营养支持治疗心力衰竭恶病质的临床观察

目的探索心力衰竭恶病质的营养支持疗法．明确营养支持治疗能否有效减轻心力衰竭恶病质。方法观察60例心力衰竭恶病质患者,在心力衰竭标准治疗基础上随机将患者分为观察组（营养支持）和对照组（普通饮食）,在治疗前及4周后观察两组分别在心功能状态、营养状态等指标方面的变化。结果营养支持治疗4周后与治疗前对比,患者的体重指数、血红蛋白浓度、血清白蛋白浓度、射血分数、NYHA心功能分级均显著提高;4周后同一时间点观察组与对照组相比,上述指标亦有显著差异,观察组明显优于对照组;4周内观察组的心脏不良事件发生率低于对照组。结论对心力衰竭恶病质患者在心力衰竭治疗同时给予合理的营养支持,可显著改善营养状态,提高心力衰竭治疗效果,有效阻止心力衰竭恶病质的进展。     

Gut microbiome and pancreatic cancer cachexia: An evolving relationship

Nearly 80% of patients with pancreatic ductal adenocarcinoma (PDAC) develop cachexia along their disease course. Cachexia is characterized by progressive weight loss, muscle wasting, and systemic inflammation and has been linked to poorer outcomes and impairments in quality of life. Management of PDAC cachexia has historically involved a multidisciplinary effort comprised of nutritional support, pancreatic enzyme replacement therapy, and/or pharmacologic interventions. Despite current interventions to mitigate PDAC cachexia, a significant proportion of patients continue to die from complications associated with cachexia underscoring the need for novel insights and treatments for this syndrome. We highlight the feasibility and effectiveness of a recent enteral feeding prospective trial at our institution to improve cachexia outcomes in patients with advanced PDAC. Additionally, we were among the first to characterize the stool microbiome composition in patients with advanced PDAC receiving enteral feeding for the treatment of cachexia. Novel insights into the relationship between enteral nutritional support, cachexia, and the gut microbiome are presented. These promising results are discussed in the context of a potential ability to modulate the stool microbiome as a new interventional strategy to mitigate PDAC cachexia.     

The relationship between body weight and inflammation: Lesson from anti-TNF-α antibody therapy

Obesity is associated with many pathological conditions. Tumor Necrosis Factor-α (TNF-α) is one of the key mediators of inflammation involved in the obesity-related insulin resistance development. We aim to review the human evidence useful to clarify the relationship between inflammation and body weight, with particular reference to TNF-α. Genetic polymorphisms and epigenetic factors, such as diet, could affect TNF-α activity. TNF-α is associated with obesity, but also with anorexia and cachexia. Despite the role of TNF-α in obesity-related diseases, anti-TNF-α antibody therapy is associated with an increase in adiposity. In conclusion the reviewed results suggest that inflammation is more likely a consequence rather than a cause of obesity.     

Linkage between postabsorptive amino acid release and glutamate uptake in skeletal muscle tissue of healthy young subjects, cancer patients, and the elderly

 Several diseases of varying etiology that are commonly associated with the loss of skeletal muscle mass were found to be associated with a decrease in muscular glutamate and glutathione levels and in glutamate uptake in the postabsorptive state. In view of the Na⁺ dependency and insulin responsiveness of glutamate transport we studied the postabsorptive glutamate exchange in more detail. Our study demonstrates a linkage between glutamate uptake and the export of other amino acids, suggesting that protein catabolism and the resulting coexport of amino acids plus Na⁺ substitute for insulin as a driving force for the Na⁺ gradient in the postabsorptive state. The regression function of the correlation between relative glutamate exchange and cumulative amino acid exchange in cancer patients was lower than that in non-tumor-bearing subjects, suggesting that cancer patients must release more amino acids to achieve the same glutamate uptake. In addition, cancer patients had a lower average cumulative amino acid exchange rate than non-tumor-bearing subjects, suggesting that the abnormally low relative glutamate exchange capacity of cancer patients results mainly from inadequate postabsorptive protein catabolism in the skeletal muscle tissue. Both cancer patients and non-tumor-bearing elderly subjects had higher arterial glutamate levels and alanine release than young subjects, indicative of a substantial glycolytic activity in the skeletal muscle. However, elderly non-tumor-bearing subjects showed, in contrast to cancer patients, in the postabsorptive state a stronger cumulative amino acid release and postabsorptive glutamate uptake than healthy young subjects. These changes are discussed in view of the age-related loss of skeletal muscle mass. Received: 22 November 1996 / Accepted: 14 February 1997     

Evaluation of mechanisms behind elevated energy expenditure in cancer patients with solid tumours

Abstract. The aim of this study was to demonstrate significant factors behind elevated resting energy expenditure in weight-losing cancer patients. There tore, weight-losing cancer patients (n= 60), with normal liver and kidney function tests, were randomized to receive one of four drug treatments for 5 days: (a) Propranolol 80 mg × 2 (β-adreneceptor blockade); (b) Indomethacin 50 mg × 2 (prostaglandin synthesis inhibition); (c) Morphine 5 mg × 3 (pain reliet) or (d) Placebo x 2. A reterence group of healthy well-nourished individuals were examined outside the formal randomization protocol and they received Propranolol 80 mg × 2. The cancer patients were randomized by a computer based algorithm stratifying for measured resting energy expenditure (REE), body composition, biochemical tests, previous therapy, tumour type and tumour stage. Resting energy expenditure was measured by indirect calorimetry in the morning after an overnight fast betore and after drug treatment. β-blockade reduced REE significantly in cancer patients from 1416 ± 95 kcal day^-1 to 1160 ± 63 kcal day^-1 (P <0.02) and from 1472 ± 69 vs. 1398 ± 62 kcal day^-1, (P <0.01) in the well-nourished reterence individuals. The reduction found in cancer patients (10%) was significantly larger than that in the group of reterence patients (5%), (P <0.01). Indomethacin, morphine or placebo did not induce any significant alteration in energy expenditure in our cancer patients. Propranolol treatment was associated with a significant reduction in plasma concentrations of free fatty acids (FFA), but not in plasma glycerol. Our results support the suggestion that adrenergic factors are the most important mediators behind elevated resting energy expenditure in weight-losing cancer patients. Such factors were more important than inflammation and cytokine production related to prostaglandin dependent pathways.     

T cell responses to myelin basic protein in experimental autoimmune encephalomyelitis-resistant BALB/c mice

In strains of mice that are susceptible to experimental autoimmune encephalomyelitis (EAE), cloned CD4⁺ T cells reactive with autologous myelin basic protein (MBP) have been shown to cause disease when transferred to naive syngeneic recipients. Recent reports indicate that under particular experimental conditions, ‘resistant’ strains of mice can also develop EAE, although cloned cells have not been isolated and characterized. An analyis of the characteristics of a panel of MBP-specific T cells and the antigen presenting capability of CNS-derived cells obtained from the resistant strain BALB/c is presented here. The data demonnstrate that immunization of EAE-resistant BALB/c mice results in the activation of a heterogeneous group of T cells reactive with autologous MBP. Both peripheral antigen presenting cells, as well as microglia isolated from brains of BALB/c mice, are capable of stimulating these cloned MBP-specific T cells to proliferate. When optimally activated in vitro and then injected in vivo into syngeneic BALB/c recipients, three clones studied induced severe cachexia, resulting in loss of up to 35% of body weight before death. Two of the clones also induced clinical and histological EAE, while the third induced only occasional histological evidence of disease. Differences in epitope recognition, T cell receptor usage, cytokine profiles or regulatory mechanisms of self tolerance, may play important roles in preventing potentially destructive autoimmune reactions by these T cells capable of recognizing autologous myelin in the central nervous system.     

外科肿瘤患者的营养支持治疗现状与进展

体重下降和营养不良是恶性肿瘤患者最常见的问题,营养支持治疗虽不是一个独立治疗方法,但对肿瘤患者而言是极其重要的辅助性治疗,贯穿于整个治疗过程,是恶病质治疗的重要组成部分,本文就其近几年国内外的研究进展作一综述。     

恶液质与肿瘤转移的相关分子机制

恶液质是一种骨骼肌量进行性下降的代谢综合征,伴随或不伴随脂肪量减少,在晚期肿瘤患者中普遍存在。恶 液质降低抗肿瘤治疗疗效,增加肿瘤放化疗不良反应,增加肿瘤患者死亡率,是预后不良的重要因素之一。恶液质促进肿 瘤的侵袭和转移,其机制尚不明确,可能与恶液质患者中存在的炎性反应、乏氧状态、瘦素水平下降、促血管生成因子释 放等有关。肿瘤恶液质的病理生理机制错综复杂,普遍认为肿瘤转移的患者,肿瘤负荷增加,患者发生恶液质的风险增加, 且其治疗效果欠佳,目前仍缺乏标准的治疗方案。进一步明确恶液质的病理生理特点及其促进肿瘤转移的机制,有助于指 导早期营养筛查和营养评估,明确恶液质的诊断,并对恶液质进行分期和分级管理,有效地预防和治疗恶液质,进而减少 肿瘤转移,改善患者生活质量及预后。本文通过探讨恶液质的病理生理特点及其促进肿瘤转移的相关分子机制,综述恶液 质与肿瘤转移的相关分子机制,为恶液质及肿瘤转移的治疗提供重要依据。     

Serum levels of tumour necrosis factor alpha and other cytokines do not correlate with weight loss and anorexia in cancer patients

Cancer anorexia-cachexia syndrome (CACS), which is characterized by progressive weight loss (WL) and anorexia (A), is present in 50% of advanced cancer patients and in 80% of terminally ill cancer patients. One of the most controversial aspects of CACS is its oetiopathogenesis; experimental studies have identified certain cytokines [Tumour necrosis factor alpha (TNF-), interleukin 1 (IL-1), interleukin 6 (IL-6), and gamma interferon (\gg-IFN)] as possible cofactors in the onset of the syndrome. The aim of our study was to investigate the correlation between serum levels of circulating cytokines and severity of CACS. The following series of parameters was indentified in 61 patients with advanced and terminal cancer: stage of disease; Karnofsky performance status (KPS) and clinical symptoms; biohumoral, anthropometric and immunological situation; level of circulating cytokines. All these parameters were evaluated for a possible link with WL/A. Our data do not show any significant correlation between circulating cytokines and WL/A. A direct correlation was identified between WL/A and nausea (P=0.03 andP<0.001, respectively) whereas inverse correlations were observed for both factors as regards arm circumference (P<0.001 for both), wrist circumference (P<0.001 for both), KPS (P<0.001 andP=0.003, respectively) and creatinine (P=0.005 andP=0.03, respectively). Other biochemical factors, such as haemoglobin, haematocrit, glycaemia, prealbumin, sodium and chlorine were also correlated with at least one of the two clinical parameters in question. Unexpected results were seen in the increases in CD20 and CD4 and in the CD4/CD8 ratio. Serum levels of these cytokines do not, therefore, appear to be critical in the onset of CACS. On the contrary, our findings confirmed the clinico-laboratory picture that is characteristic of CACS. If we consider the possibility that CACS is provoked by an aspecific response of the host's defence mechanisms against prolonged neoplastic attack, the increase in CD4 (helper lymphocytes) could be linked to the persistent response.