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Abstract Introduction Differences in predictability of ablation success for premature ventricular contractions (PVCs) between earliest isochronal map area (EIA), local activation time (LAT) differences on unipolar and bipolar electrograms (⊿LATBi‐Uni), LAT prematurity on bipolar electrograms (LATBi), and unipolar morphology of QS or Q pattern remain unclear. We verified multiple statistical predictabilities of those indicators of ablation success on mapped cardiac surface. Methods Thirty‐five patients with multiple PVCs underwent catheter ablation after LAT mapping using multipolar mapping catheters with unipolar‐based annotation. Patients were divided into success and failure groups based on ablation success on mapped cardiac surfaces. Discrimination ability, reclassification table, calibration plots, and decision curve analysis of 10 ms EIA (EIA10ms), ⊿LATBi‐Uni, and LATBi were validated. Unipolar morphology was compared between success and failure groups. Results Right ventricular outflow tract, aortic cusp, and left ventricle were mapped in 17, 10, and 8 patients, respectively. In 14/35 (40%) patients, successful ablation was performed on mapped cardiac surfaces. Area under the curve of receiver‐operating characteristic curve of EIA10ms, ⊿LATBi‐Uni, and LATBi were 0.874, 0.801, and 0.650, respectively (EIA10ms vs. LATBi, p =.014; ⊿LATBi‐Uni vs. LATBi, p =.278; EIA10ms vs. ⊿LATBi‐Uni, p =.464). EIA10ms and ⊿LATBi‐Uni demonstrated better predictability, calibration, and clinical utility on reclassification table, calibration plots, and decision curve analysis than LATBi. Unipolar morphology of QS or Q pattern did not correlate with ablation success (p =.518). Conclusion EIA10ms and ⊿LATBi‐Uni more accurately predict ablation success for PVCs on mapped cardiac surfaces than LATBi and unipolar morphology.

Introduction: Vascular tissue engineering is a key technology in the field of regenerative medicine. In tissue engineering, the separation of vascular cells without cell modification is required, as cell modifications affect the intrinsic properties of the cells. In this study, we have developed an effective method for separating vascular cells without cell modification, using a thermoresponsive anionic block copolymer. Methods: A thermoresponsive anionic block copolymer, poly(acrylic acid)-b-poly(N-isopropylacryl-amide) (PAAc-b-PNIPAAm), with various PNIPAAm segment lengths, was prepared in two steps: atom transfer radical polymerization and subsequent deprotection. Normal human umbilical vein endothelial cells (HUVECs), normal human dermal fibroblasts, and human aortic smooth muscle cells (SMCs) were seeded onto the prepared thermoresponsive anionic block copolymer brush-modified glass. The adhesion behavior of cells on the copolymer brush was observed at 37 °C and 20 °C. Results: A thermoresponsive anionic block copolymer, poly(acrylic acid)-b-poly(N-isopropylacrylamide) (PAAc-b-PNIPAAm), with various PNIPAAm segment lengths was prepared. The prepared copolymer-modified glass exhibited anionic properties attributed to the bottom PAAc segment of the copolymer brush. On the PAAc-b-PNIPAAm, which had a moderate PNIPAAm length, a high adhesion ratio of HUVECs and low adhesion ratio of SMCs were observed at 37 °C. By reducing temperature from 37 °C to 20 °C, the adhered HUVECs were detached, whereas the SMCs maintained adhesion, leading to the recovery of purified HUVECs by changing the temperature. Conclusions: The prepared thermoresponsive anionic copolymer-modified glass could be used to separate HUVECs and SMCs by changing the temperature without modifying the cell surface. Therefore, the developed cell separation method will be useful for vascular tissue engineering.

Abstract Background This study aimed to investigate the relationship between low-dose prednisolone (PSL) and the incidence of hypokalaemia at abiraterone acetate (abiraterone) plus PSL combination therapy targeting Japanese patients with metastatic castration-resistant prostate cancer (mCRPC). Methods This retrospective observational study included 153 Japanese patients treated with abiraterone and PSL for mCRPC at Kariya Toyota General Hospital and Gifu General Medical Center between September 2014 and October 2022. The incidence of grade ≥ 2 hypokalaemia as well as serum potassium level variations and the continuous combination therapy duration were compared between the low-dose (5 mg/day of PSL) and the standard-dose (10 mg/day of PSL) groups. Results This study included 153 patient of which 95 were matched to establish the analysis population. The low-dose and the standard-dose groups consisted of 13 and 82 patients, respectively. No significant difference in the incidence of grade ≥ 2 hypokalaemia was observed between the two groups [15.4% (2/13 patients) in the low-dose group and 12.2% (10/82 patients) in the standard-dose group, P = 0.667]. The low-dose group exhibited a decrease in serum potassium levels from 4.63 on day − 7 − 0 to 4.16 mmol/L on day 84 ± 10 (n = 7, P = 0.066), and serum potassium levels from day − 7 − 0 to 84 ± 10 in the low-dose group appeared to be great in the standard-dose group (n = 37, P = 0.475). The Kaplan–Meier curves for continuity of abiraterone and PSL therapy were not significantly different between the low-dose group (n = 13) and standard-dose group (n = 82, P = 0.427). Conclusion Combination therapy with abiraterone and 5 mg/day of PSL in Japanese patients with mCRPC did not change the incidence of grade ≥ 2 hypokalaemia. However, although not significant, 5 mg/day of PSL demonstrated a decreasing trend in serum potassium levels with a larger degree of change than that of 10 mg/day of PSL. Therefore, the combination of abiraterone and 5 mg/day PSL can be administered to Japanese patients with mCRPC. The patients must be monitored for hypokalaemia through measurement of serum potassium levels and observation of subjective symptoms such as muscle weakness, convulsion etc. In addition, the doctor or the pharmacist must explain these symptoms to the patient and instruct them to consult their medical staff immediately in the event of development of such symptoms.

Arterioportal fistula (APF) combined with a visceral artery pseudoaneurysm is an exceptionally rare and critical vascular disorder of the abdominal viscera, with pseudoaneurysm rupture being potentially fatal and severe APF leading to portal hypertension, both of which necessitate immediate intervention. An 87-year-old woman with a history of pancreatitis presented with upper abdomen and back pain. Laboratory tests revealed elevated amylase levels and severe anemia. A computed tomography (CT) scan showed a large dorsal pancreatic artery (DPA) pseudoaneurysm with a fistula to the main portal vein. Given her advanced age, surgery was deemed high-risk, and endovascular treatment was selected. Transcatheter arterial embolization was successfully performed using coils to embolize the DPA pseudoaneurysm. A follow-up CT 1 week postprocedure confirmed the absence of a pseudoaneurysm and no further progression of anemia.

Fallopian tube carcinoma, presenting as an inguinal hernia, is a rare entity. We report the case of a woman in her 70s with a history of hysterectomy and right oophorectomy 29 years prior who presented with left cervical lymphadenopathy and elevated CA125 levels. Imaging revealed a tubular structure in the left pelvic region extending into the inguinal hernia sac. Contrast-enhanced computed tomography revealed a tubular structure with solid components in the left pelvic region that herniated through the left inguinal canal. Magnetic resonance imaging further characterized the solid component within the tubular structure and revealed features suggestive of malignancy. Fluorodeoxyglucose positron emission tomography/computed tomography revealed fluorodeoxyglucose uptake in the solid component and multiple enlarged lymph nodes, indicating lymph node metastasis. Subsequent laparoscopic resection confirmed high-grade serous carcinoma originating from the fallopian tube. Fallopian tube carcinoma typically presents nonspecific symptoms but elevated CA125 levels. Imaging often shows sausage-shaped masses. The mechanism in this case involved increased mobility of the left adnexa after hysterectomy and tumor infiltration near the inguinal canal. This case highlights the importance of considering fallopian tube carcinoma as a differential diagnosis when evaluating inguinal hernias, particularly in high-risk patients.

We described a premature ventricular contraction arising from the left coronary sinus cusp, in which we discussed about the interpretations of the signals recorded there. Our case provided further insights into the interpretation of signals recorded at the coronary sinus cusp during premature ventricular contraction ablation.

Abstract Background Edoxaban, the only factor Xa inhibitor with active metabolites, is metabolized by carboxylesterase-1 to its main active metabolite, M-4, which is a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) and is excreted in bile and urine. Because the area under the plasma concentration–time curve ratio of M-4 to parent compound is typically less than 10% in healthy subjects, M-4 is generally considered to exhibit negligible antithrombotic activity in patients treated with edoxaban. However, we identified a case in which drug interactions and kidney impairment led to a substantive increase in plasma M-4 concentrations. Case presentation This case report involved a 68-year-old man with pancreatic cancer who was orally administered edoxaban tablets for prevention of thrombus formation in non-valvular atrial fibrillation, in addition to rifampin and clarithromycin (CAM) for treatment of mycobacterium avium complex lung disease. These medications were temporarily discontinued for a pancreaticoduodenectomy but were resumed 8 days post-surgery (POD8). On POD9, the patient developed acute kidney injury, and the trough concentrations of edoxaban and M-4 were 131.1 ng/mL and 115.8 ng/mL, respectively (M-4 ratio: 88.3%). On POD11, the M-4 trough concentration and M-4 ratio increased to 216.2 ng/mL and 186.2%, respectively. The plasma concentration of coproporphyrin-I, an endogenous biomarker of OATP1B1 activity, increased during this period. Conclusions This case suggests that in patients with impaired renal function taking edoxaban, co-administration of carboxylesterase-1 inducers such as rifampin and/or OATP1B1 inhibitors such as rifampin or clarithromycin may increase plasma concentrations of M-4 to clinically non-negligible levels.

Abstract The accumulation of monocyte-derived macrophages in the lung tissue during inflammation is important for the pathogenesis of fibrotic lung disease. Deficiencies in chemokine receptors CCR2 and CCR5 and their ligands, which mediate monocyte/macrophage migration, ameliorate bleomycin (BLM)-induced lung fibrosis. Disulfiram (DSF), which is used to treat alcoholism because of its aldehyde dehydrogenase (ALDH)-inhibiting effect, inhibits monocyte/macrophage migration by inhibiting FROUNT, an intracellular regulator of CCR2/CCR5 signalling. Here, we investigated the antifibrotic effect of oral DSF administration in a mouse model of BLM-induced lung fibrosis, focusing on macrophage response and fibrosis progression. The direct inhibitory activity of DSF on monocyte migration was measured using the Boyden chamber assay and compared with that of DSF-related inhibitors with different FROUNT-inhibition activities. Quantitative PCR was used to determine the expression of fibrosis-promoting genes in the lung tissue. DSF significantly suppressed macrophage infiltration into lung tissues and attenuated BLM-induced lung fibrosis. DSF and its metabolites, diethyldithiocarbamate (DDC) and copper diethyldithiocarbamate (Cu(DDC)2), inhibited monocyte migration toward the culture supernatant of primary mouse lung cells mainly comprising CCL2, whereas cyanamide, another ALDH inhibitor, did not. DSF, with higher inhibitory activity against FROUNT than DDC and Cu(DDC)2, inhibited monocyte migration most strongly. In BLM-induced fibrotic lung tissues, profibrotic factors were highly expressed but were reduced by DSF treatment. These results suggest DSF inhibits macrophage infiltration, which might be attributed to its inhibitory effect on FROUNT, and attenuates BLM-induced lung fibrosis. In addition, multiplex immunofluorescence imaging revealed reduced infiltration of S100A4+ macrophages into the lungs in DSF-treated mice and high expression of FROUNT in S100A4+ macrophages in idiopathic pulmonary fibrosis (IPF). These findings underscore the potential of macrophage-targeted therapy with DSF as a promising drug repositioning approach for treating fibrotic lung diseases, including IPF.

Abstract Ovarian cancer (OC) is the most lethal gynecologic cancer, mainly due to late diagnosis with widespread peritoneal spread at first presentation. We performed metabolomic analyses of ovarian and paired control tissues using capillary electrophoresis-mass spectrometry and liquid chromatography-mass spectrometry to understand its metabolomic dysregulation. Of the 130 quantified metabolites, 96 metabolites of glycometabolism, including glycolysis, tricarboxylic acid cycles, urea cycles, and one-carbon metabolites, showed significant differences between the samples. To evaluate the local and systemic metabolomic differences in OC, we also analyzed low or non-invasively available biofluids, including plasma, urine, and saliva collected from patients with OC and benign gynecological diseases. All biofluids and tissue samples showed consistently elevated concentrations of N 1,N 12-diacetylspermine compared to controls. Four metabolites, polyamines, and betaine, were significantly and consistently elevated in both plasma and tissue samples. These data indicate that plasma metabolic dysregulation, which the most reflected by those of OC tissues. Our metabolomic profiles contribute to our understanding of metabolomic abnormalities in OC and their effects on biofluids.