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.

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.

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.

Fractional flow reserve (FFR) versus angiography in guiding management to optimise outcomes in non-ST segment elevation myocardial infarction (FAMOUS-NSTEMI) developmental trial: cost-effectiveness using a mixed trial- and model-based methods.

BACKGROUND: In the Fractional flow reserve (FFR) versus angiography in guiding management to optimise outcomes in non-ST elevation myocardial infarction (FAMOUS) clinical trial, FFR was shown to significantly reduce coronary revascularisation, compared to visual interpretation of standard coronary angiography without FFR. We estimated the cost-effectiveness from a UK National Health Service perspective, based on the results of FAMOUS. METHODS: A mixed trial- and model-based approach using decision and statistical modelling was used. Within-trial (1-year) costs and QALYs were assembled at the individual level and then modelled on subsequent management strategy [coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI) or medical therapy (MT)] and major adverse coronary events (death, MI, stroke and revascularisation). One-year resource uses included: material, hospitalisation, medical, health professional service use and events. Utilities were derived from individual EQ5D responses. Unit costs were derived from the literature. Outcomes were extended to a lifetime on the basis of MACE during the 1st year. Costs and QALYs were modelled using generalized linear models whilst MACE was modelled using logistic regression. The analysis adopted a payer perspective. Costs and outcomes were discounted at 3.5 %. RESULTS: Costs were related to the subsequent management strategy and MACE whilst QALYs were not. FFR led to a modest cost increase, albeit an imprecise increase, over both the trial [£112 (-£129 to £357)] and lifetime horizons [£133 (-£199 to £499)]. FFR led to a small, albeit imprecise, increase in QALYs over both the trial [0.02 (-0.03 to 0.06)] and lifetime horizons [0.03 (-0.21 to 0.28)]. The mean ICER was £7516/QALY and £4290/QALY over the trial and lifetime horizons, respectively. Decision remained high; FFR had 64 and 59 % probability of cost-effectiveness over trial and lifetime horizons, respectively. CONCLUSIONS: FFR was cost-effective at the mean, albeit with considerable decision uncertainty. Uncertainty can be reduced with more information on long-term health events.

The Clinical Utilisation of Respiratory Elastance Software (CURE Soft): a bedside software for real-time respiratory mechanics monitoring and mechanical ventilation management.

BACKGROUND: Real-time patient respiratory mechanics estimation can be used to guide mechanical ventilation settings, particularly, positive end-expiratory pressure (PEEP). This work presents a software, Clinical Utilisation of Respiratory Elastance (CURE Soft), using a time-varying respiratory elastance model to offer this ability to aid in mechanical ventilation treatment. IMPLEMENTATION: CURE Soft is a desktop application developed in JAVA. It has two modes of operation, 1) Online real-time monitoring decision support and, 2) Offline for user education purposes, auditing, or reviewing patient care. The CURE Soft has been tested in mechanically ventilated patients with respiratory failure. The clinical protocol, software testing and use of the data were approved by the New Zealand Southern Regional Ethics Committee. RESULTS AND DISCUSSION: Using CURE Soft, patient's respiratory mechanics response to treatment and clinical protocol were monitored. Results showed that the patient's respiratory elastance (Stiffness) changed with the use of muscle relaxants, and responded differently to ventilator settings. This information can be used to guide mechanical ventilation therapy and titrate optimal ventilator PEEP. CONCLUSION: CURE Soft enables real-time calculation of model-based respiratory mechanics for mechanically ventilated patients. Results showed that the system is able to provide detailed, previously unavailable information on patient-specific respiratory mechanics and response to therapy in real-time. The additional insight available to clinicians provides the potential for improved decision-making, and thus improved patient care and outcomes.

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.

Detection of transient regional myocardial ischemia using body surface Delta map in patients referred for myocardial perfusion imaging--a pilot study.

BACKGROUND: The diagnosis of transient regional myocardial ischemia (TRMI) in patients presenting with stable chest pain is a challenge. Exercise Tolerance Test (ETT) is no longer recommended in most cases due to its flaws. Alternative tests are more expensive and less readily available. The BSM Delta map is an intuitive color display of digitally subtracted ST-segment shift derived from two 80-electrode BSM recordings at baseline and at peak stress, and has shown promise as a tool for detection of TRMI. OBJECTIVES: The purpose of this pilot study was to assess the feasibility of BSM Delta map as a tool to detect TRMI using dobutamine stress ECG gated single-photon emission computed tomography myocardial perfusion imaging (MPI) as a reference. METHOD: Forty consecutive patients were recruited who were referred for MPI with a history of angina-like symptoms. The BSM Delta map was derived from two 80-electrode body surface mapping system recordings carried out simultaneously with MPI at (a) baseline and (b) peak dobutamine stress. Standard 12-lead ECGs were also recorded at the same time points. RESULTS: The mean patient age was 68±7.1years, and 52% (21/40) were female. Using MPI as the reference the sensitivity of BSM Delta map was 82% (9/11) and specificity was 86% (25/29) (95% CI 0.688-0.992), positive likelihood ratio 5.93 (95% CI 2.29-15), negative likelihood ratio 0.21 (95% CI 0.06-0.75). The sensitive of the 12-lead ECG was 36% (4/11) and specificity was 76% (22/29) (95% CI 0.356-0.767), positive likelihood ratio 1.51 (95% CI 0.55-4.15), negative likelihood ratio 0.84 (95% CI 0.51-1.37). BSM Delta map is more sensitive and specific (McNemar's chi-square test p=0.03 (95% CI, 0.448-0.924). The PPV and NPV for BSM Delta map were 69% (9/13) and 93% (25/27) respectively, compared with 36% (4/11) and 76% (22/29) for 12-lead ECG. CONCLUSION: This pilot study confirms the feasibility of using Delta map in this context and suggests that it has promising diagnostic accuracy and is superior to the 12-lead ECG. It could potentially represent a clinically suitable screening tool for TRMI in patients presenting with stable chest pain, since it is near patient and requires little specialist training for acquisition and interpretation. A larger clinical study is now required.

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.

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.

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.

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.

Cardiac MRI of myocardial salvage at the peri-infarct border zones after primary coronary intervention.

The purpose of this study was to use cardiac MRI to define the morphology of the reversibly injured peri-infarct border zone in patients treated with primary percutaneous coronary intervention (PPCI) for acute ST elevation myocardial infarction. In 15 patients, T2-weighted myocardial edema imaging was used to identify the ischemic bed or area at risk (AAR), and late gadolinium enhancement imaging was used to measure infarct size. Images were coregistered, and the boundaries of edema and necrosis were defined using an edge-detection methodology. We observed that infarction always involved the subendocardium but showed variable transmural extension within the AAR. The mean infarct size was 22 +/- 19% (range: 8-48%), and the mean AAR was 34 +/- 12% (range: 20-57%). The infarcted myocardium was always smaller than the ischemic AAR and involved between 34% and 99% (mean 72 +/- 21%) of the ischemic bed primarily due to variation in transmural infarct extension. Although a lateral border zone of potentially viable myocardium was often present, its extent was limited (range: 0-11 mm, mean: 5 +/- 4 mm). As a result of this, infarcts occupied the majority (range: 70-100%, mean: 82 +/- 13%) of the width of the AAR. The mean fractional wall thickening in the infarcted, peri-infarcted, and remote myocardium was 3.6 +/- 16.0%, 40.5 +/- 26.4%, and 88.2 +/- 39.3%, respectively. These findings demonstrate that myocardial salvage is largely determined by epicardial limitation of the infarct within the ischemic AAR after PPCI. The lateral boundaries of necrosis approximate to the lateral extent of the ischemic bed and systolic wall motion abnormalities extend well beyond the infarct border zone.

Reperfusion hemorrhage following acute myocardial infarction: assessment with T2* mapping and effect on measuring the area at risk.

Research ethics committee approval and informed consent were obtained. The purpose of this study was to assess the feasibility of multiecho T2* mapping of the heart for detecting reperfusion hemorrhage following percutaneous primary coronary intervention (PPCI) for acute myocardial infarction, and to measure the effect of hemorrhage on quantifying the ischemic area at risk (IAR) on T2-weighted magnetic resonance images. Fifteen patients (mean age, 59 years; 13 men, two women) were imaged a mean of 3.2 days following PPCI. The mean area of hemorrhage, indicated by a T2* decay constant of less than 20 msec, was 5.0% +/- 4.9 (standard deviation) at the level of the infarct and this correlated with the infarct (r(2) = 0.76, P < .01) and microvascular obstruction (r(2) = 0.75, P < .01) volumes. When 5% or less hemorrhage was present, the IAR was underestimated by 50% at a standard deviation threshold level of five, compared with a boundary detection tool (21.8% vs 44.0%, P < .05). T2* mapping is feasible for quantifying post-reperfusion hemorrhage and boundary detection is required to accurately assess the IAR when hemorrhage is present.

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.

Sirolimus-eluting and paclitaxel-eluting stents for the treatment of coronary bifurcations.

BACKGROUND: The aim of the study was to compare the outcomes of sirolimus-eluting (SES) and paclitaxel-eluting (PES) stent implantation in coronary bifurcations treated with either a 1-stent or 2-stent strategy. METHODS: The study used a retrospective cohort analysis of consecutive de novo bifurcations, excluding left main, treated with SES or PES between April 2003 and June 2005. RESULTS: We identified 170 bifurcations in 161 patients treated with SES and 119 bifurcations in 112 patients treated with PES. During a median follow-up of 1,061 days (interquartile range 814-1,314), 43 patients (26.7%) in the SES group and 28 (25.0%) in the PES group had a major adverse cardiac event (P = .78). The angiographic restenosis rate per bifurcation was 20.9% and 25.9%, respectively (P = .41). There was no difference overall in the occurrence of target lesion revascularization (TLR) per bifurcation, 22 with SES (12.9%) and 18 with PES (15.1%), P = .61. The TLR rate was similar for SES and PES in bifurcations treated with 1 stent (6.7% vs 11.4%, P = .40) and in bifurcations treated with both branch stenting (20.0% vs 20.4%, P =1.0). CONCLUSIONS: In this cohort, the long-term clinical outcomes appear similar overall between SES and PES in the treatment of coronary bifurcations irrespective of whether a 1-stent or 2-stent strategy was used.