Cardiac arrest and post-discharge mortality in patients with myocardial infarction: A large-scale nationwide registry analysis.

Background: Cardiac arrest is a serious complication of acute myocardial infarction. The implementation of contemporary approaches to acute myocardial infarction management, including urgent revascularization procedures, has led to significant improvements in short-term outcomes. However, the extent of post-discharge mortality in patients experiencing cardiac arrest during acute myocardial infarction remains uncertain. This study aimed to determine the post-discharge outcomes of patients with cardiac arrest. Methods: We analysed data from the J-PCI OUTCOME registry, a Japanese prospectively planed, observational, multicentre, national registry of percutaneous coronary intervention involving consecutive patients from 172 institutions who underwent percutaneous coronary intervention and were discharged. Patients who underwent percutaneous coronary intervention for acute myocardial infarction between January 2017 and December 2018 and survived for 30 days were included. Mortality in patients with and without cardiac arrest from 30 days to 1 year after percutaneous coronary intervention for acute myocardial infarction was compared. Results: Of the 26,909 patients who survived for 30 days after percutaneous coronary intervention for acute myocardial infarction, 1,567 (5.8%) had cardiac arrest at the onset of acute myocardial infarction. Patients with cardiac arrest were younger and more likely to be males than patients without cardiac arrest. The 1-year all-cause mortality was significantly higher in patients with cardiac arrest than in those without (11.9% vs. 2.8%, p < 0.001) for all age groups. Multivariable analysis showed that cardiac arrest was an independent predictor of all-cause long-term mortality (hazard ratio: 2.94; 95% confidence interval: 2.29-3.76). Conclusions: Patients with acute myocardial infarction and concomitant cardiac arrest have a worse prognosis for up to 1 year after percutaneous coronary intervention than patients without cardiac arrest.

[Evaluation of the Leftover Capecitabine Tablets in Adjuvant CAPOX Chemotherapy for Gastric Cancer].

Since it is important that patients take their oral anticancer therapy as prescribed, pharmacists need to assess adherence. In addition, oral anticancer drugs are expensive, and reuse of leftover drugs at outpatient pharmacy clinics is useful in reducing drug costs. The present study aimed to clarify when and why patients have leftover capecitabine tablets, and the cost of leftover capecitabine tablets reused at an outpatient pharmacy clinic, focusing on adjuvant capecitabine plus oxaliplatin (CAPOX) chemotherapy for gastric cancer. We retrospectively studied patients who received adjuvant CAPOX chemotherapy for gastric cancer between November 1, 2015, and April 30, 2021, at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research. The cost of leftover capecitabine reused by pharmacists was calculated based on the National Health Insurance drug price standard for the study period. This study included 64 patients who received adjuvant CAPOX chemotherapy. Thirty-seven patients had 152 leftover capecitabine tablets. The most common reasons for leftover capecitabine tablets were nausea and vomiting (21.7%), missed doses (18.4%), and diarrhea (13.2%). The leftover capecitabine tablets for 25 patients were reused at the outpatient pharmacy clinic at a cost of JPY 604142.8 (JPY 24165.7 per patient). The study results suggest that evaluating capecitabine adherence and the reasons for leftover capecitabine tablets at outpatient pharmacy clinics as well as reusing leftover medication can contribute to reducing drug costs.

Hemodialysis-induced Myocardial Stunning with No Obstructive Coronary Artery Disease: Pathophysiological Significance of Coronary Microvascular Dysfunction.

Hemodialysis (HD)-induced myocardial stunning, characterized by transient left ventricular systolic dysfunction during HD, has been reported to be common and associated with a poor prognosis. However, the pathophysiology is not fully understood. We herein report a case of HD-induced myocardial stunning without obstructive coronary artery disease complicated by coronary microvascular dysfunction (CMD), suggesting that CMD plays a crucial role in the pathophysiology of this disease.

Factors associated with lenvatinib adherence in thyroid cancer and hepatocellular carcinoma.

BACKGROUND: Lenvatinib is an oral anticancer medication used to treat radioiodine-refractory thyroid cancer and unresectable hepatocellular carcinoma. The purpose of this study is to evaluate lenvatinib adherence by patients and to identify factors associated with decreased lenvatinib adherence. METHODS: Among 153 patients who started treatment with lenvatinib for unresectable thyroid cancer or unresectable hepatocellular carcinoma between May 1, 2015 and August 31 2021 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research, 102 were eligible for this study (55 thyroid cancer, 47 hepatocellular carcinoma). The lenvatinib adherence rate in a treatment cycle was defined as the number of times a patient took lenvatinib in a 28-day cycle divided by the prescribed 28 doses. The rate was determined by pill counting and self-reporting at the pharmaceutical outpatient clinic. Reasons for non-adherence were established by interview and analyzed. RESULTS: The median adherence rate of lenvatinib in the first cycle was 90.1% (n = 55) in thyroid cancer and 94.9% (n = 47) in hepatocellular carcinoma. In thyroid cancer, there were 255 incidents of lenvatinib non-adherence. Non-adherence was mainly associated with bleeding events (18.6%), followed by hand-foot skin reactions (10.6%). In hepatocellular carcinoma, there were 97 incidents of non-adherence. Hypertension accounted for 20.6%, followed by hoarseness (18.6%) and diarrhea (17.5%). CONCLUSION: The adherence rate for lenvatinib in Japanese patients with thyroid and hepatocellular carcinoma in real-world clinical practice was more than 90% in this study. Hypertension was a major reason for non-adherence, followed by hand-foot skin reactions and diarrhea.

Impact of general anesthesia on ablation catheter stability during pulmonary vein isolation based on a novel measurement approach.

Catheter ablation for atrial fibrillation (AF) during pulmonary vein isolation (PVI) is performed under general anesthesia (GA) or conscious sedation (CS). GA during PVI may improve treatment outcomes by improving catheter stability. However, the magnitude of GA-derived catheter stability compared with that of CS is unclear. We directly assessed catheter movement and determined the impact of GA compared with that of CS on ablation catheter stability during PVI. Patients who underwent initial ablation using the EnSite Precision™ mapping system were recruited and divided into two groups (GA and CS groups). The two groups were compared for ablation catheter stability during PVI based on the distance traveled by the catheter distal tip per second, clinical periprocedural characteristics, and periprocedural complications. Among 69 consecutively admitted patients, data of 30 patients (17 in the GA group and 13 in the CS group) and the distance traveled per second by the catheter on 148,976 points/patient were evaluated. The GA group had a significantly smaller catheter tip travel distance than the CS group (0.92 [0.82‒1.16] vs. 1.25 [1.14‒1.38], p = 0.01). Therefore, GA during PVI for AF provides greater catheter stability than CS and will contribute to more accessible and safer PVI procedures.

Influence of menopause on chemotherapy-induced nausea and vomiting in highly emetogenic chemotherapy for breast cancer: A retrospective observational study.

BACKGROUND: Female sex and younger age are reported risk factors for chemotherapy-induced nausea and vomiting (CINV) in highly emetogenic chemotherapy, but the underlying mechanism has not been elucidated. The purpose of this study was to clarify the impact of menopause on CINV. METHODS: This retrospective observational study analyzed data from consecutive patients who received their first cycle of perioperative anthracycline-based chemotherapy for breast cancer between January 2018 and June 2020. The endpoints were association between CINV (vomiting, ≥Grade 2 nausea, complete response [CR] failure) and menopause as well as the association between CINV and follicle-stimulating hormone [FSH]/estradiol [E2]. RESULTS: Data for 639 patients were analyzed. Among these patients, 109 (17.1%) received olanzapine (four antiemetic combinations) and 530 (82.9%) did not (three antiemetic combinations). Premenopausal state (amenorrhea lasting ≥12 months) was significantly associated with ≥Grade 2 nausea and CR failure in univariate analysis but not in multivariate analysis. The premenopausal FSH/E2 group (defined by serum levels; FSH <40 mIU/mL and E2 ≥20 pg/mL) had a significantly higher rate of ≥Grade 2 nausea than the postmenopausal FSH/E2 group (FSH ≥40 mIU/mL and E2 <20 pg/mL) (48.8% vs. 18.8%, p = 0.023). CONCLUSIONS: Our results suggest that changes in FSH and E2 due to menopause may affect the severity of nausea and that FSH and E2 (especially FSH) levels might be useful indicators for CINV risk assessment.

Isomer-Selective Conversion of Au Clusters by Au(I) Thiolate Insertion.

Isomer-selective conversion is a challenging goal in the rational design of Au clusters. Herein, we demonstrate the isomer-selective conversion of Au18(ScC6)14 (ScC6 = cyclohexanethiolate) into Au24(SR)x(ScC6)20-x in high yields by reactions with gold(I) thiolate (AuSR) complexes. Electrospray ionization mass spectrometry indicated that even numbers of AuSR units are inserted into Au18(SR)x(ScC6)14-x to generate Au24(SR)x(ScC6)20-x through intermediates Au20(SR)x(ScC6)16-x or Au22(SR)x(ScC6)18-x. These results suggest that the number of constituent atoms in surface Au(I)SR oligomers only increases, while the number of electrons in an Au core is maintained. UV-vis analysis revealed the generation of one of two Au24(SR)x(ScC6)20-x isomers in the reactions of Au18(ScC6)14 with AuSR complexes, in contrast to the formation of both isomers by reactions with thiols. When the structures of Au18(SR)14 are compared with those of the Au24(SR)20 isomers, the partial structure in the Au cores is preserved in the isomer-selective conversion with AuSR complexes, regardless of the structures of the thiolate moiety.

Association between coronary flow and aortic stenosis during transcatheter aortic valve implantation.

AIMS: In patients with aortic stenosis (AS), the coronary flow reserve decreases even in the absence of epicardial coronary artery stenosis. Systolic coronary flow reversal (SFR) reflecting reduced coronary microcirculation, often seen in patients with severe AS, has a potential negative impact on the pathogenesis of cardiac dysfunction. However, there are limited data on the relationship between the severity of AS and SFR, as well as on the benefits of transcatheter aortic valve implantation (TAVI). The aim of this study was to evaluate the relationship between the severity of AS and efficacy of TAVI in improving SFR. METHODS AND RESULTS: Consecutive patients with AS who had undergone TAVI using transoesophageal echocardiography (TEE) from November 2020 to February 2022 were prospectively enrolled. Coronary flow in the left anterior descending artery as well as the aortic valve peak velocities, and the mean aortic valve pressure gradients (AVPGs), indicating the severity of AS, were measured using intraprocedural TEE before and after TAVI. The following parameters were measured as coronary flow: systolic and diastolic peak velocity (cm/s) and systolic and diastolic velocity-time integral (VTI) (cm). SFR was defined as the presence of a reversal coronary flow component in systole. The enrolled patients were classified into two groups according to the presence or absence of SFR before TAVI. A total of 25 patients were included: 13 had SFR and 12 who had no SFR, before TAVI. Patients with SFR had significantly higher aortic valve peak velocities (451.1 ± 45.9 vs. 372.1 ± 52.1 cm/s; P < 0.001) and mean AVPGs (49.2 ± 14.5 vs. 30.3 ± 11.6 mmHg; P = 0.002) than those without. The optimal binary cut-off aortic valve peak velocity values and the mean AVPG associated with the presence of SFR before TAVI were >410.0 cm/s (specificity, 75.0%; sensitivity, 92.3%) and >37.4 mmHg (specificity, 83.3%; sensitivity, 92.3%), respectively. After TAVI, SFR immediately disappeared in 11 of 13 patients with SFR (84.6%). Overall, the systolic coronary VTI significantly increased after TAVI (2.0 ± 4.7 vs. 6.4 ± 3.2 cm, P < 0.001), and this increase was greater in patients with SFR than in those without SFR before TAVI (interaction P = 0.035). CONCLUSIONS: SFR was found to be associated with the severity of AS and with a greater increase in systolic coronary flow immediately after TAVI.

Differential Impact of Renal Function on the Diagnostic Performance of Resting Full-Cycle Ratio in Patients With Renal Dysfunction.

Background: Physiological assessments using fractional flow reserve (FFR) and resting full-cycle ratio (RFR) have been recommended for revascularization decision making. Previous studies have shown a 20% rate of discordance between FFR and RFR. In this context, the correlation between RFR and FFR in patients with renal dysfunction remains unclear. This study examined correlations between RFR and FFR according to renal function. Methods and Results: In all, 263 consecutive patients with 370 intermediate lesions were enrolled in the study. Patients were classified into 3 groups according to renal function: Group 1, estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2; Group 2, 30 mL/min/1.73 m2≤eGFR<60 mL/min/1.73 m2; Group 3, eGFR <30 mL/min/1.73 m2. The discordance between FFR and RFR was assessed using known cut-off values for FFR (≤0.80) and RFR (≤0.89). Of the 370 lesions, functional significance with FFR was observed in 154 (41.6%). RFR was significantly correlated with FFR in all groups (Group 1, R2=0.62 [P<0.001]; Group 2, R2=0.67 [P<0.001]; Group 3, R2=0.46 [P<0.001]). The rate of discordance between RFR and FFR differed significantly among the 3 groups (Group 1, 18.8%; Group 2, 18.5%; Group 3, 42.9%; P=0.02). Conclusions: The diagnostic performance of RFR differed based on renal function. A better understanding of the clinical factors contributing to FFR/RFR discordance, such as renal function, may facilitate the use of these indices.

Control over Ligand-Exchange Positions of Thiolate-Protected Gold Nanoclusters Using Steric Repulsion of Protecting Ligands.

Organic ligands on gold nanoclusters play important roles in regulating the structures of gold cores. However, the impact of the number and positions of the protecting ligands on gold-core structures remains unclear. We isolated thiolate-protected Au25 cluster anions, [Au25(SC2Ph)17(Por)1]- and [Au25(SC2Ph)16(Por)2]- (SC2Ph = 2-phenylethanethiolate), obtained by ligand exchange of [Au25(SC2Ph)18]- with one or two porphyrinthiolate (Por) ligands as mixtures of regioisomers. The ratio of two regioisomers in [Au25(SC2Ph)17(Por)1]- as measured by 1H NMR spectroscopy revealed that the selectivity could be controlled by the steric hindrance of the incoming thiols. Extended X-ray absorption fine structure studies of a series of porphyrin-coordinated gold nanoclusters clarified that the Au13 icosahedral core in the Au25 cluster was distorted through steric repulsion between porphyrin thiolates and phenylethanethiolates. This paper reveals interesting insights into the importance of the steric structures of protecting ligands for control over core structures in gold nanoclusters.

ANCA-Associated Vasculitis in a Patient with Chronic Thromboembolic Pulmonary Hypertension.

An 82-year-old woman with a history of chronic thromboembolic pulmonary hypertension (CTEPH) presented with malaise, left facial nerve paralysis and the positive seroconversion of myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA). She was diagnosed with ANCA-associated vasculitis (AAV). Administration of corticosteroids significantly improved her symptoms, with a decline in the serum MPOANCA level. Ten months later than the initial presentation, she developed an AAV exacerbation with lung infiltration and pericardial effusion, which improved with high-dose corticosteroid therapy. To date, a limited number of AAV cases concomitant with pulmonary hypertension have been reported. The case report presented herein suggests a potential role for CTEPH in the development of AAV.

Effects of ivabradine on the prevention of intradialytic hypotension in a dialytic patient with heart failure with reduced ejection fraction.

A 65-year-old man with a history of heart failure with reduced ejection fraction (HFrEF) and renal failure was admitted due to difficulty in fluid volume control during haemodialysis. He had frequent episodes of intradialytic hypotension (IDH) with presyncope during haemodialysis despite using a vasopressor agent. Before haemodialysis, his blood pressure was 130-150/60-70 mm Hg, and his heart rate was 80-100 beats/min. There were no specific causes of IDH. For refractory IDH, he was treated with oral ivabradine (2.5 mg two times per day), which resulted in reduced heart rate and decreased occurrence of IDH. This is the first report to describe a dialysis case with HFrEF presenting with an elevated heart rate and impaired fluid management as manifested by recurring IDH, which improved after ivabradine treatment. Ivabradine therapy may assist in increasing stroke volume by lowering the sinus heart rate, thus resulting in the prevention of IDH.

Dynamic Changes in Coronary Flow Pattern During Transcatheter Aortic Valve Replacement in Severe Aortic Stenosis.

Coronary flow reserve in patients with severe aortic stenosis decreases even in the absence of coronary stenosis. In this case, the dynamic changes in the coronary flow pattern around transcatheter aortic valve replacement were observed by periprocedural transesophageal echocardiography. (Level of Difficulty: Intermediate.).

Impact of ivabradine in decompensated heart failure due to cancer therapy-related cardiac dysfunction.

In cases of decompensated heart failure related to cancer therapy-related cardiac dysfunction, ivabradine administration could lead to an increased stroke volume by reducing the sinus heart rate, resulting in favorable hemodynamics. Assessment of the overlap between the E- and A-waves facilitates understanding the effects of ivabradine in such cases.

Associations among plasma concentrations of regorafenib and its metabolites, adverse events, and ABCG2 polymorphisms in patients with metastatic colorectal cancers.

PURPOSE: The association between the pharmacokinetics and pharmacodynamics of regorafenib, a multiple tyrosine kinase inhibitor, remains unclear. This study assessed the trough plasma concentrations (Ctrough) of regorafenib and its N-oxide (M2) and N-oxide/desmethyl (M5) metabolites, and evaluated the associations among these levels, adverse events, and pharmacokinetic-related genetic polymorphisms in patients with metastatic colorectal cancer. METHODS: The Ctrough levels of regorafenib and its metabolites were assessed in a single-center, prospective, observational study, 7 days after the initial treatment. The correlation between those values and adverse events was then examined. In addition, the genetic polymorphisms of ABCG2, SLCO1B1, and UGT1A9 were determined and evaluated for associations with the levels of regorafenib, M2, and M5. RESULTS: We analyzed 43 patients who received regorafenib 40-120 mg/day; among them, 35 patients started at 120 mg/day. With regard to bilirubin increase, the Ctrough values of regorafenib were significantly higher in the group with grade ≥ 2 than in groups with grades 0 and 1 (p = 0.010). The M5 Ctrough levels were significantly associated with the severity of hypertension or rash (p < 0.05). In a multivariate analysis, the M5 Ctrough values and age were significant predictors of severe rash. Lastly, significant differences were noted in the M5 concentration-to-dose ratio values between the patients with ABCG2 421A/A and ABCG2 421C/A or C/C polymorphisms (p = 0.035). CONCLUSION: This study showed that the Ctrough of regorafenib was associated with bilirubin increase, and also clarified for the first time that the Ctrough of M5 was significantly correlated with hypertension and severe rash.

Impact of skeletal muscle mass on clinical outcomes in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Low skeletal muscle mass is one of the components of sarcopenia. However, the prognostic impact of skeletal muscle mass on clinical outcomes in patients after transcatheter aortic valve replacement (TAVR) remains unclear. Therefore, we assessed the impact of skeletal muscle mass on future cardiovascular events in patients undergoing TAVR. We enrolled 71 consecutive patients who underwent TAVR for symptomatic severe aortic stenosis. We applied bilateral psoas muscles as an indicator of skeletal muscle mass. Psoas muscle volumes were measured from the origin of psoas at the level of the lumbar vertebrae to its insertion in the lesser trochanter on three-dimensional computed tomography datasets. Psoas muscle mass index (PMI) was calculated as psoas muscle volume/height2 (cm3/m2). According to the median value of PMIs (79.8 and 60.0 cm3/m2 for men and women), the enrolled patients were divided into two groups. During the follow-up, 11 (31.4%) patients in low PMI group and 4 (11.1%) in high PMI group experienced major adverse cardiovascular events (MACE) defined as a composite of death from any cause, myocardial infarction, heart failure hospitalization, and stroke. The proportion of MACE-free survival was significantly lower in low PMI group (log-rank P = 0.033), mainly due to the difference of hospital readmission for congestive heart failure. On multivariate Cox proportional hazard analysis, PMI remained an independent negative predictor of MACE [hazard ratio 0.95 (95% confidence interval 0.92-0.98, P = 0.002)]. In conclusion, low skeletal muscle mass independently predicted MACE in patients undergoing TAVR.

Neural mechanisms of language learning from social contexts.

Humans learn languages in real-life situations by integrating multiple signals, including linguistic forms, their meanings, and the actions and intentions of speakers. However, little is known about the neural bases underlying the social learning of a second language (L2) in adults. In this study, 36 adults were asked to learn two sets of L2 spoken words through translation versus simulated social interactive videos (social learning). Brain activation during word learning was measured using fMRI. Greater activation was observed in the bilateral superior temporal sulcus, posterior middle temporal gyri, and right inferior parietal lobule during social learning as compared with translation learning. Furthermore, higher activity in the right temporal parietal junction, right hippocampus, and motor areas was observed during the initial stage of social learning, with the more successful performance being at the time of overnight testing. We argue that social learning may strengthen the link from new L2 forms to rich L2 semantic representations wherein memory properties are embodied, multimodal, and richly contextualized.

Visualization by P-flow: gradient- and feature-based optical flow and vector fields extracted from image analysis.

We proposed a method for extracting the optical flow suitable for visualization, pseudo-flow (P-flow), from a natural movie [Exp. Brain Res.237, 3321 (2019)EXBRAP0014-481910.1007/s00221-019-05674-0]. The P-flow algorithm comprises two stages: (1) extraction of a local motion vector field from two successive frames and (2) tracking of vectors between two successive frame pairs. In this study, we show that while P-flow takes a feature (vector) tracking approach, it is also classified as a gradient-based approach that satisfies the brightness constancy constraint. We also incorporate interpolation and a corner detector to address the shortcomings associated with the two approaches.

Axonal Projections from Middle Temporal Area to the Pulvinar in the Common Marmoset.

The pulvinar, the largest thalamic nucleus in the primate brain, has connections with a variety of cortical areas and is involved in many aspects of higher brain functions. Among cortico-pulvino-cortical systems, the connection between the middle temporal area (MT) and the pulvinar has been thought to contribute significantly to complex motion recognition. Recently, the common marmoset (Callithrix jacchus), has become a valuable model for a variety of neuroscience studies, including visual neuroscience and translational research of neurological and psychiatric disorders. However, information on projections from MT to the pulvinar in the marmoset brain is scant. We addressed this deficiency by injecting sensitive anterograde viral tracers into MT to examine the distribution of labeled terminations in the pulvinar. The injection sites were placed retinotopically according to visual field coordinates mapped by optical intrinsic imaging. All injections produced anterograde terminal labeling, which was densest in the medial nucleus of the inferior pulvinar (PIm), sparser in the central nucleus of the inferior pulvinar, and weakest in the lateral pulvinar. Within each subnucleus, terminations formed separate retinotopic fields. Most labeled terminals were small but these comingled with a few large terminals, distributed mainly in the dorsomedial part of the PIm. Our results further delineate the organization of projections from MT to the pulvinar in the marmoset as forming parallel complex networks, which may differentially contribute to motion processing. It is interesting that the densest projections from MT target the PIm, the subnucleus recently reported to preferentially receive direct retinal projections.