To activate pordurgs in cancer, an anti-TAG-72 antibody (HuCC49ΔCH2) was used for delivery of an activation enzyme (β-galactosidase) to specifically activate geldanamycin prodrug (17-AG-C2-Gal) in colon cancer. The geldanamycin prodrug 17-AG-C2-Gal was synthesized by coupling galactose-amine derivative with geldanamycin at C-17 position. Molecular docking with two different programs (Affinity and Autodock) showed that the prodrug (17-AG-C2-Gal) was unable to bind to Hsp90; however, the enzymatically cleaved product (17-AG-C2) by β-galactosidase conjugate bound to Hsp90 in a similar way to geldanamycin and 17-AG. The computational docking results were further confirmed in experimental testing by MTS assay and Mass Spectrometry. HuCC49ΔCH2 was chemically conjugated to β-galactosidase. The antibody-enzyme conjugate was able to target tumor antigen TAG-72 with the well-preserved enzymatic activity to activate 17-AG-C2-Gal prodrug. The released active drug 17-AG-C2 was demonstrated to induce up to 70% AKT degradation, and enhance anticancer activity by more than 25-fold compared to the prodrug.

Purpose Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections have become a serious threat with high morbidity and mortality. Early identification of risk factors for CRKP infections is important, but these factors are still controversial. Therefore, we aimed to identify the risk factors and clinical outcomes of CRKP infections. Patients and Methods The retrospective, single-center study was carried out in the respiratory intensive care unit of the Chinese People’s Liberation Army General Hospital from 2017 to 2020. Patients infected with K. pneumoniae were included and categorized into the CRKP group and carbapenem-sensitive K. pneumoniae (CSKP) group based on the susceptibility to carbapenems. The independent risk factors were investigated by univariate analysis and multivariate logistic regression analysis. The clinical outcomes were also evaluated between the two groups. Results A total of 138 eligible patients were included in our study, with a median age of 80.5 years (interquartile range: 62.0–86.3), and 78.3% of them were males. Of the 138 patients, there were 97 patients in the CRKP group, and the other 41 were assigned into the CSKP group. Multivariate analysis showed that exposure to ≥three types of comorbidities (OR = 5.465, P = 0.003), previous hospitalization (OR = 4.279, P = 0.006), use of quinolones (OR = 5.872, P = 0.012), and indwelling urinary catheter (OR = 5.035, P = 0.000) were independent risk factors for CRKP infections. The in-hospital mortality rate of the CRKP group was 42.1%, which was higher compared with the CSKP group (17.5%, P = 0.006). Conclusion Exposure to ≥three types of comorbidities, previous hospitalization, use of quinolones, and indwelling urinary catheter were independent risk factors for CRKP infections, which had higher mortality compared with CSKP infections. Early detection of high-risk patients and timely control measures should be implemented to prevent the emergence of CRKP infections and thereby improve the clinical outcomes.

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Aims To evaluate a deep oropharyngeal suction intervention (NO‐ASPIRATE) in intubated patients on microaspiration, ventilator‐associated events and clinical outcomes. Design Prospective, two‐group, single‐blind, randomized clinical trial. Methods The study was conducted between 2014 ‐ 2017 in 513 participants enroled within 24 hr of intubation and randomized into NO‐ASPIRATE or usual care groups. Standard oral care was provided to all participants every 4 hr and deep oropharyngeal suctioning was added to the NO‐ASPIRATE group. Oral and tracheal specimens were obtained to quantify α‐amylase as an aspiration biomarker. Results Data were analysed for 410 study completers enrolled at least 36 hr: NO‐ASPIRATE (N = 206) and usual care (N = 204). Percent of tracheal specimens positive for α‐amylase, mean tracheal α‐amylase levels over time and ventilator‐associated events were not different between groups. The NO‐ASPIRATE group had a shorter hospital length of stay and a subgroup with moderate aspiration at baseline had significantly lower α‐amylase levels across time. Conclusion Hospital length of stay was shorter in the NO‐ASPIRATE group and a subgroup of intervention participants had lower α‐amylase across time. Delivery of standardized oral care to all participants may have been an intervention itself and possibly associated with the lack of significant findings for most outcomes. Impact This trial compared usual care to oral care with a deep suctioning intervention on microaspiration and ventilator‐associated events, as this has not been systematically studied. Further research on the usefulness of α‐amylase as an aspiration biomarker and the role of oral suctioning, especially for certain populations, is indicated. Trial registration number: ClinicalTrials.gov: NCT02284178.