McMahon, M. Molly

Abstract The vision of the ASPEN Rhoads Research Foundation is to promote innovation and research discovery to improve nutrition care and health. The Foundation was launched in 1993, incorporated in 2002, and established as a nonprofit 501(c)(3) organization in 2007. On the occasion of American Society for Parenteral and Enteral Nutrition (ASPEN)'s 50th anniversary, this article examines the creation of the Foundation, the state of clinical nutrition research funding, the Foundation's philanthropic mission, and the return on investment of Foundation grant support. To date, 114 investigators have received 2.78 million dollars in funding. The article examines the success of ASPEN research programs and Foundation grant support in career development, leadership, and mentorship. It is important to document a historical account of the ASPEN Rhoads Research Foundation and encourage innovation and discovery and ongoing financial support.

Abstract Background The Global Leadership Initiative on Malnutrition (GLIM) approach to malnutrition diagnosis is based on assessment of three phenotypic (weight loss, low body mass index, and reduced skeletal muscle mass) and two etiologic (reduced food intake/assimilation and disease burden/inflammation) criteria, with diagnosis confirmed by fulfillment of any combination of at least one phenotypic and at least one etiologic criterion. The original GLIM description provided limited guidance regarding assessment of inflammation, and this has been a factor impeding further implementation of the GLIM criteria. We now seek to provide practical guidance for assessment of inflammation. Methods A GLIM‐constituted working group with 36 participants developed consensus‐based guidance through a modified Delphi review. A multiround review and revision process served to develop seven guidance statements. Results The final round of review was highly favorable, with 99% overall “agree” or “strongly agree” responses. The presence of acute or chronic disease, infection, or injury that is usually associated with inflammatory activity may be used to fulfill the GLIM disease burden/inflammation criterion, without the need for laboratory confirmation. However, we recommend that recognition of underlying medical conditions commonly associated with inflammation be supported by C‐reactive protein (CRP) measurements when the contribution of inflammatory components is uncertain. Interpretation of CRP requires that consideration be given to the method, reference values, and units (milligrams per deciliter or milligram per liter) for the clinical laboratory that is being used. Conclusion Confirmation of inflammation should be guided by clinical judgment based on underlying diagnosis or condition, clinical signs, or CRP.

Magnesium is an essential element that is involved in the regulation of cell growth, division and differentiation. Epidemiologic studies have demonstrated that a diet poor in magnesium is associated with an increased risk of developing cancer. There are few studies investigating whether magnesium deficiency is associated with a poor prognosis in lymphomas. The recent discovery of X-linked immunodeficiency with magnesium defect, Epstein-Barr virus, and neoplasia (XMEN) disease, suggests a role of magnesium in the development of hematologic malignancies and lymphocyte function. Furthermore, a recently published study found that hypomagnesemia prior to chemotherapy is associated with inferior overall survival (OS) in patients with Burkitt Lymphoma. We hypothesized that low magnesium levels prior to autologous hematopoietic stem cell transplant (AHSCT) may lead to inferior outcomes via impaired lymphocyte recovery. We evaluated whether low serum magnesium levels were associated with inferior survival in patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) who underwent autologous hematopoietic stem cell transplant (AHSCT) between January 1998 and May 2020 using a retrospective study design. We cross-referenced our search with patients who had a magnesium level as part of their pre-transplant workup between 7 and 28 days prior to their first transplant. Two-sided Wilcoxon rank sum test and Chi square/Fischer's exact test were used to compare the continuous and categorical variables, respectively. Kaplan-Meier and log-rank tests were used to perform all time to event analysis. Hazard ratios (HR) with confidence intervals (CI) were calculated using Cox-proportional hazards. Our study included 581 patients of which 82 (14.1%) had hypomagnesemia (magnesium < 1.7 mg/dL) prior to AHSCT. Our study found that hypomagnesemia was associated with inferior OS and event-free survival (EFS) defined as re-transplant, relapse or death, compared to those with a normal magnesium level; median OS: 7.3 years (95% CI: 2.91 - upper limit not estimable) versus 9.7 years (95% CI: 6.92 - 12.3 years), p=0.0041; and median EFS: 3.9 years (95% CI: 1.63 - 8.98 years) versus 6.29 years (95% CI: 4.73 - 8.95 years), p = 0.016 respectively(B). Higher serum magnesium (HR 0.199 per doubling, 95% CI 0.078 - 0.503; p<0.001) and higher albumin (HR 0.090 per doubling, 95% CI 0.021 - 0.394; p=0.001) were associated with lower mortality rates, and higher creatinine (HR 1.669 per doubling, 95% CI 1.03 - 2.52; p=0.04) was associated with greater mortality up to 1 year post-transplantation. In a multivariate Cox regression excluding albumin, hypomagnesemia (p < 0.001) and elevated creatinine (p = 0.038) were independent predictors of poor overall survival(A). There was no significant difference between day 15 absolute lymphocyte count between patients with normal magnesium levels and low serum magnesium levels prior to their conditioning regimen. Although we hypothesized that we would find a significant difference between 15 day absolute lymphocyte count recovery and hypomagnesemia, this was not apparent. However, magnesium is an important nutrient for immune function and immune recovery is important after the bone marrow is restored post ablative therapy. Thus, low serum magnesium levels may lead to impaired OS and EFS via impaired lymphocyte function. In vitro studies will be necessary to understand this mechanism further. Magnesium may simply be a marker of illness and replacement of magnesium may not improve outcomes. However, further investigations are needed to determine whether outcomes would improve with replacement of magnesium in patients with hypomagnesemia, which our study did not address. Overall, our preliminary data suggests that hypomagnesemia is an independent prognostic factor and predictor of inferior OS and EFS in this cohort of patients. Figure Disclosures Ansell: ADC Therapeutics:Research Funding;AI Therapeutics:Research Funding;Trillium:Research Funding;Affimed:Research Funding;Regeneron:Research Funding;Seattle Genetics:Research Funding;Bristol Myers Squibb:Research Funding;Takeda:Research Funding.Witzig:Spectrum:Consultancy;Celgene:Consultancy, Research Funding;Immune Design:Research Funding;Karyopharm Therapeutics:Research Funding;Acerta:Research Funding;Incyte:Consultancy;AbbVie:Consultancy;MorphSys:Consultancy.

Abstract Background High–ω‐6 polyunsaturated fatty acids (PUFAs) are noted to contribute to development of intestinal failure–associated liver disease (IFALD) in home parenteral nutrition (HPN). Fish oil (FO) has been added to latest generation of lipid injectable emulsion (ILE) to increase ω‐3:ω‐6 PUFA ratio; however, appropriate dose of FO to treat IFALD is unknown. Methods After approval of exclusive FO ILE in the US for pediatric patients, we noted 2 adult patients with ongoing IFALD despite transition to mixed‐oil (MO) ILE. They were transitioned to off‐label FO ILE after review of literature regarding use of FO ILE in adult HPN patients was conducted to guide management. Results The first case involves a 40‐year‐old female receiving HPN with IFALD refractory to MO ILE. MO ILE (with 15% FO) was provided at 50 g/d for 3 d/wk and combined with FO ILE at 50 g/d for 4 d/wk. This combination resulted in improvement in liver studies and allowed for decrease in dextrose calories. The second case involves a 49‐year‐old male receiving HPN (secondary to complications of necrotizing pancreatitis) who developed IFALD. FO ILE was used as the sole source of lipids and led to improvement in liver function tests. No evidence of essential fatty acid deficiency was found in either case. Conclusions Current case presentations and review of literature support the use of FO ILE to increase ω‐3 PUFAs in patients with IFALD refractory to MO ILE. Additional research is necessary to delineate the dose of FO ILE necessary to achieve benefit.

AbstractBackgroundTrace‐element contamination of contemporary parenteral nutrition (PN) components exists in unknown quantities and, in combination with excessive amounts of certain trace elements provided in commercially available adult, pediatric, and neonatal multitrace‐element (MTE) products, could result in eventual accumulation and toxicity. This study aims to quantify trace‐element contamination in components used for PN compounding to further inform recommendations for MTE product reformulation and individualized trace‐element prescribing in PN.MethodsA total of 32 unique components (65 products) available for PN compounding were tested for manganese, chromium, selenium, zinc, and copper contamination, utilizing inductively coupled plasma mass spectrometry. Theoretical adult, pediatric, and neonatal PNs were formulated to assess the impact of macronutrient and micronutrient component doses on PN trace‐element contamination.ResultsTrace‐element contamination was detected in 24 (75%) components tested. Chromium and manganese were common, present in 65.6% and 51.5% of all components, respectively. Eight components did not contain detectable trace‐element contamination, most notably sterile water, concentrated dextrose, and lipid emulsion. Manganese contamination in theoretical adult, pediatric, and neonatal PN was 25.18, 9.92, and 1.37 µg, respectively. Chromium contamination was 4.85, 1.5, and 0.28 µg, respectively.ConclusionTrace‐element contamination was prevalent in components used to compound PN. Our findings support reformulation of adult, pediatric, and neonatal manufactured MTE products to eliminate chromium, decrease manganese, and supply full daily physiologic requirements of selenium, zinc, and copper. Future study is needed to assess the additional contamination that could occur through the compounding and storage processes.

AbstractDisruptions in the medication supply chain and consequent drug product shortages, including shortages of parenteral products used for parenteral nutrition (PN) compounding, have become an increasingly common occurrence. The amino acid solution shortage that resulted from the devastating impact of Hurricanes Maria and Irma on manufacturing facilities in Puerto Rico in 2017 necessitated a rapid, coordinated shift from use of compounded PN to commercial multichamber‐bag PN (MCB‐PN) at our hospitals. We describe our experience operationalizing this intervention via a framework that may be adapted for addressing other drug product shortages to promote rapid yet safe use of therapeutic alternatives.