Increased Trauma Activation Is Not Equally Beneficial For All Elderly Trauma Patients

Background Physiologic changes in the elderly lead to higher morbidity and mortality after injury. Increasing level of trauma activation has been proposed to improve geriatric outcomes; but, the increased cost to the patient and stress to the hospital system are significant downsides. The purpose of this study was to identify the age at which an increase in activation status is beneficial. Methods A retrospective review of trauma patients ≥ 70 years old from October 1, 2011, to October 1, 2016 was performed. On October 1, 2013, a policy change increased the activation criteria to the highest level for patients ≥ 70 years of age with a significant mechanism of injury. Patients who presented prior to (PRE) were compared to those after the change (POST). Data collected included age, injury severity score (ISS), length of stay (LOS), complications and mortality. Primary outcome was mortality and secondary outcome was LOS. Multivariable regressions controlled for age, ISS, injury mechanism, and number of complications. Results 4341 patients met inclusion criteria, 1919 in PRE and 2422 in POST. Mean age was 80.4 and 81 years in PRE and POST groups respectively (p=0.0155). Mean ISS values were 11.6 and 12.4 (p<0.0001) for the PRE and POST groups. POST had more level 1 activations (696 vs. 220, p<0.0001). After controlling for age, ISS, mechanism of injury, and number of complications, mortality was significantly reduced in the POST group ≥ age 77 years (OR 0.53, 95% CI: 0.3 - 0.87), (Figure 1). Hospital LOS was significantly reduced in the POST group ≥ age 78 (regression coefficient -0.55, 95% CI: -1.09, -0.01) (Figure 2). Conclusions This study suggests geriatric trauma patients ≥ 77 years benefit from the highest level of trauma activation with shorter LOS and lower mortality. A focused approach to increasing activation level for elderly patients may decrease patient cost. Level of Evidence Level III Type of Study Economic/Decisio

Evidence for the Direct Detection of the Thermal Spectrum of the Non-Transiting Hot Gas Giant HD 88133 b

We target the thermal emission spectrum of the non-transiting gas giant HD 88133 b with high-resolution near-infrared spectroscopy, by treating the planet and its host star as a spectroscopic binary. For sufficiently deep summed flux observations of the star and planet across multiple epochs, it is possible to resolve the signal of the hot gas giant's atmosphere compared to the brighter stellar spectrum, at a level consistent with the aggregate shot noise of the full data set. To do this, we first perform a principal component analysis to remove the contribution of the Earth's atmosphere to the observed spectra. Then, we use a cross-correlation analysis to tease out the spectra of the host star and HD 88133 b to determine its orbit and identify key sources of atmospheric opacity. In total, six epochs of Keck NIRSPEC L band observations and three epochs of Keck NIRSPEC K band observations of the HD 88133 system were obtained. Based on an analysis of the maximum likelihood curves calculated from the multi-epoch cross correlation of the full data set with two atmospheric models, we report the direct detection of the emission spectrum of the non-transiting exoplanet HD 88133 b and measure a radial projection of the Keplerian orbital velocity of 40 $\pm$ 15 km/s, a true mass of 1.02$^{+0.61}_{-0.28}M_J$, a nearly face-on orbital inclination of 15${^{+6}_{-5}}^{\circ}$, and an atmosphere opacity structure at high dispersion dominated by water vapor. This, combined with eleven years of radial velocity measurements of the system, provides the most up-to-date ephemeris for HD 88133.Comment: 9 pages, 6 figures; accepted for publication in Ap

Perceived loss of social support after non-neurologic injury negatively impacts recovery

Background: Traumatic injury is not only physically devastating, but also psychologically isolating, potentially leading to poor quality of life, depression and posttraumatic stress disorder (PTSD). Perceived social support (PSS) is associated with better outcomes in some populations. What is not known is if changes in PSS influence long-term outcomes following nonneurologic injury. We hypothesized that a single drop in PSS during recovery would be associated with worse quality of life. Methods: This is a post hoc analysis of a prospectively collected database that included patients 18 years or older admitted to a Level I trauma center with Injury Severity Score (ISS) of 10 or higher, and no traumatic brain or spinal cord injury. Demographic and injury data were collected at the initial hospital admission. Screening for depression, PTSD, and Medical Outcomes Study Short Form 36 Mental Composite Score (MCS) were obtained at the initial hospitalization, 1, 2, 4, and 12 months postinjury. The Multidimensional Scale of Perceived Social Support (MSPSS) was obtained at similar time points. Patients with high MSPSS (>5) at baseline were included and grouped by those that ever reported a score ≤5 (DROP), and those that remained high (STABLE). Outcomes were determined at 4 and 12 months. Results: Four hundred eleven patients were included with 96 meeting DROP criteria at 4 months, and 97 at 1 years. There were no differences in sex, race, or injury mechanism. The DROP patients were more likely to be single (p = 0.012 at 4 months, p = 0.0006 at 1 year) and unemployed (p = 0.016 at 4 months, and p = 0.026 at 1 year) compared with STABLE patients. At 4 months and 1 year, DROP patients were more likely to have PTSD, depression, and a lower MCS (p = 0.0006, p < 0.0001). Conclusion: Patients who have a drop in PSS during the first year of recovery have significantly higher odds of poor psychological outcomes. Identifying these socially frail patients provides an opportunity for intervention to positively influence an otherwise poor quality of life. Level of evidence: Therapeutic, Prognostic and Epidemiological, Level III

ICP0 antagonizes Stat 1-dependent repression of herpes simplex virus: implications for the regulation of viral latency

BACKGROUND: The herpes simplex virus type 1 (HSV-1) ICP0 protein is an E3 ubiquitin ligase, which is encoded within the HSV-1 latency-associated locus. When ICP0 is not synthesized, the HSV-1 genome is acutely susceptible to cellular repression. Reciprocally, when ICP0 is synthesized, viral replication is efficiently initiated from virions or latent HSV-1 genomes. The current study was initiated to determine if ICP0's putative role as a viral interferon (IFN) antagonist may be relevant to the process by which ICP0 influences the balance between productive replication versus cellular repression of HSV-1. RESULTS: Wild-type (ICP0(+)) strains of HSV-1 produced lethal infections in scid or rag2(-/- )mice. The replication of ICP0(- )null viruses was rapidly repressed by the innate host response of scid or rag2(-/- )mice, and the infected animals remained healthy for months. In contrast, rag2(-/- )mice that lacked the IFN-α/β receptor (rag2(-/- )ifnar(-/-)) or Stat 1 (rag2(-/- )stat1(-/-)) failed to repress ICP0(- )viral replication, resulting in uncontrolled viral spread and death. Thus, the replication of ICP0(- )viruses is potently repressed in vivo by an innate immune response that is dependent on the IFN-α/β receptor and the downstream transcription factor, Stat 1. CONCLUSION: ICP0's function as a viral IFN antagonist is necessary in vivo to prevent an innate, Stat 1-dependent host response from rapidly repressing productive HSV-1 replication. This antagonistic relationship between ICP0 and the host IFN response may be relevant in regulating whether the HSV-1 genome is expressed, or silenced, in virus-infected cells in vivo. These results may also be clinically relevant. IFN-sensitive ICP0(- )viruses are avirulent, establish long-term latent infections, and induce an adaptive immune response that is highly protective against lethal challenge with HSV-1. Therefore, ICP0(- )viruses appear to possess the desired safety and efficacy profile of a live vaccine against herpetic disease

Evidence for the Direct Detection of the Thermal Spectrum of the Non-Transiting Hot Gas Giant HD 88133 b

We target the thermal emission spectrum of the non-transiting gas giant HD 88133 b with high-resolution near-infrared spectroscopy, by treating the planet and its host star as a spectroscopic binary. For sufficiently deep summed flux observations of the star and planet across multiple epochs, it is possible to resolve the signal of the hot gas giant's atmosphere compared to the brighter stellar spectrum, at a level consistent with the aggregate shot noise of the full data set. To do this, we first perform a principal component analysis to remove the contribution of the Earth's atmosphere to the observed spectra. Then, we use a cross-correlation analysis to tease out the spectra of the host star and HD 88133 b to determine its orbit and identify key sources of atmospheric opacity. In total, six epochs of Keck NIRSPEC L-band observations and three epochs of Keck NIRSPEC K-band observations of the HD 88133 system were obtained. Based on an analysis of the maximum likelihood curves calculated from the multi-epoch cross-correlation of the full data set with two atmospheric models, we report the direct detection of the emission spectrum of the non-transiting exoplanet HD 88133 b and measure a radial projection of the Keplerian orbital velocity of 40 ± 15 km s^(−1), a true mass of 1.02^(+0.61)_(-0.28)M_J, a nearly face-on orbital inclination of 15^(+6o)_(-5), and an atmosphere opacity structure at high dispersion dominated by water vapor. This, combined with 11 years of radial velocity measurements of the system, provides the most up-to-date ephemeris for HD 88133

Detailed spectral and morphological analysis of the shell type SNR RCW 86

Aims: We aim for an understanding of the morphological and spectral properties of the supernova remnant RCW~86 and for insights into the production mechanism leading to the RCW~86 very high-energy gamma-ray emission. Methods: We analyzed High Energy Spectroscopic System data that had increased sensitivity compared to the observations presented in the RCW~86 H.E.S.S. discovery publication. Studies of the morphological correlation between the 0.5-1~keV X-ray band, the 2-5~keV X-ray band, radio, and gamma-ray emissions have been performed as well as broadband modeling of the spectral energy distribution with two different emission models. Results:We present the first conclusive evidence that the TeV gamma-ray emission region is shell-like based on our morphological studies. The comparison with 2-5~keV X-ray data reveals a correlation with the 0.4-50~TeV gamma-ray emission.The spectrum of RCW~86 is best described by a power law with an exponential cutoff at $E_{cut}=(3.5\pm 1.2_{stat})$ TeV and a spectral index of $\Gamma$~$1.6\pm 0.2$. A static leptonic one-zone model adequately describes the measured spectral energy distribution of RCW~86, with the resultant total kinetic energy of the electrons above 1 GeV being equivalent to $\sim$0.1\% of the initial kinetic energy of a Type I a supernova explosion. When using a hadronic model, a magnetic field of $B$~100$\mu$G is needed to represent the measured data. Although this is comparable to formerly published estimates, a standard E$^{-2}$ spectrum for the proton distribution cannot describe the gamma-ray data. Instead, a spectral index of $\Gamma_p$~1.7 would be required, which implies that ~$7\times 10^{49}/n_{cm^{-3}}$erg has been transferred into high-energy protons with the effective density $n_{cm^{-3}}=n/ 1$ cm^-3. This is about 10\% of the kinetic energy of a typical Type Ia supernova under the assumption of a density of 1~cm^-3.Comment: accepted for publication by A&

Characterizing the gamma-ray long-term variability of PKS 2155-304 with H.E.S.S. and Fermi-LAT

Studying the temporal variability of BL Lac objects at the highest energies provides unique insights into the extreme physical processes occurring in relativistic jets and in the vicinity of super-massive black holes. To this end, the long-term variability of the BL Lac object PKS 2155-304 is analyzed in the high (HE, 100 MeV 200 GeV) gamma-ray domain. Over the course of ~9 yr of H.E.S.S observations the VHE light curve in the quiescent state is consistent with a log-normal behavior. The VHE variability in this state is well described by flicker noise (power-spectral-density index {\ss}_VHE = 1.10 +0.10 -0.13) on time scales larger than one day. An analysis of 5.5 yr of HE Fermi LAT data gives consistent results ({\ss}_HE = 1.20 +0.21 -0.23, on time scales larger than 10 days) compatible with the VHE findings. The HE and VHE power spectral densities show a scale invariance across the probed time ranges. A direct linear correlation between the VHE and HE fluxes could neither be excluded nor firmly established. These long-term-variability properties are discussed and compared to the red noise behavior ({\ss} ~ 2) seen on shorter time scales during VHE-flaring states. The difference in power spectral noise behavior at VHE energies during quiescent and flaring states provides evidence that these states are influenced by different physical processes, while the compatibility of the HE and VHE long-term results is suggestive of a common physical link as it might be introduced by an underlying jet-disk connection.Comment: 11 pages, 16 figure

COVID-19, asthma, and biological therapies: What we need to know

Managing patients with severe asthma during the coronavirus pandemic and COVID-19 is a challenge. Authorities and physicians are still learning how COVID-19 affects people with underlying diseases, and severe asthma is not an exception. Unless relevant data emerge that change our understanding of the relative safety of medications indicated in patients with asthma during this pandemic, clinicians must follow the recommendations of current evidence-based guidelines for preventing loss of control and exacerbations. Also, with the absence of data that would indicate any potential harm, current advice is to continue the administration of biological therapies during the COVID-19 pandemic in patients with asthma for whom such therapies are clearly indicated and have been effective. For patients with severe asthma infected by SARS-CoV- 2, the decision to maintain or postpone biological therapy until the patient recovers should be a case-by-case based decision supported by a multidisciplinary team. A registry of cases of COVID- 19 in patients with severe asthma, including those treated with biologics, will help to address a clinical challenge in which we have more questions than answers

Cortical brain abnormalities in 4474 individuals with schizophrenia and 5098 control subjects via the enhancing neuro Imaging genetics through meta analysis (ENIGMA) Consortium

BACKGROUND: The profile of cortical neuroanatomical abnormalities in schizophrenia is not fully understood, despite hundreds of published structural brain imaging studies. This study presents the first meta-analysis of cortical thickness and surface area abnormalities in schizophrenia conducted by the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Schizophrenia Working Group. METHODS: The study included data from 4474 individuals with schizophrenia (mean age, 32.3 years; range, 11-78 years; 66% male) and 5098 healthy volunteers (mean age, 32.8 years; range, 10-87 years; 53% male) assessed with standardized methods at 39 centers worldwide. RESULTS: Compared with healthy volunteers, individuals with schizophrenia have widespread thinner cortex (left/right hemisphere: Cohen's d = -0.530/-0.516) and smaller surface area (left/right hemisphere: Cohen's d = -0.251/-0.254), with the largest effect sizes for both in frontal and temporal lobe regions. Regional group differences in cortical thickness remained significant when statistically controlling for global cortical thickness, suggesting regional specificity. In contrast, effects for cortical surface area appear global. Case-control, negative, cortical thickness effect sizes were two to three times larger in individuals receiving antipsychotic medication relative to unmedicated individuals. Negative correlations between age and bilateral temporal pole thickness were stronger in individuals with schizophrenia than in healthy volunteers. Regional cortical thickness showed significant negative correlations with normalized medication dose, symptom severity, and duration of illness and positive correlations with age at onset. CONCLUSIONS: The findings indicate that the ENIGMA meta-analysis approach can achieve robust findings in clinical neuroscience studies; also, medication effects should be taken into account in future genetic association studies of cortical thickness in schizophrenia