Patients with laboratory criteria of anti-phospholipid syndrome and 'non-criteria' manifestations: a multicenter cohort.

OBJECTIVES: Patients with laboratory criteria for anti-phospholipid syndrome (APS) but presenting only 'non-criteria' clinical manifestations are scarcely characterized in the literature. We aimed to analyse a cohort of these patients regarding the most prevalent manifestations, antibody profile, and treatments, while establishing a comparison with definite APS patients. METHOD: A retrospective analysis was conducted of individuals fulfilling APS laboratory criteria assessed in two tertiary European hospitals between 2005 and 2020. Patients without clinical criteria but with non-criteria manifestations (termed 'clinical non-criteria') and age-/gender-matched controls were included. RESULTS: Altogether, 75 clinical non-criteria patients were analysed, with haematological (thrombocytopenia, haemolytic anaemia) and 'mild' neurological manifestations (white-matter lesions, migraine) as the most prevalent non-obstetric involvements. These patients displayed more thrombocytopenia [odds ratio (OR) = 3.6, 95% confidence interval (CI) 1.7-7.6; p = 0.001] than controls with APS, but severe manifestations, such as valvular heart disease (p < 0.001), livedoid vasculopathy, seizures, chorea, transverse myelitis, bone necrosis, and alveolar haemorrhage, occurred only in definite APS patients. Corticosteroids were required by 40% of patients with thrombocytopenia. Manifestations in anticoagulated patients included white-matter lesions, nephropathy, superficial vein thrombosis, amaurosis fugax, and livedoid vasculopathy. Suspicion of progression towards systemic lupus erythematosus (SLE) occurred in 19% of non-SLE individuals. CONCLUSION: 'Clinical non-criteria' patients displayed significant treatment use, predominantly haematological involvement, and less severe manifestations than definite APS controls. Some patients may additionally progress to future SLE. The impact of certain manifestations flags them as potential future contributors to classifying individuals as definite APS.

Long term prognosis of acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) can be fatal if left untreated. Long-term prognosis of acute PE in the 21st century has not been fully reported. We aimed to determine the long-term prognosis of patients hospitalized with acute PE and compare survivalof patients with idiopathic and secondary PE. MATERIALS AND METHODS: We retrospectively analysed a cohort of hospitalized patients with acute PE between 2006 and 2013. EXCLUSION CRITERIA: <18 years, venous embolism of non-pulmonary veins, chronic thromboembolic pulmonary hypertension, and presumptive diagnosis without image confirmation. Only patients with a first PE episode were included. End-point: all-cause mortality. Patients were compared according to PE aetiology: idiopathic, secondary to neoplastic conditions and secondary to non-neoplastic conditions. A Cox-regression analysis was used to study the prognostic impact of PE aetiology. RESULTS: We studied 872 hospitalized acute PE patients. Median age 70 years, 56.9% were women. PE was idiopathic in 376 (43.1%), secondary to a neoplastic condition in 284 (32.6%) and secondary to a condition other than neoplasia in 212 (24.3%). Patients were followed for a median 25 months period and 508 (58.3%) died. Patients with PE attributed to a neoplastic condition had the worst survival. Patients with idiopathic PE had a multivariate-adjusted HR of mortality of 1.46 (1.08-1.99) during the over 2-year follow-up period when compared to those with acute PE attributed to a non-neoplastic condition. CONCLUSIONS: Patients with idiopathic acute PE have an almost 50% higher death risk in a median 2-year follow-up period than those with acute PE secondary to a condition other than neoplasia.

Acute heart failure and rhabdomyolysis: a clue for the diagnosis of polymyositis with cardiac involvement.

Polymyositis is an idiopathic inflammatory myopathy, characterized by proximal muscle weakness and sometimes extramuscular manifestations. We report the case of a 51-year-old male, with history of complete heart block, which required pacemaker implantation, and subsequently heart failure, presenting to the emergency department with worsening of dyspnea and peripheral edema. He was admitted to the Internal Medicine ward with acute heart failure and started on diuretic therapy. During hospitalization, he was discovered to have marked rhabdomyolysis. Examination revealed proximal symmetrical muscle weakness and arthralgia. The immunological study, electromyography and muscle biopsy confirmed polymyositis. The patient was started on prednisolone with clinical improvement and resolution of rhabdomyolysis. The presence of conduction defect, ventricular dysfunction, mitral valve regurgitation, segmental hypokinesia (myocardial scintigraphy without perfusion defects) and pulmonary hypertension, as well as elevated troponin with improvement after specific therapy, points to cardiac involvement. Polymyositis is a rare entity, with an insidious evolution and a myriad of extramuscular features that can mimic other conditions. In particular, cardiac involvement may be the first and only recognized manifestation. The key point for the diagnosis is to contemplate the possibility of polymyositis.

The lymphocyte-to-monocyte ratio: an added value for death prediction in heart failure.

BACKGROUND AND AIM: Leukocytes and their subpopulation have been long implicated in the progression of the syndrome of heart failure (HF), especially heart infiltration cells. Previous reports have suggested that they can predict worse outcome in patients with HF, and can also affect the function of other cells and myocardial extracellular matrix remodeling process. However, the lymphocyte-to-monocyte ratio (LMR) and its possible value as prognostic marker have not been evaluated. METHODS AND RESULTS: A total of 390 patients with acute HF were recruited and followed for 6 months. Their total blood count with leukocyte differential was obtained. Two groups were formed according to the endpoints of HF death and optimal cut-off value of LMR, and were compared. A multivariate Cox-regression model was used to establish the prognostic value with the endpoints of HF and all-cause mortality. Median age of the patients was 78 years and 48.5% of them were men. No major difference was observed between the clinical characteristics of the two groups. Patients who died of HF had significantly higher values of B-type natriuretic peptide and lower values of LMR. Leukocyte and monocyte counts revealed a multivariate-adjusted risk for both endpoints, whereas relative lymphocyte counts had only significant value for all-cause mortality. The multivariate-adjusted hazard ratios for the 6-month HF and all-cause mortality in patients with LMR values < 2.0 were, respectively, 2.28 (95% CI: 1.25-4.15) and 2.39 (95% CI: 1.39-4.10). CONCLUSION: Our results show that, upon discharge from hospital after an episode of acute HF, a lower value of LMR is independently associated with a higher risk of mortality within 6 months.

Efficacy of albendazole against Taenia multiceps larvae in experimentally infected goats.

A controlled trial was conducted to evaluate the efficacy of three therapeutics regimes of albendazole (ABZ) against Taenia multiceps larvae in experimental infected goats. Forty-nine goats experimentally infected with 3000 T. multiceps eggs were selected and randomly divided into treatment or control groups. Treatment with 10mg/kg for 3 days for group 1 (G1), 10mg/kg for group 2 (G2) and 20mg/kg/day for group 3 (G3) was applied 2 months after infection; group 4 (G4) served as a control group. A treatment with doses of 10mg/kg/day for 3 days on group 5 (G5) and group 6 (G6) was used as control, 5 months after the infection. The efficacy of ABZ was assessed as percentage of non-viable cysts which were determined by morphologic characteristics, movement and methyl blue staining technique. The efficacy of ABZ against 2 months old cysts was significantly different from the control and were 90.3% (28/31), 72.7% (8/11) and 73.9% (14/19) for G1, G2 and G3, respectively. No differences were observed in cyst viability between treated and control groups for 5-month old cysts. The results in this study indicate that ABZ is effective in goats against 2-month-old cysts of T. multiceps larva located in tissues outside the brain.

Is the blood pressure paradox observed in all heart failure patients?

BACKGROUND: Heart failure (HF) patients with higher systolic blood pressure (SBP) survive longer. Diabetes mellitus (DM) is a frequent comorbidity in HF. We evaluated the prognostic significance of low SBP according to DM in acute HF. METHODS: We prospectively recruited 589 patients admitted with acute HF. DM was defined according to the 2011 American Diabetes Association recommendations. Patients were followed for 6 months and HF-death was the endpoint. A multivariate Cox-regression model was used to assess the prognostic impact of SBP. A stratified analysis according to DM was performed. RESULTS: Median patients' age was 79 years and DM was present in 50.8%. Ischemic aetiology HF and hypertension history were more common in diabetics. Diabetic patients had worse renal function and lower total cholesterol and were more often discharged with antiplatelet therapy and statin. During followup, 89 patients died due to HF. The multivariate-adjusted HR for the 6-month HF death in non-diabetic patients with an admission SBP < 115 mmHg (1st quartile) was 2.94 (95% CI: 1.49-5.79), while lower admission SBP was not associated with HF mortality in diabetics. CONCLUSIONS: The blood pressure paradox in HF is only observed in non-diabetic HF patients. Diabetic patients seem to be a particular subgroup of HF patients.

B-type natriuretic peptide measured in serum--calibration using plasma samples for research purposes.

BACKGROUND: We aimed to establish an equation for the estimation of the BNP concentration in plasma when only serum is available. METHODS: We enrolled 27 subjects aged at least 45 years, participating in a Portuguese cohort study. Blood samples were collected in plastic whole blood tubes, containing either ethylenediaminetetraacetic acid to obtain plasma or clot activator to obtain serum. The natural logarithm of serum BNP was calibrated with the natural logarithm of plasma BNP using a linear equation. RESULTS: The estimated regression parameters were 0.58 (95 % CI: 0.23 - 0.93) for beta0 and 1.01 (95 % CI: 0.90 - 1.11) for beta1. The absolute agreement between plasma BNP and that predicted by the equation according to the cut-off points 30 and 100 pg/mL were 96.3% (kappa = 0.92) and 96.3% (kappa = 0.91), respectively. CONCLUSIONS: Serum samples cannot be used to estimate absolute plasma concentrations, but serum BNP values and the calibration equation can be used to classify correctly the individuals with the usual cut-offs.

Enantiomeric behaviour of albendazole and fenbendazole sulfoxides in domestic animals: pharmacological implications.

Albendazole and fenbendazole are methylcarbamate benzimidazole anthelmintics extensively used to control gastrointestinal parasites in domestic animals. These parent compounds are metabolised to albendazole sulfoxide and fenbendazole sulfoxide (oxfendazole), respectively. Both sulfoxide derivatives are anthelmintically active and are manufactured for use in animals. They metabolites have an asymmetric centre on their chemical structures and two enantiomeric forms of each sulfoxide have been identified in plasma, tissues of parasite location and within target helminths. Both the flavin-monooxygenase and cytochrome P450 systems are involved in the enantioselective biotransformation of these anthelmintic compounds in ruminant species. A relevant progress on the understanding of the relationship among enantioselective metabolism and systemic availability of each enantiomeric form has been achieved. This article reviews the current knowledge on the pharmacological implications of the enantiomeric behaviour of albendazole sulfoxide and oxfendazole in domestic animals.

[Weaning from non-invasive positive pressure ventilation: experience with progressive periods of withdraw].

BACKGROUND: In recent years non-invasive ventilation (NIV) as become a valuable therapeutic option in exacerbations of patients with chronic pulmonary obstructive disease. Although widely used there is a paucity of information on weaning from NIV. OBJECTIVES: We aimed to describe the performance of a weaning protocol based on progressive periods of NIV withdraw. METHODS: During a one year period we performed NIV in 78 patients with acute exacerbation of chronic respiratory failure. Weaning was considered in patients with 24 hours without acidosis and respiratory rate less than 25 cycles per minute. Weaning was performed as following: during the first 24 hours in each 3 hours, one hour without NIV (except during night period), in the second day in each 3 hours, two hours without NIV (except during night period) and in the third day NIV was used during the night period. RESULTS: Sixty five patients began the weaning protocol. Mean NIV time was 120,9 hours (17 to 192 hours). No adverse effects were recorded in patients who began the weaning protocol. All patients completed the weaning protocol with no re-institution of NIV or invasive ventilation during hospitalization. CONCLUSIONS: We report an excellent weaning success rate of NIV in patients with acute severe exacerbation of CRF. Although our weaning protocol required 72 hours, our results suggest that strategies based on periods with and with-out NIV are effective. Weather similar less time consuming weaning strategies are effective, merits investigation.

Pharmacokinetics of albendazole sulfoxide enantiomers administered in racemic form and separately in rats.

The pharmacokinetic behaviour of albendazole sulfoxide (ABZSO) enantiomers was studied in rats after the oral administration of 10 mg/kg of rac-ABZSO, 5 mg/kg of (-)-ABZSO or 5 mg/kg of (+)-ABZSO. The disposition profiles of ABZSO enantiomers were similar in all treatments, but the calculated area under the curve for the (-)-ABZSO was higher in all cases compared with (+)-ABZSO. The results suggest that there is no chiral inversion of ABZSO enantiomers. After the administration of rac-ABZSO, 17.2% of the total dose was recovered in urine as albendazole ABZ (0.1%), albendazole sulfone ABZSO(2) (0.3%), albendazole 2-aminosulfone (ABZ-SO(2)NH(2)) (3.1%) and ABZSO (13.7%). The ratio (+) to (-) was similar in urine (1.6) and blood (1.7).

Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans.

A key challenge of functional genomics today is to generate well-annotated data sets that can be interpreted across different platforms and technologies. Large-scale functional genomics data often fail to connect to standard experimental approaches of gene characterization in individual laboratories. Furthermore, a lack of universal annotation standards for phenotypic data sets makes it difficult to compare different screening approaches. Here we address this problem in a screen designed to identify all genes required for the first two rounds of cell division in the Caenorhabditis elegans embryo. We used RNA-mediated interference to target 98% of all genes predicted in the C. elegans genome in combination with differential interference contrast time-lapse microscopy. Through systematic annotation of the resulting movies, we developed a phenotypic profiling system, which shows high correlation with cellular processes and biochemical pathways, thus enabling us to predict new functions for previously uncharacterized genes.

Heart failure, aging, and renal synthesis of dopamine.

The present study evaluates renal dopaminergic activity in 23 patients with heart failure (HF), 10 age-matched controls, and 10 young subjects during normal-salt (NS) intake and after 8 days of low-salt (LS) intake (patients with HF and age-matched controls only). LS intake produced a marked reduction in urine volume in patients with HF but failed to affect urine volume in age-matched controls. Urinary sodium and fractional excretion of sodium were markedly reduced by LS intake in patients with HF and age-matched controls. Daily urinary excretion of L-3,4-dihydroxyphenylalanine (L-dopa) and dopamine was lower in patients with HF than in age-matched controls. LS intake failed to alter L-dopa and dopamine urinary excretion in control subjects. In patients with HF, LS intake produced a significant decrease in urinary L-dopa excretion, but failed to alter the urinary excretion of dopamine. No significant differences were observed in urinary L-dopa, dopamine, and dopamine metabolite levels between aged controls and young healthy subjects. Urinary dopamine-L-dopa ratios in patients with HF on LS intake (24.5 +/- 7.1) were significantly greater than those with NS intake (11.6 +/- 1.3). Urinary dopamine-L-dopa ratios in old control subjects (LS, 9.7 +/- 1.3; NS, 9.3 +/- 1.1) did not differ from those in young healthy subjects (9.2 +/- 0.8). LS intake produced a marked increase in plasma aldosterone levels in both patients with HF (84.6 +/- 14.4 to 148.2 +/- 20.4 pg/mL; P = 0.0008) and controls (102.1 +/- 13.4 to 151.6 +/- 15.7 pg/mL; P < 0.04). Plasma norepinephrine levels were not significantly affected by LS intake in controls (5.1 +/- 1.62 to 6.3 +/- 1.6 pmol/mL; P = 0.22), but were significantly increased in patients with HF (5.8 +/- 0.8 to 7.1 +/- 0.9 pmol/mL; P = 0.04). In conclusion, patients with HF are endowed with an enhanced ability to take up (or decarboxylate) filtered L-dopa, which might counterbalance the reduced renal delivery of L-dopa, contributing to a relative preservation of dopamine synthesis. This may result as a compensatory mechanism, activated by stimuli leading to sodium reabsorption. Age seems to have no influence on renal dopamine production.

Neurohormonal activation, the renal dopaminergic system and sodium handling in patients with severe heart failure under vasodilator therapy.

The benefits of tailoring therapy with vasodilators in patients with severe heart failure are well documented, but this may lead to neurohormonal activation and sodium retention. Renal dopamine has local natriuretic actions and interacts with other hormones involved in renal sodium handling. The aim of the present work was to determine the effects of arterial underfilling induced by vasodilator therapy on renal sodium handling, neurohormonal activation and the activity of the renal dopaminergic system in patients with severe heart failure. For this purpose we monitored haemodynamic parameters, plasma levels of type B natriuretic peptide (BNP), catecholamines, aldosterone, renin activity (PRA), sodium and creatinine, and urinary excretion of sodium, creatinine, L-DOPA, dopamine and its metabolites, before initiation of sodium nitroprusside therapy and every 6 h thereafter (for 42 h), and again after 5 days of angiotensin-converting enzyme (ACE) inhibition, in 10 male patients with severe heart failure. The results of nitroprusside therapy were a marked increase in cardiac index and a substantial decrease in systemic vascular resistance index. Plasma levels of BNP decreased significantly, while PRA, noradrenaline and aldosterone showed marked increases, resulting in a substantial reduction in urinary sodium excretion. Creatinine clearance was not affected. Urinary dopamine and dopamine metabolites increased in response to nitroprusside therapy. After 5 days of ACE inhibition, urinary sodium returned to baseline values, while urinary dopamine was markedly reduced. These results suggest that the renal dopaminergic system is activated in patients with severe heart failure by stimuli leading to sodium renal reabsorption.

[Type B natriuretic peptide in the diagnosis of heart failure with preserved systolic function]. / Peptídeo natriurético tipo B no diagnóstico de insuficiência cardíaca com função sistólica preservada.

BACKGROUND: Heart failure (HF) with preserved left ventricular systolic function (LVSF) is observed in up to 50% patients with HF. There is no consensus on non-invasive diagnosis of this entity. OBJECTIVE: Evaluation of B-type natriuretic peptide (BNP) in the diagnosis of HF with preserved left ventricular systolic function. DESIGN: Prospective study. PATIENTS: One hundred and seventy-six consecutive patients with suspected HF were evaluated. Patients were classified as having HF with preserved LVSF, if they had symptoms and signs of HF, an ejection fraction greater than 40% and an abnormal Doppler pattern of the mitral inflow or atrial fibrilation and no other causes for the symptoms. All patients had a 12-lead EKG, chest roentgenogram, simple spirometry, M-mode and 2D echocardiogram with pulsed Doppler study of transmitral inflow and determination of plasma BNP levels. RESULTS: Of the 176 patients, 65 had ejection fraction greater than 40%. Of these patients 46 were classified as having HF with preserved LVSF and 19 as not having HF. Patients with HF and preserved LVSF were older, had a higher systolic blood pressure (SBP), less pathologic Q waves on ECG and higher left ventricular ejection fraction and plasma BNP than patients without HF. Multivariate analysis revealed that BNP and SBP were independently associated with the diagnosis of HF. The accuracy of BNP in the diagnosis of HF with preserved LVSF evaluated by the area under the receiver operating characteristic curve was 0.94. CONCLUSION: These results suggest that the measurement of BNP levels can help clinicians in the diagnosis of HF with preserved LVSF. Whether BNP levels might be used in clinical practice as a test for the diagnosis of HF with preserved LVSF is a question that merits further studies.

Prognosis in patients with heart failure and preserved left ventricular systolic function.

BACKGROUND: It is recognized that heart failure patients with preserved left ventricular systolic function have better prognosis; nevertheless, there are some studies with conflicting results. Also, there is a paucity of data concerning the prognostic factors in this group of patients. OBJECTIVES: To determine possible variables with prognostic relevance in heart failure patients with preserved left ventricular systolic function (ejection fraction > 40%). METHODS: 157 consecutive ambulatory patients with heart failure were assessed; those patients with ejection fraction > 40% were included in the study (n = 46). All patients were evaluated by clinical interview and physical examination, ECG, echocardiogram (M-mode, 2D and pulsed Doppler of mitral flow), biochemical study and determination of type B natriuretic peptide (BNP). The patients were grouped according to the rhythm presented on ECG: Group I--patients with atrial fibrillation; Group II--patients in sinus rhythm Group II was further subdivided in two groups according to the presence or absence of restrictive left ventricular filling pattern. All patients had a clinical follow-up, with recording of events (death or hospitalization from cardiac cause). The mean follow-up time was 682.2 +/- 55 days. RESULTS: The mean age of the patients was 70.4 +/- 1.2 years; 54.3% were women; mean ejection fraction was 49.6 +/- 1%; mean BNP levels were 202.9 +/- 41.3 pg/ml. Mortality was 19.6% and the combined event death or hospitalization from cardiac cause) occurred in 26.1% of the patients. Among the clinical, demographic, biochemical, echocardiographic and neurohumoral parameters, only BNP levels had prognostic significance in the whole population. In Group II patients, BNP levels, heart rate and restrictive left ventricular filling pattern were identified as having prognostic significance. Kaplan-Meyer curve analysis showed that both BNP and restrictive left ventricular filling pattern seemed to be important prognostic markers. CONCLUSIONS: This preliminary study suggests thar neurohumoral activity (determined by plasma BNP levels) and a restrictive ventricular filling pattern may be important factors in prognostic stratification of heart failure patients with preserved left ventricular systolic function.

Echocardiographic patterns and prognosis in heart failure.

BACKGROUND: There are many variables with prognostic value in patients with heart failure (HF). Those related to left ventricular function are among the most important. Recently, the evaluation of the patterns of ventricular filling by pulsed Doppler echocardiography has been studied as a variable with prognostic value. OBJECTIVES: To evaluate the prognostic value of echocardiography variables (diastolic and systolic) in patients with HF. These variables were analysed in respect to hospital admission for cardiovascular reasons or death. MATERIAL AND METHODS: We evaluated 157 consecutive patients with HF and included 110 patients who were in sinus rhythm. The mean age was 68.2 +/- 0.9 years. HF was ischemic in 52.7%. Patients underwent echocardiography examination within the week of reference. The patients were grouped according to left ventricular (LV) systolic dysfunction (LV ejection fraction < 40%). We also classified patients in two groups according to the presence of a restrictive pattern in diastolic transmitral flow profile. Finally, we classified all patients in four groups according to their systolic function and diastolic pattern: Group I--systolic dysfunction and restrictive ventricular filling pattern. Group II--systolic dysfunction without restrictive ventricular filling pattern. Group III--without systolic dysfunction with restrictive ventricular filling pattern. Group IV--without systolic dysfunction without restrictive ventricular filling pattern. The events were death or hospital admission. The mean follow up time was 625 +/- 55 days. We did a statistical analysis and for all tests a p value < 0.05 was considered statistically significant. RESULTS: We found impaired LV systolic function (systolic HF) in 73.6% and restrictive ventricular filling pattern in 45.5%. During the follow-up 41.8% died or were admitted to hospital. Patients with systolic HF had lower admission free survival rate. Patients with restrictive ventricular filling pattern had lower admission free survival rate than those without. Group I had lower admission free survival rate than Group II and Group IV. Group IV had a higher admission free survival than all other Groups. CONCLUSIONS: These results support and expand previous observations that diastolic function variables, such as the pattern of ventricular filling (namely the restrictive) have independent prognostic value in patients with HF.