British Hospital

About: British Hospital is a healthcare organization based out in Montevideo, Uruguay. It is known for research contribution in the topics: Population & Lung cancer. The organization has 445 authors who have published 358 publications receiving 7878 citations. The organization is also known as: British Hospital.

Prognostic and Predictive Impact of Primary Tumor Sidedness for Previously Untreated Advanced Colorectal Cancer.

Abstract: Background Unplanned subgroup analyses from several studies have suggested primary tumor sidedness (PTS) as a potential prognostic and predictive parameter in metastatic colorectal cancer (mCRC). We aimed to investigate the impact of PTS on outcomes of mCRC patients. Methods PTS data of 9,277 mCRC patients from 12 first-line randomized trials in the ARCAD database were pooled. Overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier and Cox models adjusting for age, sex, performance status, prior radiation/chemo, and stratified by treatment arm. Predictive value was tested by interaction term between PTS and treatment (cetuximab plus chemotherapy vs. chemotherapy alone). All statistical tests were 2-sided. Results Compared to right-sided metastatic colorectal cancer patients (n = 2421, 26.1%), left-sided metastatic colorectal cancer patients (n = 6856, 73.9%) had better OS (median = 21.6 v 15.9 months; adjusted hazard ratio [HRadj] = 0.71, 95% confidence interval [CI] = 0.67–0.76, P<.001) and PFS (median = 8.6 v 7.5 months; HRadj = 0.80, 95% CI = 0.75–0.84, P<.001). Interaction between PTS and KRAS mutation was statistically significant (Pinteraction<.001): left-sidedness was associated with better prognosis among KRAS wild-type (WT) (OS HRadj = 0.59, 95% CI = 0.53–0.66; PFS HRadj =0.68, 95% CI = 0.61–0.75), but not among KRAS mutated tumors. Among KRAS-WT tumors, survival benefit from anti-EGFR was confirmed for left-sidedness (OS HRadj = 0.85, 95% CI = 0.75–0.97, P = .01; PFS HRadj = 0.77, 95% CI = 0.67–0.88, P<.001), but not for right-sidedness. Conclusions The prognostic value of PTS is restricted to the KRAS-WT population. PTS is predictive of anti-EGFR efficacy, with a statistically significant improvement of survival for left-sidedness mCRC patients. These results suggest treatment choice in mCRC should be based on both PTS and KRAS status.

Plasminogen activator inhibitor-1 activity and 4G/5G polymorphism in hemodialysis.

Abstract: Introduction: Chronic insufficiency alters homeostasis, in part due to endothelial inflammation. Plasmi- nogen activator inhibitor-1 (PAI-1) is increased in renal disease, contributing to vascular damage. We assessed PAI- 1 activity and PAI-1 4G/5G polymorphism in hemodialysis (HD) subjects and any association between thrombotic vascular access (VA) events and PAI-1 polymorphism. Methods: Prospective, observational study in 36 HD patients: mean age: 66.6 ± 12.5 yr, males n=26 (72%), time on HD: 28.71 ± 22.45 months. Vascular accesses: 10 polytetrafluoroethylene grafts (PTFEG), 22 arteriovenous fistu- lae (AVF), four dual lumen catheters (CAT). Control group (CG): 40 subjects; mean age: 60.0 ± 15 yrs, males n=30 (75%). Group A (GA): thrombotic events (n=12), and group B (GB): No events (n=24). Groups were no different according to age (69.2 ± 9.12 vs. 65.3 ± 14.5 yrs), gender (males: 7; 58.3% vs. 18; 81.8%), time on HD (26.1 ± 14.7 vs. 30.1 ± 38.7 months), causes of renal failure. Time to follow-up for access thrombosis: 12 months. Results: PAI-1 levels in HD: 7.21 ± 2.13 vs. CG: 0.42 ± 0.27 U/ml (p<0.0001). PAI-1 4G/5G polymorphic variant di- stribution in HD: 5G/5G: 6 (17%), 4G/5G: 23 (64%); 4G/4G: 7 (19%) and in CG: 5G/5G: 14 (35%); 4G/5G: 18 (45%); 4G/4G: 8 (20%). C-reactive protein (CRP) in HD: 24.5 ± 15.2 mg/L vs. in CG 2.3 ± 0.2 mg/L (p<0.0001). PAI-1 4G/5G variants: GA: 5G/5G: 3; 4G/5G: 8; 4G/4G: 1; GB: 5G/5G: 3; 4G/5G: 15; 4G/4G: 6. Thrombosis occurred in 8/10 patients (80%) with PTFEG, 3/22 (9%) in AVF, and 1/4 (25%) in CAT. Among the eight PTFEG patients with thrombosis, seven were PAI 4G/5G. Conclusions: PAI-1 levels were elevated in HD patients, independent of their polymorphic variants, 4G/5G being the most prevalent variant. Our data suggest that in patients with PTFEG the 4G/5G variant might be associated with an increased thrombosis risk. (J Vasc Access 2008; 9: 142-7)