Systemic therapy for hormone receptor-positive/human epidermal growth factor receptor 2-negative early stage and metastatic breast cancer

Hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer is defined by the presence of the estrogen receptor and/or the progesterone receptor and the absence of HER2 gene amplification. HR-positive/HER2-negative breast cancer accounts for 65%–70% of all breast cancers, and incidence increases with increasing age. Treatment varies by stage, and endocrine therapy is the mainstay of treatment in both early stage and late-stage disease. Combinations with cyclin-dependent kinase 4/6 inhibitors have reduced distant recurrence in the early stage setting and improved overall survival in the metastatic setting. Chemotherapy is used based on stage and tumor biology in the early stage setting and after endocrine resistance for advanced disease. New therapies, including novel endocrine agents and antibody-drug conjugates, are now changing the treatment landscape. With the availability of new treatment options, it is important to define the optimal sequence of treatment to maximize clinical benefit while minimizing toxicity. In this review, the authors first discuss the pathologic and molecular features of HR-positive/HER2-negative breast cancer and mechanisms of endocrine resistance. Then, they discuss current and emerging therapies for both early stage and metastatic HR-positive/HER2-negative breast cancer, including treatment algorithms based on current data.     

Could non-HDL-cholesterol be a better marker of atherogenic dyslipidemia in obstructive sleep apnea?

Background/objectiveObstructive sleep apnea (OSA) is independently associated with dyslipidemia, a surrogate marker of atherosclerosis. Low-density lipoprotein (LDL)-cholesterol is accepted as a major independent risk factor for cardiovascular disease. However, non-high-density lipoprotein (HDL)-cholesterol is a better marker of atherogenic dyslipidemia and recommended as a target of lipid lowering therapy. We aimed to assess the prevalence of atherogenic dyslipidemia, and relationship between OSA severity and serum LDL-cholesterol and non-HDL cholesterol levels in OSA patients.MethodsWe retrospectively evaluated treatment naïve 2361 subjects admitted to the sleep laboratory of a university hospital for polysomnography. All subjects’ lipid profile including total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, and non-HDL-cholesterol were measured.ResultsOut of 2361 patients (mean age 49.6 ± 11.9 years; 68.9% male, apnea-hypopnea index 36.6 ± 28.4/h), 185 (7.8%) had no OSA and 2176 (92.2%) had OSA. Atherogenic dyslipidemia prevalence was high (57–66%) in OSA patients, and especially increased in severe OSA compared to other groups (p < 0.05). Though total and LDL-cholesterol did not differ between those with and without OSA, non-HDL-cholesterol (p = 0.020), and triglycerides (p = 0.001) were higher and HDL-cholesterol levels (p = 0.018) were lower in OSA patients than non-OSA. Non-HDL-cholesterol was significantly correlated with OSA severity (p < 0.001) and hypoxia parameters (p < 0.01), whereas LDL-cholesterol showed no correlation.ConclusionsAtherogenic dyslipidemia is highly prevalent and non-HDL-cholesterol levels are significantly increased, predominantly in severe OSA patients. Non-HDL-cholesterol but not LDL-cholesterol, is significantly correlated with OSA severity and hypoxia parameters. Therefore, it could be better to use non-HDL-cholesterol, which is a guideline recommended target of lipid therapy, as a marker of atherosclerotic cardiovascular risk in OSA patients.     

Targeted literature review of the humanistic and economic burden of adult growth hormone deficiency

Background: Quality of life (QoL) and health economic data are becoming increasingly important factors in healthcare decision making. While there is a wealth of information establishing the benefit of growth hormone (GH) replacement therapy in adults with growth hormone deficiency (aGHD), recent reviews on the QoL and health economic impact of aGHD and the effect of treatment on these factors is limited.

Objective: The aim of this article is to summarize the impact of early and sustained treatment on the QoL and economic burden of aGHD by conducting a targeted literature review.

Methods: Standard electronic databases, including PubMed and the Cochrane collaboration website, were searched for publications between January 2006 and July 2016 for evidence of the humanistic and economic burden of aGHD. Search terms included growth hormone deficiency, health-related quality of life, HRQoL, patient-reported outcomes, outcome assessment, well-being and adherence.

Results: The literature search identified 732 initial hits and a final 14 publications were included. The analysis showed that the economic burden of aGHD is largely driven by the productivity losses associated with the disease. This is because most patients with aGHD are of working age and the QoL domains (memory & concentration and energy & vitality) most commonly affected by aGHD severely impair a person’s ability to work and may limit their contribution to society.

Conclusion: Untreated aGHD can seriously affect patients’ functioning. Early and continued treatment with GH replacement therapy could potentially improve the QoL and reduce the economic burden associated with aGHD. This review has limitations: only English language articles published since January 2006 were included and many of the studies were conducted in the Nordic countries; it is unclear how representative these studies are of the population as a whole. This was a literature review and not a systematic review, as it was thought to be unlikely that, in this rare disease, any additional publications would have been identified. Overall, this review reveals a paucity of data in this underserved population and points to research gaps which could be addressed with new studies.     

Glycine‐modified growth hormone secretagogues identified in seized doping material

A number of unknown pharmaceutical preparations seized by Danish customs authorities were submitted for liquid chromatography–high resolution mass spectrometry (LC–HRMS) analysis. Comparison with reference standards unequivocally identified the content of the powders as analogs of the growth hormone secretagogues GHRP‐2 (Pralmorelin), GHRP‐6, Ipamorelin, and modified growth hormone releasing factor (modified GRF 1–29), which can be used as performance‐enhancing substances in sports. In all cases, the detected modification involved the addition of an extra glycine amino acid at the N‐terminus, and analytical methods targeting growth hormone secretagogues should hence be updated accordingly.     

补肾活血汤对小卵泡排卵不孕症患者卵泡发育、卵巢动脉血流的影响

目的:观察补肾活血汤对小卵泡排卵(SFO)不孕症患者卵泡发育、卵巢动脉血流的影响。方法:将80例SFO不孕症患者随机分为两组,对照组40例接受枸橼酸氯米芬口服治疗,观察组40例,在对照组基础上加用补肾活血汤治疗,两组均治疗3个月经周期。统计两组临床疗效,并比较两组最大卵泡平均直径、子宫内膜厚度、成熟卵泡排卵率、未破裂卵泡黄素化综合征(LUFS)、妊娠率、早期自然流产率、性激素与卵巢动脉血流。结果:观察组治疗的临床总有效率为82.50%,明显高于对照组的62.50%(P<0.05)。与治疗前比较,两组治疗后最大卵泡平均直径、子宫内膜厚度均明显增加(P<0.05),且治疗后观察组以上指标均高于对照组(P<0.05)。观察组成熟卵泡排卵率和妊娠率高于对照组(P<0.05),LUFS发生率、早期自然流产率低于对照组(P<0.05)。与治疗前比较,治疗后两组血清LH、E₂水平、卵巢动脉PSV、EDV均明显增加(P<0.05),血清FSH、RI均明显降低(P<0.05),且治疗后观察组上述指标均优于对照组(P<0.05)。结论:补肾活血汤可明显促进SFO不孕症患者卵泡发育,增加成熟卵泡排卵率与妊娠率,并改善性激素与卵巢动脉血流循环。     

清热通利汤对宫颈炎并HPV感染患者生化指标与临床症状的影响研究

目的:观察清热通利汤对于宫颈炎合并人乳头瘤病毒(HPV)感染患者生化指标与临床症状的功效。方法:选取86例宫颈炎合并HPV感染患者作为观察资料,选取的患者按简单随机原则以数字表平均划分为对照组与治疗组,对照组给予常规治疗,治疗组给予清热通利汤外用; 治疗后3个月,对比临床疗效,统计临床症状的缓解时间; 评估治疗前、后患者生化指标、中医证候积分、血清炎性因子的变化情况。结果:治疗组显效率为53.49%、总有效率为95.35%,对照组依次为37.21%、72.09%,治疗组临床疗效优于对照组(P<0.05)。治疗后,治疗组患者HPV-DNA转阴率高于对照组,HPV-DNA转阴时间、HPV病毒载量均低于对照组,差异均有统计学意义(P<0.05); 治疗组患者宫颈柱状上皮异位、接触性出血、阴道清洁度异常、白带化验异常的消退时间均短于对照组(P<0.05); 治疗后两组患者各项中医证候积分、血清炎性因子与生化指标均较治疗前改善且治疗组均优于对照组(P<0.05)。结论:清热通利汤能够促进宫颈炎合并HPV感染患者HPV-DNA转阴,提高临床疗效,更有效的缓解临床症状、改善生化指标、减轻炎性反应程度。     

The effect of growth hormone treatment in a child with tricho-rhino-phalangeal syndrome: A case report and review of the literature

Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal malformations including short stature, cone-shaped phalangeal epiphyses and Perthes-like changes of the hip. We describe the response to growth hormone (GH) treatment in a boy with TRPS. The patient presented at age 3.5 years for evaluation of short stature (−3.2SD). On physical examination, the characteristic facial phenotype of TRPS was noted. Radiographs showed cone-shaped phalangeal epiphyses and bilateral small and fragmented femoral heads. The diagnosis was confirmed by Sanger sequencing of the TRPS1 gene. Two GH stimulation tests revealed GH deficiency, and GH treatment was initiated. Subsequently, growth velocity improved, as did the radiographic appearance of the femoral epiphyses, as seen on sequential pelvis radiographs.This observation suggests the possibility of a beneficial effect of GH treatment on both height and epiphyses status in TRPS patient with GH deficiency. Further studies are needed to support the observation.     

电针、敷脐疗法联合 HCG 治疗黄素化未破裂卵泡综合征临床研究

目的:观察电针、敷脐疗法联合人绒毛膜促性腺激素(HCG)治疗对黄素化未破裂卵泡综合征(LUFS)患者血清雌二醇(E2)、黄体生成素(LH)、排卵率及妊娠率的影响。方法:将60例LUFS患者按随机数字表法分为观察组和对照组各30例。对照组单纯给予HCG治疗,观察组给予电针、敷脐疗法联合HCG治疗,2组均连续治疗3个月经周期。观察2组治疗前后血清E2、LH含量的变化及排卵、妊娠情况。结果:治疗后,2组LH、E2水平均较治疗前升高,观察组LH、E2水平均高于对照组,差异均有统计学意义(P<0.05)。观察组排卵率、妊娠率均高于对照组,差异均有统计学意义(P<0.05)。结论:电针、敷脐疗法联合HCG治疗LUFS,可以提升LH、E2水平,促进排卵,提高妊娠率。