Predictors of postoperative cardiovascular complications up to 3 months after kidney transplantation.

BACKGROUND: Renal transplant patients have a high peri-operative risk for cardiovascular events. Pre-operative screening for cardiac ischaemia might lower this risk, but there are no specific guidelines. METHODS: We conducted a chart review for all renal transplants performed between January 2010 and December 2013. We collected data about patient characteristics, pre-operative cardiac evaluation before referral, diagnostic tests and interventions. Logistic regression analyses were then applied to relate these factors to the composite endpoint of cardiac death, myocardial infarction, coronary revascularisation or admission for heart failure within 3 months after transplantation. RESULTS: A total of 770 kidney transplants were performed in 751 patients. In 750 cases (97%) a referral to the cardiologist was made. Non-invasive ischaemia detection by myocardial perfusion scintigraphy, exercise stress test or dobutamine stress echocardiography was carried out in 631 cases (82%). Coronary angiography was performed in 85 cases, which revealed significant coronary artery disease in 19 cases. Prophylactic revascularisation was done in 7 cases. The incidence of the study endpoint was 8.6%. In multivariable regression analysis, age at transplantation, pre-transplant myocardial infarction or heart failure, post-operative decrease in haemoglobin and positive non-invasive ischaemia testing were significantly associated with the study endpoint. However, when analysed separately, none of the different non-invasive ischaemia detection modalities were related to the study endpoint. CONCLUSION: Especially those renal transplant candidates with a cardiac history carry a high risk for a cardiovascular event post-transplantation. Uniformity in cardiac screening of renal transplant candidates and better pre-operative preparation might lower this post-operative risk. Besides, post-transplant anaemia should be prevented.

Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

BACKGROUND: The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. DISCUSSION: Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. CONCLUSIONS: In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

Surviving critical illness: what is next? An expert consensus statement on physical rehabilitation after hospital discharge.

BACKGROUND: The study objective was to obtain consensus on physical therapy (PT) in the rehabilitation of critical illness survivors after hospital discharge. Research questions were: what are PT goals, what are recommended measurement tools, and what constitutes an optimal PT intervention for survivors of critical illness? METHODS: A Delphi consensus study was conducted. Panelists were included based on relevant fields of expertise, years of clinical experience, and publication record. A literature review determined five themes, forming the basis for Delphi round one, which was aimed at generating ideas. Statements were drafted and ranked on a 5-point Likert scale in two additional rounds with the objective to reach consensus. Results were expressed as median and semi-interquartile range, with the consensus threshold set at ≤0.5. RESULTS: Ten internationally established researchers and clinicians participated in this Delphi panel, with a response rate of 80 %, 100 %, and 100 % across three rounds. Consensus was reached on 88.5 % of the statements, resulting in a framework for PT after hospital discharge. Essential handover information should include information on 15 parameters. A core set of outcomes should test exercise capacity, skeletal muscle strength, function in activities of daily living, mobility, quality of life, and pain. PT interventions should include functional exercises, circuit and endurance training, strengthening exercises for limb and respiratory muscles, education on recovery, and a nutritional component. Screening tools to identify impairments in other health domains and referral to specialists are proposed. CONCLUSIONS: A consensus-based framework for optimal PT after hospital discharge is proposed. Future research should focus on feasibility testing of this framework, developing risk stratification tools and validating core outcome measures for ICU survivors.

The protein kinase C inhibitor sotrastaurin allows regulatory T cell function.

The novel immunosuppressant sotrastaurin is a selective inhibitor of protein kinase C isoforms that are critical in signalling pathways downstream of the T cell receptor. Sotrastaurin inhibits nuclear factor (NF)-κB, which directly promotes the transcription of forkhead box protein 3 (FoxP3), the key regulator for the development and function of regulatory T cells (Tregs). Our center participated in a randomized trial comparing sotrastaurin (n = 14) and the calcineurin inhibitor Neoral (n = 7) in renal transplant recipients. We conducted ex vivo mixed lymphocyte reaction (MLR) and flow cytometry studies on these patient samples, as well as in vitro studies on samples of blood bank volunteers (n = 38). Treg numbers remained stable after transplantation and correlated with higher trough levels of sotrastaurin (r = 0·68, P = 0·03). A dose-dependent effect of sotrastaurin on alloresponsiveness was observed: the half maximal inhibitory concentration (IC50 ) to inhibit alloactivated T cell proliferation was 45 ng/ml (90 nM). In contrast, Treg function was not affected by sotrastaurin: in the presence of in vitro-added sotrastaurin (50 ng/ml) Tregs suppressed the proliferation of alloactivated T effector cells at a 1:5 ratio by 35 versus 47% in the absence of the drug (P = 0·33). Signal transducer and activator of transcription 5 (STAT)-5 phosphorylation in Tregs remained intact after incubation with sotrastaurin. This potent Treg function was also found in cells of patients treated with sotrastaurin: Tregs inhibited the anti-donor response in MLR by 67% at month 6, which was comparable to pretransplantation (82%). Sotrastaurin is a potent inhibitor of alloreactivity in vitro, while it did not affect Treg function in patients after kidney transplantation.

An exploratory domain analysis of deployment risks and protective features and their association to mental health, cognitive functioning and job performance in military personnel.

BACKGROUND: Meta-analyses of military deployment involve the exploration of focused associations between predictors and peri and post-deployment outcomes. OBJECTIVE: We aimed to provide a large-scale and high-level perspective of deployment-related predictors across eight peri and post-deployment outcomes. DESIGN: Articles reporting effect sizes for associations between deployment-related features and indices of peri and post-deployment outcomes were selected. Three-hundred and fourteen studies (N = 2,045,067) and 1,893 relevant effects were retained. Deployment features were categorized into themes, mapped across outcomes, and integrated into a big-data visualization. METHODS: Studies of military personnel with deployment experience were included. Extracted studies investigated eight possible outcomes reflecting functioning (e.g., post-traumatic stress, burnout). To allow comparability, effects were transformed into a Fisher's Z. Moderation analyses investigating methodological features were performed. RESULTS: The strongest correlates across outcomes were emotional (e.g., guilt/shame: Z = 0.59 to 1.21) and cognitive processes (e.g., negative appraisals: Z = -0.54 to 0.26), adequate sleep on deployment (Z = -0.28 to - 0.61), motivation (Z = -0.33 to - 0.71), and use of various coping strategies/recovery strategies (Z = -0.25 to - 0.59). CONCLUSIONS: Findings pointed to interventions that target coping and recovery strategies, and the monitoring of emotional states and cognitive processes post-deployment that may indicate early risk.

Sotrastaurin in calcineurin inhibitor-free regimen using everolimus in de novo kidney transplant recipients.

Sotrastaurin, a novel selective protein-kinase-C inhibitor, inhibits early T cell activation via a calcineurin-independent pathway. Efficacy and safety of sotrastaurin in a calcineurin inhibitor-free regimen were evaluated in this two-stage Phase II study of de novo kidney transplant recipients. Stage 1 randomized 131 patients (2:1) to sotrastaurin 300 mg or cyclosporine A (CsA). Stage 2 randomized 180 patients (1:1:1) to sotrastaurin 300 or 200 mg or CsA. All patients received basiliximab, everolimus (EVR) and prednisone. Primary endpoint was composite efficacy failure rate of treated biopsy-proven acute rejection, graft loss, death or lost to follow-up. Main safety assessment was estimated glomerular filtration rate (eGFR) by MDRD-4 at Month 12. Composite efficacy failure rates at 12 months were higher in sotrastaurin arms (Stage 1: 16.5% and 10.9% for sotrastaurin 300 mg and CsA; Stage 2: 27.2%, 34.5% and 19.4% for sotrastaurin 200 mg, 300 mg and CsA). eGFR was significantly better in sotrastaurin groups versus CsA at most time points, except at 12 months. Gastrointestinal and cardiac adverse events were more frequent with sotrastaurin. Higher treatment discontinuation, deaths and graft losses occurred with sotrastaurin 300 mg. Sotrastaurin combined with EVR showed higher efficacy failure rates and some improvement in renal allograft function compared to a CsA-based therapy.

The detrimental effect of donor-specific antibodies is irrespective of its level in highly-immunized living donor kidney transplant recipients: A case-control series.

Background: The impact of donor-specific antibodies (DSA) in (highly-) immunized living donor kidney transplant recipients is reported differentially in various patient cohorts. Methods: We have performed a retrospective analysis of all consecutive HLA-incompatible living donor kidney transplant recipients in our center between 2010-2019. Recipients who underwent plasmafiltration for a positive CDC-crossmatch were excluded. For each DSA+ recipient (DSA+), one immunized recipient without DSA (pPRA+) and two non-immunized recipients (pPRA-) were included. Patient and graft survival were analyzed and a subgroup analysis of DSA+ recipients was performed. Results: For 63 DSA+ recipients, 63 PRA+ and 126 PRA- recipients were included. 26 (41%) had class I, 24 (38%) class II and 13 (21%) combined HLA class I and II DSA. Death-censored graft survival was inferior in DSA+ recipients compared to pPRA+ (HR 2.38 [95% CI 1.00-5.70]) as well as to pPRA- (HR 3.91 [1.86-8.22]). In multivariate analysis, DSA remained of negative influence on death-censored graft survival. Flowcytometric crossmatch, MFI value, HLA class and origin of DSA were not of significant impact. Conclusion: In our cohort of (highly-) immunized recipients, pretransplant DSA led to inferior death-censored graft survival. There were no "safe" DSA characteristics since only DSA per se impacted death-censored graft survival.

The Association between Frailty and Short-Term Outcomes in an Intensive Care Unit Rehabilitation Trial: An Exploratory Analysis.

BACKGROUND: Physical therapy initiated early in an ICU stay may reduce functional deficits in critically ill patients; however, the association of frailty with outcomes in those receiving early in-ICU rehabilitation is unknown. OBJECTIVE: To estimate the association between frailty and 3 outcomes in patients enrolled in an ICU randomized clinical trial (RCT). DESIGN: Exploratory secondary analyses of the CYCLE pilot RCT (NCT02377830). SETTING: 7 Canadian ICUs. PARTICIPANTS: Previously ambulatory critically ill adults. INTERVENTION: Participants were randomized to early in-bed cycling plus routine physiotherapy versus early routine physiotherapy alone. MEASUREMENTS: Using regression analyses, we modelled the association between pre-hospital Clinical Frailty Scale (CFS) scores, Physical Function in ICU Test-scored (PFIT-s), muscle strength, and mortality at hospital discharge, adjusting for illness severity (APACHE II) and the randomized intervention. We explored the influence of imputing mean PFIT-s and strength scores for decedents, and with listwise deletion of decedents in a sensitivity analysis. RESULTS: Of 66 patients, 2 had missing data, 2 had incomplete data, and 21 died by hospital discharge. At hospital discharge for 66 patients, frailty was not associated with PFIT-s (mean difference (MD) [95% CI]=0.20, [-2.08, 2.74]) or muscle strength (1.96, [-12.6, 16.6]). A sensitivity analysis yielded consistent results. Frailty was also not associated with hospital mortality (odds ratio 0.91, [0.28 to 2.93]). CONCLUSION: We found no association between pre-hospital frailty, physical function, strength, or mortality at hospital discharge in critically ill patients enrolled in an early rehabilitation trial. Larger sample sizes are needed to further explore the association of frailty with these outcomes at hospital discharge.

The calcineurin inhibitor tacrolimus allows the induction of functional CD4CD25 regulatory T cells by rabbit anti-thymocyte globulins.

Rabbit anti-thymocyte globulins (rATG) induce CD4(+)CD25(+)forkhead box P3 (FoxP3(+)) regulatory T cells that control alloreactivity. In the present study, we investigated whether rATG convert T cells into functional CD4(+)CD25(+)FoxP3(+)CD127(-/low) regulatory T cells in the presence of drugs that may hamper their induction and function, i.e. calcineurin inhibitors. CD25(neg) T cells were stimulated with rATG or control rabbit immunoglobulin G (rIgG) in the absence and presence of tacrolimus for 24 h. Flow cytometry was performed for CD4, CD25, FoxP3 and CD127 and the function of CD25(+) T cells was examined in suppression assays. MRNA expression profiles were composed to study the underlying mechanisms. After stimulation, the percentage CD4(+)CD25(+)FoxP3(+)CD127(-/low) increased (from 2% to 30%, mean, P < 0.01) and was higher in the rATG samples than in control rIgG samples (2%, P < 0.01). Interestingly, FoxP3(+)T cells were also induced when tacrolimus was present in the rATG cultures. Blockade of the interleukin (IL)-2 pathway did not affect the frequency of rATG-induced FoxP3(+) T cells. The rATG tacrolimus-induced CD25(+) T cells inhibited proliferative responses of alloantigen-stimulated effector T cells as vigorously as rATG-induced and natural CD4(+)CD25(+)FoxP3(+)CD127(-/low) T cells (67% +/- 18% versus 69% +/- 16% versus 45% +/- 20%, mean +/- standard error of the mean, respectively). At the mRNA-expression level, rATG-induced CD25(+) T cells abundantly expressed IL-10, IL-27, interferon (IFN)-gamma, perforin and granzyme B in contrast to natural CD25(+) T cells (all P = 0.03), while FoxP3 was expressed at a lower level (P = 0.03). These mRNA data were confirmed in regulatory T cells from kidney transplant patients. Our findings demonstrate that tacrolimus does not negatively affect the induction, phenotype and function of CD4(+)CD25(+) T cells, suggesting that rATG may induce regulatory T cells in patients who receive tacrolimus maintenance therapy.

Dissemination and implementation of national physical activity, sedentary behaviour, and/or sleep guidelines among community-dwelling adults aged 18 years and older: a systematic scoping review and suggestions for future reporting and research.

Strategies for dissemination (purposive distribution of a guideline to specific audiences) and implementation (actions to support the general public in meeting guideline recommendations/behavioural benchmarks) of national movement guidelines (physical activity (PA), sedentary behaviour, and sleep) have yet to be synthesized. The purpose of this systematic scoping review was to identify strategies for dissemination and implementation of national PA, sedentary behaviour, and/or sleep guidelines among community-dwelling adults (aged >18 years) and/or stakeholders in Canada and analogous countries. Five search approaches (e.g., published literature, grey literature, targeted web-based, custom Google, and content expert consultation) identified records (e.g., empirical studies, organizational reports, website pages, or guideline messages) that discussed and/or evaluated dissemination or implementation strategies for a prespecified list of guidelines. A modified strategy classification system was developed to chart the data. Forty-seven reports met inclusion criteria. Dissemination strategies (n = 42) were more frequently reported than implementation strategies (n = 24). Implementation strategies were more frequently evaluated (n = 13 vs. 7 dissemination strategies) and associated with positive outcomes. The 13 studies that evaluated strategies were at high or serious risk of bias. We identified limited information about the dissemination and implementation of national movement guidelines and identified strategies were rarely evaluated. Greater efforts are required to increase the impact of guidelines among the general public and stakeholders and to build the evidence base in this field. (Open Science Framework registration: https://osf.io/4tyw3.) Novelty An adapted movement guideline dissemination and implementation strategy classification framework is provided. Knowledge translation efforts should be documented and evaluated to advance science and practice in the movement guideline field.

Stalling of human DNA (cytosine-5) methyltransferase at single-strand conformers from a site of dynamic mutation.

Single-strand conformers (SSCs) from the C-rich strand of the triplet repeat at the FMR-1 locus are rapidly and selectively methylated by the human DNA (cytosine-5) methyltransferase. The apparent affinity of the enzyme for the FMR-1 SSC is about tenfold higher than it is for a control Watson-Crick paired duplex. The de novo methylation rate for the SSC is over 150-fold higher than the de novo rate for the control duplex. Methylation of what is generally called a hemi-methylated duplex occurs with a rate enhancement of over 100-fold, while methylation of what can be viewed as a hemi-methylated FMR-1 SSC is actually slower than the de novo rate. The pronounced inhibition of the methyltransferase by the methylated SSC suggests that the enzyme has a higher affinity for the methylated product of its reaction with the SSC than it has for the unmethylated SSC substrate. Gel retardation studies show that the methyltransferase binds selectively to SSCs from the C-rich strand of the FMR-1 triplet repeat. This suggests a two-step stalling process in which the human methyltransferase first selectively methlyates and subsequently stalls at the C-rich strand SSC. Stalling may reflect the inability of the enzyme to release a DNA product that is fixed in a conformation resembling its transition state by the unusual structure of the substrate. In particular, the data suggest that DNA methyltransferase may physically participate in biological processes that lead to dynamic mutation at FMR-1. In general, the data raise the possibility that a two-step stalling process occurs at secondary structures associated with chromosome instability, chromosome remodelling, viral replication or viral integration and may account for the local hypermethylation and global hypomethylation associated with viral and non-viral tumorigenesis.

Clinical chorioamnionitis is not predicted by an ultrasonic biophysical profile in patients with premature rupture of membranes.

A modified biophysical profile was assessed serially in 47 patients with premature rupture of membranes who were not in labor. This profile included fetal movement, fetal tone, fetal breathing, amniotic fluid volume, and placental grade. The most recent study, obtained within 2 days of delivery, was compared with pregnancy outcome as reflected by the development of chorioamnionitis and/or neonatal sepsis. No study patient received antibiotics, steroids, or tocolytics before labor. Neither the composite biophysical profile nor any of its components were found to be different between patients with and without clinical chorioamnionitis. Neonatal sepsis was not observed. These data do not support the use of the biophysical profile as a predictor of maternal infection.

The effect of low and ultra-low dosages Thymoglobulin on peripheral T, B and NK cells in kidney transplant recipients.

INTRODUCTION: Rabbit Anti-Thymocyte Globulin (r-ATG) is a polyclonal antibody preparation, used to prevent and treat acute rejection episodes after organ transplantation. However, despite more than 40 years of clinical use, the optimal dose of r-ATG is still not defined. To find a better balance between efficacy and infectious complications, we embarked on a controlled study and monitored the effect of low and ultra-low dosages Thymoglobulin (Genzyme) on peripheral T, B, and NK cells. PATIENTS AND METHODS: Kidney transplant recipients received either 0.5 mg/kg, 1.0 mg/kg or 2.0 mg/kg on the first 3 consecutive days post-transplantation. Thus, total doses were 1.5 mg/kg, 3.0 mg/kg and 6.0 mg/kg. A total of 40 patients were enrolled, including 11 controls. All patients were treated with Prednisolon, Advagraf (Astellas) and Mycophenolate Mofetil (Roche). T (CD3+), B (CD19+) and NK (CD3-CD16+56+) cells were analyzed by flow cytometry. Baseline cell counts were compared to forty age and sex matched healthy persons. Post-transplantation cell counts of the 3 Thymoglobulin groups were compared to the 11 control patients, who received no induction therapy. RESULTS: Absolute numbers of T, B, and NK cells were comparable in all patients pre-transplantation, but T and B cells were lower than in healthy persons (p=0.007 and p=0.0003, Mann Whitney test). In the first week, T cells and NK cells were significantly lower in all Thymoglobulin groups compared to controls. B cells were not affected. One month after Thymoglobulin NK cells had returned to control numbers in all groups, while T cells had already recovered to control counts in the 1.5 mg/kg group. During follow-up, T cells in the 3.0mg/kg group also returned to control values, but at one year the patients in the 6.0 mg/kg group still had significantly lower T cells (p=0.03). Patient and graft survival, rejection and infection incidence and renal function did not differ between groups. CONCLUSION: Patients with end stage renal disease have significantly lower peripheral T and B cell counts than healthy persons. (Ultra-) low Thymoglobulin schedules deplete peripheral lymphocytes in a dose dependent way. Knowledge of the duration of this depletion contributes to finding the optimal immunosuppressive strategy for kidney transplant recipients.

Hypotonic versus isotonic saline in hospitalised children: a systematic review.

BACKGROUND: The traditional recommendations which suggest that hypotonic intravenous (i.v.) maintenance fluids are the solutions of choice in paediatric patients have not been rigorously tested in clinical trials, and may not be appropriate for all children. AIMS: To systematically review the evidence from studies evaluating the safety of administering hypotonic versus isotonic i.v. maintenance fluids in hospitalised children. DATA SOURCES: Medline (1966-2006), Embase (1980-2006), the Cochrane Library, abstract proceedings, personal files, and reference lists. Studies that compared hypotonic to isotonic maintenance solutions in children were selected. Case reports and studies in neonates or patients with a pre-existing history of hyponatraemia were excluded. RESULTS: Six studies met the selection criteria. A meta-analysis combining these studies showed that hypotonic solutions significantly increased the risk of developing acute hyponatraemia (OR 17.22; 95% CI 8.67 to 34.2), and resulted in greater patient morbidity. CONCLUSIONS: The current practice of prescribing i.v. maintenance fluids in children is based on limited clinical experimental evidence from poorly and differently designed studies, where bias could possibly raise doubt about the results. They do not provide evidence for optimal fluid and electrolyte homoeostasis in hospitalised children. This systematic review indicates potential harm with hypotonic solutions in children, which can be anticipated and avoided with isotonic solutions. No single fluid rate or composition is ideal for all children. However, isotonic or near-isotonic solutions may be more physiological, and therefore a safer choice in the acute phase of illness and perioperative period.

Safety Climate Survey: reliability of results from a multicenter ICU survey.

BACKGROUND: It is important to understand the clinical properties of instruments used to measure patient safety before they are used in the setting of an intensive care unit (ICU). METHODS: The Safety Climate Survey (SCSu), an instrument endorsed by the Institute for Healthcare Improvement, the Safety Culture Scale (SCSc), and the Safety Climate Mean (SCM), a subset of seven items from the SCSu, were administered in four Canadian university affiliated ICUs. All staff including nurses, allied healthcare professionals, non-clinical staff, intensivists, and managers were invited to participate in the cross sectional survey. RESULTS: The response rate was 74% (313/426). The internal consistency of the SCSu and SCSc was 0.86 and 0.80, respectively, while the SCM performed poorly at 0.51. Because of poor internal consistency, no further analysis of the SCM was therefore performed. Test-retest reliability of the SCSu and SCSc was 0.92. Out of a maximum score of 5, the mean (SD) scores of the SCSu and SCSc were 3.4 (0.6) and 3.4 (0.7), respectively. No differences were noted between the three medical-surgical and one cardiovascular ICU. Managers perceived a significantly more positive safety climate than other staff, as measured by the SCSu and SCSc. These results need to be interpreted cautiously because of the small number of management participants. CONCLUSIONS: Of the three instruments, the SCSu and SCSc appear to be measuring one construct and are sufficiently reliable. Future research should examine the properties of patient safety instruments in other ICUs, including responsiveness to change, to ensure that they are valid outcome measures for patient safety initiatives.

Estimating fetal weight in patients with preterm premature rupture of the membranes.

Fetal weight estimation was performed in 58 women with preterm premature rupture of the membranes within 4 days of delivery. Of twelve formulas evaluated, only two met the requirements for clinical use (i.e., they had a small mean percent error and a high correlation). However, both had high random error, which may be attributable to the very low birth weights studied.

Electrolytic liver ablation is not associated with evidence of a systemic inflammatory response syndrome.

BACKGROUND: Local ablation has been proposed for treatment of liver tumours. Cryoshock, a variant of the systemic inflammatory response syndrome (SIRS), is a potentially fatal complication of cryoablation caused by systemic release of necrotic breakdown products from ablated liver. The proinflammatory cytokines tissue necrosis factor (TNF) alpha and interleukin (IL) 1 are important mediators of this response. This study assessed the risk of SIRS complicating electrolytic liver ablation by measuring circulating levels of inflammatory cytokines, other inflammatory markers and clinical markers of organ function. METHODS: Electrolytic liver ablation was performed in 16 pigs and four pigs served as controls. Platelet count, and serum levels of urea, creatinine, liver enzymes, C-reactive protein (CRP), TNF-alpha and IL-1beta were measured before treatment and for 72 h after the procedure. RESULTS: There were significant dose-related increases in CRP and alanine aminotransferase levels with liver electrolysis. There was no significant derangement in renal function or platelet count following ablation. A rise in serum TNF-alpha and IL-1beta levels was not associated with liver electrolysis. CONCLUSION: There was no evidence of organ failure or significantly raised levels of proinflammatory cytokines as a result of liver electrolysis, suggesting that this is a safe procedure for liver ablation.