Impact of sarcopenia on clinical outcome in old patients with cancer

Introduction and background: Sarcopenia was originally defined as the age-related loss of muscle mass. In addition to primary, or age-related sarcopenia, secondary sarcopenia describes muscle depletion due to physical inactivity, inadequate nutrition or disease. Therefore, particularly older patients with chronic disease, for example cancer, are at an increased risk of developing sarcopenia. In addition to the physiological age-related changes, older patients with cancer are burdened by the physical and metabolic effects of the cancer disease itself as well as its treatment. Loss of muscle mass leads to functional impairment, reduced quality of life and poor clinical outcome. This study aimed to assess the prevalence of sarcopenia in older patients with cancer and its impact on 1-year mortality. Methods: Sarcopenia was defined as suggested by the European Working Group on Sarcopenia in Older People (EWGSOP) as low skeletal muscle mass index and muscle strength assessed by bioelectric impedance analysis and isometric hand grip strength, respectively. Information on one-year mortality was collected by telephone follow-up or by contacting the local cancer death registry. A step-wise, forward Cox proportional hazards analysis was performed to identify risk factors of 1-year mortality. Results: Four-hundred thirty-nine older patients with cancer were included in the analysis (60-95 years; 43.5% women), of which 119 (27.1%) were identified as sarcopenic. Sixty-two (52.5%) of the patients with sarcopenia compared to 108 (35.1%) without sarcopenia died within one year of study entry. Patients without sarcopenia had longer survival times (291.2 days, 95% CI: 278.0-304.5 versus 244.0 days, 95% CI: 219.2-268.7, p<0.001). Advanced tumour stage IV (HR=1.87; 95% CI: 1.228-2.847; p=0.004), sarcopenia (HR=1.53; 95% CI: 1.034-2.250; p=0.033), number of drugs per day (HR=1.11; 95% CI: 1.057-1.170; p<0.001), Karnofsky Index (HR=0.98, 95% CI: 0.963-0.995; p=0.013) and tumour diagnosis (overall p=0.012) were significantly associated with 1-year mortality risk. Sex, age, number of comorbidities and involuntary 6-month weight loss ≥ 5% were not significantly associated with 1-year mortality risk in this study. Conclusion: Nearly one-third of older patients with cancer were identified as sarcopenic compared to 10% of the healthy, older population worldwide (1). Notably, sarcopenia was nearly as predictive for 1-year mortality as advanced tumour stage IV. This result underscores the importance of the timely identification and monitoring of sarcopenia in this population and adjustment of therapy accordingly in order to maximise muscle mass preservation.Einleitung: Sarkopenie wurde ursprünglich als alters-assoziierter Verlust der Muskelmasse definiert. Neben der primären, oder alters-assoziierten Sarkopenie, beschreibt die sekundäre Sarkopenie den Verlust an Muskelmasse aufgrund von physischer Inaktivität, unzureichender Nahrungszufuhr oder Krankheit. Insbesondere ältere Patienten mit chronischen Erkrankungen, wie z.B. Tumorerkrankungen, haben dadurch ein erhöhtes Risiko eine Sarkopenie zu entwickeln. Neben den physiologischen altersbedingten Veränderungen sind ältere Patienten mit Tumorerkrankungen auch mit den physischen und metabolischen Auswirkungen der Krebserkrankung sowie deren Behandlung konfrontiert. Der Muskelschwund führt zu funktionellen Beeinträchtigungen, verminderter Lebensqualität sowie schlechtem klinischen Verlauf. Diese Studie untersucht die Prävalenz von Sarkopenie bei älteren Patienten mit Tumorerkrankungen und deren Einfluss auf 1-Jahres Mortalität. Methoden: Sarkopenie wurde nach den Empfehlungen der European Working Group on Sarcopenia in Older People (EWGSOP) definiert. Hierbei wurden die Kriterien verminderter Muskelmassenindex mithilfe der bioelektrischen Impedanzanalyse und verringerter Muskelkraft durch Messung der isometrischen Handkraft mit einem Dynamometer erfasst. Informationen zu 1-Jahres Mortalität wurde bei einem telefonischen Follow-Up oder vom lokalen Krebsregister erhoben. Eine schrittweise, vorwärts Cox-Regression mit proportionalen Hazards wurde durchgeführt, um Risikofaktoren für die 1-Jahresmortalität zu identifizieren. Ergebnisse: Vierhundert neun-und-dreißig ältere Patienten mit onkologischen Erkrankungen wurden in die Studie eingeschlossen (60-95 Jahre; 43,5% Frauen), davon wiesen 119 (27.1%) eine Sarkopenie auf. Zwei-und-sechzig (52,5%) der Patienten mit Sarkopenie im Vergleich zu 108 (35.1%) ohne Sarkopenie sind innerhalb eines Jahres vom Studieneinschluss verstorben. Patienten ohne Sarkopenie wiesen eine längere Überlebenszeit auf (291,2 Tage, 95% KI: 278,0-304,5 versus 244,0 Tage, 95% KI: 219,2-268,7, p<0,001). Ein fortgeschrittenes Tumorstadium IV (HR=1,87; 95% KI: 1,228-2,847; p=0,004), Sarkopenie (HR=1,53; 95% KI: 1,034-2,250; p=0,033), Anzahl an Medikamenten pro Tag (HR=1,11; 95% KI: 1,057-1,170; p<0,001), Karnofsky Index (HR=0,98, 95% KI: 0,963-0,995; p=0,013) und Tumordiagnose (Gesamt-p=0,012) waren mit einen erhöhten Risiko, nach einem Jahr zu versterben, assoziiert. Geschlecht, Alter, Anzahl an Komorbiditäten sowie unbeabsichtigter Gewichtsverlust ≥ 5% innerhalb von 6 Monaten waren in dieser Studie nicht mit dem Sterberisiko assoziiert. Schlussfolgerung: Nahezu ein Drittel der älteren Patienten mit Tumorerkrankungen wurden im Vergleich zu 10% der gesunden, älteren Population weltweit (1) als sarkopen identifiziert. Beachtenswert ist, dass Sarkopenie fast genauso prädiktiv für die 1-Jahres Mortalität wie ein fortgeschrittenes Tumorstadium war. Diese Ergebnisse unterstreichen die Bedeutung einer frühen Erfassung und kontinuierliche Überwachung der Sarkopenie in dieser Population sowie die entsprechende Anpassung der Therapie, um den Verlust an Muskelmasse zu minimieren

Severe Weight Loss and Its Association with Fatigue in Old Patients at Discharge from a Geriatric Hospital

Although malnutrition is frequent in the old, little is known about its association with fatigue. We evaluated the relation of self-reported severe weight loss with fatigue and the predictors for fatigue in old patients at hospital discharge. Severe weight loss was defined according to involuntary weight loss ≥5% in the last three months. We determined fatigue with the validated Brief Fatigue Inventory questionnaire. The regression analyses were adjusted for age, sex, number of comorbidities, medications/day, and BMI. Of 424 patients aged between 61 and 98 y, 34.1% had severe weight loss. Fatigue was higher in patients with severe weight loss (3.7 ± 2.3 vs. 3.2 ± 2.3 points, p = 0.021). In a multinomial regression model, weight loss was independently associated with higher risk for moderate fatigue (OR:1.172, CI:1.026-1.338, p = 0.019) and with increased risk for severe fatigue (OR:1.209, CI:1.047-1.395, p = 0.010) together with the number of medications/day (OR:1.220, CI:1.023-1.455, p = 0.027). In a binary regression model, severe weight loss predicted moderate-to-severe fatigue in the study population (OR:1.651, CI:1.052-2.590, p = 0.029). In summary, patients with self-reported severe weight loss at hospital discharge exhibited higher fatigue levels and severe weight loss was an independent predictor of moderate and severe fatigue, placing these patients at risk for impaired outcome in the post-hospital period

Impact of sarcopenia on 1-year mortality in older patients with cancer

Objectives: sarcopenia is common especially in hospitalised older populations. The aim of this study was to assess the prevalence of sarcopenia, defined as low skeletal mass and muscle strength, and its impact on 1-year mortality in older patients with cancer. Methods: skeletal muscle mass was estimated using bioelectric impedance analysis and related to height2 (SMI; Janssen et al. 2002). Grip strength was measured with the JAMAR dynamometer and the cut-offs suggested by the European Sarcopenia and 1-year mortality in cancer 413 Downloaded from https://academic.oup.com/ageing/article-abstract/48/3/413/5272750 by Université de Genève user on 26 November 2019 Working Group on Sarcopenia in Older People (EWGSOP) were applied. One-year mortality was assessed by telephone follow-up and the local cancer death registry. Results: of the 439 consecutively recruited cancer patients (60–95 years; 43.5% women), 119 (27.1%) had sarcopenia. Of the patients with sarcopenia, 62 (52.5%) died within 1 year after study entry compared to 108 (35.1%) patients who did not have sarcopenia (P = 0.001). In a stepwise, forward Cox proportional hazards analysis, sarcopenia (HR = 1.53; 95% CI: 1.034–2.250; P < 0.05), advanced disease (HR = 1.87; 95% CI: 1.228–2.847; P < 0.05), number of drugs/day (HR = 1.11; 95% CI: 1.057–1.170; P < 0.001), tumour diagnosis (overall P < 0.05) and Karnofsky index (HR = 0.98, 95% CI: 0.963–0.995; P < 0.05) associated with 1-year mortality risk. The factors sex, age, co-morbidities and involuntary 6-month weight loss ≥5% were insignificant. Conclusions: sarcopenia was present in 27.1% of older patients with cancer and was independently associated with 1-year mortality. The fact that sarcopenia was nearly as predictive for 1-year mortality as an advanced disease stage underlines the importance of preservation of muscle mass and function as a potential target of intervention in older patients with cancer

Interracial contact and racial constancy: A multi-site study of racial intergroup bias in 3-5 year old Anglo-British children

This paper examined the influence of interracial contact and racial constancy on the racial intergroup bias of young Anglo-British children. This multi-site study was conducted in areas of Great Britain that varied in terms of racial diversity. The study also investigated whether preschool children express bias on positive, but not negative, valence attributions. Anglo-British children (N = 136) between 3 and 5 years of age with different levels of interracial contact undertook a racial stereotype attribution measure and three tasks to assess racial constancy. Significantly more racial bias was shown towards the African Caribbean-British compared to the Asian-British or Oriental-British racial out-groups. As predicted, only children in racially mixed areas failed to show discrimination in favor of the white in-group on both the positive and negative trait attributions. In addition, higher racial constancy was related significantly to greater racial intergroup bias. These findings suggest that racial intergroup bias amongst 3-5 year old children may be reduced through the promotion of interracial contact, because at this age children are already beginning to develop racial constancy. (PsycINFO Database Record (c) 2012 APA, all rights reserved). (journal abstract

Proceedings of the 3rd annual symposium of the German Society for Paleo Nutrition held in 2015

We present the scientific abstracts of the 3rd Annual Symposium of the German Society for Paleo Nutrition (Deutsche Gesellschaft für Paläoernährung e.V.) which was held on July 26th 2015 in Berlin, Germany. The focus of this year\u27s symposium was on the future challenges of human society including topics such as nutritional sustainability, the paleo-deficit syndrome or frailty of the elderly due to body composition change

Safety and Suitability of an Infant Formula Manufactured from Extensively Hydrolysed Protein in Healthy Term Infants

We aimed to demonstrate that healthy term infants experience noninferior growth with infant formula manufactured from extensively hydrolysed whey protein (eHF) compared to intact cow’s milk protein (control formula, CF). This prospective, randomised, double-blind, parallel-group, controlled, multicentre trial included healthy term infants who were exclusively formula-fed. Infants ≤ 25 days of age received eHF or CF for at least three months up to 120 days of age, with a follow-up until 180 days of age. A reference group included exclusively breastfed infants (BF). Of 318 infants randomised, 297 (148 CF, 149 eHF) completed the study per protocol. Weight gain up to 120 days of age was noninferior (margin −3.0 g/day) in eHF (28.95 (95% CI: 27.21; 30.68) g/day) compared to CF (28.85 (95% CI: 27.10; 30.61) g/day) with a difference in means of 0.09 g/day and a lower limit of the one-sided 97.5% CI of −0.86 g/day (p < 0.0001 for noninferiority testing). Weight gain remained comparable during follow-up. Further anthropometric parameters did not differ between the infant formula groups throughout the study. Growth was comparable in BF. No relevant safety issues were observed. To conclude, eHF meets infant requirements for adequate growth during the first six months of life and can be considered safe and suitable

<i>Tfam</i>Knockdown Results in Reduction of mtDNA Copy Number, OXPHOS Deficiency and Abnormalities in Zebrafish Embryos

High mitochondrial DNA (mtDNA) copy numbers are essential for oogenesis and embryogenesis and correlate with fertility of oocytes and viability of embryos. To understand the pathology and mechanisms associated with low mtDNA copy numbers, we knocked down mitochondrial transcription factor A (tfam), a regulator of mtDNA replication, during early zebrafish development. Reduction oftfamusing a splice-modifying morpholino (MO) resulted in a 42 +/- 17% decrease in mtDNA copy number in embryos at 4 days post fertilization. Morphant embryos displayed abnormal development of the eye, brain, heart, and muscle, as well as a 50 +/- 22% decrease in ATP production. Transcriptome analysis revealed a decrease in protein-encoding transcripts from the heavy strand of the mtDNA, and down-regulation of genes involved in haem production and the metabolism of metabolites, which appear to trigger increased rRNA and tRNA synthesis in the nucleoli. However, this stress or compensatory response appears to fall short as pathology emerges and expression of genes related to eye development are severely down-regulated. Taken together, this study highlights the importance of sufficient mtDNA copies for early zebrafish development. Zebrafish is an excellent model to manipulate the mtDNA bottleneck and study its effect on embryogenesis rapidly and in large numbers of offspring