OPTIMIZING NUTRITION IN INFANTS AT RISK OF INTESTINAL FAILURE-ASSOCIATED LIVER DISEASE

Statement of Problem: Infants undergoing intestinal surgery are at risk for feeding intolerance and resultant complications, including intestinal failure and intestinal failure-associated liver disease (IFALD). In infants, IFALD is defined as a persistent direct bilirubin (DB) >2mg/dl for >1 week in the setting of parenteral nutrition (PN) and can lead to liver failure. The optimal strategy for feeding post-operative infants to reduce PN exposure is poorly understood. We hypothesized that a more systematic approach to providing enteral nutrition (EN) would reduce the risk of IFALD. Methods: We conducted three studies: 1) A retrospective descriptive analysis of the baseline feeding practices and incidence of IFALD among surgical infants in the Neonatal Intensive Care Unit, 2) An interval analysis (pre- and post-intervention) 15 months after implementation of newly devised feeding guidelines using run-charts to measure adherence to feeding recommendations and peak direct bilirubin in real-time, and 3) A final analysis 2.5 years after guideline implementation to measure the overall impact of the feeding guidelines on IFALD incidence and severity using logistic regression. Results: We identified variable feeding practices and a high baseline incidence of IFALD, 66% (confidence interval [CI] 0.55 - 0.76) among all surgical infants and 90% (CI 0.78 – 1.01) among those needing >60 days of PN from 2007-2012. In the 15-month post-guideline analysis, a shift to reduced time to reach feeding goals (initiation and 50% EN) and decreased peak DB were seen on run-charts. In the final analysis, the initial post-operative EN median volume increased from 10 to 20 ml/kg/day (P=0.001). Time to reach 50% EN decreased from a median of 10 to 5 days (P=0.013). The overall incidence of IFALD improved from 71 to 53% in infants needing >7 days of PN (P=0.03), and the median peak DB decreased from 5.7 to 2.3 mg/dl (P=0.003). The adjusted odds for developing moderate-severe IFALD were reduced by 67% in the post-guideline cohort, compared to the pre-guideline baseline (P=0.002). Conclusions: The feeding intervention was well tolerated and resulted in shorter time to initiate EN and reach 50% of goal EN post-operatively. The incidence and severity of IFALD also improved

OPTIMIZING NUTRITION IN INFANTS AT RISK OF INTESTINAL FAILURE-ASSOCIATED LIVER DISEASE

Statement of Problem: Infants undergoing intestinal surgery are at risk for feeding intolerance and resultant complications, including intestinal failure and intestinal failure-associated liver disease (IFALD). In infants, IFALD is defined as a persistent direct bilirubin (DB) >2mg/dl for >1 week in the setting of parenteral nutrition (PN) and can lead to liver failure. The optimal strategy for feeding post-operative infants to reduce PN exposure is poorly understood. We hypothesized that a more systematic approach to providing enteral nutrition (EN) would reduce the risk of IFALD. Methods: We conducted three studies: 1) A retrospective descriptive analysis of the baseline feeding practices and incidence of IFALD among surgical infants in the Neonatal Intensive Care Unit, 2) An interval analysis (pre- and post-intervention) 15 months after implementation of newly devised feeding guidelines using run-charts to measure adherence to feeding recommendations and peak direct bilirubin in real-time, and 3) A final analysis 2.5 years after guideline implementation to measure the overall impact of the feeding guidelines on IFALD incidence and severity using logistic regression. Results: We identified variable feeding practices and a high baseline incidence of IFALD, 66% (confidence interval [CI] 0.55 - 0.76) among all surgical infants and 90% (CI 0.78 – 1.01) among those needing >60 days of PN from 2007-2012. In the 15-month post-guideline analysis, a shift to reduced time to reach feeding goals (initiation and 50% EN) and decreased peak DB were seen on run-charts. In the final analysis, the initial post-operative EN median volume increased from 10 to 20 ml/kg/day (P=0.001). Time to reach 50% EN decreased from a median of 10 to 5 days (P=0.013). The overall incidence of IFALD improved from 71 to 53% in infants needing >7 days of PN (P=0.03), and the median peak DB decreased from 5.7 to 2.3 mg/dl (P=0.003). The adjusted odds for developing moderate-severe IFALD were reduced by 67% in the post-guideline cohort, compared to the pre-guideline baseline (P=0.002). Conclusions: The feeding intervention was well tolerated and resulted in shorter time to initiate EN and reach 50% of goal EN post-operatively. The incidence and severity of IFALD also improved

Contributing factors common to COVID-19 and gastrointestinal cancer

The devastating complications of coronavirus disease 2019 (COVID-19) result from the dysfunctional immune response of an individual following the initial severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Multiple toxic stressors and behaviors contribute to underlying immune system dysfunction. SARS-CoV-2 exploits the dysfunctional immune system to trigger a chain of events, ultimately leading to COVID-19. The authors have previously identified a number of contributing factors (CFs) common to myriad chronic diseases. Based on these observations, it was hypothesized that there may be a significant overlap between CFs associated with COVID-19 and gastrointestinal cancer (GIC). Thus, in the present study, a streamlined dot-product approach was used initially to identify potential CFs that affect COVID-19 and GIC directly (i.e., the simultaneous occurrence of CFs and disease in the same article). The nascent character of the COVID-19 core literature (similar to 1-year-old) did not allow sufficient time for the direct effects of numerous CFs on COVID-19 to emerge from laboratory experiments and epidemiological studies. Therefore, a literature-related discovery approach was used to augment the COVID-19 core literature-based ‘direct impact’ CFs with discovery-based ‘indirect impact’ CFs [CFs were identified in the non-COVID-19 biomedical literature that had the same biomarker impact pattern (e.g., hyperinflammation, hypercoagulation, hypoxia, etc.) as was shown in the COVID-19 literature]. Approximately 2,250 candidate direct impact CFs in common between GIC and COVID-19 were identified, albeit some being variants of the same concept. As commonality proof of concept, 75 potential CFs that appeared promising were selected, and 63 overlapping COVID-19/GIC potential/candidate CFs were validated with biological plausibility. In total, 42 of the 63 were overlapping direct impact COVID-19/GIC CFs, and the remaining 21 were candidate GIC CFs that overlapped with indirect impact COVID-19 CFs. On the whole, the present study demonstrates that COVID-19 and GIC share a number of common risk/CFs, including behaviors and toxic exposures, that impair immune function. A key component of immune system health is the removal of those factors that contribute to immune system dysfunction in the first place. This requires a paradigm shift from traditional Western medicine, which often focuses on treatment, rather than prevention

Conjugated linoleic acid is a preferential substrate for fatty acid nitration

The oxidation and nitration of unsaturated fatty acids by oxides of nitrogen yield electrophilic derivatives that can modulate protein function via post-translational protein modifications. The biological mechanisms accounting for fatty acid nitration and the specific structural characteristics of products remain to be defined. Herein, conjugated linoleic acid (CLA) is identified as the primary endogenous substrate for fatty acid nitration in vitro and in vivo, yielding up to 105 greater extent of nitration products as compared with bis-allylic linoleic acid. Multiple enzymatic and cellular mechanisms account for CLA nitration, including reactions catalyzed by mitochondria, activated macrophages, and gastric acidification. Nitroalkene derivatives of CLA and their metabolites are detected in the plasma of healthy humans and are increased in tissues undergoing episodes of ischemia reperfusion. Dietary CLA and nitrite supplementation in rodents elevates NO2-CLA levels in plasma, urine, and tissues, which in turn induces heme oxygenase-1 (HO-1) expression in the colonic epithelium. These results affirm that metabolic and inflammatory reactions yield electrophilic products that can modulate adaptive cell signaling mechanisms.Fil: Bonacci, Gustavo Roberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Baker, Paul R. S.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Salvatore, Sonia Rosana. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Shores, Darla. University of Pittsburgh; Estados UnidosFil: Khoo, Nicholas K. H.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Koenitzer, Jeffrey R.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Vitturi, Dario A.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Woodcock, Steven R.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Golin-Bisello, Franca. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Cole, Marsha P.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Watkins, Simon. University of Pittsburgh; Estados UnidosFil: St. Croix, Claudette. University of Pittsburgh; Estados UnidosFil: Batthyany, Carlos I.. Instituto Pasteur; Uruguay. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Freeman, Bruce A.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados UnidosFil: Schopfer, Francisco J.. Univeristy Of Pittsburgh. School Of Medicine. Department Of Pharmacology And Chemical Biology; Estados Unido