Prone Vs. Supine Position Ventilation in Intubated COVID-19 Patients: A Systematic Review and Meta-Analysis

Whether prone positioning of patients undergoing mechanical ventilation for COVID-19 pneumonia has benefits over supine positioning is not clear. We conducted a systematic review with meta-analysis to determine whether prone versus supine positioning during ventilation resulted in different outcomes for patients with COVID-19 pneumonia. We searched Ovid Medline, Embase, and Web of Science for prospective and retrospective studies up through April 2023. We included studies that compared outcomes of patients with COVID-19 after ventilation in prone and supine positions. The primary outcomes were three mortality measures: hospital, overall, and intensive care unit (ICU). Secondary outcomes were mechanical ventilation days, intensive care unit (ICU) length of stay, and hospital length of stay. We conducted risk of bias analysis and used meta-analysis software to analyze results. Mean difference (MD) was used for continuous data, and odds ratio (OR) was used for dichotomous data, both with 95% CIs. Significant heterogeneity (I(2)) was considered if I(2) was \u3e50%. A statistically significant result was considered if the p-value was \u3c0.05. Of 1787 articles identified, 93 were retrieved, and seven retrospective cohort studies encompassing 5216 patients with COVID-19 were analyzed. ICU mortality was significantly higher in the prone group (OR 2.22, 95% CI 1.43-3.43; p=0.0004). No statistically significant difference was observed between prone and supine groups for hospital mortality (OR, 0.95; 95% CI, 0.66-1.37; p=0.78) or overall mortality (OR, 1.08; 95% CI, 0.72-1.64; p=0.71). Studies that analyzed primary outcomes had significant heterogeneity. Hospital length of stay was significantly higher in the prone than in the supine group (MD, 6.06; 95 % CI, 3.15-8.97; p\u3c0.0001). ICU length of stay and days of mechanical ventilation did not differ between the two groups. In conclusion, mechanical ventilation with prone positioning for all patients with COVID-19 pneumonia may not provide a mortality benefit over supine positioning

Neuron-glia crosstalk mediate the neurotoxic effects of ketamine via extracellular vesicles

Background: General anesthetics (GA) are associated with neurodevelopmental abnormalities including cell death, cognitive and behavioral changes. There is now powerful evidence for non-cell autonomous mechanisms in almost every pathological condition in the brain, especially relevant to glial cells, mainly astrocytes and microglia, that exhibit structural and functional contacts with neurons. These interactions were recently reported to occur via the secretion of extracellular vesicles (EVs). Here, we employed primary human neural cells to analyze ketamine effects focusing on the functions of glial cells and their polarization/differentiation state. We also explored the roles of extracellular vesicles (EVs) and different components of the BDNF pathway. Methods: Ketamine effects were analyzed on human neuronal and glial cell proliferation and apoptosis and astrocytic (A1/A2 ) and microglial (M1/M2) cell activation were analyzed. The impact of the neuron-glial cell interactions in the neurotoxic effects of ketamine was analyzed using transwell co-cultures. The role of the brainderived neurotrophic factor (BDNF) pathway, was analyzed using RT-PCR, ELISA western blot and gene silencing. EVs secreted by ketamine-treated cells were isolated, characterized and analyzed for their effects in neuron-glia cell interactions. Data were analyzed using analysis of variance or a Student\u27s t test with correction for data sets with unequal variances. Results: Ketamine induced neuronal and oligodendrocytic cell apoptosis and promoted the expression of proinflammatory astrocytes (A1) and microglia (M1) phenotypes. Astrocytes and microglia enhanced the neurotoxic effects of ketamine on neuronal cells, whereas neurons increased oligodendrocyte cell death. Ketamine modulated different components in the BDNF pathway: decreasing BDNF secretion in neurons and astrocytes while increasing the expression of p75 in neurons and oligodendrocytes. In addition, ketamine treatment increased the lncRNA BDNF-AS levels and the secretion of pro-BDNF secretion. We found an important role of EVs secreted by ketamine-treated astrocytes in neuronal cell death by delivering BDNF-AS. Conclusions: Ketamine neurotoxicity involves both autonomous and non-cell autonomous mechanisms andomponents of the BDNF pathway expressed by neurons and glial cells represent major regulators of ketamine effects. We demonstrated for the first time a role of EVs as important mediators of ketamine effects by the delivery of specific non-coding RNAs. These results may contribute to a better understanding of cellular and molecular mechanisms underlying ketamine neurotoxic effects in humans and to the development of potential approaches to decrease its neurodevelopmental impact

Emergent Surgical Airway Skills: Time to Re-evaluate the Competencies

Introduction: One of the most challenging scenarios an anesthesia provider can face is treating a can\u27t intubate can\u27t ventilate (CICV) patient. The incidence of CICV is estimated to be around one in 10,000 cases. According to the American Society of Anesthesiology Closed Claims Study, adverse respiratory events are the most common type of injury, with difficult intubation and ventilation contributing to the majority of these cases. The objective of this non-interventional quality improvement project was to evaluate the prior training, exposure, and self-reported confidence in handling the CICV scenario among anesthesia providers at Henry Ford Hospital in Detroit, MI. Methods: An online questionnaire was distributed via email to all residents, certified registered nurse anesthetists (CRNAs), and attending anesthesiologists in March 2021. The email contained a link to an online questionnaire via Microsoft Forms (Microsoft Corporation, Redmond, WA). Univariate group comparisons were carried out between the respondents\u27 role (attending, CRNA, or resident), as well as between the number of years that the respondents were in practice (\u3c 5 years, 5-10 years, \u3e 10 years). Results: Out of the total 170 anesthesia providers, 119 participated in the study where 54 (45%) were attendings, 44 (37%) were residents, and 21 (18%) were CRNAs. The majority (75%) did not know the surgical airway kit location, and 87% had not performed the surgical airway procedure before. The vast majority (96.7%) recommended simulation training compared to online training or lecture series, and just over 50% recommended annual training frequency. When looking at the differences in responses based on years of experience as an anesthesia provider, the majority of those with \u3e 10 years in practice knew how to perform the surgical airway technique while respondents with \u3c 5 years did not know how to perform the technique, and 50% of those with five to 10 years experience knew how to perform the surgical airway procedure for a CICV scenario. Conclusion: Although there were many significant differences observed between the various provider roles and years in practice, surprisingly, the responses revealed both a lack of experience and confidence in performing the surgical airway procedure in all provider roles. These findings highlight a need for better emergency airway teaching and training. These findings will be used to guide the design and implementation of improved surgical airway training for residents, CRNAs, and attending anesthesiologists with the goal of better preparedness for handling a CICV scenario

Sequential Organ Failure Assessment (SOFA) Score and Mortality Prediction in Patients With Severe Respiratory Distress Secondary to COVID-19

Background: This study looks at the validity of the sequential organ failure assessment score (SOFA) in detecting mortality in patients with Coronavirus disease of 2019 (COVID-19) pneumonia. Also, it is looking to determine the optimal SOFA score that will discriminate between mortality and survival. Methods: It is a retrospective chart review of the patients admitted to Henry Ford Hospital from March 2020 to December 2020 with COVID-19 pneumonia who developed severe respiratory distress. We collected the following information; patient demographics (age, sex, body mass index), co-morbidities (history of diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease, coronary artery disease, or cancer), SOFA scores (the ratio of arterial oxygen tension (PaO(2)) to the fraction of inspired oxygen, Glasgow Coma Scale (GCS) score, mean arterial pressure, serum creatinine level, bilirubin level, and platelet count) as well as inpatient mortality. Results: There were 320 patients; out of these, 111 were intubated. The receiver operating characteristic (ROC) curve for SOFA at the moment of inclusion in the study had an area under the curve of 0.883. The optimal point for discrimination between mortality and survival is SOFA of 5. A SOFA score of less than two is associated with 100% survival, while a score of more than 11 is associated with 100% mortality. Conclusions: SOFA score in COVID-19 patients with severe respiratory distress strongly correlates with the initial SOFA score. It is a valuable tool for predicting mortality in COVID-19 patients

Effect of Intubation Timing on the Outcome of Patients With Severe Respiratory Distress Secondary to COVID-19 Pneumonia.

Background: The optimal timing of intubation for critically ill patients with severe respiratory illness remains controversial among healthcare providers. The coronavirus disease 2019 (COVID-19) pandemic has raised even more questions about when to implement this life-saving therapy. While one group of providers prefers early intubation for patients with respiratory distress because these patients may deteriorate rapidly without it, other providers believe that intubation should be delayed or avoided because of its associated risks including worse outcomes. Research question: Our objective was to assess whether the timing of intubation in patients with severe COVID-19 pneumonia was associated with differences in mortality or other outcomes. Study design and methods: This was a single-center retrospective observational cohort study. We analyzed outcomes of patients who were intubated secondary to COVID-19 pneumonia between March 13, 2020, and December 12, 2020, at Henry Ford Hospital in Detroit, Michigan. Patients were categorized into two groups: early intubated (intubated within 24 hours of the onset of severe respiratory distress) and late intubated (intubated after 24 hours of the onset of severe respiratory distress). Demographics, comorbidities, respiratory rate oxygenation (ROX) index, sequential organ failure assessment (SOFA) score, and treatment received were compared between groups. The primary outcome was mortality. Secondary outcomes were ventilation time, intensive care unit stay, hospital length of stay, and discharge disposition. Post hoc and Kaplan-Meier survival analyses were performed. Results: A total of 110 patients were included: 55 early intubated and 55 late intubated. We did not observe a significant difference in overall mortality between the early intubated (43%) and the late intubated groups (53%) (p = 0.34). There was no statistically significant difference in patients\u27 baseline characteristics including SOFA scores (the early intubation group had a mean score of 7.5 compared to 6.7 in the late intubation group). Based on the ROX index, the early intubation group had significantly more patients with a reduced risk of intubation (45%) than the late group (27%) (p = 0.029). The early intubation group was treated with a high-flow nasal cannula at a significantly lower rate (47%) than the late intubation group (83%) (p \u3c 0.001). Significant differences in patient baseline characteristics, treatment received, and other outcomes were not observed. Post hoc analysis adjusting for SOFA score between 0 and 9 revealed significantly higher mortality in the late intubation group (49%) than in the early intubation group (26%) (p = 0.03). Patients in the 0 to 9 SOFA group who were intubated later had 2.7 times the odds of dying during hospital admission compared to patients who were intubated early (CI, 1.09-6.67). Interpretation: The timing of intubation for patients with severe COVID-19 pneumonia was not significantly associated with overall mortality or other patient outcomes. However, within the subgroup of patients with SOFA scores of 9 or lower at the time of intubation, patients intubated after 24 hours of the onset of respiratory distress had a higher risk of death than those who were intubated within 24 hours of respiratory distress. Thus, patients with COVID-19 pneumonia who are not at a high level of organ dysfunction may benefit from early mechanical ventilation

Propofol Inhibits Glioma Stem Cell Growth and Migration and Their Interaction with Microglia via BDNF-AS and Extracellular Vesicles

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. GBM contains a small subpopulation of glioma stem cells (GSCs) that are implicated in treatment resistance, tumor infiltration, and recurrence, and are thereby considered important therapeutic targets. Recent clinical studies have suggested that the choice of general anesthetic (GA), particularly propofol, during tumor resection, affects subsequent tumor response to treatments and patient prognosis. In this study, we investigated the molecular mechanisms underlying propofol\u27s anti-tumor effects on GSCs and their interaction with microglia cells. Propofol exerted a dose-dependent inhibitory effect on the self-renewal, expression of mesenchymal markers, and migration of GSCs and sensitized them to both temozolomide (TMZ) and radiation. At higher concentrations, propofol induced a large degree of cell death, as demonstrated using microfluid chip technology. Propofol increased the expression of the lncRNA BDNF-AS, which acts as a tumor suppressor in GBM, and silencing of this lncRNA partially abrogated propofol\u27s effects. Propofol also inhibited the pro-tumorigenic GSC-microglia crosstalk via extracellular vesicles (EVs) and delivery of BDNF-AS. In conclusion, propofol exerted anti-tumor effects on GSCs, sensitized these cells to radiation and TMZ, and inhibited their pro-tumorigenic interactions with microglia via transfer of BDNF-AS by EVs

Measurement of the flavour composition of dijet events in pp collisions at root s=7 TeV with the ATLAS detector

This paper describes a measurement of the flavour composition of dijet events produced in pp collisions at √s=7 TeV using the ATLAS detector. The measurement uses the full 2010 data sample, corresponding to an integrated luminosity of 39 pb−1. Six possible combinations of light, charm and bottom jets are identified in the dijet events, where the jet flavour is defined by the presence of bottom, charm or solely light flavour hadrons in the jet. Kinematic variables, based on the properties of displaced decay vertices and optimised for jet flavour identification, are used in a multidimensional template fit to measure the fractions of these dijet flavour states as functions of the leading jet transverse momentum in the range 40 GeV to 500 GeV and jet rapidity |y|<2.1. The fit results agree with the predictions of leading- and next-to-leading-order calculations, with the exception of the dijet fraction composed of bottom and light flavour jets, which is underestimated by all models at large transverse jet momenta. The ability to identify jets containing two b-hadrons, originating from e.g. gluon splitting, is demonstrated. The difference between bottom jet production rates in leading and subleading jets is consistent with the next-to-leading-order predictions

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN