Does cytogenetic evolution have any prognostic relevance in myelodysplastic syndromes? A study on 153 patients from a single institution

The present study was designed to establish the incidence of cytogenetic evolution (CE), defined as the acquisition of chromosomal defects during the course of MDS, in order to correlate it with the WHO classification and IPSS score, and to assess its impact on overall survival (OS) and risk of MDS/AML evolution (progression-free interval, PFI) by means of Cox models for time-dependent covariates. Adjustments for known risk factors were achieved by performing a bivariable analysis. The study was carried out in 153 MDS patients who were followed for a median period of 45.2 months. Disease progression occurred in 42.4% of patients after a 65.2-month median PFI, while CE occurred in 30.7% of patients. Our study shows that (1) CE was more common in advanced than in early MDS, and advanced MDS presented secondary chromosomal defects distinct from those of early MDS; (2) CE significantly affected OS and PFI independently of other prognostic variables; (3) del(7)(q31q34) was the only secondary chromosomal defect which significantly affected PFI; trisomy 8 had only a moderate influence.     

The clinical view through the Archives: the clinical notes of 2009

The Clinical Notes published in 2009 serve as a resource to reflect on clinical aspects relevant to different clinical entities. Through this review an attempt is likewise made to bring the reader closer to the clinical reality of our environment.     

Antithrombin Murcia (K241E) causing antithrombin deficiency: a possible role for altered glycosylation

Background

Identification of mutations in the SERPINC1 gene has revealed different mechanisms responsible for antithrombin deficiency. Deletions and nonsense mutations associate with type I deficiency. Certain missense mutations cause type II deficiency by affecting the heparin binding site or the reactive center loop, while others result in type I deficiency by intracellular retention or RNA instability.

Design and Methods

We studied the molecular, biochemical, proteomic and glycomic characterization of a new natural mutant (K241E) that may be classified as pleiotropic.

Results

The mutation caused a significant decrease in the anticoagulant activity mainly due to a reduced heparin affinity and a modification of the electrostatic potential that might explain the impaired ability of the mutant protein to form complexes with the target protease in the absence of heparin. Mass spectrometry and glycomic analyses confirmed an increased molecular weight of 800 Da in the mutant protein possibly due to core-fucosylation, provoking the loss of heparin affinity. Additionally, carriers of this mutation also have a minor mutant isoform that still followed normal glycosylation, retaining similar heparin affinity to wild-type α-antithrombin, and certain anticoagulant activity, which may explain the milder thrombotic risk of patients carrying this mutation. Similar results were observed using recombinant K241E antithrombin molecules.

Conclusions

Our data suggest a new mechanism involved in antithrombin type II deficiency by indirectly affecting the glycosylation of a natural variant. Additional studies are required to confirm this hypothesis.     

Clinical pharmacology of 5-ASA compounds in inflammatory bowel disease

Mesalamine has been the first-line of therapy in patients with inflammatory bowel disease (IBD) since the 1960s. This article serves as a review of the different 5-aminosalicylic acid compounds, release formulations, use and dosing in the treatment of IBD, in particular ulcerative colitis.     

Prospective evaluation of a clinical guideline recommending early patients discharge in bleeding peptic ulcer

Background and Aim: To validate an early discharge policy in patients admitted with upper gastrointestinal bleeding (UGIB) due to ulcers. Methods: Patients with gastroduodenal ulcer or erosive gastritis/duodenitis were included in a previous study aiming to develop a practice guideline for early discharge of patients with UGIB. Variables associated with unfavorable evolution were analyzed in order to identify patients with low‐risk of re‐bleeding. After that, a one‐year prospective analysis of all UGIB episodes was carried out. Results: A total of 341 patients were identified in the retrospective study. Variables associated with unfavorable evolution were: systolic blood pressure ≤ 100 mmHg, heart rate ≥ 100 bpm, and a Forrest endoscopic classification of severe. 10% of patients were immediately discharged; however, if predictive variables obtained in the multivariate analysis had been used, hospitalization could have been prevented in 34% of patients. A total of 77 patients were included in the prospective analysis. Although only 19.5% of patients were immediately discharged without complications, 29 patients (37.7%) were theoretically suitable for early discharge. Conclusions: Patients with UGIB who have clean‐based ulcers and are stable on admission can be safely discharged immediately after endoscopy. Implementation of the clinical practice guideline safely reduced hospital admission for those patients.