Predictors of exercise-induced pulmonary hypertension in patients with asymptomatic degenerative mitral regurgitation: mechanistic insights from 2D speckle-tracking echocardiography

Presence of exercise-induced pulmonary hypertension (EIPH) in asymptomatic degenerative mitral regurgitation (DMR) determines prognosis. This study aimed to elucidate the mechanism and predictors of EIPH in asymptomatic DMR. Ninety-one consecutive asymptomatic patients with DMR who underwent exercise stress echocardiography were prospectively included. We obtained various conventional echocardiographic parameters at rest and during peak exercise, as well as left atrial (LA) function at rest using 2-dimensional speckle-tracking analysis. The 25 patients (33.3%) with EIPH were significantly older and had a greater ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity during peak exercise than those without EIPH. LA strain (LAS)-s and LAS-e, indices of LA reservoir and conduit function, respectively, were significantly lower in those with EIPH than in those without EIPH. Multivariate analysis indicated that LAS-s was the only resting echocardiographic parameter that independently predicted EIPH, with a cut-off value of 26.9%. Furthermore, Kaplan-Meier curve analysis showed that symptom-free survival was markedly lower among those with reduced LAS-s. In conclusion, decreased LA reservoir function contributes to EIPH, and LAS-s at rest is a useful indicator for predicting EIPH in asymptomatic patients with DMR

Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: The ANSWER cohort study

Background: This multi-center, retrospective study aimed to clarify retention rates and reasons for discontinuation of 7 biological disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib (TOF), one of the janus kinase inhibitors, in bDMARDs-naïve and bDMARDs-switched patients with rheumatoid arthritis (RA). Methods: This study assessed 3897 patients and 4415 treatment courses with bDMARDs and TOF from 2001 to 2019 (2737 bDMARDs-naïve courses and 1678 bDMARDs-switched courses [59.5% of switched courses were their second agent], female 82.3%, baseline age 57.4 years, disease duration 8.5 years; rheumatoid factor positivity 78.4%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate 4.3; concomitant prednisolone [PSL] dose 6.1 mg/day [usage 42.4%], and methotrexate [MTX] dose 8.5 mg/week [usage 60.9%]). Treatment courses included abatacept (ABT; n = 663), adalimumab (ADA; n = 536), certolizumab pegol (CZP; n = 226), etanercept (ETN; n = 856), golimumab (GLM; n = 458), infliximab (IFX; n = 724), tocilizumab (TCZ; n = 851), and TOF (n = 101/only bDMARDs-switched cases). Drug discontinuation reasons (categorized into lack of effectiveness, toxic adverse events, non-toxic reasons, or remission) and rates were estimated at 36 months using Gray's test and statistically evaluated after adjusted by potential clinical confounders (age, sex, disease duration, concomitant PSL and MTX usage, starting date, and number of switched bDMARDs) using the Fine-Gray model. Results: Cumulative incidence of drug discontinuation for each reason was as follows: lack of effectiveness in the bDMARDs-naïve group (from 13.7% [ABT] to 26.9% [CZP]; P < 0.001 between agents) and the bDMARDs-switched group (from 18.9% [TCZ] to 46.1% [CZP]; P < 0.001 between agents); toxic adverse events in the bDMARDs-naïve group (from 4.6% [ABT] to 11.2% [ETN]; P < 0.001 between agents) and the bDMARDs-switched group (from 5.0% [ETN] to 15.7% [TOF]; P = 0.004 between agents); and remission in the bDMARDs-naïve group (from 2.9% [ETN] to 10.0% [IFX]; P < 0.001 between agents) and the bDMARDs-switched group (from 1.1% [CZP] to 3.3% [GLM]; P = 0.9 between agents). Conclusions: Remarkable differences were observed in drug retention of 7 bDMARDs and TOF between bDMARDs-naïve and bDMARDs-switched cases.Ebina K., Hirano T., Maeda Y., et al. Drug retention of 7 biologics and tofacitinib in biologics-naïve and biologics-switched patients with rheumatoid arthritis: The ANSWER cohort study. Arthritis Research and Therapy 22, 142 (2020); https://doi.org/10.1186/s13075-020-02232-w

The Molecular Outflows in the rho Ophiuchi Main Cloud: Implications For Turbulence Generation

We present the results of CO (J=3-2) and CO (J=1-0) mapping observations toward the active cluster forming clump, L1688, in the rho Ophiuchi molecular cloud. From the CO (J=3-2) and CO (J=1-0) data cubes, we identify five outflows, whose driving sources are VLA 1623, EL 32, LFAM 26, EL 29, and IRS 44. Among the identified outflows, the most luminous outflow is the one from the prototypical Class 0 source, VLA 1623. We also discover that the EL 32 outflow located in the Oph B2 region has very extended blueshifted and redshifted lobes with wide opening angles. This outflow is most massive and have the largest momentum among the identified outflows in the CO (J=1-0) map. We estimate the total energy injection rate due to the molecular outflows identified by the present and previous studies to be about 0.2 L_solar, larger than or at least comparable to the turbulence dissipation rate [~(0.03 - 0.1) L_solar]. Therefore, we conclude that the protostellar outflows are likely to play a significant role in replenishing the supersonic turbulence in this clump.Comment: 37 pages, 9 figures, accepted for publication in The Astrophysical Journa

Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study-

The purpose of this study was to evaluate the retention and discontinuation reasons of seven biological disease-modifying antirheumatic drugs (bDMARDs) in a real-world setting of patients with rheumatoid arthritis (RA). 1,037 treatment courses with bDMARDs from 2009 to 2016 [female, 81.8%; baseline age, 59.6 y; disease duration 7.8 y; rheumatoid factor positivity 81.5%; Disease Activity Score in 28 joints using erythrocyte sedimentation rate (DAS28-ESR), 4.4; concomitant prednisolone 43.5% and methotrexate 68.6%; Bio-naïve, 57.1%; abatacept (ABT), 21.3%; tocilizumab (TCZ), 20.7%; golimumab (GLM), 16.9%; etanercept (ETN), 13.6%; adalimumab (ADA), 11.1%; infliximab (IFX), 8.5%; certolizumab pegol (CZP), 7.9%] were included in this multi-center, retrospective study. Drug retention and discontinuation reasons at 36 months were estimated using the Kaplan-Meier method and adjusted by potent confounders using Cox proportional hazards modeling. As a result, 455 treatment courses (43.9%) were stopped, with 217 (20.9%) stopping due to inefficacy, 113 (10.9%) due to non-toxic reasons, 86 (8.3%) due to toxic adverse events, and 39 (3.8%) due to remission. Drug retention rates in the adjusted model were as follows: total retention (ABT, 60.7%; ADA, 32.7%; CZP, 43.3%; ETN, 51.9%; GLM, 45.4%; IFX, 31.1%; and TCZ, 59.2%; P < 0.001); inefficacy (ABT, 81.4%; ADA, 65.7%; CZP, 60.7%; ETN, 71.3%; GLM, 68.5%; IFX, 65.0%; and TCZ, 81.4%; P = 0.015), toxic adverse events (ABT, 89.8%; ADA, 80.5%; CZP, 83.9%; ETN, 89.2%; GLM, 85.5%; IFX, 75.6%; and TCZ, 77.2%; P = 0.50), and remission (ABT, 95.5%; ADA, 88.1%; CZP, 91.1%; ETN, 97.5%; GLM, 94.7%; IFX, 86.4%; and TCZ, 98.4%; P < 0.001). In the treatment of RA, ABT and TCZ showed higher overall retention, and TCZ showed lower inefficacy compared to IFX, while IFX showed higher discontinuation due to remission compared to ABT, ETN, GLM, and TCZ in adjusted modeling.Ebina K., Hashimoto M., Yamamoto W., et al. (2018) Drug retention and discontinuation reasons between seven biologics in patients with rheumatoid arthritis -The ANSWER cohort study-. PLoS ONE 13(3): e0194130. doi: 10.1371/journal.pone.0194130

A Patient with Non-alcoholic Steatohepatitis Complicated by Multiple Myeloma

A 68-year-old woman with liver dysfunction was diagnosed with nonalcoholic steatohepatitis (NASH) stage 1. Three years later, she showed massive ascites and jaundice. A trans-jugular liver biopsy confirmed advanced cirrhosis, suggesting that her liver fibrosis had progressed rapidly. At the same time, she was diagnosed with multiple myeloma (MM). In this case, the plasma levels of osteopontin (OPN), a proinflammatory cytokine that promotes liver fibrosis progression through the hedgehog pathway and is increased in patients with MM, were increased. This increased OPN expression was accompanied by the upregulation of the hedgehog pathway in this patient, suggesting that the MM-associated increase in OPN had promoted the progression of liver fibrosis through the hedgehog pathway. The progression of liver fibrosis should be monitored in patients with NASH if other diseases, such as MM, are present