Handa City Hospital

BackgroundInsulin resistance (IR) is a key metabolic determinant of cardiovascular risk. Ceramides, a class of bioactive lipids, have been linked to IR; however, their clinical associations in patients with established coronary artery disease (CAD) are incompletely characterized.MethodsIn a prospective, multicenter observational cohort of adults with established CAD (n=987), we quantified plasma ceramide species (Cer16:0, Cer18:0, Cer24:0, Cer24:1) and surrogate IR indices (triglyceride–glucose index (TyG), metabolic score for insulin resistance (METS-IR), and triglyceride–to–high-density lipoprotein cholesterol ratio (TG/HDL-C)). Mixed graphical models (MGM) were used to estimate conditional associations within a multivariable network. Double machine learning (DML) with causal-forest estimators provided covariate-adjusted association estimates and probed robustness values (RV) to unmeasured confounding. Exposures were standardized per standard deviation. We also developed a ceramide-augmented model to classify clinical IR, prespecified as TyG ≥ 9, and quantified discrimination by the area under the receiver operating characteristic curve (ROC–AUC).ResultsCeramides correlated with IR indices. In MGM analyses, Cer24:0 showed a direct conditional association with TyG (partial r=0.23; 95% CI, 0.17–0.29), independent of other variables in the network. In DML analyses, per 1-unit increase in ln (Cer24:0) was associated with higher TyG (estimate, 0.459; 95% CI, 0.252–0.665; P = 0.001); These estimates demonstrated moderate RV to unmeasured confounding, with an RV (theta) of 0.223. A ceramide-augmented model classified clinical IR with an ROC–AUC of 0.770 (95% CI, 0.741–0.799).ConclusionsAcross complementary analytic frameworks, Cer24:0 consistently exhibited positive associations with lipid-centric IR metrics among adults with established CAD. Although observational, these findings suggest that circulating ceramide profiling—particularly Cer24:0—may refine metabolic risk stratification beyond conventional indices in cardiology practice.

Advances in insulin therapy have contributed to improved outcomes in diabetic ketoacidosis (DKA). However, severe cases requiring vasopressor support continue to carry a poor prognosis. A 47-year-old man without a prior diagnosis of diabetes developed polydipsia following increased carbohydrate intake. Despite symptoms suggestive of hyperglycemia, he underwent an oral glucose tolerance test (OGTT) without a prior plasma glucose measurement. Immediately afterward, he developed shock with altered mental status. His plasma glucose was 1,740 mg/dL; pH, 7.091; and total ketone bodies, 13,320 μmol/L - confirming severe DKA. Despite aggressive management, he developed persistent diarrhea, followed by septic shock. Repeat computed tomography at 36 hours revealed extensive intestinal pneumatosis, which was not present on admission, suggestive of non-occlusive mesenteric ischemia (NOMI). He progressed to multiple organ failure and died 76 hours after admission. This case highlights the potential for an OGTT to precipitate severe DKA in patients with undiagnosed diabetes. Concurrent septic shock further complicates fluid management and increases the risk of NOMI. This case underscores three critical lessons: (1) plasma glucose should be measured before performing an OGTT in patients suspected of having diabetes; (2) vigilant fluid management and infection control are essential in cases of severe DKA with shock; and (3) persistent diarrhea, despite appropriate DKA treatment, may represent an early sign of bowel ischemia in patients with altered consciousness.

ObjectivesAlthough accurate assessment of polyp morphology helps endoscopists select the appropriate management for colorectal polyps, some studies have reported unsatisfactory accuracy in such assessment. This study aimed to clarify the usefulness of a short educational video available on the Internet for accurate polyp morphology assessment.MethodsThis was a multicenter randomized controlled trial. Participants were randomly assigned to the pre‐ or post‐education groups after a pre‐test comprising images of 42 polyps, including 12 laterally spreading tumors. Participants who scored ≥ 80% on the pre‐test were excluded. Only the post‐education group completed the diagnostic test after watching an online educational video. The primary outcome was the difference in diagnostic accuracy between the pre‐test and diagnostic tests for each group.ResultsOf the 296 endoscopists enrolled from 48 institutions, 34 missed the test deadline, and 29 who scored ≥ 80% in the pre‐test were excluded. The primary outcome analysis sets were 117 and 116 in the pre‐ and post‐education groups, respectively. The mean pre‐test accuracies in the pre‐education and post‐education groups were 60.6% and 60.7%, respectively. The difference in diagnostic accuracy between the pre‐test and diagnostic test was significantly higher in the post‐education than the pre‐education group (12.0 points, 95% confidence interval [CI] 9.9–14.1 and 2.3 points, 95% CI 0.9–3.6; p < 0.001).ConclusionThis multicenter randomized controlled trial demonstrated the usefulness of a short educational video for accurate polyp morphology assessment.

Background/AimThe albumin-bilirubin (ALBI) grade is an assessment tool for hepatic function and prognosis in patients with hepatocellular carcinoma (HCC). However, its significance in patients with non-small cell lung cancer (NSCLC) treated with an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) remains unclear. We retrospectively investigated the relationship between pre-treatment ALBI grade and hepatotoxicity and treatment efficacy in patients with NSCLC receiving EGFR-TKIs.Patients and MethodsWe analyzed data from 182 patients with NSCLC treated with EGFR-TKIs. Patients were categorized into ALBI grades 1/2a and 2b/3 groups. We examined the association between ALBI grade, hepatotoxicity, and time to treatment failure (TTF) using univariate and multivariate analyses.ResultsIn the univariate Kaplan-Meier analysis, ALBI grade was not associated with hepatotoxicity (log-rank p=0.56). This finding was consistent with the multivariate analysis of patients treated with gefitinib and erlotinib (n=158). However, In the univariate Kaplan-Meier analysis, the median TTF for the ALBI grade 1/2a group was 10.6 months, compared to 5.8 months for the ALBI grade 2b/3 group (hazard ratio=1.66, 95% confidence interval=1.19-2.33, p=0.003). Multivariate analysis confirmed that ALBI grade 2b/3 (hazard ratio=1.64, 95% confidence interval=1.16-2.30, p<0.01) was independently associated with shortened TTF.ConclusionPretreatment ALBI grade classification can predict efficacy in patients with NSCLC treated with EGFR-TKIs.

The objective of this study was to compare the clinical effectiveness of baricitinib and abatacept in patients with rheumatoid arthritis (RA). This study included 274 patients treated with abatacept and 241 treated with baricitinib who were followed for >52 weeks. Potential treatment selection bias was addressed by using inverse probability of treatment weighting. The paired t-test was used to assess differences in Clinical Disease Activity Index (CDAI) score relative to baseline. A generalized estimating equation was used to compare the two treatment groups. The estimated mean CDAI score was 18.2 at baseline and significantly decreased to 12.6 at 4 weeks, 8.9 at 12 weeks, 7.4 at 24 weeks, and 6.1 at 52 weeks in the abatacept group. The estimated mean CDAI score was 18.6 at baseline and significantly decreased to 9.5 at 4 weeks, 6.5 at 12 weeks, 5.7 at 24 weeks, and 5.5 at 52 weeks in the baricitinib group. The baricitinib group had significantly lower CDAI scores at 4, 12, and 24 weeks compared to the abatacept group. Subgroup analyses revealed that this difference was evident among patients with high disease activity and without concomitant use of methotrexate but was less pronounced among those with remission to moderate disease activity status with methotrexate use. Both baricitinib and abatacept were effective in reducing disease activity in patients with RA. Baricitinib demonstrated potential advantages over abatacept in terms of early disease control, particularly in patients with high disease activity and without methotrexate use.

The long-term use of surgical masks to combat coronavirus disease 2019 may irritate the skin. A 67-year-old man developed a laceration on the auricle due to prolonged wearing of a mask. The patient had poor self-management skills and was required to wear masks. The torn auricular cartilage was surgically repaired. At four months post-operation, the auricular morphology had improved, and the scar was no longer visible. Continuous wearing of surgical masks can increase the risk of lacerations on the auricle, which can be sutured and healed within a short period. The proper use of regular breaks from masks is recommended. A medical device-related pressure ulcer of the auricle associated with surgical mask use is likely to occur in the left auricle of men with psychiatric disorders.

Background:Janus kinase (JAK) inhibitors block the signaling of multiple JAK-dependent cytokines. A number of studies have reported on the clinical efficacy of JAK inhibitors in patients with rheumatoid arthritis (RA). Post-hoc analyses of clinical trials suggest that JAK inhibitors may be more effective in sero-positive patients than in sero-negative patients [1, 2]. The efficacy of JAK inhibitors has been demonstrated both as monotherapy and in combination with methotrexate (MTX). However, few studies have directly compared JAK inhibitor monotherapy with MTX combination therapy.Objectives:This study aimed to determine predictors of clinical remission in patients with rheumatoid arthritis treated with JAK inhibitors in clinical setting, and to investigate the influence of concomitant MTX on disease activity.Methods:This study was performed based on data from a multicenter registry of patients with RA, and included 396 patients treated with JAK inhibitors (220 baricitinib, 66 peficitinib, 77 upadacitinib, and 92 filgotinib) who were observed for longer than 24 weeks. The impact of patient characteristics on remission [Simple Disease Activity Index (SDAI) ≤3.3] was assessed with logistic regression models. To assess the impact of concomitant use of MTX, patients were divided into two groups by MTX use: MTX (+) (n=216) and MTX (-) (n=180) groups. Propensity score matching was performed to address potential treatment-selection bias. Baseline data and disease activity were compared between the two groups using the unpaired t test for continuous variables and the chi-square test for categorical variables. The last observation carried forward method was used in each analysis.Results:Baseline characteristics of all patients included in this study (mean ± SD or %) was as follows: age 64 ± 14 years, 80% female, disease duration 13 ± 12 years, 83% anti-CCP antibody positive, 68% previous us of b/tsDMARDs, 55% MTX use, 39% glucocorticoid use (Table 1). SDAI score was 18.9 ± 12.0 at baseline, and significantly decreased to 10.7 ± 9.5 at 4 weeks (Figure 1a). 37% of patients were in SDAI remission at 24 weeks (Figure 1b). Multivariate analysis revealed that anti-CCP antibody positivity [odds ratio (OR): 2.09, 95% confidence interval (CI): 1.05-4.15], glucocorticoid use (OR: 0.40, 95% CI: 0.24-0.67) and SDAI score (OR: 0.96, 95% CI: 0.94-0.98) independently predicted SDAI remission at 24 weeks. None of the other variables, including concomitant use of MTX, predicted remission. Before propensity score matching, relative to the MTX (-) group, the MTX (+) group were more likely to be younger (mean ± SD, 61 ± 15 vs. 69 ± 12 years, P<0.001), and have a shorter disease duration (10 ± 10 vs. 16 ± 14 years, P<0.001), lower rates of chronic kidney disease defined as an eGFR<60 mL/min/1.73m2 (22% vs. 40%, P<0.001), and lower rates of previous use of b/tsDMARDs (59% vs. 79%, P=0.008) (Table 1). A total of 119 matched pairs of patients were identified upon propensity score matching. There was good balance across all characteristics between the two groups. There was no significant difference in SDAI scores between the two groups throughout 0-24 weeks (Figure 1c). The proportion of patients who achieved SDAI remission was significantly higher in the MTX (+) group than in the MTX (-) group at 12 weeks, but it became comparable at 24 weeks (Figure 1d).Conclusion:Anti-CCP antibody positivity, no use of glucocorticoid, and lower SDAI score at baseline independently predicted SDAI remission at 24 weeks in patients treated with JAK inhibitors. Moreover, concomitant MTX contributed to achieving remission earlier.REFERENCES:[1] Genovese MC, et al. Rheumatology (Oxford) 2018;57:900-8[2] Weinblatt ME, et al. ACR Annual Meeting 2019 [ 516]Acknowledgements:NIL.Disclosure of Interests:Shuji Asai AbbVie, Astellas, Eisai, Eli Lilly, Gilead Sciences, UCB Japan, Astellas, Kenya Terabe AbbVie, Astellas, Eisai, Eli Lilly, Gilead Sciences, UCB Japan, AbbVie, Nobunori Takahashi AbbVie, Astellas, Eisai, Eli Lilly, Gilead Sciences, UCB Japan, Yutaka Yoshioka: None declared, Tatsuo Watanabe: None declared, Toshihisa Kojima AbbVie, Astellas, Eisai, Eli Lilly, Gilead Sciences, UCB Japan, Tomonori Kobayakawa: None declared, Yasumori Sobue: None declared, Yasuhide Kanayama: None declared, Takuya Matsumoto: None declared, Yuji Hirano AbbVie, Astellas, Eisai, Eli Lilly, Gilead Sciences, UCB Japan, Takefumi Kato: None declared, Takayoshi Fujibayashi: None declared, Masahiro Hanabayashi: None declared, Tsuyoshi Nishiume: None declared, Mochihito Suzuki Eisai, Shiro Imagama: None declared.

Transient pain enhancement or flare pain, is observed following the administration of immune checkpoint inhibitors (ICIs). However, the detailed mechanism of this phenomenon remains unclear. In this report, we present our experience of documenting the course of flare pain following ICI administration in six cases. Six patients with advanced solid tumors received ICI monotherapy between July 2017 and November 2019. Their pain increased within hours of ICI administration despite being stable before ICI administration. We evaluated the changes in the numerical rating scale (NRS) score over 72 h after ICI administration. Four non-small cell lung cancer patients, one gastric cancer patient, and one renal cell cancer patient were included. Four patients experienced an increase in NRS, as evidenced by scores on two or more scales compared to the day before administration, whereas two patients showed an increase only on one scale. The NRS score decreased to almost the same level as that on the day before administration. Flare pain is observed in the same area as the primary site. Most of the pain was alleviated without the need for rescue analgesics, although one patient experienced a 4-point increase in the NRS scale. Flare pain may occur following ICI administration. Healthcare providers should be aware of these events and provide patients with suitable information and coping techniques.