Cohort profile of BIGPROMISE: a perioperative biobank of a high-risk surgical population.

PURPOSE: Postoperative complications increase mortality, disability and costs. Advanced understanding of the risk factors for postoperative complications is needed to improve surgical outcomes. This paper discusses the rationale and profile of the BIGPROMISE (biomarkers to guide perioperative management and improve outcome in high-risk surgery) cohort, that aims to investigate risk factors, pathophysiology and outcomes related to postoperative complications. PARTICIPANTS: Adult patients undergoing major surgery in two tertiary teaching hospitals. Clinical data and blood samples are collected before surgery, at the end of surgery and on the first, second and third postoperative day. At each time point a panel of cardiovascular, inflammatory, renal, haematological and metabolic biomarkers is assessed. Aliquots of plasma, serum and whole blood of each time point are frozen and stored. Data on severe complications are prospectively collected during 30 days after surgery. Functional status is assessed before surgery and after 120 days using the WHO Disability Assessment Schedule (WHODAS) 2.0. Mortality is followed up until 2 years after surgery. FINDINGS TO DATE: The first patient was enrolled on 8 October 2021. Currently (1 January 2024) 3086 patients were screened for eligibility, of whom 1750 (57%) provided informed consent for study participation. Median age was 66 years (60; 73), 28% were female, and 68% of all patients were American Society of Anaesthesiologists (ASA) physical status class 3. Most common types of major surgery were cardiac (49%) and gastro-intestinal procedures (26%). The overall incidence of 30-day severe postoperative complications was 16%. FUTURE PLANS: By the end of the recruitment phase, expected in 2026, approximately 3000 patients with major surgery will have been enrolled. This cohort allows us to investigate the role of pathophysiological perioperative processes in the cause of postoperative complications, and to discover and develop new biomarkers to improve risk stratification for adverse postoperative outcomes. TRIAL REGISTRATION NUMBER: NCT05199025.

Postoperative troponin surveillance to detect myocardial infarction: an observational cohort modelling study.

BACKGROUND: Clinical presentation of postoperative myocardial infarction (POMI) is often silent. Several international guidelines recommend routine troponin surveillance in patients at risk. We compared how these different guidelines select patients for surveillance after noncardiac surgery with our established risk stratification model. METHODS: We used outcome data from two prospective studies: Measurement of Exercise Tolerance before Surgery (METS) and Troponin Elevation After Major non-cardiac Surgery (TEAMS). We compared the major American, Canadian, and European guideline recommendations for troponin surveillance with our established risk stratification model. For each guideline and model, we quantified the number of patients requiring monitoring, % POMI detected, sensitivity, specificity, diagnostic odds ratio, and number needed to screen (NNS). RESULTS: METS and TEAMS contributed 2350 patients, of whom 319 (14%) had myocardial injury, 61 (2.5%) developed POMI, and 14 (0.6%) died. Our risk stratification model selected fewer patients for troponin monitoring (20%), compared with the Canadian (78%) and European (79%) guidelines. The sensitivity to detect POMI was highest with the Canadian and European guidelines (0.85; 95% confidence interval [CI] 0.74-0.92). Specificity was highest using the American guidelines (0.91; 95% CI 0.90-0.92). Our risk stratification model had the best diagnostic odds ratio (2.5; 95% CI 1.4-4.2) and a lower NNS (21 vs 35) compared with the guidelines. CONCLUSIONS: Most postoperative myocardial infarctions were detected by the Canadian and European guidelines but at the cost of low specificity and a higher number of patients undergoing screening. Patient selection based on our risk stratification model was optimal.

Abnormal Iron Status and Adverse Outcome After Elective Cardiac Surgery: A Prospective, Observational Multicenter Study.

OBJECTIVES: To investigate the incidence of preoperative abnormal iron status and its association with packed red blood cell (PRBC) transfusion, postoperative major complications, and new onset of clinically significant disability in patients undergoing elective cardiac surgery. DESIGN: A prospective, observational multicenter cohort study. SETTING: Three cardiac surgical centers in the Netherlands between 2019 and 2021. Recruitment was on hold between March and May 2020 due to COVID-19. PATIENTS: A total of 427 patients aged 60 years and older who underwent elective on-pump cardiac surgery. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was a 30-day PRBC transfusion. Secondary endpoints were postoperative major complications within 30 days (eg, acute kidney injury, sepsis), and new onset of clinically significant disability within 120 days of surgery. Iron status was evaluated before surgery. Abnormal iron status was present in 45.2% of patients (n = 193), and most frequently the result of iron deficiency (27.4%, n = 117). An abnormal iron status was not associated with PRBC transfusion (adjusted relative risk [ARR] 1.2; 95% CI 0.9-1.8: p = 0.227) or new onset of clinically significant disability (ARR 2.0; 95% CI 0.9-4.6: p = 0.098). However, the risk of postoperative major complications was increased in patients with an abnormal iron status (ARR 1.7; 95% CI 1.1-2.5: p = 0.012). CONCLUSIONS: An abnormal iron status before elective cardiac surgery was associated with an increased risk of postoperative major complications but not with PRBC transfusion or a new onset of clinically significant disability.

Postoperative myocardial injury phenotypes and self-reported disability in patients undergoing noncardiac surgery: a multicentre observational study.

BACKGROUND: Postoperative myocardial injury (PMI) comprises a spectrum of mechanisms resulting in troponin release. The impact of different PMI phenotypes on postoperative disability remains unknown. METHODS: This was a multicentre prospective cohort study including patients aged ≥50 yr undergoing elective major noncardiac surgery. Patients were stratified in five groups based on the occurrence of PMI and clinical information on postoperative adverse events: PMI classified as myocardial infarction (MI; according to fourth definition), PMI plus adverse event other than MI, clinically silent PMI (PMI without adverse events), adverse events without PMI, and neither PMI nor an adverse event (reference). The primary endpoint was 6-month self-reported disability (assessed by WHO Disability Assessment Schedule 2.0 [WHODAS]). Disability-free survival was defined as WHODAS ≤16%. RESULTS: We included 888 patients of mean age 69 (range 53-91) yr, of which 356 (40%) were women; 151 (17%) patients experienced PMI, and 625 (71%) experienced 6-month disability-free survival. Patients with PMI, regardless of its phenotype, had higher preoperative disability scores than patients without PMI (difference in WHODAS; ß: 3.3, 95% confidence interval [CI]: 0.5-6.2), but scores remained stable after surgery (ß: 1.2, 95% CI: -3.2-5.6). Before surgery, patients with MI (n=36, 4%) were more disabled compared with patients without PMI and no adverse events (ß: 5.5, 95% CI: 0.3-10.8). At 6 months, patients with MI and patients without PMI but with adverse events worsened in disability score (ß: 11.2, 95% CI: 2.3-20.2; ß: 8.1, 95% CI: 3.0-13.2, respectively). Patients with clinically silent PMI did not change in disability score at 6 months (ß: 1.39, 95% CI: -4.50-7.29, P=0.642). CONCLUSIONS: Although patients with postoperative myocardial injury had higher preoperative self-reported disability, disability scores did not change at 6 months after surgery. However, patients experiencing myocardial infarction worsened in disability score after surgery.

The association between preoperative multidisciplinary team care and patient outcome in frail patients undergoing cardiac surgery.

OBJECTIVE: To evaluate the influence of preoperative multidisciplinary team (MDT) care on perioperative management and outcomes of frail patients undergoing cardiac surgery. BACKGROUND: Frail patients are at increased risk for complications and poor functional outcome after cardiac surgery. In these patients, preoperative MDT care may improve outcomes. METHODS: Between 2018 and 2021, 1168 patients aged 70 years or older were scheduled for cardiac surgery, of whom 98 (8.4%) frail patients were referred for MDT care. The MDT discussed surgical risk, prehabilitation, and alternative treatment. Outcomes of MDT patients were compared with 183 frail patients (non-MDT group) from a historical study cohort (2015-2017). Inverse probability of treatment weighting was used to minimize bias from nonrandom allocation of MDT versus non-MDT care. Outcomes were severe postoperative complications, total days in hospital after 120 days, disability, and health-related quality of life after 120 days. RESULTS: This study included 281 patients (98 MDT and 183 non-MDT patients). Of the MDT patients, 67 (68%) had open surgery, 21 (21%) underwent minimally invasive procedures, and 10 (10%) received conservative treatment. In the non-MDT group, all patients had open surgery. Fourteen (14%) MDT patients experienced a severe complication versus 42 (23%) non-MDT patients (adjusted relative risk, 0.76; 95% CI, 0.51-0.99). Adjusted total days in hospital after 120 days was 8 days (interquartile range, 3-12 days) versus 11 days (interquartile range, 7-16 days) for MDT and non-MDT patients, respectively (P = .01). There was no difference in disability or health-related quality of life. CONCLUSIONS: Preoperative MDT care for frail patients undergoing cardiac surgery is associated with alterations in surgical management and with a lower risk for severe complications.

Advanced glycation end products for preoperative frailty screening in older cardiac surgery patients.

BACKGROUND: Advanced glycation end products (AGEs) are potential biomarkers of biological age. Skin Auto Fluorescence (SAF) can assess AGEs non-invasively. We evaluated the association of SAF levels with frailty and its predictive ability for adverse outcomes in older cardiac surgery patients. METHODS: This was a retrospective analysis of prospectively acquired data from a two-center observational cohort study. We measured SAF level in cardiac surgery patients aged ≥70. Primary outcome was preoperative frailty. A comprehensive frailty assessment was performed before surgery based on 11 individual tests assessing the physical, mental, and social domain. Frailty was defined as at least 1 positive test in each domain. Secondary outcome measures were severe postoperative complications and a composite endpoint of 1-year disability (defined by WHO Disability Assessment Schedule 2.0 (WHODAS 2.0) questionnaire) or mortality. RESULTS: Among 555 enrolled patients, 122 (22%) were frail. SAF level was most strongly associated with dependent living status (aRR 2.45 (95% CI 1.28-4.66)) and impaired cognition (aRR 1.61 (95% CI 1.10-2.34)). A decision algorithm to identify frail patients including SAF level, sex, prescription drugs, preoperative hemoglobin, and EuroSCORE II resulted in a C-statistic of 0.72 (95% CI 0.67-0.77). SAF level was also associated with disability or death after 1 year (aRR 1.38 (95% CI 1.06-1.80)). The aRR for severe complications was 1.28 (95% CI 0.87-1.88). CONCLUSIONS: Higher SAF level is associated with frailty in older cardiac surgery patients, as well as an increased risk of death or disability. This biomarker could potentially optimize preoperative risk stratification for cardiac surgery.

Cohort profile of PLUTO: a perioperative biobank focusing on prediction and early diagnosis of postoperative complications.

PURPOSE: Although elective surgery is generally safe, some procedures remain associated with an increased risk of complications. Improved preoperative risk stratification and earlier recognition of these complications may ameliorate postoperative recovery and improve long-term outcomes. The perioperative longitudinal study of complications and long-term outcomes (PLUTO) cohort aims to establish a comprehensive biorepository that will facilitate research in this field. In this profile paper, we will discuss its design rationale and opportunities for future studies. PARTICIPANTS: Patients undergoing elective intermediate to high-risk non-cardiac surgery are eligible for enrolment. For the first seven postoperative days, participants are subjected to daily bedside visits by dedicated observers, who adjudicate clinical events and perform non-invasive physiological measurements (including handheld spirometry and single-channel electroencephalography). Blood samples and microbiome specimens are collected at preselected time points. Primary study outcomes are the postoperative occurrence of nosocomial infections, major adverse cardiac events, pulmonary complications, acute kidney injury and delirium/acute encephalopathy. Secondary outcomes include mortality and quality of life, as well as the long-term occurrence of psychopathology, cognitive dysfunction and chronic pain. FINDINGS TO DATE: Enrolment of the first participant occurred early 2020. During the inception phase of the project (first 2 years), 431 patients were eligible of whom 297 patients consented to participate (69%). Observed event rate was 42% overall, with the most frequent complication being infection. FUTURE PLANS: The main purpose of the PLUTO biorepository is to provide a framework for research in the field of perioperative medicine and anaesthesiology, by storing high-quality clinical data and biomaterials for future studies. In addition, PLUTO aims to establish a logistical platform for conducting embedded clinical trials. TRIAL REGISTRATION NUMBER: NCT05331118.

Association of a Liberal Fasting Policy of Clear Fluids Before Surgery With Fasting Duration and Patient Well-being and Safety.

Importance: Current fasting guidelines for procedures under anesthesia are poorly implemented, leading to negative metabolic sequelae. Recent studies in children showed support of liberal clear fluid intake; adult physiology can support clear fluid intake, but implementation studies are lacking. Objective: To evaluate the successfulness of implementation of a liberal clear fluid policy with regard to fasting duration, well-being, and safety in adults scheduled for anesthesia. Design, Setting, and Participants: This was a quality improvement study conducted from January 2016 to July 2021 at a tertiary referral hospital in the Netherlands. Adults scheduled for nonemergency procedures under anesthesia were included in the study. Patients undergoing obstetrics procedures or those who were intubated preoperatively were excluded. Interventions: Stepwise introduction of a liberal fluid fasting policy, allowing for ingestion of clear fluids until arrival at the operating room. Main Outcomes and Measures: The primary outcome was change in fasting duration. Secondary outcomes were patient well-being, measured as preoperative thirst, amount of fluid ingested, postoperative nausea and vomiting (PONV), and administration of antiemetics. Safety was measured as incidence of regurgitation and aspiration (pneumonia). Results: Of the 76 451 patients (mean [SD] age, 56 [17] years; 39 530 male individuals [52%] 36 921) included in the study, 59 036 (78%) followed the standard policy, and 16 815 (22%) followed the liberal policy. Time series analysis showed an estimated fasting duration decrease of 3:07 hours (IQR, 1:36-7:22; P < .001) after implementation of the liberal policy. Postimplementation median (IQR) fasting duration was 1:20 (0:48-2:24) hours. The incidence of regurgitation changed from 18 (95% CI, 14-21) to 24 (95% CI, 17-32) in 10 000 patients, and the incidence of aspiration changed from 1.7 (95% CI, 0.6-2.7) to 2.4 (95% CI, 0.5-4.7) in 10 000 patients. In the liberal policy, thirst feelings decreased (37% [4982 of 8615] vs 46% [3373 of 7362]; P < .001). PONV incidence decreased from 10.6% (6339 of 59 636) to 9.4% (1587 of 16 815; P < .001) and antiemetic administration decreased from 11.0% (6538 of 59 636) to 9.5% (1592 of 16 815; P < .001). Conclusions and Relevance: Results of this quality improvement study suggest that a liberal fasting policy was associated with a clinically relevant reduction in fasting duration and improved patient well-being with regard to preoperative thirst and PONV. Although a slightly higher incidence of regurgitation could not be ruled out, wider implementation of such a policy may be advocated as results are still within the clinically accepted risks margins. Results suggest that surgical procedures in patients who drink clear fluids within 2 hours before anticipated anesthesia should not be postponed or canceled.

Preoperative frailty and one-year functional recovery in elderly cardiac surgery patients.

OBJECTIVE: Frailty increases risk for morbidity and mortality after cardiac surgery. Its influence on functional outcome is largely unknown. We studied the association of frailty with health-related quality of life and disability after cardiac surgery. METHODS: A prospective 2-center observational cohort of 555 patients aged 70 years or more undergoing cardiac surgery. A comprehensive frailty assessment was performed before surgery based on 11 individual assessments in physical, mental, and social domains. Frailty was defined as at least 1 positive test in each domain. The primary outcome was health-related quality of life over 1 year, and the secondary outcomes were severe in-hospital complications and disability over 1 year. Adverse functional outcome was defined as the composite of a decreased health-related quality of life and disability. RESULTS: Physical frailty was most common (91%) compared with mental (39%) or social frailty (42%). Adverse functional outcome occurred in 257 patients (46%) and consisted of decreased physical health-related quality of life in 134 (24%), decreased mental health-related quality of life in 141 (25%), and disability in 120 (22%). Frailty was more common in patients with adverse functional outcome (29%) compared with patients without adverse functional outcome (16%, P < .001). Poor mobility, malnutrition, and polypharmacy were associated with a decreased health-related quality of life over time, whereas impaired physical functioning and higher self-rated health were related to increased health-related quality of life. Disability after cardiac surgery was associated with poor mobility, polypharmacy, dependent living, living alone, and lower self-rated mental health before surgery. CONCLUSIONS: Mobility, nutrition, medication use, physical functioning, and self-rated health before surgery are associated with health-related quality of life in elderly patients 1 year after cardiac surgery.

Functional brain network and trail making test changes following major surgery and postoperative delirium: a prospective, multicentre, observational cohort study.

BACKGROUND: Delirium is a frequent complication after surgery in older adults and is associated with an increased risk of long-term cognitive impairment and dementia. Disturbances in functional brain networks were previously reported during delirium. We hypothesised that alterations in functional brain networks persist after remission of postoperative delirium and that functional brain network alterations are associated with long-term cognitive impairment. METHODS: In this prospective, multicentre, observational cohort study, we included older patients who underwent clinical assessments (including the Trail Making Test B [TMT-B]) and resting-state functional MRI (rs-fMRI) before and 3 months after elective surgery. Delirium was assessed on the first seven postoperative days. RESULTS: Of the 554 enrolled patients, 246 remained after strict motion correction, of whom 38 (16%) developed postoperative delirium. The rs-fMRI functional connectivity strength increased 3 months after surgery in the total study population (ß=0.006; 95% confidence interval [CI]: 0.001-0.011; P=0.013), but it decreased after postoperative delirium (ß=-0.015; 95% CI: -0.028 to 0.002; P=0.023). No difference in TMT-B scores was found at follow-up between patients with and without postoperative delirium. Patients with decreased functional connectivity strength declined in TMT-B scores compared with those who did not (ß=11.04; 95% CI: 0.85-21.2; P=0.034). CONCLUSIONS: Postoperative delirium was associated with decreased brain functional connectivity strength after 3 months, suggesting that delirium has a long-lasting impact on brain networks. The decreased connectivity strength was associated with significant cognitive deterioration after major surgery. CLINICAL TRIAL REGISTRATION: NCT02265263.

Preoperative frailty and chronic pain after cardiac surgery: a prospective observational study.

BACKGROUND: Chronic pain after cardiac surgery, whether or not related to the operation, is common and has negative impact on health related quality of life (HRQL). Frailty is a risk factor for adverse surgical outcomes, but its relationship with chronic pain after cardiac surgery is unknown. This study aimed to address the association between frailty and chronic pain following cardiac surgery. METHODS: This sub-study of the Anesthesia Geriatric Evaluation study included 518 patients ≥ 70 years undergoing elective cardiac surgery. Pain was evaluated with the Short-Form 36 questionnaire prior to and one year after surgery. Associations between chronic postoperative pain and frailty domains, including medication use, nutritional status, mobility, physical functioning, cognition, HRQL, living situation and educational level, were investigated with multivariable regression analysis. RESULTS: Chronic pain one year after cardiac surgery was reported in 182 patients (35%). Medication use, living situation, mobility, gait speed, Nagi's physical functioning and preoperative HRQL were frailty domains associated with chronic pain after surgery. For patients with chronic pain physical HRQL after one year was worse compared to patients without chronic pain (ß -10.37, 99% CI -12.57 - -8.17). CONCLUSIONS: Preoperative polypharmacy, living alone, physical frailty and lower mental HRQL are associated with chronic pain following cardiac surgery. Chronic postoperative pain is related to worse physical HRQL one year after cardiac surgery. These findings may guide future preoperative interventions to reduce chronic pain and poor HRQL after cardiac surgery in older patients. TRIAL REGISTRATION: This trial has been registered before initiation under number NCT02535728 at clinicaltrials.gov.

External Validation of the ACTA-PORT Transfusion Risk Score in Older Cardiac Surgery Patients at Risk of Frailty.

OBJECTIVES: Accurate preoperative transfusion risk stratification may serve to better manage older patients undergoing cardiac surgery. Therefore, the aim of the present study was to externally validate the existing Association of Cardiothoracic Anesthetists perioperative risk of blood transfusion (ACTA-PORT) score in a population ≥70 years of age scheduled for cardiac surgery. Furthermore, the study authors investigated the additional prognostic value of individual frailty variables to this transfusion risk score. DESIGN: A retrospective analysis. SETTING: At a tertiary-care hospital. PARTICIPANTS: Five hundred seven patients aged ≥70 years undergoing elective cardiac surgery from July 2015 to August 2017. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the administration of a perioperative blood transfusion. Frailty domains were assessed in a preanesthesia geriatric assessment, and a priori selection of biomarkers derived from blood was determined. The original ACTA-PORT score resulted in a c-statistic of 0.78 (95% confidence interval 0.74-0.82), with moderate calibration in predicting perioperative allogeneic transfusion in older patients undergoing cardiac surgery. Model updating, using the closed testing procedure, resulted in model revision with a higher discriminatory performance (c-statistic of 0.83, 95% confidence interval 0.79-0.86) and corrected calibration slope. Iron deficiency, impaired nutritional status, and physical impairment were associated with perioperative transfusions. The addition of individual frailty variables to the updated ACTA-PORT model did not result in improved predictive performance. CONCLUSIONS: External validation of the original ACTA-PORT score showed good discrimination and moderate calibration in older patients at risk of frailty undergoing cardiac surgery. Updating the original ACTA-PORT improved the predictive performance. Careful evaluation of additional frailty domains did not add prognostic value to the ACTA-PORT score.

Critical oxygen delivery threshold during cardiopulmonary bypass in older cardiac surgery patients with increased frailty risk.

OBJECTIVES: Older patients have a higher cardiac surgery-associated acute kidney injury (CSA-AKI) related mortality. Low oxygen delivery (DO2) during cardiopulmonary bypass (CPB) is a risk factor for CSA-AKI, but critical DO2 thresholds for older patients are unknown. This study investigated critical DO2 thresholds for CSA-AKI in patients ≥70 years undergoing on-pump cardiac surgery. METHODS: Patients were enrolled from July 2015 until August 2017. CPB data from 432 patients were collected, and DO2 values were calculated per minute. The primary outcome was CSA-AKI. The association between DO2 and CSA-AKI was analysed with multivariable regression analysis. Multiple DO2 thresholds were analysed. The association between CSA-AKI and the area below the DO2 thresholds (DO2 deficit) was evaluated, as was the association between frailty and CSA-AKI. RESULTS: CSA-AKI occurred in 63 (14.6%) patients. Mean and nadir (lowest) DO2 values were lower in patients with CSA-AKI (283 vs 312 ml/min/m2; P-value <0.001 and 238 vs 270 ml/min/m2; P-value <0.001, respectively). The adjusted relative risk for CSA-AKI was 1.006 [99% confidence interval (CI) 1.001-1.012] per ml/min/m2 nadir DO2 decrease. The critical DO2 threshold was 270 ml/min/m2 [adjusted relative risk 2.06 (99% CI 1.33-2.80)]. The DO2 deficit below 270 ml/min/m2 was associated with CSA-AKI [adjusted relative risk 2.84 (99% CI 1.87-3.81)]. No association between frailty and CSA-AKI was found (P = 0.82). CONCLUSIONS: Low DO2 increased the risk for CSA-AKI in older patients who had cardiac surgery. A critical DO2 threshold of 270 ml/min/m2 was applicable for frail and non-frail patients. The efficacy of a DO2 >270 ml/min/m2 to reduce CSA-AKI in older patients needs further evaluation.

Frailty and health related quality of life three months after non-metastatic colorectal cancer diagnosis in older patients: A multi-centre prospective observational study.

BACKGROUND: Health related quality of life (HRQL) is an important outcome measure in geriatric oncology. Surgery is the main treatment for colorectal cancer (CRC) but has been associated with a loss of HRQL in older patients. This study aimed to identify determinants for a decreased HRQL at three months after CRC diagnosis. METHOD: This multi-centre observational cohort study (NCT04443816) included 273 patients aged ≥70 years diagnosed with non-metastatic CRC. A multi-domain frailty screening was performed in each patient. A decreased HRQL was defined as a mean difference ≥ 10 on the EORTC QLQ-C30 questionnaire between baseline and three months after CRC diagnosis. Determinants of a decreased HRQL were analysed using multivariable logistic regression. RESULTS: A decrease in HRQL occurred in 63 patients (23.1%). Non-surgical patients had the highest risk of decreased HRQL three months after diagnosis (adjusted odds ratio (OR) 6.4 (95% confidence interval (CI) 2.0-19.8)). The Charlson Comorbidity Index (CCI) (aOR 2.3 (95% (CI) 1.2-4.2)), the American Association of Anesthesiologists class (aOR 2.6 (95%CI 1.4-4.9)), impaired daily functioning (aOR 2.7 (95%CI 1.3-5.6)) and dependent living (aOR 1.9 (95%CI 1.1-4.5)) were associated with a decreased HRQL, mainly caused by non-surgical patients. In surgical patients, a major postoperative complication was a strong determinant of decreased HRQL and was associated with preoperative comorbidity and cognitive impairment (aOR 4.0 (95%CI 1.9-8.8)). CONCLUSION: Frailty characteristics are highly prevalent in older patients at time of CRC diagnosis but not strongly associated with a decreased HRQL after three months. Non-surgical patients and patients with major postoperative complications had the highest risk of decreased HRQL. Registered at clinicaltrials.gov trial number: NCT04443816.

The association of polypharmacy with functional decline in elderly patients undergoing cardiac surgery.

AIMS: Identifying preoperative risk factors in older patients becomes more important to reduce adverse functional outcome. This study investigated the association between preoperative medication use and functional decline in elderly cardiac surgery patients and compared polypharmacy as a preoperative screening tool to a clinical frailty assessment. METHODS: This sub-study of the Anaesthesia Geriatric Evaluation study included 518 patients aged ≥70 years undergoing elective cardiac surgery. The primary outcome was functional decline, defined as a worse health-related quality of life or disability 1 year after surgery. The association between polypharmacy (i.e. ≥5 prescriptions and <10 prescriptions) or excessive polypharmacy (i.e. ≥10 prescriptions) and functional decline was investigated using multivariable Poisson regression. Discrimination, calibration and reclassification indices were used to compare preoperative screening tools for patient selection. RESULTS: Functional decline was reported in 284 patients (55%) and preoperative polypharmacy and excessive polypharmacy showed higher risks (adjusted relative risk 1.57, 95% confidence interval [CI] 1.23-1.98 and 1.93, 95% CI 1.48-2.50, respectively). Besides cardiovascular medication, proton-pump inhibitors and central nervous system medication were significantly associated with functional decline. Discrimination between models with polypharmacy or frailty was similar (area under the curve 0.67, 95% CI 0.61-0.72). The net reclassification index improved when including polypharmacy to the basic model (17%, 95% CI 0.06-0.27). CONCLUSION: Polypharmacy is associated with functional decline in elderly cardiac surgery patients. A preoperative medication review is easily performed and could be used as screening tool to identify patients at risk for adverse outcome after cardiac surgery.

The comparative and added prognostic value of biomarkers to the Revised Cardiac Risk Index for preoperative prediction of major adverse cardiac events and all-cause mortality in patients who undergo noncardiac surgery.

BACKGROUND: The Revised Cardiac Risk Index (RCRI) is a widely acknowledged prognostic model to estimate preoperatively the probability of developing in-hospital major adverse cardiac events (MACE) in patients undergoing noncardiac surgery. However, the RCRI does not always make accurate predictions, so various studies have investigated whether biomarkers added to or compared with the RCRI could improve this. OBJECTIVES: Primary: To investigate the added predictive value of biomarkers to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Secondary: To investigate the prognostic value of biomarkers compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. Tertiary: To investigate the prognostic value of other prediction models compared to the RCRI to preoperatively predict in-hospital MACE and other adverse outcomes in patients undergoing noncardiac surgery. SEARCH METHODS: We searched MEDLINE and Embase from 1 January 1999 (the year that the RCRI was published) until 25 June 2020. We also searched ISI Web of Science and SCOPUS for articles referring to the original RCRI development study in that period. SELECTION CRITERIA: We included studies among adults who underwent noncardiac surgery, reporting on (external) validation of the RCRI and: - the addition of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of biomarker(s) to the RCRI; or - the comparison of the predictive accuracy of the RCRI to other models. Besides MACE, all other adverse outcomes were considered for inclusion. DATA COLLECTION AND ANALYSIS: We developed a data extraction form based on the CHARMS checklist. Independent pairs of authors screened references, extracted data and assessed risk of bias and concerns regarding applicability according to PROBAST. For biomarkers and prediction models that were added or compared to the RCRI in ≥ 3 different articles, we described study characteristics and findings in further detail. We did not apply GRADE as no guidance is available for prognostic model reviews. MAIN RESULTS: We screened 3960 records and included 107 articles.   Over all objectives we rated risk of bias as high in ≥ 1 domain in 90% of included studies, particularly in the analysis domain. Statistical pooling or meta-analysis of reported results was impossible due to heterogeneity in various aspects: outcomes used, scale by which the biomarker was added/compared to the RCRI, prediction horizons and studied populations.  Added predictive value of biomarkers to the RCRI Fifty-one studies reported on the added value of biomarkers to the RCRI. Sixty-nine different predictors were identified derived from blood (29%), imaging (33%) or other sources (38%). Addition of NT-proBNP, troponin or their combination improved the RCRI for predicting MACE (median delta c-statistics: 0.08, 0.14 and 0.12 for NT-proBNP, troponin and their combination, respectively). The median total net reclassification index (NRI) was 0.16 and 0.74 after addition of troponin and NT-proBNP to the RCRI, respectively. Calibration was not reported. To predict myocardial infarction, the median delta c-statistic when NT-proBNP was added to the RCRI was 0.09, and 0.06 for prediction of all-cause mortality and MACE combined. For BNP and copeptin, data were not sufficient to provide results on their added predictive performance, for any of the outcomes. Comparison of the predictive value of biomarkers to the RCRI  Fifty-one studies assessed the predictive performance of biomarkers alone compared to the RCRI. We identified 60 unique predictors derived from blood (38%), imaging (30%) or other sources, such as the American Society of Anesthesiologists (ASA) classification (32%). Predictions were similar between the ASA classification and the RCRI for all studied outcomes. In studies different from those identified in objective 1, the median delta c-statistic was 0.15 and 0.12 in favour of  BNP and NT-proBNP alone, respectively, when compared to the RCRI, for the prediction of MACE. For C-reactive protein, the predictive performance was similar to the RCRI. For other biomarkers and outcomes, data were insufficient to provide summary results. One study reported on calibration and none on reclassification. Comparison of the predictive value of other prognostic models to the RCRI   Fifty-two articles compared the predictive ability of the RCRI to other prognostic models. Of these, 42% developed a new prediction model, 22% updated the RCRI, or another prediction model, and 37% validated an existing prediction model. None of the other prediction models showed better performance in predicting MACE than the RCRI. To predict myocardial infarction and cardiac arrest, ACS-NSQIP-MICA had a higher median delta c-statistic of 0.11 compared to the RCRI. To predict all-cause mortality, the median delta c-statistic was 0.15 higher in favour of ACS-NSQIP-SRS compared to the RCRI. Predictive performance was not better for CHADS2, CHA2DS2-VASc, R2CHADS2, Goldman index, Detsky index or VSG-CRI compared to the RCRI for any of the outcomes. Calibration and reclassification were reported in only one and three studies, respectively. AUTHORS' CONCLUSIONS: Studies included in this review suggest that the predictive performance of the RCRI in predicting MACE is improved when NT-proBNP, troponin or their combination are added. Other studies indicate that BNP and NT-proBNP, when used in isolation, may even have a higher discriminative performance than the RCRI. There was insufficient evidence of a difference between the predictive accuracy of the RCRI and other prediction models in predicting MACE. However, ACS-NSQIP-MICA and ACS-NSQIP-SRS outperformed the RCRI in predicting myocardial infarction and cardiac arrest combined, and all-cause mortality, respectively. Nevertheless, the results cannot be interpreted as conclusive due to high risks of bias in a majority of papers, and pooling was impossible due to heterogeneity in outcomes, prediction horizons, biomarkers and studied populations. Future research on the added prognostic value of biomarkers to existing prediction models should focus on biomarkers with good predictive accuracy in other settings (e.g. diagnosis of myocardial infarction) and identification of biomarkers from omics data. They should be compared to novel biomarkers with so far insufficient evidence compared to established ones, including NT-proBNP or troponins. Adherence to recent guidance for prediction model studies (e.g. TRIPOD; PROBAST) and use of standardised outcome definitions in primary studies is highly recommended to facilitate systematic review and meta-analyses in the future.