Ischemic or bleeding events might occur after transcatheter aortic valve replacement (TAVR), with the potential to hamper clinical outcomes. This study aimed to characterize the average daily ...ischemic risks (ADIRs) and the average daily bleeding risks (ADBRs) over 1-year in all consecutive patients undergoing TAVR.
ADBR included all bleeding events according to VARC-2 definition, and ADIR included cardiovascular deaths, myocardial infarction and ischemic stroke. ADIRs and ADBRs were assessed within different timeframes post TAVR: acute (0–30 days), late (31–180 days), and very late (>181 days). Generalized estimating equations were used to test the least squares mean differences for the pairwise comparison of ADIRs and ADBRs. Our analysis was performed in the overall cohort and according to antithrombotic strategy (LT-OAC vs No LT-OAC).
Ischemic burden was higher than bleeding burden, independently from the indication to LT-OAC, and in all timeframes examined. In the overall population, ADIRs were three-fold ADBRs (0.0467 95% CI, 0.0431–0.0506 vs 0.0179 95% CI, 0.0174–0.0185; p < 0.001*). While ADIR was significantly higher in the acute phase, ADBR was relatively stable in all timeframes analysed. Of note, in LT-OAC population, OAC + SAPT group showed lower ischemic risk and higher bleeding events compared with OAC alone (ADIR: 0.0447 95% CI: 0.0417–0.0477 vs 0.0642 95% CI: 0.0557–0.0728; p < 0.001*, ADBR 0.0395 95% CI: 0.0381–0.0409 vs 0.0147 95% CI: 0.0138–0.0156; p < 0.001*).
In patients undergoing TAVR Average daily risk fluctuates over time. However, ADIRs overcome ADBRs in all timeframes, especially in the acute phase and regardless of antithrombotic strategy adopted.
ADR - average daily risk; ADIR - average daily ischemic risk; ADBR - average daily bleeding risk; LSMD - least mean square difference Display omitted
•This study shows the great variability between ADIR and ADBR in the first 30 days after TAVR, with the highest prevalence of ischemic risk.•ADIR overcome ADBR in all timeframes with greater differences in the acute phase, which might be related to the procedural ischemic factors.•Understanding the time-dependent trend of ADR, highlights how an oversimplified approach, might be inadequate to capture the complexity of the phenomenon.•Bearing this in mind, a tailored antithrombotic strategy could improve clinical outcomes as a result of a balance between ischemic and bleeding risk.
Knee pain is second only to the back as the most commonly reported area of pain in the human body. With an overall prevalence of 46.2%, its impact on disability, lost productivity, and cost on ...healthcare cannot be overlooked. Due to the pervasiveness of knee pain in the general population, there are no shortages of treatment options available for addressing the symptoms. Ranging from physical therapy and pharmacologic agents to interventional pain procedures to surgical options, practitioners have a wide array of options to choose from-unfortunately, there is no consensus on which treatments are "better" and when they should be offered in comparison to others. While it is generally accepted that less invasive treatments should be offered before more invasive ones, there is a lack of agreement on the order in which the less invasive are to be presented. In an effort to standardize the treatment of this extremely prevalent pathology, the authors present an all-encompassing set of guidelines on the treatment of knee pain based on an extensive literature search and data grading for each of the available alternative that will allow practitioners the ability to compare and contrast each option. Keywords: knee, knee pain, genicular nerve, ablation, regenerative medicine, platelet-rich plasma, dorsal root ganglion, peripheral nerve stimulation
Supergiant fast X-ray transients (SFXTs) are high mass X-ray binaries (HMXBs) that are defined by their hard X-ray flaring behaviour. During these flares they reach peak luminosities of 10sup ...36-10sup 37 erg ssup -1 for a few hours (in the hard X-ray), which are much shorter timescales than those characterizing Be/X-ray binaries. We investigate the characteristics of bright flares for a sample of SFXTs and their relation to the orbital phase. In particular, we observe a trend of clustering of flares at some phases as Psuborb increases, which is consistent with a progression from tight circular or mildly eccentric orbits at short periods to wider and more eccentric orbits at longer orbital periods. Finally, we estimate the expected number of flares for a given source for our limiting flux and provide the recipe for calculating them for the limiting flux of future hard X-ray observatories.
Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various ...novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.
Mining often leads to nitrate and metal contamination of groundwater and water bodies. Denitrification of acidic water was investigated in two up-flow fluidized-bed reactors (FBR) and using batch ...assays. Bacterial communities were enriched on ethanol plus nitrate in the FBRs. Initially, the effects of temperature, low-pH and ethanol/nitrate on denitrification were revealed. Batch assays showed that pH 4.8 was inhibitory to denitrification, whereas FBR characteristics permitted denitrification even at feed pH of 2.5 and at 7–8 °C. Nitrate and ethanol were removed and the feed pH was neutralized, provided that ethanol was supplied in excess to nitrate. Subsequently, Fe(II) and Cu impact on denitrification was investigated within batch tests at pH 7. Iron supplementation up to 100 mg/L resulted in iron oxidation and soluble concentrations ranging from 0.4 to 1.6 mg/L that stimulated denitrification. On the contrary, 0.7 mg/L of soluble Cu significantly slowed denitrification down resulting in about 45 % of inhibition in the first 8 h. Polymerase chain reaction—denaturant gradient gel electrophoresis demonstrated the co-existence of different denitrifying microbial consortia in FBRs.
Dechloromonas denitrificans
and
Hydrogenophaga caeni
were present in both FBRs and mainly responsible for nitrate reduction.
Circadian Biology and Stroke Lo, Eng H; Albers, Gregory W; Dichgans, Martin ...
Stroke (1970),
06/2021, Letnik:
52, Številka:
6
Journal Article
Recenzirano
Odprti dostop
Circadian biology modulates almost all aspects of mammalian physiology, disease, and response to therapies. Emerging data suggest that circadian biology may significantly affect the mechanisms of ...susceptibility, injury, recovery, and the response to therapy in stroke. In this review/perspective, we survey the accumulating literature and attempt to connect molecular, cellular, and physiological pathways in circadian biology to clinical consequences in stroke. Accounting for the complex and multifactorial effects of circadian rhythm may improve translational opportunities for stroke diagnostics and therapeutics.
Abstract
We report on a new NuSTAR observation and on the ongoing Swift X-Ray Telescope monitoring campaign of the peculiar source 1E 161348–5055, located at the centre of the supernova remnant ...RCW 103, which is recovering from its last outburst in 2016 June. The X-ray spectrum at the epoch of the NuSTAR observation can be described by either two absorbed blackbodies ($kT_{\rm BB_1}$ ∼ 0.5 keV, $kT_{\rm BB_2}$ ∼ 1.2 keV) or an absorbed blackbody plus a power law ($kT_{\rm BB_1}$ ∼ 0.6 keV, Γ ∼ 3.9). The observed flux was ∼9 × 10−12 erg s−1 cm−2, ∼3 times lower than what observed at the outburst onset, but about one order of magnitude higher than the historical quiescent level. A periodic modulation was detected at the known 6.67 h periodicity. The spectral decomposition and evolution along the outburst decay are consistent with 1E 161348–5055 being a magnetar, the slowest ever detected.
Paracetamol has been commonly used for the relief of postoperative pain following oral surgery. In this review we investigated the optimal dose of paracetamol and the optimal time for drug ...administration to provide pain relief, taking into account the side effects of different doses of the drug. This will inform dentists and their patients of the best strategy for pain relief after the surgical removal of wisdom teeth.
To assess the beneficial and harmful effects of paracetamol for pain relief after surgical removal of lower wisdom teeth, compared to placebo, at different doses and administered postoperatively.
We searched the Cochrane Oral Health Group's Trials Register; the Cochrane Pain, Palliative and Supportive Care Group's Trials Register; CENTRAL; MEDLINE; EMBASE and the Current Controlled Trials Register. Handsearching included several dental journals. We checked the bibliographies of relevant clinical trials and review articles for studies outside the handsearched journals. We wrote to authors of the identified randomised controlled trials (RCTs), to manufacturers of analgesic pharmaceuticals, we searched personal references in an attempt to identify unpublished or ongoing RCTs. No language restriction was applied. The last electronic search was conducted on 24th August 2006.
Randomised, parallel group, placebo controlled, double blind clinical trials of paracetamol for acute pain, following third molar surgery.
All trials identified were scanned independently and in duplicate by two review authors, any disagreements were resolved by discussion, or if necessary a third review author was consulted. The proportion of patients with at least 50% pain relief was calculated for both paracetamol and placebo. The number of patients experiencing adverse events, and/or the total number of adverse events reported were analysed.
Twenty-one trials met the inclusion criteria. A total of 2048 patients were initially enrolled in the trials (1148 received paracetamol, and 892 the placebo) and of these 1968 (96%) were included in the meta-analysis (1133 received paracetamol, and 835 the placebo). Paracetamol provided a statistically significant benefit when compared with placebo for pain relief and pain intensity at both 4 and 6 hours. Most studies were found to have moderate risk of bias, with poorly reported allocation concealment being the main problem. Risk ratio values for pain relief at 4 hours 2.85 (95% confidence interval (CI) 1.89 to 4.29), and at 6 hours 3.32 (95% CI 1.88 to 5.87). A statistically significant benefit was also found between up to 1000 mg and 1000 mg doses, the higher the dose giving greater benefit for each measure at both time points. There was no statistically significant difference between the number of patients who reported adverse events, overall this being 19% in the paracetamol group and 16% in the placebo group.
Paracetamol is a safe, effective drug for the treatment of postoperative pain following the surgical removal of lower wisdom teeth.
In 2013 April a new magnetar, SGR 1745−2900, was discovered as it entered an outburst, at only 2.4 arcsec angular distance from the supermassive black hole at the centre of the Milky Way, ...Sagittarius A*. SGR 1745−2900 has a surface dipolar magnetic field of ∼2 × 1014 G, and it is the neutron star closest to a black hole ever observed. The new source was detected both in the radio and X-ray bands, with a peak X-ray luminosity L
X ∼ 5 × 1035 erg s−1. Here we report on the long-term Chandra (25 observations) and XMM–Newton (eight observations) X-ray monitoring campaign of SGR 1745−2900 from the onset of the outburst in 2013 April until 2014 September. This unprecedented data set allows us to refine the timing properties of the source, as well as to study the outburst spectral evolution as a function of time and rotational phase. Our timing analysis confirms the increase in the spin period derivative by a factor of ∼2 around 2013 June, and reveals that a further increase occurred between 2013 October 30 and 2014 February 21. We find that the period derivative changed from 6.6 × 10−12 to 3.3 × 10−11 s s−1 in 1.5 yr. On the other hand, this magnetar shows a slow flux decay compared to other magnetars and a rather inefficient surface cooling. In particular, starquake-induced crustal cooling models alone have difficulty in explaining the high luminosity of the source for the first ∼200 d of its outburst, and additional heating of the star surface from currents flowing in a twisted magnetic bundle is probably playing an important role in the outburst evolution.
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