Conventional Versus Biventricular Pacing in Heart Failure and Bradyarrhythmia: The COMBAT Study

Background: Worsening in clinical and cardiac status has been noted after chronic right ventricular pacing, but it is uncertain whether atriobiventricular (BiVP) is preferable to atrio-right ventricular pacing (RVP). Conventional versus Multisite Pacing for BradyArrhythmia Therapy study (COMBAT) sought to compare BiVP versus RVP in patients with symptomatic heart failure (HF) and atrioventricular (AV) block. Methods and Results: COMBAT is a prospective multicenter randomized double blind crossover study. Patients with New York Heart Association functional class (FC) II-IV, left ventricular ejection fraction (LVEF) <40%, and AV block as an indication for pacing were enrolled. All patients underwent biventricular system implantation and then were randomized to receive successively (group A) RVP-BiVP-RVP, or (group B) BiVP-RVP-BiVP. At the end of each 3-month crossover period, patients were evaluated according to Quality of Life (QoL), FC, echocardiographic parameters, 6-Minute Walk Test (6MWT), and peak oxygen consumption (VO(2max)). Sixty patients were enrolled, and the mean follow-up period was 17.5 +/- 10.7 months. There were significant improvements in QoL, FC, LVEF, and left ventricular end-systolic volume with BiVP compared with RVP. The effects of pacing mode on 6MWT and VO(2max) were not significantly different. Death occurred more frequently with RVP. Conclusion: In patients with systolic HF and AV block requiring permanent ventricular pacing, BiVP is superior to RVP and should be considered the preferred pacing mode. (J Cardiac Fail 2010;16:293-300)

A Randomized Trial of a Skin Sealant to Reduce the Risk of Incision Contamination in Cardiac Surgery

Background. Immobilizing skin microbes is a rational approach to reducing contamination of surgical sites by endogenous microorganisms. Methods. This randomized, controlled, parallel-group, multicenter, open-label clinical trial (ClinicalTrials.gov NCT00467857) enrolled 300 adults scheduled for elective coronary artery bypass graft surgery. Patients received iodine-based skin preparations followed by a cyanoacrylate-based skin sealant or skin preparations alone. Microbiological samples collected from sternal and graft incision sites immediately before any skin preparation, at the wound border after skin incision, and at the incision after fascial closure were evaluated quantitatively. Results. In evaluable patients, mean microbial counts in collected samples increased at the sternal site after fascial closure compared with after skin incision by 0.37 log(10) colony-forming units (CFU)/mL in the skin sealant group (n = 120) and by 0.57 log10 CFU/mL in the control group (n = 132) (p = 0.047, Wilcoxon rank sum test). At the graft site, mean microbial counts increased by 0.09 (n = 119) and 0.27 (n = 127) log(10) CFU/mL, respectively (p = 0.037). There was a 35.3% relative risk reduction in surgical site infection (SSI) occurring in the skin sealant group (9 of 146 patients, 6.2%) versus the control group (14 of 147 patients, 9.5%). In obese patients (body mass index [BMI] > 30.0 to <= 37.0 kg/m(2)), the relative risk reduction for SSI associated with skin sealant was 83.3%. Conclusions. Pretreatment with skin sealant protects against contamination of the surgical incision by migration of skin microbes. Further data are needed to confirm the impact of this technology on SSI rates in clinical practice. (Ann Thorac Surg 2011;92:632-7) (C) 2011 by The Society of Thoracic Surgeons ADULT CARDIAC

The Bypass Angioplasty Revascularization Investigation 2 Diabetes Randomized Trial of Different Treatment Strategies in Type 2 Diabetes Mellitus With Stable Ischemic Heart Disease Impact of Treatment Strategy on Cardiac Mortality and Myocardial Infarction

Background-The Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial in 2368 patients with stable ischemic heart disease assigned before randomization to percutaneous coronary intervention or coronary artery bypass grafting strata reported similar 5-year all-cause mortality rates with insulin sensitization versus insulin provision therapy and with a strategy of prompt initial coronary revascularization and intensive medical therapy or intensive medical therapy alone with revascularization reserved for clinical indication(s). In this report, we examine the predefined secondary end points of cardiac death and myocardial infarction (MI). Methods and Results-Outcome data were analyzed by intention to treat; the Kaplan-Meier method was used to assess 5-year event rates. Nominal P values are presented. During an average 5.3-year follow-up, there were 316 deaths (43% were attributed to cardiac causes) and 279 first MI events. Five-year cardiac mortality did not differ between revascularization plus intensive medical therapy (5.9%) and intensive medical therapy alone groups (5.7%; P = 0.38) or between insulin sensitization (5.7%) and insulin provision therapy (6%; P = 0.76). In the coronary artery bypass grafting stratum (n = 763), MI events were significantly less frequent in revascularization plus intensive medical therapy versus intensive medical therapy alone groups (10.0% versus 17.6%; P = 0.003), and the composite end points of all-cause death or MI (21.1% versus 29.2%; P = 0.010) and cardiac death or MI (P = 0.03) were also less frequent. Reduction in MI (P = 0.001) and cardiac death/MI (P = 0.002) was significant only in the insulin sensitization group. Conclusions-In many patients with type 2 diabetes mellitus and stable ischemic coronary disease in whom angina symptoms are controlled, similar to those enrolled in the percutaneous coronary intervention stratum, intensive medical therapy alone should be the first-line strategy. In patients with more extensive coronary disease, similar to those enrolled in the coronary artery bypass grafting stratum, prompt coronary artery bypass grafting, in the absence of contraindications, intensive medical therapy, and an insulin sensitization strategy appears to be a preferred therapeutic strategy to reduce the incidence of MI. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305. (Circulation. 2009;120:2529-2540.)

Effects of Optimal Medical Treatment With or Without Coronary Revascularization on Angina and Subsequent Revascularizations in Patients With Type 2 Diabetes Mellitus and Stable Ischemic Heart Disease

Background-In the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial, an initial strategy of coronary revascularization and optimal medical treatment (REV) compared with an initial optimal medical treatment with the option of subsequent revascularization (MED) did not reduce all-cause mortality or the composite of cardiovascular death, myocardial infarction, and stroke in patients with type 2 diabetes mellitus and stable ischemic heart disease. In the same population, we tested whether the REV strategy was superior to the MED strategy in preventing worsening and new angina and subsequent coronary revascularizations. Methods and Results-Among the 2364 men and women (mean age, 62.4 years) with type 2 diabetes mellitus, documented coronary artery disease, and myocardial ischemia, 1191 were randomized to the MED and 1173 to the REV strategy preselected in the percutaneous coronary intervention (796) and coronary artery bypass graft (377) strata. Compared with the MED strategy, the REV strategy at the 3-year follow-up had a lower rate of worsening angina (8% versus 13%; P < 0.001), new angina (37% versus 51%; P = 0.001), and subsequent coronary revascularizations (18% versus 33%; P < 0.001) and a higher rate of angina-free status (66% versus 58%; P = 0.003). The coronary artery bypass graft stratum patients were at higher risk than those in the percutaneous coronary intervention stratum, and had the greatest benefits from REV. Conclusions-In these patients, the REV strategy reduced the occurrence of worsening angina, new angina, and subsequent coronary revascularizations more than the MED strategy. The symptomatic benefits were observed particularly for high-risk patients.

Real-time and Doppler US after pediatric segmental liver transplantation

Background Accurate diagnosis of portal vein (PV) stenosis by real-time and color Doppler US (CD-US) after segmental liver transplantation in children can decrease morbidity by avoiding unnecessary biopsy, PV hypertension, thrombosis and loss of the graft. Objective To evaluate CD-US parameters for the prediction of PV stenosis after segmental liver transplantation in children. Materials and methods We retrospectively reviewed 61 CD-US examinations measuring the diameter at the PV anastomosis, velocities at the anastomosis (PV1) and in the segment proximal to the anastomosis (PV2), and the PV1/PV2 velocity ratio. The study group comprised patients with stenosis confirmed by angiography and the control group comprised patients with a good clinical outcome. Results PV stenosis was seen in 12 CD-US examinations. The mean PV diameter was smaller in the study group (2.6 mm versus 5.7 mm) and a PV diameter of < 3.5 mm was highly predictive of stenosis (sensitivity 100%, specificity 91.8%). Conclusion A PV diameter of < 3.5 mm is a highly predictive CD-US parameter for the detection of hemodynamically significant stenosis on angiography.

Presentation of the HPV16E7 protein by skin grafts is insufficient to allow graft rejection in an E7-primed animal

The E7 transforming protein of Human Papillomavirus type 16 (HPV16) is expressed in the skin of a line of RIB mice transgenic for the E6 and E7 open reading frames of HPV16 driven from the alpha A crystallin promoter (FVB alpha AcryHPV16E6E7). We have transferred skin from FVB alpha AcryHPV16E6E7 mice to naive or E7-primed syngeneic NE recipients to assess whether the E7 protein of HPV16 can function as a minor transplantation antigen (MTA) and promote skin graft rejection. FVB mice did not reject E7 expressing tail or flank skin grafts. E7 immunized FVB x C57BL/6J mice recipients of FVB alpha AcryHPV16E6E7 x C57BL/6J skin generated humoral and DTH responses to E7 in vivo and E7-specific CTL precursors in the spleen, but failed to reject 57 expressing tail skin grafts by 100 days posttransfer. Thus although HPV16 E7 + ve mesenchymal and endodermal tumors can be eliminated by an E7-specific immune response, the same protein is unable to act as a MTA and promote graft rejection when expressed in skin cells. Lack of rejection of grafts expressing MTAs such as E7 may be relevant to the immunology of epithelial tumors expressing tumor-specific antigens and to our understanding of the immunology of diseases of the skin. (C) 1997 Academic Press.

Altered expression of the costimulatory molecules CD80, CD86, CD152, PD-1 and ICOS on T-cells from paracoccidioidomycosis patients: Lack of correlation with T-cell hyporesponsiveness

T-cell proliferative hypo responsiveness, a hallmark of paracoccidioidomycosis immune responses, underlies host`s failure in controlling fungus spread, being reversible with antifungal treatment. The mechanisms leading to this hypoproliferation are not well known. Since costimulatory molecules have been shown to profoundly regulate T-cell immune responses, we investigated the hypothesis that the determinants of the responder versus tolerant state may be the regulated expression of, or signaling by, costimulatory molecules. Expression of CD80, CD86, CD28, CD152, ICOS and PD-1 costimulatory molecules were examined on T-cells and monocytes harvested from stimulated and unstimulated PBMC cultures of active paracoccidioidomycosis patients and healthy individuals cured of past paracoccidioidomycosis. Stimuli were gp43, the immunodominant component of Paracoccidioides brasiliensis, and a Candida antigen. While CD28 expression, critical for optimal T-cell activation, was comparable between patients and controls, CD152, PD-1 and ICOS, which preferentially deliver negative signaling, were overexpressed on patients` stimulated and unstimutated T-cells. PBMC cultures were carried out in presence of the respective blocking antibodies which, however, failed to restore T-cell proliferation. CD80 and CD86 were equally expressed on patients` and controls` monocytes, but overexpressed on patients` T-cells. Blockade with the respective blocking antibodies on day 4 of the culture also did not restore T-cell proliferation, while, on day 0, differentially inhibited Candida and gp43 responses, suggesting that different antigens require different costimulatory pathways for antigen presentation. Our data favors the hypothesis, raised from other foreign antigen models, that prolonged in vivo antigen exposure leads to an adaptive tolerance T-cell state which is hardly reverted in vitro. (C) 2008 Elsevier Inc. All rights reserved.

Prospective evaluation of EUS versus CT scan for staging of ampullary cancer

Background: Malignancies of the biliary and pancreatic systems are associated with a poor prognosis. However, ampullary cancer carries a better prognosis and is often diagnosed when curative treatment is still possible. Accurate staging is important for the determination of the most appropriate treatment option. Objectives: (1) To determine the test performance characteristics of EUS and CT in loco-regional staging of ampullary neoplasms, and (2) to determine the impact of CT scan results on the test performance characteristics of EUS. Design and Setting: Prospective single-arm intervention study performed in 2 academic hospitals. Results and Main Outcome Measurements: Thirty-seven patients were screened and 33 staged with EUS and CT A total of 27 patients (13 men; mean age, 69.5 years; mean serum bilirubin level, 12.6 mg/dL) with locally advanced disease completed the protocol with EUS and CT and underwent surgical resection. Tumor classifications were as follows: 2 patients (7.4%), T1 tumors; 13 patients (48.1%), T2 tumors; and 12 patients (44.4%), T3 tumors, as per surgical pathology. Seventeen tumors (62.9%) were classified as NO and 10 (37.1%) as NI. The difference in proportion of correct tumor (74.1% vs 51.8%; P =.15, 95% CI, -0.06-0-50) and lymph node (81.4% vs; 55.5%; P =.07, 95% Cl, -0.01-0.53) staging by EUS and CT, respectively, was not statistically significantly different. However, the strength of tumor (kappa 0.51 vs 0.11) and nodal (kappa 0.59 vs 0.05) agreement with pathology was statistically significantly higher for EUS than for CT (P <.05). EUS was more sensitive and specific than CT for tumor and nodal staging, and the association of CT to EUS data did not improve the final test accuracy Limitation: Low number of T1 tumors. Conclusions: EUS is in accurate diagnostic test and exhibits a high level of agreement with surgical pathology. CT findings do not improve the test performance characteristics of EUS. Therefore, the evaluation for metastatic disease should not be compromised by CT protocols that aim to perform tumor and nodal staging. Further studies to determine the role of specialized CT protocols in patients with ampullary malignancies are needed. (Gastrointest Endosc 2009;70:290-6.)

Prospective randomized trial of EUS versus ERCP-guided common bile duct stone removal: an interim report (with video)

Background: EUS is being increasingly utilized for the diagnosis of choledocholithiasis and microlithiasis, especially in patients with biliary colic. Simultaneously, there is also a rising interest in the use of EUS for therapeutic interventions. Objectives: Our goal was to assess the effectiveness of EUS-directed common bile duct (CBD) stone removal to compare its safety and effectiveness with ERCP-directed intervention. Design: interim results of a prospective, randomized, single-center blinded clinical trial. Setting: A single tertiary care referral center. Patients: Fifty-two patients with uncomplicated CBD stones were prospectively randomized to CBD cannulation and stone removal under EUS or ERCP guidance. Main Outcome Measurements and Interventions: Primary outcome measure was the rate of successful cannulation of the CBD. Secondary Outcome measures included Successful removal of stones and overall complication rates. Results: CBD cannulation followed by stone extraction was successful in 23 of 26 patients (88.5%) in the EUS group (1) versus 25 of 26 patients (96.2%) in the ERCP group (11) (95% CI, -27.65%, 9.88%). Overall, there were 3 complications in the EUS group and 4 complications in the ERCP group. Limitation: The current study is an interim report from a single center report and performed by a single operator. Conclusions: Our preliminary analysis indicates that Outcomes following EUS-guided CBD stone retrieval are equivalent to those following ERCP EUS-related adverse events are similar to those following ERCP. ERCP and EUS-guided stone retrieval appears to be equally effective for therapeutic interventions of the bile duct. Additional studies are required to validate these preliminary results and to determine predictors of success of EUS-guided stone removal. (Gastrointest Endosc 2009;69:238-43.)

Solid pseudopapillary neoplasm of the pancreas: distinct patterns of onset, diagnosis, and prognosis for male versus female patients

Background. Solid pseudopapillary neoplasm of the pancreas is a distinctive pancreatic neoplasm with low metastatic potential. This study examines clinical differences and prognosis between male and female Patients. Methods. The medical records of 34 consecutive patients with pancreatic solid pseudopapillaly neoplasms between 1990 and 2006 were reviewed. Whenever feasible, organ-preserving operation was performed. Statistical analysis was performed using chi-square and Student t test. Results. There were 27 women (79%) and seven men (21%) with median age of 23 years. Mean diameter of the tumor was 7 cm. Tumor size tended to be smaller in patients treated in more recent years. Conservative surgery was possible in I I patients including spleen-preserving distal pancreatectomy in 3, central pancreatectomy in 5, and enucleation in 3 patients. Median hospital stay was 11 days, morbidity rate was 62%, including 17 patients with grade A pancreatic fistula, and there was no operative mortality. Mean follow-up time was 84 months. Tumor recurred in 2 patients (6%). Overall late morbidity rate was 12%. At the time of diagnosis, age was ((x) over bar +/- SD) higher among male patients (25 +/- 2 years vs 37 +/- 7 years, P < .05) with no difference in tumor size. The neoplasms were more aggressive in male Patients; therefore, conservative surgery was less likely. There was no correlation between tumor aggressiveness and age of the patient or size of tumor. Conclusion. This is the first single center study to demonstrate that solid pseudopapillary neoplasms in male patients have distinct Patterns Of onset and aggressiveness when compared with female patients. Although valid prognostic criteria are still lacking, it appears that male patients may be best treated by more radical operation and should be observed more closely during follow-up.

The rms1 mutant of pea has elevated indole-3-acetic acid levels and reduced root-sap zeatin riboside content but increased branching controlled by graft-transmissible signal(s)

Rms1 is one of the series of five ramosus loci in pea (Pisum sativum L.) in which recessive mutant alleles confer increased branching at basal and aerial vegetative nodes. Shoots of the nonallelic rms1 and rms2 mutants are phenotypically similar in most respects. However, we found an up to 40-fold difference in root-sap zeatin riboside ([9R]Z) concentration between rms1 and rms2 plants. Compared with wild-type (WT) plants, the concentration of [9R]Z in rms1 root sap was very low and the concentration in rms2 root sap was slightly elevated. To our knowledge, the rms1 mutant is therefore the second ramosus mutant (rms4 being the first) to be characterized with low root-sap [9R]Z content. Like rms2, the apical bud and upper nodes of rms1 plants contain elevated indole-3-acetic acid levels compared with WT shoots. Therefore, the rms1 mutant demonstrates that high shoot auxin levels and low root-sap cytokinin levels are not necessarily correlated with increased apical dominance in pea. A graft-transmissible basis of action has been demonstrated for both mutants from reciprocal grafts between mutant and WT plants. Branching was also largely inhibited in rms1 shoots when grafted to rms2 rootstocks, but was not inhibited in rms2 shoots grafted to rms1 rootstocks. These grafting results are discussed, along with the conclusion that hormone-like signals other than auxin and cytokinin are also involved.

Population versus clinical view of case fatality from acute coronary heart disease - Results from the WHO MONICA Project 1985-1990

Background The clinical view of case fatality (CF) from acute myocardial infarction (AMI) in those reaching the hospital alive is different from the population view. Registration of both hospitalized AMI cases and out-of-hospital coronary heart disease (CHD) deaths in the WHO MONICA Project allows both views to be reconciled. The WHO MONICA Project provides the largest data set worldwide to explore the relationship between CHD CF and age, sex, coronary event rate, and first versus recurrent event. Methods and Results All 79 669 events of definite AMI or possible coronary death, occurring from 1985 to 90 among 5 725 762 people, 35 to 64 years of age, in 29 MONICA populations are the basis for CF calculations. Age-adjusted CF (percentage of CHD events that were fatal) was calculated across populations, stratified for different time periods, and related to age, sex, and CHD event rate. Median 28-day population CF was 49% (range, 35% to 60%) in men and 51% (range, 34% to 70%) in women and was particularly higher in women than men in populations in which CHD event rates were low. Median 28-day CF for hospitalized events was much lower: in men 22% (range, 15% to 36%) and in women 27% (range, 19% to 46%). Among hospitalized events CF was twice as high for recurrent as for first events. Conclusions Overall 28-day CF is halved for hospitalized events compared with all events and again nearly halved for hospitalized 24-hour survivors. Because approximately two thirds of 28-day CHD deaths in men and women occurred before reaching the hospital, opportunities for reducing CF through improved care in the acute event are limited. Major emphasis should be on primary and secondary prevention.

Evaluation of interventions to reduce catheter-associated bloodstream infection: Continuous tailored education versus one basic lecture

Background: This study evaluated the impact of 2 models of educational intervention on rates of central venous catheter-associated bloodstream infections (CVC-BSIs). Methods: This was a prospective observational study conducted between January 2005 and June 2007 in 2 medical intensive care units (designated ICU A and ICU B) in a large teaching hospital. The study was divided into in 3 periods: baseline (only rates were evaluated), preintervention (questionnaire to evaluate knowledge of health care workers [HCWs] and observation of CVC care in both ICUs), and intervention (in ICU A, tailored, continuous intervention; in ICU B, a single lecture). The preintervention and intervention periods for each ICU were compared. Results: During the preintervention period, 940 CVC-days were evaluated in ICUA and 843 CVC-days were evaluated in ICU B. During the intervention period, 2175 CVC-days were evaluated in ICUA and 1694 CVC-days were evaluated in ICU B. Questions regarding CVC insertion, disinfection during catheter manipulation, and use of an alcohol-based product during dressing application were answered correctly by 70%-100% HCWs. Nevertheless, HCWs` adherence to these practices in the preintervention period was low for CVC handling and dressing, hand hygiene (6%-35%), and catheter hub disinfection (45%-68%). During the intervention period, HCWs` adherence to hand hygiene was 48%-98%, and adherence to hub disinfection was 82%-97%. CVC-BSI rates declined in both units. In ICUA, this decrease was progressive and sustained, from 12CVC-BSIs/1000 CVC-days at baseline to 0 after 9 months. In ICU B, the rate initially dropped from 16.2 to 0 CVC-BSIs/1000 CVC-days, but then increased to 13.7 CVC-BSIs/1000 CVC-days. Conclusion: Personal customized, continuous intervention seems to develop a ""culture of prevention"" and is more effective than single intervention, leading to a sustained reduction of infection rates.

Histologic Study of Perifascial Areolar Tissue Implanted in Rabbit Vocal Folds: An Experimental Study

Objectives: Perifascial areolar tissue (PAT) consists of loose areolar tissue with viscoelastic properties that are similar to those found in tissues in the superficial layer of the vocal fold. The aim of this study was to quantify the inflammatory process and the collagen content of the graft, as well as that of the host tissue, after placement of a strip of PAT into the rabbit vocal fold. Methods: Surgeries were performed on 30 rabbits. The grafts were implanted in pockets that were surgically created in the right vocal fold. The left vocal fold (control group) was subjected only to surgical manipulation. The animals were divided into 3 groups for evaluations at 15 days, 3 months, and 6 months, and their larynx tissues were subsequently reviewed by histology. Results: The grafts were characterized by disorganized and thick collagen bundles and were identified in all study groups. The collagen density stayed constant over time. There was an acute inflammatory response induced by the graft at 15 clays that did not exist in the specimens taken at 3 and 6 months. Deposition of collagen fibers in the lamina propria was observed starting at 15 days after the operation and was more intense in the experimental vocal fold than in the control vocal fold. Conclusions: Our findings indicated that PAT has a low tendency for promoting an inflammatory response. However, there was a loss of the original architecture of the graft tissue and a greater deposition of collagen in the implanted vocal folds than in the control group.