Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) ...was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
Supraventricular Tachycardia After Orthotopic Cardiac Transplantation Marmar Vaseghi, Noel G. Boyle, Rohit Kedia, Jignesh K. Patel, David A. Cesario, Isaac Wiener, Jon A. Kobashigawa, Kalyanam ...Shivkumar The incidence, clinical course, and management of supraventricular tachycardias (SVTs) were studied in 729 patients who underwent orthotopic heart transplantation. The mechanism of arrhythmias among the patients referred for electrophysiological study and ablation were also characterized. In stable cardiac transplant patients the majority of SVTs were attributed to macro-reentrant tachycardias (flutter and scar reentry). Catheter ablation is effective in management of these tachycardias. Persistent or paroxysmal atrial fibrillation was not observed in stable transplant patients (beyond the post-operative period), and its occurrence should prompt an evaluation for acute rejection and/or vasculopathy.
The efficacy of shock in converting different ventricular tachyarrhythmias has not been well characterized in a large natural-practice setting.
To determine shock success rate by energy and ...ventricular rhythm in a large cohort of patients with implantable cardioverter-defibrillators.
Two thousand patients with 5279 shock episodes were randomly sampled for analysis from the LATITUDE remote monitoring system. Within an episode, the rhythm preceding therapy (shock or antitachycardia pacing ATP) was adjudicated. Patients who died after unsuccessful implantable cardioverter-defibrillator shocks did not transmit final remote monitoring data and were not included in the study.
Of 3677 shock episodes for ventricular tachyarrhythmia, 2679 were treated with shock initially and were classified as monomorphic ventricular tachycardia ( n = 1544), polymorphic/monomorphic ventricular tachycardia (n = 371), or ventricular fibrillation (n = 764). The success rate after the first, second, and final shock averaged 90.3%, 96.4%, and 99.8%, respectively. After unsuccessful initial ATP (n = 998), the first, second, and final shock was successful in 84.8%, 92.9%, and 100% of the episodes. The success rate after the first or second shock was significantly lower after failed ATP compared to shock as first therapy (both P<.001). Among episodes treated initially with shock, the success rate for monomorphic ventricular tachycardia (89.2%) when treated with energy level ≤ 20 J was significantly higher than that for ventricular fibrillation (80.8%) (P = .04). The level of shock energy was a significant predictor of the success of the first shock (odds ratio 1.16; 95% confidence interval 1.03-1.30; P = .013).
The success rate of first shock as first therapy is approximately 90%, but was lower after failed ATP. Programming a higher level of energy after ATP is suggested.
Objectives The perioperative administration of pleomorphic statin drugs has been implicated in improving outcomes after cardiac surgery. Adaptive autophagy is a highly conserved cellular process that ...allows for the elimination of dysfunctional cell components in response to stress and survival under starving conditions. We sought to investigate the effects of the statin drug atorvastatin on autophagy in ischemic and nonischemic myocardia using a clinically relevant porcine model of metabolic syndrome. Methods Male Ossabaw swine were fed a regular diet (n = 8), a high-cholesterol diet (n = 8), or a high-cholesterol diet with supplemental atorvastatin (1.5 mg/kg/d) (n = 8). After 14 weeks, all animals underwent surgical placement of an ameroid constrictor to the circumflex coronary artery to induce chronic ischemia. Nonischemic and ischemic myocardia were harvested 6 months after initiation of the diet and processed for Western blotting. Results In the nonischemic myocardium, Western blot results demonstrate that a high cholesterol diet resulted in a statistically significant decrease in autophagy as indicated by an increase in mammalian target of rapamycin and the accumulation of several essential autophagy markers, including Beclin-1, light chain 3B-I, and light chain 3B-II. Atorvastatin supplementation prevented these changes and resulted in an increase in autophagy as indicated by a decrease in autophagy flux marker P62. In the ischemic myocardium, atorvastatin had the opposite effect, with a decrease in autophagy flux as indicated by an increase in p62 and an accumulation of light chain 3B-I, light chain B-II, and lysosome-associated membrane protein 2. Conclusions Atorvastatin administration has differential effects on autophagy in ischemic and nonischemic myocardia. In the setting of metabolic syndrome, atorvastatin stimulates autophagy in nonischemic myocardium while partly inhibiting autophagy in ischemic myocardium. The differential regulation on autophagy may, in part, explain the cardioprotective effect of statins in both ischemic and nonischemic myocardia, and these findings may have implications in the setting of cardiac surgery.
Nearly 1/3 of patients with heart failure (HF) fail to respond to cardiac resynchronization therapy (CRT). The purpose of this study was to evaluate the value of preimplantation brain natriuretic ...peptide (BNP) in predicting the clinical response to CRT. We retrospectively analyzed 164 patients who underwent CRT. Patients with New York Heart Association functional class III or IV HF symptoms despite maximal medical therapy, who were not on inotropic medications, had left ventricular ejection fraction ≤35%, and QRS duration >130 ms were included in the study. CRT response in patients who survived at 6-month follow-up was defined as no HF hospitalization and improvement of ≥1 grades in the New York Heart Association classification. BNP assays were performed before implantation and at 6-month follow-up. Patients had ischemic (47%) or nonischemic (53%) cardiopathy. Responders (n = 107) and nonresponders (n = 57) had similar baseline characteristics. Cardiac death and hospitalization for HF occurred in 5 (4.7%) and 18 (31.6%) patients, respectively. CRT responders compared with nonresponders exhibited higher preimplantation BNP levels (800 ± 823 vs 335 ± 348 pg/ml, p = 0.0002) and a significant reduction in the QRS duration after implantation (−6 ± 34 vs +7 ± 32 ms, p = 0.048). The preimplantation BNP was the only independent predictor of the CRT response (p = 0.001). A BNP value ≥447 pg/ml demonstrated a sensitivity of 62% and specificity of 79% in identifying CRT response. In a subgroup of 41 patients who underwent Doppler tissue imaging analysis, the preimplantation BNP was higher in patients presenting with intraventricular dyssynchrony (845 ± 779 vs 248 ± 290 pg/ml, p = 0.04). In conclusion, the preimplantation BNP value independently predicts CRT response and was superior to QRS duration reduction in identifying CRT responders.
Objective We have analyzed short- and long-term variations of pulmonary function in locally advanced non–small cell lung cancer after induction chemoradiotherapy. Methods Twenty-seven patients with ...stage IIIA (N2) non–small cell lung cancer underwent resection with radical intent after induction chemoradiotherapy in the period 2003 to 2006. Pulmonary function has been evaluated by spirometry, diffusing capacity of the lung for carbon monoxide, and blood gas analysis before induction chemoradiotherapy (T0), 4 weeks after induction chemoradiotherapy and before surgery (T1), and 1 (T2), 3 (T3), 6 (T4), and 12 months (T5) after surgery. Results A 22.80% decrease of diffusing capacity of the lung for carbon monoxide ( P < .001) was observed at T1. At T2 significant decreases in the following were present: vital capacity, −20.50% ( P < .001); forced vital capacity, −22.50% ( P < .001); forced expiratory volume in 1 second, −23.00% ( P < .001); peak expiratory flow, −29.0 ( P < .001); forced expiratory flow 25% to 75%, −13.7% ( P = .005); and diffusing capacity of the lung for carbon monoxide, 43.6% ( P < .001). However, in the interval between T2 and T5, a progressive improvement of lung function in most parameters was observed, but only diffusing capacity of the lung for carbon monoxide presented a significant increase ( P < .001). Within the same time gap (T2 to T5), subjects 65 years of age or younger showed an increasing trend for vital capacity, forced expiratory volume in 1 second, total lung capacity, and residual volume significantly different from that of elderly patients, in whom a decrease in these parameters is reported. Conclusions An impairment of respiratory function is evident in the immediate postoperative setting in patients with non–small cell lung cancer receiving induction chemoradiotherapy. In the long-term period, a general recovery in diffusing capacity of the lung for carbon monoxide was found, whereas an improvement of forced expiratory volume in 1 second, vital capacity, total lung capacity, and residual volume was detected in the younger population only.
Objective Despite advances in surgical techniques, neurocognitive decline after cardiopulmonary bypass remains a common and serious complication. We have previously demonstrated that patients with ...neurocognitive decline have unique genetic responses 6 hours after cardiopulmonary bypass when compared with normal patients. We used genomic microarray to objectively investigate whether patients with neurocognitive decline had associated preoperative gene expression profiles and how these profiles changed up to 4 days after surgery. Methods Patients undergoing cardiac surgery underwent neurocognitive assessments preoperatively and 4 days after surgery. Skeletal muscle was collected intraoperatively. Whole blood collected before cardiopulmonary bypass, 6 hours after cardiopulmonary bypass, and on postoperative day 4 was hybridized to Affymetrix Gene Chip U133 Plus 2.0 microarrays (Affymetrix Inc, Santa Clara, Calif). Gene expression in patients with neurocognitive decline was compared with gene expression in the normal group using JMP Genomics (SAS Institute Inc, Cary, NC). Only genes that were commonly expressed in the 2 groups with a false discovery rate of 0.05 and a fold change greater than 1.5 were carried forward to pathway analysis using Ingenuity Pathway Analysis (Ingenuity Systems, Redwood City, Calif). Microarray gene expression was validated by Green real-time polymerase chain reaction and Western blotting. Results Neurocognitive decline developed in 17 of 42 patients. A total of 54,675 common transcripts were identified on microarray in each group across all time points. Preoperatively, there were 140 genes that were significantly altered between the normal and neurocognitive decline groups ( P < .05). Pathway analysis demonstrated that preoperatively, patients with neurocognitive decline had increased regulation in genes associated with inflammation, cell death, and neurologic dysfunction. Of note, the number of significantly regulated genes between the 2 groups changed over each time point and decreased from 140 preoperatively to 64 six hours after cardiopulmonary bypass and to 25 four days after surgery. There was no correlation in gene expression between the blood and the skeletal muscle. Conclusions Patients in whom neurocognitive decline developed after cardiopulmonary bypass had increased differential gene expression before surgery versus patients in whom neurocognitive decline did not develop. Although significant differences in gene expression also existed postoperatively, these differences gradually decreased over time. Preoperative gene expression may be associated with neurologic injury after cardiopulmonary bypass. Further investigation into these genetic pathways may help predict patient outcome and guide patient selection.
Background We investigated whether mitogen-activated protein kinases (MAPKs) are changed in the hearts of patients with diabetes after cardioplegia and cardiopulmonary bypass (CP/CPB) operations. ...Methods Biopsies from the right atrial appendage were harvested pre- and post-CP/CPB from nondiabetic (ND) patients ( n = 8, hemoglobin A1c (HbA1c) = 5.4 ± 0.12); patients with controlled diabetes (CDM) ( n = 8, HbA1c = 6.5 ± 0.15); and patients with uncontrolled diabetes (UDM) ( n = 8, HbA1c = 9.6 ± 0.3) undergoing coronary artery bypass grafting. The expression and/or activation of the p38-MAPK, ERK1/2, JNK, and MKP-1 in the right-atrial tissues were analyzed by Western blotting. The vasomotor function of coronary arterioles was measured by videomicroscopy. Results The post-CP/CPB levels of total p38-MAPK were decreased in the 3 groups as compared with their pre-CP/CPB levels ( P < .05). There were increases in phospho-p38-MAPK, phospho-ERK1/2, and MKP-1 in UDM patients as compared with ND and CDM patients at baseline ( P < .05). Compared to pre-CP/CPB, the post-CP/CPB levels of phospho-p38-MAPK decreased in the UDM group but were unaltered in the ND and CDM groups; however, the post-CP/CPB levels of phospho-p38-MAPK still remained greater than the post-CP/CPB levels of the other 2 groups. Post-CP/CPB levels of phospho-ERK1/2 were increased in the ND and CDM groups but were decreased in the UDM group compared to their pre-CP/CPB levels, respectively ( P < .05). There were no significant differences in phospho-JNK in 3 groups at baseline. Post-CP/CPB levels of phospho-JNK, however, were increased in the 3 groups and were more pronounced in the myocardium of the UDM group ( P < .05). After CP/CPB, the protein levels of MKP-1 were unchanged in the 3 groups when compared with their pre-CP/CPB levels. Post-CP/CPB levels of MKP-1, however, remained greater in the UDM group than in the ND and CDM groups. The post-CP/CPB contractile responses to the thromboxane A2 analog U46619 were significantly impaired in all 3 groups compared with pre-CP/CPB contractile responses. These impairments were more pronounced in the UDM group. Conclusion Uncontrolled diabetes is associated with changes in expression of and activation of MAPKs and vasomotor dysfunction in the setting of CP/CPB.
The impact of cardiac resynchronization therapy (CRT) on dispersion of repolarization is controversial. The benefit of CRT on sudden cardiac death has been demonstrated only after 3 years follow-up.
...The purpose of this study was to explore the immediate effect of CRT on dispersion of repolarization and to define the value of dispersion of repolarization parameters as predictors of appropriate implantable cardioverter-defibrillator (ICD) therapy.
Data from 100 patients who underwent CRT-ICD placement were analyzed retrospectively. Patients had symptoms of New York Heart Association functional class III or IV heart failure, left ventricular ejection fraction < or =35%, and QRS duration >130 ms or QRS < or =130 ms with left intraventricular dyssynchrony. ECG indices of dispersion of repolarization before and immediately after CRT implantation (QT dispersion, Tpeak-Tend Tp-e, and Tp-e dispersion) were measured.
In patients who were upgraded to a biventricular system, Tp-e did not increase significantly after CRT. However, Tp-e increased significantly after CRT in patients with left bundle branch block or narrow QRS at baseline. After 12-month follow-up, 22 patients had received appropriate ICD therapy. ICD therapy and no ICD therapy groups had similar baseline characteristics, such as secondary prevention and ischemic cardiomyopathy. Postimplantation Tp-e was the only independent predictor of future ICD therapy (P = .02).
Immediately after CRT, Tp-e did not increase in patients who received a biventricular upgrade; however, Tp-e did increase in patients with preimplantation left bundle branch block or narrow QRS. Postimplantation Tp-e was the only independent predictor of appropriate ICD therapy.
PDF
