Endothelial dysfunction contributes to the pathogenesis of a variety of potentially serious infectious diseases and syndromes, including sepsis and septic shock, hemolytic-uremic syndrome, severe malaria, and dengue hemorrhagic fever. Because endothelial activation often precedes overt endothelial dysfunction, biomarkers of the activated endothelium in serum and/or plasma may be detectable before classically recognized markers of disease, and therefore, may be clinically useful as biomarkers of disease severity or prognosis in systemic infectious diseases. In this review, the current status of mediators of endothelial cell function (angiopoietins-1 and -2), components of the coagulation pathway (von Willebrand Factor, ADAMTS13, and thrombomodulin), soluble cell-surface adhesion molecules (soluble E-selectin, sICAM-1, and sVCAM-1), and regulators of vascular tone and permeability (VEGF and sFlt-1) as biomarkers in severe infectious diseases is discussed in the context of sepsis, E. coli O157:H7 infection, malaria, and dengue virus infection.

ObjectiveTo compare the efficacy, effectiveness, and safety of the herpes zoster live attenuated vaccine with the herpes zoster adjuvant recombinant subunit vaccine or placebo for adults aged 50 and older.DesignSystematic review with bayesian meta-analysis and network meta-analysis.Data sourcesMedline, Embase, and Cochrane Library (inception to January 2017), grey literature, and reference lists of included studies.Eligibility criteria for study selectionExperimental, quasi-experimental, and observational studies that compared the live attenuated vaccine with the adjuvant recombinant subunit vaccine, placebo, or no vaccine in adults aged 50 and older. Relevant outcomes were incidence of herpes zoster (primary outcome), herpes zoster ophthalmicus, post-herpetic neuralgia, quality of life, adverse events, and death.Results27 studies (22 randomised controlled trials) including 2 044 504 patients, along with 18 companion reports, were included after screening 2037 titles and abstracts, followed by 175 full text articles. Network meta-analysis of five randomised controlled trials found no statistically significant differences between the live attenuated vaccine and placebo for incidence of laboratory confirmed herpes zoster. The adjuvant recombinant subunit vaccine, however, was statistically superior to both the live attenuated vaccine (vaccine efficacy 85%, 95% credible interval 31% to 98%) and placebo (94%, 79% to 98%). Network meta-analysis of 11 randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more adverse events at injection sites than the live attenuated vaccine (relative risk 1.79, 95% credible interval 1.05 to 2.34; risk difference 30%, 95% credible interval 2% to 51%) and placebo (5.63, 3.57 to 7.29 and 53%, 30% to 73%, respectively). Network meta-analysis of nine randomised controlled trials showed the adjuvant recombinant subunit vaccine to be associated with statistically more systemic adverse events than placebo (2.28, 1.45 to 3.65 and 20%, 6% to 40%, respectively).ConclusionsUsing the adjuvant recombinant subunit vaccine might prevent more cases of herpes zoster than using the live attenuated vaccine, but the adjuvant recombinant subunit vaccine also carries a greater risk of adverse events at injection sites.Protocol registrationProspero CRD42017056389.

Hemolytic uremic syndrome (HUS) is a potentially life-threatening condition. It often occurs after gastro-intestinal infection with E. coli O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury. Stx-mediated changes in endothelial phenotype have been linked to the pathogenesis of HUS. Here we report our studies investigating Stx-induced changes in gene expression and their contribution to the pathogenesis of HUS. Stx function by inactivating host ribosomes but can also alter gene expression at concentrations that minimally affect global protein synthesis. Gene expression profiling of human microvascular endothelium treated with Stx implicated a role for activation of CXCR4 and CXCR7 by their shared cognate chemokine ligand (stromal cell-derived factor-1 [SDF-1]) in Stx-mediated pathophysiology. The changes in gene expression required a catalytically active Stx A subunit and were mediated by enhanced transcription and mRNA stability. Stx also enhanced the association of CXCR4, CXCR7, and SDF1 mRNAs with ribosomes. In a mouse model of Stx-mediated pathology, we noted changes in plasma and tissue content of CXCR4, CXCR7, and SDF-1 after Stx exposure. Furthermore, inhibition of the CXCR4/SDF-1 interaction decreased endothelial activation and organ injury and improved animal survival. Finally, in children infected with E. coli O157:H7, plasma SDF-1 levels were elevated in individuals who progressed to HUS. Collectively, these data implicate the CXCR4/CXCR7/SDF-1 pathway in Stx-mediated pathogenesis and suggest novel therapeutic strategies for prevention and/or treatment of complications associated with E. coli O157:H7 infection.

A dose of domperidone of 20 mg, 3 times daily instead of 10 mg, 3 times daily was associated with a clinical, but not statistically significant, increase in milk production.

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Mucormycosis (zygomycosis) is an invasive, opportunistic fungal infection caused by organisms of the class Zygomycetes. Immunocompromised individuals, including both solid organ and hematopoietic stem cell transplant recipients, are preferentially affected. Among solid organ transplant (SOT) recipients, the sinuses, with or without involvement of the orbits and cerebrum, are the most common sites of disease, although the pulmonary allograft appears to be targeted following lung transplantation. Here, we describe the unique case of a lung transplant recipient who developed multifocal cutaneous mucormycosis without involvement of the pulmonary allograft, and review the published literature regarding incidence, treatment, and prognosis of primary cutaneous mucormycosis following SOT.

No abstract

Escherichia coli O157:H7-associated hemolytic-uremic syndrome (HUS) is characterized by profound prothrombotic abnormalities. Endothelial dysfunction, manifested as dysregulation of angiopoietins 1 and 2 (Ang-1/2), could underlie HUS pathophysiology. We measured Ang-1/2 in 77 children with E. coli O157:H7 infection. Ang-1, Ang-2, and the Ang-2/Ang-1 ratio were significantly different in HUS vs the pre-HUS phase of illness or uncomplicated infection. Angiopoietin dysregulation preceded HUS and worsened as HUS developed. In vitro exposure of human microvascular endothelial cells to Shiga toxin recapitulated the in vivo observations. Angiopoietin regulation is profoundly affected before and during HUS, reflecting that subclinical endothelial dysfunction precedes overt microangiopathy.