Primary brain tumors, both benign and malignant, pose a high risk of perioperative venous thromboembolism (VTE) due to the development of a prothrombotic state. Perioperative pharmacologic ...thromboprophylaxis with subcutaneous (SC) unfractionated heparin (UFH) has significantly reduced VTE associated morbidity. Recent reports suggest an association between prolonged activated partial thromboplastin time (aPTT) due to prophylactic SC UFH and increased bleeding risk. We present three patients with normal baseline coagulation parameters in whom pharmacologic thromboprophylaxis with SC UFH resulted in a marked prolongation of the aPTT, leading to adverse outcomes in two patients. These cases demonstrate the uncertain kinetics of SC UFH and effect on aPTT, suggesting the significance of routine aPTT monitoring in high-risk settings. Given the wide variation in presentations of therapeutic or supratherapeutic values of aPTT in the perioperative neurosurgical setting, we propose a practical standardized approach to the evaluation and management of aPTT prolongation following prophylactic SC UFH administration.
The β-catenin signaling pathway is deregulated in nearly all colon cancers. Nonhypercalcemic vitamin D3 (1α,25-dehydroxyvitamin D3) analogues are candidate drugs to treat this neoplasia. We show that ...these compounds promote the differentiation of human colon carcinoma SW480 cells expressing vitamin D receptors (VDRs) (SW480-ADH) but not that of a malignant subline (SW480-R) or metastasic derivative (SW620) cells lacking VDR. 1α,25(OH)2D3 induced the expression of E-cadherin and other adhesion proteins (occludin, Zonula occludens ZO-1, ZO-2, vinculin) and promoted the translocation of β-catenin, plakoglobin, and ZO-1 from the nucleus to the plasma membrane. Ligand-activated VDR competed with T cell transcription factor (TCF)-4 for β-catenin binding. Accordingly, 1α,25(OH)2D3 repressed β-catenin–TCF-4 transcriptional activity. Moreover, VDR activity was enhanced by ectopic β-catenin and reduced by TCF-4. Also, 1α,25(OH)2D3 inhibited expression of β-catenin–TCF-4-responsive genes, c-myc, peroxisome proliferator-activated receptor δ, Tcf-1, and CD44, whereas it induced expression of ZO-1. Our results show that 1α,25(OH)2D3 induces E-cadherin and modulates β-catenin–TCF-4 target genes in a manner opposite to that of β-catenin, promoting the differentiation of colon carcinoma cells.
To know the overall regional or international scientific production is of vital importance to many areas of knowledge. Nevertheless, in interdisciplinary areas such as Geographic Information Science ...(GISc) it is not enough to just count papers published in specific journals. Most of them, as is the case of the International Journal of Remote Sensing (IJRS), welcome GISc papers but are not exclusive to that area so the production assignable to authors in the region must consider not only affiliation but also whether or not each paper falls into the theme of GISc. IJRS publishes far more papers than any other GISc journal, so it is important to assess quantitatively how many of them are of GISc. In this work, a representative sample of IJRS articles published over a period of almost 30 years was analyzed using a specific GISc definition. With these data, a manual classification methodology through a set of experts was carried out, and a dataset was built, analyzed, and statistically tested. As a result we estimate that between 47 and 76% of the IJRS articles can be considered from GISc, with a confidence level of 95%. Aside from the primary goal, this set could be used as a gold standard for future classification tasks. It constitutes the first GISc dataset of this kind, that may be used to train artificial intelligence systems capable of performing the same classification automatically and in a massive way. A similar procedure could be applied to other interdisciplinary fields of knowledge as well.
: Due to their ease of use, the direct oral anticoagulants (DOACs) are an attractive treatment option for cancer-associated venous thromboembolism (VTE) and have been readily adopted by many ...clinicians. A recent published study comparing a DOAC (edoxaban) to the current standard-of-care low molecular weight heparin dalteparin for the treatment of cancer-associated thrombosis showed that edoxaban was noninferior to dalteparin for recurrent VTE, but the risk of major bleeding was higher. We present three patients with high-risk gastrointestinal malignancies complicated by cancer-associated VTE with progression of thrombosis while treated with the oral direct Xa inhibitor rivaroxaban. Upon switching therapy to low molecular weight heparin, we found that these patients had clinical and radiologic improvement of VTE. More studies are needed to evaluate the efficacy of rivaroxaban in high-risk gastrointestinal-VTE. We suggest that in some patients, DOACs may not be sufficient for the treatment of VTEs related to high-risk gastrointestinal malignancies.
To assess the rate and type of maternal and infant complications among pregnant women receiving low-molecular-weight heparin (LMWH). Retrospective study of pregnant women on LMWH referred to two ...university hematology clinics from January 2001 to December 2010. We recorded the number of pregnancies, indication, dose and dose adjustments for LMWH, pregnancy outcomes (live births, maternal and infant complications) and side effects of LMWH. There were 89 pregnancies in 76 women. The most common indication for LMWH was a history of adverse outcome of pregnancy associated with thrombophilia. LMWH was adjusted in 75 and 45% of pregnancies in women on therapeutic and prophylactic doses, respectively. Live birth rate was 97%. There were 25 maternal and 11 infant complications. Side effects were minimal and included decreased bone mineral density and bleeding. LMWH use among pregnant women is associated with successful pregnancy outcomes. Although side effects were minimal, maternal and infant complications occurred in 28 and 12% of cases, respectively.
Brachytherapy (BT) and external beam radiation therapy (EBRT) are effective treatments for high-risk prostate cancer (PCa). However, the impact of these treatments on health-related quality of life ...(HRQL) remains unclear. In this study, we compared EBRT alone with EBRT plus a boost with high-dose rate (HDR)-BT to determine the impact on HRQL in patients with high-risk PCa.
Prospective, multicenter study comparing patients with high-risk PCa treated with EBRT alone or EBRT + HDR-BT from 2004 to 2006. HRQL was assessed at baseline (pre-treatment) and periodically over the 5-year follow-up, using the SF-36 (v.2), EPIC, and FACT-G and FACT-P questionnaires.
A total of 129 patients were included in the study, of these, 41 received EBRT alone and 88 EBRT + HDR-BT. All patients received hormonotherapy. Baseline clinical characteristics were similar, except for a slightly higher mean number of comorbidities in the EBRT group. During follow-up, the only significant between-group difference was a greater worsening on EPIC hormonal domain in the EBRT alone group (
= 0.028). There were no significant differences in time and interaction of treatment in SF-36, and FACT-G and FACT-P questionnaires or EPIC urinary incontinence, urinary irritative-obstructive, and bowel and sexual domains over the 5-year follow-up. Oncological outcomes were similar in both groups.
After five years of follow-up, EBRT alone or combined with HDR-BT boost had a similar impact on HRQL in patients with high-risk localized PCa. However, patients in the EBRT alone group experienced greater worsening of hormonal domain according to EPIC questionnaire.
Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of ...new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung cancer cell lines.
Expression levels of CB1, CB2, EGFR, CDH1, CDH2 and VIM were evaluated by quantitative reverse transcription-polymerase chain reaction. THC and CBD (10-100 μM), individually or in combination (1:1 ratio), were used for in vitro assays. Cell proliferation was determined by BrdU incorporation assay. Morphological changes in the cells were visualized by phase-contrast and fluorescence microscopy. Migration was studied by scratch recolonization induced by 20 ng/ml epidermal growth factor (EGF).
The tumor samples were classified according to the level of expression of CB1, CB2, or both. Patients with high expression levels of CB1, CB2, and CB1/CB2 showed increased survival reaching significance for CB1 and CB1/CB2 (p = 0.035 and 0.025, respectively). Both cannabinoid agonists inhibited the proliferation and expression of EGFR in lung cancer cells, and CBD potentiated the effect of THC. THC and CBD alone or in combination restored the epithelial phenotype, as evidenced by increased expression of CDH1 and reduced expression of CDH2 and VIM, as well as by fluorescence analysis of cellular cytoskeleton. Finally, both cannabinoids reduced the in vitro migration of the three lung cancer cells lines used.
The expression levels of CB1 and CB2 have a potential use as markers of survival in patients with NSCLC. THC and CBD inhibited the proliferation and expression of EGFR in the lung cancer cells studied. Finally, the THC/CBD combination restored the epithelial phenotype in vitro.
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