Intensive urate-lowering with pegloticase plus methotrexate co-therapy in uncontrolled gout patients with and without chronic kidney disease: A retrospective case series.

Chronic kidney disease (CKD) and gout commonly co-occur. Pegloticase lowers serum urate (SU) in uncontrolled gout patients but antidrug antibodies limit urate-lowering response and increase infusion reaction (IR) risk. Methotrexate (MTX) co-administration increases pegloticase response rate and mitigates IR risk but CKD limits MTX use.

Improvements in Patient-Reported Outcomes Through Six Months of Guselkumab Treatment in Patients With Active Psoriatic Arthritis: Real-World Data From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

Objective: Evaluate patient-reported outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry.

Methods: This analysis includes registry participants who initiated and persisted with on-label guselkumab (after US Food and Drug Administration approval for PsA; 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (On-Label Persisters). Among patients not meeting response criteria at baseline, responses at 6 months were determined for patient-reported outcomes, including patient-reported pain (0-100 mm visual analog scale), patient global assessment of arthritis + psoriasis (PtGA; 0-100 visual analog scale), and Health Assessment Questionnaire-Disability Index (HAQ-DI; 0-3).

Six-Month Persistence and Multi-domain Effectiveness of Guselkumab in Adults with Psoriatic Arthritis: Real-World Data from the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

Introduction: The aim of this work is to evaluate treatment persistence and clinical outcomes after 6 months of on-label guselkumab use in patients with rheumatologist-diagnosed active psoriatic arthritis (PsA) enrolled in the CorEvitas PsA/Spondyloarthritis Registry.

Methods: Participants with PsA who initiated and persisted with on-label guselkumab use post-Food and Drug Administration (FDA) approval for active PsA (7/13/2020; subcutaneous 100 mg at weeks 0, 4, and every 8 weeks) at their 6-month follow-up visit (occurring through 3/31/2023) comprised the primary analysis population (On-Label Persisters). Hierarchical, multiplicity-controlled primary and secondary outcomes were mean (95% confidence interval) changes from baseline at 6 months in clinical Disease Activity Index for PsA (cDAPSA; primary), Physician Global Assessment (PGA) of arthritis and psoriasis (visual analog scale [VAS] 0-100), patient-reported pain (VAS 0-100), and percent body surface area with psoriasis (%BSA).

Effectiveness and safety of intravenous golimumab with and without concomitant methotrexate in patients with rheumatoid arthritis in the prospective, noninterventional AWARE study.

Background: Biologic therapies are often prescribed for patients with rheumatoid arthritis (RA) who have inadequate responses to or are intolerant of methotrexate (MTX) and patients with poor prognostic indicators. This post hoc analysis evaluated effectiveness and safety of intravenous golimumab + MTX vs golimumab without MTX in RA patients.

Methods: AWARE, a real-world, prospective and pragmatic, Phase 4 study, compared effectiveness and safety of golimumab and infliximab in biologic-naïve and biologic-experienced patients.

Community Practice Experiences with a Variety of Immunomodulatory Agents Co-Administered with Pegloticase for the Treatment of Uncontrolled Gout.

Objective: Patients with uncontrolled/refractory gout have heavy disease burden, but few treatment options. Pegloticase lowers serum urate (SU), but anti-drug antibodies can limit treatment efficacy. Evidence supports immunomodulator-pegloticase co-administration to increase sustained urate-lowering rates, but published cases are limited.

Population Pharmacokinetic and Exposure-Response Model Simulations: Predicted Exposure and Efficacy for Maintenance Doses of Intravenous Golimumab Every 6 or 8 Weeks in Patients With Moderately to Severely Active Rheumatoid Arthritis.

Purpose: Golimumab is approved to treat moderate-to-severe active rheumatoid arthritis when given intravenously at weeks 0 and 4, then every 8 weeks (Q8W) with concomitant methotrexate. These analyses assessed whether a shorter dosing interval could ameliorate diminished efficacy experienced by a small proportion of patients toward the end of the dosing interval.

Methods: Population pharmacokinetic and exposure-response modeling simulations were performed for intravenous golimumab 2 mg/kg at weeks 0 and 4, then Q8W or every 6 weeks (Q6W) through 1 year.

Denosumab Safety and Efficacy Among Participants in the FREEDOM Extension Study With Mild to Moderate Chronic Kidney Disease.

Context: The effects of long-term exposure to denosumab in individuals with renal insufficiency are unknown.

Objective: This post hoc analysis evaluates the long-term safety and efficacy of denosumab in individuals with mild-to-moderate chronic kidney disease (CKD) (stages 2 and 3) using data from the pivotal phase 3, double-blind, 3-year FREEDOM (NCT00089791) and open-label, 7-year extension (NCT00523341) studies.

Participants And Methods: Women age 60 to 90 years with a bone mineral density (BMD) T-score of less than -2.

The Effectiveness of Intravenous Golimumab Administered Directly After Infliximab in Rheumatoid Arthritis Patients.

Purpose: For patients with rheumatoid arthritis (RA) who do not respond or lose response to anti-tumor necrosis factor (TNF) biologics, switching to a different anti-TNF can be an effective means to manage symptoms and disease progression. This study examined the utilization and effectiveness of intravenous golimumab within a real-world population of patients with RA switching directly from infliximab, a potent anti-TNF.

Methods: Patient charts (n = 113) were collected from five US-based rheumatology practices.

Localized vasculitis of the gastrointestinal tract: a case series.

Objective: To describe the clinical features and outcomes of patients with localized vasculitis of the gastrointestinal tract (LVGT).

Methods: Medical records of 608 patients diagnosed with vasculitis involving the intra-abdominal vasculature and/or abdominal viscera between January 1996 and December 2007 were reviewed. Only patients with histopathological confirmation or typical angiographic findings of vasculitis localized to the abdomen were included.

A strategy for shuffling numerous Bacillus thuringiensis crystal protein domains.

Bacillus thuringiensis that produce Cry1Ba are toxic to Lucilia cuprina Wiedemann blow fly maggots in vivo, and when applied in quantity to sheep fleece, provide up to 6 wk protection against flystrike in the field. These strains also are toxic to Epiphyas postvittana (Walker) light brown apple moth caterpillars. B.

Efficacy of native and recombinant Cry1B protein against experimentally induced and naturally acquired ovine myiasis (fly strike) in sheep.

Several hundred strains of Bacillus thuringiensis (Bt), isolated in New Zealand from samples of soil and sheep fleece, were tested for toxicity to larvae of the blowfly Lucilia cuprina Wiedemann. Characterization of the Bt strains revealed that three of the more active strains produced Cry1Ba (an insecticidal protein present in Bt mother cell crystal inclusion) that was toxic to blowflies. These strains were evaluated for the ability to prevent experimentally induced fly strike in a bioassay by using first instars.

Activities of Bacillus thuringiensis insecticidal crystal proteins Cyt1Aa and Cyt2Aa against three species of sheep blowfly.

The toxicity of Bacillus thuringiensis Cyt1Aa protein to sheep blowfly larvae depends on its solubilization and proteolytic activation. Cyt1Aa crystals were not toxic. Full-length and trypsin-digested Cyt1Aa proteins were toxic to larvae of three species of sheep blowfly.

Advance directives on hospital admission: a survey of patient attitudes.

A survey of 200 outpatients using an anonymous, self-administered questionnaire revealed that 18% had already completed an advance directive. Only 5% had received information concerning advance directives from their physicians. Eighty-seven percent stated they would not be offended if, on admission to the hospital, they were to be asked whether they had completed a living will.

Identification of an insecticidal crystal protein from Bacillus thuringiensis DSIR517 with significant sequence differences from previously described toxins.

The nucleotide (nt) sequence of a DNA segment containing the majority of a gene cloned from Bacillus thuringiensis DSIR517 encoding a 130 kDa insecticidal crystal protein has been determined. Sequence analysis reveals an open reading frame (ORF) of 3453 nt. The ATG initiation codon, which is preceded by a potential ribosome-binding site sequence, was confirmed by N-terminal amino acid sequencing.

Bacillus sphaericus as a mosquito pathogen: properties of the organism and its toxins.

In the course of sporulation, Bacillus sphaericus produces an inclusion body which is toxic to a variety of mosquito larvae. In this review we discuss the general biology of this species and concentrate on the genetics and physiology of toxin production and its processing in the midgut of the larval host. The larvicide of B.

Construction by site-directed mutagenesis of a 39-kilodalton mosquitocidal protein similar to the larva-processed toxin of Bacillus sphaericus 2362.

After ingestion of the parasporal crystals of Bacillus sphaericus, mosquito larvae process the 42-kilodalton (kDa) toxin to a protein of 39 kDa, which has an increased toxicity (A. H. Broadwell and P.

The 42- and 51-kilodalton mosquitocidal proteins of Bacillus sphaericus 2362: construction of recombinants with enhanced expression and in vivo studies of processing and toxicity.

After site-directed mutagenesis, the genes coding for the 42- and 51-kilodalton (kDa) mosquitocidal proteins of Bacillus sphaericus 2362 were placed under the regulation of the aprE (subtilisin) promoter of the Bacillus subtilis vector pUE (a derivative of pUB18). The levels of expression of the gene products in B. subtilis DB104 and B.

Sequence analysis of the mosquitocidal toxin genes encoding 51.4- and 41.9-kilodalton proteins from Bacillus sphaericus 2362 and 2297.

The nucleotide sequences of a 3,479-base-pair HindIII DNA fragment from Bacillus sphaericus 2362 and a 2,940-base-pair fragment from strain 2297 were determined; only minor differences were detected between them. Each contained two open reading frames coding for proteins of 51.4 and 41.

Cloning of the gene for the larvicidal toxin of Bacillus sphaericus 2362: evidence for a family of related sequences.

During sporulation, Bacillus sphaericus 2362 produces a parasporal crystalline protein which is toxic for the larvae of a number of mosquito species. Using the Escherichia coli cloning vector lambda gt11, in which gene products of the inserts may be fused to beta-galactosidase, we isolated 29 bacteriophages which produced peptides-reacting with antiserum to crystal protein. On the basis of restriction enzyme analyses of the recombinants and Ouchterlony immunodiffusion experiments with induced lysogens as a source of antigens, the recombinants were assigned to three groups, designated A, B, and C.

Proteolysis in the gut of mosquito larvae results in further activation of the Bacillus sphaericus toxin.

Gut proteases from the larvae of the mosquito Culex pipiens convert the 43-kilodalton (kDa) toxin from Bacillus sphaericus 2362 to a 40-kDa peptide. The 50% lethal concentration of this peptide for tissue culture-grown cells of Culex quinquefasciatus was 1.0 microgram/ml (as determined by the intracellular ATP assay), 54-fold less than that of the 43-kDa peptide.

Sporulation-associated activation of Bacillus sphaericus larvicide.

Preparations of the larvicidal crystal from 46-h cultures of Bacillus sphaericus 2362 contain 125-, 110-, 63-, and 43-kilodalton (kDa) proteins (P. Baumann, B. M.

Purification of the larvicidal toxin of Bacillus sphaericus and evidence for high-molecular-weight precursors.

Crystals were purified from spore-crystal complexes of Bacillus sphaericus 2362 by disruption in a French pressure cell followed by centrifugation through 48% (wt/vol) NaBr. Crystals from such preparations had a 50% lethal concentration of 6 ng of protein per ml for the larvae of the mosquito Culex pipiens. When subjected to polyacrylamide gel electrophoresis under denaturing conditions, the proteins in B.

A comparison of antimicrobial activity of four disclosant dyes.

Four disclosant dyes were tested for antimicrobial activity against 27 oral reference strains and five non-oral human pathogens. Erythrosine and fluorescein inhibited most gram-positive and gram-negative organisms associated with dental plaque, and were bactericidal to selected strains. Fast green and brilliant blue demonstrated little antimicrobial activity.