Kamituga General Hospital

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease for which an apparent cause has not been identified. OLP is refractory to treatment, and malignant transformation has been reported. Therefore, discovering drugs for OLP with few adverse effects over long-term administration is crucial. In this study, we established an in vitro OLP model to investigate the effects of Cepharanthin®, an alkaloid mixture derived from Stephania cephalantha Hayata, and its major four components on inflammation-related gene expression in epithelial cells and lymphocytes. Four alkaloids from Cepharanthin® suppressed expression of cytokine genes to various degrees in activated T cells, but the effect of Cepharanthin® as a drug formulation was limited. However, the four alkaloids and Cepharanthin® suppressed expression of cytokine genes in human oral epithelial cells when stimulated with IL-1β. In the OLP model, activated T cells increased inflammatory gene expression in epithelial cells, while Cepharanthin® suppressed this expression. An anti-inflammatory effect of Cepharanthin® was also observed by protein dot blot. These findings suggest that the effects of Cepharanthin® might occur in two ways: mild suppression of inflammatory cytokines production in T lymphocytes and strong suppression of the response of epithelial cells to inflammatory stimuli. The anti-inflammatory effects of Cepharanthin® on activated T cells and oral mucosal epithelial cells shown in this study support its potential clinical efficacy for OLP. Furthermore, the in vitro model established in this study could be used as a tool for examining the mechanisms of OLP pathogenesis and disease persistence.

Background: Nontuberculous Mycobacterium (NTM) infections affecting musculoskeletal structures are rare, particularly in patients with well-controlled rheumatoid arthritis (RA). This case is reported to highlight the potential risk of focal tenosynovitis due to Mycobacterium intracellulare following intra-articular glucocorticoid injection.Case presentation: A 79-year-old man with well-controlled RA developed tenosynovitis with bone destruction in the right index finger metacarpophalangeal joint following a single intra-articular injection of triamcinolone acetonide. Despite antibiotic treatment, the condition progressively worsened. Synovectomy revealed Mycobacterium intracellulare infection involving both flexor tendons, joint space, and bone marrow. The patient regularly engaged in gardening activities without protective gloves.Conclusion: This case highlights the importance of considering NTM infection in the differential diagnosis of persistent monoarthritis that worsens after intra-articular glucocorticoid injection, especially in patients with exposure risk factors such as gardening.

Oral lichen planus (OLP) is a chronic inflammatory mucosal disease, and an apparent cause has not been identified. OLP is refractory to treatment, and malignant transformation has been reported. Therefore, discovering effective drugs with few adverse effects over long-term administration is crucial. In this study, we established an in vitro OLP model to investigate the effects of Cepharanthin®, an alkaloid mixture derived from Stephania cephalantha Hayata. Four alkaloids from Cepharanthin® suppressed the expression of cytokine genes at various degrees in activated T cells. However, the effect of Cepharanthin® was limited. On the other hand, Cepharanthin® and four alkaloids suppressed the expression of various cytokine genes in human oral epithelial cells when stimulated with IL-β. In the OLP model, activated T cells increased the inflammatory gene expression in the epithelial cells, while Cepharanthin® suppressed their gene expression. Anti-inflammatory effect of Cepharanthin® was observed by protein dot blot. The effects of Cepharanthin®️ might be expressed through two aspects: its effect of mildly suppressing the activation of T lymphocytes and strongly suppressing the response of epithelial cells to inflammatory stimuli. The in vitro model established in this study could be a tool for elucidating the mechanisms of OLP pathogenesis and disease persistence.

Delayed bleeding is the most frequent adverse event associated with endoscopic mucosal resection (EMR) and hot snare polypectomy (HSP) of colorectal polyps. However, whether the incidence of delayed bleeding differs between outpatient and inpatient treatment is unknown. Therefore, in this study, we aimed to evaluate delayed bleeding rates between outpatient and inpatient endoscopic treatments and clarify the safety of outpatient treatment. We enrolled 469 patients (1077 polyps) and 420 patients (1080 polyps) in the outpatient and inpatient groups, respectively, who underwent EMR or HSP for colorectal polyps at our institution between April 2020 and May 2023. Using propensity score matching, we evaluated the delayed bleeding rates between the two groups. Delayed bleeding was defined as a hemorrhage requiring endoscopic hemostasis occurring within 14 days of the procedure. Propensity score matching created 376 (954 polyps) matched patient pairs. The median maximum diameter of polyps removed was 10 mm in both groups. Delayed bleeding rates per patients were 1.3% (5/376) in the outpatient group and 2.9% (11/376) in the inpatient group (P=0.21). In term of per polyp, early delayed bleeding (occurring within 24 hours) rates were higher in the inpatient group than outpatient group (0.2% [2/954] vs. 1.1% [10/954], respectively; P=0.04). No severe bleeding requiring a transfusion occurred in either group. Outpatient endoscopic treatment did not increase delayed bleeding compared with inpatient treatment. Outpatient treatment would be safe and common for the removal of colorectal polyps.

The present study is the first large-scale, multicenter survey on modified electroconvulsive therapy (ECT) in Japan. We aimed to comprehend the current implementation status of ECT based on the annual reports of 2016 from 21 facilities that were certified by the Japanese Society of General Hospital Psychiatry as ECT certified facilities and participated in this multicenter observational study. We investigated the distributions of diagnosis, gender, and age of patients receiving acute-phase ECT, and the efficacy, safety, and adverse events. The number of patients receiving acute-phase ECT was 524. According to International Classification of Diseases, 10th Revision, 344 patients (65.6%) were diagnosed with mood disorders (F3), 156 patients (29.8%) were diagnosed with schizophrenia and with schizotypal and delusional disorders (F2), and 151 subjects were male and 334 subjects were female. The mean age of patients was 60.4 years (SD 15.9), and patients 60 years or older accounted for 57.9%. Efficacy did not significantly differ between diagnoses, nor between genders. However, the efficacy rate was significantly higher in elderly patients. In acute-phase ECT, 4 severe adverse events occurred. Our multicenter study confirmed that F3 (mood disorders) was the most common indication for ECT at 66%, followed by F2 (schizophrenia, schizotypal, and delusional disorders) at 30%, with no difference in efficacy, indicating that ECT is still performed as 1 of the treatment options for schizophrenia in Japan. The present results suggested that accumulation of annual data from multiple centers can be useful for more effective and safer ECT practices.

Background:Most of rheumatoid arthritis (RA) practice guidelines and recommendations suggest stopping of molecular target drugs such as biological and targeted synthetic disease-modifying antirheumatic drugs before orthopaedic surgeries. However, there are still concerns on increasing complications after surgeries, and no convincing data are available yet [2].Objectives:We aimed to investigate whether stopping of molecular target drugs before operations increase postoperative complications after orthopaedic surgeries in patients with RA in clinical practice by a multicenter cohort study.Methods:We collected cases of orthopaedic surgeries for patients with RA undergone from April, 2011 to March, 2017, in 19 specialized institutions in Japan. Demographic data, types of operations, drugs used for RA, stopping time periods of them, and postoperative complications within a year were recorded. We compared the incidence ratios of postoperative complications between stopping and no-stopping groups, among drug types, and among types of operations. Multivariate analyses were performed to investigate risk factors for delayed wound healing, surgical site infection (SSI), flare-up and death.Results:A total of 1953 cases were eligible for analyses. The averages of age, duration of the disease, and disease activity score 28 (DAS28)-CRP at the time of operation were 71.8 years, 18.6 years and 2.84, respectively. Methotrexate (MTX) and oral glucocorticoid were used in 59.5% and 58.0% of the patients. We set up two standards of stopping time period, and there were no statistical differences in incidence ratios of delayed wound healing, SSI and death in both standards, but the incidence ratio of flare-up was statistically higher in the stopping group. The incidence ratio of flare up was higher in IL-6 inhibitor group, and that of delayed wound healing was higher in major surgery group.Conclusion:The perioperative stopping of molecular target drugs may increase the incidence ratio of flare up in orthopaedic surgeries in patients with RA but does not influence those of other postoperative complications such as SSI.REFERENCES:[1] Ito H, et al. Non-Drug and Surgical Treatment Algorithm and Recommendations for the 2020 Update of the Japan College of Rheumatology Clinical Practice Guidelines for the Management of Rheumatoid Arthritis - Secondary Publication. Mod Rheumatol. 2023 Jan 3;33(1):36-45.[2] Ito H, et al. Does abatacept increase postoperative adverse events in rheumatoid arthritis compared with conventional synthetic disease-modifying drugs? J Rheumatol 2020;47;502-509.Acknowledgements:NIL.Disclosure of Interests:Hiromu Ito BMS, Hajime Ishikawa: None declared, Shigeyoshi Tsuji: None declared, Masanori Nakayama: None declared, Keiichiro Nishida: None declared, Takeshi Mochizuki: None declared, Kosuke Ebina: None declared, Toshihisa Kojima: None declared, Takumi Matsumoto: None declared, Ayako Kubota: None declared, Arata Nakajima: None declared, Atsushi Kaneko: None declared, Isao Matsushita: None declared, Ryota Hara: None declared, Koji Sakuraba: None declared, Yukio Akasaki: None declared, Tsukasa Matsubara: None declared, Yuichi Mochida: None declared, Katsuaki Kanbe: None declared, Natsuko Nakagawa: None declared, Koichi Murata: None declared, Masahide Hamaguchi: None declared, Shigeki Momohara: None declared.

症例は74歳男性で，診断は大動脈弁位と三尖弁位の感染性心内膜炎，心室中隔欠損症，完全房室ブロックである．発熱と頸部痛を主訴に前医に入院し，経過中に完全房室ブロックを発症した．心エコー検査で重症大動脈弁逆流，大動脈弁の疣贅と心室中隔欠損症を指摘されて当院へ搬送され，同日緊急手術が行われた．大動脈弁尖は石灰化して肥厚しており，高度な弁尖破壊を伴っていた．疣贅は一部右冠尖と無冠尖の弁下まで及んでいた．疣贅は心房中隔から心室中隔欠損孔，三尖弁まで伸展していた．ウシ心膜パッチ2枚を用いたsandwich法による中隔再建後に大動脈弁置換術，三尖弁置換術を行った．術後は6週間の抗生剤加療が行われ，ペースメーカー植え込み術後に自宅退院した．心エコー検査で残存シャントは見られなかった．本症例の経験から，広範に心室中隔が破壊された感染性心内膜炎に対し，sandwich法は有用な中隔再建法の1つであると考えられた．

Immune checkpoint inhibitors (ICIs), including anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are significantly changing treatment strategies for human malignant diseases including oral cancer. Cancer cells usually escape from immune system and acquire proliferative capacity and invasive/metastatic potential. We have focused on the two immune checkpoints, PD-1/PD-L1 and CD47/SIRPα in the tumor microenvironment of oral squamous cell carcinoma (OSCC), and performed a retrospective analysis of the expression of seven immune-related factors (PD-L1, PD-1, CD4, CD8, CD47, CD56 and CD11c), and examined their correlation with clinicopathological status. As a result, there were no significant findings relating seven immune-related factors and several clinicopathological statuses. However, the immune-checkpoint related factors (PD-1, PD-L1, CD47) were highly expressed in non-keratinized epithelium-originated tumors when compared to those in keratinized epithelium-originated tumors. It is of interest that immunoediting via immune checkpoint-related factors was facilitated in non-keratinized sites. Several researchers reported that keratinization of oral mucosal epithelia affected the immune response, but our present finding is the first study to show a difference of the tumor immunity in the originating-epithelium of OSCC, keratinized or non-keratinized. Tumor immunity, an immune escape status of OSCC might be different in the originating-epithelium, keratinized or non-keratinized.

While many studies focus on the prognosis of individual neurological diseases, very few comprehensively compare and analyze real-world data of these diseases. To address this gap in knowledge, in this study, we comprehensively analyzed the real-life data of patients with neurological diseases. We prospectively enrolled patients with neurological diseases at three hospitals from December 1, 2016 to September 30, 2020. Neurological diseases were classified into nine groups: Dementia, Cerebrovascular disease, Parkinson's and related, Functional, Spinocerebellar degeneration, Neuroimmune, Epilepsy, Muscle dystrophy disease, and Hypertension. Patients were followed up for three years, and their prognosis and evaluation of their cognitive function served as the endpoint. A total of 426 patients were finally enrolled. Both mortality and cognitive function differed among the neurological disease categories. After 3 years, mortality was highest in the Dementia (25.5%), Parkinson's and related (21.6%), and Spinocerebellar degeneration (35.3%) groups while the cognitive function of patients in these three groups was significantly lowest. When the neurological diseases were holistically observed, both mortality and cognitive function of the Dementia, Parkinson's and related, and Spinocerebellar degeneration groups were significantly worse than the remaining diseases.