Cystatin C or creatinine for pre-operative assessment of kidney function and risk of post-operative acute kidney injury: a secondary analysis of the METS cohort study.

Background: Post-operative acute kidney injury (PO-AKI) is a common surgical complication consistently associated with subsequent morbidity and mortality. Prior kidney dysfunction is a major risk factor for PO-AKI, however it is unclear whether serum creatinine, the conventional kidney function marker, is optimal in this population. Serum cystatin C is a kidney function marker less affected by body composition and might provide better prognostic information in surgical patients. Methods: This was a pre-defined, secondary analysis of a multi-centre prospective cohort study of pre-operative functional capacity. Participants were aged ≥40 years, undergoing non-cardiac surgery. We assessed the association of pre-operative estimated glomerular filtration rate (eGFR) calculated using both serum creatinine and serum cystatin C with PO-AKI within 3 days after surgery, defined by KDIGO creatinine changes. The adjusted analysis accounted for established AKI risk factors. Results: A total of 1347 participants were included (median age 65 years, interquartile range 56-71), of whom 775 (58%) were male. A total of 82/1347 (6%) patients developed PO-AKI. These patients were older, had higher prevalence of cardiovascular disease and related medication, were more likely to have intra-abdominal procedures, had more intraoperative transfusion, and were more likely to be dead at 1 year after surgery 6/82 (7.3%) vs 33/1265 (2.7%) (P = .038). Pre-operative eGFR was lower in AKI than non-AKI patients using both creatinine and cystatin C. When both measurements were considered in a single age- and sex-adjusted model, eGFR-Cysc was strongly associated with PO-AKI, with increasing risk of AKI as eGFR-Cysc decreased below 90, while eGFR-Cr was no longer significantly associated. Conclusions: Data from over 1000 prospectively recruited surgical patients confirms pre-operative kidney function as major risk factor for PO-AKI. Of the kidney function markers available, compared with creatinine, cystatin C had greater strength of association with PO-AKI and merits further assessment in pre-operative assessment of surgical risk.

Supporting effective shared decision-making in surgical context: Why framing of choices matters for high-risk patients and clinicians.

AIM: In the context of high-risk surgery, shared decision-making (SDM) is important. However, the effectiveness of SDM can be hindered by misalignment between patients and clinicians in their expectations of postoperative outcomes. This study investigated the extent and the effects of this misalignment, as well as its amenability to interventions that encourage perspective-taking. METHOD: Lay participants with a Charlson Comorbidity Index of ≥4 (representing patients) and surgeons and anaesthetists (representing doctors) were recruited. During an online experiment, subjects in both groups forecast their expectations regarding short-term (0, 1 and 3 months after treatment) and long-term (6, 9 and 12 months after treatment) outcomes of different treatment options for one of three hypothetical clinical scenarios - ischaemic heart disease, colorectal cancer or osteoarthritis of the hip - and then chose between surgical or non-surgical treatment. Subjects in both groups were asked to consider the scenarios from their own perspective (Estimation task), and then to adopt the perspective of subjects in the other study group (Perspective task). The decisions of all participants (surgery vs. non-surgical alternative) were analysed using binomial generalized linear mixed models. RESULTS: In total, 55 lay participants and 54 doctors completed the online experiment. Systematic misalignment in expectations between high-risk patients and doctors was observed, with patients expecting better surgical outcomes than clinicians. Patients forecast a significantly higher likelihood of engaging in normal activities in the long term (ß = -1.09, standard error [SE] = 0.20, t = -5.38, p < 0.001), a lower likelihood of experiencing complications in the long term (ß = 0.92, SE = 0.21, t = 4.45, p < 0.001) and a lower likelihood of experiencing depression in both the short term and the long term (ß = 1.01, SE = 0.19, t = 5.38, p < 0.001), than did doctors. Compared with doctors, patients forecast higher estimates of experiencing complications in the short term when a non-surgical alternative was selected (ß = -0.91, SE = 0.26, t = -3.50, p = 0.003). Despite this misalignment, in both groups surgical treatment was strongly preferred (estimation task: 88.7% of doctors and 80% of patients; perspective task: 82.2% of doctors and 90.1% of patients). CONCLUSION: When high-risk surgery is discussed, a non-surgical option may be viewed as 'doing nothing', hence reducing the sense of agency and control. This biases the decision-making process, regardless of the expectations that doctors and patients might have about the outcomes of surgery. Therefore, to improve SDM and to increase the agency and control of patients regarding decisions about their care, we advocate framing the non-surgical treatment options in a way that emphasizes action, agency and change.

Long-term healthcare use after postoperative complications: an analysis of linked primary and secondary care routine data.

Background: Postoperative complications are associated with reduced long-term survival. We characterise healthcare use changes after sentinel postoperative complications. Methods: We linked primary and secondary care records of patients undergoing elective surgery at four East London hospitals (2012-7) with at least 90 days follow-up. Complication codes (wound infection, urinary tract infection, pneumonia, new stroke, and new myocardial infarction) recorded within 90 days of surgery were identified from primary or secondary care. Outcomes were change in healthcare contact days in the 2 yr before and after surgery, and 2 yr mortality. We report rate ratios (RaR) with 95% confidence intervals and adjusted for baseline healthcare use and confounders using negative binomial regression. Results: We included 49 913 patients (median age 49 yr [inter-quartile range {IQR}: 34-64]), 27 958 (56.0%) were female. Amongst 3883 (7.8%) patients with complications (median age 58 [IQR: 43-72]), there were 18.4 days per year in contact with healthcare before surgery and 25.3 days after surgery (RaR: 1.38 [1.37-1.39]). Patients without complications (median age 48 [IQR: 33-63]) had 12.3 days per year in contact with healthcare before surgery and 14.0 days after surgery (RaR: 1.14 [1.14-1.15]). The adjusted incidence rate ratio of days in contact with healthcare associated with complications was 1.67 (1.49-1.87). More patients (391; 10.1%) with complications died within 2 yr than those without (1428; 3.1%). Conclusions: Patients with postoperative complications are older with greater healthcare use before surgery. However, their absolute and relative increases in healthcare use after surgery are greater than patients without complications.

Long-term disease interactions amongst surgical patients: a population cohort study.

BACKGROUND: The average age of the surgical population continues to increase, as does prevalence of long-term diseases. However, outcomes amongst multi-morbid surgical patients are not well described. METHODS: We included adults undergoing non-obstetric surgical procedures in the English National Health Service between January 2010 and December 2015. Patients could be included multiple times in sequential 90-day procedure spells. Multi-morbidity was defined as presence of two or more long-term diseases identified using a modified Charlson comorbidity index. The primary outcome was 90-day postoperative death. Secondary outcomes included emergency hospital readmission within 90 days. We calculated age- and sex-adjusted odds ratios (OR) with 95% confidence intervals (CI) using logistic regression. We compared the outcomes associated with different disease combinations. RESULTS: We identified 20 193 659 procedure spells among 13 062 715 individuals aged 57 (standard deviation 19) yr. Multi-morbidity was present among 2 577 049 (12.8%) spells with 195 965 deaths (7.6%), compared with 17 616 610 (88.2%) spells without multi-morbidity with 163 529 deaths (0.9%). Multi-morbidity was present in 1 902 859/16 946 808 (11.2%) elective spells, with 57 663 deaths (2.7%, OR 4.9 [95% CI: 4.9-4.9]), and 674 190/3 246 851 (20.7%) non-elective spells, with 138 302 deaths (20.5%, OR 3.0 [95% CI: 3.0-3.1]). Emergency readmission followed 547 399 (22.0%) spells with multi-morbidity compared with 1 255 526 (7.2%) without. Multi-morbid patients accounted for 57 663/114 783 (50.2%) deaths after elective spells, and 138 302/244 711 (56.5%) after non-elective spells. The rate of death varied five-fold from lowest to highest risk disease pairs. CONCLUSION: One in eight patients undergoing surgery have multi-morbidity, accounting for more than half of all postoperative deaths. Disease interactions amongst multi-morbid patients is an important determinant of patient outcome.

Comparison of Cystatin C and Creatinine in the Assessment of Measured Kidney Function during Critical Illness.

BACKGROUND: Incomplete recovery of kidney function is an important adverse outcome in survivors of critical illness. However, unlike eGFR creatinine, eGFR cystatin C is not confounded by muscle loss and may improve identification of persistent kidney dysfunction. METHODS: To assess kidney function during prolonged critical illness, we enrolled 38 mechanically ventilated patients with an expected length of stay of >72 hours near admission to intensive care unit (ICU) in a single academic medical center. We assessed sequential kidney function using creatinine, cystatin C, and iohexol clearance measurements. The primary outcome was difference between eGFR creatinine and eGFR cystatin C at ICU discharge using Bayesian regression modeling. We simultaneously measured muscle mass by ultrasound of the rectus femoris to assess the confounding effect on serum creatinine generation. RESULTS: Longer length of ICU stay was associated with greater difference between eGFR creatinine and eGFR cystatin C at a predicted rate of 2 ml/min per 1.73 m 2 per day (95% confidence interval [CI], 1 to 2). By ICU discharge, the posterior mean difference between creatinine and cystatin C eGFR was 33 ml/min per 1.73 m 2 (95% credible interval [CrI], 24 to 42). In 27 patients with iohexol clearance measured close to ICU discharge, eGFR creatinine was on average two-fold greater than the iohexol gold standard, and posterior mean difference was 59 ml/min per 1.73 m 2 (95% CrI, 49 to 69). The posterior mean for eGFR cystatin C suggested a 22 ml/min per 1.73 m 2 (95% CrI, 13 to 31) overestimation of measured GFR. Each day in ICU resulted in a predicted 2% (95% CI, 1% to 3%) decrease in muscle area. Change in creatinine-to-cystatin C ratio showed good longitudinal, repeated measures correlation with muscle loss, R =0.61 (95% CI, 0.50 to 0.72). CONCLUSIONS: eGFR creatinine systematically overestimated kidney function after prolonged critical illness. Cystatin C better estimated true kidney function because it seemed unaffected by the muscle loss from prolonged critical illness. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Skeletal Muscle Wasting and Renal Dysfunction After Critical Illness Trauma - Outcomes Study (KRATOS), NCT03736005 .

Can pioglitazone be used for optimization of nutrition in critical illness? A systematic review.

BACKGROUND: Skeletal muscle wasting is a determinant of physical disability in survivors of critical illness. Intramuscular bioenergetic failure, altered substrate metabolim, and inflammation are likely underpinning mechanisms. We examined the effect of pioglitazone, a peroxisome proliferator-activated receptor γ agonist, on muscle-related outcomes in adults. METHODS: We included randomized controlled trials in which pioglitazone was administered (no dose/dosage restrictions) and muscle-related outcomes were reported. We searched MEDLINE, CENTRAL, EMBASE, CINAHL, and trial registries. Risk of bias was assessed using RoB 2. Primary outcomes were physical function and symptoms, muscle mass and function, or body composition and muscular compositional change. Secondary outcomes included muscle insulin sensitivity, mitochondrial effects, and intramuscular inflammation. RESULTS: Fourteen studies over 19 publications (n = 474 patients) were included. Lean body mass was unaffected in three studies (n = 126) and increased by 1.8-1.92 kg in two studies (P = 0.02 and 0.003, respectively; n = 48). Pioglitazone was associated with increased peripheral insulin sensitivity (+23%-72%, standardized mean difference of 0.97 from trial start point to end point [95% CI, 0.36-1.58; n = 213]). Treatment reduced intramuscular tumor necrosis factor-α (TNF-α) levels (-30%; P = 0.02; n = 29), with mixed effects on serum TNF-α and intramyocellular lipid concentrations. Treatment increased intramuscular markers of adenosine triphosphate (ATP) biosynthesis (ATP5A [+33%, P ≤ 0.05], ETFA [+60%, P ≤ 0.05], and CX6B1 [+ 33%, P = 0.01] [n = 24]), PGC1α and PGC1ß messenger RNA expression (P < 0.05; n = 26), and AMPK phosphorylation (+38%, P < 0.05; n = 26). These data have low-quality evidence profiles owing to risk of bias. CONCLUSIONS: Pioglitazone therapy increases skeletal muscle insulin sensitivity and can decrease intramuscular inflammation.

Change in healthcare utilisation after surgical treatment: observational study of routinely collected patient data from primary and secondary care.

BACKGROUND: Most patients fully recover after surgery. However, high-risk patients may experience an increased burden of medical disease. METHODS: We performed a prospectively planned analysis of linked routine primary and secondary care data describing adult patients undergoing non-obstetric surgery at four hospitals in East London between January 2012 and January 2017. We categorised patients by 90-day mortality risk using logistic regression modelling. We calculated healthcare contact days per patient year during the 2 yr before and after surgery, and express change using rate ratios (RaR) with 95% confidence intervals. RESULTS: We included 70 021 patients, aged (mean [standard deviation, sd]) 49.8 (19) yr, with 1238 deaths within 2 yr after surgery (1.8%). Most procedures were elective (51 693, 74.0%), and 20 441 patients (29.1%) were in the most deprived national quintile for social deprivation. Elective patients had 12.7 healthcare contact days per patient year before surgery, increasing to 15.5 days in the 2 yr after surgery (RaR, 1.22 [1.21-1.22]), and those at high-risk of 90-day mortality (11% of population accounting for 80% of all deaths) had the largest increase (37.0 days per patient year before vs 60.8 days after surgery; RaR, 1.64 [1.63-1.65]). Emergency patients had greater increases in healthcare burden (13.8 days per patient year before vs 24.8 days after surgery; RaR, 1.8 [1.8-1.8]), particularly in high-risk patients (28% of patients accounting for 80% of all deaths by day 90), with 21.6 days per patient year before vs 49.2 days after surgery; RaR, 2.28 [2.26-2.29]. DISCUSSION: High-risk patients who survive the immediate perioperative period experience large and persistent increases in healthcare utilisation in the years after surgery. The full implications of this require further study.

Long-term mortality following complications after elective surgery: a secondary analysis of pooled data from two prospective cohort studies.

BACKGROUND: Complications after surgery affect survival and quality of life. We aimed to confirm the relationship between postoperative complications and death within 1 yr after surgery. METHODS: We conducted a secondary analysis of pooled data from two prospective cohort studies of patients undergoing surgery in five high-income countries between 2012 and 2014. Exposure was any complication within 30 days after surgery. Primary outcome was death within 1 yr after surgery, ascertained by direct follow-up or linkage to national registers. We adjusted for clinically important covariates using a mixed-effect multivariable Cox proportional hazards regression model. We conducted a planned subgroup analysis by type of complication. Data are presented as mean with standard deviation (sd), n (%), and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs). RESULTS: The pooled cohort included 10 132 patients. After excluding 399 (3.9%) patients with missing data or incomplete follow-up, 9733 patients were analysed. The mean age was 59 [sd 16.8] yr, and 5362 (55.1%) were female. Of 9733 patients, 1841 (18.9%) had complications within 30 days after surgery, and 319 (3.3%) died within 1 yr after surgery. Of 1841 patients with complications, 138 (7.5%) died within 1 yr after surgery compared with 181 (2.3%) of 7892 patients without complications (aHR 1.94 [95% CI: 1.53-2.46]). Respiratory failure was associated with the highest risk of death, resulting in six deaths amongst 28 patients (21.4%). CONCLUSIONS: Postoperative complications are associated with increased mortality at 1 yr. Further research is needed to identify patients at risk of complications and to reduce mortality.

Postoperative Acute Kidney Injury.

Postoperative AKI is a common complication of major surgery and is associated with significant morbidity and mortality. The Kidney Disease Improving Global Outcomes AKI definition allows consensus classification and identification of postoperative AKI through changes in serum creatinine and/or urine output. However, such conventional diagnostic criteria may be inaccurate in the postoperative period, suggesting a potential to refine diagnosis by application of novel diagnostic biomarkers. Risk factors for the development of postoperative AKI can be thought of in terms of preoperative, intraoperative, and postoperative factors and, as such, represent areas that may be targeted perioperatively to minimize the risk of AKI. The treatment of postoperative AKI remains predominantly supportive, although application of management bundles may translate into improved outcomes.

Death after surgery among patients with chronic disease: prospective study of routinely collected data in the English NHS.

BACKGROUND: Five million surgeries take place in the NHS each year. Little is known about the prevalence of chronic diseases among these patients, and the association with postoperative outcomes. METHODS: Analysis of routine data from all NHS hospitals in England including patients aged ≥18 yr undergoing non-obstetric surgery between January 1, 2010 and December 31, 2015. The primary outcome was death within 90 days after surgery. For each chronic disease, we adjusted for age, sex, presence of other diseases, emergency surgery, and year using logistic regression models. We defined high-risk diseases as those with an adjusted odds ratio (OR) for death ≥2 and report associated 2-yr survival. RESULTS: We included 8 624 611 patients (median age, 53 [36-68] yr), of whom 6 913 451 (80.2%) underwent elective surgery and 1 711 160 (19.8%) emergency surgery. Overall, 2 311 600 (26.8%) patients had a chronic disease, of whom 109 686 (4.7%) died within 90 days compared with 24 136 (0.4%) of 6 313 011 without chronic disease. Respiratory disease (1 002 281 [11.6%]), diabetes mellitus (662 706 [7.7%]), and cancer (310 363; 3.6%) were the most common. Four chronic diseases accounted for 7.7% of patients but 59.0% of deaths: cancer (37 693 deaths [12.1%]; OR=8.3 [8.2-8.5]), liver disease (8638 deaths [10.3%]; OR=4.5 [4.4-4.7]), cardiac failure (26 604 deaths [12.6%]; OR=2.4 [2.4-2.5]), and dementia (19 912 deaths [17.9%]; OR=2.0 [1.9-2.0]). Two-year survival was 67.7% among patients with high-risk chronic disease, compared with 97.1% without. CONCLUSION: One in four surgical patients has a chronic disease with an associated 10-fold increase in risk of postoperative death. Two-thirds of all deaths after surgery occur among patients with high-risk diseases (cancer, cardiac failure, liver disease, dementia).

Novel methods to identify and measure catabolism.

PURPOSE OF REVIEW: Assess current potential catabolism-biomarkers to characterize patients developing prolonged critical illness. RECENT FINDINGS: A raised urea-to-creatinine ratio (UCR) during critical illness is negatively associated with muscle mass with greater increases in UCR seen patients developing persistent critical illness. Similarly, sarcopenia index (a ratio of creatinine to cystatin-c concentrations) correlates well to muscle mass in intensive care populations. Elevated growth/differentiation factor-15 (GDF-15) has been inconsistently associated with muscle loss. Although GDF-15 was a poor marker of feeding tolerance, it has been associated with worse prognosis in intensive care. SUMMARY: UCR is an available and clinically applicable biomarker of catabolism. Similarly, sarcopenia index can be used to assess muscle mass and indirectly measure catabolism based on readily available biochemical measurements. The utility of novel biomarkers, such as GDF-15 is less established.

Restrictive fluid management versus usual care in acute kidney injury (REVERSE-AKI): a pilot randomized controlled feasibility trial.

PURPOSE: We compared a restrictive fluid management strategy to usual care among critically ill patients with acute kidney injury (AKI) who had received initial fluid resuscitation. METHODS: This multicenter feasibility trial randomized 100 AKI patients 1:1 in seven ICUs in Europe and Australia. Restrictive fluid management included targeting negative or neutral daily fluid balance by minimizing fluid input and/or enhancing urine output with diuretics administered at the discretion of the clinician. Fluid boluses were administered as clinically indicated. The primary endpoint was cumulative fluid balance 72 h from randomization. RESULTS: Mean (SD) cumulative fluid balance at 72 h from randomization was - 1080 mL (2003 mL) in the restrictive fluid management arm and 61 mL (3131 mL) in the usual care arm, mean difference (95% CI) - 1148 mL (- 2200 to - 96) mL, P = 0.033. Median [IQR] duration of AKI was 2 [1-3] and 3 [2-7] days, respectively (median difference - 1.0 [- 3.0 to 0.0], P = 0.071). Altogether, 6 out of 46 (13%) patients in the restrictive fluid management arm and 15 out of 50 (30%) in the usual care arm received renal replacement therapy (RR 0.42; 95% CI 0.16-0.91), P = 0.043. Cumulative fluid balance at 24 h and 7 days was lower in the restrictive fluid management arm. The dose of diuretics was not different between the groups. Adverse events occurred more frequently in the usual care arm. CONCLUSIONS: In critically ill patients with AKI, a restrictive fluid management regimen resulted in lower cumulative fluid balance and less adverse events compared to usual care. Larger trials of this intervention are justified.

Natural history, trajectory, and management of mechanically ventilated COVID-19 patients in the United Kingdom.

PURPOSE: The trajectory of mechanically ventilated patients with coronavirus disease 2019 (COVID-19) is essential for clinical decisions, yet the focus so far has been on admission characteristics without consideration of the dynamic course of the disease in the context of applied therapeutic interventions. METHODS: We included adult patients undergoing invasive mechanical ventilation (IMV) within 48 h of intensive care unit (ICU) admission with complete clinical data until ICU death or discharge. We examined the importance of factors associated with disease progression over the first week, implementation and responsiveness to interventions used in acute respiratory distress syndrome (ARDS), and ICU outcome. We used machine learning (ML) and Explainable Artificial Intelligence (XAI) methods to characterise the evolution of clinical parameters and our ICU data visualisation tool is available as a web-based widget ( https://www.CovidUK.ICU ). RESULTS: Data for 633 adults with COVID-19 who underwent IMV between 01 March 2020 and 31 August 2020 were analysed. Overall mortality was 43.3% and highest with non-resolution of hypoxaemia [60.4% vs17.6%; P < 0.001; median PaO2/FiO2 on the day of death was 12.3(8.9-18.4) kPa] and non-response to proning (69.5% vs.31.1%; P < 0.001). Two ML models using weeklong data demonstrated an increased predictive accuracy for mortality compared to admission data (74.5% and 76.3% vs 60%, respectively). XAI models highlighted the increasing importance, over the first week, of PaO2/FiO2 in predicting mortality. Prone positioning improved oxygenation only in 45% of patients. A higher peak pressure (OR 1.42[1.06-1.91]; P < 0.05), raised respiratory component (OR 1.71[ 1.17-2.5]; P < 0.01) and cardiovascular component (OR 1.36 [1.04-1.75]; P < 0.05) of the sequential organ failure assessment (SOFA) score and raised lactate (OR 1.33 [0.99-1.79]; P = 0.057) immediately prior to application of prone positioning were associated with lack of oxygenation response. Prone positioning was not applied to 76% of patients with moderate hypoxemia and 45% of those with severe hypoxemia and patients who died without receiving proning interventions had more missed opportunities for prone intervention [7 (3-15.5) versus 2 (0-6); P < 0.001]. Despite the severity of gas exchange deficit, most patients received lung-protective ventilation with tidal volumes less than 8 mL/kg and plateau pressures less than 30cmH2O. This was despite systematic errors in measurement of height and derived ideal body weight. CONCLUSIONS: Refractory hypoxaemia remains a major association with mortality, yet evidence based ARDS interventions, in particular prone positioning, were not implemented and had delayed application with an associated reduced responsiveness. Real-time service evaluation techniques offer opportunities to assess the delivery of care and improve protocolised implementation of evidence-based ARDS interventions, which might be associated with improvements in survival.

Postoperative acute kidney injury in adult non-cardiac surgery: joint consensus report of the Acute Disease Quality Initiative and PeriOperative Quality Initiative.

Postoperative acute kidney injury (PO-AKI) is a common complication of major surgery that is strongly associated with short-term surgical complications and long-term adverse outcomes, including increased risk of chronic kidney disease, cardiovascular events and death. Risk factors for PO-AKI include older age and comorbid diseases such as chronic kidney disease and diabetes mellitus. PO-AKI is best defined as AKI occurring within 7 days of an operative intervention using the Kidney Disease Improving Global Outcomes (KDIGO) definition of AKI; however, additional prognostic information may be gained from detailed clinical assessment and other diagnostic investigations in the form of a focused kidney health assessment (KHA). Prevention of PO-AKI is largely based on identification of high baseline risk, monitoring and reduction of nephrotoxic insults, whereas treatment involves the application of a bundle of interventions to avoid secondary kidney injury and mitigate the severity of AKI. As PO-AKI is strongly associated with long-term adverse outcomes, some form of follow-up KHA is essential; however, the form and location of this will be dictated by the nature and severity of the AKI. In this Consensus Statement, we provide graded recommendations for AKI after non-cardiac surgery and highlight priorities for future research.

Ethnicity and outcomes in patients hospitalised with COVID-19 infection in East London: an observational cohort study.

OBJECTIVE: To describe outcomes within different ethnic groups of a cohort of hospitalised patients with confirmed COVID-19 infection. To quantify and describe the impact of a number of prognostic factors, including frailty and inflammatory markers. SETTING: Five acute National Health Service Hospitals in east London. DESIGN: Prospectively defined observational study using registry data. PARTICIPANTS: 1737 patients aged 16 years or over admitted to hospital with confirmed COVID-19 infection between 1 January and 13 May 2020. MAIN OUTCOME MEASURES: The primary outcome was 30-day mortality from time of first hospital admission with COVID-19 diagnosis during or prior to admission. Secondary outcomes were 90-day mortality, intensive care unit (ICU) admission, ICU and hospital length of stay and type and duration of organ support. Multivariable survival analyses were adjusted for potential confounders. RESULTS: 1737 were included in our analysis of whom 511 had died by day 30 (29%). 538 (31%) were from Asian, 340 (20%) black and 707 (40%) white backgrounds. Compared with white patients, those from minority ethnic backgrounds were younger, with differing comorbidity profiles and less frailty. Asian and black patients were more likely to be admitted to ICU and to receive invasive ventilation (OR 1.54, (95% CI 1.06 to 2.23); p=0.023 and OR 1.80 (95% CI 1.20 to 2.71); p=0.005, respectively). After adjustment for age and sex, patients from Asian (HR 1.49 (95% CI 1.19 to 1.86); p<0.001) and black (HR 1.30 (95% CI 1.02 to 1.65); p=0.036) backgrounds were more likely to die. These findings persisted across a range of risk factor-adjusted analyses accounting for major comorbidities, obesity, smoking, frailty and ABO blood group. CONCLUSIONS: Patients from Asian and black backgrounds had higher mortality from COVID-19 infection despite controlling for all previously identified confounders and frailty. Higher rates of invasive ventilation indicate greater acute disease severity. Our analyses suggest that patients of Asian and black backgrounds suffered disproportionate rates of premature death from COVID-19.

Socioeconomic deprivation and long-term outcomes after elective surgery: analysis of prospective data from two observational studies.

BACKGROUND: Socioeconomic deprivation is associated with health inequalities. We explored relationships between socioeconomic group and outcomes after elective surgery in the UK National Health Service (NHS). METHODS: We combined data from two observational studies in 115 NHS hospitals and determined socioeconomic group using the Index of Multiple Deprivation (IMD) quintiles based on place of residence. Postoperative complications and 3-yr survival were assessed using logistic and Cox regression. Univariate analyses were adjusted for age differences between IMD quintiles. Multivariable analyses were used to account for other baseline risk factors including sex and comorbid disease. Results are reported as n (%), hazard ratios (HR) or odds ratios (OR) with 95% confidence intervals. RESULTS: Postoperative complications developed in 971/9051 patients (10.7%) and 1597/9043 patients (17.7%) died within 3 yr. Complication rates increased with deprivation (reference group least-deprived IMD5): IMD1 (OR=1.44 [1.17-1.78]; P<0.001), IMD2 (OR=1.38 [1.12-1.70]; P<0.01), IMD3 (OR=1.09 [0.88-1.35]: P=0.44), IMD4 (OR=0.89 [0.71-1.11]; P=0.30). More patients from the most deprived quintile died (IMD1) (n=349, 18.8%) compared with the least deprived (IMD5) (n=297, 15.9%) with a trend across the socioeconomic spectrum (P=0.01). After age adjustment, patients in the most deprived areas experienced reduced 3-yr survival: IMD1 (HR=1.43 [1.23-1.67]; P<0.0001), IMD2 (HR=1.35 [1.15-1.57]; P<0.001), IMD3 (HR=1.04 [0.89-1.23]; P=0.60), and IMD4 (HR=1.11 [0.95-1.30]; P=0.19). This finding persisted in risk-adjusted analyses. Increased complication rates only partially explained this reduced survival. CONCLUSIONS: Socioeconomic deprivation is associated with worse long-term outcomes after elective surgery. This risk factor should be considered when planning perioperative care for patients from deprived areas.

Understanding decision making about major surgery: protocol for a qualitative study of shared decision making by high-risk patients and their clinical teams.

INTRODUCTION: Surgical treatments are being offered to more patients than ever before, and increasingly to high-risk patients (typically multimorbid and over 75). Shared decision making is seen as essential practice. However, little is currently known about what 'good' shared decision making involves nor how it applies in the context of surgery for high-risk patients. This new study aims to identify how high-risk patients, their families and clinical teams negotiate decision making for major surgery. METHODS AND ANALYSIS: Focusing on major joint replacement, colorectal and cardiac surgery, we use qualitative methods to explore how patients, their families and clinicians negotiate decision making (including interactional, communicative and informational aspects and the extent to which these are perceived as shared) and reflect back on the decisions they made. Phase 1 involves video recording 15 decision making encounters about major surgery between patients, their carers/families and clinicians; followed by up to 90 interviews (with the same patient, carer and clinician participants) immediately after a decision has been made and again 3-6 months later. Phase 2 involves focus groups with a wider group of (up to 90) patients and (up to 30) clinicians to test out emerging findings and inform development of shared decision making scenarios (3-5 summary descriptions of how decisions are made). ETHICS AND DISSEMINATION: The study forms the first part in a 6-year programme of research, Optimising Shared decision-makIng for high-RIsk major Surgery (OSIRIS). Ethical challenges around involving patients at a challenging time in their lives will be overseen by the programme steering committee, which includes strong patient representation and a lay chair. In addition to academic outputs, we will produce a typology of decision making scenarios for major surgery to feed back to patients, professionals and service providers and inform subsequent work in the OSIRIS programme.

Identification and validation of biomarkers of persistent acute kidney injury: the RUBY study.

PURPOSE: The aim of the RUBY study was to evaluate novel candidate biomarkers to enable prediction of persistence of renal dysfunction as well as further understand potential mechanisms of kidney tissue damage and repair in acute kidney injury (AKI). METHODS: The RUBY study was a multi-center international prospective observational study to identify biomarkers of the persistence of stage 3 AKI as defined by the KDIGO criteria. Patients in the intensive care unit (ICU) with moderate or severe AKI (KDIGO stage 2 or 3) were enrolled. Patients were to be enrolled within 36 h of meeting KDIGO stage 2 criteria. The primary study endpoint was the development of persistent severe AKI (KDIGO stage 3) lasting for 72 h or more (NCT01868724). RESULTS: 364 patients were enrolled of whom 331 (91%) were available for the primary analysis. One hundred ten (33%) of the analysis cohort met the primary endpoint of persistent stage 3 AKI. Of the biomarkers tested in this study, urinary C-C motif chemokine ligand 14 (CCL14) was the most predictive of persistent stage 3 AKI with an area under the receiver operating characteristic curve (AUC) (95% CI) of 0.83 (0.78-0.87). This AUC was significantly greater than values for other biomarkers associated with AKI including urinary KIM-1, plasma cystatin C, and urinary NGAL, none of which achieved an AUC > 0.75. CONCLUSION: Elevated urinary CCL14 predicts persistent AKI in a large heterogeneous cohort of critically ill patients with severe AKI. The discovery of CCL14 as a predictor of persistent AKI and thus, renal non-recovery, is novel and could help identify new therapeutic approaches to AKI.

The role of goal-directed therapy in the prevention of acute kidney injury after major gastrointestinal surgery: Substudy of the OPTIMISE trial.

BACKGROUND: Acute kidney injury (AKI) is an important adverse outcome after major surgery. Peri-operative goal-directed haemodynamic therapy (GDT) may improve outcomes by reducing complications such as AKI. OBJECTIVE: To determine if GDT was associated with a reduced incidence of postoperative AKI according to specific renal biomarkers. DESIGN: Prospective substudy of the OPTIMISE trial, a multicentre randomised controlled trial comparing peri-operative GDT to usual patient care. SETTING: Four UK National Health Service hospitals. PATIENTS: A total of 287 high-risk patients aged at least 50 years undergoing major gastrointestinal surgery. OUTCOME MEASURES: The primary outcome measure was AKI defined as urinary neutrophil gelatinase-associated lipase (NGAL) at least 150 ng ml 24 and 72 h after surgery. Secondary outcomes were between-group differences in NGAL measurements and NGAL : creatinine ratios 24 and 72 h after surgery and AKI stage 2 or greater according to Kidney Disease Improving Global Outcomes (KDIGO) criteria within 30 days of surgery. RESULTS: In total, 20 of 287 patients (7%) experienced postoperative AKI of KDIGO grade 2 or 3 within 30 days. The proportion of patients with urinary NGAL at least 150 ng ml 24 or 72 h after surgery was similar in the two groups [GDT 31/144 (21.5%) patients vs. usual patient care 28/143 (19.6%) patients; P = 0.88]. Absolute values of urinary NGAL were also similar at 24 h (GDT 53.5 vs. usual patient care 44.1 ng ml; P = 0.38) and 72 h (GDT 45.1 vs. usual patient care 41.1 ng ml; P = 0.50) as were urinary NGAL : creatinine ratios at 24 h (GDT 45 vs. usual patient care 43 ng mg; P = 0.63) and 72 h (GDT 66 vs. usual patient care 63 ng mg; P = 0.62). The incidence of KDIGO-defined AKI was also similar between the groups [GDT 9/144 (6%) patients vs. usual patient care 11/143 (8%) patients; P = 0.80]. CONCLUSION: In this trial, GDT did not reduce the incidence of AKI amongst high-risk patients undergoing major gastrointestinal surgery. This may reflect improving standards in usual patient care. TRIAL REGISTRATION: OPTIMISE Trial Registration ISRCTN04386758.

Acute Kidney Injury and Risk of Death After Elective Surgery: Prospective Analysis of Data From an International Cohort Study.

BACKGROUND: Postoperative acute kidney injury (AKI) is associated with a high mortality rate. However, the relationship among AKI, its associations, and mortality is not well understood. METHODS: Planned analysis of data was collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. AKI was defined using Kidney Disease Improving Global Outcomes criteria. Patients missing preoperative creatinine data were excluded. We used multivariable logistic regression to examine the relationships among preoperative creatinine-based estimated glomerular filtration rate (eGFR), postoperative AKI, and hospital mortality, accounting for the effects of age, major comorbid diseases, and nature and severity of surgical intervention on outcomes. We similarly modeled preoperative associations of AKI. Data are presented as n (%) or odds ratios (ORs) with 95% confidence intervals. RESULTS: A total of 36,357 patients were included, 743 (2.0%) of whom developed AKI with 73 (9.8%) deaths in hospital. AKI affected 73 of 196 (37.2%) of all patients who died. Mortality was strongly associated with the severity of AKI (stage 1: OR, 2.57 [1.3-5.0]; stage 2: OR, 8.6 [5.0-15.1]; stage 3: OR, 30.1 [18.5-49.0]). Low preoperative eGFR was strongly associated with AKI. However, in our model, lower eGFR was not associated with increasing mortality in patients who did not develop AKI. Conversely, in older patients, high preoperative eGFR (>90 mL·minute·1.73 m) was associated with an increasing risk of death, potentially reflecting poor muscle mass. CONCLUSIONS: The occurrence and severity of AKI are strongly associated with risk of death after surgery. However, the relationship between preoperative renal function as assessed by serum creatinine-based eGFR and risk of death dependent on patient age and whether AKI develops postoperatively.