Summary
Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Virus and host intrinsic characteristics ...strongly modulate the outcome of viral infections. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti‐viral immune activation and, counterintuitively, accelerates virus control. In this review we summarize the mechanisms that contribute to enforced viral replication.
Antigen‐presenting cells and CD169+ macrophages exhibit enforced viral replication after infection with the model viruses lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). Ubiquitin‐specific peptidase 18 (Usp18), an endogenous type I interferon blocker in CD169+ macrophages, has been identified as a proviral gene, as are B cell activating factor (BAFF) and carcinoembryonic antigen‐related cell adhesion molecule 1 (CEACAM1). Lymphotoxins (LT) strongly enhance viral replication in the spleen and lymph nodes. All these factors modulate splenic architecture and thereby promote the development of CD169+ macrophages. Tumor necrosis factor alpha (TNF‐α) and nuclear factor kappa‐light‐chain‐enhancer of activated B cell signaling (NF‐κB) have been found to promote the survival of infected CD169+ macrophages, thereby similarly promoting enforced viral replication.
Association of autoimmune disease with infections is evident from (1) autoimmune phenomena described during a chronic virus infection; (2) onset of autoimmune disease simultaneous to viral infections; and (3) experimental evidence. Involvement of virus infection during onset of type I diabetes is strongly evident. Epstein–Bar virus (EBV) infection was discussed to be involved in the pathogenesis of systemic lupus erythematosus.
In conclusion, several mechanisms promote viral replication in secondary lymphatic organs. Identifying such factors in humans is a challenge for future studies.
Viral infections can be fatal because of the direct cytopathic effects of the virus or the induction of a strong, uncontrolled inflammatory response. Recently we determined the circumstances under which enhanced replication of virus within the lymphoid tissue is beneficial for the outcome of a disease. This enforced viral replication promotes anti‐viral immune activation and, counterintuitively, accelerates virus control.
Fentanyl is one of the most frequently administered intraoperative drugs and may increase the risk of postoperative respiratory complications (PRCs).
We performed a pre-specified analysis of 145 735 ...adult non-cardiac surgical cases under general anaesthesia. Using multivariable logistic regression, we evaluated the association of intraoperative fentanyl dose and PRCs within 3 days after surgery (defined as reintubation, respiratory failure, pneumonia, pulmonary oedema, or atelectasis). We examined effect modification by patient characteristics, surgical site, and anaesthetics used.
PRCs within 3 days after surgery occurred in 18 839 (12.9%) patients. In comparison with high intraoperative fentanyl doses median: 3.85; inter-quartile range (IQR): 3.42–4.50 μg kg−1, quartile 4 (Q4), low intraoperative fentanyl dose median: 0.80, IQR: 0.00–1.14 μg kg−1, quartile 1 (Q1) was significantly associated with lower odds of PRCs Q1 vs Q4: 10.9% vs 16.2%; adjusted odds ratio (aOR) 0.79; 95% confidence intervals (CI) 0.75–0.84; P<0.001; adjusted absolute risk difference (aARD) −1.7%. This effect was augmented by thoracic surgery (P for interaction <0.001; aARD −6.2%), high doses of inhalation anaesthetics (P for interaction=0.016; aARD −2.2%) and neuromuscular blocking agents (NMBAs) (P for interaction=0.001; aARD −3.4%). Exploratory analysis demonstrated that compared with no fentanyl, low-dose fentanyl was associated with lower rates of PRCs (decile 2 vs decile 1: aOR 0.82, CI 0.75–0.89, P<0.001).
Intraoperative low-dose fentanyl (about 60–120 μg for a 70 kg patient) was associated with lower risk of postoperative respiratory complications compared with both no fentanyl and high-dose fentanyl. Beneficial effects of low-dose fentanyl were magnified in specific patient subgroups.
NCT03198208.
The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital ...readmission.
We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors.
Compared with low intraoperative opioid dosing quintile 1, median (inter-quartile range): 8 (4–9) mg morphine equivalents, exposure to high-dose opioids during surgery quintile 5: 32 (27–41) equivalents is an independent predictor of 30-day readmission odds ratio (OR) 1.15 (95% confidence interval 1.07–1.24); P<0.001. Ambulatory surgery patients receiving high opioid doses were found to have the greatest adjusted risk of readmission (OR 1.75; P<0.001) with a clear dose–response effect across quintiles (P for trend <0.05), and were more likely to be readmitted early (postoperative days 0–2 vs 3–30; P<0.001). Opioid class modified the association between total opioid dose and readmission, with longer-acting opioids demonstrating a stronger influence (P<0.001). We observed significant practice variability across individual anaesthetists in the utilisation of opioids that could not be explained by patient- and case-specific factors.
High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.
Precision measurements of nuclear
β
decay are among the most sensitive methods to probe beyond standard model (BSM) physics in the neutrino sector. In particular, momentum conservation between the ...emitted decay products in the final state is sensitive to any new physics that couples to the neutrino mass. One way to observe these momentum recoil effects experimentally is through high-precision measurements of nuclear electron capture (EC) decay where the final state only contains the neutrino and a recoiling atom. The Beryllium Electron capture in Superconducting Tunnel junctions (BeEST) experiment precisely measures the eV-scale radiation that follows the radioactive decay of
7
Be implanted into sensitive superconducting tunnel junction (STJ) quantum sensors. STJs are ideally suited for measurements of this type due to their high resolution at the low recoil energies in EC decay, and their high-rate counting capabilities. We present the motivation for the BeEST experiment and describe the various phases of the project.
A
bstract
We study the phenomenology of a hypercharge-zero SU (2) triplet scalar whose existence is motivated by two-step electroweak symmetry-breaking. We consider both the possibility that the ...triplets are stable and contribute to the dark matter density, or that they decay via mixing with the standard model Higgs boson. The former is constrained by disappearing charged track searches at the LHC and by dark matter direct detection experiments, while the latter is constrained by existing multilepton collider searches. We find that a two-step electroweak phase transition involving a stable triplet with a negative quadratic term is ruled out by direct detection searches, while an unstable triplet with a mass less than 230 GeV is excluded at 95% confidence level.
Introduction
This study explores the uses of microcalorimetry to detect Mycobacterium tuberculosis (TB) in sputum. Microcalorimetry measures metabolic heat evolution during cellular proliferation of ...tuberculosis (TB) and is considered as a possible alternative to conventional diagnostic tools.
Objectives
To compare the time to detection (TTD) from the BACTEC™ MGIT™ 960 and the calScreener™ calorimetric system.
Methods
Sixty‐four sputa samples were selected from patients with confirmed pulmonary tuberculosis. Those sample were then decontaminated and analysed using calorimetry and BACTEC MGIT 960 system.
Results
The incubation period until detection of M. tuberculosis in the sample was 8·5 ± 3·7 days for the MGIT system and 10·1 ± 4·1 days (mean ± SD) for calorimetry.
Conclusions
The microincubations in the 48‐well format calScreener offers potential for rapid and accurate diagnostic of TB in different samples. Although TTD from calorimetry is still longer than with the MGIT, our findings suggest that several improvements are possible. Still, the instrument is ideal for continuous, real‐time analysis of net metabolic heat release of limited sample numbers.
Significance and Impact of the Study
Our result emphasizes that with further optimization, calorimetry can become an alternative detection method for tuberculosis.
Preliminary studies that analyzed surrogate markers have suggested that operating room (OR) door openings may be a risk factor for surgical site infection (SSI). We therefore aimed to estimate the ...effect of OR door openings on SSI risk in patients undergoing cardiac surgery.
This prospective, observational study involved consecutive patients undergoing cardiac surgery in 2 prespecified ORs equipped with automatic door-counting devices from June 2016 to October 2017. Occurrence of an SSI within 30 days after cardiac surgery was our primary outcome measure. Respective outcome data were obtained from a national SSI surveillance cohort. We analyzed the relationship between mean OR door opening frequencies and SSI risk by use of uni- and multivariable Cox regression models.
A total of 301 594 OR door openings were recorded during the study period, with 87 676 eligible door openings being logged between incision and skin closure. There were 688 patients included in the study, of whom 24 (3.5%) developed an SSI within 30 days after surgery. In uni- and multivariable analysis, an increased mean door opening frequency during cardiac surgery was associated with higher risk for consecutive SSI (adjusted hazard ratio per 5-unit increment, 1.49; 95% confidence interval, 1.11-2.00; P = .008). The observed effect was driven by internal OR door openings toward the clean instrument preparation room.
Frequent door openings during cardiac surgery were independently associated with an increased risk for SSI. This finding warrants further study to establish a potentially causal relationship between OR door openings and the occurrence of SSI.
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