Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU: 2023.

Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care hospitals have implemented systems aimed at detecting and responding to such patients.

Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients.

Executive Summary: Society of Critical Care Medicine Guidelines on Recognizing and Responding to Clinical Deterioration Outside the ICU.

Rationale: Clinical deterioration of patients hospitalized outside the ICU is a source of potentially reversible morbidity and mortality. To address this, some acute care facilities have implemented systems aimed at detecting and responding to such patients.

Objectives: To provide evidence-based recommendations for hospital clinicians and administrators to optimize recognition and response to clinical deterioration in non-ICU patients.

De novo genome assembly and comparative genomics for the colonial ascidian Botrylloides violaceus.

Ascidians have the potential to reveal fundamental biological insights related to coloniality, regeneration, immune function, and the evolution of these traits. This study implements a hybrid assembly technique to produce a genome assembly and annotation for the botryllid ascidian, Botrylloides violaceus. A hybrid genome assembly was produced using Illumina, Inc.

Obexelimab in Systemic Lupus Erythematosus With Exploration of Response Based on Gene Pathway Co-Expression Patterns: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial.

Objective: Obexelimab is an investigational, bifunctional, noncytolytic monoclonal antibody that binds CD19 and FcyRIIb to inhibit B cells, plasmablasts, and plasma cells. This trial evaluated the efficacy and safety of obexelimab in the treatment of patients with systemic lupus erythematosus (SLE).

Methods: During screening, patients with active, non-organ-threatening SLE received corticosteroid injections to ameliorate symptoms while immunosuppressants were withdrawn (≤10 mg/day prednisone equivalent and ≤400 mg/day hydroxychloroquine allowed).

Metopimazine is primarily metabolized by a liver amidase in humans.

Metopimazine (MPZ) is a peripherally restricted, dopamine D2 receptor antagonist used for four decades to treat acute nausea and vomiting. MPZ is currently under clinical investigation for the treatment of gastroparesis (GP). MPZ undergoes high first-pass metabolism that produces metopimazine acid (MPZA), the major circulating metabolite in humans.

STRATUS: A Phase II Study of Abituzumab in Patients With Systemic Sclerosis-associated Interstitial Lung Disease.

Objective: To investigate the effects of abituzumab in systemic sclerosis-associated interstitial lung disease (SSc-ILD).

Methods: STRATUS was a phase II, double-blind, parallel-group, multicenter trial (ClinicalTrials.gov: NCT02745145).

Evaluating the structural effects of intra-articular sprifermin on cartilage and non-cartilaginous tissue alterations, based on sqMRI assessment over 2 years.

Objective: Sprifermin (recombinant human fibroblast growth factor-18), a potential disease-modifying osteoarthritis (OA) drug, demonstrated dose-dependent effects on femorotibial cartilage thickness (by quantitative magnetic resonance imaging [MRI]) in the phase II FORWARD study. This post-hoc analysis evaluated the potential effects of sprifermin on several articular structures in the whole joint over 24 months using semi-quantitative MRI assessment.

Design: Patients aged 40-85 years with symptomatic radiographic knee OA, Kellgren-Lawrence grade 2 or 3, and medial minimum joint space width ≥2.

Effect of Intra-Articular Sprifermin vs Placebo on Femorotibial Joint Cartilage Thickness in Patients With Osteoarthritis: The FORWARD Randomized Clinical Trial.

Importance: Sprifermin is under investigation as a disease-modifying osteoarthritis drug.

Objective: To evaluate the effects of sprifermin on changes in total femorotibial joint cartilage thickness in the more symptomatic knee of patients with osteoarthritis.

Design, Setting, And Participants: FORWARD (FGF-18 Osteoarthritis Randomized Trial with Administration of Repeated Doses) was a 5-year, dose-finding, multicenter randomized clinical trial conducted at 10 sites.

Compositional analysis of the essential oil of Boswellia dalzielii frankincense from West Africa reveals two major chemotypes.

Frankincense, an oleoresin produced by Boswellia species, has historical medicinal and religious significance, and is today used extensively for its essential oil. Boswellia dalzielii, a species found in West Africa, is one of the few frankincense species for which there is no information on the oleoresin essential oil. In order to correct this deficiency, the chemical compositions of the essential oil hydrodistilled from 21 samples of oleoresin taken directly from B.

The My Body Knows When Program Increased Intuitive Eating Characteristics in a Military Population.

Introduction: The purpose of this pilot study was to assess the effectiveness of the revised My Body Knows When (MBKW) program to promote intuitive eating behaviors within a sample of a military population through an online or in-person delivery mode.

Materials And Methods: Fifty-six overweight or obese adults (70% female); military service members (20%), retirees (38%) and family (42%) participated in the 10-week MBKW program at two military installations from 2012 to 2014. Body Mass Index, Intuitive Eating Scale-2 (IES-2; 23-item) and Motivation for Eating scale (MFES; 43-item) were collected at baseline and 10-weeks.

Ongoing clinical trials and treatment options for patients with systemic sclerosis-associated interstitial lung disease.

SSc is a rare CTD that affects multiple organ systems, resulting in substantial morbidity and mortality. Evidence of interstitial lung disease (ILD) is seen in ∼80% of patients with SSc. Currently there is no approved disease-modifying treatment for ILD and few effective treatment options are available.

Efficacy and Safety of Atacicept in Patients With Systemic Lupus Erythematosus: Results of a Twenty-Four-Week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Arm, Phase IIb Study.

Objective: To evaluate the efficacy and safety of atacicept, an antagonist of B lymphocyte stimulator/APRIL-mediated B cell activation, in patients with systemic lupus erythematosus (SLE).

Methods: ADDRESS II is a 24-week, multicenter, randomized, double-blind, placebo-controlled, parallel-arm, phase IIb study evaluating the safety and efficacy of atacicept in patients with SLE (ClinicalTrials.gov identifier NCT01972568).

Targeting BAFF and APRIL in systemic lupus erythematosus and other antibody-associated diseases.

The B cell-stimulating molecules, BAFF (B cell activating factor) and APRIL (a proliferation-inducing ligand), are critical factors in the maintenance of the B cell pool and humoral immunity. In addition, BAFF and APRIL are involved in the pathogenesis of a number of human autoimmune diseases, with elevated levels of these cytokines detected in the sera of patients with systemic lupus erythematosus (SLE), IgA nephropathy, Sjögren's syndrome, and rheumatoid arthritis. As such, both molecules are rational targets for new therapies in B cell-driven autoimmune diseases, and several inhibitors of BAFF or BAFF and APRIL together have been investigated in clinical trials.

Post Hoc Analysis of the Phase II/III APRIL-SLE Study: Association Between Response to Atacicept and Serum Biomarkers Including BLyS and APRIL.

Objective: To assess the relationship between treatment response, baseline biomarker levels, and atacicept exposure in patients with systemic lupus erythematosus (SLE) in the phase II/III APRIL-SLE study.

Methods: We performed a post hoc analysis of patients who received placebo, atacicept 75 mg, or atacicept 150 mg in a randomized, controlled, 52-week trial. Serum levels of BlyS and APRIL were measured at baseline, and serum levels of Ig and the numbers of naive B cells and plasma cells were measured at baseline and during treatment.

Prevalence of food insecurity among military households with children 5 years of age and younger.

Objective: Food insecurity increases risk of health conditions that may decrease military readiness. The aim of the present study was to define the prevalence of food insecurity among households with young children utilizing military installation childcare facilities and to describe household characteristics associated with food insecurity among this population.

Design: Cross-sectional survey including demographic questions and the US Department of Agriculture Food Security Survey Module six-item short form given to households (n 248) enrolled in Joint Base San Antonio Child Development Centers (JBSA-CDC) during the spring of 2015.

Safety and efficacy of atacicept in combination with rituximab for reducing the signs and symptoms of rheumatoid arthritis: a phase II, randomized, double-blind, placebo-controlled pilot trial.

Objective: To explore the safety and tolerability of atacicept in combination with rituximab in patients with active rheumatoid arthritis (RA) receiving rituximab re-treatment.

Methods: In this randomized, double-blind, placebo-controlled pilot trial, 2 infusions (1,000 mg per infusion) of intravenous rituximab, given 2 weeks apart, were followed by once-weekly subcutaneous injections of 150 mg atacicept or placebo for 25 weeks. Primary end points were the nature, incidence, and severity of adverse events (AEs).

Atacicept in combination with MMF and corticosteroids in lupus nephritis: results of a prematurely terminated trial.

Introduction: Atacicept is a soluble, fully human, recombinant fusion protein that inhibits B cell-stimulating factors APRIL (a proliferation-inducing ligand) and BLyS (B-lymphocyte stimulator). The APRIL- LN study aimed to evaluate the efficacy and safety of atacicept in patients with active lupus nephritis (LN), receiving newly initiated corticosteroids (CS) and mycophenolate mofetil (MMF).

Methods: This was a randomized, double-blind, placebo-controlled Phase II/III, 52-week study.

Atacicept in patients with rheumatoid arthritis and an inadequate response to methotrexate: results of a phase II, randomized, placebo-controlled trial.

Objective: To assess the efficacy, safety, and biologic activity of atacicept in tumor necrosis factor antagonist-naive patients with rheumatoid arthritis (RA) in whom the response to methotrexate treatment was inadequate.

Methods: In this phase II study, patients with active RA (n = 311) were randomized 1:1:1:1 to receive placebo, atacicept 150 mg weekly with or without a 4-week loading period (twice-weekly dosing), or open-label adalimumab 40 mg every other week, for 25 weeks. The primary end point was 20% improvement in disease severity according to the American College of Rheumatology criteria, assessed using the C-reactive protein level (ACR20-CRP), at week 26.

Low over-expression of TNFalpha in the mouse heart increases contractile performance via TNFR1.

TNFalpha is a cytokine wit pleiotropic functions in many organs. In the heart increased TNFalpha levels are not only associated with heart failure, but also, paradoxically, with protection from ischemic damage. To test whether the protective role of TNFalpha in the heart is concentration-dependent, we studied two mouse heart models with low (two- to threefold) over-expression of endogenous TNFalpha: mice deficient in a translational repressor of TNFalpha mRNA, TIA-1(-/-), and mice over-expressing human TNFalpha.

The tumor necrosis factor-alpha AU-rich element inhibits the stable association of the 40S ribosomal subunit with RNA transcripts.

Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine that is central to normal immune responses as well as autoimmune inflammatory diseases. The production of TNF-alpha protein is thus tightly regulated at multiple levels. Translational control is one of the means by which TNF-alpha production is repressed in unstimulated cells.

MK2-induced tristetraprolin:14-3-3 complexes prevent stress granule association and ARE-mRNA decay.

Stress granules (SGs) are dynamic cytoplasmic foci at which stalled translation initiation complexes accumulate in cells subjected to environmental stress. SG-associated proteins such as TIA-1, TIAR and HuR bind to AU-rich element (ARE)-containing mRNAs and control their translation and stability. Here we show that tristetraprolin (TTP), an ARE-binding protein that destabilizes ARE-mRNAs, is recruited to SGs that are assembled in response to FCCP-induced energy deprivation, but not arsenite-induced oxidative stress.

Geldanamycin inhibits the production of inflammatory cytokines in activated macrophages by reducing the stability and translation of cytokine transcripts.

Objective: Heat-shock protein 90 (Hsp90) is critical in the intracellular signaling pathways that promote inflammatory cytokine production. Geldanamycin (GD) is a benzoquinone ansamycin that inhibits the function of Hsp90. GD inhibits the production of tumor necrosis factor alpha (TNFalpha) in activated macrophages and suppresses the progression of adjuvant-induced arthritis and experimental allergic encephalomyelitis in rodents.

TIA-1 is a translational silencer that selectively regulates the expression of TNF-alpha.

TIA-1 and TIAR are related proteins that bind to an AU-rich element (ARE) in the 3' untranslated region of tumor necrosis factor alpha (TNF-alpha) transcripts. To determine the functional significance of this interaction, we used homologous recombination to produce mutant mice lacking TIA-1. Although lipopolysaccharide (LPS)-stimulated macrophages derived from wild-type and TIA-1(-/-) mice express similar amounts of TNF-alpha transcripts, macrophages lacking TIA-1 produce significantly more TNF-alpha protein than wild-type controls.

SM-20 is a novel 40-kd protein whose expression in the arterial wall is restricted to smooth muscle.

We have previously reported the identification of a novel cDNA, SM-20, whose corresponding mRNA levels are regulated by growth factors in rat aortic smooth muscle cell (SMC) culture. Affinity-purified polyclonal and monoclonal antibodies were made against a 230 amino acid region of the SM-20 putative peptide expressed in the bacterial vector, pET-3b. Western blot analyses of rat and human SMC lysates detected a single protein species of approximately 40 kd.

Identification of a novel growth factor-responsive gene in vascular smooth muscle cells.

We have employed differential screening of a rat aortic smooth muscle cell cDNA library to isolate a cDNA clone, SM-20, whose nucleotide and deduced amino acid sequences are distinct from those reported previously. SM-20 encodes an mRNA of approximately 2.5-3.