Clinical outcome and predictors of survival after TIPS insertion in patients with liver cirrhosis

AIM:To determine the clinical outcome and predictors of survival after transjugular intrahepatic portosystemic stent shunt (TIPS) implantation in cirrhotic patients. METHODS:Eighty-one patients with liver cirrhosis and consequential portal hypertension had TIPS implantation (bare metal) for either refractory ascites (RA) (n= 27) or variceal bleeding (VB) (n = 54). Endpoints for the study were:technical success, stent occlusion and stent stenosis, rebleeding, RA and mortality. Clinical records of patients were collected and analysed. Baseline characteristics [e.g., age, sex, CHILD score and the model for end-stage liver disease score (MELD score), underlying disease] were retrieved. The Kaplan-Meier method was employed to calculate survival from the time of TIPS implantation and comparisons were made by log rank test. A multivariate analysis of factors influencing survival was carried out using the Cox proportional hazards regression model. Results were expressed as medians and ranges. Comparisons between groups were performed by using the Mann-Whitney Utest and the χ 2 test as appropriate. RESULTS:No difference could be seen in terms of age, sex, underlying disease or degree of portal pressure gradient (PPG) reduction between the ascites and the bleeding group. The PPG significantly decreased from 23.4 ± 5.3 mmHg (VB) vs 22.1 ± 5.5 mmHg (RA) before TIPS to 11.8 ± 4.0 vs 11.7 ± 4.2 after TIPS implantation (P = 0.001 within each group). There was a tendency towards more patients with stage CHILD A in the bleeding group compared to the ascites group (24 vs 6, P = 0.052). The median survival for the ascites group was 29 mo compared to 60 mo for the bleeding group (P = 0.009). The number of radiological controls for stent patency was 6.3 for bleeders and 3.8 for ascites patients (P = 0.029). Kaplan-Meier calculation indicated that stent occlusion at first control (P = 0.027), ascites prior to TIPS implantation (P = 0.009), CHILD stage (P = 0.013), MELD score (P = 0.001) and those patients not having undergone liver transplantation (P = 0.024) were significant predictors of survival. In the Cox regression model, stent occlusion (P = 0.022), RA (P = 0.043), CHILD stage (P = 0.015) and MELD score (P = 0.004) turned out to be independent prognostic factors of survival. The anticoagulation management (P = 0.097), the porto-systemic pressure gradient (P= 0.460) and rebleeding episodes (P = 0.765) had no significant effect on the overall survival. CONCLUSION:RA, stent occlusion, initial CHILD stage and MELD score are independent predictors of survival in patients with TIPS, speaking for a close follow-up in these circumstances.     

Possible role of glial cells in the onset and progression of Lyme neuroborreliosis

Background  

Lyme neuroborreliosis (LNB) may present as meningitis, cranial neuropathy, acute radiculoneuropathy or, rarely, as encephalomyelitis. We hypothesized that glia, upon exposure to Borrelia burgdorferi, the Lyme disease agent, produce inflammatory mediators that promote the acute cellular infiltration of early LNB. This inflammatory context could potentiate glial and neuronal apoptosis.     

Extracorporeal membrane oxygenation in adult patients with hematologic malignancies and severe acute respiratory failure

Introduction

Acute respiratory failure (ARF) is the main reason for intensive care unit (ICU) admissions in patients with hematologic malignancies (HMs). We report the first series of adult patients with ARF and HMs treated with extracorporeal membrane oxygenation (ECMO).

Methods

This is a retrospective cohort study of 14 patients with HMs (aggressive non-Hodgkin lymphoma (NHL) n = 5; highly aggressive NHL, that is acute lymphoblastic leukemia or Burkitt lymphoma, n = 5; Hodgkin lymphoma, n = 2; acute myeloid leukemia, n = 1; multiple myeloma, n = 1) receiving ECMO support because of ARF (all data as medians and interquartile ranges; age, 32 years (22 to 51 years); simplified acute physiology score II (SAPS II): 51 (42 to 65)). Etiology of ARF was pneumonia (n = 10), thoracic manifestation of NHL (n = 2), sepsis of nonpulmonary origin (n = 1), and transfusion-related acute lung injury (n = 1). Diagnosis of HM was established during ECMO in four patients, and five first received (immuno-) chemotherapy on ECMO.

Results

Before ECMO, the PaO₂/FiO₂ ratio was 60 (53 to 65), (3.3 to 3.7). Three patients received venoarterial ECMO because of acute circulatory failure in addition to ARF; all other patients received venovenous ECMO. All patients needed vasopressors, and five needed hemofiltration. Thrombocytopenia occurred in all patients (lowest platelet count was 20 (11 to 21) G/L). Five major bleeding events were noted. ECMO duration was 8.5 (4 to 16) days. ICU and hospital survival was 50%. All survivors were alive at follow-up (36 (10 to 58) months); five patients were in complete remission, one in partial remission, and one had relapsed.

Conclusions

ECMO therapy is feasible in selected patients with HMs and ARF and can be associated with long-term disease-free survival.     

IL-22 and IL-20 are key mediators of the epidermal alterations in psoriasis while IL-17 and IFN-γ are not

Psoriasis is a common chronic skin disease with a largely unknown pathogenesis. We demonstrate here that transgenic over-expression of interleukin (IL)-22 in mice resulted in neonatal mortality and psoriasis-like skin alterations including acanthosis and hypogranularity. This cutaneous phenotype may be caused by the direct influence of IL-22 on keratinocytes, since this cytokine did not affect skin fibroblasts, endothelial cells, melanocytes, or adipocytes. The comparison of cytokines with hypothesized roles in psoriasis pathogenesis determined that neither interferon (IFN)-γ nor IL-17, but only IL-22 and, with lower potency, IL-20 caused psoriasis-like morphological changes in a three-dimensional human epidermis model. These changes were associated with inhibited keratinocyte terminal differentiation and with STAT3 upregulation. The IL-22 effect on differentiation-regulating genes was STAT3-dependent. In contrast to IL-22 and IL-20, IFN-γ and IL-17 strongly induced T-cell and neutrophilic granulocyte-attracting chemokines, respectively. Tumor necrosis factor-α potently induced diverse chemokines and additionally enhanced the expression of IL-22 receptor pathway elements and amplified some IL-22 effects. This study suggests that different cytokines are players in the psoriasis pathogenesis although only the IL-10 family members IL-22 and IL-20 directly cause the characteristic epidermal alterations. Kerstin Wolk and Harald S. Haugen equally contributed to this work.     

Percutaneous approaches to valvular heart disease

Percutaneous endovascular therapy has now become a reality. From early balloon valvotomy for valvular stenosis, technologies have been developed that allow percutaneous replacement of pulmonic and aortic valves and repair of regurgitant mitral valves in selected patients. Following extensive investigations in animals, early clinical reports have shown successes in selected patients. As criteria for patient selection and clinical safety and efficacy trials progress, the role of these new technologies in patient care strategy will become better understood.     

Uptake and presentation of hepatitis C virus-like particles by human dendritic cells

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Interaction of dendritic cells (DCs) with viral particles may play an important role in the immunopathogenesis of HCV infection. Since the synthesis or purification of infectious virions is limited, we used HCV-like particles (HCV-LPs) to study the interaction of HCV with human DCs. Immature DCs exhibited an envelope-specific and saturable binding of HCV-LPs, indicating receptor-mediated DC-HCV-LP interaction. Confocal microscopy revealed that HCV-LPs were rapidly taken up by DCs in a temperature-dependent manner. Competition experiments demonstrated that C-type lectins such as mannose receptor or DC-SIGN (DC-specific intercellular adhesion molecule 3-grabbing nonintegrin) were not sufficient for mediating HCV-LP binding. HCV-LP uptake was followed by DC activation. DCs pulsed with HCV-LPs stimulated HCV core-specific CD4(+) T cells, indicating that uptake of HCV-LPs by DCs leads to antigen processing and presentation on major histocompatibility complex (MHC) class II molecules. Finally, HCV-LP-derived antigens were efficiently cross-presented to HCV core-specific CD8(+) T cells. These findings demonstrate that HCV-LPs represent a novel model system to study HCV-DC interaction allowing definition of the molecular mechanisms of HCV uptake, DC activation, and antigen presentation to T cells. Furthermore, HCV-LP-mediated DC activation and efficient antigen presentation may explain the marked immunogenicity of HCV-LPs in vivo.     

Viral safety of a pasteurized, monoclonal antibody-purified factor VIII concentrate in previously untreated haemophilia A patients

The efficacy and viral safety of a pasteurized, immunoaffinity-purified procoagulant factor VIII protein (FVIII:C; Monoclate-P) was studied in two multicentre, prospective, open-label trials in 30 previously untreated patients, 18 with severe (< 1% FVIII:C activity), and 12 with moderate (1% to 5% FVIII:C activity) haemophilia A. Clinical assessments, performed at screening and regularly thereafter for 6 to > 24 months (maximum 34 months), showed that none of 24 assessable patients acquired illnesses consistent with monitored transfusion-transmissible diseases. No patients acquired hepatitis B surface antigen, or antibodies against hepatitis B core antigen, hepatitis C, or human immunodeficiency virus. Likewise, no patients acquired treatment-related hepatitis A antibodies or sustained elevations of alanine aminotransferase levels. The safety profile for Monoclate-P is brought about by a multi-step safety system that incorporates viral inactivation (through a combination of immunoaffinity chromatography and pasteurization) plus donor screening, plasma testing, and quality assurance. The inhibitor development rate (13% low titre, 10% high titre) was similar to that reported in the literature for other FVIII concentrates (24% to 52%). The most frequently reported adverse events were related to typical infant and childhood diseases. Monoclate-P was effective in all patients treated according to protocol, except in two, who developed inhibitors.