XIAP is a predictor of cisplatin-based chemotherapy response and prognosis for patients with advanced head and neck cancer

Background

Approximately 60–80% of patients with advanced head and neck squamous cell carcinoma (HNSCC) die within five years after diagnosis. Cisplatin-based chemotherapy is the most commonly used palliative treatment for these patients. To evaluate the prognostic value of X-linked inhibitor of apoptosis (XIAP) level as a potential biomarker in these patients, we investigated the relationship between XIAP expression and cisplatin response of these patients and their prognosis.

Methodology/Principal Findings

Sixty patients with advanced HNSCC were recruited in this study. Expression of XIAP was examined both before and after chemotherapy and was correlated with chemotherapy response, clinicopathology parameters and clinical outcomes of the patients. We found that XIAP was expressed in 17 (20.83%) of the 60 advanced HNSCC samples and the expression was significantly associated with cisplatin resistance (P = 0.036) and poor clinical outcome (P = 0.025). Cisplatin-based chemotherapy induced XIAP expression in those post-chemotherapy samples (P = 0.011), was further associated with poorer clinical outcome (P = 0.029). Multivariate analysis demonstrated that only alcohol consumption, lymph node metastasis and XIAP level were independently associated with the prognosis of advanced HNSCC patients. Inhibiting XIAP expression with siRNA in XIAP overexpressed HNSCC cells remarkably increased their sensitivity to cisplatin treatment to nearly a 3 fold difference.

Conclusions/Significance

Our results demonstrate that XIAP overexpression plays an important role in the disease course and cisplatin-resistance of advanced HNSCC. XIAP is a valuable predictor of cisplatin-response and prognosis for patients with advanced head and neck cancer. Down-regulation of XIAP might be a promising adjuvant therapy for those patients of advanced HNSCC.     

Cytokines in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is one of the most frequent cancers in the world. Standard treatment has only marginally improved the 5-year survival rate of patients with HNSCC in the last 40 years. Alterations in immune, inflammatory as well as angiogenetic responses within the HNSCC microenvironment play a critical role in tumor aggressiveness and its response to chemo- and radiation therapies as well as its influence on the immune system. Therefore, the better understanding of secretion and regulation pathways of immune suppressive and proangiogenic cytokines in HNSCC is essential to increase the clinical perspective of this tumor type with respect to an immunomodulatory intervention in patients with HNSCC.     

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age >/= 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN.     

Identifying Elements of Patient-Centered Care in Underserved Populations: A Qualitative Study of Patient Perspectives

Patient-centered care is an important goal in the delivery of healthcare. However, many patients do not engage in preventive medical care. In this pilot study, we conducted twenty in depth, semi-structured qualitative interviews at the University of Illinois at Chicago Health Sciences campus in a four month time frame. Many patients were underserved and underinsured, and we wanted to understand their experiences in the healthcare system. Using content analysis, several themes emerged from the interview data. Participants discussed the need for empathy and rapport with their providers. They identified provider behaviors that fostered a positive clinical relationship, including step-by step explanations of procedures, attention to body language and clinic atmosphere, and appropriate time management. Participants identified cost as the most common barrier to engaging in preventive care and discussed children and social support as motivating factors. A long-term relationship with a provider was an important motivator for preventive care, suggesting that the therapeutic alliance was essential to many patients. Conversely, many participants discussed a sense of dehumanization in the healthcare system, reporting that their life circumstances were overlooked, or that they were judged based on insurance status or ethnicity. We discuss implications for provider training and healthcare delivery, including the importance of patient-centered medical homes.     

Molecular characterization of head and neck cancer: how close to personalized targeted therapy?

Molecular targeted therapy in head and neck squamous cell carcinoma (HNSCC) continues to make strides, and holds much promise. Cetuximab remains the sole US FDA-approved molecular targeted therapy available for HNSCC, though several new biologic agents targeting the epidermal growth factor receptor (EGFR) and other pathways are currently in the regulatory approval pipeline. While targeted therapies have the potential to be personalized, their current use in HNSCC is not personalized. This is illustrated for EGFR-targeted drugs, where EGFR as a molecular target has yet to be individualized for HNSCC. Future research needs to identify factors that correlate with response (or lack of one) and the underlying genotype-phenotype relationship that dictates this response. Comprehensive exploration of genetic and epigenetic landscapes in HNSCC is opening new frontiers to further enlighten and mechanistically inform newer as well as existing molecular targets, and to set a course for eventually translating these discoveries into therapies for patients. This opinion offers a snapshot of the evolution of molecular subtyping in HNSCC and its current clinical applicability, as well as new emergent paradigms with implications for controlling this disease in the future.     

The cost of somatisation among the working-age population in England for the year 2008-2009

Medically unexplained symptoms are one of the most commonly encountered symptoms across all healthcare settings. They are also responsible for a large proportion of disability in the workforce and decreased quality of life. These patients represent an important clinical phenomenon with considerable direct and indirect economic consequences.This study aims to calculate the economic burden of somatisation among English adults in 2008-2009.Using existing literature, estimates of prevalence, healthcare use and disability were combined in order to calculate the annual cost of healthcare use and productivity loss associated with these patients in excess of non-somatising patients.Based on the results of our analysis, the incremental health care cost incurred by somatising patients is estimated to be ￡3 billion. This represents approximately 10% of total NHS expenditure on these services for the working-age population in 2008-2009. The cost of sickness absence and decreased quality of life associated with these patients amounts to over ￡14 billion.By highlighting the magnitude of this phenomenon at each level of the health system and the considerable impact of non-healthcare costs, this study serves to draw attention to a group of patients who are frequently unrecognised or misdiagnosed by physicians who tend to repeatedly pursue organic possibilities through multiple tests, procedures and operations. As economic perspectives play an increasing role in healthcare planning, the reduction of health care use and improvement of functioning among this group of patients should be a major goal. In order to realise these goals, changed pathways and behaviour in primary and secondary care are needed, along with improved access to psychological therapy services.     

Is sympathetic activation by stressful memories linked to the occurrence of hypertension and metabolic syndrome?

This paper is based on reported links between dementia and hypotension. Large clinical studies report that patients with Alzheimer's disease normalize previously elevated blood pressure. Among previously hypertensive, elderly persons, an unexpected minority of hypotensive elderly patients with cognitive decline has been found. A possible interpretation is that patients of both groups, instead of having cognition problems due to arterial hypotension, might have become hypotensive because they can no longer remember and worry about stress-inducing problems that have vanished from their memories.I propose that memory induced stress reactions increase the resting sympathetic tone, vascular resistance, secretion of renin and contrainsulary hormones. Dementia reduces this source of chronic stress reaction, and hence reduction on sympathetic activation could explain both the reduction in blood pressure and relief from insulin resistance. This might explain how is it possible that blocking of sympathetic activity and renin–angiotensin system prolongs human life, despite importance of these mechanisms in maintaining circulatory homeostasis in all mammals.     

37 例老年胃癌合并胰腺受侵围手术期的临床治疗分析

目的:探讨老年胃癌合并胰腺受侵患者围手术期合并症及并发症发生率与其他老年胃癌患者间的差异,优化老年胃癌合并胰腺受侵患者围手术期临床治疗护理策略。方法:收集2005年2月至2009年10月前来我院治疗的37名年龄>65岁的老年胃癌合并胰腺受侵患者作为研究对象,设置相同年龄胃癌无胰腺受侵患者37例作为对照,收集详细临床资料,对两组间围手术期合并症发生情况进行卡方(x2)检验,通过采取不同临床治疗护理手段进一步施行干预(包括不同的手术方式及临床监测管理模式),再次采用x2检验比较两组术后并发症发生率,最后通过随访实现Kaplan-Meier生存分析。结果:老年胃癌合并胰腺受侵组(组Ⅰ)与老年胃癌无胰腺受侵组(组Ⅱ)术前总体合并症发生率并无显著统计学差异(P>0.05);各项合并症中仅有血红蛋白降低(<100g/L)、白蛋白降低(<35g/L)以及合并糖尿病的患病人数存有统计学意义(P=0.020,P=0.032,P=0.013);根据两组患病情况不同采取不同手术方式,两组死亡人数未见统计学意义(P>0.05);组Ⅰ术后并发症发生率为70.27%,低于组Ⅱ的86.49%,但两组未见明显统计学差异(P>0.05);比较两组功能性、心血管类并发症,两者间存在显著统计学差异(P=0.036,P=0.013);两组术后5年生存率比较无统计学差异(P=0.8308)。结论:需加强对老年晚期胃癌合并胰腺患者围手术期的临床治疗护理策略,采取适宜的手术治疗方式,可减少术后并发症及死亡的发生,提高患者生活质量。     

Tratamiento de la diabetes mellitus tipo 2 en el paciente anciano

The prevalence of type 2 diabetes mellitus (DM2) increases markedly with age. Antidiabetic treatment and the objectives of glycaemic control in elderly patients with DM2 should be individualised according to their biopsychosocial characteristics. In elderly patients for whom the benefits of intensive antidiabetic treatment are limited, the basic objectives should be to improve the quality of life, preserve functionality and avoid adverse effects, especially hypoglycaemia.Treatment of DM2 in the elderly was the subject of a consensus document published in 2012 and endorsed by several Spanish scientific societies. Since then, new therapeutic groups and evidence have emerged that warrant an update to this consensus document. The present document focuses on the therapeutic aspects of DM2 in elderly patients, understood as being older than 75 years or frail.     

Outlier Analysis Defines Zinc Finger Gene Family DNA Methylation in Tumors and Saliva of Head and Neck Cancer Patients

Head and Neck Squamous Cell Carcinoma (HNSCC) is the fifth most common cancer, annually affecting over half a million people worldwide. Presently, there are no accepted biomarkers for clinical detection and surveillance of HNSCC. In this work, a comprehensive genome-wide analysis of epigenetic alterations in primary HNSCC tumors was employed in conjunction with cancer-specific outlier statistics to define novel biomarker genes which are differentially methylated in HNSCC. The 37 identified biomarker candidates were top-scoring outlier genes with prominent differential methylation in tumors, but with no signal in normal tissues. These putative candidates were validated in independent HNSCC cohorts from our institution and TCGA (The Cancer Genome Atlas). Using the top candidates, ZNF14, ZNF160, and ZNF420, an assay was developed for detection of HNSCC cancer in primary tissue and saliva samples with 100% specificity when compared to normal control samples. Given the high detection specificity, the analysis of ZNF DNA methylation in combination with other DNA methylation biomarkers may be useful in the clinical setting for HNSCC detection and surveillance, particularly in high-risk patients. Several additional candidates identified through this work can be further investigated toward future development of a multi-gene panel of biomarkers for the surveillance and detection of HNSCC.     

Towards remote monitoring and remotely supervised training

The growing number of elderly and people with chronic disorders in our western society puts such a pressure on our healthcare system that innovative approaches are required to make our health care more effective and more efficient. One way of innovating healthcare can be obtained by introducing new services that support and enable these elderly and people with chronic disorders in a more independent living and in self management with respect to their disorders. Examples of such services are remote monitoring and remotely supervised training (together RMT). Remote monitoring focuses on continuous monitoring of the health status with the assurance of assistance whenever required. Remotely supervised training focuses on efficient and effective individually tailored training anywhere and anytime with intensity not feasible in an intramural setting. It is expected that services of remote monitoring and remotely supervised treatment will become important for at least patients (safety, more in control, convenience), health care insurances (efficiency, cost reduction) and healthcare service providers (more effective care).RMT systems are in general quite complex distributed Information and Communication Technology (ICT) systems. RMT systems integrate ambulant sensing to measure relevant biosignals and (possibly) subject’s context information, secure data transport and storage, appropriate decisions support systems to assist in both technical and clinical decision making but also feedback on information to both patients and care providers. Feedback is essential for patients to make them aware of their health status, to give them a feeling of safety and to motivate and enable them to change/improve their health status. Feedback of information to healthcare professionals enables them in making appropriate decisions and to monitor changes/improvements in a patient’s health status.Despite this apparent complexity, these systems must be very dependable to be accepted and used in a healthcare setting. During the past years knowledge and experience has been gained with the development of the building blocks of RMT systems. In parallel, experience has been gained with respect to the challenges involved when using RMT systems in a clinical environment. Examples are: activity monitoring in low back pain, monitoring of spasticity, myofeedback in subjects with neck shoulder and lower back pain and post rehabilitation home training. Until now, the main focus has been on the technical realization of the sensing and transportation part of it. The development of intelligent decision support systems is still in its infancy and clinical validation studies and models how to implement these services and how to make them profitable are largely lacking.In conclusion, the combination of Biomedical Engineering with Information and Communication Technology has opened a new extensive area of research and development with a high potential to have substantial impact on our future healthcare.     

Measurement of quality of life in patients with dementia of Alzheimer type and their caregivers: Schedule for the Evaluation of Individual Quality of Life (SEIQoL)

Twelve patients with mild to moderate Alzheimer's Disease (AD) and their caregivers were interviewed with the SEIQoL. The SEIQoL measures quality of life by taking into account the relevant determinants for a particular individual. The subject rates 5 areas in life most important to the quality of life. The relative contribution of each area to the overall quality of life is then calculated with a multiple regression analysis programme developed for the purpose. Next the SEIQoL Index score, validity and reliability are computed. One patient was unable to complete the interview. The remaining (8 women, 3 men, mean age 71.3 years) had a mean SEIQoL Index score of 79.9 (median: 85.4), which is comparable to healthy Dutch elderly. The caregivers (10 spouses, 2 daughters; mean age 67.4 years), on the other hand, had a lower SEIQoL Index score: 62.2 (median: 63.8). Validity and reliability were good for both groups. Thus, caregivers in this pilot study experienced a lower quality of life than AD patients and healthy Dutch elderly. The SEIQoL allows quantitative measurement of completely individualised quality of life for AD patients and their caregivers.     

多西他赛单药与培美曲塞联合顺铂二线治疗老年晚期胃癌的疗效及对患者生活质量的影响

目的:探讨多西他赛单药与培美曲塞联合顺铂二线治疗老年晚期胃癌的疗效及对患者生活质量的影响,为临床用药提供参考。方法:选取我院2014年6月-2017年6月期间收治的120例一线化疗失败的老年晚期胃癌患者,按照随机数字表法将患者分为观察组和对照组各60例,观察组使用培美曲塞联合顺铂治疗,对照组单独使用多西他赛治疗,两组均治疗3个疗程。治疗3个疗程后,采用实体肿瘤的疗效评价标准(RECIST)对两组患者的临床疗效进行评价,参照抗癌药物常见毒副反应分级标准统计患者出现的不良反应,采用生活质量量表评价患者的生活质量,并对所有患者进行为期半年的随访,统计两组患者的生存率。结果:观察组有效率(RR)为30.00%,略高于对照组的25.00%,但两组比较差异无统计学意义(P>0.05)。两组患者不良反应发生率比较差异无统计学意义(P>0.05)。治疗后,观察组患者日常生活、社会活动、抑郁、焦虑得分均明显高于对照组(P<0.05)。观察组患者半年生存率为71.67%,明显高于对照组的48.33%(P<0.05)。结论:相比于多西他赛单药治疗,培美曲塞联合顺铂二线治疗老年晚期胃癌能够改善患者生活质量,延长其生存期,安全可靠。     

Dental Status in the Elderly: A Review of the Swedish Literature1

1. Elderly persons living in their own homes have over the past 20 years tended to retain an increased number of natural teeth. This tendency is confirmed especially in the ongoing studies by Tor Österberg, nr 12 and 13. These studies indicate a decreasing edentulous part of the 70-year old cohorts from 1971, 1976 and 1981. 2. Elderly persons dependent on institutional care are edentulous in as high degree today as 20 years ago. According to this criterion, therefore, their dental health has not improved. 3. Dentures worn by elderly persons frequently are defective in fit and function. For the general wellbeing and health in later life, mastication of a well-balanced diet and lack of discomfort from denture-bearing mucosal surfaces are important. Information in this respect and measures to improve masticating function are greatly needed among persons in the higher age groups, whether living at home or in institutional care. 4. Caries activity is increasing among elderly persons. 5. Periodontitis (loosening of the teeth) is very frequently found in elderly persons. 6. Oral hygiene requires improvement. 7. Among the elderly, living in their own homes or in institutions, the need for odontologic care is objectively great, but the demands currently made are remarkably low. 8. Of the aged in institutional care, about 75 per cent are suitable for measures of oral care. A change in dental health seems to be slowly taking place among the elderly, in that increasing numbers keep more of their own teeth longer in life. The demands made by the high age groups on the odontologic services, though increasing, are still very low relative to the objective and consequently great accumulated needs. This contrast is especially pronounced among geriatric patients in institutions. An aggressive, searching approach to both restorative and preventive oral care in the higher age groups is of pressing importance if optimum conditions for eating and chewing late in life are to be achieved. For timely counteraction of the tendency to a more passive attitude t o dental care that commonly accompanies rising age, information on these matters should be energetically disseminated among persons due for retirement or new-l y retired.     

Prediction of head and neck squamous cell carcinoma survival based on the expression of 15 lncRNAs

Recent evidence suggests that long noncoding RNAs (lncRNAs) are essential regulators of many cancer-related processes, including cancer cell proliferation, invasion, and migration. There is thus a reason to believe that the detection of lncRNAs may be useful as a diagnostic and prognostic strategy for cancer detection, however, at present no effective genome-wide tests are available for clinical use, constraining the use of such a strategy. In this study, we performed a comprehensive assessment of lncRNAs expressed in samples in the head and neck squamous cell carcinoma (HNSCC) cohort available in The Cancer Genome Atlas database. A risk score (RS) model was constructed based on the expression data of these 15 lncRNAs in the validation data set of HNSCC patients and was subsequently validated in validation data set and the entire data set. We were able to stratify patients into high- and low-risk categories, using our lncRNA expression panel to determine an RS, with significant differences in overall survival (OS) between these two groups in our test set (median survival, 1.863 vs. 5.484 years; log-rank test, p < 0.001). We were able to confirm the predictive value of our 15-lncRNA signature using both a validation data set and a full data set, finding our signature to be reproducible and effective as a means of predicting HNSCC patient OS. Through the multivariate Cox regression and stratified analyses, we were further able to confirm that the predictive value of this RS was independent of other predictive factors such as clinicopathological parameters. The Gene set enrichment analysis revealed potential functional roles for these 15 lncRNAs in tumor progression. Our findings indicate that an RS established based on a panel of lncRNA expression signatures can effectively predict OS and facilitate patient stratification in HNSCC.     

Multidisciplinary transmural rehabilitation for older persons with a stroke: the design of a randomised controlled trial

Background

Stroke is one of the major causes of loss of independence, decreased quality of life and mortality among elderly people. About half of the elderly stroke patients discharged after rehabilitation in a nursing home still experience serious impairments in daily functioning one year post stroke, which can lead to difficulties in picking up and managing their social life. The aim of this study is to evaluate the effectiveness and feasibility of a new multidisciplinary transmural rehabilitation programme for older stroke patients.

Methods

A two group multicentre randomised controlled trial is used to evaluate the effects of the rehabilitation programme. The programme consists of three care modules: 1) neurorehabilitation treatment for elderly stroke patients; 2) empowerment training for patient and informal caregiver; and 3) stroke education for patient and informal caregiver. The total programme has a duration of between two and six months, depending on the individual problems of the patient and informal caregiver. The control group receives usual care in the nursing home and after discharge.Patients aged 65 years and over are eligible for study participation when they are admitted to a geriatric rehabilitation unit in a nursing home due to a recent stroke and are expected to be able to return to their original home environment after discharge. Data are gathered by face-to-face interviews, self-administered questionnaires, focus groups and registration forms. Primary outcomes for patients are activity level after stroke, functional dependence, perceived quality of life and social participation. Outcomes for informal caregivers are perceived care burden, objective care burden, quality of life and perceived health. Outcome measures of the process evaluation are implementation fidelity, programme deliverance and the opinion of the stroke professionals, patients and informal caregivers about the programme. Outcome measures of the economic evaluation are the healthcare utilisation and associated costs. Data are collected at baseline, and after six and 12 months. The first results of the study will be expected in 2014.

Trial registration

International Standard Randomised Controlled Trial Register Number ISRCTN62286281, The Dutch Trial Register NTR2412

     

血管性认知功能障碍的研究进展

血管性认知功能障碍(VCI)是目前严重危害老年人健康的疾病之一。随着人类寿命的延长、人口老龄化的增加,将会有越来越多的老年人患者患上VCI。对于VCI的早期、有效的干预有重要的临床意义,也受到人们的广泛关注。如能预防甚至治疗VCI的产生,可从很大程度上提高老年人的生活质量,减轻家庭和社会的负担。现就近年来对血管性认知功能障碍的相关研究予以综述。     

Quality of Life Is Related to Social Support in Elderly Osteoporosis Patients in a Chinese Population

Objective

To explore the association between quality of life and social support in elderly osteoporosis patients in a Chinese population.

Methods

A total of 214 elderly patients who underwent bone mineral density screening were divided into two groups: elderly patients with primary osteoporosis (case group, n = 112) and normal elderly patients (control group, n = 102). Quality of life and social support were compared between the two groups.

Results

Quality of life and social support were significantly different between the case and control groups. The physical function, role-physical, bodily pain, general health, vitality, social-functioning, role-emotional and mental health scores in case group were significantly lower than those in the control group (P < 0.01). The objective support, subjective support, utilization of support, and total scores in case group were significantly lower than those in the control group (P < 0.01). Quality of life and social support were positively correlated in the case group (r = 0.672, P < 0.01).

Conclusion

Quality of life and social support in elderly patients with osteoporosis in China were poorer than in elderly patients without osteoporosis and were positively correlated. Our findings indicate that increased efforts to improve the social support and quality of life in elderly osteoporosis patients are urgently needed in China. Further longitudinal studies should be conducted to provide more clinical evidence to determine causative factors for the observed association between risk factors and outcomes.