Effect of esaxerenone on ischaemia and reperfusion injury in rat hearts.

OBJECTIVES: In myocardial infarction, the addition of mineralocorticoid receptor blockers to standard therapies, such as angiotensin-converting enzyme inhibitors or beta-blockers, reportedly reduces mortality and cardiac events. We investigated whether the non-steroidal mineralocorticoid receptor blocker esaxerenone has cardioprotective effects and its protective mechanisms. METHODS: Isolated rat hearts were Langendorff-perfused (constant pressure, 80 mmHg) with oxygenated Krebs-Henseleit bicarbonate buffer and reperfused for 60 min; afterwards, recovery of function (left ventricular pressure, measured with an intraventricular balloon) and myocardial injury were measured. In a preliminary study, we determined the optimal concentration of esaxerenone required for myocardial protection. Next, esaxerenone was administered in the pre- and post-ischaemic phases to determine the optimal timing of administration. In addition, we assessed coronary flow response to acetylcholine with and without esaxerenone. We examined whether esaxerenone-induced cardioprotection was prevented by targeting putative components in the preconditioning manner (the mitochondrial ATP-sensitive potassium [KATP] channel). RESULTS: Myocardial protection by esaxerenone was observed when esaxerenone was administered before ischaemia but not after ischaemia. The coronary flow response to acetylcholine was significantly better in the esaxerenone group than in the control group. The cardioprotective effect of esaxerenone was eliminated by the mitochondrial KATP channel blocker, 5-hydroxy decanoate. CONCLUSIONS: This study confirmed the myocardial protective effect of the pre-ischaemic administration of esaxerenone. Esaxerenone may contribute to coronary endothelial protection and exert pharmacological preconditioning via the mitochondrial KATP channel.

Characteristics of compounds with strong or weak nitrification inhibition in sewage.

To clarify the characteristics of compounds with strong or weak nitrification inhibition in sewage, 64 organic compounds including compounds registered in Pollutant Release and Transfer Register (PRTR) were evaluated in terms of their chemical structures and molecular weights. Nineteen compounds showed strong nitrification inhibition by testing with Nitrosomonas europaea. Compounds with thioamide structures had the lowest median value of EC50 (0.017 mg/L), followed by those with alkyne structures (0.121 mg/L), chlorophenol structures (0.300 mg/L), and then azole structures (0.365 mg/L). In contrast, 33 of the 64 compounds showed weak nitrification inhibition at a concentration of 10 mg/L, 27 of which were categorized into three main groups: long-chain alcohol structures, alkyne structures with a phenyl group, and aromatic structures. Most compounds with strong nitrification inhibition had a low molecular weight (MW) from 50 to 200. Meanwhile, the proportion of compounds with weak nitrification inhibition tended to be greater with increasing MW and such compounds were predominant at higher molecular weights above 300. The correlations of results derived from tests of nitrification inhibition based on ISO 9509 and N. europaea showed that 24 out of 30 compounds provided results that were highly correlated between these tests (R = 0.85), while 4 compounds with chlorophenol structures and 2 compounds with alkyne structures showed weaker inhibition rates in the ISO 9509 test than in the N. europaea test. Our results indicate that the magnitude of nitrification inhibition depends on MW in addition to the chemical structure, which is helpful in the search for the cause of nitrification inhibition in wastewater treatment plants.

Successful surgical experience for acute severe aortic valve regurgitation with acquired Gerbode defect: A case report.

INTRODUCTION AND IMPORTANCE: The incidence of acquired Gerbode defect has been increasing due to advances in cardiac imaging technology, and some closure methods have been introduced. PRESENTATION OF CASE: A 58-year-old man developed cardiogenic shock due to acute severe aortic valve regurgitation with an acquired Gerbode defect caused by infective endocarditis. Emergency surgery was performed. A large patch with a 0.4 mm extended-polytetrafluoroethylene (e-PTFE) sheet covered with autologous pericardium was used to close the Gerbode defect, and a bioprosthetic valve was used for aortic valve replacement. CLINICAL DISCUSSION: Large patch closure with 0.4 mm e-PTFE sheet and autologous pericardium for fragile Gerbode defect caused by infective endocarditis might be effective with regard to sturdiness, good fitting to the tissue, and excellent resistance to bacteria. CONCLUSION: We encountered a rare case of cardiogenic shock due to acute severe aortic valve regurgitation and acquired Gerbode defect caused by infective endocarditis. In our case, large-patch closure for perforation in a fragile membranous septum was effective.

Surgical Treatment of a Giant Popliteal Venous Aneurysm and Arteriovenous Fistula on the Adjacent Femoral Vein and Its Postoperative Findings.

A case of a giant popliteal venous aneurysm that caused massive pulmonary thromboembolism with an arteriovenous fistula draining into the adjacent proximal femoral vein is reported herein. Deep veins in the lower leg were occluded by thrombi. The inlet and outlet orifice inside the aneurysm was closed and aneurysmorraphy was performed. The fistula was retained on the estimation that it would maintain the blood flow and prevent thrombus formation inside the femoral vein. The aneurysm was shrunk, the femoral vein was patent, and the fistula was not observed 1 year later, although it still existed 1 week after the operation.

Predicting Inchinkoto efficacy, in patients with obstructive jaundice associated with malignant tumors, through pharmacomicrobiomics.

Inchinkoto (ICKT) is a popular choleretic and hepatoprotective herbal medicine that is widely used in Japan. Geniposide, a major ingredient of ICKT, is metabolized to genipin by gut microbiota, which exerts a choleretic effect. This study investigates the relationship between stool genipin-producing activity and diversity of the clinical effect of ICKT in patients with malignant obstructive jaundice. Fifty-two patients with malignant obstructive jaundice who underwent external biliary drainage were included. ICKT was administered as three packets per day (7.5 g/day) for three days and 2.5 g on the morning of the fourth day. Stool samples were collected before ICKT administration and bile flow was monitored on a daily basis. The microbiome, genipin-producing activity, and organic acids in stools were analyzed. The Shannon-Wiener (SW) index was calculated to evaluate gut microbiome diversity. The stool genipin-producing activity showed a significant positive correlation with the SW index. Stool genipin-producing activity positively correlated with the order Clostridia (obligate anaerobes), but negatively correlated with the order Lactobacillales (facultative anaerobes). Moreover, stool genipin-producing activity was positively correlated to the concentration valeric acid, but negatively correlated to the concentration of lactic acid and succinic acid. The change of bile flow at 2 and 3 days after ICKT administration showed significant positive correlation with genipin-producing activity (correlation coefficient, 0.40 and 0.29, respectively, P < 0.05). An analysis of stool profile, including stool genipin-producing activity, may predict the efficacy of ICKT. Modification of the microbiome may be a target to enhance the therapeutic effect of ICKT.

Comprehensive metabolome analysis for the pharmacological action of inchinkoto, a hepatoprotective herbal medicine.

INTRODUCTION: The precise pharmacological action of inchinkoto (ICKT, Yin-Chen-Hao-Tang in Chinese), a hepatoprotective herbal medicine, on total metabolic pathways has not been well investigated. OBJECTIVES: The aim of this study was to explore the serum metabolites reflecting the pharmacological activity of ICKT, and mechanism of action of ICKT using serum metabolome analysis. METHODS: 54 patients with obstructive jaundice due to malignancies were included in this study. ICKT was administered for 3 days. Serum and bile samples were collected before and 1 h after ICKT administration on days 1 and 4. Serum metabolome analysis including ICKT components were performed. RESULTS: The levels of total/direct bilirubin, C-reactive protein, γ-glutamyl transpeptidase, and albumin in the serum were significantly improved after ICKT administration. In the serum metabolome analysis, inosine was the only elevated metabolite on days 1 and 4. Most of the metabolites which were significantly changed after ICKT administration were lipid mediators, and all decreased on day 1. Notably, the levels of many lipid mediators were increased on day 4. The difference in serum aspartic acid 1 h after ICKT administration was significantly correlated with a decrease in the levels of total bilirubin in the serum on day 4. CONCLUSIONS: Using metabolome analysis, we demonstrated several metabolic changes that may be associated with the pharmacological mechanisms of ICKT. The biological implications of these metabolites should be further investigated in basic research studies.

Freshwater alga Raphidocelis subcapitata undergoes metabolomic changes in response to electrostatic adhesion by micrometer-sized nylon 6 particles.

Nylon powders are a type of microplastic (MP) used in personal care products such as cosmetics and sunscreens. To determine the effects of nylon polymers on freshwater microalgae, we investigated the effects of two types of micrometer-sized nylon polymers, i.e., powdered nylon 6 (Ny6-P) and nylon 12 (Ny12), and four other micrometer-sized MPs, i.e., low-density polyethylene, polyethylene terephthalate, polystyrene, and ultra-high-molecular-weight polyethylene, on the microalga Raphidocelis subcapitata. The results showed that Ny6-P inhibited R. subcapitata growth more than the other MPs; R. subcapitata growth was inhibited by 54.2% with 6.25 mg/L Ny6-P compared with the control. Ny6-P in the culture media adhered to R. subcapitata cells electrostatically, which may have disrupted growth and photosynthetic activity. Metabolomic analysis revealed that many metabolites related to the amino acid catabolic pathway and γ-glutamyl cycle were induced, which might trigger responses to avoid starvation and oxidative stress. Our study provides important information on the effects of Ny6-P on algae in freshwater environments.

Mechanism and design of a novel 8K ultra-high-definition video microscope for microsurgery.

The practical application of microscopes using 8K ultra-high definition (UHD) technology is progressing. However, due to insufficiencies in factors such as luminous intensity and stereopsis, it has not been possible to achieve sufficient image quality for close observation of submillimeter order microlymphatic anastomosis using a combination of 8K-UHD cameras with a rigid endoscope. We have improved the quality of microsurgery by the introduction of a new heads up 8K-UHD surgical system. Herein, we show the mechanisms of this next-generation technology that makes optical improvements to the electronic image input data, resolving the initial drawback. We have developed a new 8K-UHD digital microscope system with digital zooming to enable maximum 300X magnification of the surgical field. This system has specific lighting settings for shadows dropped in surgical field to expand the three-dimensional effect while still being a monocular camera. The original mechanism and design enable the increase of the depth of field with optimal angles between the imaging direction and approaching direction towards the surgical field. Assessment during a pre-clinical trial using rats demonstrated that it is possible to perform microlymphatic anastomosis in a heads-up position with a 70-inch 8K-UHD monitor and the 8K-UHD monocular camera system. Performing supermicrosurgery is difficult with conventional surgical microscopes. Our results illustrate the application of this new 8K-UHD microscope system to this new field.

Pleural dissemination of cholangiocarcinoma caused by percutaneous transhepatic biliary drainage during the management of resectable cholangiocarcinoma.

BACKGROUND: Only 3 case reports have addressed pleural dissemination in association with percutaneous transhepatic biliary drainage. The aim of this study was to investigate recurrence after resection of cholangiocarcinoma after percutaneous transhepatic biliary drainage and to clarify the incidence of and the factors responsible for pleural dissemination. METHODS: Between 2001 and 2015, we reviewed retrospectively all consecutive patients who underwent resection for perihilar or distal cholangiocarcinoma after percutaneous transhepatic biliary drainage for recurrence, including pleural dissemination. RESULTS: During the study period, all consecutive patients underwent resection of cholangiocarcinoma after management with percutaneous transhepatic biliary drainage. Of these, 100 patients (32.1%) underwent left-sided percutaneous transhepatic biliary drainage alone, and 212 (67.9%) underwent right-sided percutaneous transhepatic biliary drainage with or without left-sided percutaneous transhepatic biliary drainage. Pleural dissemination, which developed exclusively on the right side of the thoracic cavity after resection, was found in 12 patients (3.8%); these patients underwent right-sided percutaneous transhepatic biliary drainage; computed tomography demonstrated that the percutaneous transhepatic biliary drainage catheter passed through the thoracic cavity in all 12 patients. The diagnosis of pleural dissemination was made at a median of 381 days (range, 44 to 2,944 days) after operation. Survival was poor, with a median survival time of 516 days. Statistically, right-sided percutaneous transhepatic biliary drainage was identified as a risk factor for pleural dissemination. CONCLUSION: Pleural dissemination after right-sided percutaneous transhepatic biliary drainage is likely a procedure-related iatrogenic complication because of the "special route" by which the percutaneous transhepatic biliary drainage catheter must be passed through the right thoracic cavity.

8K ultra-high-definition microscopic camera for ophthalmic surgery.

BACKGROUND: We have developed a new compact lightweight 8K ultra-high-definition (UHD; 7,680×4,320 pixels) camera and started medical application with an ophthalmic surgical microscope which is interchangeable with the conventional high-definition (1,920×1,080 pixels)/4K UHD (3,840×2,160 pixels) microscopic camera. METHODS: We did a feasibility study to apply our 8K UHD microscope in cataract surgery, glaucoma surgery and vitreous surgery using pig cadaver eyes. The 8K UHD microscope comprises a surgical microscope, a camera adaptor with relay lenses, an 8K UHD camera and an 8K UHD LCD to share the 8K UHD images with all surgical staff in real time. RESULTS: In ophthalmic surgeries, higher resolution images than conventional microscopic cameras were obtained with 8K UHD LCD equivalent to the observation through the microscopic eye pieces. CONCLUSION: Based on the results of this feasibility study, clinical trials on human ophthalmic surgery using the new 8K UHD microscopic camera should be conducted in the near future.

Midterm outcomes after aortic valve neocuspidization with glutaraldehyde-treated autologous pericardium.

OBJECTIVE: We had previously reported the short-term results of the aortic valve neocuspidization (AVNeo) procedure. We have now evaluated the midterm results with the longest follow-up of 118 months. METHODS: From April 2007 through December 2015, 850 patients were treated with AVNeo using autologous pericardium. Medical records of these patients were retrospectively reviewed. The procedure was on the basis of independent tricuspid replacement using autologous pericardium. The distances between the commissures were measured with an original sizing device, the pericardial cusp was trimmed using an original template, and then sutured to the annulus. RESULTS: There were 534 patients with aortic stenosis, 254 with aortic regurgitation, 61 with aortic stenoregurgitation, 19 with infective endocarditis, and 5 with a previous aortic valve procedure. Besides 596 patients with tricuspid aortic valve, 224 patients had bicuspid valve, 28 had unicuspid valve, and 2 had quadricuspid valve. There were 444 male and 406 female patients. The median age was 71 (range, 13-90) years old. Preoperative echocardiography revealed a peak pressure gradient average of 68.9 ± 36.3 mm Hg with aortic stenosis. Surgical annular diameter was 20.9 ± 3.3 mm. There was no conversion to a prosthetic valve replacement. There were 16 in-hospital mortalities. Postoperative echocardiography revealed a peak pressure gradient average of 19.5 ± 10.3 mm Hg 1 week after surgery and 15.2 ± 6.3 mm Hg 8 years after surgery. Fifteen patients needed reoperation (13 infective endocarditis, 1 break of thread, and 1 tear of cusp case). The mean follow-up period was 53.7 ± 28.2 months. Actuarial freedom from death, cumulative incidence of reoperation, and that of recurrent moderate aortic regurgitation or greater was 85.9%, 4.2%, and 7.3%, respectively, with the longest follow-up of 118 months. CONCLUSIONS: The midterm outcomes of AVNeo using autologous pericardium were satisfactory in 850 patients with various aortic valve diseases. However, further randomized, multicenter prospective studies are needed to confirm the results of the current study.

Effect of an 8K ultra-high-definition television system in a case of laparoscopic gynecologic surgery.

Various endoscopic devices have been developed for advanced minimally invasive surgery. We recently applied a new 8K ultra-high-definition television system during laparoscopic treatment of endometriosis. The procedure, which is described in detail, stands as the first reported application of an 8K ultra-high-definition system for laparoscopic gynecologic surgery. Comparison is made between depiction of the lesion by the new system and depiction by a full high-definition system. Improved diagnostic accuracy resulted from the increased image resolution, and we believe that this and other advantages will lead to widespread acceptance and further application of 8K ultra-high-definition systems in the field of gynecologic surgery.

Ultra-high definition (8K UHD) endoscope: our first clinical success.

BACKGROUND: We have started clinical application of 8K ultra-high definition (UHD; 7680 × 4320 pixels) imaging technology, which is a 16-fold higher resolution than the current 2K high-definition (HD; 1920 × 1080 pixels) technology, to an endoscope for advanced laparoscopic surgery. RESULTS: Based on preliminary testing experience and with subsequent technical and system improvements, we then proceeded to perform two cases of cholecystectomy and were able to achieve clinical success with an 8K UHD endoscopic system, which consisted of an 8K camera, a 30-degrees angled rigid endoscope with a lens adapter, a pair of 300-W xenon light sources, an 85-inch 8K LCD and an 8K video recorder. These experimental and clinical studies revealed the engineering and clinical feasibility of the 8K UHD endoscope, enabling us to have a positive outlook on its prospective use in clinical practice. CONCLUSIONS: The 8K UHD endoscopy promises to open up new possibilities for intricate procedures including anastomoses of thin nerves and blood vessels as well as more confident surgical resections of a diversity of cancer tissues. 8K endoscopic imaging, compared to imaging by the current 2K imaging technology, is very likely to lead to major changes in the future of medical practice.

Diagnostic value of procalcitonin for acute complicated appendicitis.

A rapid and reliable test for detection of complicated appendicitis would be useful when deciding whether emergency surgery is required. We investigated the clinical usefulness of procalcitonin for identifying acute complicated appendicitis. We retrospectively analyzed 63 patients aged ≥15 years who underwent appendectomy without receiving antibiotics before admission and had preoperative data on the plasma procalcitonin level (PCT), body temperature (BT), white blood cell count (WBC), neutrophil / lymphocyte ratio (N/L ratio), and C-reactive protein level (CRP). Patients were classified into 3 groups: group A (inflammatory cell infiltration of the appendix with intact mural architecture), group B (inflammatory cell infiltration with destruction of mural architecture, but without abscess or perforation), and group C (macroscopic abscess and/or perforation). For identifying destruction of mural architecture, the diagnostic accuracy of PCT was similar to that of BT or CRP. However, the diagnostic accuracy of PCT was highest among the five inflammatory indices for identifying abscess and/or perforation, with the positive predictive value of PCT for abscess and/or perforation being higher than that of CRP (73% vs. 48%). Univariate analysis of the predictors of abscess and/or perforation revealed that a plasma PCT level ≥0.46 ng/mL had the highest odds ratio (30.3 [95% confidence interval: 6.5-140.5] versus PCT <0.46 ng/mL). These findings indicate that procalcitonin is a useful marker of acute appendicitis with abscess and/or perforation.

Fetal Gene Therapy for Ornithine Transcarbamylase Deficiency by Intrahepatic Plasmid DNA-Micro-Bubble Injection Combined with Hepatic Ultrasound Insonation.

We evaluated the therapeutic efficacy of hepatic transfection of plasmid DNA using micro-bubbles and ultrasound insonation for fetal correction of ornithine transcarbamylase (OTC) deficiency in mice. Twenty-three sparse-fur heterozygous pregnant mice (day 16 of gestation) were divided into three groups: injection of plasmid-DNA micro-bubble mixture into fetal liver with ultrasound insonation (Tr, n = 11); control group 1 (C1), injection of plasmid-DNA micro-bubble mixture into fetal liver with no insonation (n = 5); and control group 2 (C2), injection of saline-micro-bubble mixture into fetal liver with ultrasound insonation (n = 7). Levels of blood ammonia and urinary orotic acid were significantly lower in the Tr group than in the C1 and C2 groups (p < 0.05, p < 0.01, respectively), whereas OTC activity was not different between groups. Therefore, ultrasound insonation with micro-bubbles enhanced plasmid DNA transfection into fetal mouse liver, leading to one of the therapeutic methods in ammonia metabolism. This might provide more time for OTC-deficient infants until liver transplantation.

Towards scene adaptive image correspondence for placental vasculature mosaic in computer assisted fetoscopic procedures.

BACKGROUND: Visualization of the vast placental vasculature is crucial in fetoscopic laser photocoagulation for twin-to-twin transfusion syndrome treatment. However, vasculature mosaic is challenging due to the fluctuating imaging conditions during fetoscopic surgery. METHOD: A scene adaptive feature-based approach for image correspondence in free-hand endoscopic placental video is proposed. It contributes towards existing techniques by introducing a failure detection method based on statistical attributes of the feature distribution, and an updating mechanism that self-tunes parameters to recover from registration failures. RESULTS: Validations on endoscopic image sequences of a phantom and a monkey placenta are carried out to demonstrate mismatch recovery. In two 100-frame sequences, automatic self-tuned results improved by 8% compared with manual experience-based tuning and a slight 2.5% deterioration against exhaustive tuning (gold standard). CONCLUSION: This scene-adaptive image correspondence approach, which is not restricted to a set of generalized parameters, is suitable for applications associated with dynamically changing imaging conditions. Copyright © 2015 John Wiley & Sons, Ltd.

Self-contained image mapping of placental vasculature in 3D ultrasound-guided fetoscopy.

BACKGROUND: Surgical navigation technology directed at fetoscopic procedures is relatively underdeveloped compared with other forms of endoscopy. The narrow fetoscopic field of views and the vast vascular network on the placenta make examination and photocoagulation treatment of twin-to-twin transfusion syndrome challenging. Though ultrasonography is used for intraoperative guidance, its navigational ability is not fully exploited. This work aims to integrate 3D ultrasound imaging and endoscopic vision seamlessly for placental vasculature mapping through a self-contained framework without external navigational devices. METHODS: This is achieved through development, integration, and experimentation of novel navigational modules. Firstly, a framework design that addresses the current limitations based on identified gaps is conceptualized. Secondly, integration of navigational modules including (1) ultrasound-based localization, (2) image alignment, and (3) vision-based tracking to update the scene texture map is implemented. This updated texture map is projected to an ultrasound-constructed 3D model for photorealistic texturing of the 3D scene creating a panoramic view of the moving fetoscope. In addition, a collaborative scheme for the integration of the modular workflow system is proposed to schedule updates in a systematic fashion. Finally, experiments are carried out to evaluate each modular variation and an integrated collaborative scheme of the framework. RESULTS: The modules and the collaborative scheme are evaluated through a series of phantom experiments with controlled trajectories for repeatability. The collaborative framework demonstrated the best accuracy (5.2 % RMS error) compared with all the three single-module variations during the experiment. Validation on an ex vivo monkey placenta shows visual continuity of the freehand fetoscopic panorama. CONCLUSIONS: The proposed developed collaborative framework and the evaluation study of the framework variations provide analytical insights for effective integration of ultrasonography and endoscopy. This contributes to the development of navigation techniques in fetoscopic procedures and can potentially be extended to other applications in intraoperative imaging.

A Case of Severe Unicuspid Aortic Valve Stenosis: Valve Repair With Tricuspidization in an Adult.

A 33-year-old male was referred to our institute with acute heart failure. The patient was found to have a unicuspid aortic valve (UAV) and severe aortic stenosis. He had been followed at a local university hospital during childhood. However, he stopped visiting the outpatient clinic after becoming an adult. His condition subsequently worsened, and he ultimately presented to our hospital with cardiogenic shock. In Japan, some adult congenital heart disease (ACHD) patients continue to be followed by pediatric cardiologists, though the patterns of practice are variable. This report describes the case of a patient who became lost to follow-up in early adulthood. We thus focus on this ACHD case as an example of the effects of inadequate communication among doctors and the need to establish better ACHD management protocols for treating this patient population.