Is weight-based IV dosing of trastuzumab preferable to SC fixed-dose in some patients? A systematic scoping review

Trastuzumab, a key treatment for HER2-positive breast cancer, is available in weight-based IV and fixed-dose (600 mg) SC formulations. While the Phase 3 HannaH trial indicated non-inferiority of the SC formulation, there is some concern that the target plasma concentration may not be reached in overweight/obese patients whereas low-body-weight patients may be at risk of toxicity.This scoping review evaluated whether overweight/obese patients are at risk of below-target exposure with fixed-dose SC trastuzumab, whether low-body-weight patients are at risk of increased toxicity, especially cardiotoxicity, and whether IV and SC trastuzumab are equivalent in terms of treatment-emergent adverse events (TEAEs) (e.g. infections). Thirty-seven publications that met the eligibility criteria were included.Body weight is not an important determinant of exposure to trastuzumab at steady state (i.e. pre-dose cycle 8); however, real-world evidence suggests that the target concentration (20 μg/mL) may not be reached with the first SC dose in overweight/obese patients. There is no evidence that low-body-weight patients are at increased risk of cardiotoxicity with SC trastuzumab, although this may be confounded by the higher rate of cardiovascular comorbidities in overweight patients. In Phase 3 trials, SC trastuzumab was associated with higher rates of ISRs, ADAs and SAEs, the latter often requiring hospitalization and occurring during adjuvant treatment when patients are not burdened by chemotherapy.The route of administration of trastuzumab (IV vs SC) in different treatment settings should be discussed with the patient, taking into account the risks and benefits associated with each route.     

Association of malnutrition with all-cause mortality in the elderly population: A 6-year cohort study

Background and aimsFew studies have explored the association between malnutrition, defined by the Geriatric Nutritional Risk Index (GNRI), and all-cause mortality, particularly in the Chinese population. This study aimed to investigate the association between the GNRI and all-cause mortality in the elderly population.Methods and resultsParticipants aged ≥60 years were eligible for this study and were divided into three groups by the GNRI: An adequate nutrition group, participants with a GNRI ≥98; mild malnutrition group, participants with a GNRI ≥82 but <98; and a severe malnutrition group, participants with a GNRI <82. The results implied that there was a positive association between severe malnutrition and all-cause mortality in the total population (hazard ratio (HR): 2.591 and 95% confidence interval (CI): 1.729–3.884), male subjects (HR: 2.903 and 95% CI: 1.718–4.906), and female subjects (HR: 2.081 and 95% CI: 1.071–4.046). Similar associations between severe malnutrition and all-cause mortality were observed in both the 60–69 and 70–79 years age groups (HR: 2.863 and 2.600, 95% CI: 1.444–5.678 and 1.394–4.849, respectively). However, no significant association was observed between mild malnutrition and all-cause mortality.ConclusionsSevere malnutrition could increase all-cause mortality in the 60- to 79-year-old population. However, there was no association of mild malnutrition with all-cause mortality.     

Overweight/Obesity and Monoclonal Gammopathy of Undetermined Significance

BackgroundObesity and high body mass index (BMI) are associated with increased incidence of multiple myeloma (MM). MM usually evolves from a precursor asymptomatic disease, namely monoclonal gammopathy of undetermined significance (MGUS). MGUS progresses to MM at a 1% annual rate; however, risk factors predisposing to MGUS are not completely understood. We conducted a systematic review to assess the relationship between obesity and high BMI with MGUS prevalence and progression to MM. To our knowledge, this is the first systematic review evaluating the role of obesity in MGUS.Patients and MethodsWe searched the Medline database and ClinicalTrials.gov for studies investigating BMI and obesity association with MGUS incidence and progression. The algorithm consisted of a predefined combination of the words “obesity,” “obese,” “body mass index,” “overweight,” “diet,” “nutrition,” “food,” “dietary,” “adiponectin,” “monoclonal gammopathy,” and “MGUS”.ResultsOverall, 12 articles were retrieved, including 11 eligible articles and 1 clinical trial. More than 57,068 patients were evaluated in this systematic review. Discrepancies between the identified studies were noted. Multiple studies support the notion that obesity or high BMI are positively linked to MGUS prevalence and transition to MM. In contrast, other studies revealed no such association. Visceral adipose tissue metabolic activity and decreased adiponectin concentrations were identified as biomarkers of MGUS progression to MM.ConclusionObesity and increased BMI seem to be implicated both in MGUS development and progression to MM. Further studies should be designed to confirm this hypothesis.     

Trends in Physical Fitness Among 12-Year-Old Children in Urban and Rural Areas During the Social Transformation Period in China

Aims

To investigate the 29-year (1985–2014) trends in body dimensions and physical fitness test performances among 12-year-old Chinese children living in urban and rural areas.

胃癌淋巴结转移相关危险因素及其临床预测价值分析

背景与目的:淋巴结转移与胃癌患者预后之间密切关联,且淋巴结转移与否及淋巴结转移程度对患者治疗方案的选择至关重要,但目前术前淋巴结转移预测方法仍有一定局限性。本研究旨在探讨胃癌患者淋巴结转移现象的相关危险因素,为术前预测淋巴结转移提供一定途径。方法:回顾2014年1月-2015年4月收治的380例胃癌患者的临床与随访资料,分析淋巴结转移与患者相关临床病理因素的关系,从中寻找出胃癌淋巴结转移危险因素,并进一步用ROC曲线分析危险因素对胃癌淋巴结转移的预测能力,用Kaplan-Meier法分析危险因素对患者预后的影响。结果:380例患者中,241例(63.42%)发生淋巴结转移。单因素分析结果显示,BMI、肿瘤浸润深度、分化程度、Lauren’s分型、肿瘤直径以及肿瘤标志物CA125与胃癌淋巴结转移明显有关(均P<0.05);多因素分析结果显示,BMI(OR=4.175,P=0.041)和肿瘤浸润深度(OR=16.444,P<0.000 1)是胃癌淋巴结转移的独立危险因素;相关性分析结果显示,淋巴结转移阳性率与BMI值呈明显正相关(r=1.95,P=0.007)。BMI(以24 kg/m^2为临界值)与肿瘤浸润深度分级(以T4期为标准)预测是否有淋巴结转移的敏感度均为63.16%,特异度分别为76.84%、53.68%;两者联合应用特异度增高至88.36%,ROC曲线下面积达75.76%。生存分析结果显示,高BMI值患者的3年总生存率明显低于低BMI值患者(51.09% vs.53.13%,P<0.05)。结论:BMI与肿瘤浸润深度是胃癌患者淋巴结转移的独立危险因素,患者BMI值越高淋巴结转移的可能性越大,结合肿瘤浸润深度情况分析,对术前预测淋巴结转移有一定的临床实用价值。     

头部电针透穴、体针联合氟西汀治疗脑卒中后抑郁临床研究

目的:观察头部电针透穴、体针联合氟西汀治疗对脑卒中后抑郁患者脑电图及抑郁情况的影响。方法:选取122例脑卒中后抑郁患者为研究对象,按随机数字表法分为对照组和研究组各61例。对照组给予盐酸氟西汀胶囊治疗,研究组在此基础上联合头部电针透穴、体针治疗,2组均治疗4周。对比2组临床疗效,评估患者治疗前后的脑电图及抑郁情况。结果:研究组总有效率86.89%,高于对照组的68.85%,差异有统计学意义(P<0.05)。与治疗前比较,治疗后2组脑电图正常患者比率均升高,研究组脑电图正常患者比率高于对照组,差异均有统计学意义(P<0.05)。与治疗前比较,治疗后2组汉密尔顿抑郁量表(HAMD)评分均降低,且研究组HAMD评分低于对照组,差异均有统计学意义(P<0.05);2组血浆5-羟吲哚乙酸(5-HIAA)水平均升高,且研究组血浆5-HIAA水平高于对照组,差异均有统计学意义(P<0.05)。结论:头部电针透穴、体针联合氟西汀可有效改善脑卒中后抑郁患者的临床症状,调节5-HIAA水平,疗效优于单纯使用氟西汀治疗。     

Birth weight,weight over the adult life course and risk of breast cancer

Breast cancer has been suggested to potentially have prenatal origins. We examined associations between birth weight, body mass index (BMI) at four-time points over 25 years of adulthood, and risk of postmenopausal breast cancer, with emphasis on whether the association between birth weight and risk of breast cancer was mediated by weight and height changes over the adult life course. Postmenopausal women (n = 70,397) aged 50–79 years without breast cancer at enrollment (1993–1998) were followed up to 25 years. Weight and height were measured at baseline. Birth weight, and weights at ages 18, 35 and 50 were self-reported. Breast cancer cases were centrally adjudicated. Compared to women with birth weight of 6–8 pounds, women with birth weight of <6 pounds had lower risk of breast cancer (HR = 0.88 95% CI: 0.79–0.99). 44% and 21% of the relationship between birth weight and breast cancer risk was mediated by adult height and weight at baseline, respectively. Birth weight of 8 pounds or more was not associated with risk of postmenopausal breast cancer. Weight gain in adulthood was associated with increased risk of breast cancer regardless of time periods. In conclusion, lower birthweight was associated with lower risk of postmenopausal breast cancer, and this reduction in risk was significantly mediated by childhood or adolescent growth, especially by adult height. Our data suggest that reaching and maintaining a healthy weight during adulthood is key in the prevention of breast cancer.     

体部伽马刀治疗各类转移瘤临床进展

随着人类平均寿命延长,癌症对人类的威胁日益突出,已经成为我国城乡居民的第1位死因。随着病情进展,很多患者除了原发恶性肿瘤外,多数会有其他部位的转移瘤出现,因此选择有效的治疗方法至关重要。体部伽马刀治疗是一种精确的立体定向放疗方法,能够给予肿瘤较高剂量,并较好的保护周围正常组织。大量临床治疗结果显示体部伽马刀治疗肺转移瘤、肝转移瘤和肾上腺转移瘤可获得较高的局控率。本文就体部伽马刀治疗各类转移瘤进行综述。     

中医气郁质的研究进展

体质是在先天遗传和后天获得共同影响下形成的个体在形态结构和功能活动方面所固有的、相对稳定的特点,并且与心理性格具有相关性。其中气郁质的表现多与心理性格具有较大的相关性,同时由于当代社会的快速发展,各种危机和压力使年轻人成为气郁质的高发人群,因此探究气郁质的相关研究具有重大意义。本文通过对近些年来所发表的气郁质相关文献进行总结,重点从气郁质的人群分布调查研究、体病相关研究、调体干预研究以及实验室相关指标的研究四个方面进行分析阐述。最后对目前关于气郁质的研究中存在的优点和不足进行思考,并提出气郁质研究应在中医理论为指导的基础上,通过现代分子生物学实验或临床干预调体研究,揭示气郁质的本质和其量化诊疗标准,丰富气郁质的理论数据支持,促进中医体质学与多学科的交互发展。