Glioblastoma (GBM), the most common primary brain tumor, is the most aggressive human cancers, with a median survival rate of only 14.6 months. Temozolomide (TMZ) is the frontline chemotherapeutic drug in GBM. Drug resistance is the predominant obstacle in TMZ therapy. Drug resistance occurs via multiple pathways such as DNA mismatch repair and base excision repair systems, by which glioma cells acquire chemoresistance to some extent (5% and 95%, respectively). Histone3 Lysin27 residue-acetylation (H3K27ac) status regulates cis-regulatory elements, which increases the likelihood of gene transcription. Histone deacetylase (HDAC) complex deacetylate lysine residues on core histones, leading to a decrease in gene transcription. In cis-regulatory element regions, complexes with HDAC repress histones by H3K27ac deacetylation. The cis-regulating and three-dimensional transcriptional mechanism is called “super-enhancer”. RET finger protein (RFP) is a protein that is expressed in many kinds of cancer. RFP forms a protein complex with HDAC1. The disruption of the RFP–HDAC1 complex has resulted in increased drug sensitivity in other cancers. We conclude that the downregulation of RFP or the disruption of the RFP/HDAC1 complex leads to an increase in TMZ efficacy in glioblastoma by changing histone modifications which lead to changes in cell division, cell cycle and apoptosis.
This retrospective study was aimed to investigate the association between preoperative left ventricular (LV) cardiac function and the incidence of postoperative pulmonary edema (PE) in patients undergoing carotid endarterectomy (CEA). Most patients undergoing CEA for carotid artery stenosis have concomitant heart diseases, leading to hemodynamic instability that can cause postoperative cardiac complications such as cardiac heart failure. LV diastolic function has recently been recognized as an independent predictor of adverse cardiac events in patients undergoing cardiovascular surgery. We analyzed clinical data from the anesthetic and medical records of 149 consecutive patients who underwent CEA at our university hospital between March 2012 and March 2018. LV systolic and diastolic function were evaluated by ejection fraction and the ratio of LV early diastolic filling velocity to the peak velocity of mitral medial annulus (E/e′). Postoperative PE was diagnosed based on chest X-ray and arterial gas analysis by two independent physicians. Postoperative PE was developed in four patients (2.8%). Patients with postoperative PE were not related to preoperative low ventricular ejection fraction, but had a significantly higher E/e′ ratio than those without PE (P = 0.01). Furthermore, there was an increasing trend of PE according to the E/e′ category. Preoperative LV diastolic function evaluated by E/e′ was associated with the development of postoperative PE in patients who underwent CEA. The results suggest that the evaluation of LV diastolic dysfunction could be possibly useful to predict PE in patients undergoing CEA.
Japan has a rapidly aging population and the application of neuroendovascular therapy (NET) for cerebrovascular diseases among elderly patients has increased, but feasibility and safety of NET for elderly patients are still debated. Therefore, this study aimed to elucidate feasibility and safety of NET by analyzing the Japanese nationwide database, the Japanese Registry of Neuroendovascular Therapy 3 (JR-NET 3). In total, 35,972 patients in the JR-NET 3 were analyzed retrospectively. “Elderly patients” were defined as those aged ≥75 years. Approximately one-quarter of patients who received NET were elderly patients. The proportion of patients with modified Rankin Scale (mRS) 0–2 before treatment and 30 days after NET was significantly low across all diseases in the elderly patients. Technical success rates were generally high across all procedures, but complication rate was significantly higher among elderly patients; ischemic complications were significantly higher with NET for unruptured aneurysms (UA) and carotid artery stenosis (CAS). Multivariate analysis revealed that mRS 0–2 before treatment [odds ratio (OR): 0.56, 95% confidence interval (CI): 0.34–0.94, P = 0.03], middle cerebral artery aneurysm (OR: 0.33, 95% CI: 0.12–0.92, P = 0.04), and complete obliteration (OR: 0.66, 95% CI: 0.44–0.97, P = 0.03) were associated with ischemic complications with NET for UA. Moreover, mRS 0–2 before treatment (OR: 0.55, 95% CI: 0.36–0.86, P < 0.01), high intensity with time-of-flight magnetic resonance angiography (OR: 1.55, 95% CI: 1.03–2.32, P = 0.04), open-cell stent (OR: 2.20, 95% CI: 1.50–3.22, P <0.01) were associated with ischemic complications with NET for CAS. Taken together, our findings indicate that cautious and precise selection of patients suitable for NET is necessary.
Our aim was to clarify the nutritional status and energy intake needed for activities of daily living (ADL) improvement among convalescent stroke patients. This retrospective cohort study of stroke patients used data from the Japan Rehabilitation Nutrition Database. Mean energy intake per ideal body weight was 26 kcal/kg/day at 1 week after hospitalization. Patients were divided into two groups according to energy intake: ≥26 kcal/kg/day (high) and <26 kcal/kg/day (low). ADL was evaluated using Functional Independence Measure (FIM), and nutritional status was evaluated using the mini nutritional assessment short form score. We created an inverse probability weighted (IPW) model using propensity scoring to control and adjust for patient characteristics and confounders at the time of admission. The analysis included 290 patients aged 78.1 ± 7.8 years. There were 165 patients with high energy intake and 125 patients with low energy intake. FIM score was significantly higher in the high group compared with the low group (median 113 vs 71, P <0.001). FIM efficiency was also higher in the high group (median 0.31 vs 0.22, P <0.001). FIM efficiency was significantly higher in the high energy intake group than in the low energy intake group after adjustment by IPW (median 0.31 vs 0.25, P = 0.011). Nutritional status improvement was also higher in the high energy intake group after adjustment by IPW (60.6% vs 45.2%, P <0.001). High energy intake was associated with higher FIM efficiency and nutritional status improvement at discharge among convalescent stroke patients.
Anterior odontoid screw fixation (AOSF) is difficult and challenging to perform in patients with type 2 odontoid fracture with a kyphotic angulation or an anterior down-slope. To demonstrate two surgical techniques to resolve kyphotic angulation or difficult fracture direction issues. Anterior odontoid screw fixation was performed in two patients with type 2 odontoid fracture with a kyphotic angulation or an anterior down-slope. This technique can avoid sternal blocking using a percutaneous vertebroplasty puncture needle, and can reduce the kyphotic angle using a Cobb elevator in patients with type 2 odontoid fractures with a kyphotic angulation or an anterior down-sloped fracture. In both the patients, AOSF was successfully performed and a successful clinical outcome was achieved. The screws were well-maintained with reduced fracture segment and well-preserved, corrected kyphotic angles were achieved, as observed on cervical X-ray 6 months postoperatively. Our technique is a safe and effective method for the treatment of type 2 odontoid fracture with a kyphotic angulation or an anterior down-slope.
In cerebrovascular end-to-side anastomosis, thick, hard donor arteries overlying thin recipient arteries impair the view of the ostium, and may result in occlusion of the anastomosis. To improve the intraoperative view, we modified the stay sutures. After performing standard recipient arteriotomy and placing the first stay suture, we half-tied the second stay suture to leave a loop: half-tied stay suture (HSS). The thread of the HSS was secured with a clip to avoid slippage. For suturing side A, the clip pulling on the HSS was gently moved to the opposite side of side A, i.e. to side B, and the donor artery was revolved by several degrees to side B; the first stay suture was used as the fulcrum. Under the expanded view of the ostium, untied interrupted sutures were placed on side A. Then the donor vessel was revolved to the opposite side and side B was sutured in the same manner. At last, the HSS and all other sutures were tied fully. Our HSS method was used in three adults who underwent superficial temporal- to middle cerebral artery anastomosis despite anticipated poor visibility of the ostium. Compared with the conventional method, the view of the ostium was expanded with less manipulation of the vessel walls. There were no complications, and the anastomosis remained patent in all three patients. This simple modification of the stay sutures reduces the risk of anastomotic occlusion due to iatrogenic vascular damage by excessive manipulation under a restricted view.