Involvement of fibrocytes in allergen-induced T cell responses and rhinovirus infections in asthma.

Allergen exposure and rhinovirus infections that propagate from the upper to the lower airways are the most frequent causes of asthma exacerbation. In patients at increased risk of disease exacerbations, chronic airway inflammation is associated with the airway recruitment of circulating fibrocytes, bone marrow-derived CD34(+)CD45RO(+)CD11b(+)CD13(+)HLA-DR(+) progenitors that have antigen-presenting function and fibroblast-like properties. This study demonstrates that allergen-pulsed circulating fibrocytes from patients with allergic asthma are potent inducer of the predominant release of the T helper type (Th)2 cytokines IL-4 and IL-5 from autologous naïve and memory CD4(+) T cells. This study also provides evidence that circulating fibrocytes from allergic asthmatics are susceptible to rhinovirus infection. Infected cells release high amounts of pro-inflammatory cytokines with minimal production of IFN-α/ß. Moreover, allergen-pulsed fibrocytes support prolonged rhinovirus replication and release larger quantities of pro-inflammatory cytokines upon rhinovirus infection than unpulsed fibrocytes. Thus, fibrocytes may amplify allergen-induced, Th2 cell-driven inflammatory responses and promote further inflammation by functioning as a reservoir for rhinovirus replication in asthmatic airways. Through these mechanisms, fibrocytes may play an important role in the provocation of disease exacerbations.

IL-33 promotes the migration and proliferation of circulating fibrocytes from patients with allergen-exacerbated asthma.

The release of IL-33 increases in the bronchial mucosa of asthmatic patients in relation to disease severity and several studies have demonstrated that IL-33 may enhance airway inflammation in asthma. This study tested the hypothesis that IL-33 may also contribute to the development of irreversible structural changes in asthma by favoring the airway recruitment and profibrotic function of circulating fibrocytes during episodes of allergen-induced asthma exacerbation. The circulating fibrocytes from patients with allergen-exacerbated asthma (PwAA) showed increased expression of the specific IL-33 receptor component ST2L in comparison with the cells from non-asthmatic individuals (NAI). Recombinant IL-33 induced the migration of circulating fibrocytes from PwAA at clinically relevant concentrations and stimulated their proliferation in a concentration-dependent manner between 0.1 and 10 ng/ml, without affecting the constitutive release of type I collagen. The recombinant protein did not induce similar responses in circulating fibrocytes from NAI. This study uncovers an important mechanism through which fibrocytes may accumulate in the airways of allergic asthmatics when their disease is not adequately controlled by current treatment and provides novel information on the function of IL-33 in asthma.

[Cardiac surgery in octogenarians: a six-year follow-up with a multidimensional intervention]. / Vantaggi di un approccio multidimensionale personalizzato al paziente anziano sottoposto a chirurgia cardiaca: risultati a breve e lungo termine su 193 pazienti.

BACKGROUND: Elderly subjects frequently experience a decline in function following hospitalization and surgery. Specific changes in the provision of acute hospital care can improve the ability of acutely ill older patients to perform activities of daily living at the time of discharge and the quality of life. The aim of this study was to investigate outcomes of older (age > or =80 years) cardiac surgery patients managed with multicomponent intervention. METHODS: Between 1998 and 2004, we studied records of 193 octogenarian patients who underwent cardiac surgery and were treated with a multicomponent intervention that included: specially designed environment, patient-centered care, planning for patient discharge at home, and an interdisciplinary approach that incorporates in- and out-of-hospital health professionals. RESULTS: Mean follow-up was 26.4 months and 100% complete. Mean age of patients was 82.3 +/- 2 years. Eighty-nine patients had myocardial revascularization (CABG), 40 aortic valve replacement (AVR), 34 AVR + CABG, 8 mitral valve replacement (MVR), 11 MVR + CABG and 11 other interventions. Rates of hospital death, major complications and prolonged stay (> 14 days) were as follows: CABG 4 (4.4%), 3 (3.3%), 6 (6.4%); AVR 1 (2.5%), 3 (7.5%), 2 (5%); AVR + CABG 1 (2.9%), 2 (5.8%), 4 (11.7%); MVR 0 (0%), 0 (0%), 1 (12.5%); MVR + CABG 2 (18.1%), 2 (18.1%), 3 (27.2%). Multivariate predictors of hospital deaths were NYHA class, cardiopulmonary bypass and cross-clamping time, urgent procedure and ischemic mitral valve procedures. The actuarial 6-year survival was as follows: CABG 91%,AVR 92.5%, AVR + CABG 88.2%, MVR + CABG 81.8%. Total survival rate, free from rehospitalization and redo surgery, was 89.7, 69.8 and 99% respectively. Multivariate predictors of late death were urgent procedure and ischemic mitral valve procedures. At follow-up NYHA classification had improved a median of two classes. Global patients' satisfaction was excellent in 76.7% of survivors; 95.7% were autonomous, 40.5% live at home, 64% had a light-moderate physical activity, and 70% of patients had good social relationships and quality of life. Medical therapy was reduced in 29.3% and level of anxiety improved in 76%. CONCLUSIONS: An interdisciplinary approach and multicomponent intervention with an appropriate postoperative care, provides beneficial effects on outcome in geriatric cardiac surgery patients.

Left bundle-branch block is associated with increased 1-year sudden and total mortality rate in 5517 outpatients with congestive heart failure: a report from the Italian network on congestive heart failure.

BACKGROUND: A deleterious effect of complete left bundle-branch block (LBBB) on left ventricular function has been established. Nevertheless, the independent effect of a widened QRS on mortality rate in congestive heart failure (CHF) is still controversial. Therefore, we carried out this analysis to determine whether LBBB is an independent predictor of mortality in CHF. METHODS AND RESULTS: We analyzed the large Italian Network on CHF Registry of unselected outpatients with CHF of different causes. The registry was established by the Italian Association of Hospital Cardiologists in 1995. Complete 1-year follow-up data were available for 5517 patients. The main underlying cardiac diagnosis was ischemic heart disease in 2512 patients (45.6%), dilated cardiomyopathy in 1988 patients (36.0%), and hypertensive heart disease in 714 patients (12.9%). Other causes were recorded in the remaining 303 cases (5.5%). LBBB was present in 1391 patients (25.2%) and was associated with an increased 1-year mortality rate from any cause (hazard ratio, 1.70; 95% confidence interval, 1.41 to 2.05) and sudden death (hazard ratio, 1.58; 95% confidence interval, 1.21 to 2.06). Multivariate analysis showed that such an increased risk was still significant after adjusting for age, underlying cardiac disease, indicators of CHF severity, and prescription of angiotensin-converting enzyme inhibitors and beta-blockers. CONCLUSION: LBBB is an unfavorable prognostic marker in patients with CHF. The negative effect is independent of age, CHF severity, and drug prescriptions. These data may support the rationale of randomized trials to verify the effects on mortality rate of ventricular resynchronization with multisite cardiac pacing in patients with CHF and LBBB.

Intraventricular conduction defects in patients with congestive heart failure: left but not right bundle branch block is an independent predictor of prognosis. A report from the Italian Network on Congestive Heart Failure (IN-CHF database).

BACKGROUND: In industrialized countries the prevalence of congestive heart failure (CHF) is increasing. Many clinical factors have been shown to influence the prognosis of CHF. The effect of a wide QRS on mortality is debated; while left bundle branch block (LBBB) has been already identified as a negative prognostic factor, the effect of right bundle branch block (RBBB) is still unknown. The aim of this study was to compare the association of these two intraventricular conduction defects on the prognosis of CHF. METHODS: Data were derived from the Italian Registry of CHF. Entry in the Registry required that patients had a diagnosis of CHF based on the European Society of Cardiology guidelines. We analyzed the 1-year follow-up data of 5517 outpatients with CHF of different etiologies. The presence of a wide QRS was defined if the duration was > 120 ms. RESULTS: A wide QRS was present in 2066 patients (37.5%), 25.2% with LBBB, 6.1% with RBBB, 6.2% with other intraventricular defects. At univariate analysis patients with complete LBBB had a significantly higher 1-year mortality than those without (16.1 vs 11.9%) but this was not true for complete RBBB (11.9 vs 11.9%). Even after multivariate adjustment, complete LBBB still remained an independent predictor of death (relative risk 1.36, 95% confidence interval 1.15-1.61). CONCLUSIONS: LBBB but not RBBB is an independent predictor of death in CHF.

In-hospital and one-year outcomes of patients with high-risk acute myocardial infarction treated with thrombolysis or primary coronary angioplasty.

BACKGROUND: The aim of this study was to observe the outcomes of high-risk patients with acute myocardial infarction treated with primary angioplasty and intravenous thrombolysis in a community setting. METHODS: A prospective study of the in-hospital and 12-month outcomes was conducted in 17 cardiology centers where primary angioplasty was available, and in 30 where it was not. Three thousand seventy-four patients in the first 12 hours of an evolving infarction were recruited; among these, 2227 patients who met one or more pre-defined criteria of increased risk were included in the study. RESULTS: Thrombolysis and primary angioplasty were respectively performed in 1090 and in 721 patients; 416 patients (18.7%) received no reperfusion treatment. The incidence of the primary combined in-hospital endpoint (death, non-fatal reinfarction and stroke) was similar in patients treated with thrombolysis (9.2%) and with primary angioplasty (10.7%) (odds ratio--OR 1.19, 95% confidence interval--CI 0.86-1.63, p = NS), and was higher (22.6%) in patients receiving no reperfusion treatment as compared to thrombolysis (OR 3.30, 95% CI 2.36-4.63, p < 0.0001). The occurrence of the 12-month endpoint (death, reinfarction, congestive heart failure and recurrent angina) was lower after primary angioplasty than after thrombolysis (26.8 vs 35.0%, OR 0.68, 95% CI 0.55-0.84, p = 0.0003), due to a lower incidence of angina. At multivariate analysis, older age, anterior infarction, Killip class > 1, high heart rate, and low systolic blood pressure on admission were all significantly associated with a higher incidence of both endpoints. The adjusted analysis confirmed that, despite similar in-hospital results after both reperfusion treatments, primary angioplasty was independently associated with better 1-year outcomes (relative risk 0.66, 95% CI 0.56-0.79, p < 0.0001). CONCLUSIONS: In this observation in the community setting, a strategy of primary angioplasty in patients with high-risk myocardial infarction was not better than thrombolysis in terms of mortality or recurrent infarction, but was associated with less angina at 1 year.

Enumeration of circulating fibrocytes for clinical use in asthma by an optimized single-platform flow cytometry assay.

BACKGROUND: Elevated numbers of circulating fibrocytes are associated with inadequately controlled asthma, poor response to available therapies, and increased risk of adverse outcomes. The lack of reliable and clinically-applicable assays precludes a proper evaluation of blood fibrocyte count as a prognostic biomarker in asthma. This report concerns the use of a multiparameter flow cytometry assay for the enumeration of fibrocytes in the whole blood. METHODS: Consenting fibrocyte donors were 19 patients with asthma well controlled by current treatment, 16 patients with treatment-resistant asthma, 9 patients with transiently uncontrolled asthma and 14 age-matched normal individuals. Blood sampling was performed once in patients with transiently uncontrolled asthma and twice, at an interval of one week, in the other subjects. The assay was performed in 100 µl of whole blood and involved a sequential gating strategy and absolute fibrocyte counting with a single instrument (single-platform assay). RESULTS: The quantification of circulating fibrocytes by this assay was analytically and clinically valid. In individuals with stable clinical conditions, the repeatability of blood fibrocyte counts over one week was good. The intraclass correlation coefficient was 0.939 and 96.88% of the total variability reflected on-average differences among the tested subjects. Stabilized blood samples could be stored at 4 °C for up to 96 h before processing. CONCLUSIONS: The novel assay for the enumeration of fibrocytes in the whole blood is reliable and clinically applicable. GENERAL SIGNIFICANCE: This report demonstrates the validity and reliability of the first optimized assay for the enumeration of circulating fibrocytes in multicenter clinical trials.

Peribulbar anesthesia: a percutaneous single injection technique with a small volume of anesthetic.

We evaluated the efficacy and safety of a single injection technique with a small volume of anesthetic for ocular peribulbar anesthesia. We included 857 patients undergoing various ophthalmic procedures. Anesthesia consisted of a medial percutaneous injection of 5-6.5 mL of 2% lidocaine. At 2 min 85.6% of the patients had a motor block of at least 50% and at 5 min 78.6% had a motor block >80%. After 5 min 100% of the patients had adequate surgical anesthesia. There were no serious block-related complications. The described technique is a simple and satisfactory alternative to the classical techniques.

Renal, but not systemic, hemodynamic effects of dopamine are influenced by the severity of congestive heart failure.

OBJECTIVE: To determine whether the short-term systemic and renal hemodynamic response to dopamine is influenced by clinical severity of congestive heart failure. DESIGN: Effects of increasing doses of dopamine were assessed in patients consecutively admitted for acutely decompensated congestive heart failure. SETTING: Intensive care unit. PATIENTS: We enrolled 16 congestive heart failure patients stratified by clinical severity (New York Heart Association [NYHA] class III, n = 8; NYHA class IV, n = 8) and two additional NYHA class III patients as controls. INTERVENTIONS: Measurements were carried out throughout five 20-min experimental periods: baseline, dopamine infusion at 2, 4, and 6 microg x kg(-1) x min(-1), and recovery. Controls received a similar amount of saline. MEASUREMENTS AND MAIN RESULTS: Systemic and renal hemodynamics were determined respectively by right cardiac catheterization and radioisotopes (iodine 131-labeled hippuran and iodine 125-labeled iothalamate clearance). The peak increase in heart rate and cardiac index occurred at a dopamine dose of 4-6 microg x kg(-1) x min(-1). The dose-response relation was similar in NYHA classes III and IV. Improvement in effective renal plasma flow and glomerular filtration rate, peaking at 4 microg x kg(-1) x min(-1), was more rapid and marked in NYHA class III than class IV patients, in whom the renal fraction of cardiac output failed to increase. The systemic and renal effects of dopamine were independent of age. No change occurred in controls. CONCLUSIONS: The dose of dopamine producing an optimal improvement of systemic and renal hemodynamics in congestive heart failure is higher than usually reported. A greater clinical severity of congestive heart failure impairs the renal effects of dopamine, probably through a selective loss in renal vasodilating capacity.