Spectroscopic Characterization of Mn1+ Low Oxidation State in Prussian Blue-Based Battery Anodes.

Stabilization of ions in exotic oxidation states is beneficial for the development of new materials for green energy technologies. Exotic Mn1+ was proposed to play a role in the function of sodium-based Prussian blue analogues (PBA) batteries, a highly sought-out technology for industrial energy storage. Here, we report the detailed electronic structure characterization of uncharged and charged sodium-based manganese hexacyanomanganate anodes via Mn K-edge X-ray absorption spectroscopy (XAS), Kß nonresonant X-ray emission (XES), and resonant inelastic X-ray scattering (RIXS). The latter allowed us to obtain site-selective XANES information about two distinct Mn centers. The obtained spectroscopic data represent the first electronic structure characterization of low-spin Mn1+ using hard X-ray RIXS and XES and allowed us to confirm its role in anode reduction. Our experimental approach can be expanded to analysis of analogues with other 3d transition metals broadening the application of exotic ionic states in materials engineering.

Comparison of anterior nares CT values in asymptomatic and symptomatic individuals diagnosed with SARS-CoV-2 in a university screening program.

At our university based high throughput screening program, we test all members of our community weekly using RT-qPCR. RT-qPCR cycle threshold (CT) values are inversely proportional to the amount of viral RNA in a sample and are a proxy for viral load. We hypothesized that CT values would be higher, and thus the viral loads at the time of diagnosis would be lower, in individuals who were infected with the virus but remained asymptomatic throughout the course of the infection. We collected the N1 and N2 target gene CT values from 1633 SARS-CoV-2 positive RT-qPCR tests of individuals sampled between August 7, 2020, and March 18, 2021, at the BU Clinical Testing Laboratory. We matched this data with symptom reporting data from our clinical team. We found that asymptomatic patients had CT values significantly higher than symptomatic individuals on the day of diagnosis. Symptoms were followed by the clinical team for 10 days post the first positive test. Within the entire population, 78.1% experienced at least one symptom during surveillance by the clinical team (n = 1276/1633). Of those experiencing symptoms, the most common symptoms were nasal congestion (73%, n = 932/1276), cough (60.0%, n = 761/1276), fatigue (59.0%, n = 753/1276), and sore throat (53.1%, n = 678/1276). The least common symptoms were diarrhea (12.5%, n = 160/1276), dyspnea on exertion (DOE) (6.9%, n = 88/1276), foot or skin changes (including rash) (4.2%, n = 53/1276), and vomiting (2.1%, n = 27/1276). Presymptomatic individuals, those who were not symptomatic on the day of diagnosis but became symptomatic over the following 10 days, had CT values higher for both N1 (median = 27.1, IQR 20.2-32.9) and N2 (median = 26.6, IQR 20.1-32.8) than the symptomatic group N1 (median = 21.8, IQR 17.2-29.4) and N2 (median = 21.4, IQR 17.3-28.9) but lower than the asymptomatic group N1 (median = 29.9, IQR 23.6-35.5) and N2 (median = 30.0, IQR 23.1-35.7). This study supports the hypothesis that viral load in the anterior nares on the day of diagnosis is a measure of disease intensity at that time.

SPECT/CT Imaging of 111Ag for the Preclinical Evaluation of Silver-Based Antimicrobial Nanomedicines.

With the growing interest in developing silver-based antimicrobials, there is a need to better understand the behavior of silver within biological systems. To address this, we showed that single-photon emission computed tomography (SPECT) is a suitable method to noninvasively image 111Ag-labeled compounds in mice. Formed by neutron irradiation of palladium foil, 111Ag can be rapidly isolated with a high degree of purity and stably incorporated into antimicrobial silver nanoparticles. The imaging showed that nanoparticles are retained in the lungs for up to 48 h following intratracheal instillation, with limited uptake into the systemic circulation or organs of the reticuloendothelial system. Furthermore, in a mouse model of pulmonary Pseudomonas aeruginosa infection, the nanoparticles reduced the bacterial burden by 11.6-fold without inducing the production of pro-inflammatory mediators. Overall, SPECT imaging with 111Ag is a useful tool for noninvasively visualizing the biodistribution of silver-containing compounds in rodents. This knowledge of how silver nanoparticles distribute in vivo can be used to predict their therapeutic efficacy.

An Overview of Biological and Computational Methods for Designing Mechanism-Informed Anti-biofilm Agents.

Bacterial biofilms are complex and highly antibiotic-resistant aggregates of microbes that form on surfaces in the environment and body including medical devices. They are key contributors to the growing antibiotic resistance crisis and account for two-thirds of all infections. Thus, there is a critical need to develop anti-biofilm specific therapeutics. Here we discuss mechanisms of biofilm formation, current anti-biofilm agents, and strategies for developing, discovering, and testing new anti-biofilm agents. Biofilm formation involves many factors and is broadly regulated by the stringent response, quorum sensing, and c-di-GMP signaling, processes that have been targeted by anti-biofilm agents. Developing new anti-biofilm agents requires a comprehensive systems-level understanding of these mechanisms, as well as the discovery of new mechanisms. This can be accomplished through omics approaches such as transcriptomics, metabolomics, and proteomics, which can also be integrated to better understand biofilm biology. Guided by mechanistic understanding, in silico techniques such as virtual screening and machine learning can discover small molecules that can inhibit key biofilm regulators. To increase the likelihood that these candidate agents selected from in silico approaches are efficacious in humans, they must be tested in biologically relevant biofilm models. We discuss the benefits and drawbacks of in vitro and in vivo biofilm models and highlight organoids as a new biofilm model. This review offers a comprehensive guide of current and future biological and computational approaches of anti-biofilm therapeutic discovery for investigators to utilize to combat the antibiotic resistance crisis.

Utilizing Organoid and Air-Liquid Interface Models as a Screening Method in the Development of New Host Defense Peptides.

Host defense peptides (HDPs), also known as antimicrobial peptides, are naturally occurring polypeptides (~12-50 residues) composed of cationic and hydrophobic amino acids that adopt an amphipathic conformation upon folding usually after contact with membranes. HDPs have a variety of biological activities including immunomodulatory, anti-inflammatory, anti-bacterial, and anti-biofilm functions. Although HDPs have the potential to address the global threat of antibiotic resistance and to treat immune and inflammatory disorders, they have yet to achieve this promise. Indeed, there are several challenges associated with bringing peptide-based drug candidates from the lab bench to clinical practice, including identifying appropriate indications, stability, toxicity, and cost. These challenges can be addressed in part by the development of innate defense regulator (IDR) peptides and peptidomimetics, which are synthetic derivatives of HDPs with similar or better efficacy, increased stability, and reduced toxicity and cost of the original HDP. However, one of the largest gaps between basic research and clinical application is the validity and translatability of conventional model systems, such as cell lines and animal models, for screening HDPs and their derivatives as potential drug therapies. Indeed, such translation has often relied on animal models, which have only limited validity. Here we discuss the recent development of human organoids for disease modeling and drug screening, assisted by the use of omics analyses. Organoids, developed from primary cells, cell lines, or human pluripotent stem cells, are three-dimensional, self-organizing structures that closely resemble their corresponding in vivo organs with regards to immune responses, tissue organization, and physiological properties; thus, organoids represent a reliable method for studying efficacy, formulation, toxicity and to some extent drug stability and pharmacodynamics. The use of patient-derived organoids enables the study of patient-specific efficacy, toxicogenomics and drug response predictions. We outline how organoids and omics data analysis can be leveraged to aid in the clinical translation of IDR peptides.

Polymorphisms in the P2X7 receptor, and differential expression of Toll-like receptor-mediated cytokines and defensins, in a Canadian Indigenous group.

Canadian Indigenous peoples (First Nations and Inuit) exhibit a high burden of infectious diseases including tuberculosis influenced by societal factors, and biological determinants. Toll-like receptor (TLR)-mediated innate immune responses are the first line of defence against infections. We examined the production of a panel of 30 cytokines in peripheral blood-derived mononuclear cells (PBMC) isolated from Indigenous and non-Indigenous participants, following stimulation with five different TLR ligands. The levels of TLR-induced pro-inflammatory cytokines such as IL-12/23p40, IL-16, and IFN-γ, and chemokines (MCP-4, MDC and eotaxin) were different between Indigenous compared to non-Indigenous participants. Antimicrobial cationic host defence peptides (CHDP) induced by TLR activation are critical for resolution of infections and modulate the TLR-to-NFκB pathway to alter downstream cytokine responses. Therefore, we examined the expression of human CHDP defensins and cathelicidin in PBMC. mRNA expression of genes encoding for def-A1 and def-B1 were significantly higher following stimulation with TLR ligands in Indigenous compared to non-Indigenous participants. The purinergic receptor P2X7 known to be activated by ATP released following TLR stimulation, is a receptor for CHDP. Therefore, we further examined single nucleotide polymorphisms (SNP) in P2X7. Indigenous participants had a significantly higher percentage of a P2X7 SNP which is associated with reduced function and lower ability to clear infections. These results suggest that a higher frequency of non-functional P2X7 receptors may influence the activity of downstream immune mediators required for resolution of infections such as pro-inflammatory cytokines and CHDP defensins, thus contributing to higher burden of infections in Indigenous population.

Immunomodulatory Functions of the Human Cathelicidin LL-37 (aa 13-31)-Derived Peptides are Associated with Predicted α-Helical Propensity and Hydrophobic Index.

The anti-endotoxin activity of the cationic peptide LL-37 and its derivative IG-19 is attributed to electrostatic interaction of the peptides' positive charge with negatively charged bacterial lipopolysaccharides (LPS), and in part to the alteration of intracellular mechanisms independent of peptide binding to LPS. We examined the immunomodulatory responses induced by IG-19 and four IG-19-derived scrambled peptides (IG-19a-d), in the presence and absence of LPS, in macrophages and peripheral blood-derived mononuclear cells. All peptides had identical net charge (+5) and amino acid composition, but different hydrophobicity and α-helical propensity. Peptide IG-19 suppressed LPS-induced cytokine/chemokine production by >90%, IG-19a and IG-19b suppressed it by 40-50%, and IG-19c and IG-19d did not suppress cytokine/chemokine production at all. In silico prediction algorithms and the peptide retention time (RT) on a C18 RP HPLC column indicated a linear association between α-helical propensity and hydrophobicity with the ability of the peptides to inhibit LPS-induced responses. Peptide RT exhibited a significant correlation (>70%) between the suppression of LPS-induced cytokine/chemokine production and peptide-induced production of the anti-inflammatory cytokine IL-1RA. These results indicate that RT on a C18 column can be used as a predictor for the immunomodulatory functions of cationic peptides. Overall, we demonstrated that the immunomodulatory functions of LL-37-derived peptides with identical positive charge and amino acid composition are directly associated with the predicted α-helical propensity and hydrophobicity of the peptides.

Host Defense Peptide LL-37-Mediated Chemoattractant Properties, but Not Anti-Inflammatory Cytokine IL-1RA Production, Is Selectively Controlled by Cdc42 Rho GTPase via G Protein-Coupled Receptors and JNK Mitogen-Activated Protein Kinase.

The human host defense peptide LL-37 promotes immune activation such as induction of chemokine production and recruitment of leukocytes. Conversely, LL-37 also mediates anti-inflammatory responses such as production of anti-inflammatory cytokines, e.g., IL-1RA, and the control of pro-inflammatory cytokines, e.g., TNF. The mechanisms regulating these disparate immunomodulatory functions of LL-37 are not completely understood. Rho GTPases are GTP-binding proteins that promote fundamental immune functions such as chemokine production and recruitment of leukocytes. However, recent studies have shown that distinct Rho proteins can both negatively and positively regulate inflammation. Therefore, we interrogated the role of Rho GTPases in LL-37-mediated immunomodulation. We demonstrate that LL-37-induced production of chemokines, e.g., GRO-α and IL-8 is largely dependent on Cdc42/Rac1 Rho GTPase, but independent of the Ras pathway. In contrast, LL-37-induced production of the anti-inflammatory cytokine IL-1RA is not dependent on either Cdc42/Rac1 RhoGTPase or Ras GTPase. Functional studies confirmed that LL-37-induced recruitment of leukocytes (monocytes and neutrophils) is also dependent on Cdc42/Rac1 RhoGTPase activity. We demonstrate that Cdc42/Rac1-dependent bioactivity of LL-37 involves G-protein-coupled receptors (GPCR) and JNK mitogen-activated protein kinase (MAPK) signaling, but not p38 or ERK MAPK signaling. We further show that LL-37 specifically enhances the activity of Cdc42 Rho GTPase, and that the knockdown of Cdc42 suppresses LL-37-induced production of chemokines without altering the peptide's ability to induce IL-1RA. This is the first study to demonstrate the role of Rho GTPases in LL-37-mediated responses. We demonstrate that LL-37 facilitates chemokine production and leukocyte recruitment engaging Cdc42/Rac1 Rho GTPase via GPCR and the JNK MAPK pathway. In contrast, LL-37-mediated anti-inflammatory cytokine IL-1RA production is independent of either Rho or Ras GTPase. The results of this study suggest that Cdc42 Rho GTPase may be the molecular switch that controls the opposing functions of LL-37 in the process of inflammation.

Influence of muscle fiber type composition on early fat accumulation under high-fat diet challenge.

OBJECTIVE: To investigate whether differences in muscle fiber types affect early-stage fat accumulation, under high fat diet challenge in mice. METHODS: Twelve healthy male C57BL/6 mice experienced with short-term (6 weeks) diet treatment for the evaluation of early pattern changes in muscular fat. The mice were randomly divided into two groups: high fat diet (n = 8) and normal control diet (n = 4). Extra- and intra-myocellular lipid (EMCL and IMCL) in lumbar muscles (type I fiber predominant) and tibialis anterior (TA) muscle (type II fiber predominant) were determined using magnetic resonance spectroscopy (MRS). Correlation of EMCL, IMCL and their ratio between TA and lumbar muscles was evaluated. RESULTS: EMCL increased greatly in both muscle types after high fat diet. IMCL in TA and lumbar muscles increased to a much lower extent, with a slightly greater increase in TA muscles. EMCLs in the 2 muscles were positively correlated (r = 0.84, p = 0.01), but IMCLs showed a negative relationship (r = -0.84, p = 0.01). In lumbar muscles, high fat diet significantly decreased type I fiber while it increased type II fiber (all p≤0.001). In TA muscle, there was no significant fiber type shifting (p>0.05). CONCLUSIONS: Under short-time high fat diet challenge, lipid tends to initially accumulate extra-cellularly. In addition, compared to type II dominant muscle, Type I dominant muscle was less susceptible to IMCL accumulation but more to fiber type shifting. These phenomena might reflect compensative responses of skeletal muscle to dietary lipid overload in order to regulate metabolic homeostasis.

The well-being of community-dwelling near-centenarians and centenarians in Hong Kong: a qualitative study.

BACKGROUND: Hong Kong has one of the highest life expectancy rankings in the world. The number of centenarians and near-centenarians has been increasing locally and internationally. The relative growth of this population is a topic of immense importance for population and health policy makers. Living long and living well are two overlapping but distinct research topics. We previously conducted a quantitative study on 153 near-centenarians and centenarians to explore a wide range of biopsychosocial correlates of health and "living long". This paper reports a follow-up qualitative study examining the potential correlates of "living well" among near-centenarians and centenarians in Hong Kong. METHODS: Six cognitively, physically, and psychologically sound community-dwelling elders were purposively recruited from a previous quantitative study. Semi-structured interviews were conducted. RESULTS: Four major themes related to living long and well emerged from the responses of the participants: (a) Positive relations with others, (b) Positive events and happiness, (c) Hope for the future, and (d) Positive life attitude. Specifically, we found that having good interpersonal relationships, possessing a collection of positive life events, and maintaining salutary attitudes towards life are considered as important to psychological well-being by long-lived adults in Hong Kong. Most participants perceived their working life as most important to their life history and retired at very old ages. CONCLUSIONS: These findings also shed light on the relationships between health, work, and old age.

Human cathelicidin LL-37-derived peptide IG-19 confers protection in a murine model of collagen-induced arthritis.

Current therapies for autoimmune chronic inflammatory diseases e.g. rheumatoid arthritis (RA) include inhibitors of inflammatory cytokines. However, these therapies can result in increased risk of infections. There is a need to explore alternate strategies that can control inflammation without compromising the innate ability to resolve infections. In this study, we examined the effect of small peptides derived from endogenous cathelicidin peptides in a murine model of collagen-induced arthritis (CIA). Cathelicidins are immunomodulatory peptides known to control infections. We demonstrate that the administration of the peptide IG-19, which represents an internal segment of the human cathelicidin LL-37, decreased disease severity and significantly reduced the serum levels of antibodies against collagen type II in the CIA model. IG-19 peptide reduced cellular infiltration in joints, prevented cartilage degradation and suppressed pro-inflammatory cytokines in the CIA mice. We also showed that not all cathelicidin-derived peptides exhibit similar functions. A bovine cathelicidin-derived peptide IDR-1018 did not exhibit the beneficial effects observed with the human cathelicidin LL-37-derived peptide IG-19, in the same murine model of CIA. This is the first study to provide evidence demonstrating the ability of a peptide derived from the human cathelicidin LL-37 to alleviate the arthritic disease process in a murine model of RA. Our results has lead us to propose a new approach for controlling autoimmune chronic inflammatory disorders such as RA, by using specific synthetic derivatives of endogenous host defence peptides. Cathelicidin-derived peptides are particularly attractive for their dual antimicrobial and anti-inflammatory actions.

Current and potential treatments for cervical cancer.

Cervical cancer is the third most common carcinoma in women worldwide. Despite increasing efforts to improve therapy in this disease, a significant proportion of women still die, mostly from recurrent or chemoresistant disease. This review discusses current treatments for early cervical cancer, advanced disease, and recurrent cervical cancer, and covers concurrent chemoradiation, neoadjuvant chemotherapy before surgery and radiation, single agent treatment, combination treatment, platinum-based and non-platinum based therapy. We also discuss promising therapeutics trategies for cervical cancer including targeted therapy, cell-based therapy, combined siRNA and chemotherapy, and immunotherapy.

Defining TNF-α and IL-1ß induced nascent proteins: combining bio-orthogonal non-canonical amino acid tagging and proteomics.

An impediment in the development of new therapeutic strategies for chronic inflammatory diseases is the limited understanding of underlying molecular mechanisms. The objective of this study was to identify newly synthesized (nascent) proteins induced by critical inflammatory cytokines TNF-α and IL-1ß in human monocytic THP-1 cells. We optimized methods to combine two different approaches, bio-orthogonal non-canonical amino acid tagging (BONCAT) along with proteomics using isobaric tags (iTRAQ). BONCAT employed the incorporation of l-azidohomoalanine (AHA), an analog of methionine, into TNF-α or IL-1ß induced nascent proteins. The AHA-containing nascent proteins were tagged with alkyne-biotin to allow enrichment using avidin affinity purification. The differential expressions of the enriched proteins were further determined using iTRAQ reagents and mass spectrometry (MS). The combination of BONCAT and proteomics represents a unique approach that has uncovered the nascent proteome induced by inflammatory cytokines TNF-α and IL-1ß.

Stapled versus handsewn methods for ileocolic anastomoses.

BACKGROUND: Ileocolic anastomoses are commonly performed for right-sided colon cancer and Crohn's disease. The anastomosis may be constructed using a linear cutter stapler or by suturing. Individual trials comparing stapled versus handsewn ileocolic anastomoses have found little difference in the complication rate but they have lacked adequate power to detect potential small difference. This is an update of a Cochrane review first published in 2007. OBJECTIVES: To compare outcomes of ileocolic anastomoses performed using stapling and handsewn techniques. The hypothesis tested was that the stapling technique is associated with fewer complications. SEARCH STRATEGY: MEDLINE, EMBASE, Cochrane Colorectal Cancer Group specialised register SR-COLOCA, Cochrane Library were searched for randomised controlled trials comparing use of a linear cuter stapler with any type of suturing technique for ileocolic anastomoses in adults from 1970 to 2005 and were updated in December 2010. Abstracts presented to the following society meetings between 1970 and 2010 were handsearched: American Society of Colon and Rectal Surgeons, the Association of Coloproctology of Great Britain and Ireland, European Association of Coloproctology. SELECTION CRITERIA: Randomised controlled trials comparing use of linear cutter stapler (isoperistaltic side to side or functional end to end) with any type of suturing technique in adults. DATA COLLECTION AND ANALYSIS: Eligible studies were selected and their methodological quality assessed. Relevant results were extracted and missing data sought from the authors. RevMan 5 was used to perform meta-analysis when there were sufficient data. Sub-group analyses for cancer inflammatory bowel disease as indication for ileocolic anastomoses were performed. MAIN RESULTS: After obtaining individual data from authors for studies that include other anastomoses, seven trials (including one unpublished) with 1125 ileocolic participants (441 stapled, 684 handsewn) were included. The five largest trials had adequate allocation concealment.Stapled anastomosis was associated with significantly fewer anastomotic leaks compared with handsewn (S=11/441, HS=42/684, OR 0.48 [0.24, 0.95] p=0.03). One study performed routine radiology to detect asymptomatic leaks. For the sub-group of 825 cancer patients in four studies, stapled anastomosis led to significantly fewer anastomotic leaks (S=4/300, HS=35/525, OR 0.28 [0.10, 0.75] p=0.01). In subgroup analysis of non-cancer patients (3 studies, 264 patients) there were no differences for any reported outcomes. All other outcomes: stricture, anastomotic haemorrhage, anastomotic time, re-operation, mortality, intra-abdominal abscess, wound infection, length of stay, showed no significant difference. AUTHORS' CONCLUSIONS: Stapled functional end to end ileocolic anastomosis is associated with fewer leaks than handsewn anastomosis.

Inflammatory cytokines IL-32 and IL-17 have common signaling intermediates despite differential dependence on TNF-receptor 1.

Cytokines IL-32 and IL-17 are emerging as critical players in the pathophysiology of immune-mediated chronic inflammatory diseases. It has been speculated that the molecular mechanisms governing IL-32- and IL-17-mediated cellular responses are differentially dependent on the TNF pathway. In this study, kinome analysis demonstrated that following stimulation with cytokine IL-32, but not IL-17, there was increased phosphorylation of a peptide target corresponding to TNF-R1. Consistent with this observation, blocking TNF-R1 resulted in a suppression of IL-32-induced downstream responses, indicating that IL-32-mediated activity may be dependent on TNF-R1. In contrast, blocking TNF-R1 did not affect IL-17-induced downstream responses. Kinome analysis also implicated p300 (transcriptional coactivator) and death-associated protein kinase-1 (DAPK-1) as signaling intermediates for both IL-32 and IL-17. Phosphorylation of p300 and DAPK-1 upon stimulation with either IL-32 or IL-17 was confirmed by immunoblots. The presence of common targets was supported by results demonstrating similar downstream responses induced in the presence of IL-32 and IL-17, such as transcriptional responses and the direct activation of NF-κB. Furthermore, knockdown of p300 and DAPK-1 altered downstream responses induced by IL-32 and IL-17, and impacted certain cellular responses induced by TNF-α and IL-1ß. We hypothesize that p300 and DAPK-1 represent nodes where the inflammatory networks of IL-32 and IL-17 overlap, and that these proteins would affect both TNF-R1-dependent and -independent pathways. Therefore, p300 and DAPK-1 are viable potential therapeutic targets for chronic inflammatory diseases.

Derivation of a prognostic score for identifying critically ill patients in an emergency department resuscitation room.

INTRODUCTION: Several prognostic scores exist for critically ill patients, including APACHE II, Revised Trauma Score (RTS), Rapid Emergency Medicine Score (REMS) and Modified Early Warning Score (MEWS). However, there is no widely used score specifically designed to predict the likelihood of early intensive care unit (ICU) admission or death in undifferentiated emergency department (ED) resuscitation room patients. We aimed to derive such a score and compare it with other similar scores. METHODS: This was a single centre study of consecutive adult resuscitation room patients over one month. Physiological and blood test variables were compared according to the composite primary outcome: admission to ICU or death within 7 days of attendance. Multivariate logistic regression was used to derive a prediction score which was compared with other scores using ROC (receiver operating characteristic) analysis. RESULTS: 330 patients were included in the study, of whom 77 were admitted to ICU or died within 7 days. A prediction score was derived using the following parameters: systolic blood pressure; Glasgow coma score; blood glucose; bicarbonate; white cell count; and a history of metastates. This score significantly out-performed APACHE II, RTS, REMS and MEWS with an area under the ROC curve of 0.909 (95% CI 0.872-0.938). CONCLUSION: The Prince of Wales Emergency Department Score (PEDS) is a new prognostic score to predict the likelihood of early ICU admission or death in undifferentiated resuscitation room patients. Further studies are needed to validate and refine this potentially useful tool.

The role of radiofrequency ablation in the treatment of primary and metastatic tumours of the liver: initial lessons learned.

AIM: The majority of patients with hepatic malignancies are not suitable for potentially curative resection due to tumour size, location, inadequate hepatic reserve or widely spread disease. Radiofrequency ablation (RFA) is a novel technique of local tumour destruction by heat. The aim of this study was to report the initial experience with RFA in the management of primary and metastatic liver tumours in New Zealand. METHODS: Patients who underwent RFA between February 2000 and August 2001 were included. The clinical, pathological and follow-up information of individual patients entered prospectively on a computerised database was collated and analysed. RESULTS: Thirty one procedures were performed in 30 patients (18 male, median age 58 years). Nineteen procedures were performed percutaneously under ultrasound guidance and twelve were carried out as part of a surgical procedure. Eight patients had primary tumours, and 22 patients had metastatic tumours (colorectal 9, neuroendocrine 7, non-colorectal non-neuroendocrine 6). The median diameter of treated lesions was 25 mm (range 5 60 mm). The median number of treated lesions per patient was 2 (range 1 6). Twenty four of the 31 procedures were classified as curative (all disease treated). Six patients with neuroendocrine tumours underwent cytoreduction only and were classified as palliative. Eight patients (4 percutaneous, 4 surgical) developed complications leading to 3 prolonged hospital stays (bile leak, abscess and burn). There was no treatment-related mortality. At a median follow up of 12 months (range 1 22 months), 6 patients (all treated with percutaneous RFA) have developed tumour recurrence in treated lesions, 5 patients have developed new liver lesions, 16 are alive and disease free, and 3 have developed extra hepatic disease. CONCLUSIONS: RFA is safe but significant complications can occur. RFA and enteral resection should not be undertaken together, as there is an increased risk of hepatic sepsis and abscess. RFA performed percutaneously is associated with a higher rate of recurrence than RFA performed at operation.