Astegolimab or Efmarodocokin Alfa in Patients With Severe COVID-19 Pneumonia: A Randomized, Phase 2 Trial.

Objectives: Severe cases of COVID-19 pneumonia can lead to acute respiratory distress syndrome (ARDS). Release of interleukin (IL)-33, an epithelial-derived alarmin, and IL-33/ST2 pathway activation are linked with ARDS development in other viral infections. IL-22, a cytokine that modulates innate immunity through multiple regenerative and protective mechanisms in lung epithelial cells, is reduced in patients with ARDS.

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of the Monoclonal Antibody MHAA4549A in Patients With Acute Uncomplicated Influenza A Infection.

Background: MHAA4549A, a human monoclonal antibody targeting the influenza A hemagglutinin stalk, neutralizes influenza A virus in animal and human volunteer challenge studies. We investigated the safety and tolerability, efficacy, and pharmacokinetics of MHAA4549A in outpatients with acute, uncomplicated influenza A infection.

Methods: This was a phase 2, randomized, double-blind, placebo-controlled trial of single intravenous (IV) doses of 3600 mg or 8400 mg of MHAA4549A or IV placebo in adult outpatients testing positive for influenza A.

Pharmacokinetics of the Monoclonal Antibody MHAA4549A Administered in Combination With Oseltamivir in Patients Hospitalized With Severe Influenza A Infection.

MHAA4549A is a human anti-influenza A monoclonal antibody developed to treat influenza A. We report MHAA4549A serum, nasopharyngeal, and tracheal aspirate pharmacokinetics from a phase 2b study in hospitalized patients with severe influenza A. Patients were randomized 1:1:1 into 3 groups receiving single intravenous doses of 3600 mg (n = 55) or 8400 mg (n = 47) MHAA4549A or placebo (n = 56).

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial of MHAA4549A, a Monoclonal Antibody, plus Oseltamivir in Patients Hospitalized with Severe Influenza A Virus Infection.

For patients hospitalized with severe influenza A virus infection, morbidity and mortality remain high. MHAA4549A, a human monoclonal antibody targeting the influenza A virus hemagglutinin stalk, has demonstrated pharmacological activity in animal studies and in a human influenza A challenge study. We evaluated the safety and efficacy of MHAA4549A plus oseltamivir against influenza A virus infection in hospitalized patients.

Risk stratification biomarkers for bacteraemia.

Objectives: To identify risk stratification biomarkers to enrich for the subset of bacteraemia patients who develop deep-seated tissue infections with high morbidity and mortality to guide clinical trial enrolment and clinical management.

Methods: We evaluated the prognostic value of eight biomarkers for persistent bacteraemia, mortality and endovascular infection foci in a validation cohort of 160 patients with bacteraemia enrolled consecutively over 3 years.

Results: High levels of IL-17A, IL-10 or soluble E-selectin at bacteraemia diagnosis correlated with the duration of positive blood cultures.

Prognostic Power of Pathogen Cell-Free DNA in Bacteremia.

Background: is a leading global cause of bacteremia that can cause invasive tissue infections with high morbidity and mortality despite appropriate antibiotic therapy. Clinicians lack sufficient tools to rapidly identify patients with a poor prognosis to guide diagnostic workup and treatment decisions. Host cell-free DNA provides prognostic value across a spectrum of critical illnesses, including bacteremia and sepsis.

Sustained Circulating Bacterial Deoxyribonucleic Acid Is Associated With Complicated Bacteremia.

Background: (SA) bacteremia often requires a long treatment duration with antibiotics to prevent relapse due to the ability of SA to establish reservoirs of infection in sites such as heart and bone. These metastatic sites of infection cannot be serially sampled to monitor the clearance of SA infection. This study aimed to establish a link between persistence of circulating SA deoxyribonucleic acid (SA-DNA) and tissue reservoirs in patients with SA bacteremia.

A Prognostic Model of Persistent Bacteremia and Mortality in Complicated Staphylococcus aureus Bloodstream Infection.

Background: Staphylococcus aureus is a leading cause of bacteremia, yet there remains a significant knowledge gap in the identification of relevant biomarkers that predict clinical outcomes. Heterogeneity in the host response to invasive S. aureus infection suggests that specific biomarker signatures could be utilized to differentiate patients prone to severe disease, thereby facilitating earlier implementation of more aggressive therapies.

Isolation and characterization of mutant Sinorhizobium meliloti NodD1 proteins with altered responses to luteolin.

NodD1, a member of the NodD family of LysR-type transcriptional regulators (LTTRs), mediates nodulation (nod) gene expression in the soil bacterium Sinorhizobium meliloti in response to the plant-secreted flavonoid luteolin. We used genetic screens and targeted approaches to identify NodD1 residues that show altered responses to luteolin during the activation of nod gene transcription. Here we report four types of NodD1 mutants.

Diverse flavonoids stimulate NodD1 binding to nod gene promoters in Sinorhizobium meliloti.

NodD1 is a member of the NodD family of LysR-type transcriptional regulators that mediates the expression of nodulation (nod) genes in the soil bacterium Sinorhizobium meliloti. Each species of rhizobia establishes a symbiosis with a limited set of leguminous plants. This host specificity results in part from a NodD-dependent upregulation of nod genes in response to a cocktail of flavonoids in the host plant's root exudates.

The RNA polymerase alpha subunit from Sinorhizobium meliloti can assemble with RNA polymerase subunits from Escherichia coli and function in basal and activated transcription both in vivo and in vitro.

Sinorhizobium meliloti, a gram-negative soil bacterium, forms a nitrogen-fixing symbiotic relationship with members of the legume family. To facilitate our studies of transcription in S. meliloti, we cloned and characterized the gene for the alpha subunit of RNA polymerase (RNAP).

Luteolin and GroESL modulate in vitro activity of NodD.

In the early stages of symbiosis between the soil bacterium Sinorhizobium meliloti and its leguminous host plant, alfalfa, bacterial nodulation (nod) genes are controlled by NodD1, NodD2, and NodD3, members of the LysR family of transcriptional regulators, in response to flavonoid and other inducers released by alfalfa. To gain an understanding of the biochemical aspects of this action, epitope-tagged recombinant NodD1 and NodD3 were overexpressed in Escherichia coli. The DNA binding properties of the purified recombinant NodD proteins were indistinguishable from those of NodD isolated from S.