Publications by authors named "Grein J"

Article Synopsis
  • The study investigates the challenges and feasibility of performing CPR on patients with viral hemorrhagic fevers (VHF), highlighting the need for clearer guidelines in critical care interventions.
  • Using simulation, the researchers found that CPR can be effectively performed in full PPE, achieving a chest compression fraction of 72% and a manual rate of 129 compressions per minute.
  • The study identified various latent safety threats (LSTs) that impact the healthcare team’s safety and performance, suggesting that refining team roles and responsibilities could enhance both safety and CPR quality.
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In a survey of 104 US infectious disease specialists, 88% reported working in facilities that allow animal-assisted activities or pet visitation. Variability existed in the species of animals allowed, restricted areas, and veterinary assessments, demonstrating a need to standardize infection prevention approaches across health care facilities to mitigate potential risks.

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Article Synopsis
  • V937 is a genetically unmodified coxsackievirus A21 strain that targets and destroys cancer cells overexpressing ICAM-1, showing promise in treating advanced solid tumors like metastatic melanoma when used alone or with the anti-PD-1 antibody pembrolizumab.
  • In preclinical studies, V937 exhibited minimal immune response when used independently, but significantly boosted proinflammatory cytokine production and immune activation when tumor cells were co-cultured with immune cells.
  • The study highlights that combining V937 with interferon-gamma and pembrolizumab enhances ICAM-1 expression, further improving the virus's ability to kill tumors and activate immune responses, indicating a potential new treatment strategy for cancers that typically evade immune
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MASH is a prevalent liver disease that can progress to fibrosis, cirrhosis, hepatocellular carcinoma (HCC), and ultimately death, but there are no approved therapies. Leukotriene B4 (LTB4) is a potent pro-inflammatory chemoattractant that drives macrophage and neutrophil chemotaxis, and genetic loss or inhibition of its high affinity receptor, leukotriene B4 receptor 1 (BLT1), results in improved insulin sensitivity and decreased hepatic steatosis. To validate the therapeutic efficacy of BLT1 inhibition in an inflammatory and pro-fibrotic mouse model of MASH and fibrosis, mice were challenged with a choline-deficient, L-amino acid defined high fat diet and treated with a BLT1 antagonist at 30 or 90 mg/kg for 8 weeks.

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Infection prevention program leaders report frequent use of criteria to distinguish recently recovered coronavirus disease 2019 (COVID-19) cases from actively infectious cases when incidentally positive asymptomatic patients were identified on routine severe acute respiratory coronavirus virus 2 (SARS-CoV-2) polymerase chain reaction (PCR) testing. Guidance on appropriate interpretation of high-sensitivity molecular tests can prevent harm from unnecessary precautions that delay admission and impede medical care.

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In a survey of infection prevention programs, leaders reported frequent clinical and infection prevention practice modifications to avoid coronavirus disease 2019 (COVID-19) exposure that exceeded national guidance. Future pandemic responses should emphasize balanced approaches to precautions, prioritize educational campaigns to manage safety concerns, and generate an evidence-base that can guide appropriate infection prevention practices.

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Objective: To examine the impact of SARS-CoV-2 infection on CLABSI rate and characterize the patients who developed a CLABSI. We also examined the impact of a CLABSI-reduction quality-improvement project in patients with and without COVID-19.

Design: Retrospective cohort analysis.

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Research is foundational for evidence-based management of patients. Clinical research, however, takes time to plan, conduct, and disseminate-a luxury that is rarely available during a public health emergency. The University of Nebraska Medical Center (UNMC) developed a single institutional review board (IRB), with a vision to establish a rapid review resource for a network focused on clinical research of emerging pathogens in the United States.

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The National Emerging Special Pathogens Training and Education Center (NETEC) was established in 2015 to improve the capabilities of healthcare facilities to provide safe and effective care to patients with Ebola and other special pathogens in the United States. Through NETEC, a collaborative network of 10 Regional Emerging Special Pathogen Treatment Centers (RESPTCs) undertook readiness activities that included potential respiratory pathogens. These preparations, which took place before the COVID-19 pandemic, established a foundation of readiness that enabled RESPTCs to play a pivotal role in the US COVID-19 pandemic response.

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Background: Diabetic nephropathy is associated with endothelial dysfunction and oxidative stress, in which the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway is impaired. We hypothesize that sGC stimulator Compound 1 can enhance NO signaling, reduce proteinuria in a diabetic nephropathy preclinical model with diminished NO bioavailability and increased oxidized sGC. Therefore, we evaluated the effect of sGC stimulator Compound 1 on the renal effect in obese ZSF1 (ZSF1 OB) rats.

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Background: Hospitals have implemented diverse quality improvement (QI) interventions to reduce rates of catheter-associated urinary tract infections (CAUTIs). The economic value of these QI interventions is uncertain.

Objective: To systematically review economic evaluations of QI interventions designed to prevent CAUTI in acute care hospitals.

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Infectious complications are a significant cause of morbidity and mortality in patients with chemotherapy-induced neutropenia. Specific infection control practices targeting this patient population are widely endorsed, but little guidance exists on how to implement and monitor compliance with these practices. At our institution, we increased compliance with infection control measures by using a bundled neutropenic precaution (NP) audit and feedback tool.

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Healthcare personnel (HCP) with unprotected exposures to aerosol-generating procedures (AGPs) on patients with coronavirus disease 2019 (COVID-19) are at risk of infection with severe acute respiratory coronavirus virus 2 (SARS-CoV-2). A retrospective review at an academic medical center demonstrated an infection rate of <1% among HCP involved in AGPs without a respirator and/or eye protection.

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Prostaglandin E (PGE), an arachidonic acid pathway metabolite produced by cyclooxygenase (COX)-1/2, has been shown to impair anti-tumor immunity through engagement with one or more E-type prostanoid receptors (EP). Specific targeting of EP receptors, as opposed to COX-1/2 inhibition, has been proposed to achieve preferential antagonism of PGE-mediated immune suppression. Here we describe the anti-tumor activity of MF-766, a potent and highly selective small-molecule inhibitor of the EP receptor.

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Objective: We sought to determine the extent of SARS-CoV-2 seroprevalence and the factors associated with seroprevalence across a diverse cohort of healthcare workers.

Design: Observational cohort study of healthcare workers, including SARS-CoV-2 serology testing and participant questionnaires.

Settings: A multisite healthcare delivery system located in Los Angeles County.

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Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the tumor microenvironment (TME). MDSCs have been shown to dampen antitumor immune responses and promote tumor growth; however, the mechanisms of MDSC induction and their role in promoting immune suppression in cancer remain poorly understood. Here, we characterized the phenotype and function of monocytic MDSCs (M-MDSC) generated by coculture of human peripheral blood mononuclear cells with SK-MEL-5 cancer cells .

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Background: Programmed cell death protein 1 (PD-1) and CTLA4 combination blockade enhances clinical efficacy in melanoma compared with targeting either checkpoint alone; however, clinical response improvement is coupled with increased risk of developing immune-related adverse events (irAE). Delineating the mechanisms of checkpoint blockade-mediated irAE has been hampered by the lack of animal models that replicate these clinical events.

Methods: We have developed a mouse model of checkpoint blockade-mediated enterocolitis via prolonged administration of an Fc-competent anti-CTLA4 antibody.

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The molecule "T cell immunoreceptor with immunoglobulin and ITIM domain," or TIGIT, has recently received much attention as a promising target in the treatment of various malignancies. In spite of the quick progression of anti-TIGIT antibodies into clinical testing both as monotherapy and in combination with programmed cell death-1 (PD-1)-directed immune checkpoint blockade, the molecular mechanism behind the observed therapeutic benefits remains poorly understood. Here we demonstrate, using mouse tumor models, that TIGIT blocking antibodies with functional Fc binding potential induce effective anti-tumor response.

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Importance: Certain individuals, when infected by SARS-CoV-2, tend to develop the more severe forms of Covid-19 illness for reasons that remain unclear.

Objective: To determine the demographic and clinical characteristics associated with increased severity of Covid-19 infection.

Design: Retrospective observational study.

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Background: Remdesivir, a nucleotide analogue prodrug that inhibits viral RNA polymerases, has shown in vitro activity against SARS-CoV-2.

Methods: We provided remdesivir on a compassionate-use basis to patients hospitalized with Covid-19, the illness caused by infection with SARS-CoV-2. Patients were those with confirmed SARS-CoV-2 infection who had an oxygen saturation of 94% or less while they were breathing ambient air or who were receiving oxygen support.

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Objective: To evaluate the National Health Safety Network (NHSN) hospital-onset Clostridioides difficile infection (HO-CDI) standardized infection ratio (SIR) risk adjustment for general acute-care hospitals with large numbers of intensive care unit (ICU), oncology unit, and hematopoietic cell transplant (HCT) patients.

Design: Retrospective cohort study.

Setting: Eight tertiary-care referral general hospitals in California.

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We undertook a quality improvement project to address challenges with pulmonary artery catheter (PAC) line maintenance in a setting of low-baseline central-line infection rates. We observed a subsequent reduction in Staphylococcal PAC line infections and a trend toward a reduction in overall PAC infection rates over 1 year.

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In patients with β-lactam allergies, administration of non-β-lactam surgical prophylaxis is associated with increased risk of infection. Although many patients self-report β-lactam allergies, most are unconfirmed or mislabeled. A quality improvement process, utilizing a structured β-lactam allergy tool, was implemented to improve the utilization of preferred β-lactam surgical prophylaxis.

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