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Background: Although Indocyanine green (ICG) is used to find sentinel nodes (SN) in patients with breast cancer (BC), its role in clinical practice is still debated, and needs a definitive validation to be included in the standard approach to finding sentinel nodes in breast cancer., Materials and Methods: To validate the ICG methods of detecting the SN in BC we have recently concluded a prospective validation trial. Patients with clinically node-negative, invasive early BC scheduled for breast surgery and SN biopsy were included in the trial. All the patients underwent SN detection using both the standard-of-care procedure using radioisotope technetium (99mTc) and the ICG, using the Photodynamic Eye camera. A comparison of the detection rate and the diagnostic accuracy of the two methods was performed to detect the equivalency of the two approaches., Results: At the end of the enrollment, 301 patients were considered eligible and included in the trial, and 589 nodes were removed. Five hundred and eighty-three nodes (99%) were identified with ICG (median 2 nodes per patient) and 452 (76.7%) were identified with 99mTc (median 2 nodes per patient). A concordance index of 98.75% (CI, 95% = 97.1%-99.5%) was detected. The dosage given ranged from 0.3 to 1.4 ml. ICG was used in all patients eligible for SN biopsy without any significant acute side effects., Conclusions: The index of concordance between 99mTc and ICG seems to be extremely high, suggesting that ICG could be validated as an alternative method to 99mTc in the detection of SN in BC., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Multiple myeloma (MM) is characterized by a high capacity to induce alterations in the bone remodeling process. The increase in osteoclastogenesis and the suppression of osteoblast formation are both involved in the pathophysiology of the bone lesions in MM. The proteasome inhibitor (PI) bortezomib is the first drug designed and approved for the treatment of MM patients by targeting the proteasome. However, recently novel PIs have been developed to overcome bortezomib resistance. Interestingly, several preclinical data indicate that the proteasome complex is involved in both osteoclast and osteoblast formation. It is also evident that bortezomib either inhibits osteoclast differentiation induced by the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) or stimulates the osteoblast differentiation. Similarly, the new PIs including carfilzomib and ixazomib can inhibit bone resorption and stimulate the osteoblast differentiation. In a clinical setting, PIs restore the abnormal bone remodeling by normalizing the levels of bone turnover markers. In addition, a bone anabolic effect was described in responding MM patients treated with PIs, as demonstrated by the increase in the osteoblast number. This review summarizes the preclinical and clinical evidence on the effects of bortezomib and other new PIs on myeloma bone disease.

Background: Remote monitoring (RM) permits home interrogation of implantable cardioverter defibrillator (ICD) and provides an alternative option to frequent in-person visits., Objective: The Italia-RM survey aimed to investigate the current practice of ICD follow-up in Italy and to evaluate the adoption and routine use of RM., Methods: An ad hoc questionnaire on RM adoption and resource use during in-clinic and remote follow-up sessions was completed in 206 Italian implanting centers., Results: The frequency of routine in-clinic ICD visits was 2 per year in 158/206 (76.7%) centers, 3 per year in 37/206 (18.0%) centers, and 4 per year in 10/206 (4.9%) centers. Follow-up examinations were performed by a cardiologist in 203/206 (98.5%) centers, and by more than one health care worker in 184/206 (89.3%) centers. There were 137/206 (66.5%) responding centers that had already adopted an RM system, the proportion of ICD patients remotely monitored being 15% for single- and dual-chamber ICD and 20% for cardiac resynchronization therapy ICD. Remote ICD interrogations were scheduled every 3 months, and were performed by a cardiologist in 124/137 (90.5%) centers. After the adoption of RM, the mean time between in-clinic visits increased from 5 (SD 1) to 8 (SD 3) months (P<.001)., Conclusions: In current clinical practice, in-clinic ICD follow-up visits consume a large amount of health care resources. The results of this survey show that RM has only partially been adopted in Italy and, although many centers have begun to implement RM in their clinical practice, the majority of their patients continue to be routinely followed-up by means of in-clinic visits.

Background: Syncope in patients with bifascicular block (BFB) is a common event whose causes might be difficult to assess., Methods and Results: Prevention of syncope through permanent cardiac pacing in patients with bifascicular block (PRESS) is a multicenter, prospective, randomized, single-blinded study designed to demonstrate a reduction in symptomatic events in patients with bifascicular block and syncope of undetermined origin implanted with permanent pacemaker. Device programming mode (NASPE/BPEG code) at DDD with a lower rate of 60 ppm is compared with backup pacing at DDI with a lower rate of 30 ppm. The end point consisted of (1) syncope, (2) symptomatic presyncopal episodes associated with a device intervention (ventricular pacing), and (3) symptomatic episodes associated with intermittent or permanent atrioventricular block (any degree). One hundred one patients were enrolled and randomized. Primary end point events at 2 years were observed in 23 patients, with a significant lower incidence in the study group (hazard ratio, 0.32; 95% confidence interval [CI], 0.10-0.96; P=0.042). Reduction of any symptoms, associated or not with device intervention, was superior in DDD60 compared with DDI30 (hazard ratio, 0.4; 95% confidence interval, 0.25-0.78; P=0.0053). Fourteen patients developed other rhythm diseases and met class I indication for pacing. The annual incidence of rhythm disease development was 7.4%., Conclusions: In patients with bifascicular block and syncope of undetermined origin, the use of a dual chamber pacemaker programmed to DDD60 led to a significant reduction of syncope or symptomatic events associated with a cardioinhibitory origin, compared with DDI30 programming. Symptoms associated with a new onset of rhythm disease were found in 15% of the population at 2 years.

Background: Studies on the physiology of the cardiovascular system suggest that generation of the heart rate (HR) signal is governed by nonlinear dynamics. Linear and nonlinear indices of HR variability (HRV) have been shown to predict outcome in heart failure (HF). Aim of the present study is to assess if a HR-related complexity predicts adverse clinical and cardiovascular events at 1 year in patients implanted with cardiac resynchronization therapy (CRT)., Methods: In sixty patients implanted with CRT (Renewal), 24-hour HR data were retrieved at patient discharge and 1-year follow-up. A set of linear indices of HRV were considered: mean HR, standard deviation of normal beat to normal beat (SDANN), and HR footprint. Two novel nonlinear indices were calculated by means of a specific algorithm (OntoSpace): HR-complexity (HR-Co) and HR-entropy (HR-En). Predictors of adverse clinical outcome (functional class deterioration or major hospitalizations for cardiovascular causes or all-cause mortality) and of HRV recovery were sought by means of multivariate analysis., Results: HR-Co and HR-En were found to be highly correlated with the other traditional indices of HRV. Lower baseline values of COMPLEXITY WERE ASSOCIATED WITH ADVERSE CLINICAL OUTCOMES (HAZARD RATIO [HR] 0.71; 95% CONFIDENCE INTERVAL [CI] 0.54-0.95; P < 0.02)., Conclusion: Complexity and entropy indices, calculated from 24-hour normal beat to normal beat (RR) intervals well represent patient's autonomic function. In this limited set of data, HF patients with lower baseline complexity-related indices, representing a more compromised autonomic function, present worse clinical outcome at 1-year follow-up., (©2010, Wiley Periodicals, Inc.)

Background: Several studies have searched for predictors of clinical outcome in patients with heart failure (HF). However, since they were collected in clinical trials, most data were subject to selection biases and do not specifically apply to patients with nonischemic heart disease. This study examined the impact of several variables on combined all-cause mortality and hospitalization for cardiac causes, in consecutive ambulatory patients with HF included in the ALPHA registry., Methods and Results: This analysis included 446 patients with HF and nonischemic heart disease, in New York Heart Association functional class II or III, and a left ventricular (LV) ejection fraction below 40%. In 126 patients (73%) the disease was idiopathic dilated cardiomyopathy, in 72 (16%) hypertensive, in nine (2%) valvular, and in 39 (9%) of other etiologies. The median age was 61 years (range 51-69 years) and 349 (78%) patients were men. Over a median follow-up of 31 months (range 23-40), 82 patients (18%) died or were hospitalized for cardiac causes. In a proportional hazard (Cox) regression model, maximal oxygen consumption (HR 0.9, P = 0.001), LV end-diastolic diameter (HR 1.07, P < 0.001), resting systolic blood pressure (HR 0.97, P < 0.005), and hemoglobin (HR 0.86, P < 0.05) were independent predictors of the combined study endpoint., Conclusions: In an unselected population of patients with HF and nonischemic heart disease, a reduced exercise capacity, large LV end-diastolic diameter, low systolic blood pressure, and hemoglobin were correlated with long-term all-cause mortality or hospitalization for cardiac causes. These observations may help stratifying and tailoring the treatment of patients with HF and nonischemic heart disease.

The symptoms of the retrosternal goitre are due to the compression especially on airway, by thyroid growth in mediastinum. We present a case of an old woman affected by chronic obstructive broncopneumopathy, atrial fibrillation and mediastinal goitre. The previous growth in mediastinum was the cause of compression on airway with unexpected worsening of respiratory function. The risk of total thyroidectomy was related to the possible tracheomalacia. The surgery improved respiratory performance.

Objectives: The aim of this study was to assess the prognostic value of T-wave alternans (TWA) in New York Heart Association (NYHA) functional class II/III patients with nonischemic cardiomyopathy and left ventricular ejection fraction (LVEF) < or =40%., Background: There is a strong need to identify reliable risk stratifiers among heart failure candidates for implantable cardioverter-defibrillator (ICD) prophylaxis. T-wave alternans may identify low-risk subjects among post-myocardial infarction patients with depressed LVEF, but its predictive role in nonischemic cardiomyopathy is unclear., Methods: Four hundred forty-six patients were enrolled and followed up for 18 to 24 months. The primary end point was the combination of cardiac death + life-threatening arrhythmias; secondary end points were total mortality and the combination of arrhythmic death + life-threatening arrhythmias., Results: Patients with abnormal TWA (65%) compared with normal TWA (35%) tests were older (60 +/- 13 years vs. 57 +/- 12 years), were more frequently in NYHA functional class III (22% vs. 19%), and had a modestly lower LVEF (29 +/- 7% vs. 31 +/- 7%). Primary end point rates in patients with abnormal and normal TWA tests were 6.5% (95% confidence interval [CI] 4.5% to 9.4%) and 1.6% (95% CI 0.6% to 4.4%), respectively. Unadjusted and adjusted hazard ratios were 4.0 (95% CI 1.4% to 11.4%; p = 0.002) and 3.2 (95% CI 1.1% to 9.2%; p = 0.013), respectively. Hazard ratios for total mortality and for arrhythmic death + life-threatening arrhythmias were 4.6 (p = 0.002) and 5.5 (p = 0.004), respectively; 18-month negative predictive values for the 3 end points ranged between 97.3% and 98.6%., Conclusions: Among NYHA functional class II/III nonischemic cardiomyopathy patients, an abnormal TWA test is associated with a 4-fold higher risk of cardiac death and life-threatening arrhythmias. Patients with normal TWA tests have a very good prognosis and are likely to benefit little from ICD therapy.

Background: Although a more favorable neurohormonal balance may contribute to improving symptoms following cardiac resynchronization therapy (CRT), no information is available regarding the effects of CRT on insulin-like growth factor-1 (IGF-1). This study assessed the effects of CRT on IGF-1 levels and their correlation with changes in quality of life and left ventricular (LV) function., Methods and Results: Patients with cardiomyopathy in New York Heart Association class III or IV (n = 18; age 71 +/- 10 years), left ventricular ejection fraction (LVEF) < or = 40% and QRS > or = 130 ms or ventricular dyssynchrony were enrolled in the study and followed up for 6 months. After 3 months, there was an improvement in LVEF (from 29 +/- 7 to 33 +/- 10%, P = 0.0136) and quality of life (from 33 +/- 14 to 13 +/- 12, P = 0.0000) and an increase in IGF-1 levels (from 137 +/- 79 to 175 +/- 111 ng/ml, P = 0.01353). The change in quality of life correlated with changes in IGF-1 levels (P = 0.02) but not with LVEF changes., Conclusions: In patients with advanced heart failure, CRT leads to a significant increase in plasma IGF-1 levels within 3 months. This increase is correlated with the improvement in quality of life, whereas the increase in LVEF is not. This finding suggests that IGF-1 may play a role as a mediator in the early phase of symptomatic improvement after CRT.

Background: Estimates of the prevalence of atrial fibrillation (AF) in heart failure (HF) originate from patients enrolled in clinical trials., Aims: To assess the prevalence and clinical correlates of AF among HF patients in everyday clinical practice from HF patients screened for the T-wave ALternans in Patients with Heart fAilure (ALPHA) study; to investigate the correlation between AF and functional status., Methods and Results: Consecutive patients (N=3513) seen at nine Heart Failure Clinics were studied; 21.4% were in AF. AF prevalence was greater with increasing age (OR 1.04/year, p<0.001) in non-ischaemic cardiomyopathy (OR 2.34, p<0.001) and with increasing NYHA class (p<0.0001). Multiple logistic regression predictors of AF were age >70 years (OR 2.35), NYHA class II III or IV vs class I (OR 1.8, 4.4 and 3.1) and non-ischaemic cardiomyopathy (OR 3.2). A logistic model indicated that AF was associated with a 2.5 OR of being in NYHA class III-IV vs I-II while accounting for age, gender, left ventricular ejection fraction (LVEF), and aetiology of HF., Conclusions: The prevalence of AF in HF patients exceeds 20%, and increases with age and functional class. The presence of AF leads to a more severe NYHA class, indicating that AF contributes to the severity of heart failure.

The causes of blindness in 105 consecutive legally blind patients were analyzed in a large urban multidisciplinary medical center. It was found that the leading causes of blindness, in order of frequency of incidence, were glaucoma, diabetic retinopathy, senile macular degeneration, and cataract. The periodic collection of statistics on the relative frequency of the causes of blindness is strongly suggested so that possible changes and improvements in health care may be determined.