Impact of bevacizumab administered dose on overall survival of patients with progressive glioblastoma.

Bevacizumab (BEV, Avastin(®)) produces durable objective radiological responses of 20-26 %, median response durations of 16-18 weeks, and median overall survival (mOS) of 31-40 weeks. While the use of BEV is well-established, the lack of dose-response studies in glioblastoma (GBM) patients raises the question whether current dosing practice is optimal. As a result of differing approaches to BEV dosing that ranged from the FDA approved package insert dose of 10 mg/kg every 2 weeks to 7.5 mg/kg every 3-4 weeks, among physicians within Northern California Kaiser Permanente hospitals over 4+ years, we did an IRB-approved retrospective analysis of patients seen in Northern California Kaiser Permanente facilities and treated with BEV. Between September 1, 2008 and August 31, 2013, 181 patients received BEV for tumor progression/recurrence starting 2.6 weeks after completion of chemoradiation. The integrated BEV administered dose-week (AUCBEV) for all patients had a median AUCBEV of 3.6 mg·wk/kg). Maximum likelihood analysis found patients over 65 years did worse than younger patients (p = 0.004), women lived longer (p = 0.002), and patients treated below the AUCBEV did better than those treated above the median AUCBEV (p = 0.003). mOS for BEV starting 1 month after chemoradiation was 45 versus 68 weeks (p = 0.012) and BEV starting 3 months after chemoradiation was 40 versus 74 weeks (p = 0.0085). Dosing BEV at half the standard dose for progressive/recurrent GBM was at least equivalent to or, maybe better than standard dosing. Unexplained was the observation that females had longer OS with BEV than males.

Personality Traits and Traumatic Outcome Symptoms in Registered Nurses in the Aftermath of a Patient Safety Incident.

OBJECTIVES: The purpose of this study was to investigate the relationship between personality traits (perfectionism and neuroticism) and the traumatic outcomes of reexperiencing, avoidance, and alcohol abuse severity of registered nurses (RNs) who have been involved with a patient safety incident (PSI). We hypothesized that higher scores for perfectionism and neuroticism would predict higher reexperiencing and avoidance symptoms in RNs in the aftermath of a PSI. Also, RNs with higher perfectionism and neuroticism sum scores would be more likely to abuse alcohol. METHODS: A descriptive, correlational study design was used to characterize the relationships of personality traits and potential traumatic outcomes of RNs in the aftermath of a PSI. The Almost Perfect Scale-Revised, Neuroticism Scale, Posttraumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, and Alcohol Use Disorders Identification Test-Consumption measures were administered to RNs licensed in Oregon and New York. RESULTS: Perfectionist-discrepancy personality traits (P < 0.01) were the strongest predictors for reexperiencing symptoms and neuroticism (P < 0.05) was the strongest predictor for avoidance symptoms, when controlling for sociodemographics and experience. We found a negative linear relationship between perfectionism-order and alcohol abuse severity (ß = -0.15, P < 0.01; confidence interval, -0.24 to 0.05). CONCLUSIONS: This study demonstrated a statistically significant relationship between perfectionism-discrepancy and reexperiencing as well as between neuroticism and reexperiencing and avoidance, each explaining 4% of variance of their model. The results add to the nurse second victim literature by validating 2 posttraumatic stress disorder symptoms in RNs in the aftermath of a PSI. Registered nurses with perfectionism-order were less likely to abuse alcohol.

Lipolysis of emulsion models of triglyceride-rich lipoproteins is altered in male patients with abdominal aorta aneurysm.

Disorders of the lipid metabolism may play a role in the genesis of abdominal aorta aneurysm. The present study examined the intravascular catabolism of chylomicrons, the lipoproteins that carry the dietary lipids absorbed by the intestine in the circulation in patients with abdominal aorta aneurysm. Thirteen male patients (72 +/- 5 years) with abdominal aorta aneurysm with normal plasma lipid profile and 13 healthy male control subjects (73 +/- 5 years) participated in the study. The method of chylomicron-like emulsions was used to evaluate this metabolism. The emulsion labeled with 14C-cholesteryl oleate and (3)H-triolein was injected intravenously in both groups. Blood samples were taken at regular intervals over 60 min to determine the decay curves. The fractional clearance rate (FCR) of the radioactive labels was calculated by compartmental analysis. The FCR of the emulsion with (3)H-triolein was smaller in the aortic aneurysm patients than in controls (0.025 +/- 0.017 vs 0.039 +/- 0.019 min-1; P < 0.05), but the FCR of 14C-cholesteryl oleate of both groups did not differ. In conclusion, as indicated by the triglyceride FCR, chylomicron lipolysis is diminished in male patients with aortic aneurysm, whereas the remnant removal which is traced by the cholesteryl oleate FCR is not altered. The results suggest that defects in the chylomicron metabolism may represent a risk factor for development of abdominal aortic aneurysm.

N-terminal-pro-brain natriuretic peptide, but not brain natriuretic peptide, is increased in patients with severe obesity.

Elevated body mass index (BMI) has been reported as a risk factor for heart failure. Prevention of heart failure through identification and management of risk factors and preclinical phases of the disease is a priority. Levels of natriuretic peptides as well as activity of their receptors have been found altered in obese persons with some conflicting results. We investigated cardiac involvement in severely obese patients by determining N-terminal-pro-brain natriuretic peptide (NT-proBNP) and brain natriuretic peptide (BNP) and attempting to correlate the levels of these peptides in serum and plasma, respectively, with BMI, duration of obesity, waist circumference, and echocardiographic parameters. Thirty-three patients with severe obesity (mean BMI: 46.39 kg/m(2), mean age: 39 years) were studied. The control group contained 30 healthy age-matched individuals (BMI: <25 kg/m(2), mean age: 43 years). The t-test and Spearman correlation were used for statistical analysis. Log-NT-proBNP was significantly higher (P = 0.003) in obese patients (mean 1.67, 95% CI: 1.50-1.83 log pg/mL) compared to controls (mean: 1.32, 95% CI: 1.17-1.47 log pg/mL). The Log-NT-proBNP concentration correlated with duration of obesity (r = 0.339, P < 0.004). No difference was detected in the Log-BNP concentration (P = 0.63) of obese patients (mean: 0.73, 95% CI: 0.46-1.00 log pg/mL) compared to controls (mean: 0.66, 95% CI: 0.51-0.81 log pg/mL). NT-proBNP, but not BNP, is increased in severely obese patients and its concentration in serum is correlated with duration of obesity. NT-proBNP may be useful as an early diagnostic tool for the detection of cardiac burden due to severe obesity.

The role of air pollution in myocardial remodeling.

BACKGROUND: Excessive air pollution in urban environments can impact morbidity and mortality. The authors evaluated the role of particulate matter2.5 (PM2.5) in structural, geometric, and functional remodeling in hearts, using an experimental model of myocardial infarction. METHODS AND FINDINGS: Seventy-five rats were divided into 5 groups: control (CG), CG exposed to PM2.5 pollution (CGP), myocardial infarcted group (MI), infarcted group immediately exposed to pollution (IGP-I), and infarcted group previously exposed to pollution and kept exposed after infarction (IGP-II). Greater deposition of interstitial collagen occurred in the left ventricle in CGP, MI, IGP-I, and IGP-II groups compared with that in controls (p = 0.002 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). In the right ventricle, greater collagen deposition existed in CGP, MI, IGP-I, and IGP-II compared with that in CG (p<0.021 CG vs CGP and p<0.0001 CG vs MI, IGP-I, and IGP-II). At the end of the study, CG had a higher mean shortening fraction than the other groups had (p≤0.03). Left ventricular systolic diameter was lower in CG than in infarcted groups (p≤0.003). The infarcted groups had greater expression of TGF-ß (p≤0.04). PM2.5 increased the expression of TGF-ß in the IGP-II compared with the MI group (p = 0.004). The TNF-α gene was overexpressed in the IGP-II compared with the CGP group (p = 0.012). INF-γ gene expression was greater in IGP-II (p≤0.01). Oxidative stress analysis showed a higher glutathione concentration in CGP (p = 0.03), MI (p = 0.014), and IGP-I (p = 0.008) compared with that in CG. CONCLUSIONS: PM2.5 stimulates the deposition of fibrosis in the myocardium of healthy hearts, but not in infarcted hearts. PM2.5 modulates the inflammatory response, which was greater in the IGP-II group. It also modulates oxidative stress in healthy hearts but not in infarcted hearts.

Surgical treatment of endomyocardial fibrosis: a new approach.

Endomyocardial fibrosis has been treated surgically for many years. For complete removal of fibrosis from both ventricles by the classic technique, each atrioventricular (AV) valve was removed and replaced with a prosthesis. Relapse of endomyocardial fibrosis has not been observed after surgical correction. Reoperations have been carried out because of complications of valve prostheses. A new surgical technique for removal of ventricular fibrous tissue with preservation of the mitral and tricuspid valves was used in nine consecutive patients with endomyocardial fibrosis. Initial results show a reduction of pulmonary hypertension, mean right and left atrial pressures and end-diastolic pressures in both ventricles. Tricuspid annuloplasty was performed in seven patients and mitral annuloplasty in five. No valve prosthesis was used. There was no death and New York Heart Association functional class improved from class III or IV in the preoperative period to class I or II in the postoperative period. These data suggest that resection of endocardial fibrous tissue can be indicated early in the clinical course and performed with preservation of the AV valves.

Oncology Communication Skills Training: Bringing Science to the Art of Delivering Bad News.

Review of "Effect of communication skills training program for oncologists based on patient preferences for communication when receiving bad news: A randomized controlled trial" by Fujimori et al. (2014), Journal of Clinical Oncology, 32, 2166-2172. For a further discussion of survey research, please see the related article by Julie Ponto starting on page 168.

HLA and beta-myosin heavy chain do not influence susceptibility to Chagas disease cardiomyopathy.

An inflammatory dilated cardiomyopathy occurs in 30% of Chagas' disease patients, chronically infected by Trypanosoma cruzi, while the remaining infected individuals are asymptomatic. Studies have indicated a role for genetic factors in the susceptibility to Chagas' disease cardiomyopathy. In an attempt to identify the genetic factors influencing the development and outcome of Chagas' cardiomyopathy, we compared the frequencies of alleles from two candidate gene loci, class II HLA and a microsatellite marker for the human cardiac beta-myosin heavy chain gene in different clinical groups. Patients were grouped as asymptomatic or with severe or mild cardiomyopathy. The results indicate that the HLA and myosin microsatellite allele profiles in all cardiomyopathy and in asymptomatic groups are similar. In conclusion, these results establish that polymorphism of HLA-DR and -DQ molecules, as well as beta-cardiac myosin, do not influence the susceptibility to different clinical forms of Chagas' disease or the progression to severe Chagas' cardiomyopathy. On the other hand, male sex was identified as a risk factor for progression to the more severe forms of cardiomyopathy (relative risk = 8.75).

Effect of spironolactone on ventricular arrhythmias in congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy.

Epidemiologic studies have shown an important increase in the high mortality of patients with congestive heart failure (CHF) despite optimal medical management. Ventricular arrhythmia was recognized as the most common cause of death in this population. Electrolyte imbalance, myocardial fibrosis, left ventricular dysfunction, and inappropriate neurohumoral activation are presumed responsible for sudden cardiac death. In this study, we focused on the deleterious effects of the overproduction of aldosterone that occurs in patients with CHF. Secondary hyperaldersteronism can be part of several factors thought to be responsible for sudden cardiac death. We randomized 35 patients (32 men, aged 48 +/- 9 years) with systolic dysfunction (ejection fraction 33 +/- 5%) and New York Heart Association class III CHF secondary to dilated or ischemic cardiomyopathy into 2 groups. The treatment group received spironolactone, an aldosterone receptor antagonist, along with standard medical management using furosemide, angiotensin-converting enzyme inhibitors, and digoxin. The control group received only the standard medical treatment. Holter monitoring was used to assess the severity of ventricular arrhythmia. After 20 weeks, patients who received spironolactone had a reduced hourly frequency of ventricular premature complexes (VPCs) (65 +/- 18 VPCs/hour at week 0 and 17 +/- 9 VPCs/hour at week 16) and episodes of nonsustained ventricular tachycardia (VT) (3.0 +/- 0.8 episodes of VT/24-hour period at week 0, and 0.6 +/- 0.3 VT/24-hour period at week 16). During monitored treadmill exercise, a significant improvement in ventricular arrhythmia was found in the group receiving spironolactone (39 +/- 10 VPCs at week 0, and 6 +/- 2 VPCs at week 16). These findings suggest that aldosterone may contribute to the incidence of ventricular arrhythmia in patients with CHF, and spironolactone helps reduce this complication.

Relation between interstitial myocardial collagen and the degree of clinical impairment in Chagas' disease.

Cardiac performance is negatively associated with interstitial collagen in Chagas' cardiomyopathy. The magnitude of dysfunction is related to the degree of collagen, and this association seems to exhibit a threshold above it if definite cardiac deterioration occurs.

Atrial fibrillation in endomyocardial fibrosis is a marker of worse prognosis.

We studied the incidence of AF in patients with endomyocardial fibrosis (EMF) and its influence on prognosis and associated clinical events. One hundred and sixty consecutive patients with EMF were followed for a mean period of 4 years. Their mean age was 39.7 years. There were 114 women. During follow-up there were 56 deaths. Eighty-eight patients (55%) were submitted to surgical intervention. AF was observed in 58 cases (36.2%). The presence of AF was associated with a greater prevalence of dyspnea, peripheral edema, hepatomegaly, lower left ventricular ejection fraction, lower right ventricular systolic pressure (37.8 vs 45.6 mmHg, P=0.0392), and greater incidence of tricuspid regurgitation (86.0 vs 63.2%, P=0.004). AF was more frequent among patients in whom the disease involved the right ventricle, particularly those with intense fibrosis. Overall, patients with AF had a higher mortality rate than those who did not have AF (43.1 vs 30.3%, P=0.0195), but among those submitted to surgery, AF did not have an impact on survival. In conclusion, AF is frequent among patients with EMF. It is more prevalent among patients with right ventricular involvement and its presence is associated with a greater incidence of heart failure. AF is associated with worse prognosis, but surgery potentially reverses this bad evolution.

Cytokine production profile of heart-infiltrating T cells in Chagas' disease cardiomyopathy.

The hallmark of chronic Chagas' disease cardiomyopathy (CCC) is the finding of a T cell-rich inflammatory mononuclear cell infiltrate in the presence of extremely few parasites in the heart lesions. The scarcity of parasites in affected heart tissue casts doubt on the direct participation of Trypanosoma cruzi in CCC heart tissue lesions, and suggests the possible involvement of autoimmunity. The cells in the infiltrate are presumably the ultimate effectors of tissue damage, and there is evidence that such cells recognize cardiac myosin in molecular mimicry with T. cruzi proteins rather than primary reactivity to T. cruzi antigens (Cunha-Neto et al. (1996) Journal of Clinical Investigation, 98: 1709-1712). Recently, we have studied heart-infiltrating T cells at the functional level. In this short review we summarize the studies about the role of cytokines in human and experimental T. cruzi infection, along with our data on heart-infiltrating T cells in human Chagas' cardiomyopathy. The bulk of evidence points to a significant production of IFN-gamma and TNF-alpha which may be linked to T. cruzi-induced IL-12 production.

Right ventricular endomyocardial biopsy in undetermined form of Chagas' disease.

Right ventricular endomyocardial biopsy was carried out in thirty three patients with undetermined form of Chagas' disease. Fragments obtained by this method were analysed under light microscopy with hematoxilin-eosin, and Masson trichromic stains. Thirteen (39.4%) patients showed normal myocardial fragments and twenty patients (60.6%) had them altered. Alterations included fiber degeneration, volume changes, interstitial edema, inflammatory infiltrates and fibrosis. These data permit to conclude that only part of patients with this form of Chagas' disease have an incipient myocardial attack and that the alterations found in the fragments obtained are mild. The remaining patients would be either individuals with chagasic infection without cardiac disease or have spontaneous healing. This should be considered in the future treatment of the disease.

Natural history of chronic Chagas' heart disease: prognosis factors.

Chronic Chagas' disease shows several progression modes. Usually, the different clinical syndromes manifest themselves together, however, isolated forms can occur. Cardiac arrhythmias, which are very frequent, are present in about 50% of patients. The cardiac damage manifests itself later, with the emergence of heart failure. Thromboembolism can occur in both pulmonary and systemic circulation. Pulmonary embolism is the most frequent, appearing in more advanced phases of heart disease. Sudden death is the fatal outcome of these patients. It predominates in males and generally occurs in a disease stage when patients have their highest productivity. The presence of serious ventricular arrhythmias, conduction disturbances in the electrocardiogram, and heart failure, provide an unfavorable prognosis.

Apical aneurysm and left ventricular hypertrophy.

A 59-year-old woman presented with an embolic transient ischemic attack and a history of controlled hypertension for 16 years. Both echocardiogram and MRI showed severe biventricular hypertrophy and an apical aneurysm with a thrombus. The occurrence of an apical aneurysm in the presence of cardiac hypertrophy is a rare finding and has been described in patients with hypertrophic cardiomyopathy. However, it has not been reported in patients with systemic arterial hypertension. In this patient the lack of a relationship between the severity of the hypertrophy and the levels of blood pressure, together with the presence of histologic disorganization of myocardial cardiac muscle cells by endomyocardial biopsy suggested the diagnosis of hypertrophic cardiomyopathy.

[Cardiovascular diseases observed during follow-up of a group of patients with undetermined form of Chagas' disease]. / Doenças cardiovasculares observadas durante o seguimento de um grupo de pacientes na forma indeterminada da doença de Chagas.

PURPOSE: The aim of this study was to evaluate the cardiovascular outcome in patients with the undetermined form of Chagas' disease and whether or not it is related to the infectious disease in the long-term. METHODS: One hundred and sixty patients were prospectively followed-up at three month intervals for up to 177 months. RESULTS: Twenty and three (14.4%) patients developed hypertension complicated by ischemic stroke in two (1.2%) and symptomatic heart failure in one (0.6%). Cardiac arrhythmias occurred in four (2.4%) patients corresponding to isolated ventricular ectopic beats in two (1.2%), isolated supraventricular ectopic beats in one (0.6%) and an isolated episode of acute atrial fibrillation in another (0.6%). Two (1.2%) patients developed symptoms of coronary artery disease, one of them had one episode of acute chest pain diagnosed as myocardial infarction and the other had chronic chest pain diagnosed as angina. CONCLUSION: Hypertension is the most common cardiovascular disease occurring in the long-term follow-up of patients with the undetermined form of Chagas' disease. Cardiac rhythm disturbances and coronary artery disease were not more frequent than those generally found in a healthy population. These data confirm a favorable long-term prognosis in patients with the undetermined form of Chagas' disease.

[Value of pericardial biopsy in the etiologic diagnosis of pericardial diseases]. / Valor da biópsia de pericárdio no diagnóstico etiológico das pericardiopatias.

PURPOSE: To determine the value of pericardial biopsy as a complementary exam in the etiology of pericardial effusion. METHODS: We analyzed retrospectively (from 1990 to 1997) 38 patients with pericardial effusion. The age ranged between 3 months and 79 years (mean 41.15 +/- 21.78 years). Pericardial biopsy was performed in all cases through a subxiphoid incision. RESULTS: In 4 patients (10.5%) the biopsy was able to define etiology, 2 had tuberculosis and 2 neoplasias (1 undetermined adenocarcinoma, 1 mesotelioma). In 34 patients the biopsy showed non-specific chronic pericarditis. CONCLUSION: Pericardial biopsy was not an effective method to determine the etiological diagnosis in pericardial effusion patients. We believe that we have to individualize the indication of pericardial biopsy especially if tuberculosis or neoplasia are suspected.

[Idiopathic restrictive cardiomyopathy]. / Cardiomiopatia restritiva idiopática.

PURPOSE: To characterize the idiopathic restrictive cardiomyopathy (RCM) through clinical manifestations and complementary tests and to analyze the surgical benefit on the correction of tricuspid regurgitation. METHODS: Five patients with RCM idiopathic were retrospectively studied, 4 female and 1 male, with ages ranging from 30 to 59 (mean 40) years. The patients presented heart failure due to restrictive syndrome and were submitted to chest X-ray, EKG, echocardiogram, right ventricular endomyocardial biopsy, hemodynamic study and surgery. RESULTS: X-ray showed heart enlargement in all patients, but only one had pulmonary venous capillary congestion. EKG presented atrial fibrillation, complex QRS with low voltage on frontal axis, abnormal ventricular repolarization, right bundle branch block, inactive area and right ventricular hypertrophy. Complete atrioventricular block was observed in one patient. The echocardiogram study showed biatrial enlargement in all patients, and left ventricular dilatation in one patient with left ventricular dysfunction. Mild tricuspid regurgitation were observed in one patient and moderate in four. Two patients had mild mitral regurgitation. Diastolic dysfunction were observed at Doppler-cardiography in all patients. Right ventricular endomyocardial biopsy showed interstitial fibrosis, myocytes hypertrophy and myofibrils disarray. The hemodynamic study disclosed right ventricular hypertension in all patients. Three patients had hypotension in left ventricle and aorta. The left ventricular end diastolic pressure and pulmonary capillary pressure (pulmonary wedge pressure) were elevated in all patients. Dilated left ventricle with mild hypokinesia and right ventricular inferior hypokinesia and diastolic restriction were observed in one patient. One patient had similar pattern without diastolic restriction. Mild tricuspid regurgitation was observed in one patient, moderate in three and severe in one. Mild mitral regurgitation were observed in two patients. The restrictive pattern (deep and plateau) was present in three patients. Surgery were performed in all patients, and confirmed the mild tricuspid regurgitation in one and the moderate in four. De Vega plastia were performed in four patients. CONCLUSION: Among the complementary methods, echocardiogram and hemodynamic study were those of higher contribution to the diagnosis of idiopathic RCM. The disease has a poor evolution, even with clinical or surgical treatment. Heart transplantation may would be the best procedure on patients with symptomatic idiopathic restrictive cardiomyopathy.

[Male sex. Prognostic factor in Chagas' disease]. / Sexo masculino. Fator prognóstico na doença de Chagas.

PURPOSE: To verify if the ventricular function and the incidence of arrhythmias in patients of both sexes could be predominant in male patients with Chagas' disease. METHODS: Six hundred and thirty one patients were studied, 329 female and 302 male, with age of 10 to 64 years old (mean 40). All patients were submitted to M mode echocardiographic study to analyse the ejection fraction (EF). To verify the importance of the ventricular dysfunction in male and female patients, they were divided according to the EF in three groups: A) normal EF, B) EF between 0.64 and 0.45 and C) EF less than 0.44. The incidence of ventricular tachycardia was analyzed at the stress test or 24h Holter studies. RESULTS: The number of patients with depressed EF was more frequent on male patients (p < 0.0001). The incidence of ventricular tachycardia was similar in both sexes, however it was more frequent in patients with ventricular dysfunction. CONCLUSION: Our results show that there are greater myocardial dysfunction on male patients, what could explain the worse prognosis observed on patients of this sex.

[Idiopathic chylopericardium]. / Quilopericárdio idiopático.

We describe a case of a patient with idiopathic pericardial effusion that during investigation proved to be a chylopericardium. Lymphangiography showed the chylopericardium to be due to partial aplasia of the thoracic duct. A brief review the etiology, clinical feature, diagnostic procedures and therapeutic possibilities of chylopericardium is presented.