New sepsis and septic shock definitions could change the epidemiology of sepsis because of differences in criteria. We therefore compared the sepsis populations identified by the old and new ...definitions.
We used a high-quality, national, intensive care unit (ICU) database of 654 918 consecutive admissions to 189 adult ICUs in England, from January 2011 to December 2015. Primary outcome was acute hospital mortality. We compared old (Sepsis-2) and new (Sepsis-3) incidence, outcomes, trends in outcomes, and predictive validity of sepsis and septic shock populations.
From among 197 724 Sepsis-2 severe sepsis and 197 142 Sepsis-3 sepsis cases, we identified 153 257 Sepsis-2 septic shock and 39 262 Sepsis-3 septic shock cases. The extrapolated population incidence of Sepsis-3 sepsis and Sepsis-3 septic shock was 101.8 and 19.3 per 100 000 person-years, respectively, in 2015. Sepsis-2 severe sepsis and Sepsis-3 sepsis had similar incidence, similar mortality and showed significant risk-adjusted improvements in mortality over time. Sepsis-3 septic shock had a much higher Acute Physiology And Chronic Health Evaluation II (APACHE II) score, greater mortality and no risk-adjusted trends in mortality improvement compared with Sepsis-2 septic shock. ICU admissions identified either as Sepsis-3 sepsis or septic shock and as Sepsis-2 severe sepsis or septic shock had significantly greater risk-adjusted odds of death compared with non-sepsis admissions (P<0.001). The predictive validity was greatest for Sepsis-3 septic shock.
In an ICU database, compared with Sepsis-2, Sepsis-3 identifies a similar sepsis population with 92% overlap and much smaller septic shock population with improved predictive validity.
Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following ...vaccination in the general population. We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867). We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test. We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273. This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test. We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test. Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273. Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.
Recent reports highlight a new clinical syndrome in children related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
-multisystem inflammatory syndrome in children (MIS-C)-which ...comprises multiorgan dysfunction and systemic inflammation
. We performed peripheral leukocyte phenotyping in 25 children with MIS-C, in the acute (n = 23; worst illness within 72 h of admission), resolution (n = 14; clinical improvement) and convalescent (n = 10; first outpatient visit) phases of the illness and used samples from seven age-matched healthy controls for comparisons. Among the MIS-C cohort, 17 (68%) children were SARS-CoV-2 seropositive, suggesting previous SARS-CoV-2 infections
, and these children had more severe disease. In the acute phase of MIS-C, we observed high levels of interleukin-1β (IL-1β), IL-6, IL-8, IL-10, IL-17, interferon-γ and differential T and B cell subset lymphopenia. High CD64 expression on neutrophils and monocytes, and high HLA-DR expression on γδ and CD4
CCR7
T cells in the acute phase, suggested that these immune cell populations were activated. Antigen-presenting cells had low HLA-DR and CD86 expression, potentially indicative of impaired antigen presentation. These features normalized over the resolution and convalescence phases. Overall, MIS-C presents as an immunopathogenic illness
and appears distinct from Kawasaki disease.
Sepsis results in complex alterations to the immune system. Our understanding of how these alterations in immune responses could help characterize extreme immune phenotypes, identify biomarkers with ...the ability to stratify patients for therapeutic interventions, surrogates in the causal pathway of clinical end-points, and treatable traits are still rudimentary. A methodologically rigorous, consensus-based approach should enrich sepsis immune subpopulations to increase the probability of successful trials.
This article focuses on the design of super compact, polarization insensitive with wide angular stability, ultrathin triple‐band metamaterial absorber. The unit cell comprising patches achieves ...almost perfect absorption (close to 100%) at C, X, and Ku band thereby justifying the term perfect metamaterial absorber. The structure provides 99.96%, 99.98%, and 99.62% absorptivity at the 4.75 GHz (C‐band), 9.47 GHz (X‐band), and 14.40 GHz (Ku‐band), respectively. The dimension of the structure is super compact of the order of 7.2 × 7.2 × 0.8 mm3 along with the ultrathin profile. The unit cell thickness is 0.012 λlowest (where λlowest is at a lowest cut‐off frequency). The proposed absorber comprises an outermost ring, split ring, innermost ring and square line with triangle patches at the boundary. The combinational effect of rings and internal patch provides perfect absorption at designated frequencies. Further, equivalent circuit is explained for the proposed design. The absorptivity remains insensitive towards transverse electric and transverse magnetic polarized wave and exhibits matched absorption. Moreover, the stability of the proposed design is validated with the different incident (for TE and TM modes) and polarization angles. The results are found close to perfect absorption. Finally, the simulated results are validated with measured results and found in close agreement.
ABSTRACT
Polyimides possess good mechanical properties, favorable dielectric properties, and chemical inertness, which enabled them to find applications in microelectronic industries. The dielectric ...constant of the polyimides varies between 2.5 and 4, which is rather high for such applications. Hence, synthesizing polyimides with still lower dielectric constant has become one of the critical research confronts. As the properties of a terpolyimides (TPI) could be altered as per the requirement, it was synthesized by combining the dianhydrides 3,3′,4,4′‐biphenyldianhydride, 3,3′,4,4′‐oxydiphthalicdianhydride, and 4,4′‐(hexafluoroisopropylidene) with a diamine 4,4′‐(hexafluoroisopropylidene)dianiline or 2,2‐bis4‐(4‐amino phenoxy)phenylhexafluoropropane. As porous covalent triazine framework (CTF‐1) is capable of capturing much air within its pores and interfacial voids, it was combined with the TPI matrix in different loadings to obtain CTF‐1/TPI composite films with low dielectric constant. The composites exhibited high thermal stability, as their thermal decomposition occurred above 520°C. The tensile properties and the dielectric constant of the composites declined with the raise in CTF‐1 loading up to 4%. The decrease in dielectric constant is essentially due to the incorporation of air voids (dielectric constant of air ~1) in the TPI matrix due to the inclusion of porous CTF‐1.
Synthesis of CTF‐1/Terpolyimide composite
Background and Purpose
Platelet function during inflammation is dependent on activation by endogenous nucleotides. Non‐canonical signalling via the P2Y1 receptor is important for these non‐thrombotic ...functions of platelets. However, apart from ADP, the role of other endogenous nucleotides acting as agonists at P2Y1 receptors is unknown. This study compared the effects of ADP, Ap3A, NAD+, ADP‐ribose, and Up4A on platelet functions contributing to inflammation or haemostasis.
Experimental Approach
Platelets obtained from healthy human volunteers were incubated with ADP, Ap3A, NAD+, ADP‐ribose, or Up4A, with aggregation and fibrinogen binding measured (examples of function during haemostasis) or before exposure to fMLP to measure platelet chemotaxis (an inflammatory function). In silico molecular docking of these nucleotides to the binding pocket of P2Y1 receptors was then assessed.
Key Results
Platelet aggregation and binding to fibrinogen induced by ADP was not mimicked by NAD+, ADP‐ribose, and Up4A. However, these endogenous nucleotides induced P2Y1‐dependent platelet chemotaxis, an effect that required RhoA and Rac‐1 activity, but not canonical PLC activity. Analysis of molecular docking of the P2Y1 receptor revealed distinct differences of amino acid interactions and depth of fit within the binding pocket for Ap3A, NAD+, ADP‐ribose, or Up4A compared with ADP.
Conclusion and Implications
Platelet function (aggregation vs motility) can be differentially modulated by biased‐agonist activation of P2Y1 receptors. This may be due to the character of the ligand‐binding pocket interaction. This has implications for future therapeutic strategies aimed to suppress platelet activation during inflammation without affecting haemostasis as is the requirement of current ant‐platelet drugs.
LINKED ARTICLES
This article is part of a themed issue on Platelet purinergic receptor and non‐thrombotic disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.4/issuetoc
Asthma in Adults Rabin, Alexander S; Junck, Larry; Shankar, Hari M
The New England journal of medicine,
11/2023, Volume:
389, Issue:
22
Journal Article
PDF
