Saiseikai Matsuyama Hospital

Background There are no comparative studies on provoked coronary microvascular spasm (CMS) in patients undergoing both acetylcholine (ACh) and ergonovine (EM) vasoreactivity testing. Objectives We investigated the incidence of provoked CMS in patients with ischemia with nonobstructive coronary artery disease (INOCA) undergoing ACh and EM vasoreactivity testing. Methods We recruited 494 INOCA patients who underwent both ACh and EM vasoreactivity testing. ACh was injected at incremental doses of 20/50/100/200 μg into the left coronary artery (LCA) and 20/50/80 μg into the right coronary artery (RCA), whereas 40 μg of EM was administered into the RCA and 64 μg into the LCA. Positive CMS was defined as <75% transient coronary constriction, accompanied by typical chest symptoms or ischemic ECG changes. Results Among the 494 patients, CMS was observed in 23 (4.7%) patients. Eighteen patients had CMS alone, and 5 patients had coexisting epicardial spasm. The ACh test alone, EM test alone, and both tests provoked CMSs in 12 patients, 7 patients, and 4 patients, respectively. There were no marked differences in incidence between ACh- and EM-induced CMS (70% vs. 48%, p=0.2307). Conclusions Differences were observed between ACh-induced CMS and EM-induced CMS. The complementary use of vasoreactivity testing is essential for accurately documenting the presence of CMS in real-world settings.

Background and study aimsEndoscopic submucosal dissection (ESD) is a minimally invasive and effective treatment for rectal tumors but maintaining a clear surgical field during the procedure is challenging, especially for novice operators. This study aimed to investigate whether continuous drainage using a Foley catheter could enhance efficiency and safety of rectal ESD performed by novice endoscopists under expert supervision.Patients and methodsThis retrospective study involved 26 patients who underwent rectal ESD between March 2023 and October 2024. Patients were divided into two groups: those who received continuous drainage with Foley catheter placement (n = 12) and those who did not (n = 14). Key outcomes evaluated were dissection speed, total procedure time, R0 resection rates (complete tumor resection with clear margins), and occurrence of any adverse events (AEs) during or after the procedure. All procedures were performed by novice endoscopists under expert guidance.ResultsThe results showed that dissection speed was significantly higher in the Foley catheter group, with a median of 18.6 mm²/min compared with 10.5 mm²/min in the non-catheter group (P= 0.027). Although total procedure time and sodium hyaluronate usage were lower in the catheter group, these differences were not statistically significant. Importantly, no AEs were reported in either group.ConclusionsFoley catheter placement notably improved efficiency of rectal ESD performed by novice endoscopists, particularly by increasing dissection speed. This technique may contribute to safer and more effective ESD. However, larger studies are needed to confirm these findings and further assess their benefits.

The Japanese Circulation Society guidelines recommend a class I vasoreactivity test to diagnose patients with vasospastic angina (VSA). However, the acetylcholine or ergonovine test has been established as the gold standard for variant angina (VA). The sensitivity and specificity of intracoronary vasoreactivity testing in patients with VA were acceptable. Cardiologists have employed these vasoreactivity tests to conveniently diagnose the presence of coronary spasms in patients with all VSA. The majority of VSAs may have lower disease activity than VA cases. We have summarized the usefulness of spasm provocation tests in patients with VA and VSA. A positive-provoked spasm diagnosed by standard vasoreactivity testing may indicate a disease state similar to that of VA, whereas a negative-provoked spasm after standard vasoreactivity testing may indicate a lower disease state than that of VA. Cardiologists should reconsider the limited usefulness of vasoreactivity testing when diagnosing the presence of coronary spasms in all VSAs, but not VA.

症例は58歳，男性．高血圧症，僧帽弁閉鎖不全症にて近医に通院中．倦怠感，呼吸苦にて近医を受診，慢性心不全の診断にて加療を受ける．経過中Hb 3.0g/dLと高度貧血を認め，当院内科に紹介となる．下部内視鏡検査にて下行結腸脾彎曲部近傍に2型腫瘍を認め，生検にて高分化型腺癌と診断，貧血・心不全状態改善後，当科に紹介となる．Plain CTにて骨盤内左側に囊胞様構造を認めたが，これは造影CTでは拡張蛇行した血管であり左内腸骨動静脈と連続，同静脈は動脈相から造影され骨盤内動静脈奇形（AVM）と診断した．腫瘍の栄養血管は左結腸動脈であり郭清に伴うAVMへの影響はないと考え，AVMに対する処置は施行せず，腹腔鏡下左結腸切除術を施行した．術後約2年経過し，大腸癌再発・AVM増大・心不全症状等なく経過観察中である．

A male in his seventies was admitted for a patent ductus arteriosus (PDA) closure. We planned a catheter-based closure but avoided pre-procedural contrast-enhanced CT due to his low estimated glomerular filtration rate. Instead, we used magnetic resonance imaging (MRI) (Philips, 3T, Ingenia Elition, Philips Healthcare, Amsterdam, The Netherlands). An MRI of the aorta showed that the PDA was aneurysmal (Krichenko classification, type D). The Qs/Qp ratio via two-dimensional phase-contrast MRI was 1.78. Black blood imaging was used to obtain accurate diameter determination. Black Blood Imaging and aortography did not differ in any dimension. The procedure was completed using an AmplatzerVascular Plug II (Abbott, Abbott Park, IL) 16 × 12 mm, achieving PDA closure without complications, and the patient was discharged. MRI provided an accurate assessment of the vascular morphology using non-contrast-enhanced black blood imaging, suggesting a gradual change in PDA morphology.

Vasoreactivity testing, such as intracoronary acetylcholine (ACh) or ergometrine (EM), is defined as Class Ifor the diagnosis of patients with vasospastic angina (VSA) according to recommendations from the Coronary Vasomotion Disorders International Study (COVADIS) group and guidelines from the Japanese Circulation Society (JCS). Although vasoreactivity testing is a clinically useful tool, it carries some risks and limitationsindiagnosing coronary artery spasm. Previous reports on vasoreactivity testing for diagnosing the presence of coronary spasmare summarized from the perspective of Class I. There are several problemssuch as reproducibility, underestimation, overestimation, and inconclusive/nonspecificresults associated with daily spasm. Because provoked spasm caused by intracoronary ACh is not always similar to that caused by intracoronary EM, possibly due to different mediators, supplementary use of these vasoreactivity tests is necessary for cardiologists to diagnose VSAwhen a provoked spasm is not revealed by each vasoactive agent. Cardiologists should understand the imperfection of these vasoreactivity tests when diagnosing patients with VSA.

This paper presents a comprehensive protocol for predicting the three-dimensional (3D) structure of DNA aptamers and performing in silico docking calculations. The protocol includes steps for sequence input, structure prediction, sequence modification, structure minimization, and docking. The procedure is executed on a Mac environment utilizing bioinformatics tools such as mfold, RNA Composer, PyMOL, and Hdock. The protocol is intended to provide a guide for researchers in structural biology and drug design.

Abstract OBJECTIVE The prognosis of glioblastoma multiforme correlates with residual tumor volume. In fluorescence-guided surgery, 5-aminolevulinic acid (5-ALA) has been used to maximize safe resection. We searched for repositioning drugs that affect mitochondrial functions and energy metabolism, identifying berberine (BBR) as a potential enhancer of 5-ALA-mediated protoporphyrin IX (PpIX) fluorescence (5-ALA-fluorescence). Here, we investigated whether BBR can be applied to clinical practice as a 5-ALA-fluorescence enhancer. METHODS Effects of BBR on 5-ALA-fluorescence in glioma cells and GSCs were evaluated by flow cytometry (fluorescence-activated cell sorting; FACS) analysis. As 5-ALA is metabolized for heme synthesis, effects of BBR on mRNA expressions of seven enzymes in the heme-synthesis pathway were analyzed. Enzymes showing significantly higher expression than control in all cells were identified and protein analysis was performed. To examine clinical availability, the detectability and cytotoxicity of BBR in tumor-transplanted mice were analyzed. RESULTS Fluorescence microscopy revealed much more intense 5-ALA-fluorescence in both GSCs and non-stem cells with 5-ALA and BBR than with 5-ALA alone. FACS disclosed that BBR greatly enhanced 5-ALA-fluorescence compared to 5-ALA alone and enhancement was much higher for GSCs than for glioma cells. Among the seven enzymes examined, BBR upregulated mRNA expressions of ALA synthetase 1 (ALAS1) more highly in all cells, and activated ALAS1 through deregulating ALAS1 activity inhibited by the negative feedback of heme. In vivo study showed that 5-ALA-fluorescence with 5-ALA and BBR was significantly stronger than with 5-ALA alone, and the sensitivity and specificity of BBR-enhanced fluorescence were both 100%. In addition, BBR did not show any cytotoxicity for normal brain tissue. CONCLUSIONS BBR enhanced 5-ALA-mediated PpIX fluorescence by upregulating and activating ALAS1 through deregulation of negative feedback inhibition by heme. BBR is a clinically used drug with no side effects. BBR is expected to augment fluorescence-guided surgery and photodynamic therapy.

Patients with chronic kidney disease (CKD) and patients with kidney failure receiving hemodialysis (HD) receive various types of medications. However, little is known about the differences in medication preference and how to deal with leftover medication among CKD patients and HD patients. The purpose of this study was to investigate the differences in medication preference and ways of dealing with leftover medication between CKD patients, HD patients, physicians, and pharmacists via a questionnaire survey. The ethics committee of Oita University, Oita, Japan, approved this survey. Outpatients undergoing treatment by a nephrologist in four facilities in Oita prefecture, Japan, were asked to answer a questionnaire on their preference for medication and how to deal with leftover medication. Respondents gave their informed written consent. The same questionnaire was administered to nephrologists and pharmacists online. In this survey, 383 patients (260 patients with CKD and 123 patients with HD), 22 nephrologists, and 28 pharmacists responded. The response rate of valid responses was more than 90% for each of the groups. In particular, 41% of patients with CKD and 56% of patients with HD never inform their doctor about leftover medication or only inform them when there is a lot of leftover medication. On the other hand, 23% of physicians have never asked their patients about them. Ordinary logistic regression analysis indicated that there is no significant relationship between how often patients talk about leftover medication, patients' preferences, or patient states. Despite the age and state of the patients, it is important to discuss the perception of medication with each other and confirm the condition of the remaining medication to improve concordance and obtain the desired treatment effect.