Background: The anti-programmed death 1 (PD-1) antibody has led to durable clinical responses in a wide variety of human tumors. We have previously developed the caninized anti-canine PD-1 antibody (ca-4F12-E6) and evaluated its therapeutic properties in dogs with advance-staged oral malignant melanoma (OMM), however, their therapeutic effects on other types of canine tumors remain unclear. Objective: The present clinical study was carried out to evaluate the safety profile and clinical efficacy of ca-4F12-E6 in dogs with advanced solid tumors except for OMM. Methods: Thirty-eight dogs with non-OMM solid tumors were enrolled prospectively and treated with ca-4F12-E6 at 3 mg/kg every 2 weeks of each 10-week treatment cycle. Adverse events (AEs) and treatment efficacy were graded based on the criteria established by the Veterinary Cooperative Oncology Group. Results: One dog was withdrawn, and thirty-seven dogs were evaluated for the safety and efficacy of ca-4F12-E6. Treatment-related AEs of any grade occurred in 13 out of 37 cases (35.1%).Two dogs with sterile nodular panniculitis and one with myasthenia gravis and hypothyroidism were suspected of immune-related AEs. In 30 out of 37 dogs that had target tumor lesions, the overall response and clinical benefit rates were 6.9% and 27.6%, respectively. The median progression-free survival and overall survival time were 70 days and 215 days, respectively. Conclusions The present study demonstrated that ca-4F12-E6 was well-tolerated in nonOMM dogs, with a small number of cases showing objective responses. This provides evidence supporting large-scale clinical trials of anti-PD-1 antibody therapy in dogs.

Methods: HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-β and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively. Results: TGF-β administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-β–induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-β stimulation. Conclusions Our findings indicate that TGF-β induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6–mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.

A 66-year-old, postmenopausal woman was referred to our hospital because of abnormal breast cancer screening results. A tumor was found in the upper outer part of the left breast. Biopsy revealed papillotubular carcinoma, ER (Allred score total score [TS] 3 = proportion score [PS] 2 + intensity score [IS] 1), PgR (Allred score TS 3 = PS 2 + IS 1), HER2 (2+), fluorescent in situ hybridization 1.1 (negative), and Ki-67 labeling index 15%. In diagnostic imaging, the tumor size was 35 mm. The diagnosis was T2N0M0 Stage IIA, luminal B-like breast cancer. First, letrozole 2.5 mg/day was administered as preoperative hormone therapy. After 2 months of treatment with letrozole, the tumor size had increased to 44 mm and preoperative hormone therapy was discontinued. She was started on preoperative chemotherapy (4 courses of epirubicin plus cyclophsphamide followed by 4 courses of triweekly docetaxel). The tumor size decreased, becoming undetectable. After these preoperative treatments, nipple-sparing mastectomy, sentinel lymph node biopsy, and breast reconstruction with a primary latissimus dorsi flap were performed. As of 3 years and 6 months after the operation, there has been no recurrence. At first, preoperative hormone therapy is performed for Luminal B-like breast cancer as in this case, if the response is insufficient, preoperative chemotherapy after hormone therapy may be a therapeutic option.

Takotsubo cardiomyopathy is a transient wall motion abnormality of the left ventricular apex, accompanied by emotional or physical stress. Although Takotsubo cardiomyopathy is generally considered a benign disease, severe clinical complications may occur, and early detection of the disease is important. In this report, we present the case of an 86-year-old bedridden woman with a history of bronchial asthma who was transferred to our hospital because of wheezing. She was diagnosed with Alzheimer’s disease and had communication difficulties. After an asthma attack and improvement, Takotsubo cardiomyopathy was identified via electrocardiography. She was unable to complain of any symptoms but showed serial electrocardiographic changes, elevated myocardial markers, and transient left ventricular apical ballooning. The prevalence of dementia increases dramatically with age. This case indicates that Takotsubo cardiomyopathy may occur even in patients with severe dementia, who are bedridden and show communication difficulties in a clinical setting.

Methods: Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column. Results: The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively. Conclusions The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.

Here, we report 3 cases of conservatively treated ischemic colitis with hepatic portal venous gas. In Case 1, an 84-year-old man visited the emergency department because of fatigue, vomiting, and upper abdominal pain. In Case 2, a 72-year-old man was hospitalized for rehabilitation in another hospital following cervical spine trauma. He had diarrhea and mesogastric pain for 2 days and was transferred to our hospital. In Case 3, an 89-year-old woman visited the emergency department because of upper abdominal pain and vomiting. In all cases, we diagnosed the illness as ischemic colitis with hepatic portal venous gas based on computed tomography findings, and the vital signs of all patients were stable. They were treated conservatively. They were able to resume oral intake and were discharged or transferred to another hospital. Hepatic portal venous gas has been considered a poor prognostic sign of severe diseases such as intestinal necrosis. However, recently, reports of cases treated conservatively have been increasing. Conservative treatment may be selected for ischemic colitis associated with hepatic portal venous gas taking into account the patient’s general condition.

For this second report, we divided the efforts of the University of Tsukuba into two parts. In the first part, we introduced the Interprofessional program, an inter-university collaborative educational program between the University of Tsukuba and Ibaraki Prefectural University of Health Sciences. Before the COVID-19 pandemic, this program was conducted using TBL (Team-based learning) in a large conference room. After the pandemic, this was conducted online (using Zoom). The main changes due to the online implementation were the following five points; (1) online faculty meetings, (2) advance distribution of materials, (3) testing using Google Forms, (4) group work using the breakout function, and (5) simultaneous editing using Google Docs. In the future, we would like to examine the possibility of new educational methods while creating innovations that are possible only through online interprofessional educational programs.

In the second part of the second report, we introduce the Care Colloquium, an inter-university collaborative educational program between the University of Tsukuba and the Tokyo University of Science. The Care Colloquium is an interprofessional education program that uses PBL (Problem-based learning). In response to the COVID-19 pandemic, this program was implemented online using Microsoft Teams, with advance preparation including manual maintenance and communication testing. The same learning outcomes were achieved as the face-to-face implementation. Undergraduate interprofessional education tends to be a large-scale program, and the shortage of faculty and classrooms is challenging, but online education could overcome these obstacles. The development of hybrid programs that use the merits of both face-to-face and online education may lead to the promotion of interprofessional education in the future.

Methods: HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction. Results: TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs. Conclusions This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.

It is difficult to implement interprofessional education (IPE) in the classroom due to COVID-19. To share our knowledge of online IPE, we report on how we provided IPE for first-year students at two universities. At Mie University, a class was implemented to use Zoom. Quizzes and chats promoted interactions between instructors and students. At Hokkaido University of Science, an online team medical experience game was conducted via Zoom and a Learning Management System (LMS). The activity promoted interaction between students through gameplay and clear instructions. In both cases, students could successfully develop online IPE based on existing learning methods. Through their experience, it was clear that students are able to understand other professionals’ roles. They were also to commit to membership and/or teamship. On the other hand, students faced challenges with faculty familiarity and time allocation.