Predictors of the risk of falls among elderly with chronic atrial fibrillation

OBJECTIVES: Though elderly persons with chronic atrial fibrillation have more comorbidities that could limit indications for the chronic use of anticoagulants, few studies have focused on the risk of falls within this particular group. To evaluate the predictors of the risk of falls among elderly with chronic atrial fibrillation, a cross-sectional, observational study was performed. METHODS: From 295 consecutive patients aged 60 years or older with a history of atrial fibrillation who were enrolled within the last 2 years in the cardiogeriatrics outpatient clinic of the Instituto do Coracao do Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo, 107 took part in this study. Their age was 77.9 +/- 6.4 years, and 62 were female. They were divided into two groups: a) no history of falls in the previous year and b) a history of one or more falls in the previous year. Data regarding the history of falls and social, demographic, anthropometric, and clinical information were collected. Multidimensional assessment instruments and questionnaires were applied. RESULTS: At least one fall was reported in 55 patients (51.4%). Among them, 27 (49.1%) presented recurrent falls, with body lesions in 90.4% and fractures in 9.1% of the cases. Multivariate logistic regression showed that self-reported difficulty maintaining balance, use of amiodarone, and diabetes were independent variables associated with the risk of falls, with a sensitivity of 92.9% and a specificity of 44.9%. CONCLUSION: In a group of elderly patients with chronic atrial fibrillation who were relatively independent and able to attend an outpatient clinic, the occurrence of falls with recurrence and clinical consequences was high. Difficulty maintaining balance, the use of amiodarone and a diagnosis of diabetes mellitus were independent predictors of the risk for falls. Thus, simple clinical data predicted falls better than objective functional tests

IRE1α and IGF signaling predict resistance to an endoplasmic reticulum stress-inducing drug in glioblastoma cells.

To date current therapies of glioblastoma multiforme (GBM) are largely ineffective. The induction of apoptosis by an unresolvable unfolded protein response (UPR) represents a potential new therapeutic strategy. Here we tested 12ADT, a sarcoendoplasmic reticulum Ca2+ ATPase (SERCA) inhibitor, on a panel of unselected patient-derived neurosphere-forming cells and found that GBM cells can be distinguished into "responder" and "non-responder". By RNASeq analysis we found that the non-responder phenotype is significantly linked with the expression of UPR genes, and in particular ERN1 (IRE1) and ATF4. We also identified two additional genes selectively overexpressed among non-responders, IGFBP3 and IGFBP5. CRISPR-mediated deletion of the ERN1, IGFBP3, IGFBP5 signature genes in the U251 human GBM cell line increased responsiveness to 12ADT. Remarkably, >65% of GBM cases in The Cancer Genome Atlas express the non-responder (ERN1, IGFBP3, IGFBP5) gene signature. Thus, elevated levels of IRE1α and IGFBPs predict a poor response to drugs inducing unresolvable UPR and possibly other forms of chemotherapy helping in a better stratification GBM patients

Consistency of aortic distensibility and pulse wave velocity estimates with respect to the Bramwell-Hill theoretical model: a cardiovascular magnetic resonance study

<p>Abstract</p> <p>Background</p> <p>Arterial stiffness is considered as an independent predictor of cardiovascular mortality, and is increasingly used in clinical practice. This study aimed at evaluating the consistency of the automated estimation of regional and local aortic stiffness indices from cardiovascular magnetic resonance (CMR) data.</p> <p>Results</p> <p>Forty-six healthy subjects underwent carotid-femoral pulse wave velocity measurements (<it>CF_PWV</it>) by applanation tonometry and CMR with steady-state free-precession and phase contrast acquisitions at the level of the aortic arch. These data were used for the automated evaluation of the aortic arch pulse wave velocity (<it>Arch_PWV</it>), and the ascending aorta distensibility (<it>AA_Distc, AA_Distb)</it>, which were estimated from ascending aorta strain (<it>AA_Strain</it>) combined with either carotid or brachial pulse pressure. The local ascending aorta pulse wave velocity <it>AA_PWVc </it>and <it>AA_PWVb </it>were estimated respectively from these carotid and brachial derived distensibility indices according to the Bramwell-Hill theoretical model, and were compared with the <it>Arch_PWV</it>. In addition, a reproducibility analysis of <it>AA_PWV </it>measurement and its comparison with the standard <it>CF_PWV </it>was performed. Characterization according to the Bramwell-Hill equation resulted in good correlations between <it>Arch_PWV </it>and both local distensibility indices <it>AA_Distc </it>(r = 0.71, p < 0.001) and <it>AA_Distb </it>(r = 0.60, p < 0.001); and between <it>Arch_PWV </it>and both theoretical local indices <it>AA_PWVc </it>(r = 0.78, p < 0.001) and <it>AA_PWVb </it>(r = 0.78, p < 0.001). Furthermore, the <it>Arch_PWV </it>was well related to <it>CF_PWV </it>(r = 0.69, p < 0.001) and its estimation was highly reproducible (inter-operator variability: 7.1%).</p> <p>Conclusions</p> <p>The present work confirmed the consistency and robustness of the regional index <it>Arch_PWV </it>and the local indices <it>AA_Distc and AA_Distb </it>according to the theoretical model, as well as to the well established measurement of <it>CF_PWV</it>, demonstrating the relevance of the regional and local CMR indices.</p

Dendritic cell-specific delivery of Flt3L by coronavirus vectors secures induction of therapeutic antitumor immunity

Efficacy of antitumor vaccination depends to a large extent on antigen targeting to dendritic cells (DCs). Here, we assessed antitumor immunity induced by attenuated coronavirus vectors which exclusively target DCs in vivo and express either lymphocyte- or DC-activating cytokines in combination with a GFP-tagged model antigen. Tracking of in vivo transduced DCs revealed that vectors encoding for Fms-like tyrosine kinase 3 ligand (Flt3L) exhibited a higher capacity to induce DC maturation compared to vectors delivering IL-2 or IL-15. Moreover, Flt3L vectors more efficiently induced tumor-specific CD8(+) T cells, expanded the epitope repertoire, and provided both prophylactic and therapeutic tumor immunity. In contrast, IL-2- or IL-15-encoding vectors showed a substantially lower efficacy in CD8(+) T cell priming and failed to protect the host once tumors had been established. Thus, specific in vivo targeting of DCs with coronavirus vectors in conjunction with appropriate conditioning of the microenvironment through Flt3L represents an efficient strategy for the generation of therapeutic antitumor immunity