Arterial and portal circulation and parenchymal changes in Budd-Chiari syndrome: a study in 17 explanted livers

Hepatic parenchymal changes associated with Budd-Chiari syndrome (BCS) have been tentatively explained by combined arterial and portal perfusion disturbances in addition to the complete occlusion of hepatic veins. The aim of this study was to correlate pretransplant course and vascular imaging with pathologic findings in livers explanted for BCS. Seventeen consecutive white patients who underwent transplantation for severe classic BCS were retrospectively analyzed. Pretransplant course was 1 year or less in 8 patients and more than 1 year in 9 patients. Thrombophilia was found in 16 patients (94%). Imaging showed decreased portal perfusion in 16 patients (94%) and increased arterial perfusion in 9 patients. Histology showed obstructive portal venopathy and nodular regenerative hyperplasia (NRH) aspects in all cases, large regenerative nodules resembling focal nodular hyperplasia (FNH) in 9 cases, and cirrhosis in 2 cases. Patients with increased arterial inflow had large regenerative nodules and a protracted pretransplant course. Patients with acute thrombi in portal veins had parenchymal infarcts (2 cases) and a short pretransplant course. In conclusion, patients with severe BCS have a constant impaired perfusion inflow unrelated to progression of cirrhosis but related to the outcome. An early decrease in portal perfusion is observed in the short term and is responsible for NRH or infarcts if complicated with large thrombi. An increase in arterial perfusion compensates impaired portal flow in chronic BCS. Arterial hyperemia contributes to the development of large regenerative nodules that are FNH-like. This pathologic situation offers an interesting vascular model to further understand the parenchymal response to changes in hepatic blood flow.     

Current outcome of portal vein thrombosis in adults: risk and benefit of anticoagulant therapy

BACKGROUND & AIMS: The outcome of portal vein thrombosis in relation to associated prothrombotic states has not been evaluated. We assessed current outcome and predictors of bleeding and thrombotic events in a cohort of 136 adults with nonmalignant, noncirrhotic portal vein thrombosis, of whom 84 received anticoagulant therapy. METHODS: Multivariate Cox model analysis for event-free survival and analysis taking into account multiple events were used. RESULTS: Median follow-up was 46 months. The incidence rate of gastrointestinal bleeding was 12.5 (95% confidence interval [CI], 10-15) per 100 patient-years. Large varices were an independent predictor for bleeding. Anticoagulant therapy did not increase the risk or the severity of bleeding. The incidence rate of thrombotic events was 5.5 (95% CI, 3.8-7.2) per 100 patient-years. Underlying prothrombotic state and absence of anticoagulant therapy were independent predictors for thrombosis. In patients with underlying prothrombotic state, the incidence rates of splanchnic venous infarction were 0.82 and 5.2 per 100 patient-years in periods with and without anticoagulant therapy, respectively (P = 0.01). Two nonanticoagulated patients died of bleeding and thrombosis, respectively. CONCLUSIONS: In patients with portal vein thrombosis, the risk of thrombosis is currently as clinically significant as the risk of bleeding. The benefit-risk ratio favors anticoagulant therapy.     

Coagulation disorders in patients with cirrhosis and severe sepsis

Background: In patients with cirrhosis, severe sepsis may stimulate the extrinsic coagulation pathway resulting in thrombin generation and fibrin formation. Aims: To compare 23 patients with severe sepsis to 13 infected patients without severe sepsis and 18 patients without infection. Methods: Zymogen forms of clotting factors involved in the extrinsic pathway (i.e., factors VII+X, V, prothrombin), and the presence of soluble fibrin were assessed. Results: Zymogen forms of clotting factors were significantly lower, while Child–Pugh score and the proportion of patients with soluble fibrin were higher in the severe‐sepsis group than in the other groups. Decreased zymogen levels were independently correlated with an elevated Child–Pugh score and the presence of severe sepsis. In the severe‐sepsis group, after adjustment for the severity of cirrhosis, decreased zymogen levels were associated with significant increases in the relative risk ratios of in‐hospital death. Conclusions: Cirrhotic patients with severe sepsis have decreased blood levels of zymogen forms of factors VII+X, V, and prothrombin, which may be due not only to the severity of cirrhosis but also, at least in part, to the consumption of these zymogens by the extrinsic coagulation pathway.     

Effectiveness of Physical Therapy Combined With Epidural Steroid Injection for Individuals With Lumbar Spinal Stenosis: A Randomized Parallel-Group Trial

Objective

To examine the effectiveness of epidural steroid injection (ESI) and back education with and without physical therapy (PT) in individuals with lumbar spinal stenosis (LSS).

Dynamic stiffness and damping of porcine muscle specimens

The aim of this study was to quantify the mechanical properties of the muscles of the buttock, using dynamic compression (5-->30 Hz). Tests were conducted in vitro on porcine muscles, using a lever arm device, which applied a dynamic load onto cylindrical samples. A two-parameter viscoelastic model allowed the calculation of stiffness and damping of the samples with respect to frequency. The average stiffness curve showed a monotonous increase (5 Hz: 8.5 kN/m-->30 Hz: 347 kN/m). Concerning damping, between 5 and 20 Hz, values were typically inferior to 300 Ns/m, which then increased till 30 Hz (556 Ns/m). The lever arm device may be used to evaluate dynamic properties of other biological tissues also.     

Frontal EEG predictors of treatment outcome in major depressive disorder

ObjectiveTo investigate the role of frontal EEG as predictor of clinical response to SSRIs or venlafaxine in major depressive disorder (MDD).Method82 subjects (age 35.9 ± 13.0; 47.6% female) meeting DSM-IV criteria for MDD entered an 8-week prospective treatment with SSRIs or venlafaxine. At baseline and week 1 we recorded serial, 4-channel EEGs (F7-Fpz, F8-Fpz, A1-Fpz, A2-Fpz). We evaluated prospectively the relative theta power as predictor of treatment outcome. We also developed an Antidepressant Treatment Response (ATR) index using EEG parameters assessed at baseline and week 1.Results45 subjects (54.9%) responded to treatment (HAM-D-17 reduction ≥ 50%). At baseline, frontal relative theta power (i.e., 4–8 Hz power/2–20 Hz power) was significantly (p = 0.017) lower (21%) in treatment responders than in non-responders (24%). Baseline relative theta power predicted treatment response with 63% accuracy [64% sensitivity, 62% specificity, 66% area under the receiver operator curve (AUROC) (p = 0.014)]. Relative theta power at week 1 predicted treatment response with 60% accuracy [62% sensitivity, 57% specificity, 61% AUROC (p = 0.089)]. ATR predicted response with 70% accuracy [82% sensitivity, 54% specificity, 72% AUROC (p = 0.001)].ConclusionUsing automated analysis of frontal EEG collected during the first week of antidepressant treatment it may be possible to facilitate prediction of SSRI or venlafaxine efficacy in MDD.     

Pretreatment frontal EEG and changes in suicidal ideation during SSRI treatment in major depressive disorder

Objective: We investigated frontal quantitative EEG (QEEG) as predictor of changes in suicidal ideation (SI) during SSRI treatment in major depressive disorder (MDD). Method: Eighty‐two subjects meeting DSM‐IV criteria for MDD entered an 8‐week, prospective, open‐label treatment with flexible dose SSRIs and completed at least 4 weeks of treatment. We assessed MDD severity with the 17‐item Hamilton Depression Rating Scale (HAM‐D‐17); change in SI was measured with HAM‐D item no. 3. We recorded four‐channel EEGs (F7‐Fpz, F8‐Fpz, A1‐Fpz, A2‐Fpz) before treatment. Results: During the first 4 weeks of treatment 9 (11%) subjects experienced worsening SI. Left‐right asymmetry of combined theta + alpha power correlated significantly with change in SI from baseline, even when adjusting for changes in depression severity (HAM‐D‐17) and for the SSRI utilized. Conclusion: Frontal QEEG parameters before treatment may predict worsening SI during SSRI treatment in MDD.     

Nadroparin-induced skin necrosis then thrombocytosis in intensive care unit: difficulty in diagnosis

Skin necrosis is a rare complication in intensive care unit. A case-report of nadroparine-induced skin necrosis and thrombocytosis in a patient with traumatic paraplegia is reported. This case emphasised the difficulty in diagnosis despite absence of thrombopenia. A skin necrosis could suggest the diagnosis and a substitutive therapy must be administrated after heparin therapy withdrawal. A thrombocytosis is a little reported complication of low-molecular-weight heparins without complication.     

Portal vein thrombosis with ruptured oesophageal varices as presenting manifestation of hereditary protein C deficiency.

The protein C system is essential in limiting the activation of coagulation in vivo. We report the case of a 45 year old man with portal vein thrombosis complicated by ruptured oesophageal varices. Low concentration of plasma protein C was found in the patient and subsequently in one brother with a history of venous thromboembolism, and also in one son and one nephew who were asymptomatic. Hereditary protein C deficiency should be considered in patients with portal hypertension due to portal vein thrombosis.     

Aetiological factors of Budd-Chiari syndrome in Algeria

AIM: To study the clinical presentation of Budd-Chiari syndrome(BCS) and identify the aetiologies of this disease in Algeria. METHODS: Patients with BCS, hospitalised in our unit from January 2004 until June 2010 were included and the aetiological factors were assessed. Patients presenting a BCS in the setting of advanced-stage cirrhosis or a liver transplantation were excluded from the study. The diagnosis was established when an obstruction of hepatic venous outflow(thrombosis, stenosis or compression) was demonstrated. We diagnosed myeloproliferative disease(MPD) by bone marrow biopsy and V617 F JAK2 mutation. Anti-phospholipid syndrome(APLS) was detected by the presence of anticardiolipin antibodies, anti-β2 glycoprotein antibodies and Lupus anticoagulant. We also detected paroxysmal nocturnal haemoglobinuria(PNH) by flow cytometry. Celiac disease and Behcet disease were systematically investigated in our patients. Hereditary anticoagulant protein deficiencies were also assessed. We tested our patients for the G20210 A mutation at Beaujon Hospital. Imaging procedures were performed to determine a local cause of BCS, such as a hydatid cyst or a liver tumour.RESULTS: One hundred and fifteen patients were included. Mean follow up: 32.12 mo. Mean age: 34.41 years, M/F = 0.64. Chronic presentation was frequent:63.5%. The revealing symptoms for the BCS were ascites(74.8%) and abdominal pain(42.6%). The most common site of thrombosis was the hepatic veins(72.2%). Involvement of the inferior vena cava alone was observed in 3 patients. According to the radiological investigations, BCS was primary in 94.7% of the cases(n = 109) and secondary in 5.2%(n = 6). An aetiology was identified in 77.4% of the patients(n = 89); it was multifactorial in 27%(n = 31). The predominant aetiology of BCS in our patients was a myeloproliferative disease, observed in 34.6% of cases. APLS was found in 21.7% and celiac disease in 11.4%. Other acquired conditions were: PNH(n = 4), systemic disease(n = 6) and inflammatory bowel disease(n = 5). Anticoagulant protein deficiency was diagnosed in 28% of the patients(n = 18), dominated by protein C deficiency(n = 13). Secondary BCS was caused by a compressing hydatic cyst(n = 5) and hepatocellular carcinoma(n = 1). CONCLUSION: The main aetiologic factor of BCS in Algeria is MPD. The frequency of celiac disease justifies its consideration when BCS is diagnosed in our region.