Estimates of 30-day postoperative pulmonary complications after gastrointestinal endoscopic procedures: A retrospective cohort analysis of a health system population.

The incidence of 30-day postoperative pulmonary complications (PPC) of gastrointestinal endoscopic procedures (GIEP) are not well characterized in the literature. The primary aim of this study was to identify the incidence of 30-day PPC after GIEP within a large healthcare system. We conducted a retrospective cohort study of 5377 patients presenting for GIEP between January 2013 and January 2022. Our primary outcome was the Agency for Healthcare Research and Quality PPC composite (AHRQ-PPC). Secondary outcomes were sub-composites derived from the AHRQ-PPC; including pneumonia (AHRQ-PNA), respiratory failure (AHRQ-RF), aspiration pneumonia/ pneumonitis (AHRQ-ASP) and pulmonary emboli (AHRQ-PE). We performed propensity score matching (PSM) followed by multivariable logistic regression to analyze primary and secondary outcomes. Inpatients had higher 30-day AHRQ-PPC (6.0 vs. 1.2%, p<0.001), as well as sub-composite AHRQ-PNA (3.2 vs. 0.7%, p<0.001), AHRQ-RF (2.4 vs. 0.5%, p<0.001), and AHRQ-ASP (1.9 vs. 0.4%, p<0.001). After PSM adjustment, pre-procedural comorbidities of electrolyte disorder [57.9 vs. 31.1%, ORadj: 2.26, 95%CI (1.48, 3.45), p<0.001], alcohol abuse disorder [16.7 vs. 6.8%, ORadj: 2.66 95%CI (1.29, 5.49), p = 0.01], congestive heart failure (CHF) [22.3 vs. 8.7%, ORadj: 2.2 95%CI (1.17, 4.15), p = 0.02] and pulmonary circulatory disorders [21 vs. 16.9%, ORadj: 2.95, 95%CI (1.36, 6.39), p = 0.01] were associated with 30-day AHRQ-PPC. After covariate adjustment, AHRQ-PPC was associated with upper endoscopy more than lower endoscopy [5.9 vs. 1.0%, ORadj: 3.76, 95%CI (1.85, 7.66), p<0.001]. When compared to gastroenterologist-guided conscious sedation, anesthesia care team presence was protective against AHRQ-PPC [3.7 vs. 8.4%, ORadj: 0.032, 95%CI (0.01, 0.22), p<0.001] and AHRQ-ASP [1.0 vs. 3.37%, ORadj: 0.002, 95%CI (0.00, 0.55), p<0.001]. In conclusion, we report estimates of 30-day PPC after GIEP across inpatient and outpatient settings. Upper endoscopic procedures confer a higher risk, while the presence of an anesthesia care team may be protective against 30-day PPC.

D-to-E and T19V Variants of the pH-Low Insertion Peptide and Their Doxorubicin Conjugates Interact with Membrane at Higher pH Ranges Than WT.

To improve targeted cargo delivery to cancer cells, pH-Low Insertion Peptide (pHLIP) variants were developed to interact with the membrane at pH values higher than those of the WT. The Asp-to-Glu variants aim to increase side chain pKa without disturbing the sequence of protonations that underpin membrane insertion. The Thr19 variants represent efforts to perturb the critical Pro20 residue. To study the effect of cargo on pHLIP insertion, doxorubicin (Dox), a fluorescent antineoplastic drug, was conjugated to selected variants near the inserting C-terminus. Variants and conjugates were characterized on a POPC membrane using Trp and Dox fluorescence methods to define the entire pH range of insertion (pHinitial-pHfinal). Compared to WT with a pHi-pHf range of 6.7-5.6, D25E-D31E-D33E, D14E-D25E-D31E-D33E, and T19V-D25E variants demonstrated higher pHi-pHf ranges of 7.3-6.1, 7.3-6.3, and 8.2-5.4, respectively. The addition of Dox expanded the pHi-pHf range, mainly by shifting pHi to higher pH values (e.g., WT pHLIP-Dox has a pHi-pHf range of 7.7-5.2). Despite the low Hill coefficient observed for the conjugates, D14E-D25E-D31E-D33E pHLIP-Dox completed insertion by a pHf of 5.7. However, the Dox cargo remained in the hydrophobic membrane interior after pHLIP insertion, which may impede drug release. Finally, a logistic function can describe pHLIP insertion as a peripheral-to-TM (start-to-finish) two-state transition; wherever possible, we discuss data deviating from such sigmoidal fitting in support of the idea that pH-specific intermediate states distinct from the initial peripheral state and the final TM state exist at intervening pH values.