[Sudden Chest Pain due to Early Bioprosthetic Valve Dysfunction:Report of a Case].

We report a case of bioprosthetic valve dysfunction and acute aortic valve regurgitation. The case was a 75-year-old female who had sudden onset chest pain. ST-segment depression in several leads on electrocardiogram( ECG) suggested acute coronary syndrome. Coronary angiography showed no significant stenosis in coronary arteries. Transesophageal echocardiography revealed severe aortic regurgitation, suggesting that angina was caused by myocardial ischemia associated with acute aortic regurgitation. She was diagnosed as having bioprosthetic valve dysfunction, and underwent redo aortic valve replacement. One leaflet of the bioprosthetic valve was torn along the stent post and caused bioprosthetic valve dysfunction. Failed bioprosthetic valve was removed and replaced by a mechanical valve.

[Traumatic Ascending Aortic Injury with Delayed Cardiac Tamponade due to Sternal Fracture].

The case was a 63-year-old male. He had a history of surgery for funnel chest at the age of 23. He overdrank and hit the anterior chest about two weeks before. He complained of persistent chest pain and palpitation, and was admitted because of atrial fibrillation and moderate pericardial fluid. Computed tomography (CT) showed a new sternal fracture, but dislocation and instability was mild. A few days later, sinus rhythm was restored and his heart failure improved. Unfortunately, on the 7th day, he suddenly suffered cardiopulmonary arrest. Ultrasonography revealed cardiac tamponade, and pericardiocentesis yielded 400 ml of bloody pericardial fluid collection. CT demonstrated clot mainly in the anterior pericardium, and emergent operation was performed. Bleeding from the anterior wall of the ascending aorta was repaired by placing one stitch. Postoperatively the patient remained unconscious, and CT of the brain showed hypoxic encephalopathy. After prolonged ventilator management, he was transferred to a rehabilitation hospital. In retrospect, the ascending aorta was close to the sternum in this patient, and sternal fracture might have caused injury of the ascending aorta.

A Dicyanomethyl Radical Conjugated with a Pyridylamino Group: Combining Radical-based Dynamic Covalent Chemistry and Coordination Chemistry.

In this work, we aimed to develop a dicyanomethyl radical that undergoes both reversible C-C bond formation/dissociation and metal-ligand coordination reactions to combine dynamic covalent chemistry (DCC) based on organic radicals with coordination chemistry. We have previously reported a dicyanomethyl radical conjugated with a triphenylamine (1⋅) that exhibits a monomer/dimer equilibrium between the σ-bonded dimer (12 ). We designed and synthesized a novel dicyanomethyl radical with a pyridyl group as a coordination point (2⋅) by replacing the phenyl group of 1⋅ with a 3-pyridyl group. We showed that 2⋅ is also in an equilibrium with the σ-bonded dimer (22 ) in solution and has suitable thermodynamic parameters for application in DCC. 22 coordinates to PdCl2 in a 2 : 2 ratio to selectively form a metallamacrocycle (22 )2 (PdCl2 )2 , and its structure was clarified by single crystal X-ray analysis. Variable-temperature NMR, ESR, and electronic absorption measurements revealed that (22 )2 (PdCl2 )2 also undergoes the reversible C-C bond formation/dissociation reaction. Ligand-exchange experiment showed that 22 was liberated from (22 )2 (PdCl2 )2 by the addition of another ligand with a higher affinity for PdII . This work demonstrated that DCC based on dicyanomethyl radicals works orthogonally to metal-ligand coordination reactions.

Efficacy of Plasma free Hemoglobin for detecting centrifugal pump thrombosis.

INTRODUCTION: Lactate dehydrogenase (LDH) is widely used as an indicator of pump thrombosis in a centrifugal pump. However, due to the low specificity of LDH, pump thrombosis is difficult to detect in the clinical environment. We measured plasma free hemoglobin (pfHb) with the portable device in ICU. The goal of this investigation is to evaluate its diagnostic ability for pump thrombosis. METHODS: We enrolled 31 consecutive patients who needed Extracorporeal Membrane Oxygenation (ECMO) therapy and pfHb was determined with HemoCue® plasma/Low Hb photometer. Pump thrombosis was analyzed macroscopically at the timing of pump explantation or exchange. Also, we divided the pump thrombosis into a grading scale by the place of thrombosis. RESULTS: The median of peak pfHb was significantly lower in the none thrombus group (0.03 g/dL) than that of in the thrombus group (0.05g/dL) (p = 0.01). In our grading criteria, pfHb was significantly higher when the thrombus is existing near the shaft (p = 0.015). Contrary, no significant difference was found for LDH.The ROC analysis of pfHb revealed an AUC of 0.77 for detecting pump thrombosis with the best statistical cutoff value at 0.05 g/dL (specificity, 78%; sensitivity, 77%). Also, ROC analysis of LDH was performed (AUC, 0.44; cutoff value, 1200 IU/L; specificity, 59%; sensitivity, 54%) and compared with pfHb. AUC was significantly higher in pfHb (p = 0.04). CONCLUSION: Our results showed the efficacy of pfHb for detecting centrifugal pump thrombosis.

Outcomes of dogs with progressive myelomalacia treated with hemilaminectomy or with extensive hemilaminectomy and durotomy.

OBJECTIVE: To evaluate the ability of extensive hemilaminectomy and durotomy (EHLD) to control progressive myelomalacia (PMM) in dogs. STUDY DESIGN: Retrospective clinical study. ANIMALS: Twenty-eight client owned dogs that underwent EHLD (n = 10) or HL alone (n = 18). METHODS: After diagnosis by MRI, dogs were immediately treated with HL alone or EHLD at the site of intramedullary hyperintensity on T2-weighted (T2W)-MRI. Medical records were retrospectively reviewed. Follow-up data were collected via telephone interviews with the referring veterinarian and a standardized questionnaire. Postoperative survival outcome between groups was compared (log-rank test) by using Cox's proportional hazard analysis with baseline characteristics entered as covariates. RESULTS: The survival rate was higher in the EHLD group (P = .03) compared with the HL-alone group. Eleven of 18 dogs treated with HL survived, while seven of 18 dogs died (median, 5 days after surgery). In the EHLD group, 10 of 10 dogs survived postoperatively. Baseline characteristics were not associated with postoperative survival outcomes. According to multivariate analysis, EHLD was the independent factor associated with an increase in survival rate (P = .0002). CONCLUSION: EHLD durotomy at the intramedullary hyperintense region on T2W-MRI improved the survival rate of dogs with PMM compared with dogs treated with standard HL. CLINICAL SIGNIFICANCE: This study provides evidence that supports treatment with EHLD in dogs with PMM. Additional prospective studies are required.

Mitochondrial Genomics Reveals Shared Phylogeographic Patterns and Demographic History among Three Periodical Cicada Species Groups.

The mass application of whole mitogenome (MG) sequencing has great potential for resolving complex phylogeographic patterns that cannot be resolved by partial mitogenomic sequences or nuclear markers. North American periodical cicadas (Magicicada) are well known for their periodical mass emergence at 17- and 13-year intervals in the north and south, respectively. Magicicada comprises three species groups, each containing one 17-year species and one or two 13-year species. Within each life cycle, single-aged cohorts, called broods, of periodical cicadas emerge in different years, and most broods contain members of all three species groups. There are 12 and three extant broods of 17- and 13-year cicadas, respectively. The phylogeographic relationships among the populations and broods within the species groups have not been clearly resolved. We analyzed 125 whole MG sequences from all broods and seven species within three species groups to ascertain the divergence history of the geographic and allochronic populations and their life cycles. Our mitogenomic phylogeny analysis clearly revealed that each of the three species groups had largely similar phylogeographic subdivisions (east, middle, and west) and demographic histories (rapid population expansion after the last glacial period). The mitogenomic phylogeny also partly resolved the brood diversification process, which could be explained by hypothetical temporary life cycle shifts, and showed that none of the 13- and 17-year species within the species groups was monophyletic, possibly due to gene flow between them. Our findings clearly reveal phylogeographic structures in the three Magicicada species groups, demonstrating the advantage of whole MG sequence data in phylogeographic studies.

Cryptic Diversity in the Aphid-Parasitizing Wasp Protaphidius nawaii (Hymenoptera: Braconidae): Discovery of Two Attendant-Ant-Specific mtDNA Lineages.

The parasitoid wasp Protaphidius nawaii parasitizes the aphid Stomaphis japonica, which is obligatorily attended by several species of ants of genus Lasius. Subgenus Lasius or Dendrolasius ants use different defense strategies to protect the aphids that they attend (Lasius, shelter building; Dendrolasius, aggressive attack). We performed molecular phylogenetic analysis based on partial mitochondrial DNA sequences of P. nawaii and found that the parasitoid wasp consists of two highly differentiated genetic lineages. Although these two lineages distributed sympatrically, one tends to parasitize aphids attended by ants of subgenus Lasius, and the other parasitizes aphids attended by ants of subgenus Dendrolasius. The two lineages of P. nawaii appear to exhibit different oviposition behaviors adapted to the different aphid-protection strategies of the two ant subgenera.

Effect of hypoxia on progesterone production by cultured bovine early and mid luteal cells.

A major role of the corpus luteum (CL) is to produce progesterone (P4). The CL has immature vasculature shortly after ovulation, suggesting it exists under hypoxic conditions. To elucidate the mechanism involved in regulation of luteal cell function during CL development, we compared the effect of hypoxia on P4 production by cultured bovine early and mid luteal cells. Luteal cells obtained from early and mid CL were incubated under different O2 concentrations (20% and 3%) with or without hCG (1 U/ml) for 6 h and 24 h. After 6 h of culture in the presence of hCG, P4 production was not affected by hypoxia whereas decrease in its production by mid luteal cells was observed. After 24 h of culture, P4 production was significantly decreased by hypoxia in both stages of luteal cells regardless of the use of hCG. At 6 h of culture, hypoxia increased mRNA expression of hydroxyl-Δ-5-steroid dehydrogenase, 3ß- and steroid Δ-isomerase 1 (HSD3B1) in early luteal cells, and decreased mRNA expression of cytochrome P450 cholesterol side chain cleavage (CYP11A1) enzyme in mid luteal cells. At 24 h of culture, mRNA expressions of steroidogenic acute regulatory protein (STAR), CYP11A1, and HSD3B1 were not affected by hypoxia in both stages of luteal cells. The overall results suggest that early luteal cells maintain P4 production under hypoxic conditions, and hypoxia-induced HSD3B1 may support this P4 production in the bovine early CL.

[Video Assisted Left Ventricular Pseudoaneurysm Repair].

An 80-year-old male was admitted to our hospital because of subacute myocardial infarction with moderate mitral regurgitation. Though he recovered well and went home within 2 weeks, the transthoracic echocardiography revealed rapid growing aneurysmal changes at the left ventricular posterior wall. We made diagnose of a pseudoaneurysm by the multi detector-row computed tomography, and planed a surgical treatment. Following the cardiac arrest, an endoscope was inserted into the left ventricle, we inspected the relation between the mitral valve and papillary muscles to detect proper suture lines and to avoid the mitral regurgitation. The defect of the left ventricular wall was repaired with 2-layer bovine pericardial patches reinforced with fibrin glue. His postoperative course was uneventful, and he was discharged from hospital on 12th postoperative day. We consider that inspections of intra-ventricle apparatus with the endoscope are useful to prevent the mitral valve insufficiency and keep the optimal left ventricle shape.

Endoscopic management of petrous apex cholesteatoma.

We describe a technique for approaching petrous apex cholesteatoma using combined lateral microscopic/endoscopic approaches, and discuss the utility of endoscopy in managing matrix inside the petrous apex. In our two cases, total view inside the petrous apex was achieved under endoscopy without mobilizing the internal carotid artery, and the matrix was successfully removed. Neither patient has presented with postoperative recurrence thanks to the wide-angle endoscopic view inside the petrous apex. Since the number of patients was small, comparisons with microscopic treatments are not yet valid, but endoscopes could offer a helpful tool for operating inside the petrous apex.

Cochlear implantation in deaf patients with eosinophilic otitis media using subtotal petrosectomy and mastoid obliteration.

We investigated the usefulness and safety of our cochlear implantation method for two deaf patients with eosinophilic otitis media. The surgical approach was a subtotal petrosectomy to remove the theater of eosinophilic infiltration and to prevent leaching of foreign substances and entry of stimuli that are the cause of eosinophilic inflammations. The operative cavity was obliterated with abdominal fat. There were no complications or recurrent inflammation following surgery in the cases of both patients. It was confirmed by CT scan that the eustachian tube was closed and the operative cavity remained obliterated with abdominal fat. Following the procedure, the hearing threshold results of the two patients were 30 and 34 dB. Cochlear implantation procedures in this report for deaf patients resulting from eosinophilic otitis media may be effective and safe. Using steroids before surgery may be the better option. To further confirm the efficacy and safety of our surgical concept, we need to administer this treatment concept for a large number of cases in a future study.

[Aortoesophageal Fistula due to Aortic Aneurysm;Report of a Case].

A 77-year-old woman presented with general fatigue, was found to have anemia, and was referred to our hospital. Upper gastrointestinal endoscopy revealed a submucosal elevated lesion with a bleeding site and debris at the middle thoracic esophagus. Enhanced computed tomography demonstrated a thoracic aortic aneurysm compressing the esophagus. She was diagnosed with an aorto-esophageal fistula due to the thoracic aortic aneurysm. Graft replacement was performed under partial extracorporeal circulation. Because the perforation of the esophagus was small, omental flap transposition was performed without esophagectomy. Her post-operative course was uneventful, and she has been doing well without any infective episodes over 3 years after surgery.

Peripheral Veno-Arterial Extracorporeal Membrane Oxygenation as a Bridge to Decision for Pediatric Fulminant Myocarditis.

It is essential to establish an appropriate initial treatment strategy for pediatric fulminant myocarditis. We reviewed eight cases of pediatric fulminant myocarditis that required extracorporeal membrane oxygenation (ECMO) from 2012 to 2015. The median age was 8 years (range 3 months-13 years), and the median body surface area was 0.89 m(2) (range 0.35-1.34 m(2) ). Peripheral veno-arterial ECMO was initially applied, and we evaluated whether heart decompression was sufficient. If the pump flow was insufficient, central cannulation was performed via median sternotomy (central ECMO). The need for subsequent ventricular assist device (VAD) support was determined 72 h after ECMO initiation. Six patients were bridged to recovery using peripheral ECMO support only (for 3-11 days), whereas two required VAD support. One patient was switched to central ECMO before VAD implantation. Three patients died of multiorgan failure, even though cardiac function recovered in two of those patients. The duration from hospital arrival to ECMO initiation was shorter in the survival (3.3 ± 1.3 h; range 1.6-4.7 h) than in the nonsurvival group (32 ± 28 h; range 0.7-55 h). Peripheral ECMO can be useful as a bridge to decision for pediatric fulminant myocarditis, which is frequently followed by a successful bridge to recovery. It is important to determine whether ECMO support should be initiated before organ dysfunction advances to preserve organ function, which provides a better bridge to subsequent VAD therapy and heart transplant or recovery.

Stoichiometric Assembly of the Cellulosome Generates Maximum Synergy for the Degradation of Crystalline Cellulose, as Revealed by In Vitro Reconstitution of the Clostridium thermocellum Cellulosome.

The cellulosome is a supramolecular multienzyme complex formed by species-specific interactions between the cohesin modules of scaffoldin proteins and the dockerin modules of a wide variety of polysaccharide-degrading enzymes. Cellulosomal enzymes bound to the scaffoldin protein act synergistically to degrade crystalline cellulose. However, there have been few attempts to reconstitute intact cellulosomes due to the difficulty of heterologously expressing full-length scaffoldin proteins. We describe the synthesis of a full-length scaffoldin protein containing nine cohesin modules, CipA; its deletion derivative containing two cohesin modules, ΔCipA; and three major cellulosomal cellulases, Cel48S, Cel8A, and Cel9K, of the Clostridium thermocellum cellulosome. The proteins were synthesized using a wheat germ cell-free protein synthesis system, and the purified proteins were used to reconstitute cellulosomes. Analysis of the cellulosome assembly using size exclusion chromatography suggested that the dockerin module of the enzymes stoichiometrically bound to the cohesin modules of the scaffoldin protein. The activity profile of the reconstituted cellulosomes indicated that cellulosomes assembled at a CipA/enzyme molar ratio of 1/9 (cohesin/dockerin = 1/1) and showed maximum synergy (4-fold synergy) for the degradation of crystalline substrate and ∼2.4-fold-higher synergy for its degradation than minicellulosomes assembled at a ΔCipA/enzyme molar ratio of 1/2 (cohesin/dockerin = 1/1). These results suggest that the binding of more enzyme molecules on a single scaffoldin protein results in higher synergy for the degradation of crystalline cellulose and that the stoichiometric assembly of the cellulosome, without excess or insufficient enzyme, is crucial for generating maximum synergy for the degradation of crystalline cellulose.

High heat flux reduction to materials using current filaments.

Reducing high electron and ion heat fluxes is one of the critical issues for shielding satellites and spacecraft. One of the ideas for shielding high particle and heat fluxes is to apply an external magnetic field generated by injecting current filaments. In this work, we model a flow of plasma, which includes electrons and ions in a small region, by using two spatial dimensions and three coordinates for velocities (2D3V) Particle-In-Cell (PIC) code to study the effects of the injected current filaments on particle and heat fluxes to the wall. The plasma enters the simulation domain from the source region at the left boundary and is fully absorbed in the conductor wall at the right boundary. Current filaments are injected to change the magnetic field structure of the system. We compare particle density, particle flux, and heat flux with and without injecting the current filaments into the domain in two dimensions. Based on the simulation results, we found that injecting current filaments can reduce the peak fluxes to the wall and transfer some of those fluxes along the wall. Therefore, injecting the current filaments is a good candidate for shielding satellites and spacecraft from high-energy ion and electron fluxes.

[A case of post-spinal tinnitus which improved after undergoing epidural anesthesia].

A 34-year-old woman suffering from post-spinal tinnitus for 8 years was scheduled for a cesarean section under epidural anesthesia selected to prevent a deterioration of this condition due to a possible decrease in the cerebrospinal fluid level. Unexpectedly, the tinnitus disappeared completely after the epidural injection of 2% lidocaine 27 ml and following continuous epidural infusion. It is conceivable that moderate quantities of local anesthetics into the epidural space might have acted as an effective method similar to that of epidural physiologic saline injection in order to improve the cerebrospinal pressure.

Warfarin-induced toxic epidermal necrolysis after mitral valve replacement.

Stevens-Johnson syndrome and toxic epidermal necrolysis are rare diseases that cause acute destruction of the epithelium of the skin and mucous membranes, almost always attributable to drugs. However, warfarin-induced Stevens-Johnson syndrome and toxic epidermal necrolysis is extremely rare. We report the case of 71-year-old woman who died due to destructive erosion all over her skin and mucous membranes. She had received a mitral valve prosthesis, and warfarin was prescribed for antithrombotic therapy. A lymphocyte transformation test for drug hypersensitivity and the clinical history confirmed this phenomenon as warfarin-induced toxic epidermal necrolysis.

Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD).

BACKGROUND: Trastuzumab (Tmab), pertuzumab (Pmab), and taxane has been a standard first-line treatment for recurrent or metastatic human epidermal growth factor (HER2)-positive breast cancer (HER2+ mBC) but has some safety issues due to taxane-induced toxicities. This has led to ongoing efforts to seek less toxic alternatives to taxanes that are equally effective when used in combination with Tmab plus Pmab. This study aims to show the non-inferiority of eribulin, a non-taxane microtubule inhibitor, against taxane, as a partner for dual HER2 blockade. METHODS/DESIGN: This multicenter, randomized, open-label, parallel-group, phase III study will involve a total of 480 Japanese women with HER2+ mBC who meet the following requirements: (1) age 20-70 years; (2) no prior cytotoxic chemotherapy (excluding trastuzumab-emtansine) for mBC; (3) ≥ 6 months after prior neoadjuvant or adjuvant cytotoxic chemotherapy; (4) presence of any radiologically evaluable lesion; (5) left ventricular ejection fraction ≥ 50%; (6) Eastern Cooperative Oncology Group performance status score of 0 or 1; (7) adequate organ function; and (8) life expectancy of at least 6 months. They will be randomized 1:1 to receive eribulin (1.4 mg/m2 on days 1 and 8) or taxane (docetaxel 75 mg/m2 on day 1 or paclitaxel 80 mg/m2 on days 1, 8, and 15) in combination with Tmab (8 mg/kg then 6 mg/kg) plus Pmab (840 mg then 420 mg) on day 1 of each 21-day cycle. The treatment will be continued until disease progression or unmanageable toxicity. The primary endpoint is progression-free survival as per investigator according to RECIST v1.1 criteria. Key secondary endpoints include objective response rate, overall survival, quality of life and safety. Non-inferiority will be tested with two margins of 1.33 and 1.25 in a stepwise manner. If non-inferiority is shown with a margin of 1.25, superiority will then be tested. DISCUSSION: If this study shows the non-inferiority, or even superiority, of Tmab, Pmab, and eribulin against the existing taxane-containing regimen, this new regimen may become a standard first- or second-line treatment option for HER2+ mBC in Japan. TRIAL REGISTRATION: ClinicalTrials.gov, ID: NCT03264547. Registered on 28 June 2017.

Correction to: Trastuzumab, pertuzumab, and eribulin mesylate versus trastuzumab, pertuzumab, and a taxane as a first-line or second-line treatment for HER2-positive, locally advanced or metastatic breast cancer: study protocol for a randomized controlled, non-inferiority, phase III trial in Japan (JBCRG-M06/EMERALD).

An amendment to this paper has been published and can be accessed via the original article.