ABSTRACT
INTRODUCTION: Patent foramen ovale (PFO) is present in a significant proportion of young patients with stroke of undetermined etiology, but is not always causal. Therefore, classifications (RoPE, PASCAL) have been developed to determine the probability that PFO is the stroke cause. However, the presence of an initial arterial occlusion as a prediction factor was not studied when these classifications were built. Our aim was to evaluate the presence of arterial occlusion in young patients with stroke of undetermined etiology with/without high-risk PFO. METHODS: From a prospectively-built monocentric database, we identified patients aged≥18 to<60-years with strokes of undetermined etiology and complete etiological work-up, including transesophageal echocardiography. We divided patients in two groups: (i) with high-risk PFO [i.e. PFO with large interatrial shunt (>30 microbubbles) or associated with atrial septal aneurysm] and (ii) with low-risk/without PFO. We recorded the presence of arterial occlusion and large vessel occlusion (LVO) in the acute phase. RESULTS: We included 96 patients; 55 (57%) had high-risk PFO. Their median age was 48 (40-52) years, and 28 (29%) were women. The percentages of patients with arterial occlusion and with LVO were lower in the high-risk PFO group than in the low-risk/without PFO group: 11 (20%) versus 19 (46%) (P=0.008), and 5 (9%) versus 15 (37%) (P=0.002), respectively. There was no difference in the median RoPE score between groups (P=0.30). CONCLUSION: The presence of LVO could represent a "red flag" of PFO causality in stroke of undetermined etiology, and could be implemented in future PFO-related stroke classifications.
Subject(s)
Foramen Ovale, Patent , Stroke , Humans , Foramen Ovale, Patent/complications , Foramen Ovale, Patent/epidemiology , Foramen Ovale, Patent/diagnostic imaging , Female , Male , Adult , Middle Aged , Stroke/epidemiology , Stroke/etiology , Risk Factors , Prospective Studies , Young Adult , Echocardiography, Transesophageal , Adolescent , Arterial Occlusive Diseases/etiology , Arterial Occlusive Diseases/epidemiology , Arterial Occlusive Diseases/complicationsABSTRACT
Histone modifications play crucial roles in transcriptional activation, and aberrant epigenetic changes are associated with oncogenesis. Lysine (K) acetyltransferases 5 (TIP60, also known as KAT5) is reportedly implicated in cancer development and maintenance, although its function in lung cancer remains controversial. Here we demonstrate that TIP60 knockdown in non-small cell lung cancer cell lines decreased tumor cell growth, migration, and invasion. Furthermore, analysis of a mouse lung cancer model with lung-specific conditional Tip60 knockout revealed suppressed tumor formation relative to controls, but no apparent effects on normal lung homeostasis. RNA-seq and ChIP-seq analyses of inducible TIP60 knockdown H1975 cells relative to controls revealed transglutaminase enzyme (TGM5) as downstream of TIP60. Investigation of a connectivity map database identified several candidate compounds that decrease TIP60 mRNA, one that suppressed tumor growth in cell culture and in vivo. In addition, TH1834, a TIP60 acetyltransferase inhibitor, showed comparable antitumor effects in cell culture and in vivo. Taken together, suppression of TIP60 activity shows tumor-specific efficacy against lung cancer, with no overt effect on normal tissues. Our work suggests that targeting TIP60 could be a promising approach to treating lung cancer.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Animals , Mice , Carcinogenesis/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Transformation, Neoplastic/genetics , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Lung Neoplasms/genetics , HumansABSTRACT
BACKGROUND AND PURPOSE: The best transportation strategy for patients with suspected large vessel occlusion (LVO) is unknown. Here, we evaluated a new regional strategy of direct transportation to a Comprehensive Stroke Center (CSC) for patients with suspected LVO and low probability of receiving intravenous thrombolysis (IVT) at the nearest Primary Stroke Center (PSC). METHODS: Patients could be directly transported to the CSC (bypass group) if they met our pre-hospital bypass criteria: high LVO probability (i.e., severe hemiplegia) with low IVT probability (contraindications) and/or travel time difference between CSC and PSC<15 minutes. The other patients were transported to the PSC according to a "drip-and-ship" strategy. Treatment time metrics were compared in patients with pre-hospital bypass criteria and confirmed LVO in the bypass and drip-and-ship groups. RESULTS: In the bypass group (n=79), 54/79 (68.3%) patients met the bypass criteria and 29 (36.7%) had confirmed LVO. The positive predictive value of the hemiplegia criterion for LVO detection was 0.49. In the drip-and-ship group (n=457), 92/457 (20.1%) patients with confirmed LVO met our bypass criteria. Among the 121 patients with bypass criteria and confirmed LVO, direct routing decreased the time between symptom discovery and groin puncture by 55 minutes compared with the drip-and-ship strategy (325 vs. 229 minutes, P<0.001), without significantly increasing the time to IVT (P=0.19). CONCLUSIONS: Our regional strategy led to the correct identification of LVO and a significant decrease of the time to mechanical thrombectomy, without increasing the time to IVT, and could be easily implemented in other territories.
Subject(s)
Brain Ischemia , Stroke , Brain Ischemia/diagnosis , Brain Ischemia/drug therapy , Hemiplegia , Humans , Probability , Retrospective Studies , Stroke/diagnosis , Stroke/drug therapy , Thrombectomy , Thrombolytic Therapy , Treatment OutcomeABSTRACT
This exploratory study in the field of nursing informatics examined the usage of information technology, namely on-line access to MEDLINE in clinical setting, by a convenience sample of 121 nurses from a large university hospital. A descriptive correlational design was used. Guided by the conceptual frameword of Nurse-Computer Interaction and based on variables set forth in the Theory of Reasoned Action, the study tested hypotheses regarding attitudinal and normative influences on reported use of on-line bibliographic retrieval systems. It was also hypothesized that using MEDLINE coild increase and improve nurses' adoption of nursing research findings. Multiple regression analyses were conducted on nurses' responses to survey questions to test hypotheses-that those who register more favorable attitudes towards nursing research would have a higher reported use of the MEDLINE system. Findings were significant and supported the hypothesis that nurses' attitudes towards research influenced MEDLINE usage. Findings also indicated that MEDLINE usage was significantly related to nurses' research utilization.