A Case of Hiatal Hernia with Upside Down Stomach and Incarcerated Transverse Colon Successfully Treated by Laparoscopic Floppy Nissen Fundoplication

症例は50歳の女性。食後の呼吸困難感のため近医より紹介受診となった。上部消化管造影検査では胃全体が縦隔内に脱出していた。またCT検査では横行結腸の縦隔内への脱出も認めた。以上より，横行結腸嵌入を伴う upside down stomach を呈する食道裂孔ヘルニアと診断し腹腔鏡下手術を行った。食道裂孔より縦隔内の胃や横行結腸を腹腔内に還納したが虚血を疑う所見や狭窄所見は認めなかった。開大した食道裂孔を縫合閉鎖した後にメッシュを用いた食道裂孔の補強と floppy Nissen 法による噴門形成術を施行し，術後経過は良好であった。食道裂孔ヘルニアへの横行結腸嵌入はまれな病態であるが，狭窄・壊死・穿孔のため緊急手術の報告もあり早期に手術治療を行う必要があると考えられた。A 50-year-old woman suffering from dyspnea after meals consulted a nearby hospital. In the upper gastrointestinal series, the whole stomach had herniated into the mediastinum. An abdominal CT scan showed the transverse colon to have prolapsed into mediastinum. Esophageal hiatal hernia with upside down stomach and incarcerated transverse colon was diagnosed, and laparoscopic surgery was performed. We returned the stomach and transverse colon to the abdominal cavity, they didn’t become ischemic and constricted. We sutured a dilated opening of hiatal hernia by simple crural closure, additionally closed with a mesh, and a floppy Nissen fundoplication was performed. The postoperative course of the patient was uneventful. Although hiatal hernia with incarcerated transverse colon is very rare, it was necessary that surgical treatment was performed earlier because some emergency laparotomy were reported with transverse colon resection

SLAM family member 8 is expressed in and enhances the growth of anaplastic large cell lymphoma

Signaling lymphocytic activation molecule family member 8 (SLAMF8)B-lymphocyte activator macrophage expressed/CD353 is a member of the CD2 family. SLAMF8 suppresses macrophage function but enhances the growth of neoplastic mast cells via SHP-2. In this study, we found that some anaplastic large cell lymphoma (ALCL) samples were immunohistochemically positive for SLAMF8. However, we found no significant differences between SLAMF8-positive and SLAMF8-negative ALCL samples with respect to age, gender, site, or prognosis. We also identified SLAMF8 expression in ALCL cell lines, Karpas299, and SU-DHL-1. SLAMF8 knockdown decreased the activation of SHP-2 and the growth of these cell lines, and increased the apoptosis of these cell lines. In addition, we observed the interaction between SLAMF8 and SHP-2 in these cell lines using the DuoLink in situ kit. Taken together, these results suggest that SLAMF8 may enhance the growth of ALCL via SHP-2 interaction

Production and nonclinical evaluation of an autologous iPSC-derived platelet product for the iPLAT1 clinical trial

血小板減少症に対するiPS細胞由来血小板の自己輸血に関する臨床研究」の成果公表（論文発表）について. 京都大学プレスリリース. 2022-09-30.Donor-derived platelets are used to treat or prevent hemorrhage in patients with thrombocytopenia. However, ∼5% or more of these patients are complicated with alloimmune platelet transfusion refractoriness (allo-PTR) due to alloantibodies against HLA-I or human platelet antigens (HPA). In these cases, platelets from compatible donors are necessary, but it is difficult to find such donors for patients with rare HLA-I or HPA. To produce platelet products for patients with aplastic anemia with allo-PTR due to rare HPA-1 mismatch in Japan, we developed an ex vivo good manufacturing process (GMP)–based production system for an induced pluripotent stem cell–derived platelet product (iPSC-PLTs). Immortalized megakaryocyte progenitor cell lines (imMKCLs) were established from patient iPSCs, and a competent imMKCL clone was selected for the master cell bank (MCB) and confirmed for safety, including negativity of pathogens. From this MCB, iPSC-PLTs were produced using turbulent flow bioreactors and new drugs. In extensive nonclinical studies, iPSC-PLTs were confirmed for quality, safety, and efficacy, including hemostasis in a rabbit model. This report presents a complete system for the GMP-based production of iPSC-PLTs and the required nonclinical studies and thus supports the iPLAT1 study, the first-in-human clinical trial of iPSC-PLTs in a patient with allo-PTR and no compatible donor using the autologous product. It also serves as a comprehensive reference for the development of widely applicable allogeneic iPSC-PLTs and other cell products that use iPSC-derived progenitor cells as MCB

Research Activities in the Department of Physical Therapy

[Introduction] It is already fifty years since the Japanese law of physical therapists and occupational therapists has been effective. The physical therapist is referred by the law as "the professionals who implements the physical therapy to persons with disabilities under the prescription of medical doctors". In fifty years, however, the target of physical therapy has been significantly expanded. The subject for physical therapy now includes the patients in acute disease just after the surgical operation in addition to those in rehabilitation stage. In other words, the physical therapy is now recognized as the indispensable intervention to the subject with acute as well as chronic disorders. On the other hand, due to a rapid transition of the society into the aged society, prevention of diseases, and decline of activity capacity due to the aging have become major issues for the physical therapy

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

ハナス コト キク コト フレル コト カンジル コト フレラレル コト リンショウ ジッシュウ エ アンガジェ スル ホウホウ ノ ケントウ

理学療法学教育において臨床実習は重要な位置づけにある. しかし, その方法論は古くから変化しておらず, 現代の教育に必ずしも適当であるとはいえない. 今回, その課題について, 研究会を設立し検討した. その結果, 「関わること」の重要性が浮かび上がり, いかにして関われるのかを明確にする必要が示唆された. 研究会では人に関わる以前に自らに関わり, それを基盤に他者と関われると考えた. それは言語的コミュニケーションのみならず, 身体的コミュニケーションの重要性を前提としている. 関わりについてケア, クリティシズム, アンガージュマンなどのキーワードを使用し説明を加えた. 最終的に言語的・身体的コミュニケーションの経験を自らが解釈し, それを言語化できるような学習プロセスの経過(思考し表現すること)が必要であると結論づけた. 臨床実習は自己, 他者への関わりを理解し, 経験するプロセスなのである.Clinical training is the core of physical therapy education. However, its age-old methodology could be inappropriate for today\u27s education. We set up a study group and examined the issue. As a result, the importance of "participating with others" (i.e. interaction between instructors and students, and that between students and patients) came into focus and the necessity of exploring possible "participation" methods was indicated. We considered that one should be ready for participating with others by doing the same thing with oneself in advance. The idea was premised on the importance of physical communication as well as that of linguistic communication, and we discussed and tried to identify our concept of "participation" with keywords such as care, criticism or commitment (engagement). Finally we reached the conclusion that both instructors and students need a learning process, where they can interpret and verbalize (i.e. think and express) their experiences of linguistic and physical communication by themselves. Clinical training may be ultimately defined as a process of understanding what "participation" means and experiencing it

Mandibular Osteitis Leading to the Diagnosis of SAPHO Syndrome

Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a disorder characterized by pustular skin lesions and osteoarticular lesions. Mandibular involvement of SAPHO syndrome is clinically rare, and it is difficult to reach a diagnosis of SAPHO syndrome from only mandibular manifestations. This report describes the case of a 26-year-old woman who presented with mandibular osteitis. Orthopantomogram and computed tomography showed sclerotic change of the right body of the mandible with periosteal reaction without odontogenic infection, which suggested the possibility of SAPHO syndrome. Detailed medical interview found that she had a history of palmoplantar pustulosis treated at a local dermatology clinic and additional bone scintigraphy showed diffuse increased uptake in the right mandible, as well as in the sternum and the sternocostoclavicular joints. She was eventually diagnosed as having SAPHO syndrome. We should consider SAPHO syndrome when we encounter a patient with mandibular osteitis of unknown etiology

Endovascular Embolization of an Aberrant Bronchial Artery Originating from the Internal Mammary Artery in a Patient with Hemoptysis

Massive hemoptysis is a life threatening respiratory emergency with high mortality and the bronchial artery (BA) is its most frequent source. Herein, we report a case of a 76-year-old man with recurrent hemoptysis due to an aberrant right BA arising from the right internal mammary artery (IMA), an extremely rare origin, that was clearly depicted on pretreatment computed tomography angiography (CTA). The patient was treated successfully by transcatheter bronchial artery embolization (BAE) of the aberrant BA and the hemoptysis has since been controlled for 9 months. Knowledge of the detailed BA anatomy is essential for performing BAE, especially in cases of aberrant BA. CTA is a promising tool for pretreatment planning of emergency BAE in patients with hemoptysis