The tidal disruption of a star by a supermassive black hole leads to a short-lived thermal flare. Despite extensive searches, radio follow-up observations of known thermal stellar tidal disruption ...flares (TDFs) have not yet produced a conclusive detection. We present a detection of variable radio emission from a thermal TDF, which we interpret as originating from a newly launched jet. The multiwavelength properties of the source present a natural analogy with accretion-state changes of stellar mass black holes, which suggests that all TDFs could be accompanied by a jet. In the rest frame of the TDF, our radio observations are an order of magnitude more sensitive than nearly all previous upper limits, explaining how these jets, if common, could thus far have escaped detection.
Metformin treatment is associated with improved outcome after myocardial infarction in patients with diabetes. In animal experimental studies metformin preserves left ventricular function.
To ...evaluate the effect of metformin treatment on preservation of left ventricular function in patients without diabetes presenting with ST-segment elevation myocardial infarction (STEMI).
Double-blind, placebo-controlled study conducted among 380 patients who underwent primary percutaneous coronary intervention (PCI) for STEMI at the University Medical Center Groningen, The Netherlands, between January 1, 2011, and May 26, 2013.
Metformin hydrochloride (500 mg) (n = 191) or placebo (n = 189) twice daily for 4 months.
The primary efficacy measure was left ventricular ejection fraction (LVEF) after 4 months, assessed by magnetic resonance imaging. A secondary efficacy measure was the N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration after 4 months. The incidence of major adverse cardiac events (MACE; the combined end point of death, reinfarction, or target-lesion revascularization) was recorded until 4 months as a secondary efficacy measure.
At 4 months, all patients were alive and none were lost to follow-up. LVEF was 53.1% (95% CI, 51.6%-54.6%) in the metformin group (n = 135), compared with 54.8% (95% CI, 53.5%-56.1%) (P = .10) in the placebo group (n = 136). NT-proBNP concentration was 167 ng/L in the metformin group (interquartile range IQR, 65-393 ng/L) and 167 ng/L in the placebo group (IQR, 74-383 ng/L) (P = .66). MACE were observed in 6 patients (3.1%) in the metformin group and in 2 patients (1.1%) in the placebo group (P = .16). Creatinine concentration (79 µmol/L IQR, 70-87 µmol/L vs 79 µmol/L IQR, 72-89 µmol/L, P = .61) and glycated hemoglobin (5.9% IQR, 5.6%-6.1% vs 5.9% IQR, 5.7%-6.1%, P = .15) were not significantly different between both groups. No cases of lactic acidosis were observed.
Among patients without diabetes presenting with STEMI and undergoing primary PCI, the use of metformin compared with placebo did not result in improved LVEF after 4 months. The present findings do not support the use of metformin in this setting.
clinicaltrials.gov Identifier: NCT01217307.
An intrinsic correlation has been identified between the luminosity and duration of plateaus in the X-ray afterglows of gamma-ray bursts (GRBs; Dainotti et al. 2008), suggesting a central engine ...origin. The magnetar central engine model predicts an observable plateau phase, with plateau durations and luminosities being determined by the magnetic fields and spin periods of the newly formed magnetar. This paper analytically shows that the magnetar central engine model can explain, within the 1σ uncertainties, the correlation between plateau luminosity and duration. The observed scatter in the correlation most likely originates in the spread of initial spin periods of the newly formed magnetar and provides an estimate of the maximum spin period of ∼35 ms (assuming a constant mass, efficiency and beaming across the GRB sample). Additionally, by combining the observed data and simulations, we show that the magnetar emission is most likely narrowly beamed and has ≲20 per cent efficiency in conversion of rotational energy from the magnetar into the observed plateau luminosity. The beaming angles and efficiencies obtained by this method are fully consistent with both predicted and observed values. We find that short GRBs and short GRBs with extended emission lie on the same correlation but are statistically inconsistent with being drawn from the same distribution as long GRBs, this is consistent with them having a wider beaming angle than long GRBs.
Summary
Background
An important limitation in vascular malformation research is the heterogeneity in outcome measures used for the evaluation of treatment outcome.
Objectives
To reach international ...consensus on a core outcome set (COS) for clinical research on peripheral vascular malformations: lymphatic (LM), venous (VM) and arteriovenous malformations (AVM). In this consensus study, we determined what domains should constitute the COS.
Methods
Thirty‐six possibly relevant outcome domains were proposed to an international group of physicians, patients and the parents of patients. In a three‐round e‐Delphi process using online surveys, participants repeatedly rated the importance of these domains on a five‐point Likert scale. Participants could also propose other relevant domains. This process was performed for LM, VM and AVM separately. Consensus was predefined as 80% agreement on the importance of a domain among both the physician group and the patient/parent group. Outcomes were then re‐evaluated in an online consensus meeting.
Results
167 physicians and 134 patients and parents of patients with LM (n = 50), VM (n = 71) and AVM (n = 29) participated in the study. After three rounds and a consensus meeting, consensus was reached for all three types of vascular malformations on the core domains of radiological assessment, physician‐reported location‐specific signs, patient‐reported severity of symptoms, pain, quality of life, satisfaction and adverse events. Vascular malformation type‐specific signs and symptoms were included for LM, VM and AVM, separately.
Conclusions
Our recommendation is that therapeutic‐efficacy studies on peripheral vascular malformations should measure at least these core outcome domains.
What's already known about this topic?
There is considerable heterogeneity in outcomes used in clinical trials on peripheral vascular malformations.
This hampers the interpretation, comparison and aggregation of study data, and in turn the development of evidence‐based treatment guidelines.
What does this study add?
International consensus was reached on the core outcome domains that should be measured in all therapeutic‐efficacy studies in this field: radiological assessment, physician‐assessed signs, patient‐reported pain, overall severity of symptoms, health‐related quality of life, patient satisfaction with treatment and outcome, and adverse events.
The next step is to reach consensus on how these domains should be measured (core outcome instruments).
What are the clinical implications of this work?
Development of this core outcome set (COS) should lead to improved standardized outcome reporting.
It should allow the development of evidence‐based treatment guidelines.
Although this COS was primarily developed for clinical research, it may form the basis for a more concise COS that can be implemented in clinical practice.
Linked Comment: Thomas. Br J Dermatol 2018; 178:326–327.
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Monocytes are critical mediators of healing following acute myocardial infarction (AMI), making them an interesting target to improve myocardial repair. The purpose of this study was a gain of ...insight into the source and recruitment of monocytes following AMI in humans.
Post-mortem tissue specimens of myocardium, spleen and bone marrow were collected from 28 patients who died at different time points after AMI. Twelve patients who died from other causes served as controls. The presence and localization of monocytes (CD14(+) cells), and their CD14(+)CD16(-) and CD14(+)CD16(+) subsets, were evaluated by immunohistochemical and immunofluorescence analyses. CD14(+) cells localized at distinct regions of the infarcted myocardium in different phases of healing following AMI. In the inflammatory phase after AMI, CD14(+) cells were predominantly located in the infarct border zone, adjacent to cardiomyocytes, and consisted for 85% (78-92%) of CD14(+)CD16(-) cells. In contrast, in the subsequent post-AMI proliferative phase, massive accumulation of CD14(+) cells was observed in the infarct core, containing comparable proportions of both the CD14(+)CD16(-) 60% (31-67%) and CD14(+)CD16(+) subsets 40% (33-69%). Importantly, in AMI patients, of the number of CD14(+) cells was decreased by 39% in the bone marrow and by 58% in the spleen, in comparison with control patients (P = 0.02 and <0.001, respectively).
Overall, this study showed a unique spatiotemporal pattern of monocyte accumulation in the human myocardium following AMI that coincides with a marked depletion of monocytes from the spleen, suggesting that the human spleen contains an important reservoir function for monocytes.
ABSTRACT
We present high-cadence multifrequency radio observations of the long gamma-ray burst (GRB) 190829A, which was detected at photon energies above 100 GeV by the High Energy Stereoscopic ...System (H.E.S.S.). Observations with the Meer Karoo Array Telescope (MeerKAT, 1.3 GHz) and Arcminute Microkelvin Imager – Large Array (AMI-LA, 15.5 GHz) began one day post-burst and lasted nearly 200 d. We used complementary data from Swift X-Ray Telescope (XRT), which ran to 100 d post-burst. We detected a likely forward shock component with both MeerKAT and XRT up to over 100 d post-burst. Conversely, the AMI-LA light curve appears to be dominated by reverse shock emission until around 70 d post-burst when the afterglow flux drops below the level of the host galaxy. We also present previously unpublished observations of the other H.E.S.S.-detected GRB, GRB 180720B from AMI-LA, which shows likely forward shock emission that fades in less than 10 d. We present a comparison between the radio emission from the three GRBs with detected very high energy (VHE) gamma-ray emission and a sensitivity-limited radio afterglow sample. GRB 190829A has the lowest isotropic radio luminosity of any GRB in our sample, but the distribution of luminosities is otherwise consistent, as expected, with the VHE GRBs being drawn from the same parent distribution as the other radio-detected long GRBs.
ABSTRACT We report on the analysis of two deep XMM-Newton observations of the magnetar Swift J1834.9−0846 and its surrounding extended emission taken in 2014 March and October, 2.5 and 3.1 yr after ...the source went into outburst. The magnetar is only weakly detected in the first observation, with an absorption-corrected flux erg s−1 cm−2 and a upper limit during the second observation of about 3 × 10−14 erg s−1 cm−2. This flux level is more than 3 orders of magnitude lower than the flux measured at the outburst onset in 2011 September. The extended emission, centered at the magnetar position and elongated toward the southwest, is clearly seen in both observations; it is best fit by a highly absorbed power law (PL), with a hydrogen column density of cm−2 and PL photon index . Its flux is constant between the two observations at erg s−1 cm−2. We find no statistically significant changes in the spectral shape or the flux of this extended emission over a period of 9 yr from 2005 to 2014. These new results strongly support the extended emission nature as a wind nebula and firmly establish Swift J1834.9−0846 as the first magnetar to show a surrounding wind nebula. Further, our results imply that such nebulae are no longer exclusive to rotation-powered pulsars and narrow the gap between these two subpopulations of isolated neutron stars. The size and spectrum of the nebula are compatible with those of pulsar-wind nebulae, but its radiative efficiency is markedly high, possibly pointing to an additional wind component in Swift J1834.9−0846.
Background and aims
Myocardial infarction triggers an inflammatory response involved in cardiac repair. We studied the association of the interleukin 6 (IL-6) cascade with infarct size and cardiac ...function after ST-elevation myocardial infarction (STEMI).
Methods
In 369 STEMI patients IL-6, soluble IL-6 receptor (sIL-6R), and soluble glycoprotein (sgp) 130 were measured at baseline (hospital admission), 24 h, 2 weeks, 7 weeks, 4 months, and 1 year post-PCI and sIL-6R/IL-6 ratio was calculated. At 4 months, infarct size and left ventricular ejection fraction (LVEF) were assessed by magnetic resonance imaging. Diastolic function (
E
/
e
′) was determined by echocardiography.
Results
Hospital admission levels for IL-6, sIL-6R, sgp 130 were 3.7 pg/ml (IQR 2.1–6.7 pg/ml), 51.6 ng/ml (IQR 37.3–69.0 ng/ml), and 332 ng/ml (IQR 280–399 ng/ml), respectively. 24 h after admission, IL-6 had increased threefold compared to baseline (
p
< 0.001) and returned below baseline (
p
< 0.001) 2 weeks after STEMI. sIL-6R and sgp130 levels at 24 h remained similar to baseline but were increased at 2 weeks (
p
< 0.001;
p
< 0.001, respectively). IL-6 and sIL-6R/IL-6 ratio at 24 h were independently associated with infarct size
β
5.4 (95% CI 3.3–7.5);
p
< 0.001,
β
− 4.0 (95% CI − 6.1 to − 1.9);
p
< 0.001, respectively. Higher levels of IL-6 at 24 h were associated with lower LVEF
β
− 4.2 (95% CI -6.7 to − 1.8);
p
= 0.001.
Conclusions
Higher IL-6 and lower sIL-6R/IL-6 ratio early after presentation with STEMI are indicative for larger infarct size and decreased cardiac function at 4 months.
Objectives
Preclinical and clinical studies suggested cardioprotective effects of metformin treatment. In the GIPS-III trial, 4 months of metformin treatment did not improve left ventricular ejection ...fraction in patients presenting with ST-elevation myocardial infarction (STEMI). Here, we report the 2-year follow-up results.
Methods
Between January 2011 and May 2013, 379 STEMI patients without diabetes undergoing primary percutaneous coronary intervention were randomized to a 4-month treatment with metformin (500 mg twice daily) (
N
= 191) or placebo (
N
= 188) in the University Medical Center Groningen. Two-year follow-up data was collected to determine its effect on predefined secondary endpoints: the incidence of major adverse cardiac events (MACE), its individual components, all-cause mortality, and new-onset diabetes.
Results
For all 379 patients all-cause mortality data were available. For seven patients (2%) follow-up data on MACE was limited, ranging from 129 to 577 days. All others completed the 2-year follow-up visit. Incidence of MACE was 11 (5.8%) in metformin and 6 (3.2%) in placebo treated patients hazard ratio (HR) 1.84, confidence interval (CI) 0.68–4.97,
P
= 0.22. Three patients died in the metformin group and one in the placebo treatment group. Individual components of MACE were also comparable between both groups. New-onset diabetes mellitus was 34 (17.8%) in metformin and 32 (17.0%) in placebo treated patients (odds ratio 1.15, CI 0.66–1.98,
P
= 0.84). After multivariable adjustment the incidence of MACE was comparable between the treatment groups (HR 1.02, CI 0.10–10.78,
P
= 0.99).
Conclusions
Four months metformin treatment initiated at the time of hospitalization in STEMI patients without diabetes did not exert beneficial long-term effects.
Trial registration
clinicaltrials.gov Identifier: NCT01217307.
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