Scientific-linguistic editing of your manuscripts, before submission to journals or after an
unfavorable peer review. More:
English
Italian
Training in professional, scientific writing: write papers that more effectively communicate your research and your ideas. More:
English
Italian
This is a personal, informal and non-sponsored commentary on papers recently published by the Italian biomedical research community.
The purpose is to draw attention not only to good Italian research,
but also to good scientific reporting and publishing from Italy.
The selection of articles is purely subjective, but your suggestions are welcome. Write to me, Valerie Matarese, at vmatarese@ uptoit.org; copies of non-OA papers are welcome.
This is a free, occasional service of Up To it!
Up To it! Home > Italian biomedical research highlights
Current practice guidelines for unprovoked venous thromboembolism (VTE), i.e. VTE not associated with pregnancy, trauma or certain pathologies, recommend anticoagulation treatment for at least 3 months, while the full duration of treatment depends on the expected risks and benefits. Circulating levels of the fibrin degradation product D-dimer are generally used to predict the chances of recurrent VTE after withdrawal of anticoagulation therapy: high D-dimer levels indicate a high risk of recurrence, while a negative D-dimer result indicates a low (but measurable) risk. To better understand how D-dimer levels change over time in these patients and to determine if a late hypercoagulability state is associated with recurrence, researchers from 15 centers throughout Italy conducted a prospective observational study for the Italian Federation of Anticoagulation Clinics (with direct and indirect support of Instrumentation Laboratory, supplier of D-dimer tests).
The PROLONG II study enrolled 335 adults with a first episode of VTE treated for at least 6 months with warfarin or acenocoumarol. Patients with abnormal D-dimer levels continued treatment, but treatment was stopped in 336 patients with normal levels. Of these, 228 patients were followed with repeated D-dimer testing for up to 13 months. At 90 days, 31 patients (13.8%) had abnormal D-dimer levels and 3 of these (9.7%) had a recurrence (significantly higher than the 2.1% recurrence rate among patients with still normal levels). This trend was observed at some later time points. From these data, the researchers calculated a 7.9 adjusted hazards ratio (95% CI, 2.1-30.0) for VTE recurrence in patients in whom D-dimer levels became abnormal 90 days after discontinuation of anticoagulant treatment. This study illustrates the variable and unpredictable pattern of D-dimer levels over time in patients with a first unprovoked VTE. It concludes with the suggestion that D-dimer testing for 3 months after withdrawal of anticoagulants may help identify patients who will benefit from continued treatment. The study was published in the third issue of the weekly journal Blood (PMID: 19965693), and is one of the 5 freely accessible research articles of this issue. Posted 10 March 2010.
Multiple myeloma (MM) is a lethal malignancy characterized by the clonal expansion of transformed plasma cells. Although patients with MM have functional CD8+ T cells that specifically recognize the transformed plasma cells, they are unable to eradicate the malignant cells. Until now, researchers have been unable to identify any molecular change or functional defect in MM T cells that clearly explained the pathogenetic mechanism of this deadly disease. Researchers from Bari, together with a colleague from Pittsburgh, hypothesized that the pathological changes permitting the progression of MM resided not in the T cells but in the transformed plasma cells, which were somehow able to escape the normal immunosurveillance of T cells. In particular, they sought evidence for defects in the ability of the plasma cells to present tumor antigens for T cell recognition.
To look for alterations in the antigen processing-presenting machinery (APM), the researchers studied samples of CD8+ T cells and plasma cells from patients with MM, patients with MGUS (a premalignant condition that sometimes develops into MM), and healthy controls. They quantified expression levels of 12 APM proteins in plasma cells and looked for variations in the cytotoxicity of T lymphocytes from the different samples. Using fluorescence-activated cell sorting and real-time PCR, they documented significantly different patterns of APM expression in the three groups. Compared to control samples, MM samples had substantially lower levels of proteasome subunits and peptide transporters and higher levels of chaperones; MGUS samples had slightly changed or normal levels. MM CD8+ T cells were less cytotoxic than MGUS CD8+ T cells in assays using autologous transformed plasma cells. Finally, in MGUS patients studied over 24 months, a marker of clinical progression toward MM correlated with changes in APM protein expression. These findings support the researchers' hypothesis that APM defects render transformed plasma cells less susceptible to killing by CD8+ T cells, thereby permitting their clonal expansion. Further research is required to understand the cause of altered APM component expression that allows transformed plasma cells to escape immunosurveillance. The study was prepublished online in December 2009 and will appear in print in the journal Blood (PMID: 20008301) in 2010. Posted 8 January 2010.
© UpTo infotechnologies. All rights reserved.