Doxycycline Alters the Porcine Renal Proteome and Degradome during Hypothermic Machine Perfusion.

Ischemia-reperfusion injury (IRI) is a hallmark for tissue injury in donation after circulatory death (DCD) kidneys. The implementation of hypothermic machine perfusion (HMP) provides a platform for improved preservation of DCD kidneys. Doxycycline administration has shown protective effects during IRI. Therefore, we explored the impact of doxycycline on proteolytic degradation mechanisms and the urinary proteome of perfused kidney grafts. Porcine kidneys underwent 30 min of warm ischemia, 24 h of oxygenated HMP (control/doxycycline) and 240 min of ex vivo reperfusion. A proteomic analysis revealed distinctive clustering profiles between urine samples collected at T15 min and T240 min. High-efficiency undecanal-based N-termini (HUNTER) kidney tissue degradomics revealed significantly more proteolytic activity in the control group at T-10. At T240, significantly more proteolytic activity was observed in the doxycycline group, indicating that doxycycline alters protein degradation during HMP. In conclusion, doxycycline administration during HMP led to significant proteomic and proteolytic differences and protective effects by attenuating urinary NGAL levels. Ultimately, we unraveled metabolic, and complement and coagulation pathways that undergo alterations during machine perfusion and that could be targeted to attenuate IRI induced injury.

Glioma patient-reported outcomes: patients and clinicians.

INTRODUCTION: Routine assessment of patient-reported outcomes (PROs) in oncology has shown to improve the quality of the delivered care and to prolong survival. However, for successful implementation of routine assessment of PROs, more knowledge on their usability in clinical practice is needed. OBJECTIVE: This study aimed to cross-sectionally assess the perspective of patients and clinicians on the practicality of routinely measuring PROs in clinical practice for glioma patients. METHODS: Semistructured interviews were conducted evaluating the role of healthcare professionals (HCP) in discussing results of PRO measures (PROMs), and the preferred topics, methods and frequency of PRO assessment. Glioma patients, their proxies and HCPs involved in the treatment of glioma patients from eight centres in the Netherlands were included. RESULTS: Twenty-four patients, 16 proxies and 35 HCPs were interviewed. The majority of patients, proxies and HCPs (92%, 81% and 80%, respectively) were willing to discuss PRO results during consultations. Although HCPs prefer that results are discussed with the nurse specialist, only one-third of patients/proxies agreed. Functioning of daily life was considered important in all three groups. Most participants indicated that discussion of PROM results should take place during standard follow-up visits, and completed at home about 1 week in advance. On group level, there was no preference for administration of questionnaires on paper or digitally. Lastly, all centres had staff available to send questionnaires on paper. CONCLUSION: This study shows that routine assessment of PROs is desired by patients, proxies and HCP's in neuro-oncological care in Dutch hospitals.