Impact of Red Blood Cells on Function and Metabolism of Porcine Deceased Donor Kidneys During Normothermic Machine Perfusion

Background. Normothermic machine perfusion (NMP) protocols using blood-based solutions are commonly used in the assessment of kidneys before transplantation. This procedure is, nevertheless, limited by blood availability and warrants the search for alternatives. We compared a blood-based solution with a serum-like preservation solution (Aqix) enriched with colloids with and without red blood cells (RBCs). Methods. Porcine kidneys retrieved from an abattoir were subjected to 30min of warm ischemia, followed by 3h of hypothermic oxygenated machine perfusion at 4 degrees C. Subsequently, kidneys (n=6 per group) were evaluated with NMP for 4h with 5 different solutions: diluted blood, Aqix with BSARBCs, or Aqix with dextran 40RBCs. Results. Throughout NMP, markers of renal function and tubular metabolism were favorable in groups with RBCs. The addition of RBCs resulted in 4- to 6-fold higher oxygen consumption rates. Controls had significantly higher ATP levels post-NMP, exhibited decreased production of oxidative stress markers, and had the highest creatinine clearance. In conclusion, this study shows that the addition of RBCs during NMP reduced renal injury, improved function, and was associated with increased renal metabolism. Conclusions. Although the RBC-BSA-supplemented Aqix solution was also able to support metabolism and renal function, a blood-based perfusion solution remains superior

Exploring Porcine Precision-Cut Kidney Slices as a Model for Transplant-Related Ischemia-Reperfusion Injury

Marginal donor kidneys are more likely to develop ischemia-reperfusion injury (IRI), resulting in inferior long-term outcomes. Perfusion techniques are used to attenuate IRI and improve graft quality. However, machine perfusion is still in its infancy, and more research is required for optimal conditions and potential repairing therapies. Experimental machine perfusion using porcine kidneys is a great way to investigate transplant-related IRI, but these experiments are costly and time-consuming. Therefore, an intermediate model to study IRI would be of great value. We developed a precision-cut kidney slice (PCKS) model that resembles ischemia-reperfusion and provides opportunities for studying multiple interventions simultaneously. Porcine kidneys were procured from a local slaughterhouse, exposed to 30 min of warm ischemia, and cold preserved. Subsequently, PCKS were prepared and incubated under various conditions. Adenosine triphosphate (ATP) levels and histological tissue integrity were assessed for renal viability and injury. Slicing did not influence tissue viability, and PCKS remained viable up to 72 h incubation with significantly increased ATP levels. Hypothermic and normothermic incubation led to significantly higher ATP levels than baseline. William’s medium E supplemented with Ciprofloxacin (and Amphotericin-B) provided the most beneficial condition for incubation of porcine PCKS. The porcine PCKS model can be used for studying transplant IR

Postoperative recovery of accelerometer-based physical activity in older cancer patients

Introduction: Recovery of physical activity is an important functional outcome measure after cancer surgery. However, objective data on physical activity for older cancer patients is scarce. The aims of this study were to quantify perioperative physical activity levels, assess recovery of physical activity three months after surgery, and characterise patients who achieved recovery. Materials and methods: This observational cohort study analysed physical activity data collected from patients aged >65 who were scheduled for cancer surgery between May 2018 and July 2019. Perioperative daily step count was measured using a Fitbit device. The primary outcome measure was the percentage of patients who returned to (>90% of) their preoperative (baseline) physical activity levels three months after surgery. Results: Fifty patients (mean age 73) were recruited, and available Fitbit data was analysed. Median daily step counts at baseline (n = 40), before hospital discharge (n = 40), and three months postoperative (n = 37) were 5,974 (IQR 4,250-7,922),1,619 (IQR 920-2,839), and 4,674 (IQR 3,047-7,592), respectively. The 15/37 (41%) patients who had reached baseline levels three months after surgery seemed to have more preoperative self-reported physical activity, better anaesthesiologists' physical status classification, and fewer in-hospital complications compared to patients who had not, although the differences were statistically non-significant. Conclusion: Perioperative physical activity was quantified for older cancer patients, and 41% returned to baseline levels within three months. Accelerometer-based physical activity provided a valuable outcome measure for postoperative physical recovery. Future studies using objective physical activity measures are needed to evaluate effects of interventional studies aimed at improving physical activity. (C) 2020 The Authors. Published by Elsevier Ltd

Feasibility of Perioperative eHealth Interventions for Older Surgical Patients:A Systematic Review

OBJECTIVES: EHealth interventions are increasingly being applied in perioperative care but have not been adequately studied for older surgical patients who could potentially benefit from them. Therefore, we evaluated the feasibility of perioperative eHealth interventions for this population. DESIGN: A systematic review of prospective observational and interventional studies was conducted. Three electronic databases (PubMed, EMBASE, CINAHL) were searched between January 1999 and July 2019. Study quality was assessed by Methodological Index for Non-Randomized Studies (MINORS) with and without control group. SETTING AND PARTICIPANTS: Studies of surgical patients with an average age ≥65 years undergoing any perioperative eHealth intervention with active patient participation (with the exception of telerehabilitation following orthopedic surgery) were included. MEASURES: The main outcome measure was feasibility, defined as a patient's perceptions of usability, satisfaction, and/or acceptability of the intervention. Other outcomes included compliance and study completion rate. RESULTS: Screening of 1569 titles and abstracts yielded 7 single-center prospective studies with 223 patients (range n = 9-69 per study, average age 66-74 years) undergoing oncological, cardiovascular, or orthopedic surgery. The median MINORS scores were 13.5 of 16 for 6 studies without control group, and 14 of 24 for 1 study with a control group. Telemonitoring interventions were rated as "easy to use" by 89% to 95% of participants in 3 studies. Patients in 3 studies were satisfied with the eHealth intervention and would recommend it to others. Acceptability (derived from consent rate) ranged from 71% to 89%, compliance from 53% to 86%, and completion of study follow-up from 54% to 95%. CONCLUSIONS AND IMPLICATIONS: Results of 7 studies involving perioperative eHealth interventions suggest their feasibility and encourage further development of technologies for older surgical patients. Future feasibility studies require clear definitions of appropriate feasibility outcome measures and a comprehensive description of patient characteristics such as functional performance, level of education, and socioeconomic status

Remote Home Monitoring of Older Surgical Cancer Patients:Perspective on Study Implementation and Feasibility

BACKGROUND: Remote home monitoring might fill the perceived surveillance gap after hospital discharge. However, it is unclear whether older oncologic patients will be able to use the required new digital technologies. The study aimed to assess the feasibility of postoperative remote home monitoring for this population. METHODS: This observational cohort study recruited patients aged 65 years or older scheduled for oncologic surgery. The study patients used a mobile application and activity tracker preoperatively until 3 months postoperatively. A subset of the patients used additional devices (thermometer, blood pressure monitor, weight scale) and completed electronic health questionnaires 2 weeks after hospital discharge. Feasibility was assessed by the study completion rate, compliance in using components of the information technology system, acceptability [Net Promotor Score (NPS)] and usability [System Usability Scale (SUS)]. The NPS score varied from - 100 to + 100. An SUS higher than 68 was considered above average. RESULTS: Of 47 participants (mean age, 72 years; range, 65-85 years), 37 completed a follow-up assessment, yielding a completion rate of 79%. Compliance in using the activity tracker (n = 41) occurred a median of 81 days [interquartile range (IQR), 70-90 days] out of 90 post-discharge days. Compliance in measuring vital signs and completing health questionnaires varied from a median of 10.5 days (IQR, 4.5-14.0 days) to 12 days (IQR, 5-14 days) out of 14 days. The NPS was + 29.7%, and the mean SUS was 74.4 ± 19.3. CONCLUSION: Older oncologic patients in the study considered postoperative home monitoring acceptable and usable. Once they consented to participate, the patients were compliant, and the completion rate was high

Post-discharge Telemonitoring of Physical Activity, Vital Signs, and Patient-Reported Symptoms in Older Patients Undergoing Cancer Surgery

BACKGROUND: Postoperative home monitoring could potentially detect complications early, but evidence in oncogeriatric surgery is scarce. Therefore, we evaluated whether post-discharge physical activity, vital signs, and patient-reported symptoms are related to post-discharge complications and hospital readmissions in older patients undergoing cancer surgery. METHODS: In this observational cohort study, we monitored older patients (≥65 years of age) undergoing cancer surgery, for 2 weeks post-discharge using tablet-based applications and connected devices. Outcome measures were post-discharge complications and readmissions; physical activity and patient-reported symptoms over time; and threshold violations for physical activity (step count 38°C; blood pressure 150/100 mmHg; heart rate 100 bpm; weight -5% or +5% of weight at discharge); and patient-reported symptoms (pain score greater than the previous day; presence of dyspnea, vomiting, dizziness, fever). RESULTS: Of 58 patients (mean age 72 years), 24 developed a post-discharge complication and 13 were readmitted. Measured parameters indicated 392 threshold violations out of 5379 measurements (7.3%) in 40 patients, mostly because of physical inactivity. Patients with readmissions had lower physical activity at discharge and at day 9 after discharge and violated a physical activity threshold more often. Patients with post-discharge complications had a higher median pain score compared with patients without these adverse events. No differences in threshold violations of other parameters were observed between patients with and without post-discharge complications and readmissions. CONCLUSION: Our results show the potential of telemonitoring older patients after cancer surgery but confirm that detecting post-discharge complications is complex and multifactorial

Perioperative telemonitoring of older adults with cancer:Can we connect them all?

OBJECTIVES: Although the increasing cancer incidence in older patients is widely recognised, older patients remain underrepresented in clinical cancer trials and eHealth studies. The aim of this research is to identify technological and patient-related barriers to inclusion of this population in a clinical eHealth study. MATERIAL AND METHODS: This is a retrospective analysis of a prospective cohort study with older patients (≥ 65 years) undergoing cancer-related surgery, who were identified for a perioperative telemonitoring study. Reasons for ineligibility and refusal had been prospectively registered. Characteristics and postoperative outcomes were compared between participants and non-participants. RESULTS: Between May 2018 and March 2020, 151 patients were assessed for eligibility, resulting in 65 participants and 86 non-participants. The main reason for ineligibility was lack of internet access at home (n = 16), while main reasons for refusal were perceived high mental burden (n = 46) and insufficient digital skills (n = 12). Compared with participants, non-participants were significantly older (mean age 75 vs. 73, p = 0.01); more often female (64% vs. 35%, p = 0.00), unmarried (42% vs. 8%, p = 0.01) living alone (38% vs. 19%, p = 0.02); had a higher ASA classification (43% vs. 19%, p = 0.00); often had polypharmacy (67% vs. 43%, p = 0.00); and were more often discharged to skilled nursing facilities (0% vs. 15%, p = 0.00). CONCLUSION: Our results confirm the underrepresentation of older female patients with little support from a partner and higher comorbidity. We should be aware of technological and patient-related barriers to including older adults with cancer, in order to avoid further dividing patients with low and high digital health literacy

Proteomic analysis of machine perfusion solution from brain dead donor kidneys reveals that elevated complement, cytoskeleton and lipid metabolism proteins are associated with 1-year outcome

Assessment of donor kidney quality is based on clinical scores or requires biopsies for histological assessment. Noninvasive strategies to identify and predict graft outcome at an early stage are, therefore, needed. We evaluated the perfusate of donation after brain death (DBD) kidneys during nonoxygenated hypothermic machine perfusion (HMP). In particular, we compared perfusate protein profiles of good outcome (GO) and suboptimal outcome (SO) 1-year post-transplantation. Samples taken 15 min after the start HMP (T1) and before the termination of HMP (T2) were analysed using quantitative liquid chromatography-tandem mass spectrometry (LC-MS/MS). Hierarchical clustering of the 100 most abundant proteins showed discrimination between grafts with a GO and SO at T1. Elevated levels of proteins involved in classical complement cascades at both T1 and T2 and a reduced abundance of lipid metabolism at T1 and of cytoskeletal proteins at T2 in GO versus SO was observed. ATP-citrate synthase and fatty acid-binding protein 5 (T1) and immunoglobulin heavy variable 2-26 and desmoplakin (T2) showed 91% and 86% predictive values, respectively, for transplant outcome. Taken together, DBD kidney HMP perfusate profiles can distinguish between outcome 1-year post-transplantation. Furthermore, it provides insights into mechanisms that could play a role in post-transplant outcomes.</p