孟鲁司特治疗呼吸道合胞病毒毛细支气管炎症状及反复喘息疗效研究

背景　呼吸道合胞病毒（RSV）毛细支气管炎易出现反复喘息，且下呼吸道分泌物中半胱氨酸白三烯（CysLTs）水平升高。而孟鲁司特是一种白三烯受体拮抗剂，关于其治疗RSV毛细支气管炎症状的研究相对较少。目的　探讨孟鲁司特改善婴幼儿RSV毛细支气管炎后症状及减轻反复喘息发作的有效性和安全性。方法　2015年6月-2017年6月连续纳入在潍坊市妇幼保健院出院的RSV毛细支气管炎患儿，随机分为治疗组、对照组。Ⅰ期，治疗组：口服孟鲁司特颗粒（4 mg）12周，1次/d；对照组：口服安慰剂12周，1次/d。对两组无症状天数、个人日记评分进行评估。随访9个月（Ⅱ期），观察Ⅰ+Ⅱ期反复喘息人数和医疗资源应用情况等。依据意向性分析（ITT）原则，应用全分析集（FAS）分析数据。结果　共纳入研究对象186例，治疗组92例，对照组94例。治疗组完成Ⅰ期研究的患儿为89例，对照组为90例；治疗组完成Ⅰ+Ⅱ期的患儿为84例，对照组为86例。治疗组平均依从性为97.8%（7 560/7 728），对照组平均依从性为97.4%（7 690/7 896），两组患儿平均依从性比较，差异无统计学意义（χ2=3.16，P=0.07）。在Ⅰ期研究期间，两组无症状天数、日间无症状天数、夜间无症状天数、个人日记评分比较，差异均无统计学意义（P>0.05）。在整个研究过程中（Ⅰ+Ⅱ期），治疗组RSV毛细支气管炎喘息复发人数少于对照组（P<0.05），治疗组喘息患儿出现2次及以上喘息比例低于对照组（χ2=5.14，P=0.02）。Ⅰ+Ⅱ期研究期间治疗组医疗资源应用人数、β-受体激动剂应用人数、糖皮质激素应用人数、住院人数低于对照组（P<0.05）。在事后亚组分析中，治疗组有湿疹史与父母哮喘史的患儿中无症状天数〔（49.7±20.2）、（51.3±20.9）d〕多于对照组〔（36.3±20.4）、（37.8±19.3）d〕（t=2.19，P=0.03；t=2.24，P=0.03）。整个研究过程中没有患儿因不良反应退出研究，两组间胃肠道紊乱、皮疹、转氨酶升高发生率比较，差异均无统计学意义（χ2=0.23，P=0.63；χ2=0.03，P=0.86；χ2=0.15，P=0.69）。结论　口服孟鲁司特（4 mg）12周不能改善RSV毛细支气管炎患儿呼吸道症状，但能降低患儿反复喘息发作次数。口服孟鲁司特（4 mg）有一定效果且安全。     

三黄消疕膏治疗寻常型银屑病血热证的临床疗效观察

目的:探讨三黄消疕膏用于治疗寻常型银屑病血热证的临床效果和安全性。方法:选取2017年12月-2018年11月就诊于我院的寻常型银屑病患者80例,根据随机数字表法,分为治疗组和对照组,对照组口服决银颗粒治疗,治疗组除口服决银颗粒外,外用三黄消疕膏于局部皮损处,治疗2周后,分别对两组患者进行皮损面积及严重程度(Psoriasis Area and Severity Index,PASI)评分、皮肤病生活质量指数(Dermatology Life Quality Index,DLQI)评分、有效率、不良反应发生率评分。结果:治疗后,两组患者PASI评分下降,差异有统计学意义(t=3.34,P<0.05);DLQI评分下降,差异有统计学意义(t=5.59,P<0.05);治疗组有效率为91%,对照组有效率为62%,差异有统计学意义(χ^2=30.09,P<0.01);两组患者治疗后不良反应发生率较低,差异无统计学意义(P>0.05)。结论:三黄消疕膏联合决银颗粒治疗寻常型银屑病血热证可取得较好的临床效果,且安全性较高,值得推广。     

Risk of acute pancreatitis with incretin-based therapy: a systematic review and updated meta-analysis of cardiovascular outcomes trials

ABSTRACT

Background

The link of acute pancreatitis (AP) with Incretin based therapies (IBTs) in type 2 diabetes has existed since United States Food and Drug Administration alert in 2010. This issue still remains unresolved due to conflicting results among studies.     

Clinical Benefit-Risk Profile of Lenalidomide in Patients With Lower-risk Myelodysplastic Syndromes Without del(5q): Results of a Phase III Trial

BackgroundIn the phase III MDS-005 study of patients with lower-risk, non-del(5q) myelodysplastic syndromes, lenalidomide was associated with a higher rate of ≥ 8 weeks red blood cell transfusion independence (RBC-TI) compared with placebo, but also with a higher risk of hematologic adverse events (AEs).Patients and MethodsThis analysis evaluated the ratio of clinical benefit-risk in patients treated with lenalidomide or placebo, and assessed the effect of lenalidomide dose reductions on response. Clinical benefit was a composite endpoint defined as RBC-TI, transfusion reduction ≥ 4 units packed red blood cells, hemoglobin increase ≥ 1.5 g/dL, or cytogenetic response.ResultsThe rate of clinical benefit was higher with lenalidomide than with placebo (31.9% vs. 3.8%). The ratio of response (RBC-TI and clinical benefit) to risk (hematologic AEs) favored lenalidomide over placebo. Patients who underwent ≥ 1 lenalidomide dose reduction had a longer duration of treatment, received a higher cumulative dose, and were more likely to experience clinical benefit versus patients without dose reductions.ConclusionDespite the occurrence of hematologic AEs, the overall benefit-risk profile supported lenalidomide treatment. Appropriate management of hematologic AEs by dose reductions may help patients with myelodysplastic syndromes to remain on treatment and achieve clinical benefit.     

Rare patients in routine care: Treatment and outcome in advanced papillary renal cell carcinoma in the prospective German clinical RCC-Registry

Non-clear cell renal cell carcinoma is a very rare malignancy that includes several histological subtypes. Each subtype may need to be addressed separately regarding prognosis and treatment; however, no Phase III clinical trial data exist. Thus, treatment recommendations for patients with non-clear cell metastatic RCC (mRCC) remain unclear. We present first prospective data on choice of first- and second-line treatment in routine practice and outcome of patients with papillary mRCC. From the prospective German clinical cohort study (RCC-Registry), 99 patients with papillary mRCC treated with systemic first-line therapy between December 2007 and May 2017 were included. Prospectively enrolled patients who had started first-line treatment until May 15, 2016, were included into the outcome analyses (n = 82). Treatment was similar to therapies used for clear cell mRCC and consisted of tyrosine kinase inhibitors, mechanistic target of rapamycin inhibitors and recently checkpoint inhibitors. Median progression-free survival from start of first-line treatment was 5.4 months (95% confidence interval [CI], 4.1–9.2) and median overall survival was 12.0 months (95% CI, 8.1–20.0). At data cutoff, 73% of the patients died, 6% were still observed, 12% were lost to follow-up, and 9% were alive at the end of the individual 3-year observation period. Despite the lack of prospective Phase III evidence in patients with papillary mRCC, our real-world data reveal effectiveness of systemic clear cell mRCC therapy in papillary mRCC. The prognosis seems to be inferior for papillary compared to clear cell mRCC. Further studies are needed to identify drivers of effectiveness of systemic therapy for papillary mRCC.     

Extending Screening in “Elderly” Patients: Should We Consider a Selective Approach?

BackgroundBreast cancer screening has been shown to reduce breast cancer-associated mortality. However, screening is limited to the targeted age group of 45 to 69 years in New Zealand despite the recognized increased risk with age. This study aims to compare the outcomes of women aged over 70 years with screen-detected and clinically detected cancers.Patients and MethodsA retrospective review was performed of prospectively collected data from June 2000 to May 2013 by the Auckland Breast Cancer Register. Demographic and tumor characteristics of women with invasive cancer and ductal carcinoma in situ diagnosis aged 70 years and over were compared between those screened and clinically detected. Five-year disease-free and overall survival outcomes were reviewed.ResultsA total of 2128 women aged 70 years and over were diagnosed with breast cancer (median, 77 years; interquartile range [IQR], 74-84 years). Of these, 416 (19.5%) were diagnosed through mammography screening, with a median age of 74 years (IQR, 71-77 years) compared with 79 years (IQR, 74-85 years) for those with clinical detected cancer diagnosis. Screen-detected cancers accounted for a significantly higher proportion of diagnoses in those aged 70 to 74 years compared with older patients (P < .001). Screen-detected cancers were of lower T and N stages. Disease-specific survival was significantly longer in screen-detected cancers versus other cancers (5-year survival, 93.7% vs. 81.9%; P < .001), as was overall survival (5-year survival, 84.7% vs. 57.4%; P < .001).ConclusionScreening in those aged 70 years and over continues to identify breast cancer at early stages and with improved survival. Although aware of the potential for lead-time bias and the healthy volunteer effect, there should still be consideration to extend breast cancer screening to patients aged to up 74 years after appropriate assessment of comorbidities and functional status.     

微生物与结直肠癌的发病机制、早期诊断和治疗的研究进展

结直肠癌是威胁人类健康的重大疾病之一，随着近年来微生物组学技术的发展，很多研究报道了微生物与结直肠癌发生发展的关系，发现了具核梭杆菌、脆弱拟杆菌等微生物促进结直肠癌发生的分子机制以及短链脂肪酸等细菌代谢产物抑制结直肠癌发生发展的作用。利用结直肠癌患者与健康人群之间的差异微生物，可以建立基于微生物标志物的结直肠癌诊断模型，使结直肠癌的早发现、早诊断成为可能。在结直肠癌的治疗领域，微生物可能成为抑制结直肠癌发生发展的药物靶点，并且能够影响化疗药物的疗效与不良反应。本文以微生物与结直肠癌的关系为切入点，结合近年的相关文献及自身研究，对微生物与结直肠癌的发病机制、早期诊断和治疗的研究进展作一综述。     

Oncologic outcome of mixed adenoneuroendocrine carcinoma (MANEC): A single center case series

IntroductionMixed adeno-neuroendocrine carcinomas (MANEC) are rare tumors of gastrointestinal tract mostly found in stomach. There are very few case reports and case series with location of colon and rectum. We aimed to report our results in the treatment of colorectal MANEC.MethodsWe performed a prospective analysis of patients with MANEC diagnosis from December 2011 to March 2019 at National Cancer Institute, Lithuania. The demographic information, tumor details, immunohistochemical markers, clinical data, stage, treatment modalities, clinical and oncological outcomes were collected.ResultsNine patients with a diagnosis of MANEC were found in our center. The average age at diagnosis was 64.8 (48–91) years. Seven out of nine (77.8%) patients underwent surgery. Distant metastases were observed in five (55.6%) patients. The adenocarcinoma and neuroendocrine tumor as a dominant component were equal in all cases. The most common tumor localizations were sigmoid colon in three patients (33.3%) and rectum – three patients, following two in an anal canal, and one in the hepatic flexure of colon. The adenocarcinoma component was poorly differentiated (G3) in six patients and moderately differentiated (G2) in three patients. The neuroendocrine component was G3 in seven patients (77.8%), G2 – in two patients (22.2%). Median follow-up was 17 months with a median survival time of 12.5 months.ConclusionMANEC is very rare, aggressive, rapidly spreading, usually with poor prognosis disease.     

从干细胞方向研究针灸作用机制的研究进展

针灸是我国传统医学的重要组成部分，其疗效得到世界范围广泛认可，对其作用机制研究不断扩展、深入。干细胞自上世纪60年代被发现以来，其基础研究以及临床应用迅速发展，对组织的修复、再生或替代治疗产生了积极的影响。近年来，国内外也有研究报道试图从针灸对干细胞的影响方面揭示针灸的治疗机制，就此内容检索相关文献，从脑病、脊髓损伤、关节炎等不同疾病中针灸对干细胞的影响，以及不同针灸方法对干细胞的影响等方面进行综述，以期为针灸的临床应用和基础研究提供相关思路。     

从脾论治慢性肾脏病的生物学基础探讨

脾为后天之源,肾为先天之本,以后天滋先天,使从脾论治成为中医临床治疗慢性肾脏病(CKD)的经典方法。现代医学研究发现人体内最庞大的“器官”——肠道菌群与“脾”的功能非常密切。目前研究发现肠道菌群紊乱是加速CKD进展的重要环节,基于脾肾互根互用的中医原理,收集、整理肠道菌群与CKD代谢功能、免疫应答及肾脏损伤关联的文献,从肠道菌群与机体功能代谢和内环境稳态的角度进行探讨,认识到运用中医药可通过干预肠道菌群的丰度、结构和代谢功能,维持肠道微生态的平衡,从而达到调节肾脏代谢和免疫应答的作用,提出肠道菌群是从脾论治慢性肾脏病的重要生物学基础。