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  • Loss of adipose tissue mass during chemotherapy predicts reduced survival in patients with colorectal cancer treated with palliative intent

  • Erin Stella Sullivan, Louise E. Daly, Éadaoin B Ní Bhuachalla, Samantha J. Cushen, Derek G. Power, Aoife M Ryan
  • Journal:
    Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
    Published online by Cambridge University Press:
    10 June 2020, E149
    • Article
      • You have access
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  • Obesity is an established risk factor for colorectal cancer (CRC), however little is known about changes in body composition during chemotherapy and its impact on survival. The aim of this study was to examine in patients with CRC: (1) The prevalence of abnormal body composition phenotypes, (2) The impact of baseline body composition on overall survival, (3) Changes in body composition throughout treatment and its impact on overall survival.

    A prospective study of adult CRC patients undergoing chemotherapy between 2012–2016 was conducted. Longitudinal changes in body composition were examined using computed tomography (CT) images at two timepoints (interval 7 months, IQR: 5–9 months) using paired t-tests. Sarcopenia and low muscle attenuation (MA) were defined using published cut-offs. Cox proportional-hazards models were used to estimate mortality hazard ratios, adjusted for known prognostic covariates – stage, age, sex, performance status & systemic inflammation.

    In total, 268 patients were recruited (66% male, mean age 63 years) and 51% were undergoing chemotherapy with a palliative intent. At baseline, 4% were underweight (BMI < 20 kg/m2), 38% had a normal BMI, and 58% were overweight/obese. Despite this, 38% had cancer cachexia, 34% were sarcopenic and 43% had low MA. Neither sarcopenia, sarcopenic obesity nor cachexia at baseline predicted survival. Over 100 days, 68% were muscle stable (± 1 kg), while 25% lost > 1 kg and 7% gained > 1 kg. Fat mass remained stable ± 1 kg in 49%, while 28% lost > 1 kg and 23% gained > 1 kg. When adjusted for known prognostic covariates, baseline BMI (20–25 kg/m2) in those having palliative chemotherapy was independently associated with reduced survival compared to those with BMI indicating overweight (BMI 25–30 kg/m2) [HR: 1.80 (95% CI: 1.04–3.14), p = 0.037]. In those undergoing chemotherapy with palliative intent, a loss of > 6.4% subcutaneous fat (Q1 SAT) over 100 days was predictive of poor survival versus those with small losses, remaining stable or gaining SAT (Q2-4), independent of changes in muscle mass [HR: 2.22 (95% CI: 1.07–4.62), p = 0.033].

    Patients with CRC, particularly those treated with a palliative intent, experience significant losses in muscle and fat mass during chemotherapy. Loss of SAT mass during palliative chemotherapy is prognostic of poor survival, independent of changes in muscle mass. Baseline BMI in the overweight range confers a survival advantage. Nutritional strategies to prevent or attenuate weight loss during chemotherapy are advisable especially in the context of advanced CRC.

  • A phase 1, single-blind, placebo-controlled, 3-arm cross-over trial assessing the appetite enhancing effects of potentially ghrelinergic dairy-derived peptides

  • Samantha J. Cushen, Erin Stella Sullivan, Tracey Kelly, Louise E. Daly, Éadaoin B Ní Bhuachalla, Ken Howick, Harriët Schellekens, John F. Cryan, Brendan T. Griffin, Darren Dahly, Aoife M Ryan
  • Journal:
    Proceedings of the Nutrition Society / Volume 79 / Issue OCE2 / 2020
    Published online by Cambridge University Press:
    10 June 2020, E121
    • Article
      • You have access
    • PDF
    • Export citation

  • Methods to stimulate appetite in the sick or elderly remains a challenge with few safe therapeutic options. Ghrelin is an orexigenic hormone, increasing appetite and subsequent food intake. It has received considerable attention as a therapeutic target to stimulate food intake in patients with anorexia. The identification of food-grade bioactives with proven orexigenic effects would mark significant progress in the treatment of disease-related malnutrition. This study therefore investigated the effects of two milk-derived ghrelinergic peptides on appetite and energy intake in healthy humans.

    A single-blind, placebo-controlled, 3-arm (placebo, casein bioactive MF1145 and whey bioactive UL-2-141) cross-over trial was conducted in healthy male volunteers. Participants received 26 mg/kg of both the bioactives and placebo. The main outcome measures were energy & protein intake from a set breakfast and ad libitum lunch and subjective appetite sensations as assessed by visual analogue scale (VAS). Basal and postprandial levels of active ghrelin (AG) were measured. Dietary intakes were analysed using Nutritics software. Statistical analyses were performed in R.

    Overall, 22 male participants (mean age 27 years) were included, average BMI was 24.6 kg/m2, (19.8 to 30.2 kg/m2). Mean energy and protein intakes at lunch when treated with placebo were 1343 kcal (95% CI: 1215–1471 kcal) and 74 g (95% CI: 66–81 g), respectively. Energy and protein intakes were not significantly different from placebo for either treatment (p = 0.918, p = 0.319 for UL-2-141 and p = 0.889, p = 0.959 for MF1145, respectively). Similarly, appetite, hunger and satiety responses on VAS were not significantly different from placebo for either treatment. AG peak post-lunch on placebo was 653 pg/ml (95% CI: 511–794 pg/ml). Treatment with UL-2-141 resulted in 139 pg/ml reduction in post-prandial AG compared to placebo and treatment with MF1145 resulted in 114 pg/ml reduction compared to placebo. This pattern was significant for both treatments (p = 0.021 and p = 0.045, respectively) however when controlling for fasting-AG, the pattern was no longer significant (p = 0.590 and p = 0.877 respectively). Pre-prandial AG peaks were not significantly different across treatments.

    While these peptides have previously demonstrated ghrelinergic effects in rats, no effect on appetite or food intake in humans was identified by this study. This may be attributable to the small sample size or low dose. However, since healthy adults are often not in tune with their own physiological hunger, they may not respond strongly to simple physiological modulators and repeating the study in subjects with established anorexia may be prudent.

  • 17 - Standards in Subnational Environmental Constitutionalism

  • Edited by Stephen J. Turner, University of Lincoln, Dinah L. Shelton, George Washington University, Washington DC, Jona Razzaque, Owen McIntyre, University College Cork, James R. May, Widener University School of Law, Delaware
  • Book:
    Environmental Rights
    Published online:
    09 May 2019
    Print publication:
    23 May 2019, pp 367-382

  • Summary

    This chapter examines the standards that are developing in environmental constitutionalism at the subnational level in both texts and case law. Subnational governance – states, provinces states, provinces, Länder, cantons, or what some refer to as the ‘meso-level’ that exists between the national government and local governments – provides the most direct mechanism for advancing local interests and protecting basic human environmental rights that have a parochial significance. Good practices, which may evolve into standards, are developing because some subnational constitutions are far more intricate and complex than those that exist at the federal level, and can result in illuminating judicial decisions. Thus, subnational constitutions can provide additional proving grounds for environmental constitutionalism around the globe.

  • Transitioning Toward Dignity

    • By Erin Daly, Professor of Law at Delaware Law School and Co-Director of the Dignity Rights Project.
  • Edited by Jeremy Sarkin
  • Book:
    The Global Impact and Legacy of Truth Commissions
    Published by:
    Intersentia
    Published online:
    26 June 2019
    Print publication:
    01 May 2019, pp 189-210

  • Summary

    INTRODUCTION

    While each country experiences conflict differently, develops unique mechanisms of transitional justice, and structures and empowers its truth commissions to suit its particular needs and capacities, the endpoints are Often similar: at least in their public commitments, countries invariably aspire to craft an inclusive society in which all citizens are engaged for the betterment of the individuals and communities that comprise the nation. This, it is presumed, will end violence and avoid its recurrence, and bring about lasting peace. These are, without a doubt, broad and ambitious goals, indicating deep transformations in statecraft, in the social fabric, and even in the psychology of the people. Thus, there is a link between how people feel about their society, how they engage in it, and the political and social spaces that both produce and result from that engagement. Human dignity, which has both individual psychological dimensions and relational social dimensions, links the personal and the political aims of transitional justice.

    Often, the architects of transitional justice establish truth commissions for the stated purpose of moving toward the fulfilment of these goals. Truth commissions do not have the jurisdictional authority or the resources to accomplish any of these goals on their own, but they can galvanise institutions of the state and civil society to take action. They cannot draft constitutions and laws, but they can develop the framework for legal reform, identify the fundamental values that legal reform should embody, and identify the essential terms that legal reform should adopt. They typically do not have the authority to pay reparations, but they can identify the goals of a reparations programme and insist on its realisation according to a set timeframe. They cannot write a new curriculum, but they can frame the essential factual and historical accounts in a way that respects all legitimate perspectives and they can articulate the fundamental lessons of human rights to be inculcated. They cannot, on their own, define citizenship and nationhood, but they can reflect and embody the equal value of each person that demands respect for all. Truth commissions, then, have little power actually to make change, but they wield significant power to articulate the terms of debate and to create the framework in which social and political change will take place.

Implementing Environmental Constitutionalism
  • Current Global Challenges
  • Edited by Erin Daly, James R. May
  • Published online:
    02 November 2018
    Print publication:
    08 November 2018
  • Constitutions can play a central role in responding to environmental challenges, such as pollution, biodiversity loss, lack of drinking water, and climate change. The vast majority of people on earth live under constitutional systems that protect the environment or recognize environmental rights. Such environmental constitutionalism, however, falls short without effective implementation by policymakers, advocates and jurists. Implementing Environmental Constitutionalism: Current Global Challenges explains and explores this 'implementation gap'. This collection is both broad and deep. While some of the essays analyze crosscutting themes, such as climate change and the need for rule of law that affect the implementation of environmental constitutionalism throughout the world, others delve deeply into geographically contextual experiences for lessons about how constitutional environmental law might be more effectively implemented. This volume informs global conversations about whether and how environmental constitutionalism can be made more effective to protect the natural environment.

  • 3 - Learning from Constitutional Environmental Rights

  • Edited by John H. Knox, Wake Forest University, North Carolina, Ramin Pejan
  • Book:
    The Human Right to a Healthy Environment
    Published online:
    08 June 2018
    Print publication:
    28 June 2018, pp 42-58

  • Summary

    This chapter illusrates that domestic environmental constitutionalism provides several lessons for the meaning, scope, and enforcement of a global environmental right. Domestic constititutions use a very wide variety of other formulations, including references to the right to a “clean,” “harmonious,” and “balanced” environment. Some provisions are explicitly anthropocentric, others are ecocentric, and some include both perspectives. Different legal consequences can result from such different legal texts. The chpater also demonstrates that constitutions differ greatly in how clearly they link the right to other rights, and in the creation of effective enforcement mechanisms. It concludes that the drafters of an instrument recognizing the right at the global level should clarify as much as possible which elements of the environment should be protected and why, link the right explicitly to other human rights, and create effective mechanisms for vindicating the right.

  • Chapter 6 - Environmental Dignity Rights

  • from Better Legislation
    • By Erin Daly, Professor of Law, Widener University Delaware Law School (USA), James R. May, Distinguished Professor of Law, Widener University Delaware Law School
  • Edited by Sandrine Maljean-Dubois
  • Book:
    The Effectiveness of Environmental Law
    Published by:
    Intersentia
    Published online:
    27 September 2018
    Print publication:
    08 June 2017, pp 125-148

  • Summary

    ABSTRACT

    The threats to human rights caused by environmental degradation – including those caused by climate change – are increasingly evident. And yet, there continues to be confusion and a lack of consensus about how human rights will be affected, as demonstrated at the recent climate talks in Paris. Taking better advantage of the role of constitutionally-instantiated dignity rights can help to diffuse this dissonance. Most of the effects that environmental degradation have on people can be seen in threats to their ability to live in dignity, including the ability to fully develop one's personality, to live in a community and to claim other rights. The right to dignity, though rooted in international law, is recognized in most of the world's constitutions and a robust jurisprudence of dignity rights has been developing in many countries. We conclude that environmental outcomes – including climate change – can and should be informed by dignity rights and corresponding jurisprudence, a synthesis we call “environmental dignity rights.”

    “Man has the fundamental right to freedom, equality and adequate conditions of life, in an environment of a quality that permits a life of dignity and well-being, and he bears a solemn responsibility to protect and improve the environment for present and future generations.”

    – Stockholm Declaration on the Human Environment

    The importance of dignity as a founding value of the new Constitution cannot be overemphasized. Recognizing a right to dignity is the acknowledgement of the intrinsic worth of human beings: human beings are entitled to be treated as worthy of respect and concern.

    – S v. Makwanyane and Another, Constitutional Court of South Africa

    INTRODUCTION

    Environmental outcomes can and should be informed by the concept of dignity. Human dignity is an elemental value that presupposes that every human being has equal worth. It emphasizes the fundamental value and equality of all members of society – humans are not only endowed with dignity, but each is endowed with an equal quantum of dignity. In the words of the United Nation's Declaration on Human Rights, “All human beings are born free and equal in dignity and rights.” Where dignity is recognized, each person's dignity is inalienable, irreducible and infinite.

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