Evaluation of high dose N- Acetylcysteine on airway inflammation and quality of life outcomes in adults with bronchiectasis: A randomised placebo-controlled pilot study.

BACKGROUND: High dose N acetylcysteine (NAC), a mucolytic, anti-inflammatory and antioxidant agent has been shown to significantly reduce exacerbations, and improve quality of life in placebo controlled, double blind randomised (RCT) studies in patients with COPD, and in an open, randomised study in bronchiectasis. In this pilot, randomised, double-blind, placebo-controlled study, we wished to investigate the feasibility of a larger clinical trial, and the anti-inflammatory and clinical benefits of high dose NAC in bronchiectasis. AIMS: Primary outcome: to assess the efficacy of NAC 2400 mg/day at 6 weeks on sputum neutrophil elastase (NE), a surrogate marker for exacerbations. Secondary aims included assessing the efficacy of NAC on sputum MUC5B, IL-8, lung function, quality of life, and adverse effects. METHODS: Participants were randomised to receive 2400 mg or placebo for 6 weeks. They underwent 3 visits: at baseline, week 3 and week 6 where clinical and sputum measurements were assessed. RESULTS: The study was stopped early due to the COVID pandemic. In total 24/30 patients were recruited, of which 17 completed all aspects of the study. Given this, a per protocol analysis was undertaken: NAC (n = 9) vs placebo (n = 8): mean age 72 vs 62 years; male gender: 44% vs 50%; baseline median FEV11.56 L (mean 71.5 % predicted) vs 2.29L (mean 82.2% predicted). At 6 weeks, sputum NE fell by 47% in the NAC group relative to placebo (mean fold difference (95%CI: 0.53 (0.12,2.42); MUC5B increased by 48% with NAC compared with placebo. Lung function, FVC improved significantly with NAC compared with placebo at 6 weeks (mean fold difference (95%CI): 1.10 (1.00, 1.20), p = 0.045. Bronchiectasis Quality of life measures within the respiratory and social functioning domains demonstrated clinically meaningful improvements, with social functioning reaching statistical significance. Adverse effects were similar in both groups. CONCLUSION: High dose NAC exhibits anti-inflammatory benefits, and improvements in aspects of quality of life and lung function measures. It is safe and well tolerated. Further larger placebo controlled RCT's are now warranted examining its role in reducing exacerbations.

Participatory co-design and normalisation process theory with staff and patients to implement digital ways of working into routine care: the example of electronic patient-reported outcomes in UK renal services.

BACKGROUND: Successful implementation of digital health systems requires contextually sensitive solutions. Working directly with system users and drawing on implementation science frameworks are both recommended. We sought to combine Normalisation Process Theory (NPT) with participatory co-design methods, to work with healthcare stakeholders to generate implementation support recommendations for a new electronic patient reported outcome measure (ePRO) in renal services. ePROs collect data on patient-reported symptom burden and illness experience overtime, requiring sustained engagement and integration into existing systems. METHODS: We identified co-design methods that could be mapped to NPT constructs to generate relevant qualitative data. Patients and staff from three renal units in England participated in empathy and process mapping activities to understand 'coherence' (why the ePRO should be completed) and 'cognitive participation' (who would be involved in collecting the ePRO). Observation of routine unit activity was completed to understand 'collective action' (how the collection of ePRO could integrate with service routines). RESULTS: The mapping activities and observation enabled the research team to become more aware of the key needs of both staff and patients. Working within sites enabled us to consider local resources and barriers. This produced 'core and custom' recommendations specifying core needs that could be met with customised local solutions. We identified two over-arching themes which need to be considered when introducing new digital systems (1) That data collection is physical (electronic systems need to fit into physical spaces and routines), and (2) That data collection is intentional (system users must be convinced of the value of collecting the data). CONCLUSIONS: We demonstrate that NPT constructs can be operationalised through participatory co-design to work with stakeholders and within settings to collaboratively produce implementation support recommendations. This enables production of contextually sensitive implementation recommendations, informed by qualitative evidence, theory, and stakeholder input. Further longitudinal evaluation is necessary to determine how successful the recommendations are in practice.

Kidney Exchange to Overcome Financial Barriers to Kidney Transplantation.

Organ shortage is the major limitation to kidney transplantation in the developed world. Conversely, millions of patients in the developing world with end-stage renal disease die because they cannot afford renal replacement therapy-even when willing living kidney donors exist. This juxtaposition between countries with funds but no available kidneys and those with available kidneys but no funds prompts us to propose an exchange program using each nation's unique assets. Our proposal leverages the cost savings achieved through earlier transplantation over dialysis to fund the cost of kidney exchange between developed-world patient-donor pairs with immunological barriers and developing-world patient-donor pairs with financial barriers. By making developed-world health care available to impoverished patients in the developing world, we replace unethical transplant tourism with global kidney exchange-a modality equally benefitting rich and poor. We report the 1-year experience of an initial Filipino pair, whose recipient was transplanted in the United states with an American donor's kidney at no cost to him. The Filipino donor donated to an American in the United States through a kidney exchange chain. Follow-up care and medications in the Philippines were supported by funds from the United States. We show that the logistical obstacles in this approach, although considerable, are surmountable.

The Incremental Cost of Incompatible Living Donor Kidney Transplantation: A National Cohort Analysis.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p < 0.0001 for all). ILDKT was associated with longer median length of stay (12.9 vs. 7.8 days), higher Medicare payments ($91 330 vs. $63 782 p < 0.0001), and greater outlier payments. In conclusion, ILDKT increases the cost of and payments for kidney transplantation.

Utilization of Deceased Donor Kidneys to Initiate Living Donor Chains.

We propose that some deceased donor (DD) kidneys be allocated to initiate nonsimultaneous extended altruistic donor chains of living donor (LD) kidney transplants to address, in part, the huge disparity between patients on the DD kidney waitlist and available donors. The use of DD kidneys for this purpose would benefit waitlisted candidates in that most patients enrolled in kidney paired donation (KPD) systems are also waitlisted for a DD kidney transplant, and receiving a kidney through the mechanism of KPD will decrease pressure on the DD pool. In addition, a LD kidney usually provides survival potential equal or superior to that of DD kidneys. If KPD chains that are initiated by a DD can end in a donation of an LD kidney to a candidate on the DD waitlist, the quality of the kidney allocated to a waitlisted patient is likely to be improved. We hypothesize that a pilot program would show a positive impact on patients of all ethnicities and blood types.

Propensity score-matched outcomes analysis of the liver-first approach for synchronous colorectal liver metastases.

BACKGROUND: Liver resection before primary cancer resection is a novel strategy advocated for selected patients with synchronous colorectal liver metastases (sCRLM). This study measured outcomes in patients with sCRLM following a liver-first or classical approach, and used a validated propensity score. METHODS: Clinical, pathological and follow-up data were collected prospectively from consecutive patients undergoing hepatic resection for sCRLM at a single centre (2004-2014). Cumulative disease-free survival (DFS), cancer-specific survival (CSS) and overall survival (OS) were calculated by means of Kaplan-Meier analysis. Survival differences were analysed in the whole cohort and in subgroups matched according to Basingstoke Predictive Index (BPI). RESULTS: Of 582 patients, 98 had a liver-first and 467 a classical approach to treatment; 17 patients undergoing simultaneous bowel and liver resection were excluded. The median (i.q.r.) BPI was significantly higher in the liver-first compared with the classical group: 8·5 (5-10) versus 8 (4-9) (P = 0·030). Median follow-up was 34 months. The 5-year DFS rate was lower in the liver-first group than in the classical group (23 versus 45·6 per cent; P = 0·001), but there was no difference in 5-year CSS (51 versus 53·8 per cent; P = 0·379) or OS (44 versus 49·6 per cent; P = 0·305). After matching for preoperative BPI, there was no difference in 5-year DFS (37 versus 41·2 per cent for liver-first versus classical approach; P = 0·083), CSS (51 versus 53·2 per cent; P = 0·616) or OS (47 versus 49·1 per cent; P = 0·846) rates. CONCLUSION: Patients with sCRLM selected for a liver-first approach had more oncologically advanced disease and a poorer prognosis. They had inferior cumulative DFS than those undergoing a classical approach, a difference negated by matching preoperative BPI.

Planning for Uncertainty and Fallbacks Can Increase the Number of Transplants in a Kidney-Paired Donation Program.

A kidney-paired donation (KPD) pool consists of transplant candidates and their incompatible donors, along with nondirected donors (NDDs). In a match run, exchanges are arranged among pairs in the pool via cycles, as well as chains created from NDDs. A problem of importance is how to arrange cycles and chains to optimize the number of transplants. We outline and examine, through example and by simulation, four schemes for selecting potential matches in a realistic model of a KPD system; proposed schemes take account of probabilities that chosen transplants may not be completed as well as allowing for contingency plans when the optimal solution fails. Using data on candidate/donor pairs and NDDs from the Alliance for Paired Donation, the simulations extend over 8 match runs, with 30 pairs and 1 NDD added between each run. Schemes that incorporate uncertainties and fallbacks into the selection process yield substantially more transplants on average, increasing the number of transplants by as much as 40% compared to a standard selection scheme. The gain depends on the degree of uncertainty in the system. The proposed approaches can be easily implemented and provide substantial advantages over current KPD matching algorithms.

Historical Matching Strategies in Kidney Paired Donation: The 7-Year Evolution of a Web-Based Virtual Matching System.

Failure to convert computer-identified possible kidney paired donation (KPD) exchanges into transplants has prohibited KPD from reaching its full potential. This study analyzes the progress of exchanges in moving from "offers" to completed transplants. Offers were divided into individual segments called 1-way transplants in order to calculate success rates. From 2007 to 2014, the Alliance for Paired Donation performed 243 transplants, 31 in collaboration with other KPD registries and 194 independently. Sixty-one of 194 independent transplants (31.4%) occurred via cycles, while the remaining 133 (68.6%) resulted from nonsimultaneous extended altruistic donor (NEAD) chains. Thirteen of 35 (37.1%) NEAD chains with at least three NEAD segments accounted for 68% of chain transplants (8.6 tx/chain). The "offer" and 1-way success rates were 21.9 and 15.5%, respectively. Three reasons for failure were found that could be prospectively prevented by changes in protocol or software: positive laboratory crossmatch (28%), transplant center declined donor (17%) and pair transplanted outside APD (14%). Performing a root cause analysis on failures in moving from offer to transplant has allowed the APD to improve protocols and software. These changes have improved the success rate and the number of transplants performed per year.

Ethnicity can predict GLRA1 genotypes in hyperekplexia.

OBJECTIVES: Hyperekplexia is predominantly caused by mutations in the α-1 subunit of the inhibitory glycine receptor (GLRA1). Three quarters of cases show autosomal-recessive inheritance. METHODS: We carefully ascertained reports of ethnicity from our hyperekplexia research cohort. These were compared with all published cases of hyperekplexia with an identified genetic cause. Ethnicities were subgrouped as Caucasian, Asian, Arabic, Turkish, Jewish or Afro-American. RESULTS: We report the ethnicity of 90 cases: 56 cases from our service augmented by 34 cases from the literature. Homozygous deletions of exons 1 to 7 are predominantly seen in people with Turkish backgrounds (n=16/17, p<0.001). In contrast, the dominant point mutation R271 is seen in people of Asian, Caucasian and African-American heritage (n=19) but not in people with Arab or Turkish ethnicities (p<0.001). CONCLUSIONS: Self-declared ethnicity can predict gene-screening outcomes. Cultural practices influence the inheritance patterns and a Caucasian founder is postulated for R271 mutations.

The effectiveness of exercise as treatment for vasomotor menopausal symptoms: randomised controlled trial.

OBJECTIVE: To investigate the effectiveness of exercise as treatment for vasomotor menopausal symptoms. DESIGN: Three-group randomised controlled trial, two exercise interventions and a control group. SETTING: Primary Care, West Midlands UK. POPULATION: Perimenopausal and postmenopausal women experiencing at least five hot flushes/night sweats per day and not taken MHT in previous 3 months were recruited from 23 general practices. METHODS: Participants in both exercise interventions groups were offered two face-to-face consultations with a physical activity facilitator to support engagement in regular exercise. In addition, one exercise group received a menopause-specific information DVD and written materials to encourage regular exercise and the other exercise group was offered the opportunity to attend exercise social support groups in their communities. Interventions lasted 6 months. MAIN OUTCOME MEASURE: The primary outcome was frequency of hot flushes/night sweats at 6-month up. RESULTS: Two hundred and sixty-one women were randomised (n = 87 per group). Neither of the exercise intervention groups reported significantly less frequent hot flushes/night sweats per week than controls (exercise-DVD versus control: -8.9, 95% CI -20.0 to 2.2; exercise-social support versus control: -5.2, 95% CI -16.7 to 6.3). CONCLUSIONS: This trial indicates that exercise is not an effective treatment for hot flushes/night sweats. Contrary to current clinical guidance, women should not be advised that exercise will relieve their vasomotor menopausal symptoms.

Does the abundance of girellids and kyphosids correlate with cover of the palatable green algae, Ulva spp.? A test on temperate rocky intertidal reefs.

This study assessed whether the abundance of girellids and kyphosids was related to cover of the palatable green algae, Ulva australis and Ulva compressa, on rocky intertidal reefs in Jervis Bay, New South Wales, Australia. No relationship was found between Ulva spp. cover and abundance of Girella tricuspidata, Girella elevata and Kyphosus sydneyanus during a period of relatively low Ulva spp. cover (i.e. February 2011 to March 2011), but during a period of significantly higher Ulva spp. cover (i.e. October 2011 to November 2011) there was a strong correlation between Ulva spp. cover and G. tricuspidata abundance. Spatial analysis indicated that the abundance of G. tricuspidata was consistent across time, suggesting G. tricuspidata were not moving between reefs in response to variation in Ulva spp. cover between periods but rather that large schools of G. tricuspidata resided on reefs that had relatively higher Ulva spp. cover at certain times of the year.

Quantifying the risk of incompatible kidney transplantation: a multicenter study.

Incompatible live donor kidney transplantation (ILDKT) offers a survival advantage over dialysis to patients with anti-HLA donor-specific antibody (DSA). Program-specific reports (PSRs) fail to account for ILDKT, placing this practice at regulatory risk. We collected DSA data, categorized as positive Luminex, negative flow crossmatch (PLNF) (n = 185), positive flow, negative cytotoxic crossmatch (PFNC) (n = 536) or positive cytotoxic crossmatch (PCC) (n = 304), from 22 centers. We tested associations between DSA, graft loss and mortality after adjusting for PSR model factors, using 9669 compatible patients as a comparison. PLNF patients had similar graft loss; however, PFNC (adjusted hazard ratio [aHR] = 1.64, 95% confidence interval [CI]: 1.15-2.23, p = 0.007) and PCC (aHR = 5.01, 95% CI: 3.71-6.77, p < 0.001) were associated with increased graft loss in the first year. PLNF patients had similar mortality; however, PFNC (aHR = 2.04; 95% CI: 1.28-3.26; p = 0.003) and PCC (aHR = 4.59; 95% CI: 2.98-7.07; p < 0.001) were associated with increased mortality. We simulated Centers for Medicare & Medicaid Services flagging to examine ILDKT's effect on the risk of being flagged. Compared to equal-quality centers performing no ILDKT, centers performing 5%, 10% or 20% PFNC had a 1.19-, 1.33- and 1.73-fold higher odds of being flagged. Centers performing 5%, 10% or 20% PCC had a 2.22-, 4.09- and 10.72-fold higher odds. Failure to account for ILDKT's increased risk places centers providing this life-saving treatment in jeopardy of regulatory intervention.

The dynamics of recovery and growth: how defoliation affects stored resources.

Growth rate varies widely among species and the trade-off between growth rate and storage or maintenance traits is a principal axis of variation between species. Many plant species have substantial root stores, but very little is known about how growth rate modifies responses of these stores to defoliation and other stresses. Species with different growth rates are predicted to respond in distinct ways, because of variation in the pre-defoliation allocation to storage. Here, we quantified the dynamics of stored carbohydrates in seven species with varying growth rate, following defoliation in a pot experiment. For faster growing species, there was significant reduction in carbohydrate concentration following defoliation, followed by relatively fast recovery, whereas for slower growing species, carbohydrate concentration levels remained relatively invariant across treatments. Results for total carbohydrates mirrored those for concentration, but were not as significant. Our findings were consistent with the idea that faster growing species respond more rapidly than slower growers to defoliation, through changes in carbohydrate pool concentrations. Growth rate as an indicator of life-history and ecological strategy may therefore be key to understanding post-defoliation recovery and storage strategies.

Patient-reported outcomes in long-term survivors of metastatic colorectal cancer needing liver resection.

BACKGROUND: Five-year survival after hepatic resection for colorectal cancer (CRC) liver metastases is good, but data on patient-reported outcomes are lacking. This study describes the long-term impact of liver surgery for CRC metastases on patient-reported outcomes. METHODS: The study used the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the disease-specific module, EORTC QLQ-LMC21. For functional scales, mean scores out of 100 with 95 per cent c.i. were calculated; differences of 10 points or more were considered clinically significant. Responses to symptom scales and items were categorized as 'minimal' or 'severe'. Proportions and 95 per cent c.i. for symptoms were calculated. RESULTS: A total of 241 patients were recruited; nine (3·7 per cent) had unresectable disease and were excluded. Some 68 (42 men) of 80 long-term survivors participated; their mean age was 69·5 years and median follow-up was 8·0 (range 6·9-9·2) years. Values for baseline and 1-year patient-reported outcome data were similar. Scores for functional scales were excellent (emotional function: 92, 95 per cent c.i. 87 to 96; social function: 94, 89 to 99; role function: 94, 90 to 98), reflecting clinically significant improvements from baseline values of 17 (10 to 24), 12 (3 to 21) and 12 (3 to 20) respectively. Severe symptoms were uncommon (affected less than 5 per cent of patients) for most patient-reported outcome scales or items, but persistent severe symptoms were noted for sexual function (2 per cent increase from baseline), peripheral neuropathy (2 per cent increase), constipation (10 per cent increase) and diarrhoea (5 per cent increase). CONCLUSION: Long-term survivors of metastatic colorectal cancer who have undergone liver surgery have excellent global quality of life, high levels of function and few symptoms.

The AIN-76A defined rodent diet accelerates the development of heart failure in SHHF rats: a cautionary note on its use in cardiac studies.

Previous studies from our laboratory have shown positive benefits of linoleic acid (LA) feeding for attenuation of rat heart failure (HF). However, another research group concluded LA feeding was detrimental to cardiac function, using the American Institute of Nutrition 76A (AIN) diet as a background diet for the experimental animals only. To reconcile these conflicting results and determine whether (i) AIN has effects on cardiovascular function, and (ii) AIN reverses the positive effects of LA feeding, studies were performed using spontaneously hypertensive heart failure (SHHF) rats in both a survival study with lifetime feeding of AIN (control: Purina 5001) and a 2 × 2 factorial design for 6 weeks in young male SHHF rats with background diet and LA as variables. During a lifetime of AIN feeding, mortality from heart failure is significantly accelerated, cardiolipin altered and triglycerides increased. In young rats, 6 weeks on the AIN diet promoted increased systolic and diastolic blood pressure, increased fed and fasting blood glucose, increased serum inflammatory eicosanoids, decreased docosahexanoic acid, increased posterior wall thickness in diastole and an altered cardiolipin subspecies profile. The addition of LA to the AIN diet was able to rescue blood pressure. However, the combination increased retroperitoneal fat mass, body weight and fed blood glucose beyond the levels with the AIN diet alone. Because the AIN diet has wide ranging effects on cardiovascular parameters, our results suggest that it should not be used in animal studies involving the cardiovascular system unless induction of cardiac dysfunction is the desired outcome.

Model order reduction techniques to identify submarining risk in a simplified human body model.

This work investigates linear and non-linear parametric reduced order models (ROM) capable of replacing computationally expensive high-fidelity simulations of human body models (HBM) through a non-intrusive approach. Conventional crash simulation methods pose a computational barrier that restricts profound analyses such as uncertainty quantification, sensitivity analysis, or optimization studies. The non-intrusive framework couples dimensionality reduction techniques with machine learning-based surrogate models that yield a fast responding data-driven black-box model. A comparative study is made between linear and non-linear dimensionality reduction techniques. Both techniques report speed-ups of a few orders of magnitude with an accurate generalization of the design space. These accelerations make ROMs a valuable tool for engineers.

Crystalloid volume versus catecholamines for management of hemorrhagic shock during esophagectomy - assessment of microcirculatory tissue oxygenation of the gastric conduit in a porcine model using hyperspectral imaging - an experimental study.

INTRODUCTION: Oncologic esophagectomy is a two-cavity procedure with considerable morbidity and mortality. Complex anatomy and the proximity to major vessels constitute a risk for massive intraoperative hemorrhage. Currently, there is no conclusive consensus on the ideal anesthesiologic countermeasure in case of such immense blood loss. The objective of this work was to identify the most promising anesthesiologic management in case of intraoperative hemorrhage with regards to tissue perfusion of the gastric conduit during esophagectomy using hyperspectral imaging (HSI). MATERIAL AND METHODS: An established live porcine model (n=32) for esophagectomy was used with gastric conduit formation and simulation of a linear stapled side-to-side esophagogastrostomy. After a standardized procedure of controlled blood loss of about 1 L per pig, the four experimental groups (n=8 each) differed in anesthesiologic intervention i.e. (I) permissive hypotension, (II) catecholamine therapy using noradrenaline, (III) crystalloid volume supplementation and (IV) combined crystalloid volume supplementation with noradrenaline therapy. HSI tissue oxygenation (StO2) of the gastric conduit was evaluated and correlated with systemic perfusion parameters. Measurements were conducted before (T0) and after (T1) laparotomy, after hemorrhage (T2) and 60 minutes (T3) and 120 minutes (T4) after anesthesiologic intervention. RESULTS: StO2 values of the gastric conduit showed significantly different results between the four experimental groups with 63.3% (±7.6%) after permissive hypotension (I), 45.9% (±6.4%) after catecholamine therapy (II), 70.5% (±6.1%) after crystalloid volume supplementation (III) and 69.0% (±3.7%) after combined therapy (IV). StO2 values correlated strongly with systemic lactate values (r=-0.67; CI -0.77 to -0.54), which is an established prognostic factor. CONCLUSION: Crystalloid volume supplementation (III) yields the highest StO2 values and lowest systemic lactate values and therefore appears to be the superior primary treatment strategy after hemorrhage during esophagectomy with regards to microcirculatory tissue oxygenation of the gastric conduit.

Dynamic challenges inhibiting optimal adoption of kidney paired donation: findings of a consensus conference.

While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.

Fatty liver disease as a predictor of local recurrence following resection of colorectal liver metastases.

BACKGROUND: Obesity and tissue adiposity constitute a risk factor for several cancers. Whether tissue adiposity increases the risk of cancer recurrence after curative resection is not clear. The present study analysed the influence of hepatic steatosis on recurrence following resection of colorectal liver metastases. METHODS: A prospective cohort of patients who had primary resection of colorectal liver metastases in two major hepatobiliary units between 1987 and 2010 was studied. Hepatic steatosis was assessed in non-cancerous resected liver tissue. Patients were divided into two groups based on the presence of hepatic steatosis. The association between hepatic steatosis and local recurrence was analysed, adjusting for relevant patient, pathological and surgical factors using Cox regression and propensity score case-match analysis. RESULTS: A total of 2715 patients were included. The cumulative local (liver) disease-free survival rate was significantly better in the group without steatosis (hazard ratio (HR) 1·32, 95 per cent confidence interval 1·16 to 1·51; P < 0·001). On multivariable analysis, hepatic steatosis was an independent risk factor for local liver recurrence (HR 1·28, 1·11 to 1·47; P = 0·005). After one-to-one matching of cases (steatotic, 902) with controls (non-steatotic, 902), local (liver) disease-free survival remained significantly better in the group without steatosis (HR 1·27, 1·09 to 1·48; P = 0·002). Patients with steatosis had a greater risk of developing postoperative liver failure (P = 0·001). CONCLUSION: Hepatic steatosis was an independent predictor of local hepatic recurrence following resection with curative intent of colorectal liver metastases.