Family companions’ involvement during pre-surgical consent visits for major cancer surgery and its relationship to visit communication and satisfaction

Objective

To examine the association between family companion presence during pre-surgical visits to discuss major cancer surgery and patient-provider communication and satisfaction.

Randomized Controlled Trial of Emergency Transjugular Intrahepatic Portosystemic Shunt Versus Emergency Portacaval Shunt Treatment of Acute Bleeding Esophageal Varices in Cirrhosis

Background

Emergency treatment of bleeding esophageal varices (BEV) in cirrhosis is of paramount importance because of the resultant high mortality rate. Emergency therapy today consists mainly of endoscopic and pharmacologic measures, with use of transjugular intrahepatic portosystemic shunt (TIPS) when bleeding is not controlled. Surgical portosystemic shunt has been relegated to last resort salvage when all other measures fail. Regrettably, no randomized controlled trials have been reported in which TIPS and surgical portosystemic shunt were compared in unselected patients with acute BEV, with long-term follow-up. This is a report of a long-term prospective randomized controlled trial (RCT) that compared TIPS with emergency portacaval shunt (EPCS) in patients with cirrhosis and acute BEV.

Study Design

A total of 154 unselected, consecutive cirrhotic patients (??all comers??) with acute BEV were randomized to TIPS (n?=?78) or EPCS (n?=?76), and the two treatments were compared with regard to effect on survival, control of bleeding, portal?Csystemic encephalopathy (PSE), and disability. Diagnostic workup was completed within 6?h and TIPS or EPCS was initiated within 24?h. Regular follow-up was accomplished in 100?% of patients and lasted for 5 to 10?years in 85?% and 3 to 4.5?years in the remainder. This report focuses on control of bleeding and survival.

Results

The clinical characteristics of the two groups were similar, and the distribution of Child classes A, B, and C was almost identical. TIPS was successful in controlling BEV for 30?days in 80?% of patients but achieved long-term control of BEV in only 22?%. In contrast, EPCS controlled BEV immediately in all patients and permanently in 97?% (p?<?0.001). TIPS patients required almost twice as many units of blood transfusion as EPCS patients. Survival rate at all time intervals and in all Child classes was significantly greater following EPCS than after TIPS (p?<?0.001). Median survival was over 10?years following EPCS, compared to 1.99?years following TIPS. Stenosis or occlusion of TIPS was demonstrated in 84?% of patients who survived 21?days, 63?% of whom underwent TIPS revision, which failed in 80?%. In contrast, EPCS remained permanently patent in 97?% of patients. Recurrent PSE was threefold more frequent following TIPS than after EPCS (61 versus 21?%).

Conclusions

EPCS was uniformly effective in the treatment of BEV, while TIPS was disappointing. EPCS accomplished long-term survival while TIPS resulted in a survival rate that was less than one fifth that of EPCS. The results of this RCT in unselected, consecutive patients justify the use of EPCS as a first-line emergency treatment of BEV in cirrhosis (clinicaltrials.gov #NCT00734227).     

Thrombospondin-1 antagonizes nitric oxide-stimulated vascular smooth muscle cell responses

OBJECTIVE: Endothelial-derived nitric oxide (NO), by increasing cGMP, is a major physiological regulator of vascular tone and of vascular smooth muscle cell (VSMC) adhesion, chemotaxis, and proliferation. Thrombospondin-1 is a potent antagonist of NO/cGMP signaling in endothelial cells. Because endothelial and VSMC typically exhibit opposing responses to thrombospondin-1, we examined thrombospondin-1 effects on NO signaling in VSMC. METHODS: Effects of exogenous thrombospondin-1 on human VSMC adhesion, chemotaxis, proliferation, and cGMP signaling were examined. Endogenous thrombospondin-1 function was characterized by comparing NO signaling in VSMC from wild type and thrombospondin-1 null mice. RESULTS: Picomolar concentrations of exogenous thrombospondin-1 prevented adhesive, chemotactic, and proliferative responses of human aortic VSMC stimulated by low dose NO. A recombinant CD36-binding domain of thrombospondin-1 or antibody ligation of CD36 similarly inhibited NO-stimulated VSMC responses. Thrombospondin-1 and CD36 ligation inhibited NO responses in VSMC by preventing cGMP accumulation. Thrombospondin-1 null VSMC responses to NO and cGMP signaling were enhanced relative to wild type murine VSMC. CONCLUSIONS: In the presence of NO, thrombospondin-1 is converted from a weak stimulator to a potent inhibitor of VSMC responses. Both exogenous and endogenous thrombospondin-1 inhibit NO signaling in VSMC. This activity is mediated by the type 1 repeats and utilizes the same CD36-dependent cGMP signaling pathway in endothelial and VSMC.     

Characterization of CD3+ CD4- CD8- (double negative) T cells in patients with systemic lupus erythematosus: production of IL-4

Systemic lupus erythematosus (SLE) is a chronic autoimmune rheumatic disease that may affect every organ or system in the body. We have shown previously that the TCR alphabeta+ subpopulation of CD3+ CD4- CD8-, DN T cells is expanded in patients with SLE and that double negative T cells express increased levels of activation markers compared both with healthy people and with patients with rheumatoid arthritis, (RA) as autoimmune controls. The aim of this study was to characterize these cells in terms of their ability to produce IL4, a Th2 cytokine, both spontaneously and after mitogen stimulation. It was found that a higher percentage of TCR alphabeta+ double negative T cells from patients with SLE contained IL4 constitutively than did the same population of cells from healthy people or from those with RA. After mitogen stimulation, there was no significant difference in the amount of IL4 produced by each of the three groups. Further study of patients producing high levels of IL4 (about one third of the patients) indicated that they had a lower percentage of alphabeta+ T cells in the double negative compartment than did patients with fewer IL4 containing cells.     

Effect of neutralizing antibodies to IL-10 and C5 on the renal damage caused by a pathogenic human anti-dsDNA antibody

OBJECTIVES: There is considerable evidence suggesting that anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies are involved in the pathogenesis of lupus nephritis. It was shown previously using severe combined immune deficient (SCID) mice that when the hybridomas secreting human immunoglobulin G (IgG) anti-dsDNA antibodies, RH14 and DIL-6, were implanted intraperitoneally the antibodies produced by RH14, but not DIL-6, deposited in the kidneys, caused pathological changes in the renal tissues and induced proteinuria. In this study we have further analysed the effect of activated terminal complement proteins and interleukin-10 (IL-10) in the pathogenesis of glomerulonephritis caused by the RH-14. METHODS: SCID mice implanted with RH-14 or DIL-6 cell lines were treated with neutralizing antibodies to IL-10 (mAb B-S10) or anti-complement factor 5 (anti-C5) (mAb BB5.1) intraperitoneally. Control groups received either an isotype control antibody (135.8) or phosphate-buffered saline (PBS). Serum human IgG levels and proteinuria were estimated and the extent of renal involvement was examined by histopathological and electron microscopic techniques. RESULTS: While there was a tendency to reduce proteinuria in the anti-IL-10 injected group the anti-C5 injected group showed a significant reduction in proteinuria (P<0.01) compared with the groups injected with either the control mAb or PBS. There was a considerable reduction in the serum human IgG levels in the anti-IL-10 but not in the anti-C5 treated animals. Both anti-IL-10 and anti-C5 treated groups showed significantly reduced renal impairment as revealed by histopathological examination and proteinuria assessment. CONCLUSION: The findings, while confirming the role of IL-10 and activated terminal complement component in the production of antibody at the cellular level and at the site of glomerular immune deposition in this model, respectively, also suggest the beneficial effect of a combined therapy using both anti-IL-10 and anti-C5 mAb to prevent or reduce the effect of the humoral immune response in lupus disease.     

Anti-dsDNA antibodies: still a useful criterion for patients with systemic lupus erythematosus?

The presence of antibodies to dsDNA has been a criterion for systemic lupus erythematosus (SLE) in each of three attempts to classify the disease that have been undertaken by the American College of Rheumatology. The generally good specificity of the test, the fact that it is widely available and often undertaken by an enzyme linked immunosorbent assay (ELISA) which is relatively cheap and easy to perform have encouraged its continued presence in the list of lupus criteria. The detection of anti-dsDNA antibodies is not, however, straightforward and the real significance of the presence of these antibodies, their true specificity (or otherwise), the question of whether they are truly linked to disease pathogenicity and how accurately they reflect disease activity are all questions that have been posed in the past 20 years.