Summary To develop a framework for the definition and classification of cancer cachexia a panel of experts participated in a formal consensus process, including focus groups and two Delphi rounds. ...Cancer cachexia was defined as a multifactorial syndrome defined by an ongoing loss of skeletal muscle mass (with or without loss of fat mass) that cannot be fully reversed by conventional nutritional support and leads to progressive functional impairment. Its pathophysiology is characterised by a negative protein and energy balance driven by a variable combination of reduced food intake and abnormal metabolism. The agreed diagnostic criterion for cachexia was weight loss greater than 5%, or weight loss greater than 2% in individuals already showing depletion according to current bodyweight and height (body-mass index BMI <20 kg/m2 ) or skeletal muscle mass (sarcopenia). An agreement was made that the cachexia syndrome can develop progressively through various stages—precachexia to cachexia to refractory cachexia. Severity can be classified according to degree of depletion of energy stores and body protein (BMI) in combination with degree of ongoing weight loss. Assessment for classification and clinical management should include the following domains: anorexia or reduced food intake, catabolic drive, muscle mass and strength, functional and psychosocial impairment. Consensus exists on a framework for the definition and classification of cancer cachexia. After validation, this should aid clinical trial design, development of practice guidelines, and, eventually, routine clinical management.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, ie, reduced muscle mass, with limited mobility" should be considered an ...important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s.
Background Oxidative stress and RAAS play an important role in the occurrence of anthracyclines-induced cardiotoxicity. Telmisartan, an angiotensin II type 1 receptor blocker, inhibits activation of ...superoxide sources and induces anti-inflammatory effects. Methods The possible role of telmisartan in preventing myocardial damage induced by epirubicin (EPI) was investigated. Forty-nine patients free from cardiovascular diseases affected by a variety of solid cancers were examined. Eligible patients were randomized to receive telmisartan (40 mg/d; TEL, n = 25) or placebo (PLA, n = 24) starting 1 week before chemotherapy. Patients were studied by means of echocardiography, tissue Doppler, and strain and strain rate (SR) imaging. We also measured plasma levels of inflammatory and oxidative stress markers. All parameters were assessed at baseline and 7 days after every new EPI dose of 100 mg/m2. Results An impairment of the SR peak was observed at the EPI dose of 200 mg/m2 , with no significant differences between TEL and PLA (1.41 ± 0.31 vs 1.59 ± 0.36/s). At growing cumulative doses of EPI, SR normalized only in TEL, showing a significant difference in comparison to PLA at EPI doses of 300 mg/m2 (1.69 ± 0.42 vs 1.34 ± 0.18/s, P < .001) and 400 mg/m2 (1.74 ± 0.27 vs 1.38 ± 0.24/s, P < .001). Moreover, a significant increase in reactive oxygen species and interleukin-6 was found in PLA; but these remained unchanged in TEL. Conclusions We confirmed that EPI-induced cardiotoxicity is primarily related to the inactivation of the cardiac antioxidant defenses. In addition, we showed that telmisartan can reduce EPI-induced radical species, antagonize the inflammation, and reverse the early myocardial impairment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Purpose
There is little information about the nutritional status of cancer outpatients because the practice of nutritional screening is rarely performed. This study aims to define the pattern of ...scores of nutritional risk in 1,453 outpatients and factors associated with a high nutrition risk score, to facilitate the identification of such patients by the oncologists.
Methods
We prospectively screened the nutritional status of cancer outpatients according to the NRS-2002 score which combines indicators of malnutrition and of severity of the disease (1–3 points, respectively). A score ≥3 indicates “nutritional risk”. The association of the nutritional scores with some patient/tumour/therapy-related variables was investigated through univariable and multivariable linear regression models.
Results
Thirty-two percent of outpatients were at nutritional risk. Primary tumour site, Eastern Cooperative Oncology Group score and presence of anorexia or fatigue were significantly associated with the nutrition risk score. Depending on the combination of these variables, it was possible to estimate different probabilities of nutritional risk.
Conclusions
The frequency of a relevant nutritional risk was higher than expected considering the favourably selected population. The nutritional risk was associated with common clinical variables which are usually recorded in the charts and could easily alert the oncologist on the need of a further nutritional assessment or a nutritional support.
Chronic Obstructive Pulmonary Disease (COPD) is a common disease with significant health and economic consequences. This study assesses the burden of COPD in the general population, and the influence ...of exacerbations (E-COPD) on disease progression and costs.
This is a secondary data analysis of healthcare administrative databases of the region of Lombardy, in northern Italy. The study included ≥ 40 year-old patients hospitalized for a severe E-COPD (index event) during 2006. Patients were classified in relation to the number and type of E-COPD experienced in a three-year pre-index period. Subjects were followed up until December 31st, 2009, collecting data on healthcare resource use and vital status.
15857 patients were enrolled -9911 males, mean age: 76 years (SD 10). Over a mean follow-up time of 2.4 years (1.36), 81% of patients had at least one E-COPD with an annual rate of 3.2 exacerbations per person-year and an all-cause mortality of 47%. A history of exacerbation influenced the occurrence of new E-COPD and mortality after discharge for an E-COPD. On average, the healthcare system spent 6725€ per year per person (95%CI 6590-6863). Occurrence and type of exacerbations drove the direct healthcare cost. Less than one quarter of patients presented claims for pulmonary function tests.
COPD imposes a substantial burden on healthcare systems, mainly attributable to the type and occurrence of E-COPD, or in other words, to the exacerbator phenotypes. A more tailored approach to the management of COPD patients is required.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Recent progress in the field of energy homeostasis was triggered by the discovery of adipocyte hormone leptin and revealed a complex regulatory neuroendocrine network. A late addition is the novel ...stomach hormone ghrelin, which is an endogenous agonist at the growth hormone secretagogne receptor and is the motilin‐related family of regulatory peptides. In addition to its ability to stimulate GH secretion and gastric motility, ghrelin stimulates appetite and induces a positive energy balance leading to body weight gain. Leptin and ghrelin are complementary, yet antagonis¬tic, signals reflecting acute and chronic changes in energy balance, the effects of which are mediated by hypothalamic neuropeptides such as neuropeptide Y and agouti‐related peptide. Endocrine and vagal affer¬ent pathways are involved in these actions of ghrelin and leptin. Ghrelin is a novel neuroendocrine signal possessing a wide spectrum of biological activities that illustrates the importance of the stomach in providing input into the brain. Defective ghrelin signaling from the stomach could contribute to abnormalities in en¬ergy balance, growth, and associated gastrointestinal and neuroendocrine functions.—Inui, A., Asakawa, A., Bowers, C. Y., Mantovani, G., Laviano, A., Meguid, M. M., Fujimiya, M. Ghrelin, appetite, and gastric motility: the emerging role of the stomach as an endo¬crine organ.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Siponimod is an effective treatment for patients with secondary progressive multiple sclerosis (SPMS), with active disease evidenced by relapses or imaging features characteristic of multiple ...sclerosis inflammatory activity, however there is a need to evaluate its economic value and sustainability compared to other disease modifying-therapies (DMTs).
To estimate the siponimod cost-effectiveness profile and its relative budget impact compared with other DMTs, by using the Italian National Healthcare System perspective.
We performed: 1) a cost-effectiveness analysis (CEA) vs interferon beta-1b using an analytical Markov model and a life time-horizon, and 2) a budget impact analysis by using 3-years time-horizon. The results were reported as incremental cost-effectiveness ratio (ICER) and net-monetary benefit (NMB) for CEA, using a willingness to pay threshold of €40,000 per QALY gained, and as difference in the overall budget (Euro) between the scenario with and without siponimod for budget impact.
In the base case scenario siponimod resulted cost-effective compared with interferon beta-1b 28,891€ per QALY. Overall, the market access of siponimod was associated to an increased budget of about 3€ millions (+0.9%) in the next 3 years simulated.
Compared to interferon beta-1b, siponimod seems to be cost-effective in SPMS patients and sustainable, with less than 1% overall budget increased in the next 3 years. Future studies need to confirm our results in the real word setting and in other countries.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cachexia influences morbidity, mortality and quality of life of cancer patients at advanced stage of disease. Therefore, the knowledge of its pathophysiology is critical to develop effective ...therapies to be integrated in the comprehensive approach of cancer patients. Oxidative stress, unless counteracted by effective antioxidant therapies, contributes to the development of anorexia and cachexia in cancer patients. In the present review the potential role of targeting oxidative stress in the treatment of cachexia is reported. Efficacy data on the use of antioxidants in advanced cancer patients are promising. However, the optimal dosage and route of administration as well as the timing and the most effective combination are not well established. Moreover, since cachexia is a multifactorial syndrome, targeting only oxidative stress as a contributing factor would be inadequate and likely to achieve a limited clinical therapeutic benefit. According to this rationale, antioxidants should be included as essential components of a multitargeted combined treatment of cancer cachexia, which has been shown to be the most successful approach for this syndrome.
Introduction:
Anorexia and cachexia syndrome represents a complex clinical picture that occurs in the late stage of several chronic inflammatory diseases, including cancer. Unless counteracted ...cancer-related anorexia and cachexia syndrome affects quality of life (QL) and survival. However, to date a standard effective treatment is lacking.
Areas covered:
The aim of this review is to describe the current pharmacological approaches for anorexia and cachexia syndrome, focusing on cancer-related syndrome. The several pharmacological agents tested so far are discussed, distinguishing them in unproven drugs, effective drugs, and drugs under investigation. Moreover, a section is devoted to the promising use of nutritional supplements and nutraceuticals. The emerging role of a multitargeted combined treatment approach is exhaustively reviewed.
Expert opinion:
Considering the complex clinical picture and the multifactorial pathogenesis of anorexia and cachexia syndrome, we believe that its clinical management requires a multidisciplinary and multipharmacological approach. In our opinion the anorexia and cachexia syndrome treatment should include drugs that target the following conditions: inflammatory status, oxidative stress, nutritional disorders, muscle catabolism, anemia, immunosuppression, and fatigue. The multidimensional therapies for anorexia and cachexia syndrome should ideally be introduced within a context of the "best supportive care," which includes optimal symptom management and careful psychosocial counseling.
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