Effects of hybrid emergency department on extracorporeal cardiopulmonary resuscitation in out-of-hospital cardiac arrest patients.

Background: Hybrid emergency department (ED), which are equipped with fluoroscopy and computed tomography has been developed in Japan as a novel emergency care room. Although hybrid ED is effective in improving the outcomes of severe trauma, its influence on the management of out-of-hospital cardiac arrest (OHCA) requiring extracorporeal cardiopulmonary resuscitation (ECPR) remains unclear. Objectives: The aim of this study was to elucidate the impact of hybrid ED on ECPR procedures and outcome in OHCA patients focusing on time from hospital arrival to establishment of ECPR. Methods: A retrospective single-center cohort study was conducted, including adult OHCA patients who underwent ECPR between April 2013 and March 2022. Patients treated in conventional ED were compared with those in hybrid ED. Primary outcome was time from hospital arrival to ECPR initiation. Secondary outcomes included favorable neurological outcome at 30 days and incidence of cannulation-related adverse events. Results: Hybrid ED installation led to a significant decrease in time to ECPR initiation. In the interpreted time series analysis for the time from hospital arrival to establishment ECPR, there was statistically significant upward level change and downward trend change after the installation of hybrid ED. These results mean the time from hospital arrival to the establishment of ECPR was prolonged just after installation of hybrid ER, and the time from hospital arrival to the establishment of ECPR was shortened over time. There were no statistically significant differences between the conventional and hybrid ED groups on the favorable neurological outcome and cannulation-related adverse events. Conclusions: The installation of hybrid ED was associated with shortened time from hospital arrival to establishment of ECPR. Further evaluation is needed to elucidate the effects of hybrid ED on OHCA and determine an optimal strategy.

Clinical Features and Treatment Outcomes in Patients in Their Twenties with Ischemic Moyamoya Disease.

INTRODUCTION: Revascularization surgery is recommended for all pediatric patients with moyamoya disease (MMD) with ischemic symptoms because the brains of such patients are still developing. By contrast, no clear guidelines for selective revascularization surgery in adult patients (30 years or more) with ischemic presentation have been established. Regarding the age of initial onset of ischemic MMD, patients in their 20s are at the bottom of the distribution and this age group may share features with both adult and pediatric patients. The present prospective study aimed to clarify the clinical features and treatment outcomes of patients in their 20s (younger patients) with ischemic MMD compared with patients aged 30-60 years (older patients). METHODS: While patients with misery perfusion in the symptomatic cerebral hemisphere on 15O-positron emission tomography underwent combined surgery including direct and indirect revascularizations in the first study period and indirect revascularization alone in the second study period, patients without misery perfusion in that hemisphere received pharmacotherapy alone through the two study periods. Cerebral angiography via arterial catheterization and neuropsychological testing were performed before and after surgery. RESULTS: During 12 years, 12 younger patients were included and comprised 6% of all adult patients (194 patients). The incidence of misery perfusion in the affected hemisphere was significantly higher in younger (12/12 [100%]) than in older patients (57/182 [31%]) (p < 0.0001). No difference in the incidence of cerebral hyperperfusion syndrome and postoperatively declined cognition was seen between younger (2/5 [40%] and 2/5 [40%], respectively) and older (11/36 [31%] and 15/36 [42%], respectively) cerebral hemispheres undergoing combined revascularization surgery. No difference in the incidence of postoperatively formed collateral flows feeding more than one-third of the middle cerebral artery cortical territory on angiograms and postoperatively improved cognition was seen between younger (9/10 [90%] and 6/10 [60%], respectively) and older (18/22 [83%] and 14/22 [64%], respectively) cerebral hemispheres undergoing indirect revascularization surgery alone. CONCLUSION: Patients in their 20s with ischemic MMD always exhibit misery perfusion in the affected hemisphere, unlike older patients, and sometimes develop cerebral hyperperfusion syndrome after combined revascularization surgery, leading to cognitive decline, similar to older patients. Moreover, indirect revascularization surgery alone forms sufficient collateral circulation and restores cognitive function in patients in their 20s, similar to older patients.

Impact of postoperative cerebral hyperperfusion on 2-year cognitive outcomes of patients undergoing carotid endarterectomy.

OBJECTIVE: In 10% of patients undergoing carotid endarterectomy (CEA), the cognitive function declines postoperatively, primarily in association with postoperative cerebral hyperperfusion. In contrast, in the majority of patients undergoing CEA, long-term cognitive outcomes remain unclear. Furthermore, it is not known whether the decline in cognition due to cerebral hyperperfusion recovers on a long-term basis. This study aimed to understand how postoperative cerebral hyperperfusion affects the cognitive outcomes of patients who undergo CEA. METHODS: The participants in this prospective observational study were patients with internal carotid artery stenosis who underwent CEA. Cerebral hyperperfusion syndrome or asymptomatic cerebral hyperperfusion following CEA was determined based on brain perfusion SPECT scans and symptomatology before and after surgery. Neuropsychological testing was performed preoperatively, at 1-2 months postoperatively, and at 2 years postoperatively to investigate cognitive decline. RESULTS: A logistic regression analysis revealed that asymptomatic cerebral hyperperfusion (95% CI 13.0-84.5, p < 0.0001) and cerebral hyperperfusion syndrome (95% CI 449.7-14,237.4, p < 0.0001) were significantly associated with cognitive decline at 1-2 months postoperatively. The incidence of cognitive decline was significantly decreased at 2 years postoperatively (7%) in comparison to 1-2 months postoperatively (11%) (p = 0.0461). A logistic regression analysis also revealed that asymptomatic cerebral hyperperfusion (95% CI 3.7-36.7, p < 0.0001), cerebral hyperperfusion syndrome (95% CI 128.0-6183.6, p < 0.0001), and further strokes during the 2-year follow-up period (95% CI 1.5-78.7, p = 0.0167) were significantly associated with cognitive decline at 2 years postoperatively. The incidence of cognitive decline at 1-2 months postoperatively was significantly higher in patients with cerebral hyperperfusion syndrome (100%) than in those with asymptomatic cerebral hyperperfusion (44%) (p < 0.0001). No significant difference in incidence was observed in the former patients at 2 years postoperatively (88%), but significant reduction was found in patients with asymptomatic cerebral hyperperfusion and cognitive decline between the timepoints of 1-2 months postoperatively (100%) and 2 years postoperatively (39%) (p = 0.0001). CONCLUSIONS: Postoperative cerebral hyperperfusion causes prolonged cognitive decline at 2 years postoperatively in patients undergoing CEA.

Evaluating bio-physicochemical properties of raw powder prepared from whole larvae containing liquid silk of the domestic silkworm.

The domestic silkworm, Bombyx mori, has been widely used in silk production for centuries. It is also used as a bioreactor by the textile and pharmaceutical industries to mass produce recombinant bioactive proteins containing silk-based materials. Furthermore, silkworms are well-known as a source of food and have also been orally administered to prevent and treat several human disorders. In this study, we aimed to investigate the inherent bio-physicochemical properties of edible silkworms to accurately evaluate their clinical and nutritional potential. We prepared raw powder from whole larvae of silkworm. The yield rate of the powder derived from dried larvae was almost 100% (98.1-99.1% in replicates). As "percentage yield" translates to "Budomari" in Japanese, this raw powder was named "B100rw." We further prepared B100dn that was denatured through autoclaving. Thereafter, we examined whether B100rw sustained the original bio-physicochemical properties by comparing it with B100dn. There was no significant difference in nutritional content between B100rw and B100dn. B100rw contained proteins derived from silkworm larvae and mulberry leaves, whereas the proteins of B100dn were mostly degraded. On measuring the enzymatic activity of both powders using trehalase as an indicator enzyme, B100rw was found to maintain trehalase activity. B100rw also maintained a random coil conformation, similar to that of liquid silk. This suggested that B100rw sustained the unique bio-physicochemical properties of living larvae. These findings may facilitate the development of novel food products or orally administered vaccines.

The reliability and validity of a developed anxiety scale specific to primary focal hyperhidrosis symptoms.

BACKGROUND: Patients with primary focal hyperhidrosis (hyperhidrosis) are known to have higher levels of anxiety induced by sweating than those who do not. However, in hyperhidrosis, no scale has been developed to measure anxiety specific to hyperhidrosis symptoms. Therefore, this study aimed to develop an anxiety scale specific to hyperhidrosis symptoms (ASSHS) and to verify its reliability and validity. METHODS: Based on previous studies on hyperhidrosis and a preliminary survey conducted with 26 university students who met the diagnostic criteria for hyperhidrosis, 40 items that adequately reflected anxiety specific to hyperhidrosis symptoms were obtained. A survey was done to examine the internal consistency and validity of the our developed ASSHS. In total, 1,207 participants (680 male and 527 female; mean age ± standard deviation 18.7 ± 0.9 years) were included. A second survey (re-survey) was conducted three weeks later to verify the reliability. It included 201 participants (85 male and 116 female; mean age ± standard deviation 18.6 ± 0.7 years). The survey items included (1) the diagnostic criteria for hyperhidrosis, (2) our anxiety scale developed for primary focal hyperhidrosis symptoms (ASSHS), (3) Hyperhidrosis Disease Severity Scale (HDSS), (4) State-Trait Anxiety Inventory (STAI), (5) Hospital Anxiety and Depression Scale (HADS), (6) Dermatology Life Quality Index (DLQI), and (7) presence of anxiety induced by sweating. RESULTS: The results of the factor analysis revealed 10 items with one factor, "anxiety specific to hyperhidrosis symptoms." The alpha coefficient of the ASSHS was α = 0.94. The correlation coefficient between the scores at re-test was r = 0.75. A moderate positive correlation was found between the ASSHS, HDSS (r = 0.53), and anxiety induced by sweating (r = 0.47) (all p < 0.001). Additionally, participants with hyperhidrosis symptoms had significantly higher ASSHS scores than did those without hyperhidrosis symptoms (p < 0.001). Those with mild/moderate hyperhidrosis and those with severe hyperhidrosis had significantly higher the ASSHS scores than did those without hyperhidrosis (p < 0.001). CONCLUSIONS: This scale has sufficient reliability and validity as an instrument to measure anxiety specific to hyperhidrosis symptoms.

Diagnostic Accuracy of Preoperative Quantitative Susceptibility Mapping for Detecting Histologic Intraplaque Hemorrhage in Cervical ICA Stenosis in Patients Undergoing Carotid Endarterectomy.

BACKGROUND AND PURPOSE: Quantitative susceptibility mapping has been proposed to assess intraplaque hemorrhage (IPH) in the carotid artery. The purpose of this study was to compare the diagnostic accuracy of preoperative quantitative susceptibility mapping with that of the conventional T1-weighed 3D-FSE sequence for detecting IPH in cervical ICA stenosis in patients undergoing carotid endarterectomy by using histology as the reference standard. MATERIALS AND METHODS: Carotid T1-weighted 3D-FSE and QSM images were obtained from 16 patients with cervical ICA stenosis before carotid endarterectomy. Relative signal intensity and susceptibility of the ICA were measured on 3 axial images, including the location of most severe stenosis on T1-weighted 3D-FSE and quantitative susceptibility mapping images, respectively. Three transverse sections of carotid plaques excised by carotid endarterectomy, which corresponded with images on MR imaging, were stained with H&E, antibody against glycophorin A, and Prussian blue, and the relative area of histologic IPH was calculated. RESULTS: The correlation coefficient was significantly greater between susceptibility and relative area-histologic IPH (ρ = 0.691) than between relative signal intensity and relative area-histologic IPH (ρ = 0.413; P = .0259). The areas under the receiver operating characteristic curves for detecting histologic sections consisting primarily of IPH (relative area-histologic IPH > 40.7%) tended to be greater for susceptibility (0.964) than for T1WI FSE-relative signal intensity (0.811). Marginal homogeneity was observed between susceptibility and histologic sections consisting primarily of IPH (P = .0412), but not between T1-weighted FSE-relative signal intensity and histologic sections consisting primarily of IPH (P = .1824). CONCLUSIONS: Pre-carotid endarterectomy quantitative susceptibility mapping detects histologic IPH in cervical ICA stenosis more accurately than preoperative T1-weighted 3D-FSE imaging.

Chemoenzymatic tandem cyclization for the facile synthesis of bicyclic peptides.

Bicyclic peptides exhibit improved metabolic stabilities and target specificities when compared to their linear or mono-cyclic counterparts; however, efficient and straightforward synthesis remains challenging due to their intricate architectures. Here, we present a highly selective and operationally simple one-pot chemoenzymatic tandem cyclization approach to synthesize bicyclic peptides with small to medium ring sizes. Penicillin-binding protein-type thioesterases (PBP-type TEs) efficiently cyclized azide/alkyne-containing peptides in a head-to-tail manner. Successive copper (I)-catalyzed azide-alkyne cycloaddition generated bicyclic peptides in one-pot, thus omitting the purification of monocyclic intermediates. This chemoenzymatic strategy enabled the facile synthesis of bicyclic peptides bearing hexa-, octa-, and undecapeptidyl head-to-tail cyclic scaffolds.

Metaheuristic aided structural topology optimization method for heat sink design with low electromagnetic interference.

This study investigates the application of the Metaheuristic Aided Structural Topology Optimization (MASTO) method as a novel approach to address the multiphysics design challenge of creating a heat sink with both high heat conductivity and minimal Electromagnetic Interference (EMI). A distinctive 2D layout with elongated fins is examined for electromagnetic traits, highlighting resonance-related EMI concerns. MASTO proves to be a valuable tool for navigating the complex design space, yielding thoughtfully optimized solutions that harmonize efficient heat dissipation with effective EMI control. By merging simulation findings with practical observations, this study underscores the potential of the MASTO method in achieving effective designs for intricate multiphysics optimization problems. Specifically, the method's capacity to address the complex interplay of heat transfer with convection and the suppression of electromagnetic emissions is showcased. Moreover, the study demonstrates the feasibility of translating these solutions into tangible outcomes through manufacturing processes.

Association between preoperative cortical magnetic susceptibility and postoperative changes in the cerebral blood flow on cognitive improvement following carotid endarterectomy.

INTRODUCTION: While patients who experience improved cognition following carotid endarterectomy (CEA) typically demonstrate restored brain perfusion after the procedure, it is worth noting that less than 50% of patients in whom postoperative cerebral blood flow (CBF) restoration is achieved actually show improved cognition after postoperatively. This suggests that factors beyond the mere restoration of CBF may play a role in postoperative cognitive improvement. Increased iron deposition in the cerebral cortex may cause neural damage, and quantitative susceptibility mapping (QSM) obtained using magnetic resonance imaging (MRI) quantifies magnetic susceptibility in the cerebral cortex, allowing for the assessment of iron deposition in vivo. The purpose of the present study was to determine whether preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA. METHODS: Brain MRI with a three-dimensional gradient echo sequence was preoperatively performed in 53 patients undergoing CEA for ipsilateral internal carotid artery stenosis (≥70%), and QSM with brain surface correction and vein removal was obtained. Cortical magnetic susceptibility was measured in the cerebral hemisphere ipsilateral to surgery on QSM. Preoperatively and at two months after the surgery, brain perfusion single-photon emission computed tomography (SPECT) and neuropsychological assessments were conducted. Using these collected data, we evaluated alterations in CBF within the affected hemisphere and assessed cognitive improvements following the operation. RESULTS: A logistic regression analysis showed that a postoperative greater increase in CBF (95% confidence interval [CI], 1.06-1.90; p = 0.0186) and preoperative lower cortical magnetic susceptibility (95% CI, 0.03-0.74; p = 0.0201) were significantly associated with postoperatively improved cognition. Although sensitivity, specificity, and positive- and negative-predictive values with the cutoff value lying closest to the upper left corner of a receiver operating characteristic curve for the prediction of postoperatively improved cognition did not differ between postoperative changes in CBF and preoperative cortical magnetic susceptibility, the specificity and the positive-predictive value were significantly greater for the combination of postoperative changes in CBF and preoperative cortical magnetic susceptibility (specificity, 95% CI, 93-100%; positive-predictive value 95% CI, 68-100%) than for the former parameter alone (specificity, 95% CI, 63-88%; positive-predictive value 95% CI, 20-64%). CONCLUSION: Preoperative cortical magnetic susceptibility as well as postoperative changes in CBF are associated with cognitive improvement after CEA.

Correction: Arimori et al. Association between Lifestyle Factors and Weight Gain among University Students in Japan during COVID-19 Mild Lockdown: A Quantitative Study. Healthcare 2023, 11, 2630.

In our published publication [...].

Association between preoperative white matter hyperintensities and postoperative new ischemic lesions on magnetic resonance imaging in patients with cognitive decline after carotid endarterectomy.

Although cognitive decline after carotid endarterectomy (CEA) is mainly related to postoperative cerebral hyperperfusion, approximately 30% of patients with cognitive decline do not have postoperative cerebral hyperperfusion. In patients with acute ischemic events, the development of cognitive decline after such events is associated with the presence of chronic cerebral white matter hyperintensities (WMHs). The present prospective observational study aimed to determine whether preoperative WMHs and postoperative new ischemic lesions (PNILs) are associated with cognitive decline after CEA in patients without cerebral hyperperfusion after CEA. Brain magnetic resonance imaging (MRI) was performed preoperatively, and WMHs were graded according to the Fazekas scale in patients undergoing CEA for severe stenosis of the ipsilateral internal carotid. Diffusion-weighted MRI was performed before and after CEA to determine the development of PNILs. Neuropsychological testing was performed preoperatively and at 2 months postoperatively to determine the development of postoperative cognitive decline (PCD). In 142 patients without postoperative cerebral hyperperfusion, logistic regression analysis revealed that preoperative Fazekas scale of periventricular WMHs (PVWMHs) (95% confidence interval [CI]: 1.78-28.10; P = 0.0055) and PNILs in the eloquent areas (95% CI: 7.42-571.89; P = 0.0002) were significantly associated with PCD. The specificity and positive-predictive value for the prediction of PCD were significantly greater for the combination of preoperative Fazekas scale 2 or 3 of PVWMHs and PNILs in the eloquent areas than for each individually. Preoperative PVWMHs, PNILs in the eloquent areas, and the combination of both were associated with PCD in patients without cerebral hyperperfusion after CEA.

Embrittlement Fracture Behavior and Mechanical Properties in Heat-Affected Zone of Welded Maraging Steel.

In welded maraging steels, mechanical properties, particularly ductility and toughness, are often compromised in the heat-affected zone (HAZ). This study focuses on 300-grade maraging steel bars, solution annealed at 1123 K for 1.5 h (5.4 ks) and welded using gas tungsten arc welding, followed by a post-weld heat treatment at 753 K for 13.33 h (48 ks). In situ observations during three-point bending tests on HAZ samples featuring coarsened prior austenite grain sizes were conducted to examine damage behavior and the crack path near the crack tip. The main crack initiated at the peak applied load during the bending test and, upon further loading, exhibited significant deflection and extension accompanied by numerous microcracks and localized crack branching. Distinctive damage features, such as transgranular cracking across block regions, intense intergranular cracking along packet boundaries with a pronounced shear component, and crowding of microcracks ahead of the crack tip, were observed in the HAZ sample during the in situ test. The interaction between the main crack tip and microcracks and its influence on the local crack propagation driving force was discussed using fracture mechanics. Experimental results, including tensile fracture surface observations and in situ images, along with analysis of the stress anti-shielding effect by microcracks, suggest that the HAZ sample exhibits embrittlement fracture behavior with lower ductility and toughness compared to the base metal sample.

Low-flow time and outcomes in out-of-hospital cardiac arrest patients treated with extracorporeal cardiopulmonary resuscitation.

INTRODUCTION: In out-of-hospital cardiac arrest (OHCA) patients with extracorporeal cardiopulmonary resuscitation (ECPR), the association between low-flow time, the duration between the initiation of conventional cardiopulmonary resuscitation and the establishment of ECPR, and outcomes has not been clearly determined. METHODS: This was a secondary analysis of the retrospective multicenter registry in Japan. This study registered patients ≥18 years old who were admitted to the emergency department for OHCA and underwent ECPR between January, 2013 and December, 2018. Low-flow time was defined as the time from initiation of conventional cardiopulmonary resuscitation to the establishment of ECPR, and patients were categorized into two groups according to the visualized association of the restricted cubic spline curve. The primary outcome was survival discharge. Cubic spline analyses and multivariable logistic regression analyses were performed to assess the nonlinear associations between low-flow time and outcomes. RESULTS: A total of 1,524 patients were included. The median age was 60 years, and the median low-flow time was 52 (42-53) mins. The overall survival at hospital discharge and favorable neurological outcomes were 27.8% and 14.2%, respectively. The cubic spline analysis showed a decreased trend of survival discharge rates and favorable neurological outcomes with shorter low-flow time between 20 and 60 mins, with little change between the following 60 and 80 mins. The multivariable logistic regression analyses showed that patients with long low-flow time (>40 mins) compared to those with short low-flow time (0-40 mins) had significantly worse survival (adjusted odds ratio 0.42; 95% confidence intervals, 0.31-0.57) and neurological outcomes (0.65; 0.45-0.95, respectively). CONCLUSIONS: The survival discharge and neurological outcomes of patients with low-flow time shorter than 40 min are better than those of patients with longer low-flow time.

Association between Lifestyle Factors and Weight Gain among University Students in Japan during COVID-19 Mild Lockdown: A Quantitative Study.

We aimed to investigate the lifestyle factors influencing weight gain among university students in Japan during the mild lockdown imposed due to the novel coronavirus disease pandemic. In this cross-sectional study, we conducted a questionnaire survey of students who underwent health examinations at Nagasaki University in 2021. Students reporting a weight gain of ≥3 kg were included in the weight gain group; the remaining students were included in the non-weight-gain group. Fisher's exact test and binary logistic regression were performed to determine the association between weight gain and each lifestyle factor. We included 3059 respondents (response rate: 45.7%), and 9.5% of them reported a weight gain of ≥3 kg. The following factors were associated with weight gain (odds ratio (95% confidence interval), p value based on Fisher's exact test): dining out for four times or more/week (2.16 (1.40, 3.32), p = 8.7 × 10-4) and gaming time of ≥4 h/day (2.26 (1.45, 3.47), p = 2.4 × 10-4). Binary logistic regression among the four highest odds ratios revealed that after adjusting for other factors, frequent dining out and prolonged gaming time were significantly associated with weight gain in students during the mild lockdown.

Characterization of Information-Transmitting Materials Produced in Ionic Liquid-based Neuromorphic Electrochemical Devices for Physical Reservoir Computing.

Device implementation of reservoir computing, which is expected to enable high-performance data processing in simple neural networks at a low computational cost, is an important technology to accelerate the use of artificial intelligence in the real-world edge computing domain. Here, we propose an ionic liquid-based physical reservoir device (IL-PRD), in which copper cations dissolved in an IL induce diverse electrochemical current responses. The origin of the electrochemical current from the IL-PRD was investigated spectroscopically in detail. After operating the device under various operating conditions, X-ray photoelectron spectroscopy of the IL-PRD revealed that electrochemical reactions involving Cu, Cu2O, Cu(OH)2, CuSx, and H2O occur at the Pt electrode/IL interface. These products are considered information transmission materials in IL-PRD similar to neurotransmitters in biological neurons. By introducing the Faradaic current components due to the electrochemical reactions of these materials into the output signal of IL-PRD, we succeeded in improving the time-series data processing performance of the nonlinear autoregressive moving average task. In addition, the information processing efficiency in machine learning to classify electrocardiogram signal waveforms was successfully improved by using the output current from IL-PRD. Optimizing the electrochemical reaction products of IL-PRD is expected to advance data processing technology in society.

Direct Investigation of Excited C60 Dianion and Its Intramolecular Electron Transfer Behaviors.

For the first time, the dynamics of excited fullerene dianions and associated intramolecular electron transfer (ET) were directly investigated by using femtosecond pump-probe laser flash photolysis on selectively reduced C60, pyrrolidino[60]fullerene (C60H), and dyads including C60-naphthalenediimide (NDI) and C60-pyromellitimide (PI). Upon near-infrared laser excitation, the excited dianion of C60 or C60H displayed two states with lifetimes of less than one and several tens of ps, attributed to prompt internal conversion from the theoretically predicted Sn state. Furthermore, the ET processes from the excited C602- in dyad molecules, including C602--NDI•- and C602--PI•-, were confirmed with varied ET rate constants due to the difference in the driving force for ET. The current findings provide a clear description of the hitherto uncharted excited-state and photoinduced ET characteristics of fullerene dianions, paving the way for photochemical studies of excited multi-ions (excited multi-polarons) and their application in organic semiconducting materials.

Influence of atherosclerotic burden on adult patients with ischemic moyamoya disease: combined analysis of two prospective cohorts.

OBJECTIVE: This study aimed to determine the influence of atherosclerotic risk factors on initial and further cerebrovascular events in adult patients with moyamoya disease (MMD) by combined analysis of two prospective cohorts in which patients received pharmacotherapy alone and were prospectively followed-up for 5 years. METHODS: In 71 patients, smoking status, home blood pressure, hemoglobin (Hb)A1c and low-density lipoprotein cholesterol (LDL-chol) were checked at inclusion and at further cerebrovascular event or at the end of 5-year follow-up. When a patient had daily smoking, increased HbA1c, increased LDL-chol, increased systolic blood pressure, or increased diastolic blood pressure, the patient was categorized as showing atherosclerotic burden. Angiographic disease progression was determined using changes on magnetic resonance angiography. RESULTS: Eleven patients showed angiographic disease progression and seven of these 11 patients experienced further cerebrovascular events during the follow-up period. The remaining 60 patients did not exhibit either condition. At inclusion, the incidence of atherosclerotic burden was significantly greater in patients without angiographic disease progression (80%) than in those with such progression (45%; p = 0.0249). For patients without angiographic disease progression, values or incidence of almost all variables showed significant interval decreases at the end of 5-year follow-up (p < 0.05). CONCLUSIONS: Adult patients with ischemic MMD who do not exhibit angiographic disease progression appear more strongly affected by atherosclerotic burden at the initial onset of cerebrovascular events than those exhibiting angiographic disease progression. A reduction in atherosclerotic burden by medical treatments for the former patients prevents further cerebrovascular events.

Ten-year clinical outcomes from a randomized trial comparing new-generation everolimus-eluting stent versus first-generation Sirolimus-eluting stent: Results from the RESET extended study.

BACKGROUND: New-generation drug-eluting stents (DES) achieved technological innovations and reported clinical advantages as compared with first-generation DES in clinical trials with 3-5 years follow-up. However, detailed clinical outcome data in very long-term follow-up is still scarce. OBJECTIVES: To evaluate 10-year clinical outcomes after first- and new-generation DES implantation. METHODS: In this extende follow-up study of the RESET, which is a largest randomized trial comparing everolimus-eluting stent (EES) with Sirolimus-eluting stent (SES), the study population consisted of 2892 patients from 84 centers. The primary efficacy and safety endpoints were target lesion revascularization (TLR) and a composite of death or myocardial infarction (MI), respectively. Complete 10-year follow-up was achieved in 87.9% of patients. RESULTS: Cumulative 10-year incidences of TLR and non-TLR were not significantly different between EES and SES (13.9% vs. 15.7%, Log-rank p = 0.20, and 33.4% vs. 31.3%, Log-rank p = 0.30). The cumulative 10-year incidence of death/MI was also not significantly different between the groups (32.5% vs. 34.4%, Log-rank p = 0.18). Cumulative 10-year incidence of definite stent thrombosis was numerically lower in EES than in SES (1.0% vs. 1.7%, Log-rank p = 0.16). The lower risk of EES relative to SES was significant for a composite endpoint of target lesion failure (TLF: 19.6% vs. 24.9%, Log-rank p = 0.001) and target vessel failure (TVF: 26.7% vs. 31.4%, Log-rank p = 0.006). CONCLUSION: During 10-year of follow-up, the risks for primary efficacy and safety endpoints were not significantly different between new-generation EES and first-generation SES, although EES compared with SES was associated with a lower risk for composite endpoints such as TLF and TVF.

Chemo-Enzymatic Synthesis of Non-ribosomal Macrolactams by a Penicillin-Binding Protein-Type Thioesterase.

Penicillin-binding protein-type thioesterases (PBP-type TEs) are an emerging family of non-ribosomal peptide cyclases. PBP-type TEs exhibit distinct substrate scopes from the well-exploited ribosomal peptide cyclases and traditional non-ribosomal peptide cyclases. Their unique properties, as well as their stand-alone nature, highlight PBP-type TEs as valuable candidates for development as biocatalysts for peptide macrocyclization. Here in this chapter, we describe the scheme for the chemoenzymatic synthesis of non-ribosomal macrolactam by SurE, a representative member of PBP-type TEs.

Predictors of in-hospital mortality in elderly patients with heart failure treated with tolvaptan.

Objectives: We conducted an analysis of first-time tolvaptan users (≥80 years old) to determine the factors associated with the prognosis of elderly patients with heart failure. Methods: We retrospectively analyzed 66 consecutive patients with worsening heart failure (aged ≥80 years) who were admitted to Fujita Health University Bantane Hospital from 2011 to 2016 and treated with tolvaptan. Differences between the in-hospital death and survival groups were evaluated. Multivariate logistic regression analysis was also performed to identify the risk factors for mortality. Results: Sixty-six patients were included, and 26 patients died during the index hospitalization. The patients who died had a significantly higher prevalence of ischemic heart disease; a higher heart rate; higher levels of plasma C-reactive protein, blood urea nitrogen (BUN), and creatinine; a lower serum albumin level; and a lower estimated glomerular filtration rate than surviving patients. The proportion of patients requiring early initiation of tolvaptan treatment (within 3 days of admission) was significantly higher in surviving patients. On the basis of multivariate logistic regression analysis, although a high heart rate and high BUN levels were independent factors for in-hospital prognosis, they were not significantly associated with the early use of tolvaptan (≤3 days vs. ≥4 days; odds ratio=0.39; 95% confidence interval=0.07-2.21; p=0.29). Conclusions: This study revealed that a higher heart rate and higher BUN levels were independent factors for in-hospital prognosis in elderly patients who received tolvaptan and that early tolvaptan use may not always be effective in elderly patients.