Dental Surgical Activity in Hospitals during COVID-19: A Nationwide Observational Cohort Study.

INTRODUCTION: The number of surgical extractions performed in hospitals in England remains unclear. This study reports the volume of surgical extractions conducted in hospitals and change in activity during the COVID-19 pandemic. METHODS: We conducted a nationwide observational cohort study using Hospital Episode Statistics (HES) in England for patients undergoing surgical removal of a tooth (defined using OPSC-4 code F09) between April 1, 2015, and December 31, 2020. Procedures were stratified by age, gender, and urgency (elective or nonelective), reported using descriptive statistics, number, and percentage. We conducted post hoc modeling to predict surgical activity to December 2023. In addition, we contrasted this with aggregate national data on simple dental extraction procedures and drainage of dental abscesses in hospital as well as dental activity in general practice. RESULTS: We identified a total of 569,938 episodes for the surgical removal of a tooth (females 57%). Of these, 493,056/569,938 (87%) were for adults and 76,882/569,938 (13%) children ≤18 years. Surgical extractions were most frequent in adult females. Elective cases accounted for 96% (n = 548,805/569,938) of procedures. The median number of procedures carried out per quarter was 27,256, dropping to 12,003 during the COVID-19 pandemic, representing a 56% reduction in activity. This amounted to around 61,058 cancelled procedures. Modeling predicts that this activity has not returned to prepandemic levels. CONCLUSIONS: The number of surgical extractions taking place in hospitals during the pandemic fell by 56%. The true impact of this reduction is unknown, but delayed treatment increases the risk of complications, including life-threatening infections. KNOWLEDGE TRANSFER STATEMENT: The result of this study provides an evidence-based overview of the trends relating to surgical extractions of teeth in England taking place in hospitals. This information can be used to inform service and workforce planning to meet the needs of patients requiring surgical extractions. The data also provide an insight into the oral health needs of the population in England.

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M_{⊙} and 1.0 M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M_{⊙}

IL-1ra polymorphisms and risk of epidural-related maternal fever (EPIFEVER-2): study protocol for a multicentre, observational mechanistic cohort study.

BACKGROUND: Laboratory data suggest that insufficient circulating levels of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) are associated with intrapartum inflammation and epidural-related maternal fever, both of which increase the rate of obstetric interventions and antibiotic use during labour. Genetic polymorphisms strongly influence IL-1ra levels in the general population. We aim to examine the association between IL-1ra polymorphisms and epidural-related maternal fever using Mendelian randomization analysis. METHODS: EPIFEVER-2 is a multicentre UK trial enrolling 637 women receiving epidural analgesia for labour. Blood samples obtained no later than four hours after epidural insertion will provide deoxyribonucleic acid for Taqman single-nucleotide polymorphism genotyping for presence/absence of rs6743376, rs1542176 alleles for IL-1ra, to establish the genetic score. The absence of both alleles is associated with the lowest IL-1ra levels. The primary outcome is pyrexia (>38°C) or intrapartum antibiotic administration. Secondary outcomes include mode of delivery, maternal and neonatal healthcare interventions. RESULTS: The EPIFEVER-2 study was prospectively registered (ISRCTN99641204) following ethical approval. Participant recruitment began in May 2021, with 221 women recruited across three centres as of November 21, 2021. CONCLUSIONS: EPIFEVER-2 will generate the largest prospective dataset detailing the incidence and consequences of epidural-related maternal fever. Using Mendelian randomisation analysis, a causative role for lower IL1-ra levels in determining the risk of epidural-related maternal fever and/or antibiotic administration before delivery will be examined.

Functional decline after major elective non-cardiac surgery: a multicentre prospective cohort study.

Self-reported postoperative functional recovery is an important patient-centred outcome that is rarely measured or considered in research and decision-making. We conducted a secondary analysis of the measurement of exercise tolerance before surgery (METS) study for associations of peri-operative variables with functional decline after major non-cardiac surgery. Patients who were at least 40 years old, had or were at risk of, coronary artery disease and who were scheduled for non-cardiac surgery were recruited. Primary outcome was a reduction in mobility, self-care or ability to conduct usual activities (EuroQol 5 dimension) from before surgery to 30 days and 1 year after surgery. A decline in at least one function was reported by 523/1309 (40%) participants at 30 days and 320/1309 (24%) participants at 1 year. Participants who reported higher pre-operative Duke Activity Status indices more often reported functional decline 30 days after surgery and less often reported functional decline 1 year after surgery. The odds ratios (95%CI) of functional decline 30 days and 1 year after surgery with moderate or severe postoperative complications were 1.46 (1.02-2.09), p = 0.037 and 1.44 (0.98-2.13), p = 0.066. Discrimination of participants who reported functional decline 30 days and 1 year after surgery were poor (c-statistic 0.61 and 0.63, respectively). In summary, one quarter of participants reported functional decline up to one postoperative year.

Constraints on Cosmic Strings Using Data from the Third Advanced LIGO-Virgo Observing Run.

We search for gravitational-wave signals produced by cosmic strings in the Advanced LIGO and Virgo full O3 dataset. Search results are presented for gravitational waves produced by cosmic string loop features such as cusps, kinks, and, for the first time, kink-kink collisions. A template-based search for short-duration transient signals does not yield a detection. We also use the stochastic gravitational-wave background energy density upper limits derived from the O3 data to constrain the cosmic string tension Gµ as a function of the number of kinks, or the number of cusps, for two cosmic string loop distribution models. Additionally, we develop and test a third model that interpolates between these two models. Our results improve upon the previous LIGO-Virgo constraints on Gµ by 1 to 2 orders of magnitude depending on the model that is tested. In particular, for the one-loop distribution model, we set the most competitive constraints to date: Gµâ‰²4×10^{-15}. In the case of cosmic strings formed at the end of inflation in the context of grand unified theories, these results challenge simple inflationary models.

Mortality after surgery with SARS-CoV-2 infection in England: a population-wide epidemiological study.

BACKGROUND: The COVID-19 pandemic has heavily impacted elective and emergency surgery around the world. We aimed to confirm the incidence of perioperative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated mortality after surgery. METHODS: Analysis of routine electronic health record data from NHS hospitals in England. We extracted data from Hospital Episode Statistics in England describing adult patients undergoing surgery between January 1, 2020 and February 28, 2021. The exposure was SARS-CoV-2 infection defined by International Classification of Diseases (ICD)-10 codes. The primary outcome measure was 90 day in-hospital mortality. Data were analysed using multivariable logistic regression adjusted for age, sex, Charlson Comorbidity Index, Index of Multiple Deprivation, presence of cancer, surgical procedure type and admission acuity. Results are presented as n (%) and odds ratios (OR) with 95% confidence intervals (CI). RESULTS: We identified 2 666 978 patients undergoing surgery of whom 28 777 (1.1%) had SARS-CoV-2 infection. In total, 26 364 (1.0%) patients died in hospital. SARS-CoV-2 infection was associated with a much greater risk of death (SARS-CoV-2: 6153/28 777 [21.4%] vs no SARS-CoV-2: 20 211/2 638 201 [0.8%]; OR=5.7 [95% CI, 5.5-5.9]; P<0.001). Amongst patients undergoing elective surgery, 2412/1 857 586 (0.1%) had SARS-CoV-2, of whom 172/2412 (7.1%) died, compared with 1414/1 857 586 (0.1%) patients without SARS-CoV-2 (OR=25.8 [95% CI, 21.7-30.9]; P<0.001). Amongst patients undergoing emergency surgery, 22 918/582 292 (3.9%) patients had SARS-CoV-2, of whom 5752/22 918 (25.1%) died, compared with 18 060/559 374 (3.4%) patients without SARS-CoV-2 (OR=5.5 [95% CI, 5.3-5.7]; P<0.001). CONCLUSIONS: The low incidence of SARS-CoV-2 infection in NHS surgical pathways suggests current infection prevention and control policies are highly effective. However, the high mortality amongst patients with SARS-CoV-2 suggests these precautions cannot be safely relaxed.

Dark Energy Survey Year 1 Results: Cosmological Constraints from Cluster Abundances, Weak Lensing, and Galaxy Correlations.

We present the first joint analysis of cluster abundances and auto or cross-correlations of three cosmic tracer fields: galaxy density, weak gravitational lensing shear, and cluster density split by optical richness. From a joint analysis (4×2pt+N) of cluster abundances, three cluster cross-correlations, and the auto correlations of the galaxy density measured from the first year data of the Dark Energy Survey, we obtain Ω_{m}=0.305_{-0.038}^{+0.055} and σ_{8}=0.783_{-0.054}^{+0.064}. This result is consistent with constraints from the DES-Y1 galaxy clustering and weak lensing two-point correlation functions for the flat νΛCDM model. Consequently, we combine cluster abundances and all two-point correlations from across all three cosmic tracer fields (6×2pt+N) and find improved constraints on cosmological parameters as well as on the cluster observable-mass scaling relation. This analysis is an important advance in both optical cluster cosmology and multiprobe analyses of upcoming wide imaging surveys.

Constraints on Dark Matter Properties from Observations of Milky Way Satellite Galaxies.

We perform a comprehensive study of Milky Way (MW) satellite galaxies to constrain the fundamental properties of dark matter (DM). This analysis fully incorporates inhomogeneities in the spatial distribution and detectability of MW satellites and marginalizes over uncertainties in the mapping between galaxies and DM halos, the properties of the MW system, and the disruption of subhalos by the MW disk. Our results are consistent with the cold, collisionless DM paradigm and yield the strongest cosmological constraints to date on particle models of warm, interacting, and fuzzy dark matter. At 95% confidence, we report limits on (i) the mass of thermal relic warm DM, m_{WDM}>6.5 keV (free-streaming length, λ_{fs}≲10h^{-1} kpc), (ii) the velocity-independent DM-proton scattering cross section, σ_{0}<8.8×10^{-29} cm^{2} for a 100 MeV DM particle mass [DM-proton coupling, c_{p}≲(0.3 GeV)^{-2}], and (iii) the mass of fuzzy DM, m_{ϕ}>2.9×10^{-21} eV (de Broglie wavelength, λ_{dB}≲0.5 kpc). These constraints are complementary to other observational and laboratory constraints on DM properties.

Resource requirements for reintroducing elective surgery during the COVID-19 pandemic: modelling study.

BACKGROUND: The COVID-19 response required the cancellation of all but the most urgent surgical procedures. The number of cancelled surgical procedures owing to Covid-19, and the reintroduction of surgical acivirt, was modelled. METHODS: This was a modelling study using Hospital Episode Statistics data (2014-2019). Surgical procedures were grouped into four urgency classes. Expected numbers of surgical procedures performed between 1 March 2020 and 28 February 2021 were modelled. Procedure deficit was estimated using conservative assumptions and the gradual reintroduction of elective surgery from the 1 June 2020. Costs were calculated using NHS reference costs and are reported as millions or billions of euros. Estimates are reported with 95 per cent confidence intervals. RESULTS: A total of 4 547 534 (95 per cent c.i. 3 318 195 to 6 250 771) patients with a pooled mean age of 53.5 years were expected to undergo surgery between 1 March 2020 and 28 February 2021. By 31 May 2020, 749 247 (513 564 to 1 077 448) surgical procedures had been cancelled. Assuming that elective surgery is reintroduced gradually, 2 328 193 (1 483 834 - 3 450 043) patients will be awaiting surgery by 28 February 2021. The cost of delayed procedures is €5.3 (3.1 to 8.0) billion. Safe delivery of surgery during the pandemic will require substantial extra resources costing €526.8 (449.3 to 633.9) million. CONCLUSION: As a consequence of the Covid-19 pandemic, provision of elective surgery will be delayed and associated with increased healthcare costs.

Prospects for observing and localizing gravitational-wave transients with Advanced LIGO, Advanced Virgo and KAGRA.

We present our current best estimate of the plausible observing scenarios for the Advanced LIGO, Advanced Virgo and KAGRA gravitational-wave detectors over the next several years, with the intention of providing information to facilitate planning for multi-messenger astronomy with gravitational waves. We estimate the sensitivity of the network to transient gravitational-wave signals for the third (O3), fourth (O4) and fifth observing (O5) runs, including the planned upgrades of the Advanced LIGO and Advanced Virgo detectors. We study the capability of the network to determine the sky location of the source for gravitational-wave signals from the inspiral of binary systems of compact objects, that is binary neutron star, neutron star-black hole, and binary black hole systems. The ability to localize the sources is given as a sky-area probability, luminosity distance, and comoving volume. The median sky localization area (90% credible region) is expected to be a few hundreds of square degrees for all types of binary systems during O3 with the Advanced LIGO and Virgo (HLV) network. The median sky localization area will improve to a few tens of square degrees during O4 with the Advanced LIGO, Virgo, and KAGRA (HLVK) network. During O3, the median localization volume (90% credible region) is expected to be on the order of 10 5 , 10 6 , 10 7 Mpc 3 for binary neutron star, neutron star-black hole, and binary black hole systems, respectively. The localization volume in O4 is expected to be about a factor two smaller than in O3. We predict a detection count of 1 - 1 + 12 ( 10 - 10 + 52 ) for binary neutron star mergers, of 0 - 0 + 19 ( 1 - 1 + 91 ) for neutron star-black hole mergers, and 17 - 11 + 22 ( 79 - 44 + 89 ) for binary black hole mergers in a one-calendar-year observing run of the HLV network during O3 (HLVK network during O4). We evaluate sensitivity and localization expectations for unmodeled signal searches, including the search for intermediate mass black hole binary mergers.

GW190521: A Binary Black Hole Merger with a Total Mass of 150 M_{⊙}.

On May 21, 2019 at 03:02:29 UTC Advanced LIGO and Advanced Virgo observed a short duration gravitational-wave signal, GW190521, with a three-detector network signal-to-noise ratio of 14.7, and an estimated false-alarm rate of 1 in 4900 yr using a search sensitive to generic transients. If GW190521 is from a quasicircular binary inspiral, then the detected signal is consistent with the merger of two black holes with masses of 85_{-14}^{+21} M_{⊙} and 66_{-18}^{+17} M_{⊙} (90% credible intervals). We infer that the primary black hole mass lies within the gap produced by (pulsational) pair-instability supernova processes, with only a 0.32% probability of being below 65 M_{⊙}. We calculate the mass of the remnant to be 142_{-16}^{+28} M_{⊙}, which can be considered an intermediate mass black hole (IMBH). The luminosity distance of the source is 5.3_{-2.6}^{+2.4} Gpc, corresponding to a redshift of 0.82_{-0.34}^{+0.28}. The inferred rate of mergers similar to GW190521 is 0.13_{-0.11}^{+0.30} Gpc^{-3} yr^{-1}.

Search for Subsolar Mass Ultracompact Binaries in Advanced LIGO's Second Observing Run.

We present a search for subsolar mass ultracompact objects in data obtained during Advanced LIGO's second observing run. In contrast to a previous search of Advanced LIGO data from the first observing run, this search includes the effects of component spin on the gravitational waveform. We identify no viable gravitational-wave candidates consistent with subsolar mass ultracompact binaries with at least one component between 0.2 M_{⊙}-1.0 M_{⊙}. We use the null result to constrain the binary merger rate of (0.2 M_{⊙}, 0.2 M_{⊙}) binaries to be less than 3.7×10^{5} Gpc^{-3} yr^{-1} and the binary merger rate of (1.0 M_{⊙}, 1.0 M_{⊙}) binaries to be less than 5.2×10^{3} Gpc^{-3} yr^{-1}. Subsolar mass ultracompact objects are not expected to form via known stellar evolution channels, though it has been suggested that primordial density fluctuations or particle dark matter with cooling mechanisms and/or nuclear interactions could form black holes with subsolar masses. Assuming a particular primordial black hole (PBH) formation model, we constrain a population of merging 0.2 M_{⊙} black holes to account for less than 16% of the dark matter density and a population of merging 1.0 M_{⊙} black holes to account for less than 2% of the dark matter density. We discuss how constraints on the merger rate and dark matter fraction may be extended to arbitrary black hole population models that predict subsolar mass binaries.

Inflation of 430-parsec bipolar radio bubbles in the Galactic Centre by an energetic event.

The Galactic Centre contains a supermassive black hole with a mass of four million Suns1 within an environment that differs markedly from that of the Galactic disk. Although the black hole is essentially quiescent in the broader context of active galactic nuclei, X-ray observations have provided evidence for energetic outbursts from its surroundings2. Also, although the levels of star formation in the Galactic Centre have been approximately constant over the past few hundred million years, there is evidence of increased short-duration bursts3, strongly influenced by the interaction of the black hole with the enhanced gas density present within the ring-like central molecular zone4 at Galactic longitude |l| < 0.7 degrees and latitude |b| < 0.2 degrees. The inner 200-parsec region is characterized by large amounts of warm molecular gas5, a high cosmic-ray ionization rate6, unusual gas chemistry, enhanced synchrotron emission7,8, and a multitude of radio-emitting magnetized filaments9, the origin of which has not been established. Here we report radio imaging that reveals a bipolar bubble structure, with an overall span of 1 degree by 3 degrees (140 parsecs × 430 parsecs), extending above and below the Galactic plane and apparently associated with the Galactic Centre. The structure is edge-brightened and bounded, with symmetry implying creation by an energetic event in the Galactic Centre. We estimate the age of the bubbles to be a few million years, with a total energy of 7 × 1052 ergs. We postulate that the progenitor event was a major contributor to the increased cosmic-ray density in the Galactic Centre, and is in turn the principal source of the relativistic particles required to power the synchrotron emission of the radio filaments within and in the vicinity of the bubble cavities.

Tests of General Relativity with GW170817.

The recent discovery by Advanced LIGO and Advanced Virgo of a gravitational wave signal from a binary neutron star inspiral has enabled tests of general relativity (GR) with this new type of source. This source, for the first time, permits tests of strong-field dynamics of compact binaries in the presence of matter. In this Letter, we place constraints on the dipole radiation and possible deviations from GR in the post-Newtonian coefficients that govern the inspiral regime. Bounds on modified dispersion of gravitational waves are obtained; in combination with information from the observed electromagnetic counterpart we can also constrain effects due to large extra dimensions. Finally, the polarization content of the gravitational wave signal is studied. The results of all tests performed here show good agreement with GR.

Age of patients undergoing surgery.

BACKGROUND: Advancing age is independently associated with poor postoperative outcomes. The ageing of the general population is a major concern for healthcare providers. Trends in age were studied among patients undergoing surgery in the National Health Service in England. METHODS: Time trend ecological analysis was undertaken of Hospital Episode Statistics and Office for National Statistics data for England from 1999 to 2015. The proportion of patients undergoing surgery in different age groupings, their pooled mean age, and change in age profile over time were calculated. Growth in the surgical population was estimated, with associated costs, to the year 2030 by use of linear regression modelling. RESULTS: Some 68 205 695 surgical patient episodes (31 220 341 men, 45·8 per cent) were identified. The mean duration of hospital stay was 5·3 days. The surgical population was older than the general population of England; this gap increased over time (1999: 47·5 versus 38·3 years; 2015: 54·2 versus 39·7 years). The number of people aged 75 years or more undergoing surgery increased from 544 998 (14·9 per cent of that age group) in 1999 to 1 012 517 (22·9 per cent) in 2015. By 2030, it is estimated that one-fifth of the 75 years and older age category will undergo surgery each year (1·49 (95 per cent c.i. 1·43 to 1·55) million people), at a cost of €3·2 (3·1 to 3·5) billion. CONCLUSION: The population having surgery in England is ageing at a faster rate than the general population. Healthcare policies must adapt to ensure that provision of surgical treatments remains safe and sustainable.

Cosmological Constraints from Multiple Probes in the Dark Energy Survey.

The combination of multiple observational probes has long been advocated as a powerful technique to constrain cosmological parameters, in particular dark energy. The Dark Energy Survey has measured 207 spectroscopically confirmed type Ia supernova light curves, the baryon acoustic oscillation feature, weak gravitational lensing, and galaxy clustering. Here we present combined results from these probes, deriving constraints on the equation of state, w, of dark energy and its energy density in the Universe. Independently of other experiments, such as those that measure the cosmic microwave background, the probes from this single photometric survey rule out a Universe with no dark energy, finding w=-0.80_{-0.11}^{+0.09}. The geometry is shown to be consistent with a spatially flat Universe, and we obtain a constraint on the baryon density of Ω_{b}=0.069_{-0.012}^{+0.009} that is independent of early Universe measurements. These results demonstrate the potential power of large multiprobe photometric surveys and pave the way for order of magnitude advances in our constraints on properties of dark energy and cosmology over the next decade.

Constraining the p-Mode-g-Mode Tidal Instability with GW170817.

We analyze the impact of a proposed tidal instability coupling p modes and g modes within neutron stars on GW170817. This nonresonant instability transfers energy from the orbit of the binary to internal modes of the stars, accelerating the gravitational-wave driven inspiral. We model the impact of this instability on the phasing of the gravitational wave signal using three parameters per star: an overall amplitude, a saturation frequency, and a spectral index. Incorporating these additional parameters, we compute the Bayes factor (lnB_{!pg}^{pg}) comparing our p-g model to a standard one. We find that the observed signal is consistent with waveform models that neglect p-g effects, with lnB_{!pg}^{pg}=0.03_{-0.58}^{+0.70} (maximum a posteriori and 90% credible region). By injecting simulated signals that do not include p-g effects and recovering them with the p-g model, we show that there is a ≃50% probability of obtaining similar lnB_{!pg}^{pg} even when p-g effects are absent. We find that the p-g amplitude for 1.4 M_{⊙} neutron stars is constrained to less than a few tenths of the theoretical maximum, with maxima a posteriori near one-tenth this maximum and p-g saturation frequency ∼70 Hz. This suggests that there are less than a few hundred excited modes, assuming they all saturate by wave breaking. For comparison, theoretical upper bounds suggest ≲10^{3} modes saturate by wave breaking. Thus, the measured constraints only rule out extreme values of the p-g parameters. They also imply that the instability dissipates ≲10^{51} erg over the entire inspiral, i.e., less than a few percent of the energy radiated as gravitational waves.

Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury. METHODS: We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L-1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals. RESULTS: Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 [OR: 2.56 (1.92-3.41); P<0.0001]. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count [OR 1.80 (1.50-2.17); P<0.0001] and higher absolute preoperative monocyte count [OR 1.93 (1.12-3.30); P=0.017]. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03). CONCLUSIONS: Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury. CLINICAL TRIAL REGISTRATION: NCT01842568.

Cardiac vagal dysfunction and myocardial injury after non-cardiac surgery: a planned secondary analysis of the measurement of Exercise Tolerance before surgery study.

BACKGROUND: The aetiology of perioperative myocardial injury is poorly understood and not clearly linked to pre-existing cardiovascular disease. We hypothesised that loss of cardioprotective vagal tone [defined by impaired heart rate recovery ≤12 beats min-1 (HRR ≤12) 1 min after cessation of preoperative cardiopulmonary exercise testing] was associated with perioperative myocardial injury. METHODS: We conducted a pre-defined, secondary analysis of a multi-centre prospective cohort study of preoperative cardiopulmonary exercise testing. Participants were aged ≥40 yr undergoing non-cardiac surgery. The exposure was impaired HRR (HRR≤12). The primary outcome was postoperative myocardial injury, defined by serum troponin concentration within 72 h after surgery. The analysis accounted for established markers of cardiac risk [Revised Cardiac Risk Index (RCRI), N-terminal pro-brain natriuretic peptide (NT pro-BNP)]. RESULTS: A total of 1326 participants were included [mean age (standard deviation), 64 (10) yr], of whom 816 (61.5%) were male. HRR≤12 occurred in 548 patients (41.3%). Myocardial injury was more frequent amongst patients with HRR≤12 [85/548 (15.5%) vs HRR>12: 83/778 (10.7%); odds ratio (OR), 1.50 (1.08-2.08); P=0.016, adjusted for RCRI). HRR declined progressively in patients with increasing numbers of RCRI factors. Patients with ≥3 RCRI factors were more likely to have HRR≤12 [26/36 (72.2%) vs 0 factors: 167/419 (39.9%); OR, 3.92 (1.84-8.34); P<0.001]. NT pro-BNP greater than a standard prognostic threshold (>300 pg ml-1) was more frequent in patients with HRR≤12 [96/529 (18.1%) vs HRR>12 59/745 (7.9%); OR, 2.58 (1.82-3.64); P<0.001]. CONCLUSIONS: Impaired HRR is associated with an increased risk of perioperative cardiac injury. These data suggest a mechanistic role for cardiac vagal dysfunction in promoting perioperative myocardial injury.