Expanding control of the tumor cell cycle with a CDK2/4/6 inhibitor

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New advances in Amyotrophic Lateral Sclerosis genetics: Towards gene therapy opportunities for familial and young cases

Due to novel gene therapy opportunities, genetic screening is no longer restricted to familial cases of ALS (FALS) cases but also aplies to the sporadic populations (SALS). Screening of four main genes (C9orf72, SOD1, TARDBP and FUS) identified the causes in 15% of Amyotrophic Lateral Sclerosis (ALS) patients (two third of the familial cases and 8% of the sporadic ones) but their respective contribution to ALS phenotype varies according the age of disease onset. The genetic overlap between ALS and other diseases is expanding and includes frontotemporal dementia, Paget's Disease of Bone, myopathy for adult cases, HSP and CMT for young cases highlighing the importance of retrieving the exhaustive familial history for each indivdual with ALS. Incomplete disease penetrance, diversity of the possible phenotypes, as well as the lack of confidence concerning the pathogenicity of most identified variants and/or possible oligogenic inheritance are burdens of ALS genetic counseling to be delivered to patients and at risk individuals. The multitude of rare ALS genetic causes identifed seems to converge to similar cellular pathways leading to inapropriate response to stress emphacising new potential therapeutic options for the disease.     

腰椎旁神经阻滞联合全凭静脉全身麻醉对髋关节置换术患者血流动力学、应激反应、术后苏醒的影响

目的观察腰椎旁神经阻滞联合全凭静脉全身麻醉对髋关节置换术患者血流动力学、应激反应、术后苏醒的影响。方法选取2018年1月—2019年8月我院收治的行髋关节置换术患者115例,根据手术麻醉方法的不同分为观察组60例和对照组55例,观察组予腰椎旁神经阻滞联合全凭静脉全身麻醉,对照组仅予全凭静脉全身麻醉。比较两组麻醉前(T0)、麻醉后10 min(T1)、麻醉后30 min(T2)、术毕(T3)时平均动脉压、心率、去甲肾上腺素及肾上腺素水平变化,术后清醒镇静效果和苏醒时间,以及两组手术期间不良反应发生情况。结果观察组T1、T2、T3时平均动脉压、心率与T0时比较虽略有升高,但差异无统计学意义(P>0.05);对照组T1、T2、T3时平均动脉压、心率与T0时比较均升高,且以T2时平均动脉压、心率最高,T3时又回落至T1时水平,差异有统计学意义(P<0.05)。T1、T2、T3时观察组平均动脉压、心率均低于对照组(P<0.05)。T1、T2、T3时两组去甲肾上腺素、肾上腺素均较T0时升高,且观察组相同时间点去甲肾上腺素、肾上腺素水平低于对照组,差异均有统计学意义(P<0.05或P<0.01)。观察组术后唤醒时警觉/镇静评分低于对照组,苏醒时间明显短于对照组,差异均有统计学意义(P<0.05)。两组手术期间总不良反应发生率比较差异无统计学意义(P>0.05)。结论腰椎旁神经阻滞联合全凭静脉全身麻醉用于髋关节置换术可有效防止患者血流动力学指标的波动,减轻手术应激反应程度,术后苏醒快,术后苏醒质量佳,且未增加手术期间不良反应的发生。     

超声引导PVNB对老年食道癌开胸患者术后镇痛、应激及炎性因子水平的影响

目的 探讨超声引导下连续椎旁神经阻滞(PVNB)对老年食道癌开胸手术患者术后镇痛、应激及炎性因子水平的影响。方法 选取我院拟实施全麻下开胸手术的90例食道癌开胸手术患者作为研究对象,其中45例患者术前采用超声引导下PVNB麻醉复合全身麻醉(PVNB组)、对照组45例患者采用全身麻醉；两组患者术后均采用静脉自控镇痛(对照组)；对比两组患者术后2h、6h、24h及48h静息状态、咳嗽状态下的视觉模拟疼痛评分(VAS),术后镇痛药物用量及镇痛药物不良反应发生情况,术前及术后24h血清去甲肾上腺素(NE)、肾上腺素(E)、皮质醇(Cor)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)差异及术后肺部感染发生情况。结果 PVNB组患者和对照组在术后2h～术后48h的静息VAS评分及咳嗽VAS评分组间比较,差异具有统计学意义(P<0.05),PVNB组术后2h、6h及24h静息VAS评分及咳嗽VAS评分均高于对照组(P>0.05)。PVNB组患者术后的镇痛泵按压次数、舒芬太尼用量均低于对照组(P<0.05),PVNB组患者术后的镇痛泵按压次数、舒芬太尼用量均低于对照组(P<0.05),术前两组患者的血清NE、E、Cor水平差异无统计学意义(P>0.05)；术后两24h两组患者血清NE、E、Cor水平均较术前增高(P>0.05),术后24h PVNB组的血清NE、E、Cor水平低于对照组(P<0.05),术前两组患者的血清IL-6、TNF-α水平差异无统计学意义(P>0.05)；术后24h两组患者血清IL-6、IL-10、TNF-α水平均较术前增高(P<0.05),PVNB组的血清IL-6、TNF-α水平低于对照组(P<0.05),PVNB组术后发生肺部感染2例,发生率为4.4%,对照组术后发生肺部感染6例,发生率为13.3%,PVNB组术后肺部感染发生率低于对照组(P<0.05)。结论 超声引导下PVNB能够改善老年食道癌开胸患者术后镇痛效果,减轻手术创伤所致的应激反应,较少患者术后肺部感染的发生。     

Clearing hepatitis C virus with direct antiviral agents reduces cardiovascular events in patients with prediabetes. Commentary to Sasso and colleagues

Liver health is a key determinant of cardiovascular risk (CVR). Hepatic fibrosis is the shared common result of chronic hepatitis, irrespective of aetiology. Fibrosis profoundly distorts liver tissue architecture and perturbs hepatic physiology, dictates the course of chronic liver disease and is increasingly recognized as a CVR factor. The relative weights of pre-diabetes and hepatic fibrosis as risk factors for major adverse cardiac events (MACE) in patients with HCV remain an open issue. Sasso and Colleagues answered this research question by treating approximately half of 770 HCV positive pre-diabetic patients with direct antiviral agents (DAAs), while the rest served as historical controls. Data have shown that achieving HCV clearance with DAAs was associated with a 60% reduced risk of MACE, thereby implying that this antiviral strategy is recommended in HCV positive pre-diabetic patients, regardless of the severity of liver disease and concurrent CVR factors. This study paves the way for additional studies addressing the molecular patho-mechanisms and changes in the clinical spectrum involved in cardio-metabolic protection following HCV eradication in patients with pre-diabetes.     

Complete pathological response in rectal cancer utilising novel treatment strategies for neo-adjuvant therapy: A systematic review

BackgroundLocally advanced rectal cancer is routinely treated with neo-adjuvant long course chemoradiotherapy or short course radiotherapy, followed by total mesorectal excision. Not all patients respond to this treatment and there has been an emergence of novel treatment strategies designed to improve outcomes for these patients. This systematic review aims to assess the current novel neo-adjuvant treatment strategies being utilised in the treatment of patients with rectal cancer and how these impact pathological complete response (pCR) rates.MethodsA systematic review of the literature was performed to evaluate pathological response in patients with rectal cancer receiving novel neo-adjuvant therapy. EMBASE and Medline electronic databases were searched for relevant articles. Articles published between January 2008 and February 2019 were retrieved. Included studies underwent critical appraisal and complete pathological response rates were recorded.ResultsOf the initial 1074 articles identified, 217 articles fulfilled the inclusion criteria, of these 60 articles (4359 patients) were included. Neo-adjuvant therapy delivered included novel long course chemoradiation therapy, neoadjuvant chemotherapy alone, addition of a biological agent, total neo-adjuvant therapy, novel short course radiation therapy and studies utilising biomarkers to select patients for therapy. Complete pathological response rates ranged from 0 to 60%.ConclusionA validated novel neo-adjuvant therapy that significantly increases pCR rates in patients with rectal cancer has not been identified.