Timing of percutaneous endoscopic gastrostomy tube placement in post-stroke patients does not impact mortality, complications, or outcomes.

BACKGROUND: Percutaneous Endoscopic Gastrostomy (PEG) tubes are often placed for dysphagia following a stroke in order to maintain sufficient caloric intake. The 2011 ASGE guidelines recommend delaying PEG tube placement for two weeks, as half of patients with dysphagia improve within 2 wk. There are few studies comparing outcomes based on timing of PEG tube placement, and there is increasing demand for early PEG tube placement to meet requirements for timely discharge to rehab and skilled nursing facilities. AIM: To assess the safety of early (≤ 7 d post stroke) vs late (> 7 d post stroke) PEG tube placement and evaluate whether pre-procedural risk factors could predict mortality or complications. METHODS: We performed a retrospective study of patients undergoing PEG tube placement for dysphagia following a stroke at two hospitals in Saint Louis, MO between January 2011 and December 2017. Patients were identified by keyword search of endoscopy reports. Mortality, peri-procedural complication rates, and post-procedural complication rates were compared in both groups. Predictors of morbidity and mortality such as protein-calorie malnutrition, presence of an independent cardiovascular risk equivalent, and presence of Systemic inflammatory response syndrome (SIRS) criteria or documented infection were evaluated by multivariate logistic regression. RESULTS: 154 patients had a PEG tube placed for dysphagia following a stroke, 92 in the late group and 62 in the early group. There were 32 observed deaths, with 8 occurring within 30 d of the procedure. There was an increase in peri-procedural and post-procedural complications with delayed PEG placement which was not statistically significant. Hospital length of stay was significantly less in patients with early PEG tube placement (12.9 vs 22.34 d, P < 0.001). Protein calorie malnutrition, presence of SIRS criteria and/or documented infection prior to procedure or having a cardiovascular disease risk equivalent did not significantly predict mortality or complications. CONCLUSION: Early PEG tube placement following a stroke did not result in a higher rate of mortality or complications and significantly decreased hospital length of stay. Given similar safety outcomes in both groups, early PEG tube placement should be considered in the appropriate patient to potentially reduce length of hospital stay and incurred costs.

Studies towards the synthesis of methionine aminopeptidase inhibitors: diversification utilizing a ROMP-derived coupling reagent.

Efforts to synthesize potential methionine aminopeptidase inhibitors is described. Preliminary SAR and docking studies served as a guide to design the compound libraries. "Chromatography-free" synthesis of various heterocyclic amides was realized by using a high-load, soluble coupling reagent derived via ring-opening metathesis polymerization (ROMP). Subsequent microwave-assisted Suzuki reactions with ortho-substituted arylboronic acids, followed by chromatographic purification afforded a 55-member library in high yields and purities. While the biological testing was not satisfactory, concurrent X-ray crystallography studies revealed key structural features essential for inhibition of methionine aminopeptidase, which directed fruitful results reported in the accompanying manuscript. In addition, in silico Lipinksi profiles and ADME properties of the library are also reported.

Ionic immobilization, diversification, and release: application to the generation of a library of methionine aminopeptidase inhibitors.

Development of an ionic immobilization, diversification, and release method for the generation of methionine aminopeptidase inhibitors is reported. This method involves the immobilization of 5-bromofuran-2-carboxylic acid and 5-bromothiophene-2-carboxylic acid onto PS-BEMP, followed by Suzuki reaction on a resin-bound intermediate and subsequent release to provide products in moderate yields and excellent purities. Compound potencies were evaluated on the Co(II), Mn(II), Ni(II), and Fe(II) forms of Escherichia coli MetAP1. The furoic-acid analogs were found to be Mn(II) selective with IC 50 values in the low micromolar range. Qualitative SAR analysis, supplemented by molecular modeling studies, provides valuable information on structural elements responsible for potency and selectivity.