Paula Dias

Prognostic information provided by serial measurements of brain natriuretic peptide in heart failure

BACKGROUND Brain natriuretic peptide (BNP) levels predict prognosis in heart failure patients. We aimed to evaluate if serial measurements of BNP can give additional prognostic information. METHODS Eighty-four patients with systolic dysfunction had two measurements of BNP with an interval of 8 to 12 months and were followed in order to register the occurrence of death. The study was observational and prospectively designed. During follow-up, patients were treated according to state of the art. Physicians were kept blind to BNP levels. RESULTS The median follow-up was 1190 days. The median initial BNP level was 260.4 pg/ml and decreased to 123 pg/ml in the second measurement (P=0.001). The decrease in BNP was significantly associated with ACE-i dosage and with the use of a beta-blocker. All-cause mortality was 20.2%. Patients whose initial BNP level was above the median had a significantly higher hazard of dying (HR 2.96, 95% CI 1.06-8.26). The same was observed for those whose BNP increased between the first and the second measurement (HR 2.64, 95% CI 1.00-7.00). In multivariable analysis, baseline BNP above the median and increasing BNP were associated with shorter survival. CONCLUSIONS Higher baseline BNP and the increasing levels during follow-up were independently associated with mortality. The decrease in BNP levels was proportional to ACE-i dosage and larger among patients on beta-blockers. These results confirm the prognostic information provided by BNP determination and suggest that serial measurements give additional prognostic information.

Evaluation of Brain Natriuretic Peptide in the Diagnosis of Heart Failure

A diagnosis of heart failure (HF) can be difficult, especially in patients with mild symptomatology. The purpose of this study was to evaluate the significance of brain natriuretic peptide (BNP) in the diagnosis of HF with systolic or isolated diastolic ventricular dysfunction. One hundred patients and 9 controls were included in the study. Eighty-five patients were diagnosed with HF, based on clinical and echocardiographic findings. BNP levels were accurate for the diagnosis of HF, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.92. In addition, BNP levels showed an excellent accuracy for the diagnosis of isolated diastolic HF (AUC = 0.89). These data suggest that the measurement of BNP levels may be helpful in the diagnosis of HF and in selecting patients for further evaluation. Furthermore, BNP measurement can play an important role in the diagnosis of isolated diastolic HF.

On the stability enhancement of cuprous oxide water splitting photocathodes by low temperature steam annealing

Given the intermittent nature of solar radiation, the large-scale use of solar energy requires an efficient energy storage solution. So far, the only practical way to store such large amounts of energy is in the form of a chemical energy carrier, i.e., a fuel. Photoelectrochemical (PEC) cells offer the ability to convert solar energy directly into chemical energy in the form of hydrogen. Cuprous oxide (Cu2O) is being investigated for photoelectrochemical solar water splitting since it has a band gap of 2.0 eV with favorable energy band positions for water cleavage; it is abundant and environmentally friendly. A major challenge with Cu2O is its limited chemical stability in aqueous environments. We present a simple and low-cost treatment to create a highly stable photocathode configuration for H2 production, consisting of steam treatment of the multilayer structures. The role of this treatment was investigated and the optimized electrodes have shown photocurrents over −5 mA cm−2 with 90% stability over more than 50 h of light chopping (biased at 0 VRHE in pH 5 electrolyte).

Effect of a heart failure clinic on survival and hospital readmission in patients discharged from acute hospital care

Ambulatory care by physicians especially devoted to the management of heart failure (HF) has been reported to have beneficial effects. The aim of this work was to assess the effect of outpatient management at a HF clinic, as compared with care by the usual assistant physician, on prognosis of HF patients. In this non‐randomised study, we prospectively followed 339 patients after a hospitalisation index for HF, in order to compare prognosis between two groups of HF patients according to the ambulatory assistance setting: either a specific outpatient clinic (n‐157) or the usual assistant physician (n‐182). The outcomes assessed were all‐cause death or cardiac‐cause rehospitalisation during the first month after discharge and survival over the longer term. The risk of dying or being readmitted during the first month after discharge was significantly lower in patients followed at the HF clinic (adjusted odds ratio 0.23; 95% CI 0.12–0.46). Patients followed in the HF clinic also had an independent significantly lower hazard of dying during a longer‐term follow up of average length 373 days (adjusted hazard ratio 0.52; 95% CI 0.34–0.81). The results support the fact that a multidisciplinary and permanently available medical staff might be of relevance in improving outcomes in HF patients.

Accurate detection of upper tract urothelial carcinoma in tissue and urine by means of quantitative GDF15, TMEFF2 and VIM promoter methylation

AIM OF THE STUDY Upper tract urothelial carcinoma (UTUC) accounts for 5-10% of all urothelial tumours. It is mostly diagnosed at advanced stages, entailing a worse prognosis, owing to the lack of early and specific symptoms as well as of effective diagnostic tools. We previously identified a panel of epigenetic biomarkers (GDF15, TMEFF2 and VIM promoter methylation) that accurately identifies bladder cancer in urine. Herein, we assessed the performance of the same panel for UTUC detection and prognosis, in tissue and urine. MATERIAL AND METHODS Methylation levels of reference and target genes were determined using real-time quantitative methylation-specific polymerase chain reaction (MSP) in bisulphite-modified DNA of 57 UTUC tissues, 36 normal upper tract urothelium (NUTUs), 22 urines from UTUC suspects and 20 urines from controls. Receiver operator characteristics (ROC)-curve analysis was performed to determine the performance of the biomarker panel and survival analyses were conducted to evaluate their prognostic value. RESULTS Methylation levels of GDF15, TMEFF2 and VIM were significantly higher in UTUC compared to NUTUs (P=0.022; P<0.001; P<0.001, respectively). The panel accurately identified UTUC with 100% and 91% sensitivity, corresponding to an area under the curve of 1.000 and 0.923 in tissue and urines, respectively, with 100% specificity. Low VIM promoter methylation levels independently predicted poor disease-specific survival. CONCLUSIONS GDF15, TMEFF2 and VIM promoter methylation allows for accurate identification of UTUC, in tissue and urine and VIM methylation provides relevant prognostic information, especially in high-stage disease. This assay may improve the clinical management of UTUC patients.

Population based study on the prevalence of the stages of heart failure

Heart failure (HF) is a major health issue. The heterogeneous nature of the syndrome impairs agreement on a standard definition. The high prevalence of HF with preserved left ventricular (LV) systolic function and asymptomatic LV systolic dysfunction, and the need for objective evidence of cardiac structural or functional abnormalities for HF diagnosis increase the difficulty in achieving a consensual definition. We aimed at estimating the age and sex specific prevalence of the American College of Cardiology (ACC)/American Heart Association (AHA)1 stages of HF in a representative sample of non-institutionalised adults from Porto, Portugal. Within a population health survey (participation 70%),2 we measured the prevalence of HF among participants aged ⩾ 45 years.2 The local ethics committee approved the study. Participants provided written informed consent. Hypertension was defined as blood pressure ⩾ 140/90 mm Hg or treatment with medication, and diabetes mellitus was defined as self reported or fasting blood glucose ⩾ 7 mmol/l. The metabolic syndrome was defined according to the National Cholesterol Education Program-Adult Treatment Panel III, obesity as body mass index ⩾ 30 kg/m2, and excessive alcohol intake as > 100 or > 80 g/day in men and women, respectively. Coronary artery disease was defined as self reported diagnosis of angina or myocardial infarction or pathological Q waves on ECG. Chronic lung disease was defined as previous chronic bronchitis or moderate to severe obstruction …

Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

BackgroundSevere toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (DPYD).MethodsIn this study, we evaluated DPYD promoter methylation through quantitative methylation-specific PCR and screened DPYD for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. DPYD promoter methylation was also assessed in tumor tissue from 29 patientsResultsTwo cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, DPYD promoter methylation and large DPYD intragenic rearrangements were absent in all cases analyzed.ConclusionsOur results indicate that DPYD promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.

Expression of histone methyltransferases as novel biomarkers for renal cell tumor diagnosis and prognostication.

Renal cell tumors (RCTs) are the most lethal of the common urological cancers. The widespread use of imaging entailed an increased detection of small renal masses, emphasizing the need for accurate distinction between benign and malignant RCTs, which is critical for adequate therapeutic management. Histone methylation has been implicated in renal tumorigenesis, but its potential clinical value as RCT biomarker remains mostly unexplored. Hence, the main goal of this study was to identify differentially expressed histone methyltransferases (HMTs) and histone demethylases (HDMs) that might prove useful for RCT diagnosis and prognostication, emphasizing the discrimination between oncocytoma (a benign tumor) and renal cell carcinoma (RCC), especially the chromophobe subtype (chRCC). We found that the expression levels of 3 genes—SMYD2, SETD3, and NO66—was significantly altered in a set of RCTs, which was further validated in a large independent cohort. Higher expression levels were found in RCTs compared to normal renal tissues (RNTs) and in chRCCs comparatively to oncocytomas. SMYD2 and SETD3 mRNA levels correlated with protein expression assessed by immunohistochemistry. SMYD2 transcript levels discriminated RCTs from RNT, with 82.1% sensitivity and 100% specificity [area under curve (AUC) = 0.959], and distinguished chRCCs from oncocytomas, with 71.0% sensitivity and 73.3% specificity (AUC = 0.784). Low expression levels of SMYD2, SETD3, and NO66 were significantly associated with shorter disease-specific and disease-free survival, especially in patients with non-organ confined tumors. We conclude that expression of selected HMTs and HDMs might constitute novel biomarkers to assist in RCT diagnosis and assessment of tumor aggressiveness.

Long-term survival, autonomy, and quality of life of elderly patients undergoing aortic valve replacement.

Abstract  Aims: We reviewed the long‐term survival, autonomy, and quality of life (QoL) of elderly patients undergoing aortic valve replacement (AVR). Methods: Records of patients ≥75 years old that underwent AVR from 2002 to 2006 were retrospectively analyzed. Functional status was classified with Barthel Index (BI). QoL was presumed as the self‐perception of well‐being after AVR. Independent predictors of mortality were identified using the Cox proportional hazards model. Results: We included 114 patients, with a mean age of 78.5 ± 2.5 years. Seventy (59.8%) patients were females. Mean additive and logistic EuroSCORE were 7 ± 2 and 9 ± 7, respectively. Follow‐up on vital status was achieved for 113 (99.1%) patients after a mean period of 47.2 ± 23.4 months. Twenty‐seven (23.7%) patients died (including three operative deaths). Survival up to one, three, and five years of follow‐up was 94.4%, 86.7%, and 76.1%, respectively. Multivariate analysis showed that pulmonary hypertension and diabetes were independent predictors of all‐cause mortality. Information on BI score and QoL was obtained for 77 (89.5%) and patients. Among those, 69 (89.6%) were autonomous according to BI and 72 (93.5%) considered having had an improvement in QoL. Conclusion: Patients ≥75 years old undergoing AVR presented good medium‐term survival. Predictors of an adverse outcome were significant pulmonary hypertension and diabetes. At follow‐up, most achieved improvement of QoL and remained autonomous. These results stress that excellent long‐term outcomes with AVR can be achieved in appropriately selected elderly patients. (J Card Surg 2012;27:20–23)

Early Diagnosis of Nonaneurysmal Infectious Thoracic Aortitis Using Transesophageal Echocardiogram in a Patient with Purulent Meningitis

Infectious thoracic aortitis is a rare entity in the antibiotic era and usually appears in patients with prior aortic disease and/or associated infective endocarditis. Infected nonaneurysmal aorta will likely progress to mycotic aneurysm if left untreated. In most of the reports, infectious thoracic aortitis presents with a mycotic aneurysm. We report the case of a patient with a nonaneurysmal infectious thoracic aortitis, probably secondary to purulent meningitis, early diagnosed by transesophageal echocardiogram.