The effects of sarilumab as monotherapy and in combination with non-methotrexate disease-modifying anti-rheumatic drugs on unacceptable pain in patients with rheumatoid arthritis: A post-hoc analysis of the HARUKA phase 3 study.

Objectives: To investigate unacceptable pain [UP; visual analogue scale (VAS) >40 mm] and uncontrolled inflammation [C-reactive protein (CRP) ≥1.0 mg/dL] in patients with active rheumatoid arthritis (RA) receiving sarilumab (SAR) as monotherapy or in combination with non-methotrexate conventional synthetic disease-modifying antirheumatic drugs (SAR + csDMARDs).

Methods: In the HARUKA Phase 3 study (NCT02373202), Japanese patients received either SAR monotherapy (n = 61) or SAR + csDMARDs (n = 30).

Efficacy and safety of sarilumab in patients with rheumatoid arthritis stratified by age (<65 and ≥65 years): A post hoc analysis of Japanese Phase 3 clinical trials.

Objectives: This study aimed to assess the efficacy and safety of sarilumab in older patients with active rheumatoid arthritis (RA).

Methods: This is a post hoc analysis of KAKEHASI (NCT02293902) and HARUKA (NCT02373202) trials with stratification by age (<65 and ≥65 years). Patients with moderately to severely active RA were treated with sarilumab in combination with methotrexate or with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or as monotherapy.

Risk of Urogenital Bacterial Infection with Sodium-Glucose Cotransporter-2 Inhibitors: A Retrospective Cohort Study Using a Claims Database.

Introduction: The association between sodium-glucose cotransporter-2 (SGLT2) inhibitors and the risk of urogenital infections remains controversial. This study aimed to investigate the association between SGLT2 inhibitors and the incidence of perineal soft tissue infections, including Fournier's gangrene (FG), genital bacterial infections, and urinary tract infections (UTIs), using administrative claims data in Japan.

Methods: In this retrospective cohort study, we utilized the JMDC Claims Database.

Glucocorticoid treatment and clinical outcomes in patients with polymyalgia rheumatica: A cohort study using routinely collected health data.

Objective: We aimed to describe the following in patients with polymyalgia rheumatica (PMR): (1) real-world glucocorticoid (GC) therapy, (2) improvement in inflammatory parameters associated with disease activity (C-reactive protein [CRP] level and erythrocyte sedimentation rate [ESR]), and (3) incidence of GC-related adverse events (AEs).

Methods: A cohort study was conducted using a Japanese electronic medical records database. We included newly diagnosed PMR patients aged≥50years with baseline CRP levels≥10mg/L and/or ESR>30mm/h and an initial GC dose of≥5mg/day.

Effect of sarilumab on unacceptable pain and inflammation control in Japanese patients with moderately-to-severely active rheumatoid arthritis: Post hoc analysis of a Phase III study (KAKEHASI).

Objective: The aim of this study is to investigate the effects of sarilumab on unacceptable pain [UP; visual analogue scale (VAS) >40 mm] and inflammation in patients with moderately-to-severely active rheumatoid arthritis.

Methods: In this post hoc analysis of the KAKEHASI study, 243 patients received methotrexate with sarilumab 150 or 200 mg or placebo every other week, over 52 weeks. The proportion of patients with UP and correlations of changes in pain VAS from baseline with uncontrolled inflammation (C-reactive protein ≥1 mg/dl) and disease activity indices were assessed.

Clinical features of polymyalgia rheumatica patients in Japan: Analysis of real-world data from 2015 to 2020.

Objectives: To assess clinical features in patients with polymyalgia rheumatica (PMR) in Japan by the International Classification of Disease (ICD)-10 code assignment.

Methods: Demographics, treatment patterns, and concomitant diseases (identified using ICD-10 code only) in patients who were assigned the PMR ICD-10 code M35.3 at least once between 1 January 2015 and 31 December 2020 were aggregated from a nationwide medical information database owned by the Health, Clinic, and Education Information Evaluation Institute.

Haemoglobin changes and disease activity in Japanese patients with rheumatoid arthritis treated with sarilumab.

Objectives: Anaemia is a frequent extra-articular manifestation in rheumatoid arthritis (RA); haemoglobin level changes are associated with changes in disease activity. This post-hoc analysis assessed potential relationships between haemoglobin and disease activity in Japanese patients with RA, enrolled in the KAKEHASI study (NCT02293902).

Methods: In this study, adult patients with moderate-to-severe active RA, who had an inadequate response to methotrexate, were randomised to subcutaneous sarilumab 150 mg every 2 weeks (q2w) or 200 mg q2w or placebo for 24 weeks.

Immunogenicity of sarilumab and impact on safety and efficacy in Japanese patients with rheumatoid arthritis: analysis of two Phase 3 randomised clinical trials.

Objectives: To describe the immunogenicity profile of sarilumab in Japanese patients with rheumatoid arthritis (RA).

Methods: Patients enrolled in the KAKEHASI and HARUKA studies were included in our analysis. In these studies, patients received sarilumab 150 mg or 200 mg every 2 weeks for 52 or 28 weeks in combination with methotrexate (MTX) (KAKEHASI), or for 52 weeks as monotherapy or in combination with non-MTX conventional synthetic disease-modifying anti-rheumatic drugs (HARUKA).

Metabolic engineering of Corynebacterium glutamicum for hyperproduction of polymer-grade L- and D-lactic acid.

Strain development is critical for microbial production of bio-based chemicals. The stereo-complex form of polylactic acid, a complex of poly-L- and poly-D-lactic acid, is a promising polymer candidate due to its high thermotolerance. Here, we developed Corynebacterium glutamicum strains producing high amounts of L- and D-lactic acid through intensive metabolic engineering.

Enhanced production of d-lactate from mixed sugars in Corynebacterium glutamicum by overexpression of glycolytic genes encoding phosphofructokinase and triosephosphate isomerase.

The use of mixed sugars containing glucose and xylose in lignocellulosic biomass is desirable for the microbial production of chemicals and fuels. We investigated the effect of individual or simultaneous overexpression of glycolytic genes on d-lactate production from a mixture of glucose and xylose by a recombinant xylose-assimilating Corynebacterium glutamicum strain. The individual overexpression of genes encoding phosphofructokinase (PFK) and triosephosphate isomerase (TPI) increased d-lactate production rate by 71% and 34%, respectively, with corresponding increases (2.

Stable (sila)difluoromethylboranes via C-F activation of fluoroform derivatives.

Lithium 1,3-bis(2,6-diisopropylphenyl)-2,3-dihydro-1H-1,3,2-diazaborol-2-uide activates the C-F linkage of fluoroform (CFH) and the Ruppert-Prakash reagent (CFSiMe) to provide difluoromethyl-substituted boranes as air-stable compounds.

Induction and antagonism of pica induced by teriparatide in rats.

Intermittent subcutaneous injection of teriparatide, an active fragment of human parathyroid hormone, is clinically used for the treatment of osteoporosis. Patients suffer from nausea, which is one of the side effects teriparatide induces; however, the etiology of teriparatide-induced nausea remains unknown. We have reported pica, kaolin ingestion behavior, can be used as an assessment of nausea-related response in rats.

Overexpression of the phosphofructokinase encoding gene is crucial for achieving high production of D-lactate in Corynebacterium glutamicum under oxygen deprivation.

We previously reported on the impacts of the overexpression of individual genes of the glycolytic pathway encoding glucokinase (GLK), glyceraldehyde phosphate dehydrogenase (GAPDH), phosphofructokinase (PFK), triosephosphate isomerase (TPI), and bisphosphate aldolase (FBA) on D-lactate productivity in Corynebacterium glutamicum under oxygen-deprived conditions. Searching for synergies, in the current study, we simultaneously overexpressed the five glycolytic genes in a stepwise fashion to evaluate the effect of the cumulative overexpression of glycolytic genes on D-lactate production. Interestingly, the final D-lactate concentration markedly differed depending on whether or not the PFK encoding gene was overexpressed when combined with overexpressing other glycolytic genes.

Once-weekly teriparatide increases bone mineral density in the distal 1/10 radius, but not in the distal 1/3 radius.

Teriparatide significantly increases bone mineral density (BMD) of the lumbar vertebrae and femur and has a strong effect in reducing the risk of bone fractures. However, few detailed investigations with dual-energy X-ray absorptiometry (DXA) of the effects of teriparatide on the radius have been reported; specifically, there are no reports of the use of once-weekly teriparatide. In this study, the effect of once-weekly teriparatide in increasing BMD was examined in the distal 1/10 of the radius and the distal 1/3 of the radius using a DXA system for the radius.

[A case of adenocarcinoma of small intestine surviving for many years].

In adenocarcinoma of the small intestine, delays in diagnosis are frequent. The majority of patients present with advancedstage disease, and have either lymph node involvement or distant metastatic disease. Surgical resection is a mainstay in treatment of this disease, and the effectiveness of chemotherapy for advanced-stage or metastatic disease has been reported.

Ultrafine cellulose fibers produced by Asaia bogorensis, an acetic acid bacterium.

The ability to synthesize cellulose by Asaia bogorensis, a member of the acetic acid bacteria, was studied in two substrains, AJ and JCM. Although both strains have identical 16S rDNA sequence, only the AJ strain formed a solid pellicle at the air-liquid interface in static culture medium, and we analyzed this pellicle using a variety of techniques. In the presence of cellulase, glucose and cellobiose were released from the pellicle suggesting that it is made of cellulose.

Optimal risk management of human alveolar echinococcosis with vermifuge.

In this study, we develop a bioeconomic model of human alveolar echinococcosis (HAE) and formulate the optimal strategies for managing the infection risks in humans by applying optimal control theory. The model has the following novel features: (i) the complex transmission cycle of HAE has been tractably incorporated into the framework of optimal control problems and (ii) the volume of vermifuge spreading to manage the risk is considered a control variable. With this model, we first obtain the stability conditions for the transmission dynamics under the condition of constant control.

[Rectal perforation in a patient treated with combination chemotherapy for lung cancer].

A 74-year old man was treated with first-cycle chemotherapy of paclitaxel (70 mg/m2=110 mg day 1, 8, 15) and carboplatin (AUC5=500 mg day 1) for lung cancer (c-T3N2M0, stage III A). On day 6 abdominal pain appeared, while on day 7 abdominal CT showed a perforation of the digestive tract. Thirty-three hours after the onset he underwent Hartmann operation during which we recognized a perforation 1.

Selective CB1 cannabinoid receptor antagonist, SR141716A, attenuates liver injury induced by Concanavalin A.

Aim: The aim of this study was to investigate the hepatoprotective activity of a selective cannabinoid receptor 1 (CB1) antagonist, SR141716A, in a Concanavalin A (Con A)-induced mouse liver injury model and to determine whether SR141716A has an effect on the production of inflammatory cytokines and chemokines induced by Con A.

Results: Injection of Con A (20 mg/kg) to mice developed hepatitis determined by plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) elevation and necrosis in the liver. Pretreatment with SR141716A (30 mg/kg) significantly reduced plasma AST and ALT level, protected against necrosis in the liver, and significantly reduced plasma cytokine and chemokine levels, including TNFalpha, IFN-gamma, CXCL9, MIP1-alpha, and IL-10 and no change decreased in IL-4.

Synthesis and structure-activity relationships of oxamyl dipeptide caspase inhibitors developed for the treatment of liver disease.

The P4 region of a series of oxamyl dipeptide caspase inhibitors was optimized by the combination of anti-apoptotic activity in the Jurkat/Fas (JFas) cellular assay and membrane permeability in the PAMPA assay. Two highly potent anti-apoptotic agents with moderate membrane permeability, 29 and 36, showed strong in vivo efficacy in a murine model of alpha-Fas-induced liver injury.

Orally-administered caspase inhibitor PF-03491390 is retained in the liver for prolonged periods with low systemic exposure, exerting a hepatoprotective effect against alpha-fas-induced liver injury in a mouse model.

In a mouse model of alpha-Fas-induced acute liver injury, the orally-administered caspase inhibitor PF-03491390 (formerly named IDN-6556) was retained in the liver for prolonged periods with a low systemic exposure. Reductions in the elevated plasma levels of alanine aminotransferase (ALT) revealed that the retention of PF-03491390 in the liver exerted a hepatoprotective effect, even when pre-administered to mice 4 h before alpha-Fas insult. Prolonged retention of PF-03491390 in the liver after oral administration has the benefit of low systemic exposure, making this a beneficial agent for the treatment of liver diseases.