Kani Tono Hospital

Abstract AimsGLP-1 and GIP-GLP-1 agonists have emerged as potent weight loss medications. These incretin mimetics often have low patient adherence, and as with any medication, clinically meaningful efficacy requires adequate adherence. But what constitutes “adequate” adherence for incretin mimetics? The purpose of this paper is to address this question.Materials and MethodsWe use mathematical modeling and stochastic simulation to investigate the weight loss efficacy of incretin mimetics under imperfect adherence. We use validated pharmacokinetic and pharmacodynamic models of semaglutide and tirzepatide and assume that simulated patients randomly miss doses.ResultsWe find that semaglutide and tirzepatide forgive nonadherence, meaning that strong weight loss efficacy persists despite missed doses. For example, taking 80% of the prescribed doses yields around 90% of the weight loss achieved under perfect adherence. Taking only 50% of prescribed doses yields nearly 70% of the weight loss of perfect adherence. Furthermore, such nonadherence causes only small fluctuations in body weight, assuming that patient do not typically miss more than several consecutive doses.ConclusionIncretin mimetics are powerful tools for combating obesity, perhaps even if patients can consistently take only half of their prescribed doses. The common assumption that significant weight loss requires at least 80% adherence needs revision.

The data that support the findings of this study are available from the corresponding author upon reasonable request. Figure S1. Table S1. Table S2. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

BackgroundContinuation of methotrexate (MTX) treatment is recommended in both MTX responder and non-responder elderly-onset RA (EORA) patients. However, there are insufficient data on its effectiveness and long-term safety, although we have previously reported that a treat-to-target (T2T) strategy targeting low disease activity (LDA) is safe and effective in the prospective CRANE cohort study of MTX-naïve EORA patients [1, 2].ObjectivesTo identify factors predicting failure to achieve LDA by month 6 in EORA patients starting MTX, and effectiveness and safety of MTX over 5 years in MTX responders and non-responders.MethodsMTX-naïve patients (mean age 73.8 years, n=163) from the CRANE cohort [2] had started MTX with moderate-to-high disease activity. Maximum dose of MTX was 0.19±0.06 mg/week/kg with folate supplementation. Treatment was adjusted to target LDA. Treatment intensification using biological disease-modifying antirheumatic drugs (bDMARDs) for EULAR-unresponsive patients by month 3 and moderate-high disease activity at month 6 was applied. MTX non-responsiveness was defined as no LDA and/or initiation of bDMARDs by month 6. Primary outcomes were achievement of Simplified disease activity index (SDAI) LDA and discontinuation of MTX due to adverse events (AEs). Secondly outcomes were achievement of remission and Health Assessment Questionnaire Disability Index (HAQ-DI) ≤0.5, and incidence of serious AEs.ResultsAt week 24, 77 (47.2%) patients achieved LDA without bDMARDs (MTX responders), and of the remaining 86 (MTX non-responders), 35 (21.5%) had started bDMARDs by month 6 and 51 (31.3%) had moderate-to-high disease activity on MTX at week 24. At baseline, MTX non-responders had longer disease duration, higher SDAI and HAQ-DI, higher prevalence of erosion score ≥2 (modified total sharp score) and chronic lung disease (CLD), but baseline glucocorticoid use was similar. Multivariable analysis identified CLD as a predictor of MTX non-responsiveness. Regarding long-term outcomes, 14 (18.2%) of the 77 MTX responders and 55 (64%) of the 86 MTX non-responders received intensified treatment with bDMARDs within 5 years. MTX was continued in 65 (94.2%) of the 69 patients at the start of bDMARDs. The Cumulative rate of MTX discontinuation due to AEs was similar in MTX responders and non-responders (34.0% and 33.1%) as was the time to discontinuation of MTX due to AEs. The time to discontinuation of MTX for any reason was also similar. SDAI LDA and HAQ-DI ≤0.5 achievement by year 5 applying the last observation carried forward (LOCF) method was 92.2% and 74.0% respectively for MTX responders and 77.9% and 53.5% for MTX non-responders, respectively (p=0.011 for SDAI LDA and 0.007 for HAQ-DI). SDAI remission at year 5 by LOCF was similar (62.6% and 52.3% in MTX responders-vs-non responders). The time to serious AEs was also similar, as was the cumulative incidence of serious AEs over the 5 years was 32.6% and 44.3% in MTX responders-vs-non-responders.ConclusionCLD was a predictive factor of non-achievement of LDA by month 6 in EORA patients starting MTX, and early application of bDMARDs may be adequate for treating EORA with CLD at baseline. The 5-year long-term outcome for MTX responders was excellent, and continuation of MTX was tolerable even in MTX non-responders. Treatment intensification on MTX could be an optimal T2T strategy for EORA.

Rheumatoid arthritis (RA) patients often exhibit finger/wrist joint symptoms and reduced grip strength. This study aimed to validate grip strength as a measure of frailty in RA patients. Subjects were 424 female RA patients (mean age ± standard deviation, 66.8 ± 14.5 years). Frailty was defined as a score of ≥ 8 points on the Kihon Checklist (KCL). Finger/wrist joint symptoms were defined based on tender or swollen joints. Associations between frailty and grip strength were determined using receiver operating characteristic (ROC) curve analysis and multivariable logistic regression analysis. There were 179 subjects with frailty (42.2%). Multivariable logistic regression analysis revealed that frailty was significantly associated with grip strength independently of finger/wrist joint symptoms. In ROC curves, cut-off scores of grip strength for frailty in subjects without and with finger/wrist joint symptoms were 17 kg (sensitivity, 62.1%; specificity, 69.0%) and 14 kg (sensitivity, 63.2%; specificity, 73.0%), respectively. The results of the present study suggest that grip strength in female RA patients is associated with frailty, with a cut-off score of 17 kg (equivalent to Cardiovascular Health Study criteria, < 18 kg) when RA patients have no finger/wrist joint symptoms. However, when RA patients have finger/wrist joint symptoms, it may be considered to reduce the cut-off score of grip strength.

To investigate factors associated with frailty in rheumatoid arthritis (RA) patients with decreased renal function. RA patients who visited outpatient clinics from June to August 2021 were included (N = 625). Patients with estimated glomerular filtration rate <60 ml/min/1.73 m2 were defined as having decreased renal function (N = 221) and divided into the non-frailty (N = 153) and frailty (N = 58) groups. Patient characteristics were compared between the two groups by univariate analysis. Significant factors in univariate analysis were assessed by logistic regression analysis to determine their association with frailty in patients with decreased renal function. Patients in the frailty group were older (74.0 vs.79.0 years) and had a longer duration of disease (11.1 vs. 17.8 years), higher Disease Activity Score erythrocyte sedimentation rate (DAS28-ESR; 2.99 vs. 3.80), higher Health Assessment Questionnaire Disability Index (0.42 vs. 1.43), and a lower rate of methotrexate (MTX) use (46.4% vs. 25.9) compared to those in the non-frailty group. Factors associated with frailty in patients with decreased renal function were age (odds ratio: 1.07), duration of disease (1.06), DAS28-ESR (1.85), and MTX use (0.42). Among factors associated with frailty in RA patients with decreased renal function, improving DAS28-ESR is likely to be the most feasible approach to promote recovery from frailty (200/200 words).

This study aimed to evaluate the association between locomotive syndrome (LS) and frailty in rheumatoid arthritis (RA) patients. Subjects were 538 RA patients (female, 72.9%; mean age ± standard deviation, 66.8 ± 13.4 years). LS and frailty were defined as ≥16 points on the 25-question Geriatric Locomotive Function Scale (Stage ≥2) and ≥8 points on the Kihon Checklist (KCL), respectively. There were 214 subjects with Stage ≥2 LS (39.8%) and 213 subjects with frailty (39.6%). Among subjects with Stage 0, 1, 2, and 3 LS, 11.0%, 21.9%, 48.3%, and 84.6% had frailty, respectively. The KCL points for cognitive and psychosocial factors had no significant differences across LS stages. Multivariable logistic regression analysis revealed that the Health Assessment Questionnaire was independently associated with frailty and LS stage, and the Clinical Disease Activity Index was associated with LS stage but not frailty. As LS worsens in RA patients, the likelihood of developing physical frailty increases. RA patients with a low LS stage can still develop frailty, and suppressing disease activity may not be sufficient to prevent frailty. These findings highlight the need to screen for frailty in RA patients and consider appropriate interventions based on each patient's condition, focusing on nonphysical factors.

乳腺原発の神経内分泌癌（腫瘍）は全乳癌の0.08-0.8％と報告されており，極めてまれである．嚢胞内腫瘍という形態で発生する本邦報告は自験例を含め4例であった．

This study aimed to determine the clinical significance of MRI characteristics as a possible predictor of responsiveness to meloxicam treatment in patients with desmoid-type fibromatosis (DF). Additionally, it analysed the correlation between CTNNB1 mutation status and signal intensity of MRI. Forty-six patients consecutively treated with meloxicam composed this study. The low-intensity area (LIA) on T2-weighted MRI was determined. We divided patients into two groups based on the efficacy of meloxicam: a clinical benefit group (CB group, including CR: complete response; PR: partial response; and SD: stable disease) and non-clinical benefit group (NB group, including PD: progressive disease). Correlations of the efficacy with LIA and CTNNB1 mutation status with LIA were investigated. In total, 11, 17 and 18 patients showed PR, SD and PD, respectively. The mean LIA ratio before treatment was significantly higher (P<0.001) in the CB group than in the NB group. For predicting the efficacy, sensitivity was 68%, and specificity was 89% when setting the cut-off value as 20% for LIA. Mean changes in the LIA ratio before and after treatment were significantly higher (P=0.01) in the CB group than in the NB group. Mean LIA ratio before treatment was significantly lower (P<0.001) in the S45F mutation group than in the other mutation group. In multivariate analysis, the LIA ratio before treatment was a significant predictor of responsiveness (P=0.02). MRI characteristics were a useful predictor of the efficacy of meloxicam in DF patients. It may be possible to predict the clinical outcome more accurately when combined with other factors, such as CTNNB1 mutantion status.

今回われわれは，術前に肝外胆管走向異常を正確に診断し，安全に手術しえた2例を経験したので報告する．症例1は76歳の女性で，穿孔性虫垂炎術後に急性胆石胆嚢炎を発症した．症例2は59歳の男性で，健診で胆嚢腺筋症を指摘され当院に受診された．2例とも術前DIC-CTで左右肝管低位合流部に胆嚢管が合流する肝外胆管走向異常と診断され，腹腔鏡下胆嚢摘出術が施行された．術中胆管損傷の予防のために順行性胆嚢摘出術を施行し，術中・術後合併症は認めなかった．胆嚢摘出術における術中胆管損傷は比較的稀な合併症ではあるが，胆道系には様々な走向異常があるため，術前の画像診断による胆管像の把握は重要である．DIC-CTは簡便かつ非侵襲的な検査であり，腹腔鏡下胆嚢摘出術の術前検査として非常に有用であった．