The association of the N-terminal pro-brain-type natriuretic peptide response to exercise with disease severity in therapy-naive pulmonary arterial hypertension: a cohort study.

BACKGROUND: While the N-terminal pro-brain-type natriuretic peptide (NT-proBNP) at rest is known to be associated with prognosis in pulmonary arterial hypertension (PAH), it is unclear if the NT-proBNP response to exercise (ΔNT-proBNP) can contribute to a better assessment of disease severity. METHODS: We investigated the association of NT-proBNP values at rest and during peak exercise with hemodynamics and cardiopulmonary exercise testing parameters in 63 therapy-naive PAH patients. RESULTS: The median NT-proBNP increases from 1414 at rest to 1500 pg/ml at peak exercise. The ΔNT-proBNP is baseline-dependent in PAH. Both, NT-proBNP at rest and NT-proBNP at peak exercise, are significantly correlated with hemodynamics and functional capacity. However, neither NT-proBNP at peak exercise nor ΔNT-proBNP correlated better with surrogate markers of disease severity than NT-proBNP at rest. CONCLUSION: The ΔNT-proBNP does not contribute to a better assessment of disease severity in PAH.

The association of N-terminal pro-brain-type natriuretic peptide with hemodynamics and functional capacity in therapy-naive precapillary pulmonary hypertension: results from a cohort study.

BACKGROUND: N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used as a surrogate marker for disease severity in pulmonary hypertension (PH). However, NT-proBNP tends to have a high variability and may insufficiently correlate with hemodynamics and exercise capacity. METHODS: To investigate the association of NT-proBNP with hemodynamics and cardio-pulmonary exercise testing (CPET) in 84 therapy-naive patients with precapillary PH. RESULTS: NT-proBNP levels were significantly correlated with hemodynamics and CPET parameters except for cardiac index, diffusion capacity, PaO2 at peak exercise, and peak minute ventilation. NT-proBNP correlated best with hemodynamics and CPET in women and patients >65 years. NT-proBNP correlated better with CPET in pulmonary arterial hypertension compared to chronic thromboembolic PH (CTEPH). CONCLUSION: NT-proBNP is associated with disease severity in precapillary PH. The association might be age- and gender-dependent. NT-proBNP may insufficiently correlate with disease severity in CTEPH, possibly due to comorbidity.

Obstructive sleep apnea might trigger acute pulmonary embolism: results from a cohort study.

BACKGROUND: Obstructive sleep apnea (OSA) might be an independent risk factor for acute pulmonary embolism (APE). AIM OF THE STUDY: A prospective cohort study was conducted to investigate if APE is sleep-related in untreated OSA syndrome or not. METHODS: 206 APE patients were evaluated by portable monitoring and polysomnography. APE symptoms which caused an arousal from sleep or occurred within the first hour after wake-up were considered to be sleep-related. RESULTS: APE manifestation is significantly more often sleep-related in patients with moderate or severe OSA compared to subjects with an apnea-hypopnea index ≤15/h (p < 0.001). The relative risk of sleep-related APE increases with the severity of OSA. CONCLUSIONS: OSA might trigger APE, possibly reflecting a pathophysiological relationship between these two conditions.

The N-terminal pro-brain-type natriuretic peptide based short-term prognosis in patients with acute pulmonary embolism according to renal function.

N-terminal pro-brain-type natriuretic peptide (NT-proBNP) is currently used for risk stratification in acute pulmonary embolism (PE). We aimed to clarify the impact of renal function on the validity of the NT-proBNP based prognosis, assuming that the biomarker is accumulated in renal insufficiency. The NT-proBNP based prediction of PE related in-hospital death was investigated according to renal function in 329 patients with acute PE. The normalized NT-proBNP ratios (NT-proBNP level divided by the age-adjusted normal upper range) were inversely correlated (r = -0.414, P < 0.001) to the estimated glomerular filtration rates (eGFR). A cut-off point of ≥ 2.5 for the normalized NT-proBNP ratio was found to be best for the prediction of mortality (AUC 0.716, 95% CI 0.626-0.805, P < 0.001) and was a significant predictor for death in univariate and multivariate analysis. A normalized NT-proBNP ratio ≥ 2.5 was a significant predictor for PE-mortality only in patients with an eGFR ≥ 60 ml/min/1.73 m². Renal insufficiency significantly predicted mortality in univariate but not in multivariate analysis. High-risk PE and cerebrovascular diseases were significantly more frequent in renal dysfunction and significantly predicted death in univariate and multivariate analysis. The validity of the NT-proBNP based short-term prognosis might be limited in renal dysfunction not only by accumulation, but also because renal insufficiency itself and concurrent conditions are contributing to PE related mortality.

The impact of age on the delay in diagnosis in patients with acute pulmonary embolism.

It has been speculated that the atypical clinical presentation of acute pulmonary embolism (PE) in older patients leads to a late diagnosis and therefore contributes to a worse prognosis. Therefore, we prospectively evaluated the delay in diagnosis and its relation to the in-hospital mortality in 202 patients with acute PE. Patients >65 years presented more often with hypoxia (P = .017) and with a history of syncope (P = .046). Delay in diagnosis was not statistically different in both age groups. Older age was significantly associated with an increased risk for in-hospital mortality (OR 4.36, 95% CI 0.93-20.37, P = .043), whereas the delay in diagnosis was not associated with an increase of in-hospital mortality. We therefore conclude that the clinical presentation of acute PE in older patients cannot be considered as a risk factor for late diagnosis and is not responsible for their higher in-hospital death rate.

[Chronic thromboembolic pulmonary hypertension: recommendations of the Cologne Consensus Conference 2010]. / Chronisch thromboembolische pulmonale Hypertonie: Empfehlungen der Kölner Konsensus-Konferenz 2010.

In the 2009 European Guidelines on pulmonary hypertension one section covers aspects of pathophysiology, diagnosis and treatment of chronic thromboembolic pulmonary hypertension (CTEPH). The practical implementation of the guidelines for this disease is of crucial importance, because CTEPH is a form of pulmonary hypertension which can be surgically cured. It is, however, frequently diagnosed late in the course of disease and often treated not correctly. In the European Guidelines CTEPH is addressed relatively briefly, although it is a common form of PH which is often overlooked. Any patient with unexplained PH should be evaluated for the presence of CTEPH. A ventilation/perfusion lung scan is recommended as the first step to exclude CTEPH. If the ventilation/perfusion lung scan or multislice CT angiography reveals perfusions defects suggesting the diagnosis of CTEPH, the patient should be referred to a centre with expertise in the medical and surgical management of these patients. After diagnosis of CTEPH the case has to be reviewed by an experienced surgeon in a PEA centre for assessment of operability. The recommendations of the European guidelines are summarized in the current manuscript with additional comments regarding diagnosis and treatment according to most recent evidence.

Effectiveness of thrombolysis in patients with intermediate-risk pulmonary embolism: influence on length of hospital stay.

INTRODUCTION: The effects of thrombolysis on the clinical outcome of patients with intermediate-risk pulmonary embolism (PE) are still under debate. The effect of thrombolysis on the length of stay (LOS) in hospital is unknown. The aim of this study was to identify factors associated with LOS and to investigate whether LOS is suitable to assess effectiveness of thrombolysis in patients with intermediate-risk PE. METHODS: Data were reviewed from December 2005 until October 2009. The LOS in the intensive care unit (ICU) was expressed in hours, and total LOS was recorded in days. Total LOS was not noted in case of preterm withdrawal of therapy or death. RESULTS: Of a total of 202 patients, 84 received alteplase plus heparin and 118 patients were treated with anticoagulants alone. Total median LOS was significantly shorter (10 vs. 12 days) in the alteplase group (P=0.005), while there was no difference in the LOS in the ICU. Age above 65 years (P=0.036) and comorbidity (P<0.001) were independent predictors for a prolonged hospital stay, whereas thrombolysis independently predicted a shorter total LOS in multivariate analysis (P=0.001). Thrombolysis has shown to be able to independently predict home discharge (P=0.029). CONCLUSION: LOS is influenced by patient-related factors such as age and comorbidity. Thrombolysis may lead to a reduction of total median LOS for patients with intermediate-risk PE, possibly indicating that it is more effective than anticoagulant therapy alone in this group of patients.

Central thromboembolism is a possible predictor of right heart dysfunction in normotensive patients with acute pulmonary embolism.

BACKGROUND: Right heart dysfunction is a crucial factor in risk stratification of normotensive patients with pulmonary embolism. Apart from biomarkers, determinants of right heart dysfunction in this group of patients are not yet well established. AIM AND METHOD: In order to identify such determinants, we analysed data of 252 patients with acute pulmonary embolism admitted to our hospital in 2008. RESULTS: 69 out of 140 patients showed right heart dysfunction by echocardiography within 24 hours after diagnosis, 71 did not. Right ventricular dysfunction was significantly more frequent in patients with central clots on computed tomography (p=0.004), a history of syncope (p<0.001) and among women on oral contraceptives (p=0.003). In multiple regression analysis, only central thromboembolism (p<0.001) was identified as individual predictor of right ventricular dysfunction. Age, gender, body mass index, idiopathic or recurrent thromboembolism, duration of symptoms, preceding surgery, room air oxygen saturation, carcinoma, hypertension, diabetes, renal disease, congestive left heart failure and concomitant lung disease were equally distributed. In comparison with NT-pro brain natriuretic peptide (PPV 67%, NPV 75%, p=0.782) and troponin I (PPV 76%, NPV 62%, p=0.336), central thromboembolism has shown to have a greater statistical power in predicting right heart dysfunction in normotensive patients with pulmonary embolism (PPV 78%, NPV 88%, p<0.001). CONCLUSION: Among normotensive patients with acute pulmonary embolism, those with central clots seem to be at greater risk for echocardiographically evaluated right ventricular dysfunction.

[Lipoid pneumonia - an underestimated syndrome]. / Lipidpneumonie - ein unterschätztes Krankheitsbild?

Lipoid pneumonia, first described by Laughlen 1925 may be classified as endogenous or exogenous. The endogenous form is seen when fat is deposited into the lung tissue. It is usually associated with proximal obstructive lesions, necrotic tissue after radio- or chemotherapy, with lipid storage disease or hyperlipidemia . Exogenous lipoid pneumonia results from inhaling or aspirating animal, vegetable or mineral oil. There are usually some underlying neurological defects or esophageal abnormalities. Patients may present with cough, sputum, hemoptysis and chest pain or may be asymptomatic. There is no classic chest film appearance: it may appear as diffuse airspace infiltration or localized consolidation simulating tumour. Computed tomography is diagnostically helpful and shows hypodense areas measuring from -100 to - 30 Hounsfield units. Bronchoscopic biopsies are mandatory for histological confirmation of the diagnosis. Treatment of exogenous lipoid pneumonia has always been conservative by discontinuing the use of oil, correction of underlying defects that may favor aspiration and treatment of intercurrent pneumonia. Other measures, for example corticosteroid therapy, are of uncertain benefit. Complications of lipoid pneumonia that worsen prognosis are recurrent bacterial pneumonias including nontuberculous mycobacteria or aspergillus, or lung cancer that has developed in areas of pre-existing exogenous lipoid pneumonia.

Near-field and confocal surface-enhanced resonance Raman spectroscopy at cryogenic temperatures.

For laser spectroscopy at variable temperatures with high spatial resolution a combined scanning near-field optical and confocal microscope was developed. Rhodamine 6G (R6G) dye molecules dispersed on silver nano-particles or nano-clusters were investigated. For optical excitation of the molecules, either an aperture probe or a focused laser spot in confocal arrangement were employed. Raman spectra in the wavenumber range between 300 cm-1 and 3000 cm-1 at room temperatures down to 8.5 K were recorded. Many of the observed Raman lines can be associated with the structure of the adsorbed molecule. Intensity fluctuations in spectral sequences were observed down to 77 K and are indicative of single molecule sensitivity.

[Alcoholic and non-alcoholic fatty liver hepatitis. When is abstaining from alcohol enough, when do steroids help?]. / Alkoholische und nicht alkoholische Fettleberhepatitis. Wann reicht die Alkoholkarenz, wann nützen Steroide?

Alcoholic and non-alcoholic steatohepatitis (NASH) are often histopathologically indistinguishable. Apart from the clinical and laboratory findings, the patient's history is of key importance for differentiating between alcoholic steatohepatitis with its poor prognosis, and NASH, with its usually bland course. While the latter rarely requires specific treatment, the former, in particular in its severe form, is a therapeutic challenge. In addition to suitable dietary measures, patients with a Maddrey Score > 32, may need corticosteroids. In patients with mild to moderate steatohepatitis, the daily alcohol consumption appears to be decisive for the prognosis. In severe forms of this condition, in contrast, mortality is high, and patients surviving the acute phase often develop cirrhosis, irrespective of their further drinking habits.

Essential fatty acids and their long-chain polyunsaturated metabolites in maternal and cord plasma triglycerides during late gestation.

The fatty acid composition of plasma lipids was determined in 41 pairs of mothers and their term infants at time of birth (38-42 postmenstrual weeks) by high-resolution capillary gas-liquid chromatography. Linoleic and alpha-linolenic acids were found at smaller concentrations in cord than in maternal triglycerides, in contrast to strikingly higher proportions of their long-chain polyunsaturated metabolites (LC-PUFA), which indicates a preferential maternofetal transport for certain physiologically important LC-PUFA. While no significant gestational age-dependent changes occurred in maternal plasma triglycerides, the values for most of the fetal long-chain n-3 metabolites increased with the duration of gestation, possibly reflecting an increased transplacental fatty acid passage during late pregnancy or a maturation of desaturation in the fetal liver.

Fatty acid composition of lipid classes in maternal and cord plasma at birth.

UNLABELLED: The fatty acid composition of plasma phospholipids, triglycerides, cholesterol esters and nonesterified fatty acids was determined by high-resolution capillary gas-liquid chromatography in 41 pairs of mothers and their term infants at time of birth. The total free fatty acid content in maternal and cord plasma was positively correlated, possibly reflecting a passive, gradient dependent transplacental passage of nonesterified fatty acids. Higher percentage values of several saturated and monounsaturated fatty acids in cord than in maternal plasma phospholipids, triglycerides and nonesterified fatty acids may have resulted from an active fetal fatty acid synthesis. Trans fatty acids were found in every lipid class at similar or slightly lower percentages in neonatal as in maternal plasma, thus confirming their placental passage. Long-chain n-6 and n-3 polyunsaturated fatty acids are preferentially incorporated into phospholipids and sterolesters of both maternal and cord plasma. Linoleic and alpha-linolenic acids were found in smaller portions in cord than in maternal fatty acids, in contrast to strikingly higher proportions of their long-chain polyunsaturated metabolites, which may indicate a discriminating placental transport for certain physiologically important long-chain polyunsaturated fatty acids. CONCLUSION: The fetus appears to obtain fatty acids from a combination of de novo synthesis, a passive gradient dependent transplacental passage of nonesterified fatty acids and a selective materno-fetal placental transport for certain fatty acids, such as physiologically important long-chain polyunsaturated fatty acids.