Sequoia Hospital

BACKGROUND: Directional coronary atherectomy is a new technique of coronary revascularization by which atherosclerotic plaque is excised and retrieved from target lesions. With respect to the rate of restenosis and clinical outcomes, it is not known how this procedure compares with balloon angioplasty, which relies on dilation of the plaque and vessel wall. We compared the rate of restenosis after angioplasty with that after atherectomy. METHODS: At 35 sites in the United States and Europe, 1012 patients were randomly assigned to either atherectomy (512 patients) or angioplasty (500 patients). The patients underwent coronary angiography at base line and again after six months; the paired angiograms were quantitatively assessed at one laboratory by investigators unaware of the treatment assignments. RESULTS: Stenosis was reduced to 50 percent or less more often with atherectomy than with angioplasty (89 percent vs. 80 percent; P < 0.001), and there was a greater immediate increase in vessel caliber (1.05 vs. 0.86 mm, P < 0.001). This was accompanied by a higher rate of early complications (11 percent vs. 5 percent, P < 0.001) and higher in-hospital costs ($11,904 vs $10,637; P = 0.006). At six months, the rate of restenosis was 50 percent for atherectomy and 57 percent for angioplasty (P = 0.06). However, the probability of death or myocardial infarction within six months was higher in the atherectomy group (8.6 percent vs. 4.6 percent, P = 0.007). CONCLUSIONS: Removing coronary artery plaque with atherectomy led to a larger luminal diameter and a small reduction in angiographic restenosis, the latter being confined largely to the proximal left anterior descending coronary artery. However, atherectomy led to a higher rate of early complications, increased cost, and no apparent clinical benefit after six months of follow-up.

AIM: To quantify the effects of hormone-replacement therapy (HRT) on components of the metabolic syndrome in postmenopausal women. METHODS: Comprehensive searches of electronic databases were performed from April 1966 to October 2004. We included randomized controlled trials that were of at least 8 weeks duration and evaluated the effect of HRT on metabolic, inflammatory or thrombotic components. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Subgroup analysis evaluated the effects for transdermal and oral treatment and for diabetic and non-diabetic women. RESULTS: Pooled results of 107 trials showed that HRT reduced abdominal fat [-6.8% (CI, -11.8 to -1.9%)], HOMA-IR [-12.9% (CI, -17.1 to -8.6%)] and new-onset diabetes [relative risk 0.7 (CI, 0.6-0.9)] in women without diabetes. In women with diabetes, HRT reduced fasting glucose [-11.5% (CI, -18.0 to -5.1%)] and HOMA-IR [-35.8% (CI, -51.7 to -19.8%)]. HRT also reduced low-density lipoprotein/high-density lipoprotein cholesterol ratio [-15.7% (CI, -18.0 to -13.5%)], lipoprotein(a) [Lp(a)] [-25.0% [CI, -32.9 to -17.1%)], mean blood pressure [-1.7% (CI, -2.9 to -0.5%)], E-selectin [-17.3% (CI, -22.4 to -12.1%)], fibrinogen [-5.5% (CI, -7.8 to -3.2%)] and plasminogen activator inhibitor-1 [-25.1% (CI, -33.6 to -15.5%)]. Oral agents produced larger beneficial effects than transdermal agents, but increased C-reactive protein (CRP) [37.6% (CI, 17.4-61.3%)] and decreased protein S [-8.6% CI, -13.1 to -4.1%)], while transdermal agents had no effect. CONCLUSIONS: HRT reduces abdominal obesity, insulin resistance, new-onset diabetes, lipids, blood pressure, adhesion molecules and procoagulant factors in women without diabetes and reduced insulin resistance and fasting glucose in women with diabetes. Oral agents adversely affected CRP and protein S, while transdermal agents had no effects.

The herbicide glyphosate is effectively detoxified by N-acetylation. We screened a collection of microbial isolates and discovered enzymes exhibiting glyphosate N-acetyltransferase (GAT) activity. Kinetic properties of the discovered enzymes were insufficient to confer glyphosate tolerance to transgenic organisms. Eleven iterations of DNA shuffling improved enzyme efficiency by nearly four orders of magnitude from 0.87 mM-1 min-1 to 8320 mM-1 min-1. From the fifth iteration and beyond, GAT enzymes conferred increasing glyphosate tolerance to Escherichia coli, Arabidopsis, tobacco, and maize. Glyphosate acetylation provides an alternative strategy for supporting glyphosate use on crops.

OBJECTIVES: We sought to determine the response rate and safety of intravenous amiodarone in patients with ventricular tachyarrhythmias refractory to standard therapies. BACKGROUND: Numerous small retrospective reports suggest a response of refractory ventricular tachyarrhythmias to intravenous amiodarone, yet no controlled prospective trials exist. METHODS: Two hundred seventy-three patients with recurrent hypotensive ventricular tachyarrhythmias refractory to lidocaine, procainamide and bretylium were randomized to receive one of three doses of intravenous amiodarone: 525, 1,050 or 2,100 mg/24 h (mean [+/- SE] dose 743.7 +/- 418.7, 1,175.2 +/- 483.7, 1,921.2 +/- 688.8 mg, respectively) by continuous infusion over 24 h. RESULTS: Of the 273 patients, 110 (40.3% response rate) survived 24 h without another hypotensive ventricular tachyarrhythmic event while being treated with intravenous amiodarone as a single agent (primary end point). A significant difference in the time to first recurrence of ventricular tachyarrhythmia (post hoc analysis) over the first 12 h was observed when the combined 1,050- and 2,100-mg dose groups were compared with the 525-mg dose group (p = 0.046). The number of supplemental (150 mg) infusions of intravenous amiodarone (given for breakthrough destabilizing tachyarrhythmias) during hours 0 to 6 (prespecified secondary end point) was significantly greater in the 525-mg dose group than in the 2,100-mg dose group (1.09 +/- 1.57 vs. 0.51 +/- 0.97, p = 0.0043). However, there was no clear dose-response relation observed in this trial with respect to success rates (primary end point), time to first recurrence of tachyarrhythmia (post hoc analysis) or mortality (secondary end point) over 24 h. CONCLUSIONS: Intravenous amiodarone is a relatively safe therapy for ventricular tachyarrhythmias refractory to other medications.

BACKGROUND: The extravascular implantable cardioverter-defibrillator (ICD) has a single lead implanted substernally to enable pause-prevention pacing, antitachycardia pacing, and defibrillation energy similar to that of transvenous ICDs. The safety and efficacy of extravascular ICDs are not yet known. METHODS: We conducted a prospective, single-group, nonrandomized, premarket global clinical study involving patients with a class I or IIa indication for an ICD, all of whom received an extravascular ICD system. The primary efficacy end point was successful defibrillation at implantation. The efficacy objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients with successful defibrillation was greater than 88%. The primary safety end point was freedom from major system- or procedure-related complications at 6 months. The safety objective would be met if the lower boundary of the one-sided 97.5% confidence interval for the percentage of patients free from such complications was greater than 79%. RESULTS: A total of 356 patients were enrolled, 316 of whom had an implantation attempt. Among the 302 patients in whom ventricular arrhythmia could be induced and who completed the defibrillation testing protocol, the percentage of patients with successful defibrillation was 98.7% (lower boundary of the one-sided 97.5% confidence interval [CI], 96.6%; P<0.001 for the comparison with the performance goal of 88%); 299 of 316 patients (94.6%) were discharged with a working ICD system. The Kaplan-Meier estimate of the percentage of patients free from major system- or procedure-related complications at 6 months was 92.6% (lower boundary of the one-sided 97.5% CI, 89.0%; P<0.001 for the comparison with the performance goal of 79%). No major intraprocedural complications were reported. At 6 months, 25 major complications were observed, in 23 of 316 patients (7.3%). The success rate of antitachycardia pacing, as assessed with generalized estimating equations, was 50.8% (95% CI, 23.3 to 77.8). A total of 29 patients received 118 inappropriate shocks for 81 arrhythmic episodes. Eight systems were explanted without extravascular ICD replacement over the 10.6-month mean follow-up period. CONCLUSIONS: In this prospective global study, we found that extravascular ICDs were implanted safely and were able to detect and terminate induced ventricular arrhythmias at the time of implantation. (Funded by Medtronic; ClinicalTrials.gov number, NCT04060680.).

BackgroundPatients with a variety of clinical presentations undergo atrial fibrillation (AF) ablation. Long-term ablation success rates can vary considerably.ObjectiveThe purpose of this study was to develop a clinical scoring system to predict long-term freedom from AF after ablation.MethodsWe retrospectively derived the scoring system on a development cohort (DC) of 1125 patients undergoing AF ablation and tested it prospectively in a test cohort (TC) of 937 patients undergoing AF ablation.ResultsThe demographics of the DC patients were as follows: age 62.3 ± 10.3 years, male sex 801 (71.2%), left atrial size 4.30 ± 0.69 cm, paroxysmal AF 348 (30.9%), number of drugs failed 1.3 ± 1.1, hypertension 525 (46.7%), diabetes 100 (8.9%), prior stroke/transient ischemic attack 78 (6.9%), prior cardioversion 528 (46.9%), and CHADS2 score 0.87 ± 0.97. Multivariate analysis showed 6 independent variables predicting freedom from AF after final ablation: coronary artery disease (P = .021), atrial diameter (P = .0003), age (P = .004), persistent or long-standing AF (P < .0001), number of antiarrhythmic drugs failed (P < .0001), and female sex (P = .0001). We created a scoring system (CAAP-AF) using these 6 variables, with scores ranging from 0 to 13 points. The 2-year AF-free rates by CAAP-AF scores were as follows: 0 = 100%, 1 = 95.7%, 2 = 96.3%, 3 = 83.1%, 4 = 85.5%, 5 = 79.9%, 6 = 76.1%, 7 = 63.4%, 8 = 51.1%, 9 = 53.6%, and ≥10 = 29.1%. Ablation success decreased as CAAP-AF scores increased (P < .0001). The CAAP-AF score also predicted freedom from AF in the TC. The 2-year Kaplan-Meier AF-free rates by CAAP-AF scores were as follows: 0 = 100%, 1 = 87.0%, 2 = 89.0%, 3 = 91.6%, 4 = 90.5%, 5 = 84.4%, 6 = 70.1%, 7 = 71.0%, 8 = 60.7%, 9 = 68.9%, and ≥10 = 51.3%. As CAAP-AF scores increased, 2-year freedom from AF in the TC decreased (P < .0001).ConclusionAn easily determined clinical scoring system was derived retrospectively and applied prospectively. The CAAP-AF score predicted freedom from AF after ablation in both a DC and a TC of patients undergoing AF ablation. The CAAP-AF score provides a realistic AF ablation outcome expectation for individual patients. Patients with a variety of clinical presentations undergo atrial fibrillation (AF) ablation. Long-term ablation success rates can vary considerably. The purpose of this study was to develop a clinical scoring system to predict long-term freedom from AF after ablation. We retrospectively derived the scoring system on a development cohort (DC) of 1125 patients undergoing AF ablation and tested it prospectively in a test cohort (TC) of 937 patients undergoing AF ablation. The demographics of the DC patients were as follows: age 62.3 ± 10.3 years, male sex 801 (71.2%), left atrial size 4.30 ± 0.69 cm, paroxysmal AF 348 (30.9%), number of drugs failed 1.3 ± 1.1, hypertension 525 (46.7%), diabetes 100 (8.9%), prior stroke/transient ischemic attack 78 (6.9%), prior cardioversion 528 (46.9%), and CHADS2 score 0.87 ± 0.97. Multivariate analysis showed 6 independent variables predicting freedom from AF after final ablation: coronary artery disease (P = .021), atrial diameter (P = .0003), age (P = .004), persistent or long-standing AF (P < .0001), number of antiarrhythmic drugs failed (P < .0001), and female sex (P = .0001). We created a scoring system (CAAP-AF) using these 6 variables, with scores ranging from 0 to 13 points. The 2-year AF-free rates by CAAP-AF scores were as follows: 0 = 100%, 1 = 95.7%, 2 = 96.3%, 3 = 83.1%, 4 = 85.5%, 5 = 79.9%, 6 = 76.1%, 7 = 63.4%, 8 = 51.1%, 9 = 53.6%, and ≥10 = 29.1%. Ablation success decreased as CAAP-AF scores increased (P < .0001). The CAAP-AF score also predicted freedom from AF in the TC. The 2-year Kaplan-Meier AF-free rates by CAAP-AF scores were as follows: 0 = 100%, 1 = 87.0%, 2 = 89.0%, 3 = 91.6%, 4 = 90.5%, 5 = 84.4%, 6 = 70.1%, 7 = 71.0%, 8 = 60.7%, 9 = 68.9%, and ≥10 = 51.3%. As CAAP-AF scores increased, 2-year freedom from AF in the TC decreased (P < .0001). An easily determined clinical scoring system was derived retrospectively and applied prospectively. The CAAP-AF score predicted freedom from AF after ablation in both a DC and a TC of patients undergoing AF ablation. The CAAP-AF score provides a realistic AF ablation outcome expectation for individual patients.

A prospective study evaluating the functionality and ease of use of the Medtronic CareLink Network, "CareLink," was conducted at ten investigational sites. This internet-based remote monitoring service allows clinicians to remotely manage their patients' implantable cardioverter defibrillators (ICDs) and chronic diseases. The network is comprised of a patient monitor, a secure server, and clinician and patient websites. Under clinician direction, patients interrogated their ICDs at home, and transmitted data to secure servers via a standard telephone line. Comprehensive device data and a 10-second presenting rhythm electrogram were captured by the monitor and available for access and review on the clinician website. The information could also be printed using a standard desktop computer with internet access. During this study, patients were asked to transmit device data twice, at least 7 days apart, as scheduled by the clinic. Monitor functionality was assessed, and ease of using the system components was evaluated via questionnaires completed by patients and clinicians following each data transmission and review. Fifty-nine patients (64 +/- 14 years, range 22-85 years) completed 119 transmissions with only 14 calls to the study support center. Clinician review of data transmissions revealed several clinically significant findings, including silent AF discovery, assessment of antiarrhythmic drug efficacy in a previously diagnosed AF patient, previously unobserved atrial undersensing, and ventricular tachycardia. ICD patients found the monitor easy to use. Clinicians were pleased with the performance of the network and the quality of the web-accessed data, and found it comparable to an in-office device interrogation. CareLink is a practical tool for routine device management and may allow timely identification of clinically important issues.

PURPOSE: Cyclooxygenase inhibitors show promise in chemoprevention and therapy of certain carcinomas, an effect that may be additive to that of standard chemotherapy. The purpose of this study was to evaluate the efficacy of combined therapy using the cyclooxygenase inhibitor, piroxicam, and mitoxantrone against a relevant canine model of human invasive bladder cancer. EXPERIMENTAL DESIGN: Fifty-five dogs with transitional cell carcinoma of the urinary bladder were enrolled in this nonrandomized one-armed prospective multi-institutional clinical trial. Mitoxantrone was administered i.v. (5 mg/m(2)) every 21 days for four treatments, and piroxicam was administered p.o. (0.3 mg/kg/day) for the study duration. Tumor staging was performed at baseline, day 42 and every 3 months after protocol completion. Endpoints included time-to-treatment failure and survival time (ST). RESULTS: Response data were available for 48 dogs and included one complete response, 16 partial responses, 22 with disease stabilization, and 9 with progressive disease for an overall 35.4% measurable response rate. Subjective improvement occurred in 75% of treated dogs. Median time-to-treatment failure and ST were 194 and 350 days, respectively. Using censoring and end point definitions similar to those of previous reports of dogs treated with piroxicam alone, the median ST in this study was 291 days, compared with 181 days with piroxicam alone. Diarrhea and azotemia were the most common treatment complications. CONCLUSIONS: Mitoxantrone/piroxicam induced remission more frequently than previously reported for either drug as a single agent in this canine model of invasive human transitional cell carcinoma. Additional evaluation of these drugs in combination protocols should be explored.

BACKGROUND: Previous clinical trials of directional coronary atherectomy (DCA) have failed to show significant improvement in early or late outcomes compared with balloon angioplasty (PTCA). The present study tested the hypothesis that more aggressive "optimal" atherectomy could be performed safely to produce larger initial lumen diameters and a lower late restenosis rate. METHODS AND RESULTS: The present study was a prospective multicenter registry of consecutive patients undergoing optimal DCA of de novo or restenotic lesions in 3.0- to 4.5-mm native coronary arteries. Optimal DCA was defined as using a 7F atherectomy device and adjunctive PTCA if necessary to achieve a < 15% residual stenosis. Six-month angiographic and 1-year clinical follow-up was planned in all patients. A total of 199 patients with 213 lesions met eligibility criteria for enrollment. Short-term procedural success was achieved in 97.5%, with a major complication rate (death, emergency bypass surgery, or Q-wave myocardial infarction [MI]) of 2.5%. There were no early deaths. Non-Q-wave MI (CK-MB > 3 times normal) occurred in 14% of patients. Mean reference vessel diameter was 3.28 mm. Mean diameter stenosis was reduced from 63.5% to a final stenosis of 7%. Late 1-year clinical follow-up revealed one cardiac death and a target lesion revascularization rate of 17.8%. The angiographic restenosis rate at 6 months was 28.9%, with the major predictor of restenosis being a smaller postprocedure lumen diameter. CONCLUSIONS: Optimal DCA produced a low residual percent diameter stenosis and a lower restenosis rate than seen in previous trials without an increase in early or late major adverse events.

INTRODUCTION: Atrial fibrillation (AF) ablation requires postprocedural anticoagulation to prevent thromboembolic events because of the ablation procedure itself or due to recurrent AF postprocedure. Dabigatran is a new anticoagulant and may be useful after AF ablation to prevent thromboembolic events. METHODS AND RESULTS: We evaluated 123 consecutive patients who were started on dabigatran after AF ablation. Patients were given enoxaparin 0.5 mg/kg at the end of the procedure, which was repeated 12 hours later and then discontinued. Dabigatran was started 22 hours postablation with drug dose based on renal function. Primary outcomes were thromboembolic events, bleeding complications, and side effects over a 30-day follow-up period. The preablation anticoagulant was warfarin in 56 (45.5%) patients, dabigatran in 34 (27.6%), and aspirin in 26 (21.1%). Seven (5.7%) patients were on no anticoagulant before ablation. The patients on dabigatran before ablation with normal renal function had the drug stopped 36 hours preablation. There were no preprocedural or intraprocedural thromboembolic episodes or bleeding. Three patients received dabigatran 75 mg bid and the rest 150 mg bid. There were no postablation strokes, transient ischemic attacks, or systemic thromboemboli in any patient. Three patients discontinued dabigatran and were changed to warfarin, 2 because of gastrointestinal side effects and 1 because of a diffuse rash. CONCLUSIONS: Dabigatran is safe and well tolerated after AF ablation. It did not cause bleeding complications and there were no thromboembolic events. Dabigatran appears to be an alternative to warfarin after AF ablation.

<h3>Background</h3> There is an association between obesity and atrial fibrillation (AF). The impact of obesity on AF ablation procedures is unclear. <h3>Objective</h3> The purpose of this study was to evaluate the influence of body mass index (BMI) on patient characteristics, long-term ablation outcomes, and procedural complications. <h3>Methods</h3> We evaluated 2715 patients undergoing 3742 AF ablation procedures. BMI was ≥30 kg/m² in 1058 (39%) and ≥40 kg/m² in 129 (4.8%). Patients were grouped by BMI ranges (<25, 25–<30, 30–<35, 35–<40, and ≥40 kg/m²). <h3>Results</h3> As BMI increased from <25 to ≥40 kg/m², age decreased from 65.3 ± 11.2 to 61.2 ± 9.2 years (<i>P</i> < .001), left atrial size increased from 3.91 ± 0.68 to 4.72 ± 0.62 cm (<i>P</i> < .005), and CHADS₂ scores increased from 1.24 ± 1.10 to 1.62 ± 1.09 (P < .001). As BMI increased, paroxysmal AF decreased from 48.0% to 16.3% (<i>P</i> < .0001) and there was an increase in dilated cardiomyopathy (from 7.6% to 12.4%; <i>P</i> < .0001), hypertension (from 41.0% to 72.9%; <i>P</i> < .0001), diabetes (from 4.3% to 23.3%; <i>P</i> < .0001), and sleep apnea (from 7.0% to 46.9%; <i>P</i> < .0001). For the entire cohort, for BMI ≥35 kg/m² the 5-year ablation freedom from AF decreased from 67%–72% to 57% (<i>P</i> = .036). For paroxysmal AF, when BMI was ≥40 kg/m² ablation success decreased from 79%–82% to 60% (<i>P</i> = .064), and for persistent AF, when BMI was ≥35 kg/m² ablation success decreased from 64%–70% to 52%–57% (<i>P</i> = .021). For long-standing AF, there was no impact of BMI on outcomes (<i>P</i> = .624). In multivariate analysis, BMI ≥35 kg/m² predicted worse outcomes (<i>P</i> = .036). Higher BMI did not impact major complication rates (<i>P</i> = .336). However, when BMI was ≥40 kg/m², minor (from 2.1% to 4.4%; <i>P</i> = .035) and total (from 3.5% to 6.7%; <i>P</i> = .023) complications increased. <h3>Conclusion</h3> In patients undergoing AF ablation, increasing BMI is associated with more patient comorbidities and more persistent and long-standing AF. BMI ≥35 kg/m² adversely impacts ablation outcomes, and BMI ≥40 kg/m² increases minor complications.

An advisory panel of academicians, private practice physicians, nurse clinicians, and research nurses was chosen to develop guidelines (minimum standards) for the treatment of arterial insufficiency ulcers of the lower extremities. Previous guidelines, meta-analyses, PubMed, MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews, recent review articles of arterial ulcer treatment, and the Medicare/CMS consensus of usual treatment of chronic wounds were all searched and reviewed for evidence. Guidelines were formulated, the underlying principle(s) enumerated, and evidence references listed and coded. The code abbreviations for the evidence citations were as follows: There were major differences between our approach to evidence citations and past approaches to evidence-based guidelines. Most past approaches relied only on publications regarding clinical human studies. Laboratory or animal studies were not cited. We have used well-controlled animal studies that present proof of principle, especially when a clinical series corroborated the laboratory results. It was also clear that principles that have been validated for other chronic wound types often are applicable to arterial ulcers. Therefore, evidence was sometimes cited that was not specific for arterial ulcers. Because of these variations, a different system was used to grade the evidence weight supporting a given guideline. The level strength of evidence supporting a guideline is listed as Levels I, II, or III. The guideline levels are: Level I: Meta-analysis of multiple RCTs or at least two RCTs support the intervention of the guideline. Another route would be multiple laboratory or animal experiments with at least two clinical series supporting the laboratory results. Level II: Less than Level I, but at least one RCT and at least two significant clinical series or expert opinion papers with literature reviews supporting the intervention. Experimental evidence that is quite convincing, but not yet supported by adequate human experience is included. Level III: Suggestive data of proof-of-principle, but lacking sufficient data such as meta analysis, RCT, or multiple clinical series. N.B. The suggestion in the guideline can be positive or negative at the proposed level (e.g., meta-analysis and two RCTs stating intervention is not of use in treating arterial ulcers). In addition to Level of Evidence, the committee agreed to classify the strength of the recommendation. The purpose is to correlate Level of Evidence with Level of Strength. The Levels of Strength supporting a guideline are listed as Level A, Level B, Level C, or Level D. The guideline levels of strength are: Level A: Strongly recommended/Likely to be of benefit. Level B: Recommended. Level C: Recommended but not essential. Level D: NOT recommended. Guidelines have been formulated in seven categories for the treatment of arterial ulcers of the lower extremities. The categories are: Diagnosis Surgery Infection control Wound bed preparation Dressings Adjuvant therapy (device, systemic, local/topical) Long-term maintenance Each of the guidelines underwent a Delphi consensus among the panel members. Each set was critically evaluated by all panel members. There was a consensus of at least ten panel members on each individual guideline. The majority of the guidelines had unanimous concurrence. The resultant GUIDELINES FOR THE TREATMENT OF ARTERIAL INSUFFICIENCY ULCERS are attached. These are guidelines for treatment. They are intended to guide wound caretakers in choosing the best available options. They are NOT meant to be standards of care. Preamble: Peripheral arterial occlusive disease (PAOD) affects approximately 10 million people in the United States and is highly associated with significant morbidity and mortality. Because of its high prevalence and associated co-morbidities, there must be an effort to detect arterial disease in patients with wounds and to select appropriate therapy when arterial insufficiency is identified as a significant or primary etiology for an ulcer. 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Transforming growth factor-beta (TGF-beta) plays an important role in vascular lesion formation and possibly the renarrowing process ("restenosis") that occurs after balloon angioplasty. Secreted in a latent form by most cells, TFG-beta requires enzymatic conversion before it is biologically active. TGF-beta-inducible gene h3 (beta ig-h3) is a novel molecule that is induced when cells are treated with TGF-beta1. This study examined the expression of beta ig-h3 in normal and diseased human vascular tissue. To determine the expression pattern of beta ig-h3 in human arteries, immunocytochemistry was performed on tissue sections from (1) normal internal mammary arteries, (2) the proximal left anterior descending coronary artery (with minimal intimal thickening) of 15 patients aged 18 to 40 years, (3) primary and restenotic coronary lesions from 7 patients, and (4) fresh directional atherectomy tissue from 11 patients. A polyclonal antibody consistently immunodetected beta ig-h3 protein in endothelial cells of all vascular tissue. In normal coronary arteries of young individuals, beta ig-h3 protein was absent from the intima and media but was found in the subendothelial smooth muscle cells of some arteries with modest intimal thickening. In diseased arteries beta ig-h3 protein was more abundant in the intima than the media. Restenotic coronary lesions tended to show higher levels of immunodetectable beta ig-h3 protein, especially in areas of dense fibrous connective tissue. Beta ig-h3 protein was immunodetected in the cytoplasm of plaque macrophages as well as smooth muscle and endothelial cells. By using in situ hybridization on fresh directional atherectomy specimens, we found beta ig-h3 mRNA to be overexpressed by plaque macrophages and smooth muscle cells. Nondiseased human internal mammary arteries also expressed beta ig-h3 mRNA in endothelial cells but not in the smooth muscle cells of the normal intima and media. These results document the expression of beta ig-h3 in diseased human arterial tissue and support the hypothesis that active TGF-beta plays a role in atherogenesis and restenosis.

The increasingly daunting problem of antimicrobial resistance has led to an intense focus on optimization of antibiotic therapy, with simultaneous goals of improving patient outcomes and minimizing the contribution of that therapy to making the available antibiotics obsolete. Although even appropriate antibiotic therapy drives resistance, inappropriate therapy may also have adverse effects on the individual patient, as well as on the bacterial ecology. Recent research has validated the benefit of intelligent utilization of both microbiological data and clinical assessment in the empirical selection of initial broad-spectrum therapy and in further guidance of therapeutic decisions throughout the course of illness by use of a systems approach. Thus, the optimal approach to the critically ill patient with infection involves the initiation of aggressive broad-spectrum empirical therapy followed by timely responses to microbiological and clinical results as they become available. An appropriate response to this information often involves de-escalation of therapy or even its discontinuation.

BACKGROUND: The StarClose Vascular Closure System is a femoral access site closure technology that uses a flexible nitinol clip to complete a circumferential, extravascular arteriotomy close. The Clip CLosure In Percutaneous Procedures study was initiated to study the safety and efficacy of the StarClose device in subjects undergoing diagnostic and interventional catheterization procedures. METHODS: A total of 17 U.S. sites enrolled 596 subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or standard compression of the arteriotomy after the percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. RESULTS: The results of the diagnostic StarClose cohort have been reported separately. Results for the interventional arm revealed major vascular complications occurring in 1.1% of StarClose subjects (2/184) and 1.1% in manual compression subjects (1/91; P = 1.00). No infections were seen in either cohort. Minor complications in the StarClose interventional group occurred at a rate of 4.3% (8/184) and with compression at 9.9% (9/91; P = 0.107). Pseudoaneurysm or arteriovenous fistula was not seen with StarClose. With StarClose, procedural success was 100% (136/136) for the diagnostic group and 98.9% (181/183) in the interventional group. Device success for the treatment group was 86.8%. In the interventional cohort, 87.3% (158/181) of StarClose subjects reported a pain scale of 0-3 compared with 93.3% (84/90) in the compression group, which was not statistically different. CONCLUSIONS: The clinical results of this study demonstrate that the StarClose Vascular Closure System is noninferior to manual compression with respect to the primary safety endpoint of major vascular events in subjects who undergo percutaneous interventional procedures. StarClose significantly reduced time to hemostasis, ambulation, and dischargeability when compared with compression.

PURPOSE: The optimal radiofrequency (RF) power and lesion duration using contact force (CF) sensing catheters for atrial fibrillation (AF) ablation are unknown. We evaluate 50 W RF power for very short durations using CF sensing catheters during AF ablation. METHODS: We evaluated 51 patients with paroxysmal (n = 20) or persistent (n = 31) AF undergoing initial RF ablation. RESULTS: A total of 3961 50 W RF lesions were given (average 77.6 ± 19.1/patient) for an average duration of only 11.2 ± 3.7 s. As CF increased from < 10 to > 40 g, the RF application duration decreased from 13.7 ± 4.4 to 8.6 ± 2.5 s (p < 0.0005). Impedance drops occurred in all ablations, and for patients in sinus rhythm, there was loss of pacing capture during RF delivery suggesting lesion creation. Only 3% of the ablation lesions were at < 5 g and 1% at > 40 g of force. As CF increased, the force time integral (FTI) increased from 47 ± 24 to 376 ± 102 gs (p < 0.0005) and the lesion index (LSI) increased from 4.10 ± 0.51 to 7.63 ± 0.50 (p < 0.0005). Both procedure time (101 ± 19.7 min) and total RF energy time (895 ± 258 s) were very short. For paroxysmal AF, the single procedure freedom from AF was 86% at 1 and 2 years. For persistent AF, it was 83% at 1 year and 72% at 2 years. There were no complications. CONCLUSIONS: Short duration 50 W ablations using CF sensing catheters are safe and result in excellent long-term freedom from AF for both paroxysmal and persistent AF with short procedure times and small amounts of total RF energy delivery.

Atherectomy is defined as the controlled removal of atherosclerotic tissue from vessel walls. The directional atherectomy catheter consists of a cup-shaped cutter within a housing unit and a small balloon. It was developed to perform transluminal atherectomy for the treatment of atherosclerotic vascular disease. This new procedure was performed on 195 lesions in peripheral arteries of lower limbs in 134 procedures, and 52 lesions in coronary arteries in 50 procedures. A successful angiographic outcome was obtained in 89% of procedures and 90% of lesions in peripheral experience, and 60% of procedures and 62% of lesions in coronary experience. A higher success rate (81%) was achieved in our more recent experience with coronary atherectomy, as compared with a 42% success rate in our earlier experience. The incidence of major complications was infrequent in both peripheral and coronary experiences. In the peripheral experience, one patient had delayed occlusion that required bypass surgery, and two patients had distal embolization. In the coronary experience, one patient had acute occlusion that required emergency bypass surgery. There were no vessel perforations. Conclusively, transluminal atherectomy is a feasible, predictable, and safe procedure for the treatment of peripheral and coronary artery disease. Further studies, however, are necessary to evaluate the long-term efficacy of this new procedure.

The currently available automatic implantable cardioverter-defibrillator has proven highly successful for termination of ventricular tachycardia and fibrillation. Newer devices, however, permit lower energy shocks to be delivered initially and longer episodes of arrhythmia to occur before shocks are delivered. These changes may result in longer durations of arrhythmia before successful termination. Little is known about the effects of the duration of ventricular fibrillation on the efficacy of defibrillating shocks. In this study, we examined the efficacy of defibrillating shocks in 22 patients undergoing automatic implantable cardioverter-defibrillator implantation or generator change. Defibrillating shocks ranging from 300 to 600 V (5.9-24.2 J) were delivered in matched pairs after 5 and 15 seconds of ventricular fibrillation. For the 300-V shocks (5.9 J), defibrillation was accomplished in 82% of patients when the shocks were given after 5 seconds of ventricular fibrillation and in only 45% of patients when the shocks were delivered after 15 seconds (p less than 0.01). At higher energies, there was no difference in the efficacy of defibrillation shocks delivered after 5 compared with 15 seconds of ventricular fibrillation. The postshock aortic, systolic, and diastolic blood pressures were significantly lower when the shocks were given after 15 seconds of ventricular fibrillation than after only 5 seconds. We conclude that the duration of ventricular fibrillation affects defibrillation efficacy especially at energies that are relatively low compared with maximal device outputs and that longer episodes of ventricular fibrillation cause more postshock hemodynamic depression. These observations have implications for defibrillation threshold testing at the time of device implantation and for the design and programming of future automatic implantable antitachycardia devices.

The Ventritex Cadence Model V-100 Tiered Therapy Defibrillator is a third generation antitachyarrhythmia device currently completing clinical trials in the United States. The implantable pulse generator is capable of high energy defibrillation, low energy cardioversion, as well as antitachycardia and bradycardia pacing. In addition, this microprocessor controlled device can deliver monophasic or biphasic defibrillation/cardioversion shocks, is noncommitted to deliver shock therapy after initiating charging for defibrillation or cardioversion therapy, and can store electrograms of spontaneous tachyarrhythmia episodes. These expanded device capabilities should improve therapy efficacy and patient management, and represent a major advance in the treatment of patients with ventricular tachyarrhythmias.

Fish oil supplements are currently being nationally advertised, and many physicians are being queried about their clinical utility. Epidemiologic studies reveal a low incidence of cardiovascular disease in people, such as the Eskimos, who eat large amounts of seafood. Cardiovascular health may be improved because fish and fish oil supplements lower plasma lipid levels (especially triglycerides), inhibit platelet aggregation, and may decrease blood pressure and viscosity and increase high-density lipoprotein (HDL) levels. Preliminary observations also suggest a potential future role for fish oils in the treatment of some autoimmune diseases, such as atopic dermatitis, psoriasis, and rheumatoid arthritis. Patients with serum triglyceride levels greater than 5.64 mmol/L and/or cholesterol levels greater than 7.75 mmol/L refractory to dietary management may benefit from a medically supervised trial of fish oil supplements. Data currently available are insufficient to recommend fish oil supplements for the general public, or for patients with other diseases, and side effects must also be considered. These include occasional adverse lipid changes, potential for bleeding and vitamin E deficiency, and, with some preparations, vitamin A and D toxicity.