Personalized medicine: understanding probabilities and managing expectations

Personalized medicine promises to represent a transformation in clinical care that will be ushered in by the unprecedented growth and development in the field of human genetics. Further examination of the scientific foundations of this new hope reveals a great number of challenges that lie ahead. While basic science research feverishly races to produce solutions, we continue to wait for the translation of deliverables. Products that have and will come to market may leave our clinical communities and systems exposed and unprepared. At each step, from basic science research to infrastructure development, a great deal of creativity and investment are required before the arsenal of more personalized tools can be assimilated into our current models of health care. This commentary seeks to share perspectives on the current status of personalized medicine from the vantage point of several potential investors, and integrate them into a common set of goals and understanding. We conclude that the stylized model of personalized medicine is more akin to a marketing tool than a literal prediction of the future.     

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1病历资料患者女,54岁。因"间断陈旧性血便50余天"于2010-04-22入院。既往史:1995年患甲亢,药物治疗后好转,已停药近3年。KPS评分:90分。入院后体格检查未见异常,患者体表面积约1.57 m2。纤维结肠镜(2010-04-23)示回盲瓣对侧可见一溃疡型病变,大小约4.0 cm×3.5 cm,占     

Novel strategies for managing pancreatic cancer

With the incidence reports of pancreatic cancer increasing every year, research over the last several decades has been focused on the means to achieve early diagnosis in patients that are at a high risk of developing the malignancy. This review covers current strategies for managing pancreatic cancer and further discusses efforts in understanding the role of early onset symptoms leading to tumor progression. Recent investigations in this discussion include type 3c diabetes, selected biomarkers and pathways related to pancreatic intraepithelial neoplasia lesions, drug resistance, and advances in nanomedicine which may provide significant solutions for improving early detection and treatments in future medicine.     

Neuronal-binding antibodies from patients with antiphospholipid syndrome induce cognitive deficits following intrathecal passive transfer

Antiphospholipid antibodies (aPL) have been suggested to play a role in causing cognitive and behavioral impairments. In the present study we investigated the pathogenic potential of aPL by intracerebro-ventricular (ICV) administration of immunoglobulins (IgG) from patients with antiphospholipid syndrome (APS). IgG, purified from the sera of four APS patients, was tested for binding to normal mouse brain by immunohistological staining. These IgG (7.5 microg) were injected ICV unilaterally to male C3H mice. Mice injected with IgG purified from pooled sera derived from healthy subjects served as controls. The mice were examined neurologically for motor function and coordination, and cognitively in a Morris water maze. The cognitive tests were performed with the experimenter blinded to the treatment. The performance of the mice in four separate experiments was compared by analysis of variance with repeated measures. IgG from one APS patient was found to bind best to neuronal structures in the hippocampus and cerebral cortex. Mice (n = 43) injected with this IgG performed worse in the water maze compared to the controls (n = 45) with significant effects of the aPL IgG on the overall performance of the mice (treatment, P < 0.03), on learning throughout the experiment (treatment x day, P < 0.02) and on short term memory (treatment x day xtrial, P < 0.002). IgG injected from two of the three other patients also bound specifically to mouse brain neurons and produced an impairment in performance of the water maze. These results support the hypothesis that aPL that gain access to the central nervous system may play a direct role in the pathogenesis of neurological manifestations of APS.     

Patients strategies for managing medication for chronic heart failure

OBJECTIVES: To explore patients views of the management of medication of chronic heart failure (CHF); to explore in what circumstances they have difficulties in managing medication. DESIGN: Qualitative analysis of in-depth interviews using a constant comparative approach. PARTICIPANTS: Patients attending an outpatients clinic with a primary diagnosis of CHF due to left ventricular systolic dysfunction, NYHA Class II or III symptoms, and a history of hospital admission for heart failure. RESULTS: 50 patients were recruited, average age 67.1 years with ranges between 41 and 80 years. 26 were classified as NYHA Class II and 24 Class III. Patients reported developing routines and back up strategies to help with the complex task of medication-taking. They also described circumstances in which they were more likely not to take medication. CONCLUSIONS: This study demonstrates, with a large sample of respondents, the complexities of medication-taking and the difficulties of maintaining constant medication over a long period of time. The study provides examples of patients' strategies for so doing. Health care professionals should recognise that concordance may vary but explore ways in which they can help patients establish routines.     

遗传性帕金森病患者的脑功能显像

在过去的20年中,脑功能显像在帕金森病(Parkinson disease,PD)早期诊断、随访病情严重度中应用价值已经有比较深入的研究[1-3]。近年来,随着越来越多的单基因遗传性PD的发现,对这部分患者脑功能显像研究具有特别的价值,     

Personalised medicine: The cognitive side of patients

BackgroundAlthough the fashion for the “personalised” or “stratified” approach to medicine is valuable in exploiting the omic signatures of the individual patient, too little attention has been paid to the influence of psychological and cognitive factors in the care process. The aim of this paper is to highlight the importance of those individual psycho-cognitive components in affecting how people act to prevent, cope and react to illness, decide about different therapeutic options, interact with health care providers, and adhere to treatment.MethodsWe reviewed the medical and psychological literature about the effect of cognitive and psychological dimensions on treatment efficacy, on patients' global satisfaction, and on treatment compliance.ResultsPsychological dimensions have been proved to impact on treatment efficacy, on patients' global satisfaction, and on compliance to treatment. However, there are substantial individual differences among patients; therefore, it is important that physicians recognise how to apply these general recommendations to each individual patient, alongside the omic information emerging from the molecular diagnostic laboratory.ConclusionThe exam of the current literature allows one to derive several strategies which can help health professionals to improve the patients' understanding of their disease and involvement in the whole care process.     

Rehabilitation of therapy-related cognitive deficits in patients after hematopoietic stem cell transplantation

Neuropsychological deficits are potential side effects of hematopoietic stem cell therapy (HSCT). Systematic data on the long-term course of and therapeutic options for these consequences are limited. One hundred fifty-seven patients were screened for cognitive deficits following HSCT for malignant diseases at an in-patient oncologic rehabilitation clinic. Patients showing evidence of impairment were randomly assigned to one of two training groups: individualized PC-supported training or neuropsychological group therapy. The control group consisted of patients who received no specific training. During in-patient rehabilitation, the results of a comprehensive neuropsychological test battery improved significantly in all three groups, and no specific intervention effects were identified. Neuropsychological deficits were still evident in a subgroup of patients 6 months later. Correlation between neuropsychological testing and patients' self-evaluation of cognitive functioning in daily life was generally low. Sustained attention and verbal-semantic memory played the main role for self-appraisal and in the designation as 'neuropsychologically impaired'. In conclusion, a substantial number of patients revealed evidence of cognitive deficits a long time after HSCT. There is a need for more studies and for the development of differentiated rehabilitative measures for such therapeutic consequences.     

Depression and helplessness-induced cognitive deficits in the aged

Sixty-six community-residing elderly (mean age = 72.5) were categorized as depressed (mean = 11.3) or nondepressed (mean = 3.9) based on Beck Depression Inventory scores. After a pre-test battery measuring short-term memory and crystallized/fluid intelligence, the subjects responded to a word association task, disguised as a test of interpersonal empathy, under response dependent or response independent reinforcement conditions, or were assigned to a no treatment control. A post-test battery of alternate forms followed. Four of seven measures showed significant pre- to post-test declines in performance. For two of these four, response dependent reinforcement prevented otherwise significant declines. With pre-test differences statistically controlled, depression produced significant post-test deficits in three measures. Response dependent reinforcement eliminated this depression deficit in one measure. The results indicate that depression may exacerbate fatigue effects for the elderly and response dependent reinforcement may prevent fatigue-caused deficits in short-term memory.     

Early identification of cognitive deficits: preclinical Alzheimer's disease and mild cognitive impairment

With the projected dramatic increase in the number of people who will be diagnosed with Alzheimer's disease (AD) in the coming years, interest is growing in identifying and treating adults at high risk for developing the disorder. Recent research suggests that individuals who will go on to receive a diagnosis of AD exhibit deficits in cognitive performance years beforehand. Those with mild cognitive impairment (MCI), for example, have characteristic cognitive deficits, such as memory loss, and convert to a diagnosis of AD at a faster rate than cognitively healthy controls. MCI has thus become a focus of research because it may help identify high-risk individuals for whom prophylactic treatments designed to slow the progress toward AD can be prescribed. After describing the diagnostic criteria and dementia outcomes associated with MCI, this article discusses several challenges to the study of cognitive impairment before the diagnosis of AD.     

A prospective study of cognitive emotion regulation strategies and depressive symptoms in patients with essential hypertension

The objective of the current study was to examine the relationships between cognitive emotion regulation strategies and depressive symptoms in essential hypertension patients. Both cross-sectional and prospective relationships were studied in a sample of 650 essential hypertension patients. The cognitive emotion regulation strategies accounted for considerable amounts of variance in depressive symptoms. The following subscales were significantly positively correlated with first-time measurement and follow-up measurement of depressive symptoms: self-blame, rumination, catastrophizing, and blaming others. Positive reappraisal was significantly and positively correlated with first-time measurement of depressive symptoms. In contrast, the following subscales were significantly negatively correlated with follow-up measurement of depressive symptoms: acceptance, positive refocus, refocus on planning, positive reappraisal. Results of multiple regression analyses shows that elevated levels of self-blame, rumination, catastrophizing, and blaming others predicted increases in follow-up measurement of depressive symptoms, while elevated levels of acceptance and refocus on planning predicted decreases follow-up measurement of depressive symptoms. These findings provide us with important targets for intervention programs.     

Expanded algorithm for managing patients with acute decompensated heart failure

Heart failure is a complex disease process, the manifestation of various cardiac and noncardiac abnormalities. General treatment approaches for heart failure have remained the same over the past decades despite the advent of novel therapies and monitoring modalities. In the same vein, the readmission rates for heart failure patients remain high and portend a poor prognosis for morbidity and mortality. In this context, development and implementation of improved algorithms for assessing and treating HF patients during hospitalization remains an unmet need. We propose an expanded algorithm for both monitoring and treating patients admitted for acute decompensated heart failure with the goal to improve post-discharge outcomes and decrease rates of rehospitalizations.