基于“肝阳虚”理论探讨化疗所致周围神经病变的病机与治疗＊

化疗所致周围神经病变（Chemotherapy-induced peripheral neuropathy，CIPN）是临床常见的由化疗药物引起的一系列神经毒性症状，易造成神经功能障碍，四肢感觉弱化、缺失等，严重影响肿瘤患者生活质量及临床疗效。CIPN的发病机制尚不十分明确，目前也没有可广泛用于临床的特效药物治疗。中医药治疗CIPN具有特定的优势，取得了一定成绩，但在理论依据和临床疗效方面仍有一定的局限性。本文通过分析CIPN的临床症状特点，深入剖析其与中医肝阳虚理论之间的关系，探讨CIPN的中医病因病机与用药规律，指导临床治疗CIPN，以期更好地发挥中医药在肿瘤治疗中的减毒增效作用。     

A case-control study of risk factors for intussusception among infants in eastern France after the introduction of the rotavirus vaccine

ObjectiveThe objective of the present study was to investigate the risk factors for intussusception (IS) among infants, including vaccination against rotavirus.MethodsCase-control study with systematic inclusion of all infants aged <1 year with suspected IS admitted to emergency departments in the eastern region of France between 1 April 2008 and 31 March 2012. All cases classed level 1 according to the Brighton classification were matched to 4 hospital controls. Two exposure windows were examined; exposure to the first dose of rotavirus vaccine in the 7 and in the 14 days prior to the occurrence of IS.ResultsA total of 115 cases were matched with 457 controls. The average vaccination coverage rate over the 4 years of study was 8.6%. Rotavirus vaccine was not found to be significantly associated with the occurrence of IS in the 7 days (odds ratio (OR) not calculated; p = 0.99) and in the 14 days after administration of one dose vaccine (OR 1.33, 95% confidence interval (CI) 0.14–12.82). Infant formula alone or combined with breastfeeding was associated with an excess risk of IS (OR 2.74, 95% CI 1.10–6.79). A history of gastroenteritis within 2 weeks prior to hospitalisation was also associated with an increased risk (OR 2.24, 95% CI 1.07–4.67).ConclusionOur study indicates that infant formula alone or combined with breastfeeding is a risk factor for IS. A small, non-significant increase in the risk of IS was observed after rotavirus vaccination, although the low vaccine coverage rate likely precluded detection of a significant increase in risk.     

养精种玉汤的现代研究进展

养精种玉汤临床多用于治疗各种不孕症、多囊卵巢综合征、月经过少、闭经溢乳综合征、体外受精-胚胎移植等疾病,疗效确切。但是记载养精种玉汤的古代文献资料较少,现代研究大部分是临床试验和基础实验研究,且存在一些不足:①有些临床试验缺乏中医辨证,治疗疾病未辨证而直接辨病论治;②缺少治疗后随访及远期疗效评价,对妊娠结局的随访亦未予以特定的描述,不便于对研究结果做进一步分析;③相关研究中应完善血清激素水平指标的监测,以增加研究结果的说服力;④大部分研究样本量偏少,影响统计学结果,降低了结果的可靠性;⑤该方的安全性研究仅仅停留在动物实验阶段。因此,今后的研究应以辨证论治为基础,增加样本量,完善相关激素水平的检测,关注随访结果,为临床用药安全性提供更可靠的依据。     

杨宇飞教授运用健脾补肾序贯法防治结直肠癌化疗副反应的经验＊

细胞毒性化疗能提高早中期结直肠癌根治率，延长晚期患者生存期，而化疗的消化道和骨髓毒性严重影响患者的化疗依从性。中国中医科学院西苑医院杨宇飞教授从事中西医结合肿瘤防治临床和科研工作30余年。根据化疗期间消化道及骨髓毒副反应出现的先后顺序，创立第1周以健脾为主，第2、3周以补肾为重的序贯疗法，把化疗期间的中药协同治疗总结为“两阶段三步曲”，临床疗效满意，介绍其学术思想及临床经验。     

Automated brain MRI metrics in the EPIRMEX cohort of preterm newborns: Correlation with the neurodevelopmental outcome at 2 years

PurposeThe purpose of this study was to identify in the EPIRMEX cohort the correlations between MRI brain metrics, including diffuse excessive high signal intensities (DEHSI) obtained with an automated quantitative method and neurodevelopmental outcomes at 2 years.Materials and methodsA total of 390 very preterm infants (gestational age at birth ≤ 32 weeks) who underwent brain MRI at term equivalent age at 1.5T (n = 338) or 3T (n = 52) were prospectively included. Using a validated algorithm, automated metrics of the main brain surfaces (cortical and deep gray matter, white matter, cerebrospinal fluid) and DEHSI with three thresholds were obtained. Linear adjust regressions were performed to assess the correlation between brain metrics with the ages and stages questionnaire (ASQ) score at 2 years.ResultsBasal ganglia and thalami, cortex and white matter surfaces positively and significantly correlated with the global ASQ score. For all ASQ sub-domains, basal ganglia and thalami surfaces significantly correlated with the scores. DEHSI was present in 289 premature newborns (74%) without any correlation with the ASQ score. Metrics of DEHSI were greater at 3T than at 1.5T.ConclusionBrain MRI metrics obtained in our multicentric cohort correlate with the neurodevelopmental outcome at 2 years of age. The quantitative detection of DEHSI is not predictive of adverse outcomes. Our automated algorithm might easily provide useful predictive information in daily practice.     

A Randomized,Double-Blind,Placebo-Controlled,Phase III Noninferiority Study of the Long-Term Safety and Efficacy of Darbepoetin Alfa for Chemotherapy-Induced Anemia in Patients With Advanced NSCLC

IntroductionThis study evaluated noninferiority of darbepoetin alfa versus placebo for overall survival (OS) and progression-free survival (PFS) in anemic patients with NSCLC treated to a 12.0-g/dL hemoglobin (Hb) ceiling.MethodsAdults with stage IV NSCLC expected to receive two or more cycles of myelosuppressive chemotherapy and Hb less than or equal to 11.0 g/dL were randomized 2:1 to blinded 500 μg darbepoetin alfa or placebo every 3 weeks. The primary endpoint was OS; a stratified Cox proportional hazards model was used to evaluate noninferiority (upper confidence limit for hazard ratio [HR] < 1.15). Secondary endpoints were PFS and incidence of transfusions or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period.ResultsThe primary analysis set included 2516 patients: 1680 were randomized to darbepoetin alfa; 836 to placebo. The study was stopped early per independent Data Monitoring Committee recommendation after the primary endpoint was met with no new safety concerns. Darbepoetin alfa was noninferior to placebo for OS (stratified HR = 0.92; 95% confidence interval [CI]: 0.83‒1.01) and PFS (stratified HR = 0.95; 95% CI: 0.87‒1.04). Darbepoetin alfa was superior to placebo for transfusion or Hb less than or equal to 8.0 g/dL from week 5 to end of the efficacy treatment period (stratified odds ratio = 0.70; 95% CI: 0.57‒0.86; p < 0.001). Objective tumor response was similar between the groups (darbepoetin alfa, 36.4%; placebo, 32.6%). Incidence of serious adverse events was 31.1% in both groups. No unexpected adverse events were observed.ConclusionsDarbepoetin alfa dosed to a 12.0-g/dL Hb ceiling was noninferior to placebo for OS and PFS and significantly reduced odds of transfusion or Hb less than or equal to 8.0 g/dL in anemic patients with NSCLC receiving myelosuppressive chemotherapy.     

Gonadoblastoma-Associated Mixed Gonadal Germ Cell Tumor with Dysgerminoma and Hepatoid Yolk Sac Tumor Components in 46XY Gonadal Dysgenesis

BackgroundDisorders of sex development are congenital conditions with atypical chromosomal, gonadal, or anatomical sex development. Gonadal dysgenesis in patients containing a Y chromosome have a high risk of developing germ cell tumors with potential for malignant transformation.CaseWe present the case of a 17-year-old phenotypic female with primary amenorrhea and 46,XY complete gonadal dysgenesis. Pelvic ultrasound showed a solid cystic lesion in the right gonad. Pathology showed a gonadoblastoma-associated mixed gonadal germ cell tumor with dysgerminoma and hepatoid yolk sac tumor.Summary and ConclusionTo our knowledge, this mixed neoplasm association has not been previously reported and this case illustrates the challenges for the diagnosis of gonadal dysgenesis-associated tumors, emphasizing its recognition and prognostic implications.     

中西医治疗下丘脑性闭经疗效观察

目的:探讨激素、中药联合针刺治疗下丘脑性闭经(Hypothalamic Amenorrhea,HA)的临床疗效,旨在为下丘脑性闭经治疗提供新的方法和理论依据。方法:选取2018年3月-2019年3月郑州颐和医院门诊收治的90例下丘脑性闭经痰湿阻滞型患者为研究对象,根据随机数字表法分为对照组、观察组和实验组,对照组采用单纯激素治疗,观察组采用激素联合中药治疗,实验组采用激素、中药联合针刺治疗,比较三组患者的临床疗效和激素水平。结果:实验组临床疗效明显高于对照组和观察组,差异有统计学意义(P<0.05)。结论:对下丘脑性闭经患者采用激素、中药联合针刺治疗,可有效治疗患者闭经症状,且复发率低。     

Impact of chemotherapy-induced neutropenia on quality of life: a prospective pilot investigation

Purpose In this exploratory, prospective study evaluated quality of life (QoL) changes in patients with diverse cancers during the first cycle of myelosuppressive chemotherapy.Patients and methods Of 80 patients enrolled, 71 were observed during one of five chemotherapy regimens: docetaxel; CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone); carboplatin-paclitaxel; carboplatin-docetaxel; and carboplatin-gemcitabine. Complete blood counts were taken weekly. QoL and symptom burden measures were administered at baseline and throughout the cycle, and included SF-36, Cancer Care Monitor (CCM), Hospital Anxiety and Depression Scale (HADS), and Psychosocial Adjustment to Illness Scale (PAIS). Using generalized estimating equations, we modeled the change in each measure from baseline to the end of each week using the following covariates: baseline QoL measure, baseline SF-36 Physical and Mental Health Summary scores, sex, age, cycle week, grade 4 neutropenia any time in the past 7 days (yes/no), and the interaction of the latter two covariates.Results Of the 71 patients observed, 33 developed grade 4 neutropenia during the first 2 weeks. Changes from baseline in SF-36 Bodily Pain, HADS Anxiety, and PAIS Social Environment scores were significantly less favorable (P<0.05) when patients experienced grade 4 neutropenia any time in the past 7 days compared to when they did not (grade 0–3). A similar, but non-significant, trend was also observed for 12 other QoL measures.Conclusion QoL may be adversely affected up to 7 days after patients experience grade 4 (versus grade 0–3) neutropenia. Such findings need to be examined further in studies with adequate statistical power to test a priori hypotheses regarding specific QoL measures.Support for this work was provided by Amgen Inc.Portions of the research were previously presented at: Mayo Clinic Assessing Clinical Significance for QoL Measures in Oncology Research, State-of-the-Science, March 2002, Rochester, MN; the 27th Meeting of the European Society of Medical Oncology, October 2002, Nice, France; and the American Society of Hematology, December 2002, Philadelphia, PA.