Human umbilical cord blood cells protect oligodendrocytes from brain ischemia through Akt signal transduction.

Human umbilical cord blood (HUCB) cells protect the brain against ischemic injury, yet the mechanism of protection remains unclear. Using both in vitro and in vivo paradigms, this study examined the role of Akt signaling and peroxiredoxin 4 expression in human umbilical cord blood cell-mediated protection of oligodendrocytes from ischemic conditions. As previously reported, the addition of HUCB cells to oligodendrocyte cultures prior to oxygen glucose deprivation significantly enhanced oligodendrocyte survival. The presence of human umbilical cord blood cells also increased Akt phosphorylation and elevated peroxiredoxin 4 expression in oligodendrocytes. Blocking either Akt or peroxiredoxin 4 activity with Akt Inhibitor IV or a peroxiredoxin 4-neutralizing antibody, respectively, negated the protective effects of human umbilical cord blood cells. In vivo, systemic administration of human umbilical cord blood cells 48 h after middle cerebral artery occlusion increased Akt phosphorylation and peroxiredoxin 4 protein expression while reducing proteolytic cleavage of caspase 3 in oligodendrocytes residing in the ipsilateral external capsule. Moreover, human umbilical cord blood cells protected striatal white matter bundles from degeneration following middle cerebral artery occlusion. These results suggest that the soluble factors released from human umbilical cord blood cells converge on Akt to elevate peroxiredoxin 4 levels, and these effects contribute to oligodendrocyte survival.

[Safety and tolerance of beta-blocker treatment in elderly patients with heart failure. BETANIC study]. / Seguridad y tolerancia del tratamiento con bloqueadores beta en el paciente anciano con insuficiencia cardíaca. Estudio BETANIC.

BACKGROUND AND OBJECTIVE: Prescription of beta-blockers (BB) in elderly patients with heart failure (HF) is very low, and it probably owes to an excessive concern about the risk of adverse reactions. The objective of our study was to determine the safety and tolerance of BB in elderly patients with HF in an Internal Medicine clinical practice. MATERIAL AND METHODS: This observational prospective study of clinical practice included 119 patients older than 70 years with HF evaluated in 10 Internal Medicine services. Patients must have started treatment with BB (carvedilol or bisoprolol) within the last month. After 6 months of follow-up, the percentage of patients on BB, the dose achieved and the causes of withdrawal were analyzed. RESULTS: At the end of the study, 100 patients (84%) were on BB treatment. There were 3 deaths (2.5%), none related to BB use, and 6 losses to follow-up (5%). The treatment was stopped in 10 patients (8.4%). Maximum dose was achieved in 38.7% of the patients. Adverse reactions responsible for treatment withdrawal were: symptomatic hypotension (3 cases; 2.5%); asymptomatic hypotension (1 case; 0.8%); heart failure (2 cases; 1.7%); bradycardia (2 cases; 1.7%); bronchospasm (1 case; 0.8%); and unknown cause (1 case; 0.8%). CONCLUSIONS: BB are excellently tolerated in elderly patients with HF treated in an Internal Medicine setting.

Insights into Chronic Obstructive Pulmonary Disease as Critical Risk Factor for Cardiovascular Disease.

In patients with chronic obstructive pulmonary disease (COPD), cardiovascular comorbidities are highly prevalent and associated with considerable morbidity and mortality. This coincidence is increasingly seen in the context of a "cardiopulmonary continuum" rather than being simply attributed to shared risk factors, in particular, cigarette smoking. Both disease entities are centrally linked to systemic inflammation as well as aging, arterial stiffness, and several common biomarkers that led to the development of pulmonary hypertension, left ventricular diastolic dysfunction, atherosclerosis, and reduced physical activity and exercise capacity. For these reasons, COPD should be considered an independent factor of high cardiovascular risk, and efforts should be directed to early identification of cardiovascular disease (CVD) in COPD patients. Assessment of the overall cardiovascular risk is especially important in patients with severe exacerbation episodes, and the same therapeutic target levels for glycosylated hemoglobin, low-density lipoprotein cholesterol (LDL-C), or blood pressure than those recommended by clinical practice guidelines for patients at high cardiovascular risk, should be achieved. In this review, we will discuss the most recent evidence of the role of COPD as a critical cardiovascular risk factor and try to find new insights and potential prevention strategies for this disease.

[Utility of NT-proBNP for diagnosing heart failure in a heterogeneous population of patients with dyspnea. Spanish multicenter study]. / Utilidad del NT-proBNP para el diagnóstico de insuficiencia cardiaca en una población heterogénea de pacientes con disnea. Estudio multicéntrico español.

INTRODUCTION AND OBJECTIVES: Recent studies have shown that brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are useful in the diagnosis of heart failure in patients presenting with dyspnea. However, the cutoff values used with these markers vary according to patient characteristics and dyspnea severity. The aim of this study was to investigate the diagnostic accuracy of using the plasma NT-proBNP level for identifying heart failure in a heterogeneous population of patients with dyspnea. METHODS: A multicentre study involving 247 consecutive patients with recent-onset dyspnea was carried out at 12 Spanish hospitals. Patients previously diagnosed with heart failure or any other condition known to cause dyspnea were excluded. RESULTS: Of the 247 patients, 161 (65%) had heart failure. The remaining 86 (35%) presented with dyspnea of non-cardiac origin. Plasma NT-proBNP levels were higher in patients with heart failure (5600 [7988] pg/mL vs 1182 [4406] pg/mL; P=.0001), and increased as functional status deteriorated (P=.036). The area under the receiver operating characteristic curve was 0.87 (0.02) (95% CI, 0.81-0.91) for the optimum cutoff value of 1335 pg/mL. The sensitivity of this cutoff value for diagnosing heart failure was 77% (95% CI, 70%-83%), the specificity was 92% (95% CI, 84%-97%), the positive predictive value was 94%, and the negative predictive value was 68%. CONCLUSIONS: The plasma NT-proBNP concentration provides an accurate means of diagnosing heart failure. However, the negative predictive value found in this study was somewhat lower than the values found in previous studies involving more homogeneous patient populations.

Bacterial flora in the sputum and comorbidity in patients with acute exacerbations of COPD.

OBJECTIVE: To determine in patients admitted with an acute exacerbation of chronic obstructive pulmonary disease (AE-COPD) the association between the isolation of potential pathogens in a conventional sputum culture and comorbidities. PATIENTS AND METHODS: The ESMI study is a multicenter observational study. Patients with AE-COPD admitted to the Internal Medicine departments of 70 hospitals were included. The clinical characteristics, treatments, and comorbidities were gathered. The results of conventional sputum cultures were recorded. RESULTS: A total of 536 patients were included, of which 161 produced valid sputum and a potentially pathogenic microorganism was isolated from 88 subjects (16.4%). The isolation of Pseudomonas aeruginosa (30.7%) was associated with a greater severity of the lung disease (previous admissions [P= 0.026], dyspnea scale [P=0.047], post-broncodilator forced expiratory volume in 1 second (FEV1) [P=0.005], and the BODEx index [P=0.009]); also with higher prevalence of cor pulmonale (P=0.017), heart failure (P=0.048), and cerebrovascular disease (P=0.026). Streptococcus pneumoniae (26.1%) was associated with more comorbidity according to number of diseases (P=0.018); notably, peripheral artery disease (P=0.033), hypertension (P=0.029), dyslipidemia (P=0.039), osteoporosis (P=0.0001), and depression (P=0.005). CONCLUSION: Patients with AE-COPD and P. aeruginosa present higher severity of COPD, while those with S. pneumoniae present greater comorbidity. The potentially pathogenic microorganism obtained in the sputum culture depends on the associated comorbidities.

[Clinical profile and treatment of elderly patients hospitalized for acute exacerbation of chronic obstructive pulmonary disease in Spanish Internal Medicine services. ECCO study]. / Características clínicas y tratamiento de los pacientes ancianos hospitalizados por descompensación de enfermedad pulmonar obstructiva crónica en los servicios de Medicina Interna españoles. Estudio ECCO.

BACKGROUND AND OBJECTIVE: Hospitalizations for chronic obstructive pulmonary disease (COPD) occur mostly in elderly patients. We describe the characteristics and treatment of elderly patients hospitalized for COPD in Internal Medicine Services, compared with the younger age group. PATIENTS AND METHODS: Observational, prospective, multicenter study. We compared the differences between patients older than 80 years and the rest regarding comorbidity, severity of COPD, previous admissions, length of stay and treatment prescribed. Comorbidity was assessed by the Charlson index and a questionnaire was designed for this purpose. RESULTS: We included 398 subjects, 353 men (89%) with a mean age of 73.7 years (SD 8.8), of whom about 107 (26.9%) were older than 80 years. These patients had less severe COPD according to the GOLD classification (P<.02). Although the overall morbidity was similar in both groups, elderly patients had greater presence of arrhythmias (P<.01), left ventricular hypertrophy (P<.01) and received more diuretics (P<.05). Dyspnoea, length of stay and mortality were similar between both populations. Home oxygen therapy prior to and use of inhaled corticosteroids and oxygen therapy was lower in older patients, even when they were clinically indicated. CONCLUSIONS: A quarter of patients hospitalized for COPD in Internal Medicine Services are over 80 years. Although they present less obstruction, they have a similar degree of dyspnea, increased cardiac morbidity and their treatment is less consistent with the recommendations of the guidelines.

Factors associated with mortality in patients with exacerbation of chronic obstructive pulmonary disease hospitalized in General Medicine departments.

We aim to improve knowledge on risk factors that relate to mortality in subjects with exacerbation of chronic obstructive pulmonary disease (COPD) who are hospitalized in General Medicine departments. In a cross-sectional multicenter study, by means of a logistic regression analysis, we assessed the possible association of death during hospitalization with the following groups of variables of participating patients: sociodemographic features, treatment received prior to admission and during hospitalization, COPD-related clinical features recorded prior to admission, comorbidity diagnosed prior to admission, clinical data recorded during hospitalization, laboratory results recorded during hospitalization, and electrocardiographic findings recorded during hospitalization. A total of 398 patients was included; 353 (88.7%) were male, and the median age of the patients was 75 years. Of these patients, 21 (5.3%) died during hospitalization. Only 270 (67.8%) received inhaled ß(2) agonists during hospitalization, while 162 (40.7%) received angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers. The median of predicted FEV(1) prior to admission was 42%. A total of 350 patients (87.9%) had been diagnosed with two or more comorbid conditions prior to admission. An association was found between increased risk of death during hospitalization and the previous diagnoses of pneumonia, coronary heart disease, and stroke. In conclusion, comorbidity is an important contributor to mortality among patients hospitalized in General Medicine departments because of COPD exacerbation.

Randomized clinical trial of the effectiveness of a home-based intervention in patients with heart failure: the IC-DOM study.

INTRODUCTION AND OBJECTIVES: The objective of this study was to determine whether a home-based intervention can reduce mortality and hospital readmissions and improve quality of life in patients with heart failure. METHODS: A randomized clinical trial was carried out between January 2004 and October 2006. In total, 283 patients admitted to hospital with a diagnosis of heart failure were randomly allocated to a home-based intervention (intervention group) or usual care (control group). The primary end-point was the combination of all-cause mortality and hospital readmission for worsening heart failure at 1-year follow-up. RESULTS: The primary end-point was observed in 41.7% of patients in the intervention group and in 54.3% in the control group. The hazard ratio was 0.70 (95% confidence interval [CI] 0.55-0.99). Taking significant clinical variables into account slightly reduced the hazard ratio to 0.62 (95% CI 0.50-0.87). At the end of the study, the quality of life of patients in the intervention group was better than in the control group (18.57 vs. 31.11; P< .001). CONCLUSIONS: A home-based intervention for patients with heart failure reduced the aggregate of mortality and hospital readmissions and improved quality of life.

Polymorphonuclear elastase in the early diagnosis of complicated pyogenic pleural effusions.

BACKGROUND: Polymorphonuclear elastase (PMN-E) is a neutrophilic marker that has been implicated in acute inflammatory responses. OBJECTIVES: To evaluate the accuracy of PMN-E in the diagnosis of complicated pyogenic effusions. PATIENTS AND METHOD: We studied 536 patients with pleural effusion of various etiologies. There were 125 pyogenic bacterial effusions (42 typical parapneumonic, 17 borderline complicated parapneumonic and 66 complicated parapneumonic or empyema), 83 tuberculous, 91 malignant, 42 paramalignant, 95 transudates, 28 miscellaneous and 72 effusions of unknown origin. Classic markers (pH, glucose, proteins, adenosine deaminase, LDH, leukocytes and differential count) and the PMN-E level were quantified in pleural fluid. The accuracy of PMN-E as an early marker in the diagnosis of complicated pyogenic infectious effusions was evaluated among pleural effusions that were not diagnosed with classic biochemical markers, radiological findings or Gram stain. Since results of pleural fluid culture and cytological examination are generally available after a 48-hour delay, they were not included as early markers in the initial diagnosis of pleural effusions. RESULTS: Early diagnosis of complicated pyogenic bacterial effusions was achieved in only 48 of 66 cases with classic markers. Among those that were not diagnosed with these parameters, a pleural PMN-E value >3,500 microg/l discriminated between complicated and noncomplicated pyogenic bacterial effusions with a sensitivity of 67% and a specificity of 97%. CONCLUSIONS: PMN-E is useful in the early diagnosis and management of complicated pyogenic infectious effusions, which may be delayed with classic markers.