Optical coherence tomography findings in acute myocardial infarction patients with familial moyamoya disease.

It has been reported that patients with moyamoya disease have a high prevalence of coronary artery disease. On the other hand, the pathology of coronary artery disease is not fully understood. We were able to evaluate vascular properties using optical coherence tomography in a case of acute myocardial infarction that occurred in a relatively young woman with moyamoya disease. Previous reports using intravascular ultrasound have shown that coronary artery lesions in patients with moyamoya disease are caused by fibrous cell proliferation. Optical coherence tomography of our case showed a fibrous plaque rich in macrophages and a lipidic plaque. We believe that our case may lead to elucidation of the etiology of coronary artery disease in patients with moyamoya disease. Learning objective: It is known that patients with moyamoya disease develop coronary artery disease at a young age, but the etiology has not been clarified. We used optical coherence tomography to evaluate the intravascular conditions of coronary artery disease patients with moyamoya disease. The lesions of coronary artery disease associated with moyamoya disease were mainly arteriosclerotic lesions rich in inflammation.

Observation of a critical charge mode in a strange metal.

Understanding the strange metallic behavior that develops at the brink of localization in quantum materials requires probing the underlying electronic charge dynamics. Using synchrotron radiation-based Mössbauer spectroscopy, we studied the charge fluctuations of the strange metal phase of ß-YbAlB4 as a function of temperature and pressure. We found that the usual single absorption peak in the Fermi-liquid regime splits into two peaks upon entering the critical regime. We interpret this spectrum as a single nuclear transition, modulated by nearby electronic valence fluctuations whose long time scales are further enhanced by the formation of charged polarons. These critical charge fluctuations may prove to be a distinct signature of strange metals.

Usefulness of Balloon-Assisted Ultrasound-Guided Percutaneous Thrombin Injection to Femoral Artery Pseudoaneurysm by Transradial Artery Approach.

Balloon-Assisted Ultrasound-Guided Percutaneous Thrombin Injection (BATI) is useful for iatrogenic pseudoaneurysm. In previous reports, BATI for pseudoaneurysm of the femoral artery was performed by contralateral transfemoral approach. It has been reported that patients with obesity, hypertension, and diabetes have more hemorrhagic complications at the puncture site of the femoral artery. We report a case in which BATI by transradial artery approach was useful for patients with obesity, hypertension, and diabetes who were expected to be at high risk of hemorrhagic complications of transfemoral artery approach.

Investigation of the Structure of Atomically Dispersed NiNx Sites in Ni and N-Doped Carbon Electrocatalysts by 61Ni Mössbauer Spectroscopy and Simulations.

Ni and nitrogen-doped carbons are selective catalysts for CO2 reduction to CO (CO2R), but the hypothesized NiNx active sites are challenging to probe with traditional characterization methods. Here, we synthesize 61Ni-enriched model catalysts, termed 61NiPACN, in order to apply 61Ni Mössbauer spectroscopy using synchrotron radiation (61Ni-SR-MS) to characterize the structure of these atomically dispersed NiNx sites. First, we demonstrate that the CO2R results and standard characterization techniques (SEM, PXRD, XPS, XANES, EXAFS) point to the existence of dispersed Ni active sites. Then, 61Ni-SR-MS reveal significant internal magnetic fields of ∼5.4 T, which is characteristic of paramagnetic, high-spin Ni2+, in the 61NiPACN samples. Finally, theoretical calculations for a variety of Ni-Nx moieties confirm that high-spin Ni2+ is stable in non-planar, tetrahedrally distorted geometries, which results in calculated isotropic hyperfine coupling that is consistent with 61Ni-SR-MS measurements.

The Thermal Stability of the Collagen Triple Helix Is Tuned According to the Environmental Temperature.

Triple helix formation of procollagen occurs in the endoplasmic reticulum (ER) where the single-stranded α-chains of procollagen undergo extensive post-translational modifications. The modifications include prolyl 4- and 3-hydroxylations, lysyl hydroxylation, and following glycosylations. The modifications, especially prolyl 4-hydroxylation, enhance the thermal stability of the procollagen triple helix. Procollagen molecules are transported to the Golgi and secreted from the cell, after the triple helix is formed in the ER. In this study, we investigated the relationship between the thermal stability of the collagen triple helix and environmental temperature. We analyzed the number of collagen post-translational modifications and thermal melting temperature and α-chain composition of secreted type I collagen in zebrafish embryonic fibroblasts (ZF4) cultured at various temperatures (18, 23, 28, and 33 °C). The results revealed that thermal stability and other properties of collagen were almost constant when ZF4 cells were cultured below 28 °C. By contrast, at a higher temperature (33 °C), an increase in the number of post-translational modifications and a change in α-chain composition of type I collagen were observed; hence, the collagen acquired higher thermal stability. The results indicate that the thermal stability of collagen could be autonomously tuned according to the environmental temperature in poikilotherms.

Impact of small diameter and low level of emission laser coronary atherectomy in patients with acute myocardial infarction.

Excimer laser coronary atherectomy (ELCA) is an effective treatment to remove intracoronary thrombi. In the present study, we compared in-hospital mortality in patients with acute myocardial infarction (AMI) who underwent conventional treatment and conventional treatment plus ELCA. Among 656 patients who were admitted to our hospital through the Tokyo CCU Network, 104 patients with AMI who were treated by percutaneous coronary intervention between January 2013 and December 2016 met inclusions criteria and underwent conventional treatment with ELCA (ELCA group) and 89 underwent conventional treatment alone (conventional group). We retrospectively evaluated in-hospital mortality within 30 days and used propensity score (PS) matching to reduce assignment bias and multivariate analysis to detect the predictors of in-hospital mortality. In-hospital mortality rate was significantly lower in the ELCA group before and after PS matching (2.9% vs. 13.5%, p = 0.006 before PS matching, and 2.8% vs. 14.1%, p = 0.016 after PS matching). After PS matching, ß-blocker or statins use, incidence of shock, Killip classification, and door-to-balloon time were not significantly different. A multivariate logistic regression analysis identified ELCA, dyslipidemia, shock, and left ventricular ejection fraction as independent predictors of in-hospital mortality (odds ratio (OR), 0.147, 95% confidence interval [CI], 0.022-0.959, p = 0.045; OR, 0.077, 95% CI, 0.007-0.805, p = 0.032; OR, 6.494, 95% CI, 1.228-34.34, p = 0.028; OR, 0.890, 95% CI, 0.828-0.957, p = 0.002, respectively). Our data indicate that ELCA with the small diameter and low level emission may reduce the in-hospital mortality compared to conventional methods in patients with AMI in drug-eluting stent era.

[Case of Recurrent Breast Cancer with BRCA2 Mutation Successfully Treated with Olaparib Therapy].

A 70-year-old woman was diagnosed with cT2N2M0 left triple negative breast cancer. She received neoadjuvant chemotherapy. Around 30 months after the surgery, she developed carcinomatous pericardial tamponade, carcinomatous pleurisy, and metastatic thyroid cancer due to the breast cancer. Around the same time, a BRCA2 mutation was confirmed. Thus, olaparib therapy was started. Around 45 days after the start of olaparib administration, the therapeutic effect was cPR. The treatment remains effective even after approximately 1 year.

Peptide precursors that acquire denatured collagen-hybridizing ability by O-to-N acyl migration at physiological pH.

Here, we report peptide probes with either single or cyclic double stranded collagen-like sequences that spontaneously acquire collagen-hybridizing ability at physiological pH. These peptides have ester bonds derived from O-acyl isopeptide units that are converted to amide bonds via intramolecular O-to-N acyl migration by a pH shift. The peptides that do not require pre-treatment for disassembly will be useful as prodrugs in theranostic treatments targeting unfolded collagen.

Long-Term Performance of Right Ventricular Implantable Cardioverter-Defibrillator Leads in Arrhythmogenic Right Ventricular Cardiomyopathy and Hypertrophic Cardiomyopathy.

Patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and hypertrophic cardiomyopathy (HCM) implanted with implantable cardioverter-defibrillators (ICDs) may show a large decrease in R-wave amplitude during long-term follow-up. However, it is unclear whether this decrease is higher in these patients than in those without structural heart disease. This study investigated ICD-lead intracardiac parameters over a long duration in patients with ARVC and HCM and compared these parameters with those of a control group. We included 50 patients (mean age, 55.2 ± 17.2 years; 26% female) with ICD leads in the right ventricular apex, and compared 7 ARVC and 14 HCM patients with 29 control patients without structural heart disease. ICD-lead parameters, including R-wave amplitude, pacing threshold, and impedance during follow-up, were compared. The difference in these parameters between the time of implantation and year 5 were also compared. There were no significant differences in R-wave amplitude at implantation among the 3 groups. The change in R-wave amplitude between the time of implantation and year 5 was significantly greater in the ARVC group (-3.3 ± 5.4 mV, P = 0.012) in comparison to the control group (1.3 ± 2.8 mV); the HCM group showed no significant difference (-0.4 ± 2.3 mV, P = 0.06). Thus, in the ARVC group, R-wave amplitude at year 5 was significantly lower than that in the control group (5.7 ± 4.8 mV versus 12.5 ± 4.5 mV, P = 0.001). In ARVC patients with ICDs, ventricular sensing is likely to deteriorate during long-term follow-up; however, in HCM patients, sensing may not deteriorate.

Development of a collagen-like peptide polymer via end-to-end disulfide cross-linking and its application as a biomaterial.

Collagen is the most abundant protein in the animal kingdom and has a unique triple-helical structure. It not only provides mechanical strength to tissues, but also performs specific biological functions as a multifaceted signaling molecule. Animal-derived collagen is therefore widely used as a biocompatible material in vitro and in vivo. In this study, we developed a novel peptide-based material that mimicked both the polymeric properties and a selected biological function of native collagen. This material was prepared by end-to-end multiple disulfide cross-linking of chemically synthesized triple-helical peptides. The peptide polymer showed a gel-forming property, and receptor-specific cell binding was observed in vitro by incorporating a peptide harboring an integrin α2ß1-binding sequence. Furthermore, cell signaling activity and biodegradability were tunable according to the polymer contents. The results demonstrated the potential of this material as a designer collagen. STATEMENT OF SIGNIFICANCE: Collagen is a useful biomaterial with the gel-forming property. It also exhibits various biological activities through the interaction of specific amino acid sequences displayed on the triple helix with functional biomacromolecules. Here we report a novel synthetic material, artificial collagen, by end-to-end cross-linking of chemically synthesized collagen-like triple-helical peptides. The material allows independent regulation of polymer properties, i.e. gel stiffness, and sequence-specific bioactivities by altering peptide compositions. This material can also be variously shaped, for example, thin films with high transparency. In addition, it has low inflamatogenic properties and tunable biodegradability in vivo.

A Strategy for Discovering Heterochiral Bioactive Peptides by Using the OB2n P Library and SPOTs Method.

d-Amino acid containing peptides are promising as drug lead compounds because of their expected higher stability in vivo. A heterochiral random peptide library called the one-bead-2n -peptide (OB2n P) library, which can display 2n peptide diastereomers per bead, has been developed. Through screening of the OB2n P library and subsequent binding assay among the peptide diastereomers synthesized in parallel by means of the SPOTs method, new heterochiral mimotopes for the anti-ß-endorphin monoclonal antibody have been obtained. One mimotope was a new ligand for the µ-opioid receptor. The screening strategy enabled d-amino acid containing drug leads to be obtained efficiently by expanding searchable chemical space without increasing the experimental scale.

Impact of the preprocedural nutrition status on the clinical outcomes of patients after pacemaker implantation for bradycardia.

BACKGROUND: Malnutrition is associated with a poor prognosis in heart failure, angina pectoris, and peripheral artery disease. However, the clinical importance of the preprocedural nutrition status of patients requiring pacemaker implantation (PMI) for bradycardia is unclear. METHODS: We retrospectively enrolled 521 patients (median 79 years) who underwent their first PMI between January 1, 2012 and June 30, 2017. The nutrition status before implantation was assessed by the geriatric nutritional risk index (GNRI). The association between the preprocedural GNRI-based nutritional status and all-cause mortality was investigated. RESULTS: GNRI-based high (GNRI <82) and moderate (GNRI 82 to <92) malnutrition status were found in 9.2% and 34.0%, respectively. During a median follow-up of 1178 days, 71 patients died. The mortality rate, which was analyzed using survival curves, was significantly stratified by the GNRI-based malnutrition status [high: 52.0% (25/48), moderate: 16.9% (30/177), low: 5.4% (16/296), p<0.001). On a multivariate Cox-proportional hazard analysis, GNRI-based high malnutrition status independently predicted all-cause death (hazard ratio: 4.49, 95% confidence interval: 2.59-7.80, p<0.001). A sensitivity analysis based on the controlling nutritional status score showed consistent results. On a receiver operating characteristic curve analysis, GNRI had a high predictive value for all-cause mortality (area under the curve, 0.78, 95% confidence interval: 0.72-0.84, p<0.001). CONCLUSIONS: Preprocedural malnutrition was significantly associated with poor outcomes of patients who underwent PMI. Assessing the nutritional status in advance is important for risk stratification, and improving the nutritional status may be an option for managing these patients.

Hemorrhagic shock due to branch injury of the left internal thoracic artery two days after pericardiocentesis.

Pericardiocentesis is a definitive strategy to remove pericardial effusion. In this report, we present a rare case of a 23-year-old man with sudden delayed hemorrhagic shock due to branch bleeding of the left internal thoracic artery (LITA) two days after undergoing pericardiocentesis. Angiography, embolization, and drainage were effective. As far as we know, this is the first report that shows delayed bleeding due to branch injury of the LITA as a possible complication after pericardiocentesis. .

Geranylgeraniol-induced Myogenic Differentiation of C2C12 Cells.

BACKGROUND: Geranylgeraniol (GGOH) is a C20 isoprenoid found in fruits, vegetables, and grains, including rice. As a food substance, GGOH is categorized as 'Generally Recognized as Safe'. GGOH is an intermediate product in the mevalonate pathway and acts as a precursor to geranylgeranyl pyrophosphate. MATERIALS AND METHODS: C2C12 mouse myoblasts derived from muscle satellite cells were used. Quantitative reverse-transcriptase polymerase chain reaction, western blotting analysis, and immunocytochemical analysis were performed to respectively assess mRNA expression, protein levels, and the number of myofibers. RESULTS: GGOH reduced the expression levels of skeletal muscle atrophy-related ubiquitin ligases in myofibers derived from C2C12 cells. GGOH induced myogenic differentiation of C2C12 cells via geranylgeranylation. GGOH did not adversely affect the proliferation of C2C12 cells. CONCLUSION: GGOH induces myoblast differentiation in C2C12 cells.

Comparison of direct oral anticoagulants and warfarin regarding midterm adverse events in patients with atrial fibrillation undergoing catheter ablation.

BACKGROUND: Oral anticoagulants, including direct oral anticoagulants (DOACs), are usually required in atrial fibrillation (AF) patients who are at a high risk of thromboembolism (TE), even if they had undergone catheter ablation (CA). Although several studies have reported the safety and efficacy of DOACs around CA in AF patients, there are only limited data regarding the midterm incidence of TE and bleeding complications post-CA among AF patients treated with warfarin or DOACs. METHODS: We studied 629 AF patients (mean age: 65.3 ± 10.3 years; 442 men) undergoing CA, to calculate the midterm incidence of TE and bleeding complications associated with warfarin or DOACs. RESULTS: In total, 292 patients used warfarin and 337 used DOACs (dabigatran: 90 patients; rivaroxaban: 137; and apixaban: 110). At baseline, the CHA2DS2-VASc and HAS-BLED scores were similar between the 2 groups. During a median follow-up period of 7 months, no TE complications occurred. The warfarin group had a significantly higher bleeding event rate than did the DOACs group (all bleeding complications: 32 [11.0%] vs 15 [4.5%], respectively, P = .002). The rate of all bleeding complications was significantly higher in the warfarin group than in the DOACs group (10.1% vs 3.7%, respectively, at 10 months; P = .024). In Cox proportional hazards modeling, DOAC use was significantly associated with a decreased risk of bleeding (adjusted hazard ratio: 0.497; 95% confidence interval: 0.261-0.906, P = .022). CONCLUSIONS: Direct oral anticoagulant use in AF patients undergoing CA may be associated with a similar risk of TE as warfarin but is associated with a lower risk of bleeding.

Early Transfer of Patients with Acute Heart Failure from a Core Hospital to Collaborating Hospitals and Their Prognoses.

Japan is facing problems associated with "heart failure (HF) pandemics" and bed shortages in core hospitals that can accommodate patients with acute HF. The prognosis is currently unknown for acute HF patients who were transferred from core hospitals to collaborating hospitals during the very early treatment phase and whose treatment strategies are in place.We enrolled 166 acute HF patients who were hospitalized between January 1, 2015, and December 31, 2015, and compared the conditions of transferred patients (n = 53, median duration before transfer = 6 days) and nontransferred patients (n = 113). The transferred and nontransferred patients had similar one-year mortality rates (24.5% versus 19.5%, log-rank P = 0.27) and composite one-year mortality and HF readmission rates (35.8% versus 31.0%, log-rank P = 0.32). Multivariate analysis determined that patient transfers were not associated with a higher composite endpoint (hazard ratio, 1.08; 95% confidence interval, 0.58-1.99, P = 0.82). Transferred patients with low composite congestion scores (CCSs) had significantly lower composite endpoints than those with high CCSs (23.5% versus 57.9%, log-rank P = 0.005).Acute HF patients who were transferred did not have inferior prognoses compared with nontransferred patients when the treatment strategies were correctly assumed by cardiologists. The implementation of early and strict decongestion strategies before transfer may be important for reducing cardiovascular events.

Cyclic Peptides for Efficient Detection of Collagen.

We report here a new class of collagen-binding peptides, cyclic collagen-mimetic peptides (cCMPs), that efficiently hybridize with the triple-helix-forming portions of collagen. cCMPs are composed of two parallel collagen-like (Xaa-Yaa-Gly)n strands with both termini tethered by covalent linkages. Enzyme-linked immunosorbent assays and western blotting analysis showed that cCMPs exhibit more potent affinity toward collagen than reported collagen-binding peptides and can specifically detect different collagen polypeptides in a mixture of proteins. Collagen secreted from cultured cells was detected by confocal microscopy with fluorescein-labeled cCMP. The cCMP is also shown to detect sensitively folding intermediates in the endoplasmic reticulum, something that was difficult to visualize with conventional collagen detectors. Molecular-dynamics simulations suggested that a cCMP forms a more stably hybridized product than its single-chain counterpart; this could explain why cCMP has higher affinity toward denatured collagen. These results indicate the usefulness of cCMPs as tools for detecting denatured collagen.

Basic Fibroblast Growth Factor Fused with Tandem Collagen-Binding Domains from Clostridium histolyticum Collagenase ColG Increases Bone Formation.

Basic fibroblast growth factor 2 (bFGF) accelerates bone formation during fracture healing. Because the efficacy of bFGF decreases rapidly following its diffusion from fracture sites, however, repeated dosing is required to ensure a sustained therapeutic effect. We previously developed a fusion protein comprising bFGF, a polycystic kidney disease domain (PKD; s2b), and collagen-binding domain (CBD; s3) sourced from the Clostridium histolyticum class II collagenase, ColH, and reported that the combination of this fusion protein with a collagen-like peptide, poly(Pro-Hyp-Gly)10, induced mesenchymal cell proliferation and callus formation at fracture sites. In addition, C. histolyticum produces class I collagenase (ColG) with tandem CBDs (s3a and s3b) at the C-terminus. We therefore hypothesized that a bFGF fusion protein containing ColG-derived tandem CBDs (s3a and s3b) would show enhanced collagen-binding activity, leading to improved bone formation. Here, we examined the binding affinity of four collagen anchors derived from the two clostridial collagenases to H-Gly-Pro-Arg-Gly-(Pro-Hyp-Gly)12-NH2, a collagenous peptide, by surface plasmon resonance and found that tandem CBDs (s3a-s3b) have the highest affinity for the collagenous peptide. We also constructed four fusion proteins consisting of bFGF and s3 (bFGF-s3), s2b-s3b (bFGF-s2b-s3), s3b (bFGF-s3b), and s3a-s3b (bFGF-s3a-s3b) and compared their biological activities to those of a previous fusion construct (bFGF-s2b-s3) using a cell proliferation assay in vitro and a mouse femoral fracture model in vivo. Among these CB-bFGFs, bFGF-s3a-s3b showed the highest capacity to induce mesenchymal cell proliferation and callus formation in the mice fracture model. The poly(Pro-Hyp-Gly)10/bFGF-s3a-s3b construct may therefore have the potential to promote bone formation in clinical settings.

Treatment Outcomes of Anticoagulant Therapy and Temporary Inferior Vena Cava Filter Implantation for Pregnancy Complicated by Venous Thrombosis.

Objective: Although deep vein thrombosis (DVT) followed by pulmonary thromboembolism (PE) is a critical complication during pregnancy, there have been few reports about its intrapartum management. We evaluated intrapartum management by using a temporary inferior vena cava filter (IVCF) in pregnant women with PE/DVT. Materials and Methods: Eleven women with PE/DVT during pregnancy between January 2004 and December 2016 were included. The patients were hospitalized for intravenous unfractionated heparin infusion after acute PE/DVT onset. Seven patients were discharged and continued treatment with subcutaneous injection of heparin at the outpatient unit. IVCF was implanted 1-3 days before delivery in 10 patients. Anticoagulant therapy was discontinued 6-12 h before delivery. We retrospectively analyzed rates of maternal or perinatal death, and recurrence of symptomatic PE/DVT. Results: One patient was diagnosed as having PE/DVT and 10 had DVT alone. One patient suffered hemorrhagic shock during delivery; however, maternal or perinatal death and recurrence of symptomatic PE/DVT did not occur in any patient. Conclusion: Maternal or perinatal death and recurrence of symptomatic PE/DVT was not seen in women diagnosed as having PE/DVT during pregnancy and treated with anticoagulant therapy and IVCF.

Effect of Optimizing Guideline-Directed Medical Therapy Before Discharge on Mortality and Heart Failure Readmission in Patients Hospitalized With Heart Failure With Reduced Ejection Fraction.

Guideline-directed medical therapy (GDMT) is recommended for patients with heart failure with reduced ejection fraction (HFrEF). However, the prognostic impact of medication optimization at the time of discharge in patients hospitalized with heart failure (HF) is unclear. We analyzed 534 patients (73 ± 13 years old) with HFrEF. The status of GDMT at the time of discharge (prescription of angiotensin converting enzyme inhibitor [ACE-I]/angiotensin receptor blocker [ARB] and ß blocker [BB]) and its association with 1-year all-cause mortality and HF readmission were investigated. Patients were divided into 3 groups: those treated with both ACE-I/ARB and BB (Both group: n = 332, 62%), either ACE-I/ARB or BB (Either group: n = 169, 32%), and neither ACE-I/ARB nor BB (None group: n = 33, 6%), respectively. One-year mortality, but not 1-year HF readmission rate, was significantly different in the 3 groups, in favor of the Either and Both groups. A favorable impact of being on GDMT at the time of discharge on 1-year mortality was retained even after adjustment for covariates (Either group: hazard ratio [HR] 0.44, 95% confidence interval [CI] 0.21 to 0.90, p = 0.025 and Both group: HR 0.29, 95% CI 0.13-0.65, p = 0.002, vs None group). For 1-year HF readmission, no such association was found. In conclusion, optimization of GDMT before the time of discharge was associated with a lower 1-year mortality, but not with HF readmission rate, in patients hospitalized with HFrEF.