Increased thrombin generation in splanchnic vein thrombosis is related to the presence of liver cirrhosis and not to the thrombotic event

Introduction

In recent years there have been increasing evidence associating liver disease with hypercoagulability, rather than bleeding. The aim of the study was to evaluate the haemostatic potential in patients with liver disease.

Patients and methods

We measured thrombin generation in the presence and absence of thrombomodulin in patients with portal vein thrombosis (PVT, n = 47), Budd-Chiari syndrome (BCS, n = 15) and cirrhosis (n = 24) and compared the results to those obtained from healthy controls (n = 21). Fifteen patients with PVT and 10 patients with BCS were treated with warfarin and were compared to an equal number of patients with atrial fibrillation matched for prothrombin time-international normalized ratio. We assessed resistance to thrombomodulin by using ratios [marker measured in the presence/absence of thrombomodulin].

Results

There were no differences in thrombin generation between patients on warfarin treatment and their controls. Cirrhotic patients generated more thrombin in the presence of thrombomodulin and exhibited thrombomodulin resistance compared to controls [p = 0.006 for endogenous thrombin potential (ETP) and p < 0.001 for peak thrombin and both ratios ETP and peak] and patients with non-cirrhotic PVT (p = 0.001, p = 0.006, p < 0.001, p < 0.001 for ETP, peak, ratio ETP, ratio peak, respectively). The patients with cirrhotic PVT exhibited higher ETP (p = 0.044) and peak (p = 0.02) in the presence of thrombomodulin than controls, as well as thrombomodulin resistance (ETP and peak ratios: p = 0.001).

Conclusions

Hypercoagulability and thrombomodulin resistance in patients with cirrhosis were independent of the presence of splanchnic vein thrombosis. The hypercoagulability in patients with cirrhotic PVT could have implications for considering longer or more intensive treatment with anticoagulants in this group.     

Associations between oral sugar clearance,dental caries,and related factors among 71-year-olds

Objective. To investigate the associations between oral sugar clearance and the prevalence of dental decay. Material and Methods. A total of 92 (44 F, 48 M) 71-year-old subjects in Göteborg, Sweden were consecutively chosen from a representative cohort study. The subjects were examined for: 1) caries-related status, 2) oral function, 3) salivary conditions, 4) cariogenic micro-organisms, and 5) oral sugar clearance. A factor analysis was used to investigate the possible existence of latent variables within these five areas. The latent variables from the factor analyses were used to study the associations between clearance and caries in multivariate regression models. Results. Only one latent variable relating to oral sugar clearance was found. In the regression model with the latent variable related to oral sugar clearance as a dependent variable and gender plus the latent variables related to oral function and salivary conditions as an independent variable, there were associations with gender and some latent variables reflecting oral function and one reflecting glucose in saliva (R²=0.20/0.17). Three latent variables relating to caries-related status were found and these were associated with the number of teeth, the percentage of filled tooth surfaces, and the percentage of decayed tooth surfaces (DS%). In the regression analysis using the latent variable associated with DS% as a dependent variable, this variable was related to the latent variables of oral sugar clearance and to some reflecting oral function, as well as glucose in saliva (R²=0.28). Conclusions: Oral sugar clearance appears to be independently associated with the prevalence of dental caries in the elderly.     

Late occurring clinical deep vein thrombosis in joint-operated patients

In a prospective study of 4,840 patients, we determined the annual incidence of clinical deep vein thrombosis (DVT) in mobilized, discharged orthopedic-operated "high-risk" patients (hip replacement surgery, knee replacement surgery, nailed hip fracture) and assumed "low-risk" patients (diagnostic knee arthroscopy). In addition, the time from the operation to the time when the patients were readmitted with clinically suspected DVT and the distribution of radiologically-confirmed DVT were recorded. Thromboprophylaxis was routinely given for about 10 days to the high-risk groups during the hospital stay but not to patients undergoing knee arthroscopy. During 9 years, the annual incidence of DVT following major procedures was 2.1% (95% CI 1.6-2.6) vs. 0.6% (95% CI 0.2-1.1) after diagnostic knee arthroscopy. Symptoms appeared, on average, 27 (3-150) days after total hip replacement surgery, 36 (3-150) days after nailed hip fracture, 17 (6-30) days after total knee replacement and 1 (1-6) day after knee arthroscopy. In hip-operated patients, 50% of the DVT's were found in the proximal veins vs. 40% following knee arthroplasty.     

Changes in brain amino acid content induced by hyposmolar stress and energy deprivation

The changes in endogenous amino acids in brain extracellular and intracellular compartments evoked by hyposmotic stress and energy deprivation were compared. Tissue content and release of ten amino acids were measured simultaneously in rat hippocampal slices by means of high performance liquid chromatography Hyposmotic stress induced a large release of taurine (25568 pmol mg-7 protein), and a smaller release of glutamate, accompanied by an inverse change in tissue content. Adding mannitol to correct osmolarity blocked these changes. Energy deprivation caused an increase in the release of all amino acids except glutamine. The release was particularly large for glutamate and GABA (31141 and 13282 pmol mg^–1 respectively). The intracellular concentrations were generally reduced, but the total amount of the released amino acids increased. In contrast to the effect seen during hyposmolar stress, mannitol enhanced the changes due to energy deprivation. The results show that hyposmolar stress and energy deprivation cause different content and release profiles, suggesting that the mechanisms involved in the two situations are either different, or modulated in different ways. The intracellular amino acid depletion seen during energy deprivation shows that increased outward transport is probably a primary eventL, and increased amino acid formation likely secondary to this release. [Neurol Res 1995; 17: 402–408]     

Major depressive disorder and attenuated negative symptoms in a child and adolescent sample with psychosis risk syndrome: the CAPRIS study

Some 70–80% of subjects with psychotic risk syndrome (PRS) have lifetime comorbidity, with depressive disorders being the most common. A high proportion of patients with PRS present nonspecific symptoms which can be confounding factors for diagnosis. Depressive and negative symptoms may be difficult to distinguish and it is important to differentiate them. The aim of this study is to assess the presence of depressive disorder in a child and adolescent sample of PRS and to examine the presence of negative symptoms and detect possible confounding characteristics between them and depressive symptoms. This is a naturalistic multi-site study with subjects who met PRS criteria. A sample of 89 PRS adolescent patients was included. Major depressive disorder (MDD) is the most prevalent comorbid disorder (34.83%). The sample was divided into patients who met criteria for MDD (PRS-MDD, n = 31) and those who did not have this disorder (PRS-ND, n = 44). We obtained significant differences in the attenuated negative symptoms (ANS) between PRS-MDD and PRS-ND (68.18 vs. 90.32%, respectively, p = 0.021). Subjects with MDD presented a higher score in ANS and Hamilton Depression Rating Scale (HDRS). Moreover, we obtained a correlation between negative symptomatology and HDRS score with a higher score on HDRS in subjects with higher negative symptom scores (r = 0.533, p < 0.001). More research is needed to fine tune differentiation between depressive and negative symptoms and learn more about the possible impact of MDD on PRS children and adolescents.

     

Clinical features,exercise hemodynamics,and determinants of left ventricular elevated filling pressure in heart‐transplanted patients

This study aimed to assess clinical, functional, and hemodynamic characteristics of heart‐transplanted (HTX) patients during exercise. We performed comprehensive echocardiographic graft function assessment during invasive hemodynamic semi‐supine exercise test in 57 HTX patients. According to hemodynamics findings, patients were divided into Group A: normal left ventricular (LV) filling pressure (FP): pulmonary capillary wedge pressure (PCWP) <15 mmHg at rest and <25 mmHg at peak exercise, and Group B: elevated LV‐FP: PCWP ≥15 mmHg at rest or ≥25 mmHg at peak exercise. Thirty‐one patients (54%) had normal LV‐FP and 26 patients (46%) had elevated LV‐FP. The latter had higher cumulative rejection burden (P < 0.01) and were more symptomatic (NYHA class >1) (P < 0.05), and cardiac allograft vasculopathy (CAV) was more prevalent (P < 0.05). With exercise, the changes in both left‐ and right‐sided filling pressures were significantly increased, whereas LV longitudinal myocardial deformation was lower (P < 0.05) in patients with elevated LV‐FP than in patients with normal LV‐FP. No between‐group difference was observed for cardiac index or LV ejection fraction (LVEF) during exercise. In conclusion, elevated LV‐FP can be demonstrated in approximately 50% of HTX patients. Patients with elevated LV‐FP have impaired myocardial deformation capacity, higher prevalence of CAV, and higher rejection burden, and were more symptomatic. Exercise test with the assessment of longitudinal myocardial deformation should be considered in routine surveillance of HTX patients as a marker of restrictive filling (ClinicalTrials.gov Identifier: NCT02077764).     

Starring roles for astroglia in barrier pathologies of gut and brain

The gastrointestinal tract is a highly innervated organ and enteric neuropathy is emerging as a central feature of a wide range of gut diseases. Although most considerations of the enteric nervous system have focused on neuronal dysfunction, a large population of astrocyte-like glia populates gut muscle layers and the intestinal mucosa, and mounting new evidence points toward enteric glia as active participants in gut pathology. Similarly, in the central nervous system increasing evidence suggests that dysfunctions of astrocytes play central roles in disease mechanisms. On the basis of the premise that gut-brain disease paradigms may exist, we explore the possibility that enteric glia constitute a previously unrecognized disease target in pathologies associated with intestinal barrier dysfunction, notably inflammatory bowel disease, necrotizing enterocolitis, irritable bowel syndrome, diabetes, autoimmune disease and neurotrophic virus infection of the gut.