Letter by Harris et al regarding article, outcomes of patients with acute type a aortic intramural hematoma

Comment on Outcomes of patients with acute type a aortic intramural hematoma

STAT2 is a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways

STAT2 is the quintessential transcription factor for type 1 interferons (IFNs), where it functions as a heterodimer with STAT1. However, the human and murine STAT2-deficient phenotypes suggest important additional and currently unidentified type 1 IFN-independent activities. Here we show that STAT2 constitutively bound to STAT1, but not STAT3, via a conserved interface. While this interaction was irrelevant for type 1 interferon signaling and STAT1 activation, it precluded the nuclear translocation specifically of STAT1 in response to IFN-γ, interleukin-6 (IL-6) and IL-27. This is explained by the dimerization between activated STAT1 and unphosphorylated STAT2, whereby the semiphosphorylated dimers adopted a conformation incapable of importin-α binding. This, in turn, substantially attenuated cardinal IFN-γ responses including MHC expression, senescence, and antiparasitic immunity, and shifted the transcriptional output of IL-27 from STAT1 to STAT3. Our results uncover STAT2 as a pervasive cytokine regulator due to its inhibition of STAT1 in multiple signaling pathways and provide an understanding of the type 1 interferon independent activities of this protein

Lower Rates of Heart Failure and All-Cause Hospitalizations During Pulmonary Artery Pressure-Guided Therapy for Ambulatory Heart Failure: One-Year Outcomes From the CardioMEMS Post-Approval Study.

BACKGROUND: Ambulatory hemodynamic monitoring with an implantable pulmonary artery (PA) sensor is approved for patients with New York Heart Association Class III heart failure (HF) and a prior HF hospitalization (HFH) within 12 months. The objective of this study was to assess the efficacy and safety of PA pressure-guided therapy in routine clinical practice with special focus on subgroups defined by sex, race, and ejection fraction. METHODS: This multi-center, prospective, open-label, observational, single-arm trial of 1200 patients across 104 centers within the United States with New York Heart Association class III HF and a prior HFH within 12 months evaluated patients undergoing PA pressure sensor implantation between September 1, 2014, and October 11, 2017. The primary efficacy outcome was the difference between rates of adjudicated HFH 1 year after compared with the 1 year before sensor implantation. Safety end points were freedom from device- or system-related complications at 2 years and freedom from pressure sensor failure at 2 years. RESULTS: Mean age for the population was 69 years, 37.7% were women, 17.2% were non-White, and 46.8% had preserved ejection fraction. During the year after sensor implantation, the mean rate of daily pressure transmission was 76±24% and PA pressures declined significantly. The rate of HFH was significantly lower at 1 year compared with the year before implantation (0.54 versus 1.25 events/patient-years, hazard ratio 0.43 [95% CI, 0.39-0.47], CONCLUSIONS: In routine clinical practice as in clinical trials, PA pressure-guided therapy for HF was associated with lower PA pressures, lower rates of HFH and all-cause hospitalization, and low rates of adverse events across a broad range of patients with symptomatic HF and prior HFH. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02279888

International Heterogeniety in Diagnostic Frequency and Clinical Outcomes of Ascending Aortic Intramural Hematoma

BACKGROUND: Differing diagnostic frequencies and management strategies for intramural hematoma (IMH) have been described in North American (NA)/European and Japanese/Korean studies. METHODS: All publications including type-A aortic IMH were reviewed for details on patient demographics, treatment strategy, and clinical outcomes. Publications were stratified by the geographic region (NA/Europe or Japan/Korea). RESULTS: IMH, as a percentage of aortic dissection, occurs more frequently in Japan/Korea versus NA/Europe (31.7% vs 10.9%, P \u3c .0001). The proportion of patients treated with early medical therapy is greater in Japanese/Korean studies (77.9% vs 48.8% in NA/Europe, P \u3c .0001). However, the overall mortality is significantly lower in Japan/Korea compared with NA/Europe (9.4% vs 20.6%, odds ratio = 2.80, P = .003) in part because of the lower mortality with early medical therapy (7.8% vs 33.3%, P \u3c .0001). CONCLUSION: There is significant international heterogeneity in the diagnosis and clinical outcomes of ascending IMH. IMH is diagnosed more frequently and has better overall outcomes in Japan/Korea

Predicting the Geographic Range of an Invasive Livestock Disease across the Contiguous USA under Current and Future Climate Conditions

Vesicular stomatitis (VS) is the most common vesicular livestock disease in North America. Transmitted by direct contact and by several biting insect species, this disease results in quarantines and animal movement restrictions in horses, cattle and swine. As changes in climate drive shifts in geographic distributions of vectors and the viruses they transmit, there is considerable need to improve understanding of relationships among environmental drivers and patterns of disease occurrence. Multidisciplinary approaches integrating pathology, ecology, climatology, and biogeophysics are increasingly relied upon to disentangle complex relationships governing disease. We used a big data model integration approach combined with machine learning to estimate the potential geographic range of VS across the continental United States (CONUS) under long-term mean climate conditions over the past 30 years. The current extent of VS is confined to the western portion of the US and is related to summer and winter precipitation, winter maximum temperature, elevation, fall vegetation biomass, horse density, and proximity to water. Comparison with a climate-only model illustrates the importance of current processes-based parameters and identifies regions where uncertainty is likely to be greatest if mechanistic processes change. We then forecast shifts in the range of VS using climate change projections selected from CMIP5 climate models that most realistically simulate seasonal temperature and precipitation. Climate change scenarios that altered climatic conditions resulted in greater changes to potential range of VS, generally had non-uniform impacts in core areas of the current potential range of VS and expanded the range north and east. We expect that the heterogeneous impacts of climate change across the CONUS will be exacerbated with additional changes in land use and land cover affecting biodiversity and hydrological cycles that are connected to the ecology of insect vectors involved in VS transmission