Reduced Pneumonia Risk in Advanced Dementia Patients on Careful Hand Feeding Compared With Nasogastric Tube Feeding.

OBJECTIVES: To compare survival and pneumonia risk among hospitalized patients with advanced dementia on nasogastric tube feeding (NGF) vs careful hand feeding (CHF) and to examine outcomes by feeding problem type. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Advanced dementia patients aged ≥60 years with indication for tube feeding admitted to 2 geriatric convalescent hospitals between January 1, 2015, and June 30, 2019. METHODS: Comparison on the effect of NGF and CHF on survival and pneumonia risk using Kaplan Meier survival analysis and Cox proportional hazards models. RESULTS: Of the 764 patients (mean age 89 years, 61% female, 74% residential care home residents), 464 (61%) were initiated on NGF and 300 (39%) on CHF. The primary feeding problem types were dysphagia (50%), behavioral feeding problem (33%), or both (17%). There was no difference in 1-year survival rate between NGF and CHF groups (36% vs 37%, P = .71) and survival did not differ by feeding problem type. Nasogastric tube feeding was not a significant predictor for survival (adjusted hazard ratio 1.15, 95% CI 0.94-1.39). Among 577 (76%) patients who survived to discharge, pneumonia rates were lower in the CHF group (48% vs 60%, P = .004). After adjusting for cofounders, NGF was a significant risk factor for pneumonia (adjusted hazard ratio 1.41, 95% CI 1.08-1.85). In subgroup analyses, NGF was associated with increased pneumonia risk for patients with both dysphagia and behavioral feeding problem (P = .01) but not in patients with behavioral feeding problem alone (P = .24) or dysphagia alone (P = .30). CONCLUSIONS AND IMPLICATIONS: For advanced dementia patients with feeding problems, there is no difference in survival between NGF and CHF. However, NGF is associated with a higher pneumonia risk, particularly for patients with both dysphagia and behavioral feeding problem. Further research on how the feeding problem type impacts pneumonia risk for patients on NGF is needed.

Identification and Mitigation of Defensins in the Immunopurification of Peptide MHC-I Antigens from Lung Tissue.

The class I major histocompatibility (MHC-I) complex is a set of diverse cell surface receptors encoded by the human leukocyte antigen gene complex. These receptors present intracellular antigens to cytotoxic T cells providing information on the state and health of cells. Changes in the immunopeptidome during cancer may provide novel targets for therapeutic intervention. To understand how the tumor immunopeptidome is altered, we developed a mass spectrometry (MS) based platform for isolating and identifying MHC-I peptide antigens in lung tumors. In the course of our work, we encountered several large unknown peptide contaminants which had not been previously reported. To understand the source of these major contaminants, we isolated them using offline fractionation and identified them by liquid chromatography-tandem mass spectrometry (LC-MS/MS) as members of the host defense protein family known as the defensins. To mitigate their detrimental effects, we modified our "Original" data-dependent acquisition (DDA) MS method to narrowly target the MHC-I peptides based on their physical properties including charge state and molecular weight ("z state" DDA), evaluated field asymmetric ion mobility spectrometry to attempt gas-phase separation prior to MS analysis, and developed an immunodepletion approach using defensin specific antibodies. This modified approach improves peptide identification and reduces the impact of defensin contamination in lung tissue samples.

High-throughput logP measurement using parallel liquid chromatography/ultraviolet/mass spectrometry and sample-pooling.

A novel approach to high-throughput logP measurement based on liquid chromatography/ultraviolet/mass spectrometry (LC/UV/MS) is proposed. The logP value is determined by correlation with the logk value, where k is the capacity factor k = (t(r)-t(0))/t(0), with the logP value using a defined set of standards. Since the analyte retention time (t(r)) is determined from the appropriate extracted ion chromatogram (EIC), there are no interferences from impurities and this allows the pooling of multiple compounds into one injection. To ensure the accuracy and instrument robustness in a routine high-throughput environment, a simple and MS-friendly mobile phase consisting of 20 mM ammonium carbonate (pH 8.0) for basic compounds or 20 mM ammonium formate (pH 1.0) for acidic compounds, both in combination with methanol at a ratio of 45:55, is used. This approach has been successfully used on single as well as parallel multi-channel LC/UV/MS systems to screen small to large sets of lead compounds and their analogs. A high-throughput capability to analyze over 1000 compounds per day has been achieved.