Supplementary Material for: Localization of the Patency Capsule by Abdominal Tomosynthesis

<b><i>Background/Aims:</i></b> A patency capsule (PC) is used to assess intestinal patency in patients with known or suspected stricture, but PC localization by plain abdominal X-ray (AXR) is difficult in those patients in whom the PC is not detected in the feces. Tomosynthesis is a promising, cost-effective, and low-radiation digital tomographic technique. This prospective study evaluated its use for PC localization in the intestinal tract. <b><i>Methods:</i></b> The study subjects were 49 patients in whom the PC was not detected in the feces and was identified intra-abdominally on AXR films. PC localization in the small or large intestines by AXR alone or by tomosynthesis with AXR was compared with abdominal computed tomography (CT), which is the gold standard. <b><i>Results:</i></b> The PC was judged in the large and small intestines in 22 and 27 patients by AXR alone versus 34 and 15 patients, respectively, by tomosynthesis combined with AXR. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for PC detection by AXR alone were 52.9, 53.3, 56.2, 50.0, and 53.1%, respectively. The same parameters were 100, 100, 100, 100, and 100%, respectively, for tomosynthesis with AXR, which were identical to those of CT. <b><i>Conclusions:</i></b> Tomosynthesis with AXR is superior to AXR alone, though similar to CT, with respect to localization of the PC

Supplementary Material for: Present Status and Road Map to Achieve Inclusive and Holistic Care for Dementia in a Japanese Community: Analysis Using the Delphi Method

<b><i>Background/Aims:</i></b> Dementia is a priority issue in the public health realm. However, few reports address problems of dementia in the real world or provide comprehensive road maps to solve these problems. <b><i>Methods:</i></b> Nine groups of questions covering 4 topics were discussed using the Delphi method, relating to (1) current achievements and challenges regarding inclusive and holistic care in the community, (2) patients who are at a high risk of being excluded from care, (3) suggestions for a road map for the establishment of better and more inclusive medical and social care, and (4) unmet needs of patients with dementia. <b><i>Results:</i></b> In total, 477 opinions were obtained. Family issues, psychological/behavioral symptoms, and complications secondary to physical disorders are main factors for being excluded from care. To create a road map for care we have to address the topics of reaffirming care principles, multidisciplinary coalitions, and education for stakeholders. <b><i>Conclusion:</i></b> Further effective collaboration to promote dementia care is required

Supplementary Material for: Effectiveness and Safety of Golimumab in the Treatment of Ulcerative Colitis: 52-week Results from Post-marketing Surveillance in Japan

Introduction: Real-world evidence for the effectiveness and safety of golimumab (GLM) in patients with ulcerative colitis (UC) is limited. The aim of this study was to investigate the 52-week effectiveness and safety of GLM treatment for UC. Methods: This prospective, multicentre, post-marketing surveillance study is conducted in 393 patients with UC in Japan (UMIN000027542). Clinical remission (partial Mayo score ≤2), adverse drug reactions (ADRs) and their predictors, and treatment persistence were analysed. Results: The safety analysis sets comprised 391 patients. Patients in clinical remission at baseline were excluded, and 336 were used for effectiveness analysis. Clinical remission was 47.9%, 48.5%, 44.6%, and 39.6% at weeks 6, 22, 36, and 52, respectively, in the intent-to-treat analysis. In biologic-naïve patients, clinical remission was slightly higher than that in biologic-experienced patients. At week 52, patients who concomitantly used corticosteroids at baseline showed numerically lower clinical remission rates than non-users of corticosteroids (34.9% vs 44.5%). Multivariate analysis showed that smoking history (P=0.040, odds ratio [OR]=1.911, 95% confidence interval [CI] 1.030–3.546) was an independent factor associated with clinical remission at week 52. ADRs occurred in 71 patients (18.2%) and included 9 cases of rash. Serious ADRs occurred in 40 patients (10.2%), including 8 cases of UC exacerbation. Additionally, the presence of comorbidities was associated with ADR incidence (P=0.010, OR=2.000, 95% CI 1.183–3.380). Conclusion: The real-world effectiveness of GLM treatment was confirmed in biologic-naïve and -experienced populations. The safety profile of GLM treatment was consistent with previous findings

Supplementary Material for: Isoliquiritigenin Ameliorates Indomethacin-Induced Small Intestinal Damage by Inhibiting NOD-Like Receptor Family, Pyrin Domain-Containing 3 Inflammasome Activation

Activation of the NOD-Like Receptor Family, Pyrin Domain-Containing 3 (NLRP3) inflammasome, which consists of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and pro-caspase-1, triggers pro-caspase-1 cleavage promoting the processing of pro-interleukin (IL)-1β into mature IL-1β, which is critical for the development of non-steroidal anti-inflammatory drug (NSAID)-induced enteropathy. We investigated the effects of isoliquiritigenin, a flavonoid derived from the roots of <i>Glycyrrhiza</i> species, on NSAID-induced small intestinal damage and the inflammasome activation. To induce enteropathy, mice were administered indomethacin by gavage with or without isoliquiritigenin pretreatment. Some mice received an intraperitoneal injection of recombinant murine IL-1β in addition to isoliquiritigenin and indomethacin. Indomethacin induced small intestinal damage and increased protein levels of cleaved caspase-1 and mature IL-1β in the small intestine. Treatment with 7.5 and 75 mg/kg isoliquiritigenin inhibited indomethacin-induced small intestinal damage by 40 and 56%, respectively. Isoliquiritigenin also inhibited the indomethacin-induced increase in cleaved caspase-1 and mature IL-1β protein levels, whereas it did not affect the mRNA expression of NLRP3, ASC, caspase-1, and IL-1β. Protection against intestinal damage in isoliquiritigenin-treated mice was completely abolished with exogenous IL-1β. NLRP3^–/– and caspase-1^–/– mice exhibited resistance to intestinal damage, and isoliquiritigenin treatment failed to inhibit the damage in NLRP3^–/– and caspase-1^–/– mice. Isoliquiritigenin prevents NSAID-induced small intestinal damage by inhibiting NLRP3 inflammasome activation

Supplementary Material for: Current Status of the Management of Hereditary Breast and Ovarian Cancer in Asia: First Report by the Asian BRCA Consortium

<b><i>Background:</i></b><i>BRCA1/BRCA2</i> mutations are associated with an increased lifetime risk for hereditary breast and ovarian cancer (HBOC). Compared with the Western developed countries, genetic testing and risk assessment for HBOC in Asia are less available, thus prohibiting the appropriate surveillance, clinical strategies and cancer management. <b><i>Methods:</i></b> The current status of HBOC management in 14 Asian countries, including genetic counselling/testing uptakes and clinical management options, was reviewed. We analysed how economic factors, healthcare and legal frameworks, and cultural issues affect the genetic service availability in Asia. <b><i>Results:</i></b> In 2012, only an estimated 4,000 breast cancer cases from 14 Asian countries have benefited from genetic services. Genetic testing costs and the absence of their adoption into national healthcare systems are the main economic barriers for approaching genetic services. Training programmes, regional accredited laboratories and healthcare professionals are not readily available in most of the studied countries. A lack of legal frameworks against genetic discrimination and a lack of public awareness of cancer risk assessment also provide challenges to HBOC management in Asia. <b><i>Conclusions:</i></b> The Asian BRCA Consortium reports the current disparities in genetic services for HBOC in Asia and urges the policy makers, healthcare sectors and researchers to address the limitations in HBOC management

Supplementary Material for: Relationship of atezolizumab plus bevacizumab treatment with muscle volume loss in unresectable hepatocellular carcinoma patients– multicenter analysis

Background/Aim: There is no known report regarding the relationship of atezolizumab plus bevacizumab (Atez/Bev) treatment with muscle volume loss (MVL) in unresectable hepatocellular carcinoma (u-HCC) patients. This study aimed to elucidate the clinical relationship between MVL and Atez/Bev. Materials/Methods: From September 2020 to December 2021, 229 u-HCC patients treated with Atez/Bev and with muscle volume data obtained by computed tomography at the baseline available were analyzed (median age, 74 years; males, 186 (81.2%); ECOG PS 0/1, 221 (96.5%); HCV:HBV:alcohol:others=81:33:40:75; Child-Pugh A, 212 (92.6%); mALBI grade 1:2a:2b=79:60:90; BCLC 0:A:B:C =1:24:87:117; median observation period, 6.8 months). Japan Society of Hepatology criteria were used for definition of MVL and prognostic factors were retrospectively evaluated. Results: Multivariate Cox-hazard analysis of prognostic factors for progression-free survival (PFS) showed elevated alpha-fetoprotein (AFP) (≥100 ng/mL) (HR 1.848, 95%CI 1.264-2.702, P=0.002), modified albumin-bilirubin (mALBI) grade (≥2a) (HR 1.563, 95%CI 1.035-2.359, P=0.034), and MVL (HR 1.479, 95%CI 1.020-2.144, P=0.039) as significant factors. For overall survival (OS), significant factors included elevated AFP (≥100 ng/mL) (HR 3.564, 95%CI 1.856-6.844, P<0.001), mALBI grade (≥2a) (HR 3.451, 95%CI 1.580-7.538, P=0.002), and MVL (HR 2.119, 95%CI 1.150-3.904, P=0.016). Patients with MVL (MVL group, n=91) showed worse PFS than those without (non-MVL group, n=138) (median PFS 5.3 vs. 7.6 months, P=0.025), while the MVL group showed worse OS (P=0.038), though neither reached the median survival time. Conclusion: MVL may be a clinical factor related to poor prognosis in patients receiving Atez/Bev treatment for u-HCC