Objective: To investigate an association between the gut microbiome and efficacy of poly(ADP-ribose) polymerase inhibitors (PARPi) in ovarian cancer. Methods: This study conducted fecal microbiome analysis (16S rRNA gene sequencing) and circulating tumor DNA (ctDNA) profiling for ovarian cancer patients who underwent PARPi maintenance therapy. Fecal and blood samples were collected at the baseline and the progressive disease (PD) or last follow-up. The relative abundance of gut microbes and progression-free survival (PFS) were analyzed using linear discriminant analysis of effect size and the Cox proportional hazard model according to BRCA1/2 mutation (BRCA1/2mut) status detected by ctDNA sequencing. Results: Baseline samples were available from 23 BRCA1/2mut-positive patients and 33 BRCA1/2mut-negative patients. The microbes enriched in the baseline samples with long PFS were Bifidobacterium, Roseburia, Dialister, Butyricicoccus, and Bilophila for BRCA1/2mut-positive patients and Phascolarctobacterium for BRCA1/2mut-negative patients. In multivariate analyses dividing patients by the median values of relative abundances, no bacteria were associated with PFS in BRCA1/2mut-positive patients, whereas high Phascolarctobacterium abundances (≥1.11%) was significantly associated with longer PFS in BRCA1/2mut-negative patients (median 14.0 vs. 5.9 months, hazard ratio=0.28; 95% confidence interval=0.11–0.69; p=0.014). In the last samples, the relative abundances of Phascolarctobacterium were significantly higher in patients without PD (n=5) than those with PD (n=15) (median 1.25% vs. 0.06%; p=0.016). Conclusion High fecal composition of Phascolarctobacterium was associated with prolonged PFS in patients with BRCA1/2mut-negative ovarian cancer receiving PARPi therapy. Our results would provide new insights for future research.

Objective：To investigate the purposes, reasons, and issues of Real World Data (RWD) utilization by data source among pharmaceutical companies in Japan. In this study, we focus on RWDs such as Electronic Medical Records (EMR), Personal Health Records, and registries, which are expected to be utilized in the future. Design：Web based-questionnaire surveyMethods：This questionnaire survey was conducted on 68 companies affiliated with Clinical Evaluation Expert Committee in Japan Pharmaceutical Manufacturers Association from January 18th to February 14th in 2022. In principle, the survey covered four divisions (Clinical development, Pharmacovigilance, Medical Affairs, Health Economics & Outcomes Research) of each company, and other cross-functional divisions were also acceptable to answer. Results：［Background］ Of 40 companies out of 68 companies, 102 respondents were responded to this survey. Overall, 75 respondents (73.5％) have “experienced in utilization of RWD”, and 12 (11.8％) have “experienced in considering utilization of RWD”. ［Utilization by RWD Type］ By data source, hospital-based claim data was the most frequently used (65 cases, 63.7％), followed by insurance-based claim data (61 cases, 59.8％), surveys (38 cases, 37.3％), and EMR (36 cases, 35.3％) in experienced RWD utilization. Conclusion：This study revealed the current status and issues related to the utilization of each type of RWDs in Japan. It is expected that data linkage among multiple RWDs and data standardization enable further utilization of RWDs in future.

Objective：To investigate the purposes, reasons, and issues of Real World Data (RWD) utilization by data source among pharmaceutical companies in Japan. In this study, we focus on RWDs such as Electronic Medical Records (EMR), Personal Health Records, and registries, which are expected to be utilized in the future. Design：Web based-questionnaire surveyMethods：This questionnaire survey was conducted on 68 companies affiliated with Clinical Evaluation Expert Committee in Japan Pharmaceutical Manufacturers Association from January 18th to February 14th in 2022. In principle, the survey covered four divisions (Clinical development, Pharmacovigilance, Medical Affairs, Health Economics & Outcomes Research) of each company, and other cross-functional divisions were also acceptable to answer. Results：［Background］ Of 40 companies out of 68 companies, 102 respondents were responded to this survey. Overall, 75 respondents (73.5％) have “experienced in utilization of RWD”, and 12 (11.8％) have “experienced in considering utilization of RWD”. ［Utilization by RWD Type］ By data source, hospital-based claim data was the most frequently used (65 cases, 63.7％), followed by insurance-based claim data (61 cases, 59.8％), surveys (38 cases, 37.3％), and EMR (36 cases, 35.3％) in experienced RWD utilization. Conclusion：This study revealed the current status and issues related to the utilization of each type of RWDs in Japan. It is expected that data linkage among multiple RWDs and data standardization enable further utilization of RWDs in future.

Takayasu Arteritis causes annuloaortic ectasia and coronary ostial stenosis, which may necessitate open heart surgery. However, pseudoaneurysms are sometimes observed postoperatively, making subsequent treatment difficult. We report thoracic endovascular aortic repair of a pseudoaneurysm of the ascending aorta with an anastomosis of the great saphenous vein in a 61-year-old female with a history of multiple open-heart procedures. Thirty years earlier, she underwent aortic valve replacement and coronary artery bypass surgery for aortic regurgitation, and right coronary ostial stenosis. Eleven years after surgery, an ascending aortic aneurysm was found and Bentall's surgery was performed. Multiple open thoracotomies were subsequently performed. Postoperatively, a pseudoaneurysm was found at the anastomosis between the ascending aorta and the great saphenous vein. The patient was transferred to the emergency room owing to hemoptysis and was diagnosed with a ruptured pseudoaneurysm at the anastomosis of the ascending aorta and the great saphenous vein. By inserting a stent graft into the ascending aorta, we avoided further complications and her prognosis was good. She was discharged on postoperative day 18 and did not experience any end leak for a year. Thoracic endovascular aortic repair in the ascending aorta is a minimally invasive procedure that may be useful for high-risk patients.

In the 2022 Model Core Curriculum for Medical Education in Japan, "Chapter 3, Educational strategies and assessment" section II. "Learner Assessment," consists of three parts : II-1. Approaches to learner assessment, II-2. Assessment methods, and II-3. Questions about learner assessment. Based on the idea that "the way assessment is done varies from institution to institution," the answer to the "Question" is deliberately not included. We hope that readers will refer to this chapter when planning learning assessments in curriculum development while considering the curriculum's background and context.

An 81-year-old man who visited a local physician for evaluation of hoarseness was admitted to our hospital for management of a thoracic aortic aneurysm. Careful examination revealed a thoracic aortic aneurysm, aortic regurgitation, and left ventricular aneurysm. We performed total arch replacement using a frozen elephant trunk prosthesis (combined right axillary artery bypass and coil embolization), aortic valve replacement, papillary muscle approximation, and a septal anterior ventricular exclusion operation. The patient's postoperative course was uneventful, and he was discharged on the 25th postoperative day. A Kommerell diverticulum is located at the origin of an aberrant subclavian artery, and subclavian artery reconstruction via thoracotomy is challenging in such cases. Although increasing numbers of thoracic endovascular aortic repairs have been performed in recent years, the procedure is associated with complications such as endoleak and aortic esophageal fistula, and the surgical risk-benefit ratio should be carefully determined. We report a case of safe non-anatomical subclavian artery reconstruction and coil embolization.

This study aimed to examine the effects of college baseball pitching on movement, performance, physical strength, and physiological and psychological functions of pitchers. The participants were 10 right-handed male pitchers from the University baseball team. The number of pitches were 15 per inning and 135 per nine innings. Ball speed and accuracy were measured for each pitching. The grip strength, back muscle strength, and standing long jump were measured before and after all pitches. Blood lactate levels were measured before pitching, at the end of the 5th and 7th innings, and at 3rd, 6th, and 9th minutes after pitching. The participant’s heart rate and subjective exercise intensity were measured at the beginning and end of each inning using the Borg scale measurement. Five high-speed cameras were used to capture the pitching motions. The displacement of the center of gravity, lower and upper limb joint angles, and the speed of each segment were calculated. The baseball speed and accuracy did not change with the increased number of pitches. However, the grip strength decreased. Although blood lactate and heart rate were not altered, subjective exercise intensity was increased. The lower limb kinematics remained unchanged; however, elbow height was reduced in the upper limb. These results suggest that highly competitive pitchers experience subjective fatigue with the increased number of pitches, however, they maintain pitch performance, speed, and accuracy without altering whole-body physiology and lower-body function and form.

Background: Type 1 diabetes mellitus induced by immune-checkpoint inhibitors (ICI-T1DM) is a rare critical entity. However, the etiology of ICI-T1DM remains unclear. Methods: In order to elucidate risk factors for ICI-T1DM, we evaluated the clinical course and immunological status of patients with ICI-T1DM who had been diagnosed during 2016 to 2021. Results: Seven of 871 (0.8%, six men and one woman) patients developed ICI-T1DM. We revealed that the allele frequencies of human leukocyte antigen (HLA)-DPA1*02:02 and DPB1*05:01 were significantly higher in the patients with ICI-T1DM In comparison to the controls who received ICI (11/14 vs. 10/26, P=0.022; 11/14 vs. 7/26, P=0.0027, respectively). HLA-DRB1*04:05, which has been found to be a T1DM susceptibility allele in Asians, was also observed as a high-risk allele for ICI-T1DM. The significance of the HLA-DPB1*05:01 and DRB1*04:05 alleles was confirmed by an analysis of four additional patients. The absolute/relative neutrophil count, neutrophils-lymphocyte ratio, and neutrophil-eosinophil ratio increased, and the absolute lymphocyte count and absolute/relative eosinophil count decreased at the onset as compared with 6 weeks before. In two patients, alterations in cytokines and chemokines were found at the onset. Conclusion Novel high-risk HLA alleles and haplotypes were identified in ICI-T1DM, and peripheral blood factors may be utilized as biomarkers.

Background: Poly (adenosine diphosphate)-ribose polymerase (PARP) inhibitors for tumors with homologous recombination deficiency (HRD), including pathogenic mutations in BRCA1/2, have been developed. Genomic analysis revealed that about 20% of uterine leiomyosarcoma (uLMS) have HRD, including 7.5%–10% of BRCA1/2 alterations and 4%–6% of carcinomas of the uterine corpus, and 2.5%–4% of the uterine cervix have alterations of BRCA1/2. Preclinical and clinical case reports suggest that PARP inhibitors may be effective against those targets. The Japanese Gynecologic Oncology Group (JGOG) is now planning to conduct a new investigator-initiated clinical trial, JGOG2052. Methods JGOG2052 is a single-arm, open-label, multi-center, phase 2 clinical trial to evaluate the efficacy and safety of niraparib monotherapy for a recurrent or persistent rare fraction of gynecologic malignancies with BRCA1/2 mutations except for ovarian cancers. We will independently consider the effect of niraparib for uLMS or other gynecologic malignancies with BRCA1/2 mutations (cohort A, C) and HRD positive uLMS without BRCA1/2 mutations (cohort B). Participants must have 1–3 lines of previous chemotherapy and at least one measurable lesion according to RECIST (v.1.1). Niraparib will be orally administered once a day until lesion exacerbation or unacceptable adverse events occur. Efficacy will be evaluated by imaging through an additional computed tomography scan every 8 weeks. Safety will be measured weekly in cycle 1 and every 4 weeks after cycle 2 by blood tests and physical examinations. The sample size is 16–20 in each of cohort A and B, and 31 in cohort C. Primary endpoint is the objective response rate.

The Japan Society for Oriental Medicine (JSOM) has made various efforts against coronavirus disease (COVID-19) to build evidence. JSOM has launched an academic society-led clinical research project on COVID-19 based on the concept and characteristics of Kampo medicine, including (1) prevention of disease by activating the immune system to regulate body conditions (pre-symptomatic stage of illness), (2) symptom alleviation in the mild and moderate stage and prevention of aggravation (acute to subacute stage of illness), and (3) early recovery and improvement of prolonged symptoms (late stage of illness). Since the declaration of the pandemic, the special working group has conducted the following activities : enlightening academic members, lobbying other academic societies, preparing research protocols, establishing research groups, conducting ethical reviews, responding to the research disclosure system, preparing protocol papers and review articles as the basis for the research, reporting research progress, soliciting case reports, warning against Chinese medicine use, requesting for research support funding, and revising the JSOM website. We also discuss the interpretation of COVID-19 from the perspective of Kampo medicine and the direction of the selection of Kampo formulas in this report.