Phosphate Binder Impact on Bone Remodeling and Coronary Calcification - Results from the BRiC Study

Background and Aims: Calcium-containing phosphate binders have been shown to increase the progression of vascular calcification in hemodialysis patients. This is a prospective study that compares the effects of calcium acetate and sevelamer on coronary calcification (CAC) and bone histology. Methods: 101 hemodialysis patients were randomized for each phosphate binder and submitted to multislice coronary tomographies and bone biopsies at entry and 12 months. Results: The 71 patients who concluded the study had similar baseline characteristics. On follow-up, the sevelamer group had higher levels of intact parathyroid hormone (498 +/- 352 vs. 326 +/- 236 pg/ml, p = 0.017), bone alkaline phosphatase (38 +/- 24 vs. 28 +/- 15 U/l, p = 0.03) and deoxypyridinoline (135 +/- 107 vs. 89 +/- 71 nmol/l, p = 0.03) and lower LDL cholesterol (74 +/- 21 vs. 91 +/- 28 mg/dl, p = 0.015). Phosphorus (5.8 +/- 1.0 vs. 6 +/- 1.0 mg/dl, p = 0.47) and calcium (1.27 +/- 0.07 vs. 1.23 +/- 0.08 mmol/l, p = 0.68) levels did not differ between groups. CAC progression (35 vs. 24%, p = 0.94) and bone histological diagnosis at baseline and 12 months were similar in both groups. Patients of the sevelamer group with a high turnover at baseline had an increase in bone resorption (eroded surface, ES/BS = 9.0 +/- 5.9 vs. 13.1 +/- 9.5%, p = 0.05), whereas patients of both groups with low turnover at baseline had an improvement in bone formation rate (BFR/BS = 0.015 +/- 0.016 vs. 0.062 +/- 0.078, p = 0.003 for calcium and 0.017 +/- 0.016 vs. 0.071 +/- 0.084 mu m(3)/mu m(2)/day, p = 0.010 for sevelamer). Conclusions: There was no difference in CAC progression or changes in bone remodeling between the calcium and the sevelamer groups. Copyright (C) 2008 S. Karger AG, Basel

Optical Quality in Eyes Implanted With Aspheric and Spherical Intraocular Lenses Assessed by NIDEK OPD-Scan: A Randomized, Bilateral, Clinical Trial

PURPOSE: To determine whether implantation of an intraocular lens (IOL) with an aspheric surface (Akreos AO, Bausch & Lomb Inc) results in reduced ocular aberrations (spherical aberration) and improved Strehl ratio and modulation transfer function (MTF) after cataract surgery. METHODS: In an intraindividual, randomized, double-masked, prospective study of 50 eyes (25 patients) with bilateral cataract, an IOL with modified anterior and posterior surfaces (Akreos AO) was implanted in one eye and a biconvex IOL with spherical surfaces (Akreos Fit, Bausch & Lomb Inc) implanted in the fellow eye. Ocular aberrations, Strehl ratio, and MTF curve with 4.5-, 5.0-, and 6.0-mm pupils were measured with a NIDEK OPD-Scan dynamic retinoscopy aberrometer 3 months after surgery. Uncorrected and corrected distance visual acuity (UDVA and CDVA, respectively) were also measured. RESULTS: No statistically significant difference was noted between eyes in postoperative UDVA and CDVA at 1 month. At 3 months, the Akreos AO IOL group obtained statistically significant lower values of higher order and spherical aberrations with 4.5-, 5.0-, and 6.0-mm pupil diameters than the Akreos Fit IOL group (P<.05). The value of Strehl ratio was statistically significantly higher in eyes with the Akreos AO IOL for 4.5- and 6.0-mm pupils (P<.05). The MTF curve was better in the Akreos AO IOL group in 4.5-, 5.0-, and 6.0-mm pupils (P<.05). CONCLUSIONS: The aspheric Akreos AO IOL induced significantly less spherical aberration than the Akreos Fit IOL for 4.5-, 5.0-, and 6.0-mm pupils. Modulation transfer function and Strehl ratio were also better in eyes implanted with the Akreos AO IOL than the Akreos Fit. [J Refract Surg. 2011;27(4):287-292.] doi:10.3928/1081597X-20100714-01

Transfusion Requirements After Cardiac Surgery The TRACS Randomized Controlled Trial

Context Perioperative red blood cell transfusion is commonly used to address anemia, an independent risk factor for morbidity and mortality after cardiac operations; however, evidence regarding optimal blood transfusion practice in patients undergoing cardiac surgery is lacking. Objective To define whether a restrictive perioperative red blood cell transfusion strategy is as safe as a liberal strategy in patients undergoing elective cardiac surgery. Design, Setting, and Patients The Transfusion Requirements After Cardiac Surgery (TRACS) study, a prospective, randomized, controlled clinical noninferiority trial conducted between February 2009 and February 2010 in an intensive care unit at a university hospital cardiac surgery referral center in Brazil. Consecutive adult patients (n=502) who underwent cardiac surgery with cardiopulmonary bypass were eligible; analysis was by intention-to-treat. Intervention Patients were randomly assigned to a liberal strategy of blood transfusion (to maintain a hematocrit >= 30%) or to a restrictive strategy (hematocrit >= 24%). Main Outcome Measure Composite end point of 30-day all-cause mortality and severe morbidity (cardiogenic shock, acute respiratory distress syndrome, or acute renal injury requiring dialysis or hemofiltration) occurring during the hospital stay. The noninferiority margin was predefined at -8% (ie, 8% minimal clinically important increase in occurrence of the composite end point). Results Hemoglobin concentrations were maintained at a mean of 10.5 g/dL(95% confidence interval [CI], 10.4-10.6) in the liberal-strategy group and 9.1 g/dL (95% CI, 9.09.2) in the restrictive-strategy group (P<.001). A total of 198 of 253 patients (78%) in the liberal-strategy group and 118 of 249 (47%) in the restrictive-strategy group received a blood transfusion (P<.001). Occurrence of the primary end point was similar between groups (10% liberal vs 11% restrictive; between-group difference, 1% [95% CI, -6% to 4%]; P=.85). Independent of transfusion strategy, the number of transfused red blood cell units was an independent risk factor for clinical complications or death at 30 days (hazard ratio for each additional unit transfused, 1.2 [95% CI, 1.1-1.4]; P=.002). Conclusion Among patients undergoing cardiac surgery, the use of a restrictive perioperative transfusion strategy compared with a more liberal strategy resulted in noninferior rates of the combined outcome of 30-day all-cause mortality and severe morbidity. Trial Registration clinicaltrials.gov Identifier: NCT01021631 JAMA. 2010; 304(14):1559-1567 www.jama.com

Inflammatory Cytokines during Liver Transplantation: Prospective Randomized Trial Comparing Conventional and Piggyback Techniques

Background/Aims: Cytokines have a significant role in the response to injury following liver transplantation, but the origin and course of such molecules are not completely known. The aim of this study was to evaluate the production and liver metabolism of the inflammatory cytokines interleukin (IL)-1 beta, IL-6, IL-8, interferon (IFN)-Y and tumor necrosis factor (TNF)-alpha in orthotopic liver transplantation (OLT), comparing the conventional and the piggyback methods. Methodology: We performed a study of 30 patients who underwent elective OLT and were randomized for the conventional or piggyback techniques at the beginning of the operation. The amount of cytokines and their hepatic metabolism were calculated based on plasma concentrations and vascular blood flow at 2, 5, 10, 15, 30, 60, 90, and 120 minutes after revascularization. Results: The amount of IL-1 beta in portal blood was higher in patients who underwent surgery using the conventional technique (estimate interest = 63,783.9 +/- 16,586.1 pg/min, versus 11,979.6 +/- 16,585.7 pg/min in the piggyback group, p=0.035). There were no significant differences between the two operative`s methods for IL-6, IL-8, IFN-Y and TNF-alpha production. The hepatic metabolism of cytokines was not different between groups. Although all the curves showed higher amounts of cytokines with the conventional technique, these were not statistically significant. Conclusion: The study shows the similarity between the two techniques concerning the stimuli for the production of inflammatory molecules.

Impact of Stent-Graft Oversizing on the Thoracic Aorta: Experimental Study in a Porcine Model

Purpose: To analyze in an experimental animal model the effect of 4 different levels of stents-graft oversizing on non-atherosclerotic aortas such as those found in young individuals who undergo stent-graft repair for traumatic aortic injuries. Methods: The diameter of the porcine thoracic aorta is similar to the aorta of young adults (18-20 mm), so 25 pigs were randomized into 5 groups: 1 control (without stent-graft) and 4 oversizing groups (A: 10%-19%, B: 20%-29%, C: 30%-39%, and D: >40%). Two types of biomechanical tests were performed on all aortas 4 weeks after endoprosthesis deployment. Results: The results of the detachment test, which analyzed the strength necessary to remove the stent-graft from the aorta, were similar in the 4 groups (A: 42 N, B: 41 N, C: 46 N, and D: 46 N). However, 2 aortas ruptured during the tests (groups C and D). The second test was performed in 3 aortic segments. Maximum shear strength, maximum stress, and maximum tension supported by the aortic wall had a negative and linear correlation with oversizing. There were significant differences in all 4 groups when compared with the control group. Strain, which reflects the elastic properties of the aortic wall, was very similar in all 4 groups, but a great difference was found when compared with the control group (p<0.0001). Conclusion: The study showed an important subacute change in the biomechanical properties of the aortic wall after implantation of an oversized endoprosthesis. This weakness of the aortic wall was confirmed by 2 ruptures during the detachment test. These results partially explain the interaction of stent-grafts with non-atherosclerotic thoracic aortas and may serve as a basis for further studies and the development of specific material to be used in vascular trauma and young patients. J Endovasc Ther. 2011; 18: 576-584

Exhaled nitric oxide as a predictor of exacerbation in children with moderate-to-severe asthma: a prospective, 5-month study

Background: Inhaled corticosteroids (ICSs) are recommended as the first line of treatment in children with moderate-to-severe asthma. Exhaled nitric oxide (ENO) has been proposed as a clinically useful marker of control that might help identify patients in whom ICS dose may be safely reduced. Objective: To evaluate the ability of ENO to predict future asthma exacerbations in children with moderate-to-severe asthma undergoing ICS tapering. Methods: This is an observational study with no control group. ENO was measured biweekly for 14 weeks in 32 children with moderate-to-severe asthma who were undergoing ICS tapering. Clinical evaluations and spirometry were performed concomitantly, and families kept daily diaries to record symptoms between visits. We used generalized estimating equations to model the In (odds) of an asthma exacerbation in the subsequent 2-week interval as a function of ENO level at the start of the interval while adjusting for age, sex, asthma severity, and current medication use. Results: We were able to successfully lower ICS doses in 10 (56%) of the 18 children with moderate asthma and in 3 (21%) of the 14 children with severe asthma. In 83 of the 187 follow-up clinical evaluations, children were determined to have had an exacerbation during the preceding 2 weeks. ENO levels, whether expressed as a continuous variable or dichotomized, were not associated with future risk for exacerbations in either unadjusted or adjusted models. Conclusion: ENO was not a useful clinical predictor of future asthma exacerbations for children with moderate-to-severe asthma undergoing ICS tapering. Ann Allergy Asthma Immunol. 2009; 103:206-211.

Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial

Creatine supplementation may have a therapeutic role in diabetes, but it is uncertain whether this supplement is safe for kidney function. The aim of this study was to investigate the effects of creatine supplementation on kidney function in type 2 diabetic patients. A randomized, double-blind, placebo-controlled trial was performed. The patients were randomly allocated to receive either creatine or placebo for 12 weeks. All the patients underwent exercise training throughout the trial. Subjects were assessed at baseline and after the intervention. Blood samples and 24-h urine samples were obtained for kidney function assessments. Additionally, (51)Cr-EDTA clearance was performed. To ensure the compliance with creatine intake, we also assessed muscle phosphorylcreatine content. The creatine group presented higher muscle phosphorylcreatine content when compared to placebo group (CR Pre 44 +/- A 10, Post 70 +/- A 18 mmol/kg/wt; PL Pre 52 +/- A 13, Post 46 +/- A 13 mmol/kg/wt; p = 0.03; estimated difference between means 23.6; 95% confidence interval 1.42-45.8). No significant differences were observed for (51)Cr-EDTA clearance (CR Pre 90.4 +/- A 16.9, Post 96.1 +/- A 15.0 mL/min/1.73 m(2); PL Pre 97.9 +/- A 21.6, Post 96.4 +/- A 26.8 mL/min/1.73 m(2); p = 0.58; estimated difference between means -0.3; 95% confidence interval -24.9 to 24.2). Creatinine clearance, serum and urinary urea, electrolytes, proteinuria, and albuminuria were unchanged. CR supplementation does not affect kidney function in type 2 diabetic patients, opening a window of opportunities to explore its promising therapeutic role in this population. ClinicalTrials.gov registration number: NCT00992043.

A 12-month randomized controlled trial of balance training in elderly women with ostebporosis: Improvement of quality of life

Objective: Physical and psychological incapacity, including fear of falling is related to decreased satisfaction with life in osteoporosis (OP). The impact of a balance exercise program on improving the quality of life is not well established. We have, therefore, investigated the effect of 12-month Balance Training Program in quality of life, functional balance and falls in elderly OP women. Methods: Sixty consecutive women with senile OP were randomized into a Balance Training Group (BT) of 30 patients and no intervention control group (CG) of 30 patients. The BT program included techniques to improve balance over a period of 12 months (1 h exercise session/week and home-based exercises). The quality of life was evaluated before and at the end of the trial using the Osteoporosis Assessment Questionnaire (OPAQ), functional balance was evaluated by Berg Balance Scale (BBS). Falls in the preceding year were noted and compared to the period of study. Results: The comparison of OPAQ variations (INITIAL-FINAL) revealed a significant improvement in quality of life in all parameters for BT compared to CG: well-being (1.61 +/- 1.44 vs. -1.46 +/- 1.32, p < 0001), physical function (1.30 +/- 1.33 vs. -0.36 +/- 0.82, p < 0.001), psychological status (1.58 +/- 1.36 vs. -1.02 +/- 0.83, p < 0.001), symptoms (2.76 +/- 1.96 vs. -0.63 +/- 0.87, p < 0.001), social interaction (1.01 +/- 1.51 vs. 0.35 +/- 1.08, p < 0.001). Of note, this overall benefit was paralleled by an improvement of BBS (-5.5 +/- 5.67 vs. +0.5 +/- 4.88 p < 0.001) and a reduction of falls in 50% in BT group vs. 26.6% for the CG (RR: 1.88, p < 0.025). Conclusion: The long-term Balance Training Program of OP women provides a striking overall health quality of life improvement in parallel with improving functional balance and reduced falls. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

Hemodynamic response in one session of strength exercise with and without electrostimulation in heart failure patients: A randomized controlled trial

Background: Studies have investigated the influence of neuromuscular electrostimulation on the exercise/muscle capacity of patients with heart failure (HF), but the hemodynamic overload has never been investigated. The aim of our study was to evaluate the heart rate (HR), systolic and diastolic blood pressures in one session of strength exercises with and without neuromuscular electrostimulation (quadriceps) in HF patients and in healthy subjects. Methods: Ten (50% male) HF patients and healthy subjects performed three sets of eight repetitions with and without neuromuscular electrostimulation randomly, with one week between sessions. Throughout, electromyography was performed to guarantee the electrostimulation was effective. The hemodynamic variables were measured at rest, again immediately after the end of each set of exercises, and during the recovery period. Results: Systolic and diastolic blood pressures did not change during each set of exercises among either the HF patients or the controls. Without electrostimulation: among the controls, the HR corresponding to the first (85 +/- 13 bpm, p = 0.002), second (84 +/- 10 bpm, p < 0.001), third (89 +/- 17, p < 0.001) sets and recuperation (83 +/- 16 bpm, p = 0.012) were different compared to the resting HR (77 bpm). Moreover, the recuperation was different to the third set (0.018). Among HF patients, the HR corresponding to the first (84 +/- 9 bpm, p = 0.041) and third (84 +/- 10 bpm, p = 0.036) sets were different compared to the resting HR (80 +/- 7 bpm), but this increase of 4 bpm is clinically irrelevant to HF. With electrostimulation: among the controls, the HR corresponding to the third set (84 +/- 9 bpm) was different compared to the resting HR (80 +/- 7 bmp, p = 0.016). Among HF patients, there were no statistical differences between the sets. The procedure was well tolerated and no subjects reported muscle pain after 24 hours. Conclusions: One session of strength exercises with and without neuromuscular electrostimulation does not promote a hemodynamic overload in HF patients. (Cardiol J 2011; 18,1: 39-46)

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)

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.)

The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial: study design and rationale

Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies. (Am Heart J 2009; 158:327-34.)

Efficacy of Antibiotic Prophylaxis Before the Implantation of Pacemakers and Cardioverter-Defibrillators Results of a Large, Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial

Background-Although routinely administered, definitive evidence for the benefits of prophylactic antibiotics before the implantation of permanent pacemakers and implantable cardioverter-defibrillators from a large double-blinded placebo-controlled trial is lacking. The purpose of this study was to determine whether prophylactic antibiotic administration reduces the incidence of infection related to device implantation. Methods and Results-This double blinded study included 1000 consecutive patients who presented for primary device (Pacemaker and implantable cardioverter-defibrillators) implantation or generator replacement randomized in a 1:1 fashion to prophylactic antibiotics or placebo. Intravenous administration of I g of cefazolin (group 1) or placebo (group 2) was done immediately before the procedure. Follow-up was performed 10 days, 1, 3, and 6 months after discharge. The primary end point was any evidence of infection at the surgical incision (pulse generator pocket), or systemic infection related to be procedure. The safety committee interrupted the trial after 649 patients were enrolled due to a significant difference in favor of the antibiotic arm (group 1: 2 of 314 infected patients-0.63%; group 11: 11 of 335 to 3.28%; RR=0.19; P=0.016). The following risk factors were positively correlated with infection by univariate analysis: nonuse of preventive antibiotic (P=0.016); implant procedures (versus generator replacement: P=0.02); presence of postoperative hematoma (P=0.03) and procedure duration (P=0.009). Multivariable analysis identified nonuse of antibiotic (P=0.037) and postoperative hematoma (P=0.023) as independent predictors of infection. Conclusions-Anti biotic prophylaxis significantly reduces infectious complications in patients undergoing implantation of pacemakers or cardioverter-defibrillators. (Circ Arrhythmia Electrophysiol. 2009;2:29-34.)

Multicenter double blind trial of autologous bone marrow mononuclear cell transplantation through intracoronary injection post acute myocardium infarction - MiHeart/AMI study

Background: Myocardial infarction remains as a major cause of mortality worldwide and a high rate of survivors develop heart failure as a sequel, resulting in a high morbidity and elevated expenditures for health system resources. We have designed a multicenter trial to test for the efficacy of autologous bone marrow (ABM) mononuclear cell (MC) transplantation in this subgroup of patients. The main hypothesis to be tested is that treated patients will have a significantly higher ejection fraction (EF) improvement after 6 months than controls. Methods: A sample of 300 patients admitted with ST elevation acute myocardial infarction (STEMI) and left ventricle (LV) systolic dysfunction, and submitted to successful mechanical or chemical recanalization of the infarct-related coronary artery will be selected for inclusion and randomized to either treated or control group in a double blind manner. The former group will receive 100 x 106 MC suspended in saline with 5% autologous serum in the culprit vessel, while the latter will receive placebo (saline with 5% autologous serum). Implications: Many phase I/II clinical trials using cell therapy for STEMI have been reported, demonstrating that cell transplantation is safe and may lead to better preserved LV function. Patients with high risk to develop systolic dysfunction have the potential to benefit more. Larger randomized, double blind and controlled trials to test for the efficacy of cell therapies in patients with high risk for developing heart failure are required.

PHASE I/II STUDY OF ERLOTINIB COMBINED WITH CISPLATIN AND RADIOTHERAPY IN PATIENTS WITH LOCALLY ADVANCED SQUAMOUS CELL CARCINOMA OF THE HEAD AND NECK

Purpose: Erlotinib, an oral tyrosine kinase inhibitor, is active against head-and-neck squamous cell carcinoma (HNSCC) and possibly has a synergistic interaction with chemotherapy and radiotherapy. We investigated the safety and efficacy of erlotinib added to cisplatin and radiotherapy in locally advanced HNSCC. Methods and Materials: In this Phase I/II trial 100 mg/m(2) of cisplatin was administered on Days 8, 29, and 50, and radiotherapy at 70 Gy was started on Day 8. During Phase I, the erlotinib dose was escalated (50 mg, 100 mg, and 150 mg) in consecutive cohorts of 3 patients, starting on Day 1 and continuing during radiotherapy. Dose-limiting toxicity was defined as any Grade 4 event requiring radiotherapy interruptions. Phase 11 was initiated 8 weeks after the last Phase I enrollment. Results: The study accrued 9 patients in Phase I and 28 in Phase II; all were evaluable for efficacy and safety. No dose-limiting toxicity occurred in Phase I, and the recommended Phase 11 dose was 150 mg. The most frequent nonhematologic toxicities were nausea/vomiting, dysphagia, stomatitis, xerostomia and in-field dermatitis, acneiform rash, and diarrhea. Of the 31 patients receiving a 150-mg daily dose of erlotinib, 23 (74%; 95% confidence interval, 56.8%-86.3%) had a complete response, 3 were disease free after salvage surgery, 4 had inoperable residual disease, and 1 died of sepsis during treatment. With a median 37 months` follow-up, the 3-year progression-free and overall survival rates were 61% and 72%, respectively. Conclusions: This combination appears safe, has encouraging activity, and deserves further studies in locally advanced HNSCC. (C) 2010 Elsevier Inc.