ADCT-602, a Novel PBD Dimer-containing Antibody-Drug Conjugate for Treating CD22-positive Hematologic Malignancies.

Relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) and lymphomas have poor patient outcomes; novel therapies are needed. CD22 is an attractive target for antibody-drug conjugates (ADCs), being highly expressed in R/R B-ALL with rapid internalization kinetics. ADCT-602 is a novel CD22-targeting ADC, consisting of humanized mAb hLL2-C220, site specifically conjugated to the pyrrolobenzodiazepine dimer-based payload tesirine. In preclinical studies, ADCT-602 demonstrated potent, specific cytotoxicity in CD22-positive lymphomas and leukemias. ADCT-602 was specifically bound, internalized, and trafficked to lysosomes in CD22-positive tumor cells; after cytotoxin release, DNA interstrand crosslink formation persisted for 48 hours. In the presence of CD22-positive tumor cells, ADCT-602 caused bystander killing of CD22-negative tumor cells. A single ADCT-602 dose led to potent, dose-dependent, in vivo antitumor activity in subcutaneous and disseminated human lymphoma/leukemia models. Pharmacokinetic analyses (rat and cynomolgus monkey) showed excellent stability and tolerability of ADCT-602. Cynomolgus monkey B cells were efficiently depleted from circulation after one dose. Gene signature association analysis revealed IRAK1 as a potential marker for ADCT-602 resistance. Combining ADCT-602 + pacritinib was beneficial in ADCT-602-resistant cells. Chidamide increased CD22 expression on B-cell tumor surfaces, increasing ADCT-602 activity. These data support clinical testing of ADCT-602 in R/R B-ALL (NCT03698552) and CD22-positive hematologic cancers.

Self-heating allows athermal laser diode wavelength control using a thermally insulating sub-mount over a 70 °C range.

The wavelength of a single frequency quantum dot distributed feedback (DFB) laser operating in the O-band is athermalised over a 74 °C ambient temperature range. Two techniques are presented, one utilising the laser self-heating for tuning control, the other using a resistive heater. Both techniques show greatly improved power efficiency over conventional wavelength control schemes, and both demonstrate wavelength stability of better than 0.1 nm (17.5 GHz) without mode hops over the entire temperature range. The use of a high operating temperature quantum dot laser together with an innovative submount design to increase the thermal impedance of the device enables the improved use of the laser self-heating for wavelength tuning. The submount design entails the laser being suspended over an air gap with the use of glass supports, preventing heat from escaping from the diode.

Association between troponin level and medium-term mortality in 20 000 hospital patients.

INTRODUCTION: Cardiac troponin (cTn) concentrations above the manufacturer recommended upper limit of normal (ULN) are frequently seen in hospital patients without a clinical presentation consistent with type 1 myocardial infarction, and the significance of this is uncertain. The aim of this study was to assess the relationship between medium-term mortality and cTn concentration in a large consecutive hospital population, regardless of whether there was a clinical indication for performing the test. METHOD: This prospective observational study included 20 000 consecutive in-hospital and outpatient patients who had a blood test for any reason at a large teaching hospital, and in whom a hs-cTnI assay was measured, regardless of the original clinical indication. Mortality was obtained via NHS Digital. RESULTS: A total of 20 000 patients were included in the analysis and 18 282 of these (91.4%) did not have a clinical indication for cardiac troponin I (cTnI) testing. Overall, 2825 (14.1%) patients died at a median of 809 days. The mortality was significantly higher if the cTnI concentration was above the ULN (45.3% vs 12.3% p<0.001 log rank). Multivariable Cox analysis demonstrated that the log10 cTnI concentration was independently associated with mortality (HR 1.76 (95% CI 1.65 to 1.88)). Landmark analysis, excluding deaths within 30 days, showed the relationship between cTnI concentration and mortality persisted. CONCLUSION: In a large, unselected hospital population, in 91.4% of whom there was no clinical indication for testing, cTnI concentration was independently associated with medium-term cardiovascular and non-cardiovascular mortality in the statistical model tested.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial.

BACKGROUND: Patients hospitalized with COVID-19 suffer thrombotic complications. Risk factors for poor outcomes are shared with coronary artery disease. OBJECTIVES: To investigate the efficacy of an acute coronary syndrome regimen in patients hospitalized with COVID-19 and coronary disease risk factors. METHODS: A randomized controlled, open-label trial across acute hospitals (United Kingdom and Brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28 days. Primary efficacy and safety outcomes were 30-day mortality and bleeding. The key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, or death). RESULTS: Three hundred twenty patients from 9 centers were randomized. The trial terminated early due to low recruitment. At 30 days, there was no significant difference in mortality (intervention vs control, 11.5% vs 15%; unadjusted odds ratio [OR], 0.73; 95% CI, 0.38-1.41; p = .355). Significant bleeds were infrequent and were not significantly different between the arms (intervention vs control, 1.9% vs 1.9%; p > .999). Using a Bayesian Markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (OR, 1.46; 95% credible interval [CrI], 0.88-2.37; Pr [beta > 0], 93%; adjusted OR, 1.50; 95% CrI, 0.91-2.45; Pr [beta > 0], 95%) and median time to discharge to home was 2 days shorter (95% CrI, -4 to 0; 2% probability that it was worse). CONCLUSION: Acute coronary syndrome treatment regimen was associated with a reduction in the length of hospital stay without an excess in major bleeding. A larger trial is needed to evaluate mortality.

A randomized controlled trial to investigate the use of acute coronary syndrome therapy in patients hospitalized with COVID-19: the COVID-19 Acute Coronary Syndrome trial

BACKGROUND: patients hospitalised with covid-19 suffer thrombotic complications. risk factors for poor outcomes are shared with coronary artery disease. Objectives: to investigate efficacy of an acute coronary syndrome regimen in patients hospitalised with covid-19 and coronary disease risk factors. PATIENTS/METHODS: a randomised controlled open-label trial across acute hospitals (uk and brazil) added aspirin, clopidogrel, low-dose rivaroxaban, atorvastatin, and omeprazole to standard care for 28-days. primary efficacy and safety outcomes were 30-day mortality and bleeding. the key secondary outcome was a daily clinical status (at home, in hospital, on intensive therapy unit admission, death). RESULTS: 320 patients from 9 centres were randomised. the trial terminated early due to low recruitment. at 30 days there was no significant difference in mortality (intervention: 11.5% vs control: 15%, unadjusted or 0.73, 95%ci 0.38 to 1.41, p=0.355). significant bleeds were infrequent and not significantly different between the arms (intervention: 1.9% vs control 1.9%, p>0.999). using a bayesian markov longitudinal ordinal model, it was 93% probable that intervention arm participants were more likely to transition to a better clinical state each day (or 1.46, 95% cri 0.88 to 95 2.37, pr(beta>0) =93%; adjusted or 1.50, 95% cri 0.91 to 2.45, pr(beta>0) =95%) and median time to discharge home was two days shorter (95% cri -4 to 0, 2% probability that it was worse). CONCLUSIONS: acute coronary syndrome treatment regimen was associated with a 99 reduction in the length of hospital stay without an excess in major bleeding. a larger trial is needed to evaluate mortality.

Relation of High-Sensitivity Troponin to 1 Year Mortality in 20,000 Consecutive Hospital Patients Undergoing a Blood Test for Any Reason.

This was an observational study of the 1-year outcomes of the 20,000 patients included in the original CHARIOT study. The aim of the study was to assess the association between high sensitivity troponin I (hs-cTnI) concentration and 1 year mortality in this cohort. The original CHARIOT study included a consecutive cohort of in- and out-patients undergoing blood tests for any reason. Hs-cTnI concentrations were measured regardless of whether the clinician requested them. These results were nested and not revealed to the team unless requested for clinical reasons. One year mortality data was obtained from NHS Digital as originally planned. Overall, 1782 (8.9%) patients had died at 1 year. Multivariable Cox regression analysis showed that a hs-cTnI concentration above the upper limit of normal was independently associated with the hazard of mortality (HR 2.23; 95% confidence intervals 1.97 to 2.52). Furthermore, the log (10) hs-cTnI concentration was independently associated with the hazard of 1 year mortality (HR 1.77; 95% confidence intervals 1.64 to 1.91). In conclusion, in a large, unselected hospital population of both in- and out-patients, in 18,282 (91.4%) of whom there was no clinical indication for testing, hs-cTnI concentration was associated with 1 year mortality.

Electrodeposited Thin-Film Micro-Thermoelectric Coolers with Extreme Heat Flux Handling and Microsecond Time Response.

Thin-film thermoelectric coolers are emerging as a viable option for the on-chip temperature management of electronic and photonic integrated circuits. In this work, we demonstrate the record heat flux handling capability of electrodeposited Bi2Te3 films of 720(±60) W cm-2 at room temperature, achieved by careful control of the contact interfaces to reduce contact resistance. The characteristic parameters of a single leg thin-film devices were measured in situ, giving a Seebeck coefficient of S = -121(±6) µV K-1, thermal conductivity of κ = 0.85(±0.08) W m-1 K-1, electrical conductivity of σ = 5.2(±0.32) × 104 S m-1, and electrical contact resistivity of ∼10-11 Ω m2. These thermoelectric parameters lead to a material ZT = 0.26(±0.04), which, for our device structure, allowed a net cooling of ΔTmax = 4.4(±0.12) K. A response time of τ = 20 µs was measured experimentally. This work shows that with the correct treatment of contact interfaces, electrodeposited thin-film thermoelectrics can compete with more complicated and expensive technologies such as metal organic chemical vapor deposition (MOCVD) multilayers.

The Role of Specific ATP-Binding Cassette Transporters in the Acquired Resistance to Pyrrolobenzodiazepine Dimer-Containing Antibody-Drug Conjugates.

Antibody-drug conjugates (ADC) containing pyrrolobenzodiazepine (PBD) dimers are being evaluated clinically in both hematologic and solid tumors. These include ADCT-301 (camidanlumab tesirine) and ADCT-402 (loncastuximab tesirine) in pivotal phase II trials that contain the payload tesirine, which releases the PBD dimer warhead SG3199. An important consideration in future clinical development is acquired resistance. The aim was to generate and characterize PBD acquired resistant cell lines in both hematologic and solid tumor settings. Human Karpas-299 (ALCL) and NCI-N87 (gastric cancer) cells were incubated with increasing IC50 doses of ADC (targeting CD25 and HER2, respectively) or SG3199 in a pulsed manner until stable acquired resistance was established. The level of resistance achieved was approximately 3,000-fold for ADCT-301 and 3-fold for SG3199 in Karpas-299, and 8-fold for ADCT-502 and 4-fold for SG3199 in NCI-N87. Cross-resistance between ADC and SG3199, and with an alternative PBD-containing ADC or PBD dimer was observed. The acquired resistant lines produced fewer DNA interstrand cross-links, indicating an upstream mechanism of resistance. Loss of antibody binding or internalization was not observed. A human drug transporter PCR Array revealed several genes upregulated in all the resistant cell lines, including ABCG2 and ABCC2, but not ABCB1(MDR1). These findings were confirmed by RT-PCR and Western blot, and inhibitors and siRNA knockdown of ABCG2 and ABCC2 recovered drug sensitivity. These data show that acquired resistance to PBD-ADCs and SG3199 can involve specific ATP-binding cassette drug transporters. This has clinical implications as potential biomarkers of resistance and for the rational design of drug combinations.

Machine learning detection of Atrial Fibrillation using wearable technology.

BACKGROUND: Atrial Fibrillation is the most common arrhythmia worldwide with a global age adjusted prevalence of 0.5% in 2010. Anticoagulation treatment using warfarin or direct oral anticoagulants is effective in reducing the risk of AF-related stroke by approximately two-thirds and can provide a 10% reduction in overall mortality. There has been increased interest in detecting AF due to its increased incidence and the possibility to prevent AF-related strokes. Inexpensive consumer devices which measure the ECG may have the potential to accurately detect AF but do not generally incorporate diagnostic algorithms. Machine learning algorithms have the potential to improve patient outcomes particularly where diagnoses are made from large volumes or complex patterns of data such as in AF. METHODS: We designed a novel AF detection algorithm using a de-correlated Lorenz plot of 60 consecutive RR intervals. In order to reduce the volume of data, the resulting images were compressed using a wavelet transformation (JPEG200 algorithm) and the compressed images were used as input data to a Support Vector Machine (SVM) classifier. We used the Massachusetts Institute of Technology (MIT)-Beth Israel Hospital (BIH) Atrial Fibrillation database and the MIT-BIH Arrhythmia database as training data and verified the algorithm performance using RR intervals collected using an inexpensive consumer heart rate monitor device (Polar-H7) in a case-control study. RESULTS: The SVM algorithm yielded excellent discrimination in the training data with a sensitivity of 99.2% and a specificity of 99.5% for AF. In the validation data, the SVM algorithm correctly identified AF in 79/79 cases; sensitivity 100% (95% CI 95.4%-100%) and non-AF in 328/336 cases; specificity 97.6% (95% CI 95.4%-99.0%). CONCLUSIONS: An inexpensive wearable heart rate monitor and machine learning algorithm can be used to detect AF with very high accuracy and has the capability to transmit ECG data which could be used to confirm AF. It could potentially be used for intermittent screening or continuously for prolonged periods to detect paroxysmal AF. Further work could lead to cost-effective and accurate estimation of AF burden and improved risk stratification in AF.

True 99th centile of high sensitivity cardiac troponin for hospital patients: prospective, observational cohort study.

OBJECTIVE: To determine the distribution, and specifically the true 99th centile, of high sensitivity cardiac troponin I (hs-cTnI) for a whole hospital population by applying the hs-cTnI assay currently used routinely at a large teaching hospital. DESIGN: Prospective, observational cohort study. SETTING: University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom, between 29 June 2017 and 24 August 2017. PARTICIPANTS: 20 000 consecutive inpatients and outpatients undergoing blood tests for any clinical reason. Hs-cTnI concentrations were measured in all study participants and nested for analysis except when the supervising doctor had requested hs-cTnI for clinical reasons. MAIN OUTCOME MEASURES: Distribution of hs-cTnI concentrations of all study participants and specifically the 99th centile. RESULTS: The 99th centile of hs-cTnI for the whole population was 296 ng/L compared with the manufacturer's quoted level of 40 ng/L (currently used clinically as the upper limit of normal; ULN). Hs-cTnI concentrations were greater than 40 ng/L in one in 20 (5.4%, n=1080) of the total population. After excluding participants diagnosed as having acute myocardial infarction (n=122) and those in whom hs-cTnI was requested for clinical reasons (n=1707), the 99th centile was 189 ng/L for the remainder (n=18 171). The 99th centile was 563 ng/L for inpatients (n=4759) and 65 ng/L for outpatients (n=9280). Patients from the emergency department (n=3706) had a 99th centile of 215 ng/L, with 6.07% (n=225) greater than the recommended ULN. 39.02% (n=48) of all patients from the critical care units (n=123) and 14.16% (n=67) of all medical inpatients had an hs-cTnI concentration greater than the recommended ULN. CONCLUSIONS: Of 20 000 consecutive patients undergoing a blood test for any clinical reason at our hospital, one in 20 had an hs-cTnI greater than the recommended ULN. These data highlight the need for clinical staff to interpret hs-cTnI concentrations carefully, particularly when applying the recommended ULN to diagnose acute myocardial infarction, in order to avoid misdiagnosis in the absence of an appropriate clinical presentation. TRIAL REGISTRATION: Clinicaltrials.gov NCT03047785.

Antitumor Activity of MEDI3726 (ADCT-401), a Pyrrolobenzodiazepine Antibody-Drug Conjugate Targeting PSMA, in Preclinical Models of Prostate Cancer.

Prostate-specific membrane antigen (PSMA) is a membrane-bound glutamate carboxypeptidase that is highly expressed in nearly all prostate cancers with the highest expression in metastatic castration-resistant prostate cancer (mCRPC). The prevalence of increased surface expression and constitutive internalization of PSMA make it an attractive target for an antibody-drug conjugate (ADC) approach to treating patients with mCRPC. MEDI3726 (previously known as ADCT-401) is an ADC consisting of an engineered version of the anti-PSMA antibody J591 site specifically conjugated to the pyrrolobenzodiazepine (PBD) dimer tesirine. MEDI3726 specifically binds the extracellular domain of PSMA and, once internalized, releases the PBD dimer to crosslink DNA and trigger cell death. In vitro, MEDI3726 demonstrated potent and specific cytotoxicity in a panel of PSMA-positive prostate cancer cell lines, consistent with internalization and DNA interstrand crosslinking. In vivo, MEDI3726 showed robust antitumor activity against the LNCaP and the castration-resistant CWR22Rv1 prostate cancer cell line xenografts. MEDI3726 also demonstrated durable antitumor activity in the PSMA-positive human prostate cancer patient-derived xenograft (PDX) LuCaP models. This activity correlated with increased phosphorylated Histone H2AX in tumor xenografts treated with MEDI3726. MEDI3726 is being evaluated in a phase I clinical trial as a treatment for patients with metastatic castrate-resistant prostate cancer (NCT02991911). Mol Cancer Ther; 17(10); 2176-86. ©2018 AACR.

Screening for Atrial Fibrillation Using Economical and Accurate Technology (From the SAFETY Study).

The prevalence of atrial fibrillation (AF) is estimated at more than 3% in the adult population and there has been increased interest in screening for AF. In the SAFETY trial we chose to evaluate if inexpensive, wearable, consumer electrocardiography (ECG) sensing devices (Polar-H7 [PH7] and Firstbeat Bodyguard 2 [BG2]), could be used to detect AF accurately. We undertook a case-control study of 418 participants aged >65 (82 with AF and/or flutter at the study visit and 336 without) attending 3 general practice surgeries in Hampshire, UK for a single screening visit. The PH7 and BG2 devices were tested alongside 2 established AF detection devices (AliveCor and WatchBP) in random order and the diagnosis of AF was confirmed by 12-Lead ECG interpreted by a panel of cardiologists. The sensitivity (95% confidence interval [CI] range), specificity (95% CI range), and overall accuracy (95% CI range) of the 4 devices were: AliveCor: 87.8% (78.7% to 94.0%), 98.8% (97.0% to 99.7%), 96.7% (94.4% to 98.2%); WatchBP: 96.3% (89.7% to 99.2%), 93.5% (90.3% to 95.9%), 94.0% (91.3% to 96.1%): PH7: 96.3% (89.7% to 99.2%), 98.2% (96.2% to 99.3%), 97.9% (96.0% to 99.0%). BG2: 96.3% (89.7% to 99.2%), 98.5% (96.6% to 99.5%), 98.1% (96.3% to 99.2%). The PH7 and BG2 devices were highly reliable (the devices acquired sufficient data and obtained a diagnostic result in all but 1 participant on the first attempt). In conclusion, inexpensive, consumer heart rate monitoring devices (PH7 and BG2) can be used to detect AF accurately with sensitivity and specificity >95%. The consumer devices performed as well or better than WatchBP and AliveCor and have the capability to store or transmit ECG data which could be used to confirm AF.

Pre-clinical pharmacology and mechanism of action of SG3199, the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine.

Synthetic pyrrolobenzodiazepine (PBD) dimers, where two PBD monomers are linked through their aromatic A-ring phenolic C8-positions via a flexible propyldioxy tether, are highly efficient DNA minor groove cross-linking agents with potent cytotoxicity. PBD dimer SG3199 is the released warhead component of the antibody-drug conjugate (ADC) payload tesirine (SG3249), currently being evaluated in several ADC clinical trials. SG3199 was potently cytotoxic against a panel of human solid tumour and haematological cancer cell lines with a mean GI50 of 151.5 pM. Cells defective in DNA repair protein ERCC1 or homologous recombination repair showed increased sensitivity to SG3199 and the drug was only moderately susceptible to multidrug resistance mechanisms. SG3199 was highly efficient at producing DNA interstrand cross-links in naked linear plasmid DNA and dose-dependent cross-linking was observed in cells. Cross-links formed rapidly in cells and persisted over 36 hours. Following intravenous (iv) administration to rats SG3199 showed a very rapid clearance with a half life as short as 8 minutes. These combined properties of cytotoxic potency, rapid formation and persistence of DNA interstrand cross-links and very short half-life contribute to the emerging success of SG3199 as a warhead in clinical stage ADCs.

ADCT-402, a PBD dimer-containing antibody drug conjugate targeting CD19-expressing malignancies.

Human CD19 antigen is a 95-kDa type I membrane glycoprotein in the immunoglobulin superfamily whose expression is limited to the various stages of B-cell development and differentiation and is maintained in the majority of B-cell malignancies, including leukemias and non-Hodgkin lymphomas of B-cell origin. Coupled with its differential and favorable expression profile, CD19 has rapid internalization kinetics and is not shed into the circulation, making it an ideal target for the development of antibody-drug conjugates (ADCs) to treat B-cell malignancies. ADCT-402 (loncastuximab tesirine) is a novel CD19-targeted ADC delivering SG3199, a highly cytotoxic DNA minor groove interstrand crosslinking pyrrolobenzodiazepine (PDB) dimer warhead. It showed potent and highly targeted in vitro cytotoxicity in CD19-expressing human cell lines. ADCT-402 was specifically bound, internalized, and trafficked to lysosomes in CD19-expressing cells and, following release of the PBD warhead, resulted in formation of DNA crosslinks that persisted for 36 hours. Bystander killing of CD19- cells by ADCT-402 was also observed. In vivo, single doses of ADCT-402 resulted in highly potent, dose-dependent antitumor activity in several subcutaneous and disseminated human tumor models with marked superiority to comparator ADCs delivering tubulin inhibitors. Dose-dependent DNA crosslinks and γ-H2AX DNA damage response were measured in tumors by 24 hours after single dose administration, whereas matched peripheral blood mononuclear cells showed no evidence of DNA damage. Pharmacokinetic analysis in rat and cynomolgus monkey showed excellent stability and tolerability of ADCT-402 in vivo. Together, these impressive data were used to support the clinical testing of this novel ADC in patients with CD19-expressing B-cell malignancies.

Synthesis and in vitro evaluation of SG3227, a pyrrolobenzodiazepine dimer antibody-drug conjugate payload based on sibiromycin.

A novel pyrrolobenzodiazepine dimer payload, SG3227, was rationally designed based on the naturally occurring antitumour compound sibiromycin. SG3227 was synthesized from a dimeric core in an efficient fashion. An unexpected room temperature Diels-Alder reaction occurred during the final step of the synthesis and was circumvented by use of an iodoacetamide conjugation moiety in place of a maleimide. The payload was successfully conjugated to trastuzumab and the resulting ADC exhibited potent activity against a HER2-expressing human cancer cell line in vitro.

Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload.

Pyrrolobenzodiazepine dimers are an emerging class of warhead in the field of antibody-drug conjugates (ADCs). Tesirine (SG3249) was designed to combine potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics. One of the reactive imines was capped with a cathepsin B-cleavable valine-alanine linker. A robust synthetic route was developed to allow the production of tesirine on clinical scale, employing a flexible, convergent strategy. Tesirine was evaluated in vitro both in stochastic and engineered ADC constructs and was confirmed as a potent and versatile payload. The conjugation of tesirine to anti-DLL3 rovalpituzumab has resulted in rovalpituzumab-tesirine (Rova-T), currently under evaluation for the treatment of small cell lung cancer.

Predictors of inhospital mortality following out-of-hospital cardiac arrest: Insights from a single-centre consecutive case series.

PURPOSE OF THE STUDY: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis despite bystander resuscitation and rapid transfer to hospital. Optimal management of patients after arrival to hospital continues to be contentious, especially the timing of emergency coronary angiography±revascularisation. Robust predictors of inhospital outcome would be of clinical value for initial decision-making. STUDY DESIGN: A retrospective analysis of consecutive patients who presented to a university hospital following OHCA over a 70-month period (2008-2013). Patients were identified from the emergency department electronic patient registration and coding system. For those patients who underwent emergency percutaneous coronary intervention, details were crosschecked with national databases. RESULTS: We identified 350 consecutive patients who were brought to our hospital following OHCA. Return of spontaneous circulation (ROSC) for >20 min was achieved either before arrival or inhospital in 196 individuals. From the 350 subjects, 114 (32.6%) survived to hospital discharge. When sustained ROSC was achieved, either before or inhospital, survival to discharge was 58.2% (114 of 196). Non-shockable rhythm, absence of bystander cardiopulmonary resuscitation, 'downtime' >15 min and initial pH ≤7.11 were predictors of inhospital death. 12% patients who underwent angiography in the presence of ST elevation had no acute coronary occlusion. 21% patients with acute coronary occlusion at angiography did not have ST elevation. CONCLUSIONS: In our cohort of patients with OHCA, those who achieve ROSC had a survival-to-discharge rate of 58.2%. We identified four predictors of inhospital death, which are readily available at the time of patient presentation. Reliance on ST elevation to decide about coronary angiography and revascularisation may be flawed. More data are required.