symptomatic benefit from CRT were sustained at 12 months, and if so, in what proportion of patients this occurred. Methods and Results— Serial Doppler echocardiograms were obtained at baseline and 6 and 12 months after CRT in 228 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Measurements were made of LV end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E wave) and late (A wave) diastolic filling, and myocardial performance index. At both 6 and 12 months, respectively, CRT was associated with reduced LV EDV ( P <0.0001 and P =0.007) and LV ESV ( P <0.0001 and P <0.0001), improved ejection fraction ( P <0.0001 and P <0.0001), regression of LV mass ( P =0.012 and P <0.0001), and reduced MR ( P <0.0001 and P <0.0001). LV filling time, transmitral E/A ratio, and myocardial performance index all improved at 12 months compared with baseline ( P <0.001, P =0.031, and P <0.0001). Reverse LV remodeling with CRT occurred in more patients at 6 than at 12 months (74% versus 60%, respectively; P <0.05) and was greater in patients with a nonischemic than an ischemic etiology. Conclusions— Reverse LV remodeling and symptom benefit with CRT are sustained at 12 months in patients with New York Heart Association class III/IV heart failure but occur to a lesser degree in patients with an ischemic versus a nonischemic etiology, most likely owing to the inexorable progression of ischemic disease.

Palpable thyroid nodules can be seen on sonograms with a high degree of accuracy. Although most thyroid nodules are benign, it is important to recognize the sonographic features that make a nodule worrisome for malignancy. Thyroid cancer often appears sonographically as solid and hypoechoic. Fine punctate internal calcifications within a hypoechoic solid mass are features commonly seen with papillary thyroid cancer, which is the most common form of thyroid malignancy.

Background— Coronary bypass surgery (CABG) and angioplasty (PTCA) have been compared in several randomized trials, but data about long-term economic and quality-of-life outcomes are limited. Methods and Results— Cost and quality-of-life data were collected prospectively from 934 patients who were randomized in the Bypass Angioplasty Revascularization Investigation (BARI) and followed up for 10 to12 years. CABG had 53% higher costs initially, but the gap closed to <5% during the first 2 years; after 12 years, the mean cumulative cost of CABG patients was $123 000 versus $120 750 for PTCA, yielding a cost-effectiveness ratio of $14 300/life-year added. CABG patients experienced significantly greater improvement in their physical functioning for the first 3 years but not in later follow-up. Recurrent angina substantially reduced all quality-of-life measures throughout follow-up. Cumulative costs were significantly higher among patients with diabetes, heart failure, and comorbid conditions and among women; costs also were increased by angina, by the number of revascularization procedures, and among patients who died. Conclusion— Early differences between CABG and PTCA in costs and quality of life were no longer significant at 10 to 12 years of follow-up. CABG was cost-effective as compared with PTCA for multivessel disease.

Objective.To determine why people do or do not wear helmets while bicycling.Methods.A survey was conducted from August through October 1999. Two survey areas were chosen for this study: local public schools and paved bicycle trails. For the school arm of the study, 3 public elementary, middle, and high schools were selected from 3 different regions of Rochester, Minnesota, for participation in the study. For the bicycle arm of the study, 3 paved trails located in southeastern Minnesota were selected. A total of 2970 surveys were distributed to the public school system, and 463 surveys were collected from bicyclists on the paved bicycle trails. The survey population was split into 3 age categories for analysis: child (7–10), adolescent (11–19), and adult (older than 19).Results.Of the 2970 surveys distributed to Rochester public schools, 2039 (69%) were returned for analysis. Seventy-eight of the surveys that were completed in the public school system were discarded for the following reasons: age &lt;10 years (35), insufficient completion (24), and selection of every reason for not wearing a bicycle helmet (19). A total of 463 surveys were completed on the 3 paved bicycle trails. One survey from the paved bicycle trail arm of the study was discarded because of insufficient completion. The total number of surveys used for statistical analysis was 2424. The distribution of male (52.7%) and female (47.3%) participants was similar. No significant difference in bicycle helmet use was found between genders.The age groups with the highest rate of bicycle helmet use were 50 to 59 years (62%) and older than 59 years (70%). The age groups with the lowest rate of bicycle helmet use were 11 to 19 years (31%) and 30 to 39 years (30%). The most common reasons given for not wearing a bicycle helmet were “uncomfortable,” “annoying,” “it's hot,” “don't need it,” and “don't own one.” Bicycle helmet use was significantly influenced by peer helmet use in all 3 age groups. Children also were more likely to wear a bicycle helmet when their parents wore bicycle helmets.A majority of respondents in all 3 age groups indicated that bicycle helmets provided either “moderate” or “great” protection from head injury, although significantly more adults (65.9%) than adolescents (43.9%) believed that the protection afforded by bicycle helmets was “great.” Despite this belief, a majority of adolescents and adults indicated that there was only a “slight risk” of head injury when bicycling without a helmet. Participants in all 3 categories were more likely to wear a bicycle helmet when they indicated either that there was a “great risk” of head injury when bicycling without a helmet or that helmets provided “great protection” from head injury. Adolescents and adults who believed that bicycling without a helmet put one at “great risk” for head injury also were more likely to indicate that helmets provided “great protection” from head injury.Conclusions.The prevalence of bicycle helmet use remains low despite research indicating the high level of head injury risk when bicycling without a helmet and the significant protection afforded by bicycle helmets. With the information provided by this survey, a well-designed intervention to increase the use of bicycle helmets can be implemented. Suggestions for a campaign to promote an increase in bicycle helmet use include focusing efforts on males and females between 11 and 19 years and 30 and 39 years of age; educating the public on new bicycle helmet designs that address comfort, ventilation, and fashion; educating adolescents on the significant protection from head injury afforded by bicycle helmets; and educating the public on the risk and severity of head injury associated with bicycling without a helmet. The influence of parents and peers on bicycle helmet use may be targeted through education and statements such as, “If you wear a bicycle helmet, you are not only protecting yourself, you are also helping to protect your friends and/or children.” bicycle, helmet, injury, accident, prevention.

SUMMARYHuman membrane cofactor protein (MCP; CD46) is a widely distributed complement regulator. In the mouse, expression of MCP is largely restricted to the testis while a related, widely expressed protein (Crry) appears to perform MCP's (CD46) regulatory activity. We have developed two mouse strains transgenic for human MCP (CD46) utilizing an ∼ 400 kb YAC clone carrying the complete gene. A third mouse strain was generated using an overlapping YAC clone isolated from a second library. The expression of human MCP (CD46) in these mouse strains was characterized by immunohistochemistry, FACS, Western blotting and RT-PCR. No differences were detected in the isoform pattern or distribution among the three strains, although the expression level varied according to how many copies of the gene were integrated. The expression profile closely mimicked that observed in humans, including the same pattern of isoform expression as the donor. In addition, tissue-specific isoform expression in the kidney, salivary gland and brain paralleled that observed in man. The transgenic mice expressed low levels of MCP (CD46) on their E, in contrast to humans but in line with most other primates. These mice should be a useful tool to analyse tissue-specific expression, to establish animal models of infections and to characterize the role of MCP (CD46) in reproduction.

Background— Outcomes in patients with mild to moderate renal function (RF) abnormalities presenting with acute coronary syndromes (ACS) are not well defined. Methods and Results— A convenience sample of 4 ACS trial databases including all enrolled patients was assessed to determine 30- and 180-day outcomes. The 4 trials were Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb, GUSTO-III, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), and Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON-A). Patients were stratified into ST-segment elevation (STE) and non–ST-segment elevation (NSE) groups and by the presence or absence of abnormal RF (creatinine clearance <70 mL/min). In the STE group, 7670 of 18 621 patients (41%) had abnormal RF. In the NSE group, 8152 of 19 304 (42%) had abnormal RF. Patients with abnormal RF were older, more often female, and more likely to have adverse baseline characteristics. They had higher mortality and higher mortality/nonfatal myocardial infarction (MI) at both 30 and 180 days, regardless of ST-segment status. Creatinine clearance was independently associated with risk of mortality (hazard ratio 0.79 in the STE group and 0.81 in the NSE group) and with risk of mortality/MI (hazard ratio 0.93) in the NSE group at 180 days. Conclusions— Patients presenting with ACS frequently have abnormal RF. Abnormal RF is a marker of adverse baseline clinical characteristics and is independently associated with increased risk of death and death/MI.