A comparison of the semiflexed (MTP) view with the standing extended view (SEV) in the radiographic assessment of knee osteoarthritis in a busy routine X-ray department

Objective. To compare the reproducibility of the standing extendedview (SEV) (also known as the standing anteroposterior view)with the semiflexed, postero-anterior view [the ‘metatarsophalangeal’(MTP)] view for assessing joint space width (JSW) and osteophytesin osteoarthritis of the knee when used in a busy routine X-raydepartment. Methods. Forty-seven patients (24 men) had both SEV and MTPviews taken on the same day in a busy National Health Serviceradiography department. Repeat views were taken as entirelyseparate procedures some time over the following 2 weeks, inthe same department and with no special arrangements for theselection of radiographers, time of day, or X-ray machine. Thefirst 24 patients had second views in the SEV position whilstthe remaining 23 had second MTP views. Radiographs were readindependently by two experienced observers who measured JSWwith a transparent ruler to the nearest 0.5 mm at the narrowestpoint in both medial and lateral compartments of the tibiofemoraljoint in both knees. Osteophytes were graded 0–2 accordingto a standard atlas. Ten SEV and 10 MTP radiographs selectedrandomly were re-read by one observer. Results. Mean (95% confidence interval) JSW in the medial compartmentmeasured on SEV radiographs was 3.54 mm (3.08, 3.99) and onMTP radiographs it was 2.80 mm (2.37, 3.23); in the lateralcompartment it was 6.04 mm (5.71, 6.37) when measured on SEVradiographs and 5.47 mm (5.09, 5.85) on MTP radiographs. Theestimated variances for the medial compartment were 2.0 mm²for SEV and 0.2 mm² for MTP (P<0.001) and for the lateralcompartment 1.4 mm² for SEV and 0.5 mm² for MTP (P<0.001).The proportion of radiographs for which there was disagreementbetween observers regarding osteophyte grade was not statisticallydifferent between SEV and MTP views (SEV, medial 40%, lateral44%; MTP, medial 39%, lateral 39%). Conclusions. Even when radiographs are taken in a busy NationalHealth Service radiography department, measurement of JSW fromthe MTP view is more reproducible than from the SEV view, theMTP view gives a slightly lower measurement of JSW, and thereis no advantage in using either view in recording osteophytegrade. We recommend the wider adoption of the MTP method. KEY WORDS: Osteoarthritis, Knee, Joint space width, X-ray     

Impact of device-host interaction on paravalvular aortic regurgitation with different transcatheter heart valves

Aims

We sought to evaluate the interaction of different aortic root phenotypes with self-expanding (SEV), balloon-expandable (BEV) and mechanically expanded (MEV) and the impact on significant aortic regurgitation.

Implications of Transcatheter Heart Valve Selection on Early and Late Pacemaker Rate and on Length of Stay

Background

Transcatheter aortic valve replacement (TAVR) can cause injury to the atrioventricular conduction system. We evaluated the effect of transcatheter heart valve (THV) type on the rate of new pacemaker implantation and length of hospital stay.

Prosthesis-Patient Mismatch Following Transcatheter Aortic Valve Replacement With Supra-Annular and Intra-Annular Prostheses

ObjectivesThis study sought to compare the frequency of prosthesis-patient mismatch (PPM) with self-expandable valves (SEV) to balloon-expandable valves (BEV).BackgroundPPM has been associated with increased mortality after transcatheter aortic valve replacement. Data on the frequency of PPM as a function of supra-annular or intra-annular position of transcatheter heart valves are insufficient.MethodsA total of 757 patients treated with SEV (CoreValve, Evolut R) and BEV (SAPIEN THV/XT/3) were enrolled in the present analysis between August 2007 and June 2017. PPM was classified based on discharge prosthetic effective orifice area indexed to body surface area (BSA) as severe (<0.65 cm²/m²) or moderate (0.65 to 0.85 cm²/m²) in the general population, and as severe (<0.60 cm²/m²) or moderate (0.60 to 0.90 cm²/m²) in the obese population (body mass index ≥30 kg/m²).ResultsPropensity score matching resulted in 224 matched pairs. At discharge, SEV were associated with a lower incidence of PPM compared with BEV (PPM, 33.5% vs. 46.9%; p = 0.004; severe PPM, 6.7% vs. 15.6%; p = 0.003). The lower frequency of severe PPM in SEV was observed even in patients with larger annulus. Although patients with BSA >1.83 m² had a significantly lower incidence of PPM with SEV compared with BEV, there was no significant difference in patients with BSA ≤1.83 m². We found no impact of PPM on cardiovascular mortality or New York Heart Association functional class at 1 year.ConclusionsSEV were associated with a lower frequency of PPM compared with BEV irrespective of annulus area. The difference was mainly driven by larger patients with BSA >1.83 m².     

Effect of pharmacological preconditioning with sevoflurane during hepatectomy with intermittent portal triad clamping

BackgroundDuring hepatectomy, intermittent portal triad clamping (IPC) reduces ischemia-reperfusion injuries. Pharmacological preconditioning with sevoflurane revealed similar properties. The aim of the study was to evaluate the combination of a sevoflurane preconditioning regimen with IPC on ischemia-reperfusion injuries.MethodsThree regimens of anesthesia were applied: group SEV with continuous application of sevoflurane, group PRO with continuous propofol infusion and group PC where continuous propofol was substituted by sevoflurane (adjusted to reach MAC11.5) for 15 min before IPC. Endpoints were the values of AST and ALT, factor V, prothrombin time, bilirubinemia over the 5-postoperative days (POD), morbidity and mortality at POD30 and POD90.ResultsThe ALT values at POD5 were lower in the PC group (n = 27) 74 (48 –98) IU/L compared to PRO (n = 26) and SEV (n = 67) respectively 110 (75 –152) and 100 (64 –168) IU/L (p = 0.038). The variation of factor V compared to preoperative values was less important in the PC and SEV groups respectively −14% and −16% vs −30% (PRO) (p = 0.047).ConclusionOur study suggests that sevoflurane attenuates ischemia-reperfusion injuries on liver function, compared to propofol, without benefit for a specific regimen of pharmacological preconditioning when IPC is applied.     

人胶质瘤细胞及组织中miRNA-221、miRNA-222表达变化及意义

目的观察人胶质瘤细胞及组织中miRNA-221、miRNA-222的表达变化,探讨其与肿瘤放射敏感性的相关性。方法根据Trizol试剂盒说明书,从体外培养的人胶质瘤细胞系U87、U251、A172、LN229和60例胶质瘤组织(手术切除获得)中提取其总RNA,采用RT-PCR法测定miRNA-221及miRNA-222,以正常脑组织为对照。60例胶质瘤患者术后均予以放疗,治疗后MRI检查随访,分析胶质瘤患者的放疗疗效。采用克隆形成实验测算X线照射后(照射剂量为2 Gy)的胶质瘤细胞存活率(SF),以胃黏膜上皮细胞(ges)为对照。结果与对照组织及细胞相比,胶质瘤组织及细胞中miRNA-221、miRNA-222呈高表达(P<0.05),其中高度恶性胶质瘤组织中miRNA-221、miRNA-222均明显高于低度恶性者(P<0.05)。X线照射后胶质瘤细胞SF明显高于ges(P均<0.05),胶质瘤各细胞中miRNA-221、miRNA-222表达量与X线照射后胶质瘤SF呈正相关(r=0.673、0.696,P均<0.01)。胶质瘤组织中miRNA-221、miRNA-222高表达的患者较低表达者生存时间短(P均<0.05)。结论人胶质瘤细胞及组织中miRNA-221、miRNA-222均呈高表达。miRNA-221、miRNA-222表达量与胶质瘤细胞的放射抗性呈正相关关系,胶质瘤组织中miRNA-221、miRNA-222表达量与患者生存时间呈负相关关系。     

Sevoflurane impedes glioma progression via regulating circ_0000215/miR-1200/NCR3LG1 axis

Sevoflurane has been reported to have anti-tumorigenic effects in glioma. Circ_0000215 was found to play vital functions in the pathological progressions of glioma. However, whether circ_0000215 mediates the inhibitory effects of sevoflurane on glioma cells remains unclear. In vitro assays were performed using cell counting kit-8, flow cytometry, transwell and Western blot assays. The expression levels of circ_0000215, microRNA (miR)-1200 and NCR3LG1 (Natural Killer Cell Cytotoxicity Receptor 3 Ligand 1) were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and/or Western blot. The dual-luciferase reporter assay and pull-down assay were used to investigate the relationship between miR-1200 and circ_0000215 or NCR3LG1. In vivo assay was conducted using xenograft nude mice model. In vitro assays suggested that sevoflurane repressed glioma cell proliferation, metastasis and induced apoptosis as well as hindered tumor growth in vivo, which were reversed by circ_0000215 overexpression. Mechanically, circ_0000215 was confirmed to directly target miR-1200, and NCR3LG1 was a target of miR-1200 in glioma cells. Importantly, circ_0000215 could regulate NCR3LG1 expression via miR-1200. Besides that, rescue assay suggested that circ_0000215 attenuated the inhibitory effects of sevoflurane on glioma cell growth and metastasis, which were reversed by miR-1200 overexpression or NCR3LG1 knockdown. Our study revealed that sevoflurane could suppress glioma tumorigenesis by regulating circ_0000215/miR-1200/NCR3LG1 axis, suggesting a new insight into the therapeutic potential of sevoflurane in glioma treatment.

     

Impact of Anesthesia Strategy and Valve Type on Clinical Outcomes After Transcatheter Aortic Valve Replacement

BackgroundThe randomized SOLVE-TAVI (compariSon of secOnd-generation seLf-expandable vs. balloon-expandable Valves and gEneral vs. local anesthesia in Transcatheter Aortic Valve Implantation) trial compared newer-generation self-expanding valves (SEV) and balloon-expandable valves (BEV) as well as local anesthesia with conscious sedation (CS) and general anesthesia (GA) in patients undergoing transfemoral transcatheter aortic valve replacement (TAVR). Both strategies showed similar outcomes at 30 days.ObjectivesThe purpose of this study was to compare clinical outcomes during 1-year follow-up in the randomized SOLVE-TAVI trial.MethodsUsing a 2 × 2 factorial design 447 intermediate- to high-risk patients with severe, symptomatic aortic stenosis were randomly assigned to transfemoral TAVR using either the SEV (Evolut R, Medtronic Inc., Minneapolis, Minnesota) or the BEV (Sapien 3, Edwards Lifesciences, Irvine, California) as well as CS or GA at 7 sites.ResultsIn the valve-comparison strategy, rates of the combined endpoint of all-cause mortality, stroke, moderate or severe paravalvular leakage, and permanent pacemaker implantation were similar between the BEV and SEV group (n = 84, 38.3% vs. n = 87, 40.4%; hazard ratio: 0.94; 95% confidence interval: 0.70 to 1.26; p = 0.66) at 1 year. Regarding the anesthesia comparison, the combined endpoint of all-cause mortality, stroke, myocardial infarction, and acute kidney injury occurred with similar rates in the GA and CS groups (n = 61, 25.7% vs. n = 54, 23.8%; hazard ratio: 1.09; 95% confidence interval: 0.76 to 1.57; p = 0.63).ConclusionsIn intermediate- to high-risk patients undergoing transfemoral TAVR, newer-generation SEV and BEV as well as CS and GA showed similar clinical outcomes at 1 year using a combined clinical endpoint. (SecOnd-generation seLf-expandable Versus Balloon-expandable Valves and gEneral Versus Local Anesthesia in TAVI [SOLVE-TAVI]; NCT02737150)     

Contemporary transcatheter aortic valve replacement with third‐generation balloon‐expandable versus self‐expanding devices

Objectives

To evaluate balloon‐expandable and self‐expanding third‐generation transcatheter aortic valve replacement (TAVR) devices according to patient selection criteria and outcomes.

Background

Two competing third‐generation TAVR technologies are currently commercially available in the US. There are no published head‐to‐head comparisons of the relative performance of these two devices.

Methods

257 consecutive patients undergoing TAVR with a third‐generation balloon‐expandable (Edwards Sapien 3) or self‐expanding device (Medtronic CoreValve Evolut R) at a single US medical center were included. Choice of TAVR device was at the discretion of the multidisciplinary Heart Team. Baseline clinical characteristics, echocardiographic and CT imaging, procedural and 30‐day outcomes were prospectively collected.

Results

74 patients received a self‐expanding valve (SEV) and 183 received a balloon‐expandable valve (BEV). Patients selected for SEV were more frequently women, with lower body surface area and smaller calcified iliofemoral arteries. Three SEV patients required implantation of a second valve to successfully treat paravalvular leak. Only one BEV patient had moderate paravalvular regurgitation. There was no difference in the rate of stroke, major vascular complication or bleeding. Permanent pacemaker implantation rate was significantly higher with SEV (12.7% vs 4.7%, P = 0.49) and hospital length of stay was longer (8.3% vs 6.5%, P = 0.043), but 30‐day mortality was comparable (1.4% vs 1.6%, P = 1.00).

Conclusions

Short‐term outcomes were equivalent between the two technologies. Clinically significant paravalvular regurgitation was rare. SEV were more frequently selected in women and patients with challenging transfemoral access, but were associated with higher permanent pacemaker implantation rate and longer hospital length of stay.

     

基于TCGA和CGGA数据库探究 KIF15在胶质瘤中的表达及临床意义

目的通过挖掘美国癌症基因图谱计划（TCGA）和中国脑胶质瘤基因图谱计划（CGGA）中胶质瘤基因谱数据库,分析KIF15在胶质瘤中的表达及临床意义。 方法通过人类蛋白数据库探究KIF15在神经系统中的表达特征。获取TCGA和CGGA中胶质瘤患者肿瘤样本全基因转录组（mRNAseq）数据,分析KIF15在不同级别和病理类型胶质瘤中的转录水平差异,及其与患者中位生存期的关系。通过胶质瘤标本芯片进行KIF15的免疫组织化学染色,分析KIF15在胶质瘤不同级别中的蛋白水平差异,通过转录组数据分析KIF15与肿瘤增殖指标Ki67的相关性,并通过差异基因（DEGs）进行基因本体（GO）分析和信号通路富集（KEGG）分析探讨KIF15在胶质瘤中参与调控的分子信号通路。 结果在中枢神经系统大脑中,各部位组织可检测到KIF15的蛋白水平和转录水平均较低。TCGA和CGGA转录组数据分析显示,胶质瘤WHO级别越高,KIF15的mRNA水平显著增高,WHO Ⅳ级相较于WHO Ⅱ级和Ⅲ级,差异有统计学意义（P<0.05）;并且,在胶质母细胞瘤中KIF15的mRNA水平最高,相比较于星形胶质细胞、少突胶质细胞瘤、少突星形胶质细胞瘤、间变性星形胶质细胞瘤、间变性少突胶质细胞瘤,差异均有统计学意义（P<0.05）。KIF15高水平组患者的中位生存期较KIF15低水平组更短,差异有统计学意义（P<0.05）。胶质瘤组织芯片染色结果显示,WHO级别越高,胶质瘤组织染色强度评分趋向更高,WHO Ⅳ级胶质瘤评分以2、3分为主,而WHO Ⅱ级以0、1分为主。KIF15和Ki67的mRNA水平之间为显著性正相关关系,在TCGA转录组数据和CGGA转录组数据库中r值分别为0.725、0.706。TCGA转录组数据共筛选到707个DEGs,KIF15高水平组相比较于KIF15低水平组,表达水平升高的DEGs有328个,表达水平降低的DEGs有379个。GO分析显示这些DEGs参与的生物学过程前10位包括有细胞周期转换和细胞有丝分裂调控。分子信号通路KEGG分析显示DEGs参与的分子信号通路包括细胞周期、P53通路和DNA复制。 结论KIF15在胶质瘤中高表达,并且高水平KIF15预示胶质瘤恶性程度高,患者生存期较差。KIF15参与调控了肿瘤细胞周期通路,可能是一个潜在的胶质瘤基因治疗靶点。     

Thrombocytopenia after transcatheter aortic valve replacement: What is really going on?

• In a multivariate model, the drop‐in platelet count (DPC) was significantly higher in patients treated with a balloon expandable valve (BEV) than a self‐expandable valve (SEV) (36.3% ± 15.1% vs. 27.7% ± 14.4%, p < .001).
• In a univariate model, a higher DPC post‐transcatheter aortic valve replacement was observed in patients requiring alternate access and lower contrast volume.
• The platelet count nadir was nearly a day later in patients implanted with a BEV compared with an SEV.
• At 30 days, there was a higher rate of adverse events and mortality in patients with a high DPC.
• At 1 year, there was no significant difference in mortality rates between the high DPC group and the low DPC group.

     

ClC-3、BK型离子通道与胶质瘤的侵袭性生长关系

目的观察ClC-3与BK离子通道在大鼠胶质瘤细胞中的表达,推测ClC-3与BK在胶质瘤细胞侵袭性生长中的作用。 方法常规建立Wistar大鼠C6脑胶质瘤模型,随机分为5组（荷瘤模型组、荷瘤模型+ ClC-3阻断剂Chlorotoxin组、荷瘤模型+BK阻断剂Iberiotoxin组、假手术组及空白对照组）,免疫组织化学技术检测ClC-3与BK在荷瘤动物模型中的表达情况,并进一步观察荷瘤动物在分别给予相应离子通道特异性阻滞剂后各个时间点（7、14、21 d）成瘤体积的变化情况。 结果C6胶质瘤系高度表达ClC-3离子通道,而BK离子通道在该系中的表达相对较低;应用Chlorotoxin后荷瘤动物各个时间点成瘤体积与对照组相比显著降低（P<0.05）,而应用Iberiotoxin后荷瘤动物的成瘤体积与对照组相比无显著变化（P>0.05）。 结论ClC-3离子通道在胶质瘤侵袭性生长发挥重要作用,可作为未来治疗胶质瘤的新靶标。     

C6/IL-24对鼠脑胶质瘤治疗作用的研究

目的 观察C6/IL-24对大鼠脑胶质瘤的治疗作用.方法 建立SD大鼠脑胶质瘤模型,实验组皮下注射C6/IL-24细胞,对照组皮下注射同等体积的生理盐水,观察大鼠的生存期及颅内肿瘤的生长变化.结果 实验组肿瘤生长速度明显减慢,实验组大鼠各时段肿瘤体积明显小于对照组,实验组大鼠存活时间明显长于对照组.结论 通过逆转录病毒将IL-24导入C6细胞而形成的C6/IL-24细胞对鼠脑胶质瘤具有较好的治疗效果,建立稳定可靠的脑胶质瘤动物模型是进行各种脑胶质瘤在体实验研究的基础,治疗时间窗的选择应在肿瘤指数生长期以前.     

初步探索DIM-C-pPhOH（ NR4A1拮抗剂）对胶质瘤细胞增殖、迁移及侵袭的抑制作用及作用机制

目的探索DIM-C-pPhOH（NR4A1拮抗剂）对胶质瘤细胞增殖、迁移、侵袭的抑制作用及其作用机制，以及对于胶质瘤小鼠模型生存期及肿瘤生长的影响。 方法不同浓度DIM-C-pPhOH处理胶质瘤细胞系（GL261、U251、U118）48 h后，用CellTiter法检测细胞活性及IC₅₀；采用划痕实验和3D-invasion实验检测DIM-C-pPhOH对U251细胞系侵袭迁移作用的影响；通过腹腔注射该化合物治疗小鼠胶质瘤模型，观察DIM-C-pPhOH对于小鼠胶质瘤生长以及生存期的影响。 结果U251、GL261和U118胶质瘤细胞系经DIM-C-pPhOH处理48 h后，细胞活性随药物浓度增加显著降低，IC₅₀分别为5.76、6.87、9.93 μmol/L；U251细胞系经10 μmol/L DIM-C-pPhOH处理后其迁移和侵袭能力显著下降；同时DIM-C-pPhOH可以抑制由TGF-β诱导的NR4A1出核表达；小鼠胶质瘤模型中DIM-C-pPhOH治疗组生存期延长，肿瘤生长受到抑制。蛋白免疫印迹显示DIM-C-pPhOH可以明显抑制Akt、P70S6K蛋白表达，通过抑制PI3K/Akt/mTOR/p70s6k信号通路，诱导细胞自噬发生。 结论DIM-C-pPhOH可以抑制胶质瘤的迁移及侵袭能力，延长小鼠胶质瘤模型的生存期并抑制肿瘤生长，作用机制可能与DIM-C-pPhOH诱导细胞发生自噬有关。     

Sensitivity to a neurosteroid is increased during addition of progestagen to postmenopausal hormone replacement therapy.

The aim of this study was to compare the pharmacodynamic response to a neuroactive steroid, pregnanolone, before and during different hormonal settings of postmenopausal hormone replacement therapy (HRT). Twenty-seven postmenopausal women with climacteric symptoms were administered HRT in a randomized, double-blinded, placebo-controlled crossover study. The women received 2 mg estradiol (E2) continuously during four 28-day cycles and 10 mg medroxyprogesterone acetate (MPA), 1 mg norethisterone acetate (NETA) or placebo sequentially for the last 14 days in each cycle. The pharmacodynamic response to pregnanolone was assessed before treatment and during the last week of each treatment, by comparing the effects of intravenous pregnanolone (3alpha-hydroxy-5beta-pregnan-20-one) on saccadic eye velocity (SEV), saccade deceleration, saccade latency and self-rated sedation. Throughout the study daily symptom rating scales were kept. During the progesta gen phase of the treatment cycles, negative mood symptoms and physical symptoms were increased, whereas positive mood symptoms were decreased. Compared to pretretreatment conditions, E2 alone did not change the responsiveness to pregnanolone. During progestagen addition to E2, the responsiveness to pregnanolone was increased. The sedation response increased compared to pretreatment conditions during both E2 + MPA and E2 + NETA treatment. Compared to E2 treatment alone, addition of MPA increased the postpregnanolone effect on saccade deceleration, whereas the SEV response to pregnanolone was increased during E2 + NETA treatment. It is concluded that pregnanolone sensitivity increases together with deterioration in mood symptoms during addition of progestagen to HRT.     

胶质瘤组织中EGFR、p27^kip1的表达变化及意义

目的观察胶质瘤组织中表皮生长因子受体（EGFR）和p27kip1的表达变化,并探讨其临床意义。方法采用免疫组化SP法检测60例胶质瘤组织、5例正常脑组织中EGFR和p27kip1。结果 60例胶质瘤患者中有39例表达EGFR,20例表达p27kip1。EGFR在正常脑组织中无表达,在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性表达率分别为52.4%、60.9%、87.5%（P〈0.05）;p27kip1在正常脑组织中表达率为80.0%,在Ⅱ、Ⅲ、Ⅳ级胶质瘤中阳性表达率分别为57.1%、26.1%、12.5%（P〈0.05）。EGFR表达与胶质瘤病理分级呈正相关（r=0.426,P〈0.05）,p27kip1表达与胶质瘤病理分级呈负相关（r=-0.325,P〈0.05）。结论 EGFR、p27kip1表达与胶质瘤的恶性程度有关,其表达异常可能在肿瘤形成中起促进作用。     

Correlation between preoperative inflammatory markers,Ki-67 and the pathological grade of glioma

To investigate the correlation between preoperative inflammatory markers, Ki-67 expression and the pathological grade of glioma, and to provide a reference for clinical prediction of glioma prognosis.A total of 45 glioma patients who underwent surgery with complete clinical and pathological data were in our hospital from January 2012 to December 2018 were enrolled. Glioma was divided into WHO grade I to IV. Forty-five healthy health examiners with matched clinical characteristics were included to the control group. Blood routine tests were recorded at admission in both the glioma and control group. The ratio of neutrophil to lymphocyte cytometry (NLR), derived neutrophil to lymphocyte ratio (dNLR) (white blood cell count – neutrophil count to neutrophil count), platelet to lymphocyte ratio (PLR) and prognostic nutritional index (PNI, serum albumin content + 5 × lymphocyte count) were calculated. The expression of Ki-67 in glioma was detected by immunohistochemistry. The relationship between the above markers, Ki-67 expression and pathological grade of glioma was evaluated with receiver operating characteristics curve analysis and Spearman correlation test. The correlation between the markers and Ki-67 were also determined.NLR, dNLR, PLR were increased in the glioma group (P < .001, <.001, .002), whereas red blood cell distribution width (RDW) was decreased (P = .009). All the glioma samples expressed Ki-67 with varying degree. Receiver operating characteristics curve analysis reveals NLR, dNLR, PLR, and RDW have significant discriminating ability in differentiating the glioma and control sample. NLR, PLR, PNI, and Ki-67 were significantly correlated with glioma pathology grade (P = .023, .006, .019, <.05), while dNLR and RDW were not associated with glioma grade. Finally, NLR and PLR were related to Ki-67 expression in glioma patients (P = .002, .022), while dNLR and RDW were not related to Ki-67 expression.Preoperative inflammatory markers NLR, PLR, PNI, and postoperative Ki-67 expression are associated with pathological grade of glioma. Detection of these markers may aid in better prediction of glioma prognosis.     

Neurofibromatosis-1 regulates mTOR-mediated astrocyte growth and glioma formation in a TSC/Rheb-independent manner

Converging evidence from the analysis of human brain tumors and genetically engineered mice has revealed that the mammalian target of rapamycin (mTOR) pathway is a central regulator of glial and glioma cell growth. In this regard, mutational inactivation of neurofibromatosis-1 (NF1), tuberous sclerosis complex (TSC), and PTEN genes is associated with glioma formation, such that pharmacologic inhibition of mTOR signaling results in attenuated tumor growth. This shared dependence on mTOR suggests that PTEN and NF1 (neurofibromin) glial growth regulation requires TSC/Rheb (Ras homolog enriched in brain) control of mTOR function. In this report, we use a combination of genetic silencing in vitro and conditional mouse transgenesis approaches in vivo to demonstrate that neurofibromin regulates astrocyte cell growth and glioma formation in a TSC/Rheb-independent fashion. First, we show that Nf1 or Pten inactivation, but not Tsc1 loss or Rheb overexpression, increases astrocyte cell growth in vitro. Second, Nf1-deficient increased mTOR signaling and astrocyte hyperproliferation is unaffected by Rheb shRNA silencing. Third, conditional Tsc1 inactivation or Rheb overexpression in glial progenitors of Nf1(+/-) mice does not lead to glioma formation. Collectively, these findings establish TSC/Rheb-independent mechanisms for mTOR-dependent glial cell growth control and gliomagenesis relevant to the design of therapies for individuals with glioma.     

Present and future economic impact of transcatheter aortic valve replacement on the Portuguese national healthcare system

IntroductionTranscatheter aortic valve replacement (TAVR) has changed the treatment paradigm of severe aortic stenosis (AS). Nevertheless, in Portugal the penetration rate of TAVR is still very low and there is a paucity of data regarding its economic impact on the Portuguese healthcare system.AimsTo perform an economic analysis of the present and future impact of TAVR in Portugal and to propose health policy recommendations for a new reimbursement model.MethodsHospital data from a high-volume center were used as a sample to calculate the costs of TAVR in Portugal. Information regarding the national penetration rate was derived from the EAPCI Valve for Life initiative. To estimate the future demand for TAVR, three scenarios (S) were constructed: S1, TAVR penetration according to current guidelines; S2, including intermediate-risk patients; and S3, including low-risk patients aged over 75 years.ResultsThe total cost of each TAVR procedure in Portugal was 22 134.50 euros for the self-expanding valve (SEV) and 23 321.50 euros for the balloon-expanding valves (BEV). Most of the cost was driven by the price of the valve (SEV 74.5% vs. BEV 81.5%). The current national economic impact is estimated at 12 500 000 euros per year. In S1, the expected penetration rate would be 189 procedures per million population; in S2 we estimated an increase of 28% to 241 procedures per million population and in S3 an increase of 107% to 391 procedures per million population. The total economic impact would increase to 43 770 586 euros in S1 and to 90 754 310 euros in S3.ConclusionsTAVR is associated with a significant present and future economic impact on the Portuguese healthcare system. A new model of reimbursement in Portugal should be discussed and implemented.