Minimizing the risk of infection as an early complication of autologous stem cell transplantation.

This quality improvement project aimed to reduce institutional incidence of infection (CDI) following autologous stem cell transplantation. CDI incidence per transplant was .17 in a baseline period and .

Effect of a Multidisciplinary Pulmonary Embolism Response Team on Patient Mortality.

Multidisciplinary Pulmonary Embolism Response Teams (PERTs) may improve the care of patients with a high risk of pulmonary embolism (PE). The impact of a PERT on long-term mortality has never been evaluated. An observational analysis was conducted of 137 patients before PERT implementation (between 2014 and 2015) and 231 patients after PERT implementation (between 2016 and 2019), presenting to the emergency department of an academic medical center with submassive and massive PE.

Effect of platelet inhibitors on thrombus burden in patients with acute pulmonary embolism.

Venous thromboembolism (VTE) whether provoked or not can be life-threatening due to an acute increase in load on the right ventricle (RV) from obstruction of the pulmonary artery (PA). Treatment for and prevention of VTE involves anti-thrombotic agents; more specifically, medications targeting the anticoagulation cascade. In spite of the widespread acceptance of anticoagulants in the treatment of VTE, there appears to be an ongoing belief that platelet reactivity contributes to thrombus burden in patients with acute pulmonary embolism (PE).

Crystal Structure and Immunogenicity of the DS-Cav1-Stabilized Fusion Glycoprotein From Respiratory Syncytial Virus Subtype B.

Background: Respiratory syncytial virus (RSV) subtypes, A and B, co-circulate in annual epidemics and alternate in dominance. We have shown that a subtype A RSV fusion (F) glycoprotein, stabilized in its prefusion conformation by DS-Cav1 mutations, is a promising RSV-vaccine immunogen, capable of boosting RSV-neutralizing titers in healthy adults. In both humans and vaccine-tested animals, neutralizing titers elicited by this subtype A DS-Cav1 immunogen were ~ 2- to 3-fold higher against the homologous subtype A virus than against the heterologous subtype B virus.

The impact of a pulmonary embolism response team on the efficiency of patient care in the emergency department.

The concept of a pulmonary embolism response team (PERT) is multidisciplinary, with the hope that it may positively impact patient care, hospital efficiency, and outcomes in the treatment of patients with intermediate and high risk pulmonary embolism (PE). Clinical characteristics of a baseline population of patients presenting with submassive and massive PE to URMC between 2014 and 2016 were examined (n = 159). We compared this baseline population before implementation of a PERT to a similar population of patients at 3-month periods, and then as a group at 18 months after PERT implementation (n = 146).

Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape.

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ∼35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV.

Two-Component Ferritin Nanoparticles for Multimerization of Diverse Trimeric Antigens.

Antigen multimerization on a nanoparticle can result in improved neutralizing antibody responses. A platform that has been successfully used for displaying antigens from a number of different viruses is ferritin, a self-assembling protein nanoparticle that allows the attachment of multiple copies (24 monomers or 8 trimers) of a single antigen. Here, we design two-component ferritin variants that allow the attachment of two different antigens on a single particle in a defined ratio and geometric pattern.

Soluble Prefusion Closed DS-SOSIP.664-Env Trimers of Diverse HIV-1 Strains.

The elicitation of autologous neutralizing responses by immunization with HIV-1 envelope (Env) trimers conformationally stabilized in a prefusion closed state has generated considerable interest in the HIV-1 vaccine field. However, soluble prefusion closed Env trimers have been produced from only a handful of HIV-1 strains, limiting their utility as vaccine antigens and B cell probes. Here, we report the engineering from 81 HIV-1 strains of soluble, fully cleaved, prefusion Env trimers with appropriate antigenicity.

Risk factors for wound complications following spine surgery.

Background: Wound complications, including surgical site infections (SSIs) and wound dehiscence, are among the most common complications following spine surgery often leading to readmission. The authors sought to identify preoperative characteristics predictive of wound complications after spine surgery.

Methods: The American College of Surgeons National Surgical Quality Improvement Program database for years 2012-2014 was reviewed for patients undergoing spine surgery, defined by the Current Procedural Terminology codes.

Iterative structure-based improvement of a fusion-glycoprotein vaccine against RSV.

Structure-based design of vaccines, particularly the iterative optimization used so successfully in the structure-based design of drugs, has been a long-sought goal. We previously developed a first-generation vaccine antigen called DS-Cav1, comprising a prefusion-stabilized form of the fusion (F) glycoprotein, which elicits high-titer protective responses against respiratory syncytial virus (RSV) in mice and macaques. Here we report the improvement of DS-Cav1 through iterative cycles of structure-based design that significantly increased the titer of RSV-protective responses.

Single-Chain Soluble BG505.SOSIP gp140 Trimers as Structural and Antigenic Mimics of Mature Closed HIV-1 Env.

Unlabelled: Similar to other type I fusion machines, the HIV-1 envelope glycoprotein (Env) requires proteolytic activation; specifically, cleavage of a gp160 precursor into gp120 and gp41 subunits creates an N-terminal gp41 fusion peptide and permits folding from an immature uncleaved state to a mature closed state. While the atomic-level consequences of cleavage for HIV-1 Env are still being determined, the uncleaved state is antigenically distinct from the mature closed state, and cleavage has been reported to be essential for mimicry of the mature viral spike by soluble versions of Env. Here we report the redesign of a current state-of-the-art soluble Env mimic, BG505.