Cytokine storm syndrome (CSS) is a critical clinical condition induced by a cascade of cytokine activation, characterized by overwhelming systemic inflammation, hyperferritinaemia, haemodynamic ...instability and multiple organ failure (MOF). At the end of 2019, the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) emerged in Wuhan, China, and rapidly developed into a global pandemic. More and more evidence shows that there is a dramatic increase of inflammatory cytokines in patients with COVID‐19, suggesting the existence of cytokine storm in some critical illness patients. Here, we summarize the pathogenesis, clinical manifestation of CSS, and highlight the current understanding about the recognition and potential therapeutic options of CSS in COVID‐19.
Background
Patients undergoing major non‐cardiac surgery are at risk of cardiovascular complications. Raised levels of high‐sensitivity troponin are frequently detected before operation among these ...patients. However, the prognostic value of high‐sensitivity troponin in predicting postoperative outcomes remains unclear.
Methods
A systematic search of PubMed, Embase and Science Citation Index Expanded was undertaken for observational studies published before March 2018 that reported associations between raised preoperative levels of high‐sensitivity troponin and postoperative major adverse cardiac events and/or mortality after non‐cardiac surgery. Meta‐analyses were performed, where possible, using random‐effects models.
Results
Seven cohort studies with a total of 4836 patients were included. A raised preoperative high‐sensitivity troponin level was associated with a higher risk of short‐term major adverse cardiac events (risk ratio (RR) 2·92, 95 per cent c.i. 1·96 to 4·37; I2 = 82·6 per cent), short‐term mortality (RR 5·39, 3·21 to 9·06; I2 = 0 per cent) and long‐term mortality (RR 2·90, 1·83 to 4·59, I2 = 74·2 per cent). The addition of preoperative high‐sensitivity troponin measurement provided improvements in cardiovascular risk discrimination (increase in C‐index ranged from 0·058 to 0·109) and classification (quantified by continuous net reclassification improvement) compared with Lee's Revised Cardiac Risk Index alone. There was substantial heterogeneity and inadequate risk stratification analysis in the included studies.
Conclusion
Raised preoperative levels of high‐sensitivity troponin appear to represent a risk for postoperative major adverse cardiac events and mortality. Further study is required before high‐sensitivity troponin can be used to predict risk stratification in routine clinical practice.
Antecedentes
Los pacientes a los que se realiza una cirugía mayor no cardíaca tienen riesgo de presentar complicaciones cardiovasculares. En estos pacientes se observan con frecuencia niveles preoperatorios elevados de troponina de alta sensibilidad (high‐sensitivity troponin, hs‐cTn). Sin embargo, el valor pronóstico de la hs‐cTn para predecir los resultados postoperatorios no está bien definido.
Métodos
Se realizó una búsqueda sistemática en las bases de datos PubMed, EMBASE y Science Citation Index Expanded de estudios observacionales publicados antes de marzo de 2018 que analizasen la posible relación de los niveles elevados preoperatorios de hs‐cTn y los efectos adversos graves de tipo cardíaco (major adverse cardiac events, MACE) postoperatorios y/o la mortalidad después de la cirugía no cardíaca. Se realizó el metaanálisis utilizando modelos de efectos aleatorios siempre que fuera posible.
Resultados
Se incluyeron siete estudios de cohortes con un total de 4.836 pacientes. La elevación preoperatoria de hs‐cTn se asoció con un mayor riesgo de MACE a corto plazo (tasa de riesgo, risk ratio, RR 2,92, i.c. del 95% 1,96‐4,37, I2 = 82,6%) y con la mortalidad a corto plazo (RR 5,39, i.c. del 95 % 3,21‐9,06, I2 = 0%) y a largo plazo (RR 2,90, i.c. del 95% 1,83‐4,59, I2 = 74,2%). Añadir la medición preoperatoria de hs‐cTn mejoró la capacidad discriminativa para el riesgo cardiovascular (aumento de 5,8% a 10,9% en el índice C) y también la clasificación de los pacientes (cuantificada mediante el índice de reclasificación neta continua) en comparación con el uso de solo el índice de riesgo cardíaco revisado de Lee. En los estudios incluidos, hubo gran heterogeneidad y análisis inadecuado de la estratificación del riesgo.
Conclusión
Los niveles preoperatorios elevados de troponina de alta sensibilidad parecen ser un marcador de riesgo de efectos adversos graves de tipo cardíaco en el postoperatorio y de mortalidad. Se requieren más estudios antes de utilizar la troponina de alta sensibilidad para la estratificación del riesgo en la práctica clínica rutinaria.
This systematic review and meta‐analysis explored the prognostic implication of preoperative high‐sensitivity cardiac troponin (hs‐cTn) level in patients undergoing non‐cardiac surgery who are at risk of cardiovascular complications. An increase in preoperative hs‐cTn level was identified as a risk marker for postoperative major adverse cardiac events (MACE) and death. Further study is required before hs‐cTn assays could be used for routine preoperative risk stratification.
High‐sensitivity cardiac troponin appears useful
Abstract
Spin-valley locking in monolayer transition metal dichalcogenides has attracted enormous interest, since it offers potential for valleytronic and optoelectronic applications. Such an exotic ...electronic state has sparsely been seen in bulk materials. Here, we report spin-valley locking in a Dirac semimetal BaMnSb
2
. This is revealed by comprehensive studies using first principles calculations, tight-binding and effective model analyses, angle-resolved photoemission spectroscopy measurements. Moreover, this material also exhibits a stacked quantum Hall effect (QHE). The spin-valley degeneracy extracted from the QHE is close to 2. This result, together with the Landau level spin splitting, further confirms the spin-valley locking picture. In the extreme quantum limit, we also observed a plateau in the
z
-axis resistance, suggestive of a two-dimensional chiral surface state present in the quantum Hall state. These findings establish BaMnSb
2
as a rare platform for exploring coupled spin and valley physics in bulk single crystals and accessing 3D interacting topological states.
We report terahertz (THz) light-induced second harmonic generation, in superconductors with inversion symmetry that forbid even-order nonlinearities. The THz second harmonic emission vanishes above ...the superconductor critical temperature and arises from precession of twisted Anderson pseudospins at a multicycle, THz driving frequency that is not allowed by equilibrium symmetry. We explain the microscopic physics by a dynamical symmetry breaking principle at sub-THz-cycle by using quantum kinetic modeling of the interplay between strong THz-lightwave nonlinearity and pulse propagation. The resulting nonzero integrated pulse area inside the superconductor leads to light-induced nonlinear supercurrents due to subcycle Cooper pair acceleration, in contrast to dc-biased superconductors, which can be controlled by the band structure and THz driving field below the superconducting gap.
Cracks in solid-state materials are typically irreversible. Here we report electrically reversible opening and closing of nanoscale cracks in an intermetallic thin film grown on a ferroelectric ...substrate driven by a small electric field (~0.83 kV/cm). Accordingly, a nonvolatile colossal electroresistance on-off ratio of more than 10
is measured across the cracks in the intermetallic film at room temperature. Cracks are easily formed with low-frequency voltage cycling and remain stable when the device is operated at high frequency, which offers intriguing potential for next-generation high-frequency memory applications. Moreover, endurance testing demonstrates that the opening and closing of such cracks can reach over 10
cycles under 10-μs pulses, without catastrophic failure of the film.
A number of poleward moving events were observed between 1130 and 1300 UT on 11 February 2004, during periods of southward interplanetary magnetic field (IMF), while the steerable antenna of the ...European Incoherent Scatter (EISCAT) Svalbard radar (ESR) and the Tromsø VHF radar pointed nearly northward at low elevation. In this interval, simultaneous SuperDARN CUTLASS Finland radar measurements showed poleward moving radar aurora forms (PMRAFs) which appeared very similar to the density enhancements observed by the ESR northward pointing antenna. These events appeared quasiperiodically with a period of about 10 min. Comparing the observations from the above three radars, it is inferred that there is an almost one‐to‐one correspondence between the poleward moving plasma concentration enhancements (PMPCEs) observed by the ESR and the VHF radar and the PMRAFs measured by the CUTLASS Finland radar. These observations are consistent with the interpretation that the polar cap patch material was generated by photoionization at subauroral latitudes and that the plasma was structured by bursts of magnetopause reconnection giving access to the polar cap. There is clear evidence that plasma structuring into patches was dependent on the variability in IMF ∣By∣. The duration of these events implies that the average evolution time of the newly opened flux tubes from the subauroral region to the polar cap was about 33 min.
Key Points
The observations reveal the formation of polar cap patches
The formation of polar cap patch was dependent on the variability in IMF By
Implied open flux tube evolves ∼33 min from subauroral region to the polar cap
Leptomeningeal metastases (LM) are more frequent in non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutations. Due to limited access to leptomeningeal lesions, the ...purpose of this study was to explore the potential role of cerebrospinal fluid (CSF) as a source of liquid biopsy in patients with LM.
Primary tumor, CSF, and plasma in NSCLC with LM were tested by next-generation sequencing. In total, 45 patients with suspected LM underwent lumbar puncture, and those with EGFR mutations diagnosed with LM were enrolled.
A total of 28 patients were enrolled in this cohort; CSF and plasma were available in 26 patients, respectively. Driver genes were detected in 100% (26/26), 84.6% (22/26), and 73.1% (19/26) of samples comprising CSF cell-free DNA (cfDNA), CSF precipitates, and plasma, respectively; 92.3% (24/26) of patients had much higher allele fractions in CSF cfDNA than the other two media. Unique genetic profiles were captured in CSF cfDNA compared with those in plasma and primary tissue. Multiple copy number variations (CNVs) were mainly identified in CSF cfDNA, and MET copy number gain identified in 47.8% (11/23) of patients was the most frequent one, while other CNVs included ERBB2, KRAS, ALK, and MYC. Moreover, loss of heterozygosity (LOH) of TP53 was identified in 73.1% (19/26) CSF cfDNA, which was much higher than that in plasma (2/26, 7.7%; P<0.001). There was a trend towards a higher frequency of concomitant resistance mutations in patients with TP53 LOH than those without (70.6% versus 33.3%; P=0.162). EGFR T790M was identified in CSF cfDNA of 30.4% (7/23) of patients who experienced TKI progression.
CSF cfDNA could reveal the unique genetic profiles of LM and should be considered as the most representative liquid biopsy medium for LM in EGFR-mutant NSCLC.
This article presents a hysteretic water retention curve (WRC) and unsaturated hydraulic conductivity model for deformable soils based on the change in pore-size distribution (PSD). The PSD plays a ...decisive role in the water retention behaviour of soils. Although its evolution during deformation is rather complicated, experimental data showed that, the overall shapes and distribution characteristics of the PSD function are not significantly altered. Based on these findings, the PSD function at a deformed state is obtained by horizontal shifting, and vertical scaling of the corresponding PSD function at a reference state. On this basis, a hysteretic WRC model is formulated to account for the influences of deformation and hysteresis on the variation of saturation, using seven model parameters with clear physical meanings. The proposed model is then incorporated in the Mualem model to predict the unsaturated hydraulic conductivity for deformable soils, using only one additional parameter. A large number of published laboratory tests are used to validate the proposed model, showing that, it can reasonably capture important features of retention and permeability properties for deformable soils in most cases under consideration.
The biological processes that are disrupted in the Alzheimer's disease (AD) brain remain incompletely understood. In this study, we analyzed the proteomes of more than 1,000 brain tissues to reveal ...new AD-related protein co-expression modules that were highly preserved across cohorts and brain regions. Nearly half of the protein co-expression modules, including modules significantly altered in AD, were not observed in RNA networks from the same cohorts and brain regions, highlighting the proteopathic nature of AD. Two such AD-associated modules unique to the proteomic network included a module related to MAPK signaling and metabolism and a module related to the matrisome. The matrisome module was influenced by the APOE ε4 allele but was not related to the rate of cognitive decline after adjustment for neuropathology. By contrast, the MAPK/metabolism module was strongly associated with the rate of cognitive decline. Disease-associated modules unique to the proteome are sources of promising therapeutic targets and biomarkers for AD.
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