Abnormal troponin level as short-term predictor of poor outcome in acute atrial fibrillation

Background

The link between minor troponin (cardiac troponin I [cTnI]) elevations and atrial fibrillation (AF) is still debated.

Methods

A total of 948 patients with AF lasting less than 48 hours participated in the study and were required to undergo 1-month and 12-month follow-up. The exclusion criteria were represented by younger than 18 years, the presence of hemodynamic instability, or severe comorbidity. Primary end point was the composite of ischemic vascular events inclusive of stroke, acute coronary syndrome, revascularization, and death.

Results

In the short term, 4 patients (5%) of 78 with abnormal cTnI reached the primary end point (P = .001 vs others). Conversely, in the long term, 13 patients (17%) with abnormal cTnI, 21 (10%) with known ischemic vascular disease, and 50 (5%) aged patients (75 ± 10 years) reached the primary end point (P < .001, P < .001, and P = .002, respectively). At multivariate analysis, abnormal cTnI (hazard ratio [HR], 2.84; 95% confidence interval, 1.38-5.84; P = .005), known ischemic vascular disease (HR, 2.03; 95% confidence interval, 1.11-3.70; P = .021), and age (HR, 1.05; 95 confidence interval, 1.02-1.08; P = .002) were predictors of the primary end point. Minimal or minor cTnI elevation (< 0.45 or ≥ 0.45 ng/mL, respectively) showed no differences when associated with the primary end point. The C-statistic demonstrated the significant prognostic value of older age and known ischemic vascular disease, beyond troponin. Clinical parameters inclusive of heart rate, blood pressure, and risk factors for arteriosclerosis showed no relationship with adverse events. Readmission rate did not differ between groups.

Conclusions

In patients with acute AF, minor cTnI elevations link to short-term adverse events. Known ischemic vascular disease and older age showed prognostic value only in the long term.     

P-cresol, a uremic retention solute, alters the endothelial barrier function in vitro

Patients with chronic renal failure (CRF) exhibit endothelial dysfunction, which may involve uremic retention solutes that accumulate in blood and tissues. In this study, we investigated the in vitro effect of the uremic retention solute p-cresol on the barrier function of endothelial cells (HUVEC). P-cresol was tested at concentrations found in CRF patients, and since p-cresol is protein-bound, experiments were performed with and without physiological concentration of human albumin (4 g/dl). With albumin, we showed that p-cresol caused a strong increase in endothelial permeability after a 24-hour exposure. Concomitant with this increase in endothelial permeability, p-cresol induced a reorganization of the actin cytoskeleton and an alteration of adherens junctions. These molecular events were demonstrated by the decreased staining of cortical actin, associated with the formation of stress fibers across the cell, and by the decreased staining of junctional VE-cadherin. This decrease in junctional VE-cadherin staining was not associated with a reduction of membrane expression. Without albumin, the effects of p-cresol were more pronounced.The specific Rho kinase inhibitor, Y-27632, inhibited the effects of p-cresol, indicating that p-cresol mediates the increase in endothelial permeability in a Rho kinase-dependent way. In conclusion, these results show that p-cresol causes a severe dysfunction of endothelial barrier function in vitro and suggest this uremic retention solute may participate in the endothelium dysfunction observed in CRF patients.     

Imaging of bone micro-injuries

PURPOSE: We evaluated the fundamental signs of each imaging modality to define the role of MRI in identifying and characterizing bone micro-injuries. MATERIALS AND METHODS: We retrospectively reviewed 50 MRI examinations performed after preliminary conventional radiography on 25 stress fractures and 25 insufficiency fractures between 1989 and 2002. The number of lesions identified was 55: 11 were evaluated with CT and 9 with radionuclide bone scan. RESULTS: Although bone micro-injuries have different pathogenetic mechanisms, the final outcome is a cortical and/or spongy bone fissure, followed by repair processes. Conventional x-ray showed the presence of a lesion in 24/55 cases. Radionuclide bone scanning allowed suspicion or confirmation of the lesion in 8/9 cases. MR identified the lesion in all cases. CT allowed recognition of the lesion in 10/11 cases. CONCLUSIONS: When a bone micro-injury is suspected following conventional radiography, MRI is the most sensitive and specific modality able to complete the diagnostic work-up.     

Effects of nitroglycerin on forearm haemodynamics in patients with cirrhosis

1. Basal forearm haemodynamics were studied by venous occlusion plethysmography in three groups of subjects: group I, healthy controls, group II, patients with cirrhosis age- and sex-matched with group I, and group III, an older group of patients with cirrhosis. Subsequently, responses to sublingual nitroglycerin were measured in group I and II subjects. 2. Controls responded to nitroglycerin with an increase in venous distensibility; group II patients had higher initial venous distensibility but did not respond to nitroglycerin. No other variables in either group were affected by nitroglycerin. 3. Group II and III patients differed in forearm blood flow and vascular resistance and venous distensibility. A significant inverse correlation was found between age and forearm blood flow (r = 0.57, P less than 0.001) in all patients with cirrhosis. 4. We conclude that (a) venous tone is reduced in cirrhosis, possibly as a result of chronic venodilatation; (b) this venodilatation impedes further dilatory response to a small dose of nitroglycerin; (c) cirrhosis is also associated with age-related decreases in peripheral haemodynamics.     

Decreased entorhinal cortex volumes in schizophrenia

BACKGROUND: The entorhinal cortex is located in the medial temporal lobe and is involved in memory and learning. Previous MRI studies reported conflicting findings in schizophrenia, showing normal or reduced entorhinal size. OBJECTIVES: To explore entorhinal cortex volumes in a large sample of patients with schizophrenia recruited from the geographically defined catchment area of South Verona (i.e. 100,000 inhabitants). We also investigated the size of hippocampus as part of the medial temporal lobe. METHODS: 70 patients with schizophrenia and 77 normal controls underwent a session of MRI (TR=2060 ms, TE=3.9 ms, slice thickness=1.25 mm). Entorhinal and hippocampal volumes were explored using the Brains2 software. RESULTS: A significant group effect was found for total entorhinal cortex but not for hippocampus, with patients suffering from schizophrenia having smaller entorhinal volumes compared to normal subjects (F=6.24, p=0.01), particularly on the right side (F=9.76, p=0.002). Also, the laterality index for entorhinal cortex was higher in normal individuals than in patients with schizophrenia (F=5.45, p=0.02). CONCLUSIONS: Consistent with some of the previous reports, our study confirmed the presence of abnormally decreased entorhinal volumes, particularly on the right side, in a large number of patients with schizophrenia and also found altered asymmetry. This may play a major role in the psychopathology and cognitive disturbances of the disease. Future longitudinal MRI studies including high-risk subjects and drug-free, first-episode patients are crucial to further understand whether entorhinal cortex shrinkage is already present at the onset of the illness or appears as a consequence of the illness.     

Microstructural thalamic changes in schizophrenia: a combined anatomic and diffusion weighted magnetic resonance imaging study

Objective

Several magnetic resonance imaging (MRI) and postmortem studies have supported the role of the thalamus in the pathophysiology of schizophrenia. Interestingly, a recent small diffusion weighted imaging (DWI) study showed abnormal thalamic microstructure in patients with schizophrenia. The objective of our study was to use structural MRI and DWI to explore for the first time both thalamic volumes and integrity in schizophrenia.

Methods

We measured thalamic volumes and apparent diffusion coefficient (ADC) measures bilaterally in 71 patients with schizophrenia, representative of those living in the geographically defined catchment area of South Verona (i.e., 100 000 inhabitants), and 75 individuals without schizophrenia. The presence of the adhesio interthalamica was also detected.

Results

We found no significant differences in thalamus size between patients with schizophrenia and participants in the control group, with only a trend for decreased left volumes. No abnormal frequency of the adhesio interthalamica was found. In contrast, significantly increased thalamic ADC values were shown in schizophrenia patients. Age significantly inversely correlated with thalamic volumes in both groups and correlated positively with posterior ADCs in patients with schizophrenia. No significant associations between clinical variables and either volumes or ADC values were reported.

Conclusion

Widespread altered microstructure integrity and partially preserved thalamus size were found in schizophrenia patients. Therefore, subtle thalamic structural abnormalities are present in schizophrenia, even with maintained volumes. This may result from disruption at the cytoarchitecture level, ultimately supporting corticothalamic misconnection. Future imaging studies should further explore thalamic tissue coherence and its role for cognitive disturbances in patients at high risk for schizophrenia and in first-degree relatives.Medical subject headings: psychotic disorders, magnetic resonance, neurosciences     

Protein-Bound Toxins—Update 2009

Protein-bound uremic retention solutes constitute a group whose common characteristic is their difficult removal by dialysis. In 2003, the EUTox group described 25 protein-bound solutes. They comprised six advanced glycation end products (AGE), four phenols (including p -cresol), six indoles (including indoxylsulfate), two hippurates, three polyamines, and two peptides, homocysteine and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). As then, three new compounds have been added to the list: phenylacetic acid, dinucleoside polyphosphates, and IL-18. During the last years, protein-bound compounds have been identified as some of the main toxins involved in vascular lesions of chronic kidney disease. The removal of these solutes by conventional hemodialysis (HD) is low because only the free fraction of the solute is available for diffusion. The increase in the convective part with hemodiafiltration improves the performance of depuration but convection only applies to the free fraction and its benefit is limited. One possibility to improve the removal of a protein-bound solute would be to stimulate its dissociation from the binding protein. This could be obtained in experiments by setting the dialysate flow rate and the dialyzer mass transfer area coefficient (KoA) at much higher levels than the plasma flow rate, or by adding to the dialysate a sorbent such as activated charcoal or albumin. In the future, specific adsorbents may be developed. Today, the only possibility is to use approaches such as daily HD and long HD which could allow better equilibration between extravascular and vascular compartments and consequently result in greater removal of protein-bound compounds.