Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies

The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens

Tratamiento del síndrome antifosfolípido

The antiphospholipid syndrome (APS) is a disorder of recurrent thrombosis and/or pregnancy loss associated with the presence of antiphospholipid antibodies and persistently positive lupus anticoagulant, anticardiolipin or anti beta2-glycoprotein1. Oral anticoagulants are the best available and most effective treatment for the secondary prevention of recurrent venous or arterial thrombosis. Patients with APS are treated with long-term therapy to prolong the INR to 2.0-3.0. Low-molecular-weight heparin in combination with low-aspirin dose is a reasonable strategy to avoid pregnancy loss in women with this syndrome

Diagnóstico y tratamiento de la trombosis venosa profunda

Deep-vein thrombosis (DVT) is a common condition that can lead to complications such as postphlebitic syndrome, pulmonary embolism and death. Currently, an algorithm strategy combining pretest probability, D-dimer testing and compression ultrasonography imaging allows for safe and convenient estimation of suspected lower-limb thrombosis. The mainstay of treatment is anticoagulation therapy. The use of low-molecular-weight heparin or pentasaccharide (fondaparinux) allows for outpatient management of most patients with DVT. The duration of anticoagulation depends on whether the primary event was idiopathic or secondary to a transient risk factor. Interventions such as thrombolysis and placement of inferior vena cava filter are reserved for special situations

Expansion of CD8+CD57+ T Cells in an Immunocompetent Patient with Acute Toxoplasmosis

CD57+ T cells increase in several viral infections like cytomegalovirus, herpesvirus, parvovirus, HIV and hepatitis C virus and are associated with several clinical conditions related to immune dysfunction and ageing. We report for the first time an expansion of CD8+ CD57+ T cells in a young patient with an acute infection with Toxoplasma gondii. Our report supports the concept that CD8+ CD57+ T cells could be important in the control of chronic phase of intracellular microorganisms and that the high numbers of these cells may reflect the continuing survey of the immune system, searching for parasite proliferation in the tissues

Lexical frequency effects in English and Spanish word misperceptions

When listeners misperceive words in noise, do they report words that are more common? Lexical frequency differences between misperceived and target words in English and Spanish were examined for five masker types. Misperceptions had a higher lexical frequency in the presence of pure energetic maskers, but frequency effects were reduced or absent for informational maskers. The tendency to report more common words increased with the degree of energetic masking, suggesting that uncertainty about segment identity provides a role for lexical frequency. However, acoustic-phonetic information from an informational masker may additionally constrain lexical choice

Cross-accent intelligibility of speech in noise: Long-term familiarity and short-term familiarization

Listeners must cope with a great deal of variability in the speech signal, and thus theories of speech perception must also account for variability, which comes from a number of sources, including variation between accents. It is well-known that there is a processing cost when listening to speech in an accent other than one’s own, but recent work has suggested that this cost is reduced when listening to a familiar accent widely represented in the media, and/or when short amounts of exposure to an accent are provided. Little is known, however, about how these factors (long-term familiarity and short-term familiarization with an accent) interact. The current study tested this interaction by playing listeners difficult-to-segment sentences in noise, before and after a familiarization period where the same sentences were heard in the clear, allowing us to manipulate short-term familiarization. Listeners were speakers of either Glasgow English or Standard Southern British English, and they listened to speech in either their own or the other accent, thereby allowing us to manipulate long-term familiarity. Results suggest that both long-term familiarity and short-term familiarization mitigate the perceptual processing costs of listening to an accent that is not one’s own, but seem not to compensate for them entirely, even when the accent is widely heard in the media

Minimal residual disease negativity by next-generation flow cytometry is associated with improved organ response in AL amyloidosis

Light chain (AL) amyloidosis is caused by a small B-cell clone producing light chains that form amyloid deposits and cause organ dysfunction. Chemotherapy aims at suppressing the production of the toxic light chain (LC) and restore organ function. However, even complete hematologic response (CR), defined as negative serum and urine immunofixation and normalized free LC ratio, does not always translate into organ response. Next-generation flow (NGF) cytometry is used to detect minimal residual disease (MRD) in multiple myeloma. We evaluated MRD by NGF in 92 AL amyloidosis patients in CR. Fifty-four percent had persistent MRD (median 0.03% abnormal plasma cells). There were no differences in baseline clinical variables in patients with or without detectable MRD. Undetectable MRD was associated with higher rates of renal (90% vs 62%, p = 0.006) and cardiac response (95% vs 75%, p = 0.023). Hematologic progression was more frequent in MRD positive (0 vs 25% at 1 year, p = 0.001). Altogether, NGF can detect MRD in approximately half the AL amyloidosis patients in CR, and persistent MRD can explain persistent organ dysfunction. Thus, this study supports testing MRD in CR patients, especially if not accompanied by organ response. In case MRD persists, further treatment could be considered, carefully balancing residual organ damage, patient frailty, and possible toxicity

Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies

Investment in the long-tail of biodiversity data: from local research to global knowledge

In business, the "long-tail economy" refers to a market strategy where the gravity center shifts from a few high-demand products to many, varied products focused on small niches. Commercialization of individually low-demand products can be profitable as long as their production cost is low and, all taken together, they aggregate into a big chunk of the market. Similarly, in the "business" of biodiversity data acquisition, we can find several mainstream products that produce zillions of bits of information every year and account for most of the budget allocated to increase our primary data-based knowledge about Earth's biological diversity. These products play a crucial role in biodiversity research. However, along with these large global projects, there is a constellation of small-scale institutions that work locally, but whose contribution to our understanding of natural processes should not be dismissed. These information datasets can be collectively referred to as the "long-tail biodiversity data"