sj-docx-1-tab-10.1177_1759720X221091450 – Supplemental material for Comparison of the efficacy and risk of discontinuation between non-TNF-targeted treatment and a second TNF inhibitor in patients with rheumatoid arthritis after first TNF inhibitor failure

Supplemental material, sj-docx-1-tab-10.1177_1759720X221091450 for Comparison of the efficacy and risk of discontinuation between non-TNF-targeted treatment and a second TNF inhibitor in patients with rheumatoid arthritis after first TNF inhibitor failure by Dong-Jin Park, Sung-Eun Choi, Ji-Hyoun Kang, Kichul Shin, Yoon-Kyoung Sung and Shin-Seok Lee in Therapeutic Advances in Musculoskeletal Disease</p

Table_1_Assessment of nematicidal and plant growth-promoting effects of Burkholderia sp. JB-2 in root-knot nematode-infested soil.docx

Root-knot nematodes (RKN), Meloidogyne spp., are plant-parasitic nematodes that are responsible for considerable economic losses worldwide, because of the damage they cause to numerous plant species and the inadequate biological agents available to combat them. Therefore, developing novel and eco-friendly nematicides is necessary. In the present study, Burkholderia sp. JB-2, isolated from RKN-infested rhizosphere soil in South Korea, was evaluated to determine its nematicidal and plant growth-promoting effects under in vitro and in vivo conditions. Cell-free filtrates of the JB-2 strain showed high levels of nematicidal activity against second-stage juveniles (J2) of M. incognita, with 87.5% mortality following two days of treatment. In addition, the assessment of the activity against other six plant parasitic nematodes (M. javanica, M. hapla, M. arenaria, Ditylenchus destructor, Aphelenchoides subtenuis, and Heterodera trifolii) showed that the cell-free filtrates have a broad nematicidal spectrum. The three defense-responsive (MiMIF-2, MiDaf16-like1, and MiSkn1-like1) genes were activated, while Mi-cm-3 was downregulated when treated with cell-free filtrates of JB-2 cultures on J2. The greenhouse experiments suggested that the cell-free filtrates of the JB-2 strain efficiently controlled the nematode population in soil and egg mass formations of M. incognita in tomato (Solanum lycopersicum L., cv. Rutgers). An improvement in the host plant growth was observed, in which the shoot length and fresh weights of shoots and roots increased. The treatment with 10% of JB-2 cell-free filtrates significantly upregulated the expression levels of plant defenses (SlPR1, SlPR5, and SlPAL) and growth-promoting (ACO1, Exp18, and SlIAA1) genes compared with the corresponding parameters of the control group. Therefore, JB-2 could be a promising candidate for the sustainable management of RKN.</p

Table_2_Assessment of nematicidal and plant growth-promoting effects of Burkholderia sp. JB-2 in root-knot nematode-infested soil.docx

Root-knot nematodes (RKN), Meloidogyne spp., are plant-parasitic nematodes that are responsible for considerable economic losses worldwide, because of the damage they cause to numerous plant species and the inadequate biological agents available to combat them. Therefore, developing novel and eco-friendly nematicides is necessary. In the present study, Burkholderia sp. JB-2, isolated from RKN-infested rhizosphere soil in South Korea, was evaluated to determine its nematicidal and plant growth-promoting effects under in vitro and in vivo conditions. Cell-free filtrates of the JB-2 strain showed high levels of nematicidal activity against second-stage juveniles (J2) of M. incognita, with 87.5% mortality following two days of treatment. In addition, the assessment of the activity against other six plant parasitic nematodes (M. javanica, M. hapla, M. arenaria, Ditylenchus destructor, Aphelenchoides subtenuis, and Heterodera trifolii) showed that the cell-free filtrates have a broad nematicidal spectrum. The three defense-responsive (MiMIF-2, MiDaf16-like1, and MiSkn1-like1) genes were activated, while Mi-cm-3 was downregulated when treated with cell-free filtrates of JB-2 cultures on J2. The greenhouse experiments suggested that the cell-free filtrates of the JB-2 strain efficiently controlled the nematode population in soil and egg mass formations of M. incognita in tomato (Solanum lycopersicum L., cv. Rutgers). An improvement in the host plant growth was observed, in which the shoot length and fresh weights of shoots and roots increased. The treatment with 10% of JB-2 cell-free filtrates significantly upregulated the expression levels of plant defenses (SlPR1, SlPR5, and SlPAL) and growth-promoting (ACO1, Exp18, and SlIAA1) genes compared with the corresponding parameters of the control group. Therefore, JB-2 could be a promising candidate for the sustainable management of RKN.</p

<i>Streptomyces</i>-derived actinomycin D inhibits biofilm formation by <i>Staphylococcus aureus</i> and its hemolytic activity

<p><i>Staphylococcus aureus</i> is a versatile human pathogen that produces diverse virulence factors, and its biofilm cells are difficult to eradicate due to their inherent ability to tolerate antibiotics. The anti-biofilm activities of the spent media of 252 diverse endophytic microorganisms were investigated using three <i>S. aureus</i> strains. An attempt was made to identify anti-biofilm compounds in active spent media and to assess their anti-hemolytic activities and hydrophobicities in order to investigate action mechanisms. Unlike other antibiotics, actinomycin D (0.5 μg ml⁻¹) from <i>Streptomyces parvulus</i> significantly inhibited biofilm formation by all three <i>S. aureus</i> strains. Actinomycin D inhibited slime production in <i>S. aureus</i> and it inhibited hemolysis by <i>S. aureus</i> and caused <i>S. aureus</i> cells to become less hydrophobic, thus supporting its anti-biofilm effect. In addition, surface coatings containing actinomycin D prevented <i>S. aureus</i> biofilm formation on glass surfaces. Given these results, FDA-approved actinomycin D warrants further attention as a potential antivirulence agent against <i>S. aureus</i> infections.</p

Number of patients according to the course of treatment.

<p>TNF, tumor necrosis factor.</p><p>Number of patients according to the course of treatment.</p

Baseline characteristics and laboratory findings of patients starting their first TNF-α inhibitor according to whether they subsequently switched or not.

<p>TNF, tumor necrosis factor; BMI, body mass index; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INH, isoniazid; NSAIDs, non-steroidal anti-inflammatory drugs; DMARDs, disease-modifying anti-rheumatic drugs. Continuous variables are shown as medians and interquartile range.</p><p>Baseline characteristics and laboratory findings of patients starting their first TNF-α inhibitor according to whether they subsequently switched or not.</p

Predictors of Switching Anti-Tumor Necrosis Factor Therapy in Patients with Ankylosing Spondylitis

<div><p>The aim of this study was to investigate the potential predictors of switching tumor necrosis factor (TNF)-α inhibitors in Korean patients with ankylosing spondylitis (AS). The patients who had been treated with TNF-α inhibitors were divided into two groups depending on whether they had switched TNF-α inhibitors. Demographic, clinical, laboratory, and treatment data at the time of initiation of TNF-α inhibitor treatment were compared between switchers and non-switchers, and within switchers according to the reasons for switching. Of the 269 patients, 70 (23%) had switched TNF-α inhibitors once; of these, 11 switched again. The median follow-up time was 52.7 months. Three- and five-year drug survival rates were 52%/48% for infliximab, 62%/42% for etanercept, and 71%/51% for adalimumab, respectively. Switchers were more likely to be prescribed disease-modifying anti-rheumatic drugs than non-switchers. A history of joint surgery and complete ankylosis of the sacroiliac joint was more frequent in switchers. Multivariate Cox’s proportional hazard analysis showed that the use of adalimumab as the first TNF-α inhibitor was less likely to lead to switching and complete ankylosis of the sacroiliac joints was more likely to lead to switching. The principal reasons for switching were drug inefficacy and adverse events, but the differences in the clinical data of these two groups of switchers were not significant. In AS patients who are candidates for TNF-α inhibitor therapy, switching may improve the therapeutic outcome based on clinical information.</p></div

Number of patients according to the course of treatment.

<p>TNF, tumor necrosis factor.</p><p>Number of patients according to the course of treatment.</p

Baseline characteristics of patients at the time of TNF-α inhibitor initiation according to the reason for subsequent switching.

<p>TNF, tumor necrosis factor; BMI, body mass index; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; AST, aspartate aminotransferase; ALT, alanine aminotransferase; INH, isoniazid; NSAIDs, non-steroidal anti-inflammatory drugs; DMARDs, disease-modifying anti-rheumatic drugs.</p><p>Continuous variables are shown as medians and interquartile range.</p><p>Baseline characteristics of patients at the time of TNF-α inhibitor initiation according to the reason for subsequent switching.</p

Predictors of TNF-α inhibitor switching.

<p>ESR, erythrocyte sedimentation rate; CRP, C-reactive protein; DMARDs, disease-modifying anti-rheumatic drugs.</p><p>Predictors of TNF-α inhibitor switching.</p