Where Are the Children? A Thematic Analysis of State, Territory, and Tribal Organization Comprehensive Cancer Control Plans.

BACKGROUND: The Center for Disease Control's Comprehensive Cancer Control Program (CCCP) funds initiatives in fifty states, the District of Columbia, seven U.S. territories, and seven tribal organizations to prevent and control cancer. These initiatives influence policy, care, research, and advocacy for cancer treatment. We performed an analysis of CCCP plans for states, U.S. territories, and tribal organizations to understand the extent of inclusion of pediatric cancer care. METHODS: We conducted a thematic and quantitative analysis of CCCP plans for states, U.S. territories, and tribal organizations. Plans were assessed by two reviewers and scored for discussion of cancer prevention, risk factors, early detection and screening, treatment and innovation, access, barriers to care, and survivorship in childhood cancer. RESULTS: Plans from fifty states, the District of Columbia, seven territories, seven tribal organizations, and one Pacific Regional (USAPI) plan were reviewed, for a total of sixty-six plans. Up-to-date CCCP plans were available through the CDC or state websites for 74% of states, 57% of territories, and 71% of tribal organizations; older plans were available for all groups without up-to-date CCCP plans. While all plans referenced children, most did so in the context of childhood exposures influencing adult cancer risks (e.g., sun, tobacco, HPV). Few plans contained a section dedicated to childhood cancer (30% states, 14.3% territories, 14.3% tribes). A minority of plans specifically discussed early detection and screening (14% states, 0% territories, 14.3% tribes), treatment and innovation (32% states, 0% territories, 28.6% tribes), access to cancer care (38% states, 28.6% territories, 28.6% tribes), reducing barriers to cancer care (28% states, 42.9% territories, 28.6% tribes), and pediatric cancer survivorship (42% states, 0% territories, 28.6% tribes). CONCLUSIONS: Promoting inclusion of pediatric cancer in CCPs will help to standardize pediatric cancer care, eliminate treatment disparities across state lines, and allow for comprehensive understanding of pediatric oncology. LEVEL OF EVIDENCE: Level IV.

Change to Mixed-Lipid Emulsion From Soybean Oil-Based Lipid Emulsion in Pediatric Patients.

Importance: Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes. Objective: To examine the association of a hospital-wide switch to a mixed-lipid formula (4-OLE) with pediatric outcomes. Design, Setting, and Participants: Retrospective cohort study at a large US academic referral center. Pediatric patients aged 1 month to 17 years requiring parenteral nutrition from May 2016 to September 2019 were included. Data were analyzed from October 2020 to February 2023. Exposure: In 2017, Duke University Health System fully converted to a soybean oil/MCT/olive/fish oil lipid (4-OLE) from pure soybean oil-based LE in pediatric patients. Pediatric patients before the change (Intralipid [IL] group) were compared with patients after (4-OLE group). Main Outcomes and Measures: Clinical outcomes were compared between treatment periods via multivariable regression models. The primary outcome was hospital length of stay (LOS). Fourteen secondary outcomes included hospital mortality of any cause, 30-day or 90-day readmission, pneumonia, urinary tract infections (UTIs), total caloric delivery, and liver function tests (aspartate aminotransferase, alanine transaminase, alkaline phosphatase, and total bilirubin). Results: A total of 684 children dependent on PN were identified (342 were critically ill), with 30% (206 children) in the preswitch (IL) period and 70% (478 children) in the postswitch (4-OLE) period; 123 were male (59.7%). In comparing IL vs 4-OLE, there was a significant difference in median (IQR) age (4.0 [1.2-13.0] vs 3.0 [0.8-9.0] years, respectively; P = .04), without difference in body mass index or baseline comorbidities except for significant differences in cancer diagnosis (26 patients in the IL group [12.6%] vs 29 patients in the 4-OLE group [6.1%]; P = .004) and chronic obstructive pulmonary disease (24 patients in the IL group [11.7%] vs 30 patients in the 4-OLE group [6.3%]; P = .02). In the all children cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.05-0.78), and reduced UTI risk (OR, 0.33; 95% CI, 0.18-0.64). In the ICU cohort, 4-OLE was associated with shorter hospital LOS (IRR, 0.81; 95% CI, 0.78-0.83), and reduced UTI risk (OR, 0.23; 95% CI, 0.11-0.51). Other secondary outcomes were not significant. Conclusions and Relevance: In this observational study of clinical outcomes among children dependent on PN, a switch to 4-OLE in a large academic hospital was associated with a significant decrease in hospital LOS in ICU and non-ICU patients. These findings suggest switching to a soy-LE sparing strategy using 4-OLE is feasible, safe, and associated with improved clinical outcomes in pediatric PN patients.

Lipid emulsions in parenteral nutrition: does it matter?

PURPOSE OF REVIEW: Recently, clinicians have shown interest in switching patients to nonsoybean-based intravenous lipid emulsion (ILE) formulas for parental nutrition (PN) due to adverse outcomes related to high Omega-6 content in soybean oil (SO) ILE's. This review summarizes recent literature on improved clinical outcomes with new Omega-6 lipid-sparing ILE's in PN management. RECENT FINDINGS: Although there is a paucity of large-scale studies directly comparing Omega-6 lipid sparing ILE's with SO-based lipid emulsion use in PN in ICU patients, there is strong translational and meta-analysis evidence to suggest that lipid formulations containing fish oil (FO) and/or olive oil (OO) have favorable effects on immune function and improve clinical outcomes in ICU populations. SUMMARY: More research is needed to directly compare omega-6-sparing PN formulas with FO and/or OO versus traditional SO ILE's. However, current evidence is promising for improved outcomes using newer ILE's including reduced infections, shorter lengths of stay, and reduced costs.

Optimal Nutrition in the Older Adult: Beneficial Versus Ineffective Supplements.

PURPOSE OF REVIEW: Proper nutrition in older adults is essential, as nutritional deficiencies are common in this population. This review aims to summarize the benefits and risks of nutritional supplementation in the older adult population including the efficacy of various supplements, their risks, and common drug interactions with frequently prescribed medications. RECENT FINDINGS: In recent years, a growing percentage of older adults have been found to take multiple daily nutritional supplements. This population has complex nutritional needs due to the physiology of aging and the presence of comorbidities. However, many primary care providers are unaware of the benefits and drawbacks of nutritional supplementation in the elderly. This review summarizes the current literature to provide more clarity to providers on how to support this population's nutritional needs. Nutritional supplementation is essential for elderly populations who may not be able to obtain adequate nutrition from dietary sources. Supplements vary widely in efficacy and safety. As such, supplementation should be individualized and guided by a qualified healthcare provider to ensure patients receive effective, beneficial nutrition.

Hospital change to mixed lipid emulsion from soybean oil-based lipid emulsion for parenteral nutrition in hospitalized and critically ill adults improves outcomes: a pre-post-comparative study.

INTRODUCTION: Early data suggest use of a mixed lipid emulsion (LE) with a soybean oil reduction strategy in parenteral nutrition (PN) may improve clinical outcomes. Duke University Hospital made a full switch to a Soybean oil/MCT/Olive/Fish Oil lipid (4-OLE) from pure soybean oil-based LE (Intralipid, Baxter Inc) in May 2017. Since 4-OLE has limited evidence related to its effects on clinical outcome parameters in US hospitals, evidence for clinical benefits of switching to 4-OLE is needed. Therefore, we examined the clinical utility of a hospital-wide switch to 4-OLE and its effect on patient outcomes. METHODS: We conducted a single-center retrospective cohort study among adult patients (> 18 years) requiring PN from 2016 to 2019. Our primary exposure was treatment period (1-year pre-4-OLE switch versus 2-year post). We used multivariable regression models to examine our primary outcomes, the association of treatment period with hospital length of stay (LOS), and secondary outcomes liver function, infections, and ICU LOS. Analyses were stratified into critically ill and entire adult cohort. RESULTS: We identified 1200 adults hospitalized patients. 28% of PN patients (n = 341) were treated pre-4-OLE switch and 72% post-4-OLE (n = 859). In the adult cohort, 4-OLE was associated with shorter hospital LOS (IRR 0.97, 95% CI 0.95-0.99, p = 0.039). The ICU cohort included 447 subjects, of which 25% (n = 110) were treated pre-4-OLE switch and 75% (n = 337) were post-switch. ICU patients receiving 4-OLE were associated with shorter hospital LOS (IRR 0.91, 95% CI 0.87-0.93, p < 0.0001), as well as a shorter ICU LOS (IRR 0.90, 95% CI 0.82-0.99, p = 0.036). 4-OLE ICU patients also had a significantly lower delta total bilirubin (- 1.6, 95% CI - 2.8 to - 0.2, p = 0.021) and reduced urinary tract infection (UTI) rates (OR 0.50, 95% CI 0.26-0.96, p = 0.038). There were no associations in AST, ALT, or total bilirubin in ICU and all adult patients. CONCLUSION: 4-OLE was successfully implemented and reduced soybean oil LE exposure in a large academic hospital setting. The introduction of 4-OLE was associated with reduced LOS, UTI rates, and mitigated hepatic dysfunction in critically ill patients. Overall, these findings prove a switch to a soybean oil-LE sparing strategy using 4-OLE is feasible and safe and is associated with improved clinical outcomes in adult PN patients.

Micronutrient deficiencies in critically ill patients receiving continuous renal replacement therapy.

BACKGROUND & AIMS: Continuous renal replacement therapy (CRRT) is essential to the management of acute kidney injury (AKI) in critical illness. Unfortunately, large quantities of micronutrients are shown to be lost in CRRT effluent. Current literature describes serum micronutrient values in CRRT patients to be below-reference range, yet seldom compares such values to other critically ill populations unexposed to CRRT. The aim of this study was to describe and compare the prevalence of micronutrient and carnitine deficiencies in critically ill patients at high malnutrition risk exposed to CRRT to a group of patient unexposed to CRRT. METHODS: A retrospective chart review was conducted at Duke University Hospital using the electronic medical record. The study group consisted of patients at high malnutrition risk requiring intensive care unit (ICU) admission from 01/01/2017-12/31/2018 with one or more of the following serum micronutrient levels checked: carnitine, copper, zinc, selenium, and vitamins B1, B6, B9, and C. Micronutrient deficiencies were defined as below the reference range and carnitine deficiencies were interpreted as an acyl to free carnitine ratio (ACFR) of >0.4. RESULTS: 106 ICU patients met inclusion criteria and 46% were exposed to CRRT. At least one micronutrient deficiency was reported in 90% of CRRT patients compared to 61% patients unexposed to CRRT (p = 0.002). A greater percentage of copper (p < 0.001) and carnitine (p < 0.001) deficiencies were found among patients exposed to CRRT, while more zinc deficiencies were noted among non-CRRT patients (p = 0.001). CONCLUSIONS: The vast majority of CRRT patients presented with micronutrient deficiencies. Clinicians should have a heightened awareness of the risk for serum copper, carnitine, and vitamin B6 deficiencies among CRRT patients. Further prospective and randomized-controlled trials are needed to better define this new category of malnutrition and test supplementation strategies to address and prevent these clinically-relevant deficiencies.

Point-Counterpoint: Indirect Calorimetry Is Essential for Optimal Nutrition Therapy in the Intensive Care Unit.

Iatrogenic malnutrition and underfeeding are ubiquitous in intensive care units (ICUs) worldwide for prolonged periods after ICU admission. A major driver leading to the lack of emphasis on timely ICU nutrition delivery is lack of objective data to guide nutrition care. If we are to ultimately overcome current fundamental challenges to effective ICU nutrition delivery, we must all adopt routine objective, longitudinal measurement of energy targets via indirect calorimetry (IC). Key evidence supporting the routine use of IC in the ICU includes (1) universal societal ICU nutrition guidelines recommending IC to determine energy requirements; (2) data showing predictive equations or body weight calculations that are consistently inaccurate and correlate poorly with measured energy expenditure, ultimately leading to routine overfeeding and underfeeding, which are both associated with poor ICU outcomes; (3) recent development and worldwide availability of a new validated, accurate, easy-to-use IC device; and (4) recent data in ICU patients with coronavirus disease 2019 (COVID-19) showing progressive hypermetabolism throughout ICU stay, emphasizing the inaccuracy of predictive equations and marked day-to-day variability in nutrition needs. Thus, given the availability of a new validated IC device, these findings emphasize that routine longitudinal IC measures should be considered the new standard of care for ICU and post-ICU nutrition delivery. As we would not deliver vasopressors without accurate blood pressure measurements, the ICU community is only likely to embrace an increased focus on the importance of early nutrition delivery when we can consistently provide objective IC measures to ensure personalized nutrition care delivers the right nutrition dose, in the right patient, at the right time to optimize clinical outcomes.

The role of p65 NF-kappaB/RelA in pancreatitis-induced Kupffer cell apoptosis.

Acute pancreatitis induces liver injury by upregulating Kupffer cell-derived Fas/FasL; on the other hand, acute pancreatitis induces apoptosis of Kupffer cells via NF-kappaB-dependent pathways. The balance between upregulation of Fas/FasL and Fas/FasL-induced apoptosis of its originator cell may determine the severity of pancreatitis-related liver injury. The aim of our study was to determine the role of p65 NF-kappaB/RelA in pancreatitis-induced Kupffer cell apoptosis. Acute pancreatitis was induced in NIH Swiss mice by a choline-deficient ethionine-supplement (CDE) diet. In vitro mouse Kupffer cell line was transfected with p65 siRNA and treated with pancreatic elastase to mimic pancreatitis. CDE pancreatitis upregulated nuclear translocation of p65 NF-kappaB/RelA, Fas/FasL, caspase-3, and DNA fragmentation in mice livers (all P < 0.001). In vitro, pancreatic elastase mimicked CDE-pancreatitis by upregulating nuclear translocation of p65 NF-kappaB/RelA, Fas/FasL, caspase-3, DNA fragmentation, and apoptosis in Kupffer cells (all P < 0.001). Transfection with p65 siRNA attenuated the elastase-induced nuclear translocation of p65 NF-kappaB/RelA, upregulation of Fas/FasL, caspase-3, DNA fragmentation, and apoptosis in Kupffer cells (all P < 0.001). Acute pancreatitis activates p65 NF-kappaB/RelA and induces apoptosis of Kupffer cells. Inhibition of p65NF-kappaB/RelA attenuates elastase-induced upregulation of proapoptotic pathways and apoptosis in Kupffer cells. The ability of Kupffer cells to autoregulate their stress response by inducing self-apoptosis warrants further investigation.

Fas/FasL play a central role in pancreatitis-induced hepatocyte apoptosis.

Liver injury is a clinical prognostic indicator in acute pancreatitis (AP). We have demonstrated that Kupffer cell-derived FasL mediates liver injury during AP and sought to determine its role in AP-induced hepatocyte apoptosis. AP was induced in National Institutes of Health (NIH) Swiss mice, C57/C57, and Fas-/-, FasL-/- mice by a choline-deficient ethionine-supplement diet. Liver Fas, FasL, p38-mitogen activated phosphokinase (p38-MAPK), poly-ADP ribose polymerase (PARP), and cytochrome C were measured by immunoblotting. Apoptosis was assessed by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) and DNA fragmentation (ELISA). AP upregulated liver FasL (4280 +/- 580 vs. 733 +/- 336), Fas (2866 +/- 595 vs. 649 +/- 111), cytochrome C (6980 +/- 237 vs. 903 +/- 156), and PARP (6393 +/- 591 vs. 466 +/- 261) as well as increased TUNEL staining (40 +/- 2 vs. 14 +/- 1) and DNA fragmentation (all P < 0.03 vs. control). In FasL-/- and Fas-/- mice, AP-induced upregulation of p38-MAPK, PARP, and cytochrome C was significantly attenuated (all P < 0.01 compared to C57/C57 control). In addition, AP-induced DNA fragmentation was reduced 60% in Fas-/- and FasL-/- mice (P < 0.01 vs. C57/C57). AP induces apoptosis by transcriptional activation of Fas/FasL. AP-induced apoptosis was significantly reduced in Fas and FasL knockout mice along with downregulation of p38-MAPK, PARP, and cytochrome C, thereby suggesting a central role for Fas/FasL in hepatocyte apoptosis. The manipulation of interactions between Kupffer cell-derived FasL and hepatocytes may have important therapeutic implications.