Overview of the 87th Annual Scientific Meeting of the Japanese Circulation Society (JCS2023)　- New Challenge With Next Generation.

The 87thAnnual Meeting of the Japanese Circulation Society (JCS2023) was held in March 2023 in Fukuoka, Japan, marking the first in-person gathering after the COVID-19 pandemic. With the theme of "New Challenge With Next Generation" the conference emphasized the development of future cardiovascular leaders and technologies such as artificial intelligence (AI). Notable sessions included the Mikamo Lecture on heart failure and the Mashimo Lecture on AI in medicine. Various hands-on sessions and participatory events were well received, promoting learning and networking. Post-event surveys showed high satisfaction among participants, with positive feedback on face-to-face interactions and the overall experience. JCS2023, attended by 17,852 participants, concluded successfully, marking a significant milestone in post-pandemic meetings, and advancing cardiovascular medicine.

Transient EDTA-dependent pseudothrombocytopenia and ulcerative colitis recurrence during chemotherapy: A case of misleading platelet count results attributable to a laboratory artifact.

Key Clinical Message: EDTA-dependent pseudothrombocytopenia as well as myelosuppression should be suspected when thrombocytopenia occurs in patients with autoimmune disease during chemotherapy. Abstract: A patient with pancreatic cancer and ulcerative colitis developed transient ethylenediaminetetraacetic acid (EDTA)-dependent pseudothrombocytopenia with exacerbation of ulcerative colitis during chemotherapy. Unfortunately, pseudothrombocytopenia could not be immediately detected because thrombocytopenia was masked by a reasonable time course of adverse events associated with chemotherapy and ulcerative colitis recurrence. When thrombocytopenia occurs during chemotherapy, especially in patients with autoimmune diseases, EDTA-dependent pseudothrombocytopenia and bone marrow suppression caused by anti-cancer agents should be suspected.

[Collision Tumor Involving Primary Ascending Colon Cancer and Malignant Lymphoma].

A 78-year-old male was diagnosed with a primary gastric B-cell malignant lymphoma and metastatic lung tumor 10 years ago. He underwent chemotherapy at another hospital, achieved complete remission, and was actively undergoing follow- up. He presented to our hospital with a 1-month history of a bulge in his right lower abdomen. CT revealed thickening of the ascending colon and dilatation of the oral intestine. He was diagnosed with ascending colon cancer and underwent right hemicolectomy. The subsequent pathological examination revealed a collision tumor involving diffuse, large B-cell lymphoma and well-differentiated adenocarcinoma. He was discharged from our hospital and received chemotherapy at another institution. Unfortunately, the patient died of interstitial pneumonia 31 months postoperatively. This report describes the resection of a collision tumor involving ascending colon cancer and malignant lymphoma. Surgical treatment combined with postoperative chemotherapy improved this patient's long-term survival.

A super-geriatric patient with gastrostomy underwent life-threatening prothrombin time-international normalized ratio prolongation by warfarin following fasting and antibiotic therapy.

Key Clinical Message: A 97-year-old woman with gastrostomy had a drastic enhancement for PT-INR after starting antibiotic therapy. Possible causes include (1) vitamin K deficiency due to fasting and (2) a combination of warfarin and antibiotics. Abstract: Geriatric and Asian-descent patients are more sensitive to the effects of warfarin, a key anticoagulant drug. In this report, we present a 97-year-old bedridden woman being treated with warfarin for cardiogenic cerebral infarction and femoral neck replacement as part of in-home medical care with a gastrostomy and was admitted to our hospital after developing pneumonia. We discontinued warfarin and started antibiotics, and her pneumonia-related symptoms improved. Eleven days after restarting warfarin, the patient's PT-INR surpassed the upper limit for measurement (over 10). We considered the mechanism might be triggered by (1) fasting, low nutrition status; and (2) antibiotics secondary to risk factors such as gastrostomy and being a super-geriatric woman. We recommend careful monitoring of PT-INR in patients treated with warfarin and antibiotics, especially in the setting of gastrostomy or older persons.

Efficacy of Early Catheter Ablation for Atrial Fibrillation After Admission for Heart Failure.

BACKGROUND: Advances in catheter ablation (CA) for atrial fibrillation (AF) have improved the prognosis of patients with heart failure (HF) and AF. However, its optimal timing remains to be fully elucidated. OBJECTIVES: The aim of this study was to investigate the prognostic impact of early CA in patients with HF and AF hospitalized for worsening HF. METHODS: From JROADHF (Japanese Registry of Acute Decompensated Heart Failure) (n = 13,238), patients with HF and AF who underwent CA within 90 days after admission for HF (early CA; n = 103) and those who did not (control; n = 2,683) were identified. Mortality was compared between these groups in the crude cohort, as well as in the propensity-matched cohort (n = 83 in each group). RESULTS: In the crude cohort, all-cause mortality was significantly lower in the early CA group than in the control group (log-rank P < 0.001; HR: 0.38; 95% CI: 0.24-0.60). In the matched cohort, all-cause mortality was likewise significantly lower in the early CA group (log-rank P = 0.014; HR: 0.47; 95% CI: 0.25-0.88). Cardiovascular death and HF mortality were significantly lower in both cohorts (crude: Gray' test: P < 0.001 and P = 0.005; subdistribution HR: 0.28 [95% CI: 0.13-0.63] and HR: 0.31 [95% CI: 0.13-0.75]; matched: Gray's test: P = 0.006 and P = 0.017; subdistribution HR: 0.24 [95% CI: 0.08-0.70] and HR: 0.28 [95% CI: 0.09-0.84], respectively). CONCLUSIONS: In a nationwide representative real-world cohort, CA for AF within 90 days after admission for HF was associated with improved long-term outcomes, including cardiovascular and HF death in patients with HF and AF.

Dexamethasone to prednisolone rotation relieved hiccups in colorectal cancer patient continuing teleworking during anticancer therapy.

We present a case of chemotherapy-induced hiccups that were alleviated by steroid rotation. Hiccups are often overlooked, but they have an impact on the patient's quality of life. In the COVID-19 era, web-based teleworking has become an important tool, hiccups during a teleconference should be noted as a concern for patients.

Drug Delivery with Hyaluronic Acid-Coated Polymeric Micelles in Liver Fibrosis Therapy.

Developing delivery vehicles that achieve drug accumulation in the liver and transferability into hepatic stellate cells (HSCs) across the liver sinusoidal endothelium is essential to establish a treatment for hepatic fibrosis. We previously developed hyaluronic acid (HA)-coated polymeric micelles that exhibited affinity to liver sinusoidal endothelial cells. HA-coated micelles possess a core-shell structure of self-assembled biodegradable poly(l-lysine)-b-poly(lactic acid) AB-diblock copolymer (PLys+-b-PLLA), and its exterior is coated with HA through polyion complex formation via electrostatic interaction between anionic HAs and cationic PLys segments. In this study, we prepared HA-coated micelles entrapping olmesartan medoxomil (OLM), an anti-fibrotic drug, and evaluated their possibility as drug delivery vehicles. HA-coated micelles exhibited specific cellular uptake into LX-2 cells (human HSC line) in vitro. In vivo imaging analysis after intravenous (i.v.) injection of HA-coated micelles into mice revealed that the micelles exhibited high accumulation in the liver. Observation of mouse liver tissue sections suggested that HA-coated micelles were distributed in liver tissue. Furthermore, i.v. injection of HA-coated micelles entrapping OLM showed a remarkable anti-fibrotic effect against the liver cirrhosis mouse model. Therefore, HA-coated micelles are promising candidates as drug delivery vehicles for the clinical management of liver fibrosis.

Beneficial Effects of Dipeptidyl Peptidase-4 Inhibitors on Heart Failure With Preserved Ejection Fraction and Diabetes.

Background: Dipeptidyl peptidase-4 (DPP-4) inhibitors have been shown to exert pleiotropic effects on heart failure (HF) in animal experiments. Objectives: This study sought to investigate the impact of DPP-4 inhibitors on HF patients with diabetes mellitus (DM). Methods: We analyzed hospitalized patients with HF and DM enrolled in the JROADHF (Japanese Registry Of Acute Decompensated Heart Failure) registry, a nationwide registry of acute decompensated HF. Primary exposure was the use of a DPP-4 inhibitor. The primary outcome was a composite of cardiovascular death or HF hospitalization during the median follow-up of 3.6 years according to left ventricular ejection fraction. Results: Out of 2,999 eligible patients, 1,130 had heart failure with preserved ejection fraction (HFpEF), 572 had heart failure with midrange ejection fraction (HFmrEF), and 1,297 had heart failure with reduced ejection fraction (HFrEF). In each cohort, 444, 232, and 574 patients received a DPP-4 inhibitor, respectively. A multivariable Cox regression model showed that DPP-4 inhibitor use was associated with a lower composite of cardiovascular death or HF hospitalization in HFpEF (HR: 0.69; 95% CI: 0.55-0.87; P = 0.002) but not in HFmrEF and HFrEF. Restricted cubic spline analysis demonstrated that DPP-4 inhibitors were beneficial in patients with higher left ventricular ejection fraction. In HFpEF cohort, propensity score matching yielded 263 pairs. DPP-4 inhibitor use was associated with a lower incidence rate of the composite of cardiovascular death or HF hospitalization (19.2 vs 25.9 events per 100 patient-years; rate ratio: 0.74; 95% CI: 0.57-0.97; P = 0.027) in matched patients. Conclusions: DPP-4 inhibitor use was associated with better long-term outcomes in HFpEF patients with DM.

Association between Serum Oxysterols and Coronary Plaque Regression during Lipid-Lowering Therapy with Statin and Ezetimibe: Insights from the CuVIC Trial.

AIM: Several clinical trials using intravascular ultrasound (IVUS) evaluation have demonstrated that intensive lipid-lowering therapy by statin or a combination therapy with statin and ezetimibe results in significant regression of coronary plaque volume. However, it remains unclear whether adding ezetimibe to statin therapy affects coronary plaque composition and the molecular mechanisms of plaque regression. We conducted this prospective IVUS analysis in a subgroup from the CuVIC trial. METHODS: The CuVIC trial was a prospective randomized, open, blinded-endpoint trial conducted among 11 cardiovascular centers, where 260 patients with coronary artery disease who received coronary stenting were randomly allocated into either the statin group (S) or the combined statin and ezetimibe group (S＋E). We enrolled 79 patients (S group, 39 patients; S＋E group, 40 patients) in this substudy, for whom serial IVUS images of nonculprit lesion were available at both baseline and after 6-8 months of follow-up. RESULTS: After the treatment period, the S＋E group had significantly lower level of low-density lipoprotein cholesterol (LDL-C; 80.9±3.7 vs. 67.7±3.8 mg/dL, p=0.0143). Campesterol, a marker of cholesterol absorption, and oxysterols (ß-epoxycholesterol, 4ß-hydroxycholesterol, and 27-hydroxycholesterol) were also lower in the S＋E group. IVUS analyses revealed greater plaque regression in the S＋E group than in the S group (-6.14% vs. -1.18% for each group, p=0.042). It was noteworthy that the lowering of campesterol and 27-hydroxycholesterol, but not LDL-C, had a significant positive correlation with plaque regression. CONCLUSIONS: Compared with statin monotherapy, ezetimibe in combination with statin achieved significantly lower LDL-C, campesterol, and 27-hydroxycholesterol, which resulted in greater coronary plaque regression.

[Malignant Melanoma of a Male Breast That Was Difficult to Differentiate from Breast Cancer-A Case Report].

INTRODUCTION: Malignant melanoma in the male breast is extremely rare. Here we report a case of malignant melanoma in which a small cystic lesion in the male breast gradually increased during follow-up and was difficult to distinguish from breast cancer. CASE: A 65-year-old male was diagnosed with a tumor in the right breast and was referred to our department for further examination. At 42 years of age, he underwent tumor resection of a malignant melanoma of the abdominal skin. Mammary ultrasonography showed a 0.6 cm cystic mass in his right breast. Eight months later, the right breast mass had increased to 1.4 cm, and a core needle biopsy suggested breast cancer. Total mastectomy with axillary lymph node dissection was performed. HE staining of the resected tumor showed intranuclear inclusion bodies and some large nucleoli. On the basis of various immunostaining methods, malignant melanoma was diagnosed instead of breast cancer. After surgery, adjuvant chemotherapy with molecularly targeted drugs was administered. DISCUSSION: This might have been a case of male breast metastasis of malignant melanoma with very late recurrence.

[Laparoscopic Tumor Resection for Asymptomatic Paraganglioma-A Case Study].

A 55-year-old man was referred for the close examination of an abdominal mass noted on abdominal ultrasonography during a physical examination. A contrast-enhanced computed tomography(CT)scan of his abdomen revealed a 36-mm heterogeneously contrast-enhanced mass on the left side of the aorta. He was referred for laparoscopic tumor resection without preoperative histological examination. The tumor was identified from the dorsal aspect of the mesentery of the transverse colon and was resected only because it was detachable from the duodenum. A temporary abnormal hypertension was observed intraoperatively. However, he exhibited a favorable postoperative course and was discharged on the 8th postoperative day. Grossly, it was a nodular tumor with a diameter of 38 mm. Histopathological examination revealed that the tumor cells having abundant cytoplasm formed large foci and were surrounded by sinusoidal vessels. Immunohistochemistry results were positive for chromogranin A, synaptophysin, and neural cell adhesion molecule; thus, paraganglioma was diagnosed. Herein, we report a case of laparoscopic resection of an asymptomatic paraganglioma.

Intravenous immunoglobulin for acute exacerbation of fibrotic idiopathic interstitial pneumonias.

BACKGROUND AND AIM: Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) is a fatal condition with no established treatment. Intravenous immunoglobulin (IVIG) is a unique therapy with both anti-inflammatory and anti-infective effects. Therefore, we hypothesized that IVIG may have a positive effect on AE of interstitial pneumonia. This study aimed to determine the effect of IVIG in patients with AE of fibrotic idiopathic interstitial pneumonias (IIPs), including IPF. METHODS: We retrospectively analyzed consecutive patients who were diagnosed with AE of fibrotic IIPs and treated with pulse corticosteroid therapy (methylprednisolone 500-1000 mg/day for 3 days) between April 2018 and May 2021 at Kagawa Rosai Hospital and KKR Takamatsu Hospital. RESULTS: This study included 52 patients with AE of fibrotic IIPs (IPF,41; fibrotic IIPs other than IPF,11). Thirteen patients received IVIG (5 g/day for 3-5 days) concurrently with pulse corticosteroid therapy. The remaining 39 patients were assigned to the control group. The survival rate on day 90 was significantly higher in the IVIG group than that in the control group (76.9% vs. 38.5%, p = 0.02). IVIG administration (odds ratio [OR], 0.11; 95% confidence interval [CI], 0.02-0.69; p = 0.02) and C- reactive protein (OR, 1.19; 95% CI, 1.06-1.33, p < 0.01) were independently associated with 90-day mortality. CONCLUSIONS: The results indicate that administration of IVIG may improve the survival of patients with AE of fibrotic IIPs. We are now conducting a prospective study to confirm the effect of IVIG on AE of IPF since May 2022 (jRCT1061220010).

A Survey of Near-Miss Dispensing Errors in Hospital Pharmacies in Japan: DEPP-J Study-Multi-Center Prospective Observational Study-

The aim of this study was to determine the proportion of near-miss dispensing errors in hospital pharmacies in Japan. A prospective multi-center observational study was conducted between December 2018 and March 2019. The primary objective was to determine the proportion of near-miss dispensing errors in hospital pharmacy departments. The secondary objective was to determine the predictive factors for near-miss dispensing errors using multiple logistic regression analysis. The study was approved by the ethical committee at The Institute of Medical Sciences, University of Tokyo, Japan. A multi-center prospective observational study was conducted in 20 hospitals comprising 8862 beds. Across the 20 hospitals, we assessed data from 553 pharmacists and 53039 prescriptions. A near-miss dispensing error proportion of 0.87% (n = 461) was observed in the study. We found predictive factors for dispensing errors in day-time shifts: a higher number of drugs in a prescription, higher number of quantified drugs, such as liquid or powder formula, in a prescription, and higher number of topical agents in a prescription; but we did not observe for career experience level for clinical pharmacists. For night-time and weekend shifts, we observed a negative correlation of near-miss dispensing errors with clinical pharmacist experience level. We found an overall incidence of near-miss dispensing errors of 0.87%. Predictive factors for errors in night-time and weekend shifts was inexperienced pharmacists. We recommended that pharmacy managers should consider education or improved work flow to avoid near-miss dispensing errors by younger pharmacists, especially those working night or weekend shifts.

Home-based cardiac rehabilitation using information and communication technology for heart failure patients with frailty.

AIMS: Cardiac rehabilitation (CR) is an evidence-based, secondary preventive strategy that improves mortality and morbidity rates in patients with heart failure (HF). However, the implementation and continuation of CR remains unsatisfactory, particularly for outpatients with physical frailty. This study investigated the efficacy and safety of a comprehensive home-based cardiac rehabilitation (HBCR) programme that combines patient education, exercise guidance, and nutritional guidance using information and communication technology (ICT). METHODS AND RESULTS: This study was a single-centre, open-label, randomized, controlled trial. Between April 2020 and November 2020, 30 outpatients with chronic HF (New York Heart Association II-III) and physical frailty were enrolled. The control group (n = 15) continued with standard care, while the HBCR group (n = 15) also received comprehensive, individualized CR, including ICT-based exercise and nutrition guidance using ICT via a Fitbit® device for 3 months. The CR team communicated with each patient in HBCR group once a week via the application messaging tool and planned the training frequency and intensity of training individually for the next week according to each patient's symptoms and recorded pulse data during exercise. Dietitians conducted a nutritional assessment and then provided individual nutritional advice using the picture-posting function of the application. The primary outcome was the change in the 6 min walking distance (6MWD). The participants' mean age was 63.7 ± 10.1 years, 53% were male, and 87% had non-ischaemic heart disease. The observed change in the 6MWD was significantly greater in the HBCR group (52.1 ± 43.9 m vs. -4.3 ± 38.8 m; P < 0.001) at a 73% of adherence rate. There was no significant change in adverse events in either group. CONCLUSIONS: Our comprehensive HBCR programme using ICT for HF patients with physical frailty improved exercise tolerance and improved lower extremity muscle strength in our sample, suggesting management with individualized ICT-based programmes as a safe and effective approach. Considering the increasing number of HF patients with frailty worldwide, our approach provides an efficient method to keep patients engaged in physical activity in their daily life.

Indications for SARS-CoV-2 nucleic acid amplification test for areas with low endemicity.

INTRODUCTION: The optimal indication for the nucleic acid amplification test (NAAT) in areas with low endemicity for coronavirus disease 2019 (COVID-19) is unclear. This study aimed to identify patients who should undergo the NAAT for COVID-19 diagnosis. METHODS: We retrospectively analyzed the clinical data of patients with suspected COVID-19 who underwent NAAT between October 5, 2020, and May 31, 2021 in our institution. RESULTS: A total of 1238 patients were enrolled and NAAT positive results were observed in 40 patients (3.2%). The NAAT positivity rate was 34.3% (23/67) in patients with a history of close contact and 1.5% (17/1171) in patients without a history of close contact. Olfactory/gustatory dysfunction and a history of stay in other prefectures were independent risk factors of COVID-19 in patients without a history of close contact. On the other hand, the NAAT positivity rate was only 0.7% (8/1073) in patients without olfactory/gustatory dysfunction and a history of stay in other prefectures. Among them, the group without respiratory symptoms/sign had only one NAAT-positive case (0.1%: 1/1073). CONCLUSIONS: This study revealed that a history of close contact, olfactory/gustatory dysfunction, and a history of stay in other prefectures are key eligibility criteria for NAAT in areas with relatively few patients with COVID-19. On the other hand, NAAT may not be necessary in cases without all of these factors and respiratory symptoms/sign.

Mammary Paget's Disease Presenting as an Annular Plaque.

Dear Editor,Mammary Paget's disease (MPD) is an adenocarcinoma localized within the epidermis of the nipple and/or the areola of the breast, and it is as a rule associated with a carcinoma of the underlying lactiferous ducts, where it usually starts. MPD is relatively rare, observed in 0.7-4.3% of all breast cancers (1). We present a patient with MPD and atypical clinical finding as an annular plaque. A 74-year-old Japanese woman with a past medical history of hypothyroidism presented with a 6-month history of an itching plaque on the left areola. The patient had been treated with the application of topical steroids for a duration of approximately 5 months, and showed no clinical improvement. Physical examination showed a pink plaque encircling the nipple on the left areola (Figure 1, a). The right nipple and areola appeared normal (Figure 1, b). No palpable masses were detected within either breast. A 3.5 mm punch biopsy of the skin at the 6 o'clock position of the left areola was performed. Histological examination showed single and small aggregations of atypical cells with large hyperchromatic nuclei and pale-staining, ample cytoplasm throughout the epidermis. There was a lymphocytic infiltration in the dermis (Figure 1, c). Immunohistochemical studies were positive for CK7 and negative for S-100 and HMB45. With the diagnosis of MPD, the patient underwent a partial mastectomy of the left breast center area, consisting of surgical excision of the left nipple, the adjacent surrounding areolar skin, and subcutaneous tissues. Subsequently, radiation therapy for the residual breast was prepared. As has been described in detail by Kanitakis, the skin lesion develops insidiously as a scaly, fissured, or oozing erythema of the nipple and, more rarely, the areola. Advanced lesions present as a well-demarcated, round, ovoid, or polycyclic eczema-like plaque with a pink or red hue. It is occasionally slightly infiltrated and has an erosive, oozing, scaly, or crusted surface. The lesions are almost invariably unilateral, showing centrifugal spread. Retraction or ulceration of the nipple are often noted (1). The present case exhibited a very rare clinical finding of a plaque encircling the nipple, which has not been reported previously. It was initially difficult to establish the diagnosis of MPD, and biopsy was needed to obtain a definitive diagnosis. Differential diagnosis of MPD comprises eczema as atopic dermatitis or contact dermatitis, erosive adenomatosis, and malignant skin condition such as Bowen's disease, superficial basal cell carcinoma, or superficially spreading melanoma. As in the present case, individuals presenting with an annular plaque are often considered to have sebaceous hyperplasia. Sebaceous hyperplasia is a common, benign skin condition involving hypertrophy of the sebaceous glands, common in middle-aged or older adults (2). These lesions can be single or multiple and manifest as yellow, soft, small papules. These papules are occasionally seen around the nipple, forming an annular plaque. In general, sebaceous hyperplasia is described as yellow-colored papules among Caucasians. However, caution is needed, since it is characterized by skin-colored papules among some Asians.In the present case, some pigmentation (2 to 3 mm in diameter) was observed on the left nipple. Pigmented MPD have been reported, and the mechanism underlying the pigmentation is not yet fully understood, but it has been proposed that Paget cells may release melanocytic chemoattractants or basic fibroblast growth factors that stimulate the proliferation of melanocytes within the tumor nests (3). The possibility of physiological pigmentation cannot be ruled out in the present case; on the other hand, the possibility of pigmented MPD cannot be ruled out either, since no pigmentation was observed on the right nipple.

Comparison of adherence tendencies of pesticide residues sprayed on small-, medium-, and large-sized tomatoes.

Crop field trials were conducted to investigate the residues of sprayed pesticides on the different sizes of tomatoes. Pesticide residue data in tomatoes varied due to different locations of the three crop fields selected and/or physicochemical properties of the three pesticides tested. The pesticide residue levels in the medium- and small-sized tomatoes were 1.5 and 2.4 times higher than the level in large-sized tomatoes under similar spray conditions, whereas amount of pesticides adhered per unit surface area were approximately equal among all three sizes of tomatoes. The results of this study suggested that the differences in pesticide residue levels were due to differences in the degree of specific surface area of each tomato size. Resultant residue data of medium-sized tomatoes demonstrated a proportional relationship between pesticide residue levels and the specific surface area of tomatoes.

Clinical course involving thrombocytosis and thrombocytopenia in a patient with bladder cancer treated with gemcitabine and cisplatin.

Gemcitabine induce thrombocytopenia and thrombocytosis as toxicity. In this report, we show detailed time-course for platelet fluctuation. Our case emphasis attention to monitor see-saw-like toxicity on platelet count.