SummaryMonkeypox is a disease that is endemic in Central and Western Africa. However, in 2003, there was an outbreak in the US, representing the first documented monkeypox cases in the Western hemisphere. Although monkeypox virus is less fatal and not as transmissible as variola virus, the causative agent of smallpox, there is concern that monkeypox virus could become a more efficient human pathogen. The reason for this may lie in the virus' genetic makeup, ecological changes, changes in host behavior, and the fact that with the eradication of variola virus, routine smallpox vaccination is no longer carried out. In this review, we focus on the viral proteins that are predicted to modulate the host immune response and compare the genome of monkeypox virus with the genomes of variola virus and the vaccinia virus, the orthopoxvirus that represented the smallpox vaccine. There are differences found in several of these immune-modulating genes including genes that express proteins that affect cytokines such as interleukin-1, tumor necrosis factor, and interferon. There are also differences in genes that code for virulence factors and host range proteins. Genetic differences likely also explain the differences in virulence between two strains of monkeypox virus found in two different regions of Africa. In the current setting of limited smallpox vaccination and little orthopoxvirus immunity in parts of the world, monkeypox could become a more efficient human pathogen under the right circumstances.

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Th22 cells are a major source of IL-22 and have been found at sites of infection and in a range of inflammatory diseases. However, their molecular characteristics and functional roles remain largely unknown due to our inability to generate and isolate pure populations. We developed a novel Th22 differentiation assay and generated dual IL-22/IL-17A reporter mice to isolate and compare pure populations of cultured Th22 and Th17 cells. Il17a fate-mapping and transcriptional profiling provide evidence that these Th22 cells have never expressed IL-17A, suggesting that they are potentially a distinct cell lineage from Th17 cells under in vitro culture conditions. Interestingly, Th22 cells also expressed granzymes, IL-13 and increased levels of Tbet. Using transcription factor-deficient cells, we demonstrate that RORγt and Tbet act as positive and negative regulators of Th22 differentiation, respectively. Furthermore, under Th1 culture conditions in vitro, as well as in an IFN-γ-rich inflammatory environment in vivo, Th22 cells displayed marked plasticity towards IFN-γ production. Th22 cells also displayed plasticity under Th2 conditions in vitro by up-regulating IL-13 expression. Our work has identified conditions to generate and characterize Th22 cells in vitro. Further, it provides evidence that Th22 cells develop independently of the Th17 lineage, whilst demonstrating plasticity towards both Th1 and Th2 type cells.

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BACKGROUND:Outcomes following pancreatic trauma have not improved significantly over the past two decades. A 2013 Western Trauma Association algorithm highlighted emerging data that might improve the diagnosis and management of high-grade pancreatic injuries (HGPIs; grades III-V). We hypothesized that the use of magnetic resonance cholangiopancreatography, pancreatic duct stenting, operative drainage versus resection, and nonoperative management of HGPIs increased over time. METHODS:Multicenter retrospective review of diagnosis, management, and outcomes of adult pancreatic injuries from 2010 to 2018 was performed. Data were analyzed by grade and time period (PRE, 2010(PRE, -2013 POST, 2014 POST, -2018 using various statistical tests where appropriate. RESULTS:Thirty-two centers reported data on 515 HGPI patients. A total of 270 (53%) had penetrating trauma, and 58% went directly to the operating room without imaging. Eighty-nine (17%) died within 24 hours. Management and outcomes of 426 24-hour survivors were evaluated. Agreement between computed tomography and operating room grading was 38%. Magnetic resonance cholangiopancreatography use doubled in grade IV/V injuries over time but was still low.Overall HGPI treatment and outcomes did not change over time. Resection was performed in 78% of grade III injuries and remained stable over time, while resection of grade IV/V injuries trended downward (56% to 39%, p = 0.11). Pancreas-related complications (PRCs) occurred more frequently in grade IV/V injuries managed with drainage versus resection (61% vs. 32%, p = 0.0051), but there was no difference in PRCs for grade III injuries between resection and drainage.Pancreatectomy closure had no impact on PRCs. Pancreatic duct stenting increased over time in grade IV/V injuries, with 76% used to treat PRCs. CONCLUSION:Intraoperative and computed tomography grading are different in the majority of HGPI cases. Resection is still used for most patients with grade III injuries; however, drainage may be a noninferior alternative. Drainage trended upward for grade IV/V injuries, but the higher rate of PRCs calls for caution in this practice.