The role of CDK4/6 inhibitors in early breast cancer

The use of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) has proven to be a successful strategy in the treatment of advanced hormone receptor-positive (HR⁺) and human epidermal growth factor receptor 2-negative (HER2^-) breast cancer (BC), leading to a strong interest in their possible role in the treatment of early luminal BC. In this review we collect the most relevant and recent information on the use of CDK4/6i for the treatment of early BC in the neoadjuvant and adjuvant settings. Specifically, we evaluate the results of the large phase 3 adjuvant trials recently released, which have yielded apparently divergent results. We also examine the relevance of biomarkers as response predictive factors for CDI4/6i, the combination between radiotherapy and CDK4/6i, and provide a critical discussion on the evidence that we have so far and future directions of the role of these drugs in the treatment of early BC.     

The effect of postmastectomy radiation therapy on high-risk patients with T1-2N0 breast cancer

BackgroundThe prognostic impact of postmastectomy radiation therapy (PMRT) on high-risk patients with T1-2N0 breast cancer is controversial. We aimed to investigate the effect of PMRT on high-risk patients with T1-2N0 breast cancer.MethodsA total of 3439 patients diagnosed with T1-2N0 breast cancer who received mastectomy between 2000 and 2016 in our institute were retrospectively analyzed. Leveraging the Fine and Gray competing risks regression in unirradiated patients, risk factors of locoregional recurrence (LRR) were identified. All patients were stratified into high-risk (3 or 4 risk factors) and low-risk (no more than 2 risk factors) groups. The prognostic effect of PMRT was estimated in two subgroups. This subgroup analysis was also performed in patients with T2N0 breast cancer.ResultsThe median follow-up was 89 months. The 5-year cumulative incidence of LRR was 2.2% in unirradiated patients. Tumor size, estrogen receptor (ER) status, histologic grade and lymphovascular invasion (LVI) were identified as independent risk factors of LRR. In the high-risk group, PMRT was correlated with a 8.3% risk reduction of 5-year LRR, 7.8% risk reduction of 5-year distant recurrence (DR), and 6.4% risk reduction of 5-year breast cancer mortality (BCM), whereas it was not correlated with LRR, DR, or BCM in low-risk group. In patients with T2N0 breast cancer, PMRT was associated with decreased LRR, DR and BCM in high-risk group, other than low-risk group.ConclusionsPMRT presented heterogenous effect on patients with T1-2N0 breast cancer. Patients at high risk of LRR were more likely to benefit from PMRT.     

Change in granulation tissue coverage and bacteriological load using Low Cost Negative Pressure Wound Therapy in acute musculoskeletal wounds

BackgroundLow cost Negative Pressure Wound Therapy (NPWT) dressings have been considered as an alternative to traditional daily dressings. There is scanty literature evaluating the change in the percentage area of wound covered by granulation tissue following application of low-cost NPWT. The change in the bacteriological flora following application of low-cost NPWT devices has also not been evaluated.MethodsPatients above the age of 18 years with acute musculoskeletal injuries of <3 weeks duration which underwent a surgical debridement and required subsequent wound coverage were included in the study. Area of the wound and the area covered by the granulation tissue as well as the bacteriological count were measured before and after application of NPWT. A low cost NPWT using wall mounted vacuum device was put on the patient giving a constant negative pressure of 125 mm of Hg for 2 days. The findings before and after application of NPWT were compared and analyzed using Wilcoxin Signed-rank test.Results21 patients with mean age of 35.52±15.075 were included. The pre-NPWT granulation tissue area ranged from 122 mm² to 8483 mm² with a mean of 1648.38 mm² (SD = 1933.866). The post-NPWT granulation tissue area ranged from 234 mm² to 7847 mm² with a mean of 2364.48 mm² (SD = 1857.716). The mean increase in granulation tissue was 716.1 mm².The pre-NPWT wound area ranged from 422 mm² to 10847 mm² with a mean of 4009.62 mm² (SD = 3026.209). The post-NPWT wound area ranged from 326 mm² to 9143 mm² with a mean of 3410.33 mm² (SD = 2636.206). The mean reduction in wound size was 599.29 mm².The pre-NPWT bacteriological count ranged from 3000/ml to 130000000/ml with a mean of 12616761.90/ml (SD = 29664589.37). The post-NPWT bacteriological count ranged from 1000/ml to 380000000/ml with a mean of 26401523.81/ml. The mean increase in bacteriological count was 13784761.91/ml.ConclusionThere was a statistically significant decrease in wound size (p = 0.001) and statistically significant increase in percentage area of granulation tissue coverage (p = 0.000) following low cost NPWT application. However there was no statistically significant increase in bacteriological clearance in these patients.     

A European consensus statement on the use of four-factor prothrombin complex concentrate for cardiac and non-cardiac surgical patients

Modern four-factor prothrombin complex concentrate was designed originally for rapid targeted replacement of the coagulation factors II, VII, IX and X. Dosing strategies for the approved indication of vitamin K antagonist-related bleeding vary greatly. They include INR and bodyweight-related protocols as well as fixed dose regimens. Particularly in the massively bleeding trauma and cardiac surgery patient, four-factor prothrombin complex concentrate is used increasingly for haemostatic resuscitation. Members of the Transfusion and Haemostasis Subcommittee of the European Association of Cardiothoracic Anaesthesiology performed a systematic literature review on four-factor prothrombin complex concentrate. The available evidence has been summarised for dosing, efficacy, drug safety and monitoring strategies in different scenarios. Whereas there is evidence for the efficacy of four-factor prothrombin concentrate for a variety of bleeding scenarios, convincing safety data are clearly missing. In the massively bleeding patient with coagulopathy, our group recommends the administration of an initial bolus of 25 IU.kg^-1. This applies for: the acute reversal of vitamin K antagonist therapy; haemostatic resuscitation, particularly in trauma; and the reversal of direct oral anticoagulants when no specific antidote is available. In patients with a high risk for thromboembolic complications, e.g. cardiac surgery, the administration of an initial half-dose bolus (12.5 IU.kg^-1) should be considered. A second bolus may be indicated if coagulopathy and microvascular bleeding persists and other reasons for bleeding are largely ruled out. Tissue-factor-activated, factor VII-dependent and heparin insensitive point-of-care tests may be used for peri-operative monitoring and guiding of prothrombin complex concentrate therapy.     

中医外治法在慢性萎缩性胃炎中的应用研究进展

慢性萎缩性胃炎（CAG）是消化系统常见的慢性疾病,被认为是胃癌癌前病变,严重危害人类健康。如何有效促进胃黏膜的修复、抑制腺体的萎缩、阻断癌变是临床研究的热点。目前西医尚缺乏特效的治疗手段,近年来,大量研究结果表明,中医外治法在治疗CAG方面取得了显著成果,且具有简、便、效、廉等优势,深受患者青睐。现查阅近年来包括针刺法、灸法及贴敷法等在内的常用中医外治法治疗CAG的相关文献并进行综述,以期为临床治疗该病提供参考。     

中医药治疗糖尿病肾病实验研究进展

糖尿病肾病（DN）是糖尿病常见慢性并发症之一,白蛋白尿和肾小球滤过率下降是目前糖尿病肾病诊断的重要临床指征。DN严重影响着患者的生命质量,尽早地干预糖尿病肾病的危险因素,纠正胰岛素代谢障碍导致的长期高血糖因素影响下的肾脏损伤,是有效阻止其进展为终末期肾脏疾病的关键。中医药秉持其特色理论取得了独特的治疗优势,随着中医药对于DN的认识与研究的加深,实验研究方面也取得了一定的进展。本文总结了中医研究DN动物模型的常用构建方法,同时从中医药调节免疫炎症反应、降低氧化应激水平、改善肾脏血流动力学改变、纠正糖脂代谢紊乱等机制方面列举分析中医药辨治糖尿病实验研究进展,探讨中医药防治DN的机制,以期对临床有所裨益。     

和胃安神方对失眠模型大鼠5-羟色胺、多巴胺及去甲肾上腺素水平的影响

目的：探讨和胃安神方对失眠模型大鼠下丘脑5-羟色胺（5-HT）、多巴胺（DA）和去甲肾上腺素（NE）水平的影响。方法：将60只雄性Wistar大鼠随机分为6组,即正常对照组、失眠模型组、地西泮组、和胃安神方低剂量组、和胃安神方中剂量组、和胃安神方高剂量组。采用酶联免疫吸附试验（ELISA）检测各组大鼠下丘脑组织5-HT、DA、NE的水平。结果：与正常对照组比较,失眠模型组大鼠5-HT水平显著下降,差异有统计学意义（P<0.05),DA、NE水平较正常对照组显著升高,差异有统计学意义（P<0.05);与失眠模型组比较,地西泮组、和胃安神方低剂量组5-HT、DA、NE水平差异均无统计学意义(均P>0.05);和胃安神方中剂量组、和胃安神方高剂量组5-HT水平均较失眠模型组显著升高,差异有统计学意义(P<0.05),DA、NE水平较失眠模型组显著下降,差异有统计学意义（P<0.05)。结论：和胃安神方治疗失眠症的疗效机制可能与调节脑内5-HT、DA、NE水平有关。     

Guidelines for the diagnosis,treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.     

聚焦式体外冲击波联合离心锻炼治疗大转子疼痛综合征

目的：探讨聚焦式体外冲击波联合离心锻炼治疗股骨大转子疼痛综合征的临床疗效。方法：2017年9月至2019年6月,将符合研究标准的53例股骨大转子疼痛综合征（greater trochanteric pain syndrome,GTPS）的患者分为观察组（29例）和对照组（24例）。观察组,男8例,女21例,年龄38~62（49.96±6.39）岁,病程6~13（8.58±1.99）个月,采用聚焦式体外冲击波联合离心锻炼治疗;对照组,男5例,女19例,年龄39~62（52.79±5.86）岁,病程6~14（9.04±2.51）个月,单纯采用离心锻炼治疗。分别使用疼痛视觉模拟评分（visual analogue scale,VAS）和髋关节Harris评分评估两组患者治疗前及治疗后1、2、6个月时髋部疼痛缓解程度及髋关节功能恢复情况,比较治疗效果。结果：治疗后1个月,两组VAS、髋关节Harris评分及治疗成功率比较差异无统计学意义（P>0.05）;2个月时,观察组VAS （3.20±0.81）分低于对照组的（3.87±0.61）分（P<0.05）,髋关节Harris评分（81.93±2.43）分与对照组（82.12±2.34）分比较差异无统计学意义（P=0.770）,治疗成功率（58.62%,17/29）高于对照组（29.16%,7/24）（P=0.032）;6个月时,观察组VAS （2.24±0.68）分低于对照组的（3.12±0.53）分（P<0.001）,髋关节Harris评分（85.10±1.75）分高于对照组的（83.66±1.78）分（P=0.005）,治疗成功率（82.75%,24/29）与对照组（62.50%,15/24）比较差异无统计学意义（P=0.096）。结论：聚焦式体外冲击波联合离心锻炼能够显著缓解大转子疼痛综合征患者髋部疼痛症状,改善髋关节功能,安全性可靠,值得在临床实践中应用推广。     

肝癌系统治疗中肿瘤超进展研究现状

随着肝癌系统治疗的快速发展,靶向治疗、免疫治疗等系统治疗已广泛应用于不可切除肝癌或交界可切除肝癌的转化治疗。肿瘤的超进展是一种肿瘤加速生长的现象,在接受系统治疗的肝癌等实体瘤病人中均有发生,主要与免疫治疗相关。目前,临床上对肝癌中肿瘤超进展的认识不足,缺乏相关的临床研究,尚无法正确评估肿瘤超进展是否发生及严重程度。