Background
A virtual reality (VR) tour of the operating theatre before anaesthesia could provide a realistic experience for children. This study was designed to determine whether a preoperative VR ...tour could reduce preoperative anxiety in children.
Methods
Children scheduled for elective surgery under general anaesthesia were randomized into a control or VR group. The control group received conventional information regarding anaesthesia and surgery. The VR group watched a 4‐min video showing Pororo, the famous little penguin, visiting the operating theatre and explaining what is in it. The main outcome was preoperative anxiety, assessed using the modified Yale Preoperative Anxiety Scale (m‐YPAS) before entering the operating theatre. Secondary outcomes included induction compliance checklist (ICC) and procedural behaviour rating scale (PBRS) scores during anaesthesia.
Results
A total of 69 children were included in the analysis, 35 in the control group and 34 in the VR group. Demographic data and induction time were similar in the two groups. Children in the VR group had a significantly lower m‐YPAS score than those in the control group (median 31·7 (i.q.r. 23·3–37·9) and 51·7 (28·3–63·3) respectively; P < 0·001). During anaesthesia, the VR group had lower ICC and PBRS scores than the control group.
Conclusion
This preoperative VR tour of the operating theatre was effective in alleviating preoperative anxiety and increasing compliance during induction of anaesthesia in children undergoing elective surgery. Registration number: UMIN000025232 (http://www.umin.ac.jp/ctr).
Reduces anxiety
Manic episodes are one of the major diagnostic symptoms in a spectrum of neuropsychiatric disorders that include schizophrenia, obsessive-compulsive disorder and bipolar disorder (BD). Despite a ...possible association between BD and the gene encoding phospholipase Cγ1 (PLCG1), its etiological basis remains unclear. Here, we report that mice lacking phospholipase Cγ1 (PLCγ1) in the forebrain (Plcg1
; CaMKII) exhibit hyperactivity, decreased anxiety-like behavior, reduced depressive-related behavior, hyperhedonia, hyperphagia, impaired learning and memory and exaggerated startle responses. Inhibitory transmission in hippocampal pyramidal neurons and striatal dopamine receptor D1-expressing neurons of Plcg1-deficient mice was significantly reduced. The decrease in inhibitory transmission is likely due to a reduced number of γ-aminobutyric acid (GABA)-ergic boutons, which may result from impaired localization and/or stabilization of postsynaptic CaMKII (Ca
/calmodulin-dependent protein kinase II) at inhibitory synapses. Moreover, mutant mice display impaired brain-derived neurotrophic factor-tropomyosin receptor kinase B-dependent synaptic plasticity in the hippocampus, which could account for deficits of spatial memory. Lithium and valproate, the drugs presently used to treat mania associated with BD, rescued the hyperactive phenotypes of Plcg1
; CaMKII mice. These findings provide evidence that PLCγ1 is critical for synaptic function and plasticity and that the loss of PLCγ1 from the forebrain results in manic-like behavior.
Summary Objective Hypoxia-inducible factor-2α (HIF-2α) transcriptionally upregulates Nampt in articular chondrocytes. NAMPT, which exhibits nicotinamide phosphoribosyltransferase activity, in turn ...causes osteoarthritis (OA) in mice by stimulating the expression of matrix-degrading enzymes. Here, we sought to elucidate whether HIF-2α activates the NAMPT-NAD+ -SIRT axis in chondrocytes and thereby contributes to the pathogenesis of OA. Methods Assays of NAD levels, SIRT activity, reporter gene activity, mRNA, and protein levels were conducted in primary cultured mouse articular chondrocytes. Experimental OA in mice was induced by intra-articular (IA) injection of adenovirus expressing HIF-2α (Ad- Epas1 ) or NAMPT (Ad- Nampt ). The functions of SIRT in OA were examined by IA co-injection of SIRT inhibitors or adenovirus expressing individual SIRT isoforms or shRNA targeting specific SIRT isoforms. Results HIF-2α activated the NAMPT-NAD+ -SIRT axis in chondrocytes by upregulating NAMPT, which stimulated NAD+ synthesis and thereby activated SIRT family members. The activated NAMPT-SIRT pathway, in turn, promoted HIF-2α protein stability by negatively regulating its hydroxylation and 26S proteasome-mediated degradation, resulting in increased HIF-2α transcriptional activity. Among SIRT family members (SIRT1–7), SIRT2 and SIRT4 were positively associated with HIF-2α stability and transcriptional activity in chondrocytes. This reciprocal regulation was required for the expression of catabolic matrix metalloproteinases (MMP3, MMP12, and MMP13) and OA cartilage destruction caused by IA injection of Ad- Epas1 Ad- Nampt. Conclusion The reciprocal regulation of HIF-2α and the NAMPT-NAD+ -SIRT axis in articular chondrocytes is involved in OA cartilage destruction caused by HIF-2α or NAMPT.
Abstract Purpose The purpose of this study is to evaluate the correlation between lymph node count (LNC) and survival and to evaluate whether lymph node ratio (LNR) which is related to LNC is a ...better predictor of survival for gastric cancer than the N category of UICC/AJCC through a multi-institutional cohort study. Methods The study cohort included 3284 patients from eight institutions. Lower and upper quartiles of LNC were used for comparisons. The cut-off values (0, 0.06, 0.27, and 0.49) for the LNR categories were based on Classification and Regression Trees techniques. Akaike information criteria (AIC) for Cox regression models was used to evaluate goodness of fit between competing predictor variables (LNR vs. N category). Results The 5-year disease-specific survival (DSS) rates of lower and upper quartiles of LNC were 82.2% and 84.8%. In the subgroup analysis of pN category, the upper quartile of LNC showed better survival than the lower quartile in pN2, pN3a, and pN3b subgroups. Regarding LNR, 5-year DSS of LNR 0, 0–0.06, 0.06–0.27, 0.27–0.49, and >0.49 was 95.3%, 88.7%, 70.6%, 42.7%, and 17.2% respectively. Multivariate analysis showed that pT, pN, LNR, residual tumor status, distant metastasis, and tumor differentiation significantly affected survival. The analysis also confirmed superiority of LNR compared with N category in the AIC analysis. Conclusion Higher LNC correlated with better survival in patients with pN2, pN3a, and pN3b gastric cancer. Our data indicate that LNR is a better predictor of survival than N category of UICC/AJCC.
Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to ...be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance.
We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.
Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting.
Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.
Cabozantinib inhibits tyrosine kinases, including vascular endothelial growth factor receptors 1, 2, and 3, MET, and AXL, which are implicated in the progression of hepatocellular carcinoma and the ...development of resistance to sorafenib, the standard initial treatment for advanced disease. This randomized, double-blind, phase 3 trial evaluated cabozantinib as compared with placebo in previously treated patients with advanced hepatocellular carcinoma.
A total of 707 patients were randomly assigned in a 2:1 ratio to receive cabozantinib (60 mg once daily) or matching placebo. Eligible patients had received previous treatment with sorafenib, had disease progression after at least one systemic treatment for hepatocellular carcinoma, and may have received up to two previous systemic regimens for advanced hepatocellular carcinoma. The primary end point was overall survival. Secondary end points were progression-free survival and the objective response rate.
At the second planned interim analysis, the trial showed significantly longer overall survival with cabozantinib than with placebo. Median overall survival was 10.2 months with cabozantinib and 8.0 months with placebo (hazard ratio for death, 0.76; 95% confidence interval CI, 0.63 to 0.92; P=0.005). Median progression-free survival was 5.2 months with cabozantinib and 1.9 months with placebo (hazard ratio for disease progression or death, 0.44; 95% CI, 0.36 to 0.52; P<0.001), and the objective response rates were 4% and less than 1%, respectively (P=0.009). Grade 3 or 4 adverse events occurred in 68% of patients in the cabozantinib group and in 36% in the placebo group. The most common high-grade events were palmar-plantar erythrodysesthesia (17% with cabozantinib vs. 0% with placebo), hypertension (16% vs. 2%), increased aspartate aminotransferase level (12% vs. 7%), fatigue (10% vs. 4%), and diarrhea (10% vs. 2%).
Among patients with previously treated advanced hepatocellular carcinoma, treatment with cabozantinib resulted in longer overall survival and progression-free survival than placebo. The rate of high-grade adverse events in the cabozantinib group was approximately twice that observed in the placebo group. (Funded by Exelixis; CELESTIAL ClinicalTrials.gov number, NCT01908426 .).
In the lungs, parenchymal and vascular remodelling share pathomechanisms that may explain the relatively high prevalence (30-40%) of pulmonary hypertension (PH) in interstitial lung disease (ILD) ...patients. Notably, PH significantly contributes to exercise limitation and dismal prognosis of ILD patients. The absence of specific clinical symptoms commonly leads to delayed diagnosis. Besides clinical judgment and out-of-proportion reduction in diffusing capacity, severe hypoxaemia or exercise oxygen desaturation, echocardiography and biomarkers such as B-type natriuretic peptide (BNP) and N-terminal pro-hormone BNP are potentially helpful tools in identifying PH. However, right heart catheterisation is still necessary to confirm the diagnosis. Management of PH in ILD comprises treatment of the underlying disease process and long-term oxygen therapy. Affected patients should be listed for lung transplantation without delay, when appropriate. However, due to age and comorbidities only a minority of ILD patients will be eligible for lung transplantation. In the absence of satisfactory therapies for many ILDs, and considering the clinical burden of PH in affected patients, specific vasomodulatory therapies presently approved for PAH may be promising options for ILD patients. Consequently, there is an urgent need for adequately designed clinical trials to assess the effectiveness of specific PH therapy in the context of ILDs.
PDF
