Two different types of tandem sequences mediate the overexpression of TinCYP51B in azole-resistant Trichophyton indotineae.

Trichophyton indotineae is an emerging dermatophyte that causes severe tinea corporis and tinea cruris. Numerous cases of terbinafine- and azole-recalcitrant T. indotineae-related dermatophytosis have been observed in India over the past decade, and cases are now being recorded worldwide. Whole genome sequencing of three azole-resistant strains revealed a variable number of repeats of a 2,404 base pair (bp) sequence encoding TinCYP51B in tandem specifically at the CYP51B locus position. However, many other resistant strains (itraconazole MIC ≥0.25 µg/mL; voriconazole MIC ≥0.25 µg/mL) did not contain such duplications. Whole-genome sequencing of three of these strains revealed a variable number of 7,374 bp tandem repeat blocks harboring TinCYP51B. Consequently, two types of T. indotineae azole-resistant strains were found to host TinCYP51B in tandem sequences (type I with 2,404 bp TinCYP51B blocks and type II with 7,374 bp TinCYP51B blocks). Using the CRISPR/Cas9 genome-editing tool, the copy number of TinCYP51B within the genome of types I and II strains was brought back to a single copy. The azole susceptibility of these modified strains was similar to that of strains without TinCYP51B duplication, showing that azole resistance in T. indotineae strains is mediated by one of two types of TinCYP51B amplification. Type II strains were prevalent among 32 resistant strains analyzed using a rapid and reliable PCR test.

Impact of Preoperative Nutritional Status on the Outcome of Catheter Ablation for Atrial Fibrillation.

BACKGROUND: The relationship between nutritional status and the incidence or prognosis of atrial fibrillation (AF) has been reported, but no studies have described the relationship between the outcomes of AF catheter ablation (CA) and nutritional status as assessed by various scoring tools. We aimed to verify the hypothesis that preoperative nutritional status is associated with arrhythmia recurrence after CA for AF.Methods and Results:We evaluated 913 patients (age, 67±10 years; men, 72%; paroxysmal AF, 56%) who underwent CA for AF between November 2011 and November 2017. Patients were systematically followed with an endpoint of atrial tachyarrhythmia recurrence, the predictive value of which was compared among 3 scoring tools (Controlling Nutritional Status [CONUT] score / Geriatric Nutritional Risk Index [GNRI] / Prognostic Nutritional Index [PNI]). Patients were divided into normal nutrition (CONUT <2 [n=637] / GNRI >98 [n=836] / PNI >38 [n=910]) and undernutrition (CONUT ≥2 [n=276] / GNRI ≤98 [n=77] / PNI ≤3 [n=3]) groups. AF recurred in 274 patients (mean follow-up, 2.3±0.8 years). The AF recurrence rate was higher in patients with undernutrition than in those with normal nutrition (CONUT/GNRI) status. Multivariate Cox regression analysis identified undernutrition status (GNRI ≤98) as an independent predictor of atrial tachyarrhythmia recurrence. CONCLUSIONS: The AF recurrence rate after CA was higher in patients with undernutrition than in those with normal nutrition as stratified by the nutrition scoring tools.

Prevalence and prognosis of isolated posterior ST-segment elevation acute myocardial infarction using synthesized-V7-9 lead.

Limited data exist on the prevalence and prognosis of isolated posterior ST-segment elevation acute myocardial infarction (STEMI), revealed with a posterior chest lead. Furthermore, the utility of a synthesized-V7-9 lead in the diagnosis of STEMI is unclear; therefore, we aimed to evaluate its usefulness. We enrolled 142 consecutive patients with STEMI with the culprit lesion on the left circumflex artery (STEMI-LCx) undergoing percutaneous coronary intervention (PCI) between January 2009 and December 2019. We retrospectively checked the ST-segment change of both standard 12-lead and synthesized-V7-9 lead in all patients with STEMI-LCx. Based on electrocardiogram (ECG) findings, isolated posterior STEMI that was only revealed in synthesized-V7-9 lead was classified as "STEMI-LCx-synV7-9" and the remaining as "STEMI-LCx-12ECG." The prevalence of STEMI-LCx-synV7-9 in patients with STEMI-LCx was assessed. The incidence of all-cause death, cardiac death, and mechanical complications within 30 days, 3 months, and 1 year was also assessed according to each STEMI-LCx. STEMI-LCx-synV7-9 and STEMI-LCx-12ECG occurred in 10 (7.0%) and 132 (93.0%) patients, respectively. No significant difference was found in patients' characteristics between the two groups. The patients with STEMI-LCx-synV7-9 had significantly higher incidences of cardiac death within 3 months and 1 year (30.0% vs. 6.1%, P = 0.031, 30.0% vs. 7.6%, P = 0.050, respectively) and mechanical complications in each follow-up period (20.0% vs. 1.5%, P = 0.025) than those with STEMI-LCx-12ECG. STEMI-LCx-synV7-9 was observed in 7.0% of the patients with STEMI-LCx. Our findings suggest that the synthesized-V7-9 lead helps diagnose isolated posterior STEMI and might improve prognosis in patients with STEMI-LCx.

Assessment of appropriate body mass index cut-off points for long-term mortality among ST-elevation myocardial infarction survivors in Asian population using machine learning algorithm.

Low body mass index (BMI) is a predictor of adverse events in patients with ST-elevated myocardial infarction (STEMI) in Western countries. Because the average BMI of Asians is significantly lower than that of the Western population, the appropriate cut-off BMI value and its role in long-term mortality are unclear in Asian patients. Between January 2006 and December 2017, 1215 patients who underwent percutaneous coronary intervention (PCI) for acute STEMI and were alive at discharge (mean age, 67.7 years; male, 75.4%) were evaluated. The cut-off BMI value, which could predict all-cause mortality within 10 years, was detected using a survival classification and regression tree (CART) model. The causes of death according to the BMI value were evaluated in each group. Based on the CART model, the patients were divided into three groups (BMI < 18 kg/m2: 54 patients, 18 kg/m2 ≤ BMI ≤ 20 kg/m2: 109 patients, and BMI > 20 kg/m2: 1052 patients). The BMI decreased with age; with an increased BMI, patients with dyslipidemia, diabetes mellitus, and smoking habit increased. During the study period (median, 4.9 years), 194 patients (26.8%) died (cardiac death, 59 patients; non-cardiac death, 135 patients). All-cause mortality was more frequent as the BMI decreased (BMI < 18 kg/m2; 72.8%, 18 kg/m2 ≤ BMI ≤ 20 kg/m2; 40.5%, and BMI > 20 kg/m2; 22.8%; log-rank p < 0.001). Non-cardiac deaths were more frequent than cardiac deaths in all groups, and the dominance of non-cardiac death was highest in the lowest BMI group. Cut-off BMI values of 18 kg/m2 and 20 kg/m2 can predict long-term mortality after PCI in Asian STEMI survivors, whose cut-off value is lower than that in the Western populations. The main causes of death in this cohort differed according to the BMI values.

Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan.

BACKGROUND: A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. METHODS: A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. RESULTS: Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. CONCLUSIONS: Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

Ten-Year Mortality in Patients With ST-Elevation Myocardial Infarction.

Knowledge of the long-term prognosis (>10 years) and mortality predictors of ST-elevation myocardial infarction (STEMI) patients who have undergone primary percutaneous coronary intervention (p-PCI) is scarce. Therefore, this study evaluated the long-term prognosis and determined the predictors of long-term outcomes for STEMI patients after p-PCI. Between January, 2006 and December, 2010, we collected data and analyzed 459 consecutive patients with acute STEMI who underwent p-PCI and were discharged from the hospital (mean age, 66.8 years; male, 75.2%; peak creatine phosphokinase level, 2,292.5 IU/L). The primary endpoint was 10-year all-cause mortality. The cumulative 10-year incidence of all-cause death was 23.8%. The Cox multivariate regression analysis identified age ≥ 65 years (adjusted hazard ratio [aHR], p <0.001), body mass index (aHR, 0.93, p = 0.033), presence of atrial fibrillation (aHR, 1.69, p = 0.038), mineralocorticoid receptor antagonist use (aHR, 1.95, p = 0.008), ejection fraction <40% (aHR, 2.14, p = 0.005), and albumin <3.5 g/dL (aHR, 2.01, p = 0.005) as independent predictors of all-cause mortality. In conclusion, a post-discharge 10-year survival rate of 76.2% was identified for STEMI patients who underwent p-PCI.

Catheter ablation for non-paroxysmal atrial fibrillation accompanied by heart failure with preserved ejection fraction: feasibility and benefits in functions and B-type natriuretic peptide.

AIMS: We aimed to examine the benefits of catheter ablation in patients with non-paroxysmal atrial fibrillation (AF) accompanied by heart failure (HF) with preserved ejection fraction (HFpEF), in comparison with the benefits in patients with AF accompanied by HF with reduced ejection fraction (HFrEF) or patients with no HF. METHODS AND RESULTS: From 1173 consecutive patients undergoing catheter ablation, 502 with non-paroxysmal AF were divided into three groups: no history of HF [plasma B-type natriuretic peptide (BNP) <100 pg/mL and no HF hospitalization; n = 125], HFpEF [left ventricular (LV) EF ≥50%; n = 293], and HF with midrange EF (HFmrEF) + HFrEF (LVEF <50%; n = 84) groups. The endpoints were AF recurrence at 1 year, changes in symptomatic and image-based functional status, and changes in BNP levels from baseline to 1 year. In the HFpEF group, AF recurred in 48 patients (16.4%) and 278 patients (94.8%) had sinus rhythm at 1 year; these values were comparable with those in the other groups. Significant improvement was observed in the left atrial diameter, LVEF, and New York Heart Association functional class in the HFpEF and HFmrEF + HFrEF groups. The BNP level significantly decreased irrespective of the index rate control status, and freedom from AF recurrence was an independent predictor of HF remission, defined as BNP <100 pg/mL at 1 year, in the HFpEF group. CONCLUSION: Catheter ablation is highly feasible for restoring sinus rhythm in non-paroxysmal AF with coexisting HFpEF, thereby improving cardiac function and BNP levels. Catheter ablation for AF may be an optional management strategy.

Bleeding events and mid-term mortality in the patients undergoing endovascular interventions for peripheral artery disease of the lower limbs based on the academic research consortium high bleeding risk criteria.

This study applied the Academic Research Consortium for HBR (ARC-HBR) criteria to peripheral artery disease (PAD) patients after Endovascular therapy (EVT) and assessed the prevalence of HBR, as well as the association between HBR and clinical outcomes. This is a single-center, non-randomized, controlled, and retrospective study. EVTs for symptomatic PAD are minimally invasive and efficient. Although bleeding can be a serious adverse event, the criteria for HBR and assessment of bleeding events in patients who underwent EVT have been limited. A total of 156 patients with PAD who underwent EVT were divided into two groups according to ARC-HBR criteria. The associations between HBR and bleeding events, which was defined as Bleeding Academic Research Consortium Type 3 or Type 5 bleeding within 1 year and all-cause mortality within 1 year, were analyzed. The percentage of patients who were categorized as having HBR was 75.0%. Bleeding events occurred in 12.6% of the patients. All bleeding events occurred in the HBR group, while no bleeding events occurred in the no-HBR group. (16.9% vs. 0.0%, respectively; p = 0.008). During the follow-up period, 11.1% of the patients had died. All-cause mortality was significantly higher in the HBR group than in the no-HBR group (14.7% vs. 0.0%, respectively; p = 0.019). Most patients with PAD were classified as having HBR as assessed by ARC-HBR criteria, and patients with HBR were at a higher risk of not only bleeding events but also mid-term mortality compared to those without HBR. ARC-HBR criteria can be a helpful parameter when treating PAD patients after EVT.

A comparative study between two antifungal agents, Luliconazole and Efinaconazole, of their preventive effects in a Trichophyton-infected guinea pig onychomycosis model.

An efficacious period of two topical antifungal drugs was compared in a Trichophyton mentagrophytes-infected onychomycosis model in guinea pigs treated with antifungal drugs prior to infection. Luliconazole 5% (LLCZ) and efinaconazole 10% (EFCZ) test solutions were applied to the animals' nails once daily for 2 weeks followed by a nontreatment period of 2, 4, and 8 weeks. After each nontreatment period, the nails were artificially infected by the fungus. Drug efficacy was quantitatively evaluated by qPCR and histopathological examination of the nails collected following a 4-week post-infection period. The fungal infection was confirmed in the untreated group. Both LLCZ and EFCZ prevented fungal infection in the treated groups with the nontreatment period of 2 weeks. After the nontreatment period of 4 weeks, no infection was observed in the LLCZ-treated group; however, infection into the nail surface and fungal invasion into the nail bed were observed in the EFCZ-treated group. After the nontreatment period of 8 weeks, fungi were found in the nail surface and nail bed in some nails treated with EFCZ; however, no infection was observed in the nail bed of the LLCZ-treated group. The results suggest that LLCZ possesses longer-lasting antifungal effect in nails of the guinea pigs than EFCZ, and that this animal model could be useful for translational research between preclinical and clinical studies to evaluate the pharmacological efficacy of antifungal drugs to treat onychomycosis. This experimentally shown longer-lasting preventive effects of LLCZ could also decrease the likelihoods of onychomycosis recurrence clinically.

The Mid-term Mortality and Mode of Death in Survivors with ST-elevation Myocardial Infarction.

Objective The popularity of primary percutaneous coronary intervention (p-PCI) for ST-elevation myocardial infarction (STEMI) has increased over the past decades. Despite improvements in in-hospital mortality rates, it is clinically important to investigate the prognoses after discharge. However, data on the mode of death and prognostic factors are limited. We analyzed these factors in a Japanese cohort in the modern p-PCI era. Methods Between January 2004 and December 2017, a total of 1,222 patients who underwent p-PCI within 24 hours from the onset of STEMI and were alive at discharge (mean age, 67.7 years old; men, 75.5%), were evaluated. The two-year mortality was analyzed using a Cox regression model, and the mode of death was evaluated. Results The rate of mortality at 2 years was 5.7%. Non-cardiac death was more frequent than cardiac death (62.6% vs. 37.4%). A Cox multivariate analysis identified the following as independent predictors of the 2-year mortality: hemoglobin (log-transformed) [adjusted hazard ratio (HR), 0.048; 95% confidence interval (CI), 0.008-0.29; p<0.001], age above 80 years old (adjusted HR, 2.26; 95% CI, 1.30-3.91; p=0.004), Killip class ≥II (adjusted HR, 1.99; 95% CI, 1.17-3.39; p=0.011), brain natriuretic peptide level (log-transformed) (adjusted HR, 1.47; 95% CI, 1.09-2.01; p=0.013), and body mass index (log-transformed) (adjusted HR, 0.16; 95% CI, 0.030-0.84; p=0.030). Conclusion This study demonstrated that the 2-year mortality was 5.7% in STEMI survivors after p-PCI. Non-cardiac death was more frequent than cardiac death. Compared to well-known clinical variables, angiographic findings did not have a significant influence on the mid-term mortality.

Myocardial salvage after ST-segment-elevation myocardial infarction: comparison between prasugrel and clopidogrel in the presence or absence of high-residual platelet reactivity.

BACKGROUND: The effect of prasugrel over clopidogrel on myocardial salvage in ST-segment-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (p-PCI) is not fully elucidated. METHODS: Among 854 consecutive STEMI patients who underwent p-PCI, 446 patients were evaluated by two-phase (7 days and 3 months) single-photo emission computed tomography (SPECT). Patients were divided into two groups based on the loading P2Y12 inhibitor. The clopidogrel group was further divided based on the result of platelet function testing. Thus, the prasugrel group included 227 patients; the clopidogrel without high-residual platelet reactivity (HRPR) group, 109 patients; and the clopidogrel with HRPR group, 107 patients. The primary endpoint was the Myocardial Salvage Index (MSI), determined by SPECT. RESULTS: The incidence of final TIMI 0/1 and TIMI myocardial perfusion grade 0/1 was higher in the clopidogrel with HRPR group (0.9%, 1.8%, and 7.5%, P =  .002; 19.8%, 29.4%, and 41.1%, P = .0002, in the prasugrel, clopidogrel without HRPR, and clopidogrel with HRPR groups, respectively). The MSI was significantly lower in the clopidogrel with HRPR group (48% [27-66], 44% [30-72], and 36% [15-55], P =  .006, respectively). CONCLUSIONS: Prasugrel in STEMI patients was associated with an increased MSI compared with clopidogrel in the presence of HRPR.

Quantitative comparison of the mRNA content of human iPSC-derived motor neurons and their extracellular vesicles.

Extracellular vesicles (EVs) contain various cargo molecules, including RNAs and proteins. EVs, which include exosomes, are predicted to be suitable surrogates of their source cells for liquid biopsy to measure biomarkers. Several studies have performed qualitative comparisons of cargo molecule repertoires between source cells and their EVs. However, quantitative comparisons have not been reported so far. Furthermore, many studies analyzed microRNAs or proteins in EVs, but not mRNAs. In this study, we analyzed mRNAs in motor neurons and their EVs. Normal human-induced pluripotent stem cells were differentiated into motor neurons, and comprehensive analysis of mRNAs in the cells and their EVs was performed by RNA sequencing. Differential analysis between cellular and EV mRNAs was performed by edgeR after normalization of read count. The results suggest that signatures in the abundance of EV mRNAs were different from those of cellular mRNAs. Comparison of intracellular vesicle and EV mRNA abundance showed negatively and positively biased genes in the EVs. Gene Ontology analysis revealed that the genes showing negatively biased abundance in the EVs were enriched in many functions regarding neuronal development. In contrast, the positively biased genes were enriched in functions regarding cellular metabolism and protein synthesis. These results suggest that mRNAs in motor neurons are loaded into EVs to regulate certain mechanisms, which are yet to be elucidated.

Synthetic mRNA-based differentiation method enables early detection of Parkinson's phenotypes in neurons derived from Gaucher disease-induced pluripotent stem cells.

Gaucher disease, the most prevalent metabolic storage disorder, is caused by mutations in the glucocerebrosidase gene GBA1, which lead to the accumulation of glucosylceramide (GlcCer) in affected cells. Gaucher disease type 1 (GD1), although defined as a nonneuronopathic subtype, is accompanied by an increased risk of Parkinson's disease. To gain insights into the association of progressive accumulation of GlcCer and the Parkinson's disease phenotypes, we generated dopaminergic (DA) neurons from induced pluripotent stem cells (iPSCs) derived from a GD1 patient and a healthy donor control, and measured GlcCer accumulation by liquid chromatography-mass spectrometry. We tested two DA neuron differentiation methods: a well-established method that mimics a step-wise developmental process from iPSCs to neural progenitor cells, and to DA neurons; and a synthetic mRNA-based method that overexpresses a transcription factor in iPSCs. GD1-specific accumulation of GlcCer was detected after 60 days of differentiation by the former method, whereas it was detected after only 10 days by the latter method. With this synthetic mRNA-based rapid differentiation method, we found that the metabolic defect in GD1 patient cells can be rescued by the overexpression of wild-type GBA1 or the treatment with an inhibitor for GlcCer synthesis. Furthermore, we detected the increased phosphorylation of α-synuclein, a biomarker for Parkinson's disease, in DA neurons derived from a GD1 patient, which was significantly decreased by the overexpression of wild-type GBA1. These results suggest that synthetic mRNA-based method accelerates the analyses of the pathological mechanisms of Parkinson's disease in GD1 patients and possibly facilitates drug discovery processes.

Development of a novel fungicide, pyraziflumid.

Pyraziflumid is a novel succinate dehydrogenase inhibitor (SDHI) fungicide discovered and developed by Nihon Nohyaku Co., Ltd. It exhibits excellent fungicidal activities against a broad range of plant diseases and has a favorable safety profile for the Integrated Pest Management (IPM) program. This compound was found by researching the unique chemical derivatives, 3-(trifluoromethyl)pyrazine-2-carboxamides, and has good biological properties, such as preventive, residual and curative activity, and rain-fastness. Pyraziflumid was registered and launched in Japan in 2018. It was registered in South Korea in 2018 and is now under development in other countries. This paper describes the discovery, synthesis, biological activity, safety profile and mode of action of pyraziflumid.

Predicting long-term freedom from atrial fibrillation after catheter ablation by a machine learning algorithm: Validation of the CAAP-AF score.

BACKGROUND: Preprocedural clinical predictors of the successful maintenance of sinus rhythm may contribute to optimal treatment strategies for atrial fibrillation (AF). The CAAP-AF score, a novel simple tool scored as 0-13 points (including six independent variables) has been proposed to predict long-term freedom from AF after catheter ablation. To clarify its reproducibility, we examined the CAAP-AF score's predictive performance and then created subgroups to best predict AF recurrence by using a machine learning algorithm. METHODS: We studied 583 consecutive patients who underwent initial AF catheter ablation at our institute (median CAAP-AF score, 5; age, 66 ± 10 years old; female, 28.3%; coronary artery disease, 10.8%; left atrial diameter, 39.9 ± 6.6 mm; number of antiarrhythmic drugs failed, 0.4 ± 0.6; nonparoxysmal AF, 45.3%). All were systematically followed up with an endpoint of atrial tachyarrhythmia recurrence after the last ablation procedure. RESULTS: During the 1.8 ± 1.2-year follow-up, 157 patients had atrial tachyarrhythmia recurrence. Repeated procedures were performed (n = 115). Arrhythmia recurrence after the last session occurred in 69 patients. We created Kaplan-Meier curves for freedom from AF after final AF ablation for ranges of CAAP-AF scores; these confirmed the original study results. The machine learning using Classification and Regression Trees divided the patients into three categories by the risk score: low (score ≤5), intermediate (score 6-8), and high (score ≥9). CONCLUSIONS: The CAAP-AF score was useful to stratify the atrial tachyarrhythmia recurrence risk in AF patients undergoing catheter ablation into three categories. The score should be considered when deciding whether to perform AF ablation in clinical practice.

Usefulness of excimer laser in acute coronary syndrome with left main coronary artery: a case series.

BACKGROUND: Acute coronary syndrome caused by unprotected left main coronary artery (ACS-ULMCA) occlusion has a high mortality due to the formation of plaques and rich thrombi. Although excimer laser coronary angioplasty (ELCA) is effective in debulking and ablation of plaque burden and rich thrombi, its effectiveness in ACS-ULMCA remains unknown. CASE SUMMARY: We conducted percutaneous coronary intervention (PCI) using ELCA for six patients with ACS-ULMCA from February 2016 to May 2019. This case series includes a 65-year-old man who presented with sudden-onset chest pain. Angiography revealed subtotal occlusion of the left main coronary artery (LMCA). The use of a 0.9-mm ELCA catheter advanced from LMCA to the left anterior descending artery markedly improved coronary blood flow, and intravascular ultrasound revealed debulking of the plaque and thrombus. Another 79-year-old man presented with chest pain. Angiography revealed total occlusion of LMCA. Use of a 0.9-mm ELCA catheter improved coronary blood flow. Subsequent kissing balloon technique led to satisfactory results. All cases needed mechanical support (such as intra-aortic balloon pumping or percutaneous cardiopulmonary support) prior to PCI. Five patients survived finally, and one died 34 days after primary PCI. DISCUSSION: After stabilizing haemodynamics by mechanical support, ELCA could be a good option to improve coronary blood flow in patients with ACS-ULMCA.

The impact of the excimer laser on myocardial salvage in ST-elevation acute myocardial infarction via nuclear scintigraphy.

Data on the efficacy of excimer laser coronary atherectomy (ELCA) for patients with ST-elevation myocardial infarction (STEMI) are limited. Therefore, we sought to evaluate the impact of ELCA on myocardial salvage using nuclear scintigraphy in patients with STEMI. Between September 2014 and April 2017, we retrospectively enrolled 316 consecutive patients undergoing primary PCI (p-PCI) after their first STEMI in our institute. Of those, 72 patients with STEMI, an initial thrombolysis in myocardial infarction (TIMI) flow-0/1, and an onset to balloon time (OBT) < 6 h were included (ELCA, n = 32; non-ELCA, n = 40). The endpoint was the myocardial salvage index (MSI) based on a 17-segment model with a 5-point scoring system. MSI was calculated as: MSI = (∑123I-BMIPP defect score at 3-7 days after p-PCI - ∑99mTc-tetrofosmin defect score at 3-6 months after p-PCI)/∑123I-BMIPP defect score × 100 (%) at 3-7 days after p-PCI. The groups were compatible except in age (ELCA: 62.9 ± 12.4 years vs. non-ELCA: 69.8 ± 11.0 years) and loading antiplatelet drug (prasugrel: 100% vs. 40.0%). Direct implantation of shorter stents more frequently occurred in the ELCA group than in the non-ELCA group. MSI seemed to be better in the ELCA group compared with the non-ELCA group (57.6% vs. 45.6%, p = 0.09). This trend was emphasized when the final TIMI-3 flow was achieved (67.1% vs. 45.7%, p = 0.01). The nuclear scintigraphy results showed that ELCA can potentially improve myocardial salvage in patients with STEMI with OBT < 6 h and initial TIMI flow-0/1.

Comparative Incidences and Biological Outcomes for Thymoma in Various Rat Strains in National Toxicology Program Studies.

Thymomas from 277 Fischer 344/N (F344/N), 10 Sprague Dawley (HSD:Sprague Dawley SD) (SD), 129 Wistar Han [Crl:WI(Han)] (WH), and 4 Wistar Outbred (WO) rats were reviewed from long-term studies in the National Toxicology Program (NTP) database. The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males. Only male WO rats were used in NTP studies. Of the 277 thymomas in F344/N rats, 235 (84.8%) were benign and 42 (15.2%) malignant, 14 of which exhibited metastasis. Of the 10 thymomas in SD rats, 5 (50%) were benign and 5 (50%) were malignant, one of which exhibited metastasis. Of the 129 thymomas in WH rats, 126 (98%) were benign and 3 (2%) were malignant, 1 with metastasis. Of the 4 thymomas in WO rats, 3 (75%) were benign and 1 (25%) was malignant, with no metastases. Malignant thymomas in F344/N and WH rats showed a propensity to be the cause of death and to result in early mortality, whereas the benign thymomas were associated less often with decreased survival. No occurrences of this neoplasm were reported to be related to exposure to any test articles.

Impact of the clinical frailty scale on mid-term mortality in patients with ST-elevated myocardial infarction.

BACKGROUND: "Frailty" is associated with poor prognosis in ST-elevated myocardial infarction (STEMI). However, there is little data regarding the impact of the Canadian Study of Health and Aging Clinical Frailty Scale (CFS), a simple and semiquantitative tool for assessing frailty, on mid-term mortality in STEMI patients. METHODS: A total of 354 consecutive STEMI patients (mean age 69.8 ±â€¯12.4 years; male 76.6%) who underwent percutaneous intervention between July 2014 and March 2017 were retrospectively reviewed. The study endpoint was mid-term mortality according to the CFS classification. Furthermore, in order to clarify the impact of CFS upon admission on mid-term mortality, the independent predictors of all-cause death were evaluated. RESULTS: Patients were categorized into three groups (CFS 1-3, n = 281; CFS 4-5, n = 62; and CFS 6-7, n = 11). During the study period (median 474 days), all-cause death was observed in 39 patients. After multivariate Cox regression analysis, higher CFS (adjusted hazard ratio [HR] 2.34, 95% confidence interval [CI] 1.43-3.85, p < 0.001), higher Killip score (adjusted HR 2.46, 95%CI 1.30-5.78, p = 0.002), and lower serum albumin level (adjusted HR 4.29, 95%CI 2.16-8.51, p < 0.001) were significantly associated with an increased risk of all-cause death. CONCLUSION: In conclusion, severe frailty was associated with mid-term mortality in STEMI patients who underwent PCI.

The Early Initiation of Extracorporeal Life Support May Improve the Neurological Outcome in Adults with Cardiac Arrest due to Cardiac Events.

Objective Extracorporeal life support (ECLS) is effective for improving the survival rate of patients with refractory cardiac arrest (rCA). As little data are available regarding the impact of ECLS on a favorable neurological outcome, the predictors of a favorable neurological outcome were evaluated in this study. Methods Between January 2007 and August 2016, we retrospectively recruited patients with rCA caused by cardiac events treated with ECLS in our institute. A favorable neurological outcome was defined as a Glasgow-Pittsburgh cerebral performance category score 1 at discharge. The study endpoint was the clinical outcomes and predictors of favorable neurologic patients at discharge. Results During the study period, 67 patients with CA caused by cardiac events (acute coronary syndrome, 57 patients; idiopathic ventricular fibrillation, 10 patients) were included. Of these, 20 patients (29.9%) were classified into the favorable neurological group. No marked difference was observed in the patient characteristics between those with and without a favorable outcome except for in the time from CA to starting ECLS (ECLS initiation time). A short ECLS initiation time resulted in a favorable outcome (37.8±28.1 minutes vs. 53.6±30.7 minutes, p=0.05). The cut-off time of ECLS initiation was 46 minutes, which was prolonged by the temporary return of spontaneous circulation before ECLS [odds ratio (OR), 3.69; 95% confidence interval (CI), 1.34-10.19; p=0.01] and transfer to the angiographic room (OR, 4.07; 95% CI, 1.44-11.53, p=0.008). Conclusion The early initiation of ECLS (within 46 minutes) might be associated with a favorable neurological outcome for patients with rCA caused by cardiac events.