Externalized conductors and electrical dysfunction in transvenous ventricular leads: Results of the Cardiac Lead Assessment Study.

Background: The Cardiac Lead Assessment Study (CLAS) was a large prospective, multicenter, international postmarket surveillance study conducted at 45 sites. Objective: The purpose of CLAS was to examine the prevalence and incidence of externalized conductors and electrical dysfunction in subjects with selected St. Jude Medical defibrillator and left ventricular leads. Methods: Cinefluoroscopy was used to determine the presence of externalized conductors at enrollment and at 12-, 24-, and 36-month follow-up visits. Lead electrical measurements were collected systematically. Results: The study enrolled 2216 subjects with a total of 2847 study leads. The prevalence of externalized conductors through 36 months for Riata leads was 30.9%, Riata ST leads 12.6%, Durata leads 0.5%, and QuickSite/QuickFlex leads 4.7%. The prevalence of electrical dysfunction through 36 months for Riata was 4.0%, Riata ST 3.3%, Durata 2.4%, and QuickSite/QuickFlex 0.3%. In Riata and Riata ST leads with externalized conductors, there was a low risk of electrical dysfunction. None of the Durata or QuickSite/QuickFlex leads with externalized conductors developed electrical dysfunction. There was no evidence of an electrical short in a high-voltage shocking circuit leading to failed shock. Conclusion: A high prevalence of externalized conductors was found in Riata and Riata ST defibrillator leads, with a higher risk of externalization for 8F Riata leads than for 7F Riata ST leads. The 98% reduction in prevalence of externalized conductors in Durata leads compared to Riata/Riata ST leads confirms that the design improvements culminating in Durata leads significantly improved abrasion resistance and durability.

Inflammatory Mediators and Clinical Outcome in Patients With Advanced Heart Failure Receiving Cardiac Resynchronization Therapy.

Expression of different cytokines and growth factors after myocardial injury has been associated with fibroplasia and dilatation versus reverse remodeling and myocardial repair. Specifically, the proinflammatory/fibrotic mediators: interleukin (IL)-6, epidermal growth factor, and fibroblast growth factor (FGF)-2 cause fibroplasia, whereas reparative cytokines including: IL-1α, IL-1ß, IL-4, and IL-13 can limit fibrosis. In appropriate patients, cardiac resynchronization therapy (CRT) reverses cardiomyopathy and improves outcome. However, a significant proportion will not respond to this therapy. We conducted this study to assess the association of proinflammatory/fibrotic and/or reparative immune response mediators at baseline with outcome after CRT. In the multicenter RISK study, plasma samples were collected prospectively before CRT implantation. Plasma IL-6, epidermal growth factor, FGF-2, IL-1α, IL-1ß, IL-4, and IL-13 were evaluated by Luminex technology. The primary outcome was predefined as freedom from heart failure hospitalization or death and a decrease in echocardiographic end-systolic volume of >15% at 12 months. To determine associations with the outcome, multivariate logistic regression models including baseline clinical characteristics and the specific cytokines and growth factors were constructed. On multivariate analysis of 257 patients, detectable reparative cytokine IL-13 was significantly associated with the primary outcome (odds ratio 3.79; 95% CI 2.10 to 6.82, p <0.0001). In contrast, detectable proinflammatory/fibrotic growth factor FGF-2 was negatively associated (odds ratio 0.31; 95% CI, 0.14 to 0.68; p = 0.004). In conclusion, in CRT recipients, baseline levels of inflammatory mediators affecting cardiac fibrosis versus repair were associated with subsequent clinical outcome.

Association of BNP and Troponin Levels with Outcome among Cardiac Resynchronization Therapy Recipients.

BACKGROUND: We conducted a prospective multicenter study to assess the prognostic value of combined baseline preimplant plasma levels of the biomarkers cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) among cardiac resynchronization therapy (CRT) with or without defibrillator capability (CRT-D) recipients. METHODS: At CRT-D implant, patients were stratified based on detectable TnT (≥0.01 ng/mL) and elevated BNP (predefined as >440 pg/mL) levels. Patients were classified into three groups: high (both detectable TnT and high BNP), intermediate (either detectable TnT or high BNP), or low (nondetectable TnT and low BNP). Patients were followed for 12 months. Survival curves free from mortality or heart failure hospitalizations (HFH) were assessed. To assess the predictive value of biomarker category, we constructed a multivariate Cox regression model, including the covariates of age, New York Heart Association class, left ventricular ejection fraction (LVEF), and QRS duration. RESULTS: A total of 267 patients (age 66 ± 12 years, males 80%, LVEF 25% ± 8%, ischemic cardiomyopathy 52%, QRSd 155 ± 26 ms) were studied. After 1 year, there were 13 deaths and 25 HFH events. A significant difference in event-free survival among the three groups was observed, with high and intermediate categories having worse survival than low (log-rank test, P < 0.001). In the multivariate model, risk category was a significant predictor of outcome: hazard ratios were 7.34 (95% confidence interval [CI]: 2.48-21.69) and 2.50 (95% confidence interval [CI]: 1.04-6.04) for high-risk and intermediate-risk groups, respectively (P < 0.0001). CONCLUSION: Among CRT-D recipients, baseline TnT and BNP values alone or in combination provide significant prognostic value for the outcome of mortality or HFH.

The current state of dermatopathology education: a survey of the Association of Professors of Dermatology.

BACKGROUND: Dermatology training programs develop program-specific dermatopathology (DP) curricula. We summarize the current state of DP education in dermatology residency programs and identify opportunities for DP education resource development. METHODS: A 27-question survey was emailed to members of the Association of Professors of Dermatology (APD). RESULTS: Fifty-two of 109 programs responded for a response rate of 48%. Results were calculated using a non-response adjustment. Thirty per cent of the overall education time during residency is spent in DP-specific education. Lever and Weedon are the texts most often cited as primary texts utilized for DP education. Three-quarters of programs have third year residents spend three or more weeks on the DP service. The majority of dermatology residency programs have a specific DP service rotation at some point during residency. CONCLUSIONS: The majority of training programs use a variety of resources and mechanisms for teaching DP to dermatology residents. Some programs list barriers to DP education including lack of cases, microscopes, resident education time for DP-related teaching and availability of educators. We conclude that a greater depth and breadth of resources for DP education would be of benefit to dermatology residency programs.

Results and repeatability of retinal thickness measurements from certification submissions.

OBJECTIVES: To present the results for subgroups defined by center point (CP) measurement and to assess the repeatability of the Fast Retinal Thickness Map analysis results from the Stratus OCT3 machine. METHODS: Two hundred eighty-one replicate OCT3 scans from 134 operators' certification submissions to a reading center were analyzed, including scans from eyes that were reported to be normal and eyes with exudative age-related macular degeneration and with macular edema due to diabetic retinopathy or retinal vascular occlusion. RESULTS: The mean (SD) of the CP was 284 (150) microm and the center subfield (CC) was 301 (130) microm. The CP coefficient of repeatability (CR) was 49 microm and the CC CR was 27 microm. The CR increased by increasing retinal thickness for the CP and the CC within arbitrarily defined subgroups. For the 87 eyes with a session 1 CP of 175 microm or less, the CP CR was 17 microm and the CC CR was 10 microm. CONCLUSIONS: Among experienced operators, given the same operator, machine, and eye at the same sitting, OCT3 retinal thickness maps appear to have a CR that is likely to be less than the clinically important difference.

Phase I trial of combined treatment with ch14.18 and R24 monoclonal antibodies and interleukin-2 for patients with melanoma or sarcoma.

PURPOSE: We conducted a phase I trial of interleukin 2 (IL-2) in combination with chimeric 14.18 (ch14.18) and murine R24 antibodies to determine the maximal tolerated dose (MTD), immunological effects, and toxicity of this treatment combination. EXPERIMENTAL DESIGN: Twenty-seven patients with either melanoma (23 patients) or sarcoma (4 patients) were enrolled to receive a combination therapy with ch14.18 and R24 antibodies together with continuous infusion of Roche IL-2 (1.5 x 10(6) U/m(2)/day, 26 patients) or Chiron IL-2 (4.5 x 10(6) U/m(2)/day, 1 patient) given 4 days/week for 3 weeks. The antibodies ch14.18 (2-7.5 mg/m(2)/day) and R24 (1-10 mg/m(2)/day) were scheduled to be administered for 5 days during the second week of IL-2 therapy. RESULTS: When given in combination in this study, the MTD for ch14.18 was 5 mg/m(2)/day and the MTD for R24 was 5 mg/m(2)/day. Dose-limiting toxicities were severe allergic reactions to both ch14.18 and R24 as well as pain related to ch14.18. This ch14.18 MTD was lower than the 7.5 mg/m(2)/day MTD previously determined for ch14.18 given alone with the same dose and schedule of IL-2. Immunological effects included the induction of lymphokine-activated killer (LAK) activity and antibody-dependent cell-mediated cytoxicity (ADCC). Anti-idiotype response to ch14.18 was seen in six patients, including two melanoma patients who had a partial response to treatment. In addition to two partial responses, four patients had a stable disease and one patient remained without any evidence of disease. CONCLUSIONS: Immunotherapy with IL-2 in combination with ch14.18 and R24 antibodies augments LAK function and ADCC measured in vitro in all patients. While there exist theoretical advantages of combining these two antibodies, the MTD of ch14.18 and of R24 were lower than the MTD of each antibody in prior studies evaluating single antibody therapy with IL-2. As such, the combination of these two antibodies together with IL-2 therapy appeared to influence the MTD and toxicity of each of the administered antibodies.

The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17.

OBJECTIVE: To develop a fundus photographic severity scale for age-related macular degeneration (AMD). METHODS: In the Age-Related Eye Disease Study, stereoscopic color fundus photographs were taken at baseline, at the 2-year follow-up visit, and annually thereafter. Photographs were graded for drusen characteristics (size, type, area), pigmentary abnormalities (increased pigment, depigmentation, geographic atrophy), and presence of abnormalities characteristic of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic sensory retinal detachment, subretinal or sub-retinal pigment epithelial hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1 or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic atrophy involving the center of the macula. We explored associations among right eyes of 3212 participants between severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up. RESULTS: A 9-step severity scale that combines a 6-step drusen area scale with a 5-step pigmentary abnormality scale was developed, on which the 5-year risk of advanced AMD increased progressively from less than 1% in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step progression on the scale between the baseline and 5-year visits, almost half showed stepwise progression through intervening severity levels at intervening visits. Replicate gradings showed agreement within 1 step on the scale in 87% of eyes. CONCLUSIONS: The scale provides convenient risk categories and has acceptable reproducibility. Progression along it may prove to be useful as a surrogate for progression to advanced AMD.

A simplified severity scale for age-related macular degeneration: AREDS Report No. 18.

OBJECTIVE: To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). METHODS: Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. RESULTS: The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.