Renal Biomarkers in the Early Detection of Acute Kidney Injury After Off-Pump Coronary Artery Bypass Grafting.

BACKGROUND: Cardiac surgery-associated (CSA) acute kidney injury (AKI) is a severe postoperative complication in patients undergoing off-pump coronary artery bypass grafting (OPCAB). Early detection of postoperative CSA-AKI may be key to improving patient outcomes. This study explored the use of renal biomarkers measured immediately after surgery for the early detection of CSA-AKI in patients undergoing OPCAB.Methods and Results: In all, 111 patients who underwent OPCAB at Kumamoto University Hospital between June 2020 and October 2022 were included in this study. Urinary neutrophil gelatinase-associated lipocalin, liver-type fatty acid-binding protein, and N-acetyl-ß-D-glucosaminidase (NAG) were measured upon arrival in the intensive care unit (ICU) after surgery. AKI was diagnosed using KDIGO criteria. Of the 111 patients, 32 (28.8%) developed postoperative AKI. Regarding AKI staging, 19 (59.4%), 11 (34.4%), and 2 (6.3%) patients had Stage 1, 2, and 3 AKI, respectively. There were significant differences in chronic kidney disease, preoperative estimated glomerular filtration rate (eGFR), and NAG between the AKI and non-AKI groups. Multivariate analysis showed that preoperative eGFR (odds ratio [OR] for 5-mL/min/1.73 m2increase in eGFR 0.75; 95% confidence interval [CI] 0.63-0.89) and increasing urinary NAG concentrations at ICU admission (OR 2.44; 95% CI 1.30-4.60) were significant risk factors for CSA-AKI in OPCAB patients. CONCLUSIONS: NAG and eGFR may be valuable biomarkers for the early detection of CSA-AKI in patients undergoing OPCAB.

Free Jejunal Graft Interposition with Vascular Reconstruction in Patients Undergoing Pharyngo Laryngo Esophagectomy.

BACKGROUND: Pharyngo-esophageal reconstruction using free jejunal grafts has been widely used for the treatment of locally advanced carcinomas of the hypopharynx and cervical esophagus. However, the procedure is technically demanding and requires complex recontractions. The aim of this study was to evaluate our institutional outcomes of reconstruction using a free jejunal graft with vascular reconstruction in patients undergoing pharyngo laryngo esophagectomy with a multidisciplinary surgical team. METHODS: There were 90 consecutive patients between October 2006 and February 2021. The mean age was 64.6 ± 10.3 years, and there were 76 male patients. Of 90 patients, 49 underwent preoperative chemotherapy and/or radiotherapy. Jejunal vessels were commonly anastomosed to the common carotid artery and the internal jugular vein (77.8% and 92.2%, respectively). Continuous intravenous infusion of heparin was used postoperatively. RESULTS: Necrosis of the graft was observed in 5 patients. An isolated revision of vein was necessary in 1 patient. In all cases of graft failure, heparin was not used postoperatively. On the other hand, among the patients without graft failure, heparin was used for about two-thirds of the patients and was significantly different (0% vs. 66%, P = 0.01). CONCLUSIONS: Free jejunal graft with vessel reconstruction is a safe and effective method for patients undergoing pharyngo laryngo esophagectomy. The position for the prevention of kinking as well anastomosis maneuver of vein is especially important. Moreover, early postoperative anticoagulation is essential.

[A Combination Therapy with Antibiotic and Surgical Treatment in a Patient with Patent Ductus Arteriosus with Pulmonary Vegetation:Report of a Case].

We present a case of a 24-year-old female who presented with a history of fever and back pain. She had no particular medical history and was not taking any medication. Transthoracic echocardiology and computed tomography showed a patent ductus arteriosus with vegetation in the pulmonary artery. She was treated with penicillin G;however, the vegetation embolized into the left pulmonary artery. After the antibiotics was changed to clindamycin and ceftriaxone, the resolution of the lung abscess was shown by computed tomography( CT). Two months later, a surgical repair of the patent ductus arteriosus was successfully performed. Patent ductus arteriosus-associated infectious endocarditis is relatively rare in adulthood.

Diversity-oriented synthesis yields novel multistage antimalarial inhibitors.

Antimalarial drugs have thus far been chiefly derived from two sources-natural products and synthetic drug-like compounds. Here we investigate whether antimalarial agents with novel mechanisms of action could be discovered using a diverse collection of synthetic compounds that have three-dimensional features reminiscent of natural products and are underrepresented in typical screening collections. We report the identification of such compounds with both previously reported and undescribed mechanisms of action, including a series of bicyclic azetidines that inhibit a new antimalarial target, phenylalanyl-tRNA synthetase. These molecules are curative in mice at a single, low dose and show activity against all parasite life stages in multiple in vivo efficacy models. Our findings identify bicyclic azetidines with the potential to both cure and prevent transmission of the disease as well as protect at-risk populations with a single oral dose, highlighting the strength of diversity-oriented synthesis in revealing promising therapeutic targets.

Development and evaluation of the effectiveness of educational material for radiological protection that uses augmented reality and virtual reality to visualise the behaviour of scattered radiation.

Understanding the behaviour of scattered radiation is important for learning appropriate radiation protection methods, but many existing visualisation systems for radiation require special devices, making it difficult to use them in education. The purpose of this study was to develop teaching material for radiation protection that can help visualise the scattered radiation with augmented reality (AR) and virtual reality (VR) on a web browser, develop a method for using it in education and examine its effectiveness. The distribution of radiation during radiography was calculated using Monte Carlo simulation, and teaching material was created. The material was used in a class for department of radiological technology students and its influence on motivation was evaluated using a questionnaire based on the evaluation model for teaching materials. In addition, text mining was used to evaluate impressions objectively. Educational material was developed that can be used in AR and VR for studying the behaviour of scattered radiation. The results of the questionnaire showed that the average value of each item was more than four on a five-point scale, indicating that the teaching material attracted the interest of users. Through text mining, it could be concluded that there was improved understanding of, and confidence in, radiation protection.

[Coronary Artery Bypass Grafting via Partial Sternotomy Late after Partial Chest Wall Resection:Report of a Case].

A 74-year-old man was referred to our department to receive coronary artery bypass grafting (CABG) because of severe triple vessel disease. He had undergone a chest wall resection including the right clavicle and the first and second ribs for the fibrosarcoma 40 years ago. The right internal thoracic artery was resected at the operation. Twenty-nine years after the operation, the plate used for the reconstruction of the chest wall was removed because of its infection. Off-pump CABG using left internal thoracic artery and vein grafts with lower partial sternotomy was successfully performed for the complete revascularization. This patient had a high possibility of sternum dehiscence and postoperative mediastinitis due to poor blood flow in the right upper sternum.

[Concurrent Surgical Venous Repair during Laser-assisted Pacemaker Lead Extraction].

Pacemakers are widely used to treat arrhythmia, however, one of problems after implantation of pacemaker is device infection. Total removal of leads and generator is recommended for radical cure. Recently, transvenous laser-assisted extraction of pacemaker leads has been developed and has achieved good results. However, catastrophic complications during pacemaker and implantable cardioverter-defibrillator leads extraction have been reported, and cases requiring surgical reconstruction have been also reported. Most of the repair technique include a direct suturing or a partial repair with patch. We herein report two cases of superior vena cava and innominate vein reconstruction with bovine pericardium during transvenous laser-assisted extraction. A hybrid approach using transvenous laser-assisted extraction and surgical repair through median sternotomy should be considered to perform complete lead extraction in complex cases with pacemaker lead infection.

Development of an application to visualise the spread of scattered radiation in radiography using augmented reality.

As radiation is widely used in medical institutions, the lack of radiation protection education for health workers increases the risk of radiation exposure. The purpose of this study is to develop an application for radiation medical personnel that visualises the distribution of scattered radiation by using augmented reality (AR). The irradiation conditions for mobile chest and pelvic radiography were simulated using Monte Carlo simulations (Particle and Heavy Ion Transport code System). Monte Carlo results were verified using physical measurements. The behaviour of scattered radiation was displayed three-dimensionally in virtual reality using ParaView. Subsequently, an application to visualise scattered rays was developed in Unity for tablet devices. An application with a sense of reality was developed by visualising the scattered radiation distribution of a mobile imaging in a real space in AR in a three-dimensional size, which is close to the actual size. The radiation dose could be estimated at any position and the behaviour of scattered radiation became easier to understand.

Risk of Out-of-Hospital Cardiac Arrest in Aged Individuals in Relation to Cold Ambient Temperature　- A Report From North Tochigi Experience.

BACKGROUND: The impact of cold ambient temperature on out-of-hospital cardiac arrest (OHCA) in aged individuals caused by cardiovascular events in indoor environments has not been investigated sufficiently.Methods and Results:We conducted a case-crossover study. The relationship between OHCA caused by cardiovascular events and exposure to minimum temperature <0℃ was analyzed. Conditional logistic regression analysis was performed to estimate the odds ratios for the relationship between exposure to minimum temperature <0℃ and the risk of OHCA. Between January 1, 2011, and December 31, 2015, a total of 1,452 cases of OHCA were documented, and patients were screened for enrollment. A total of 458 individuals were enrolled in this analysis, and were divided into 2 groups of 110 (elderly group: 65-74 years old) and 348 (aged group: ≥75 years old). The aged individuals had a significant increased risk of OHCA after exposure to minimum temperature <0℃ (odds ratio [OR]: 1.528, 95% confidence interval [CI] 1.009-2.315, P=0.045). Cold ambient temperature was an especially significant increased risk for OHCA occurrence for males (OR: 1.997, 95% CI 1.036-3.773, P=0.039) and during winter (OR: 2.391, 95% CI 1.312-4.360, P=0.004) in the aged group. CONCLUSIONS: Cold ambient temperature significantly affected aged individuals (≥75 years old) experiencing an OHCA caused by cardiovascular events in indoor environments.

4-Substituted carbamazepine derivatives: Conformational analysis and sodium channel-blocking properties.

The physicochemical properties of 4-substituted carbamazepine derivatives were investigated. It was elucidated that the 4-substitution is not effective in reducing the rotations (E/Z) about the N-C1' axes around the outer carbamoyl moiety. However, the atropisomers were isolated with high stereochemical stability, meaning that the 4-substitution reduced the butterfly motion of the tricyclic ring system efficiently. The Cl/CH3-substituted carbamazepine derivatives showed greater inhibitory effects on hNav1.2 channel currents compared with carbamazepine, although no difference in the activity between enantiomers was observed.

Development of torsadogenic risk assessment using human induced pluripotent stem cell-derived cardiomyocytes: Japan iPS Cardiac Safety Assessment (JiCSA) update.

Cardiac safety assessment is challenging because a better understanding of torsadogenic mechanisms beyond hERG blockade and QT interval prolongation is necessary for patient safety. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) provide a new human cell-based platform to assess cardiac safety in non-clinical testing during drug development. The multi-electrode array (MEA) platform is a promising electrophysiological technology to assess QT interval prolongation and proarrhythmic potential of drug candidates using hiPSC-CMs. The Japan iPS Cardiac Safety Assessment (JiCSA) has established an MEA protocol to evaluate the applicability of hiPSC-CMs for assessing the torsadogenic potential of compounds and completed a large-scale validation study using 60 compounds. During our study, an international multi-site study of hiPSC-CMs was performed by the Comprehensive in Vitro Proarrhythmia Assay (CiPA) initiative using 28 compounds. We have comparatively analyzed our JiCSA datasets with those of CiPA using the CiPA logistical and ordinal linear regression model. Regardless of the protocol differences, the evaluation results of the 28 compounds were very similar and highly predictable for torsadogenic risks. Thus, an MEA-based approach using hiPSC-CMs would be a standard testing method to evaluate proarrhythmic potentials. This review paper would provide new insights into the hiPSC-CMs/MEA method required for its regulatory use.

Yield Visualization Based on Farm Work Information Measured by Smart Devices.

This paper proposes a new approach to visualizing spatial variation of plant status in a tomato greenhouse based on farm work information operated by laborers. Farm work information consists of a farm laborer's position and action. A farm laborer's position is estimated based on radio wave strength measured by using a smartphone carried by the farm laborer and Bluetooth beacons placed in the greenhouse. A farm laborer's action is recognized based on motion data measured by using smartwatches worn on both wrists of the farm laborer. As experiment, harvesting information operated by one farm laborer in a part of a tomato greenhouse is obtained, and the spatial distribution of yields in the experimental field, called a harvesting map, is visualized. The mean absolute error of the number of harvested tomatoes in each small section of the experimental field is 0.35. An interview with the farm manager shows that the harvesting map is useful for intuitively grasping the states of the greenhouse.

[Redo Aortic and Mitral Valve Replacement by Manouguian's Procedure for Active Prosthetic Valve Infection].

The damage to the intervalvular fibrous trigone (IVFT) by infective endocarditis makes combined aortic and mitral valve replacement difficult. We performed Manouguian's double valve replacement for such a case and obtained a good result. A 81-year-old male underwent emergency operation due to active prosthetic valve endocarditis. He had a history of receiving combined aortic and mitral valve replacement because of active infective endocarditis at the age of 74 and redo aortic valve replacement 3 years after that. The infectious lesion extended from the mitral annulus to the IVFT and the aortic annulus, and it caused the prosthetic valve detachment from the aortic annulus. Manouguian's double valve replacement was required for radical resection and reconstruction of the IVFT. No recurrent infection or paravalvular leakage was observed during 49months follow up period. Manouguian's procedure is useful for complete resection of the infected IVFT and makes combined aortic and mitral valve replacement safer.

Contractility assessment using aligned human iPSC-derived cardiomyocytes.

INTRODUCTION: Cardiac safety assessment, such as lethal arrhythmias and contractility dysfunction, is critical during drug development. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been shown to be useful in predicting drug-induced proarrhythmic risk through international validation studies. Although cardiac contractility is another key function, fit-for-purpose hiPSC-CMs in evaluating drug-induced contractile dysfunction remain poorly understood. In this study, we investigated whether alignment of hiPSC-CMs on nanopatterned culture plates can assess drug-induced contractile changes more efficiently than non-aligned monolayer culture. METHODS: Aligned hiPSC-CMs were obtained by culturing on 96-well culture plates with a ridge-groove-ridge nanopattern on the bottom surface, while non-aligned hiPSC-CMs were cultured on regular 96-well plates. Next-generation sequencing and qPCR experiments were performed for gene expression analysis. Contractility of the hiPSC-CMs was assessed using an imaging-based motion analysis system. RESULTS: When cultured on nanopatterned plates, hiPSC-CMs exhibited an aligned morphology and enhanced expression of genes encoding proteins that regulate contractility, including myosin heavy chain, calcium channel, and ryanodine receptor. Compared to cultures on regular plates, the aligned hiPSC-CMs also showed both enhanced contraction and relaxation velocity. In addition, the aligned hiPSC-CMs showed a more physiological response to positive and negative inotropic agents, such as isoproterenol and verapamil. DISCUSSION: Taken together, the aligned hiPSC-CMs exhibited enhanced structural and functional properties, leading to an improved capacity for contractility assessment compared to the non-aligned cells. These findings suggest that the aligned hiPSC-CMs can be used to evaluate drug-induced cardiac contractile changes.

Macrophage-derived angiopoietin-like protein 2 accelerates development of abdominal aortic aneurysm.

OBJECTIVE: Recently, we reported that angiopoietin-like protein 2 (Angptl2) functions in various chronic inflammatory diseases. In the present study, we asked whether Angptl2 and its associated chronic inflammation contribute to abdominal aortic aneurysm (AAA). METHODS AND RESULTS: Immunohistochemistry revealed that Angptl2 is abundantly expressed in infiltrating macrophages within the vessel wall of patients with AAA and in a CaCl(2)-induced AAA mouse model. When Angptl2-deficient mice were used in the mouse model, they showed decreased AAA development compared with wild-type mice, as evidenced by reduction in aneurysmal size, less severe destruction of vessel structure, and lower expression of proinflammatory cytokines and matrix metalloproteinase-9. However, no difference in the number of infiltrating macrophages within the aortic aneurysmal vessel wall was observed between genotypes. AAA development was also significantly suppressed in wild-type mice that underwent Angptl2-deficient bone marrow transplantation. Expression levels of proinflammatory cytokines and metalloproteinase-9 in Angptl2-deficient macrophages were significantly decreased, and those decreases were rescued by treatment of Angptl2 deficient macrophages with exogenous Angptl2. CONCLUSIONS: Macrophage-derived Angptl2 contributes to AAA development by inducing inflammation and degradation of extracellular matrix in the vessel wall, suggesting that targeting the Angptl2-induced inflammatory axis in macrophages could represent a new strategy for AAA therapy.

Acute heart failure due to coronary subclavian steal syndrome after coronary artery bypass grafting.

Key clinical message: An axillo-axillary bypass grafting is useful for coronary subclavian steal syndrome when occlusion of the proximal left subclavian artery. Abstract: An 81-year-old female who had undergone coronary artery bypass grafting 15 years previously was admitted and diagnosed with coronary subclavian steal syndrome. Preoperative angiography showed backflow from the left anterior descending coronary artery to the left internal thoracic artery and occlusion of the proximal left subclavian artery. Axillo-axillary bypass grafting was successfully performed.

Outcomes of mitral valve replacement with complete annular decalcification.

BACKGROUND: This study aimed to examine the clinical outcomes of mitral valve replacement (MVR) in patients with severe mitral annular calcification (MAC) who required extensive decalcification and mitral annular reconstruction. METHODS: We reviewed 15 patients with severe MAC who underwent MVR between January 2016 and May 2022. In all cases, the calcified mitral annulus was resected completely using a Cavitron Ultrasound Surgical Aspirator, and a new annulus was created using bovine pericardium. In the acute postoperative phase, strict afterload reduction therapy using an intra-aortic balloon pump (IABP) was administered. RESULTS: The mean age of patients was 73 ± 8 years, and 13 (86.7%) were women. Concomitant aortic valve replacement was performed in 11 (73.3%) patients, tricuspid annuloplasty in 9 (60.0%), coronary artery bypass grafting in 1 (6.7%), and arrhythmia surgery in 7 (46.7%). The mean aortic cross-clamp and cardiopulmonary bypass times were 143 ± 32 min and 175 ± 34 min, respectively. In 13 patients, an IABP was used for 2 or 3 days postoperatively. There were no in-hospital deaths, left ventricular ruptures, or other MAC-related complications. Postoperative echocardiography revealed no paravalvular leakages. CONCLUSION: Our strategy for managing severe MAC is safe and reproducible even in relatively high-risk patients. Afterload reduction using an IABP in the acute postoperative phase may reduce the risk of fatal complications after extensive decalcification and mitral annular reconstruction.

Mitral valve replacement with annuloplasty in a patient with infected mitral annular calcification.

Key Clinical Message: Extensive resection of the infected calcified annulus and the reconstruction with a pericardial patch for the debrided annulus is an effective surgical option for the treatment of infectious endocarditis in patients with mitral annular calcification. Abstract: A 78-year-old woman was referred to our hospital because of left-sided hemiparesis. During the treatment for cerebral infarction, the patient became feverish and lost consciousness. Transthoracic echocardiography revealed mitral annular calcification and a tumor-like mass on the posterior leaflet despite no findings of mitral regurgitation. She underwent successful mitral valve replacement with debridement of the infected mitral annulus and reconstruction of the posterior annulus (annuloplasty) with bovine pericardium after removal of the mitral annular calcification.

Do chronic total occlusive lesions affect patency of coronary bypass grafts to the right coronary artery?

OBJECTIVES: To evaluate the impact of chronic total occlusion (CTO) lesions on the patency of bypass grafts to the right coronary artery territory. METHODS: Two hundred patients undergoing primary isolated coronary artery bypass grafting with revascularization to the right coronary artery territory between April 2015 and July 2022 were retrospectively analyzed. Study patients were divided into two groups according to their right coronary artery lesion: patients with CTO lesions (n = 76) and those without CTO lesions (n = 124). Graft flow of the right coronary artery territory was evaluated by intraoperative transit time flow measurement and patency of the bypass graft was evaluated by multidetector row computed tomography. RESULTS: A total of 200 patients (76 patients with CTO and 124 patients without CTO) were included in this study. Intraoperative transit time flow measurement demonstrated that there was no significant difference in the median mean graft flow (30 ml/min vs. 25 ml/min; p = 0.114), pulsatility index (2.1 vs. 2.4; p = 0.079), and diastolic filling rate (65% vs. 64%; p = 0.844) between patients with CTO and those without CTO. Postoperative multidetector row computed tomography demonstrated that the patency of bypass grafts to the right coronary artery territory was similar between the groups (94.7% in patients with CTO vs. 96.0% in those without CTO; p = 0.733). In patients with CTO, the patency of bypass graft tended to be worse in subgroup with rich collateral blood flow (Rentrop grade 3). CONCLUSIONS: Chronic total occlusion lesions do not affect the patency of bypass grafts to the right coronary artery territory.

Factors Affecting Recovery of 6-Minute Walk Distance After Coronary Artery Bypass Grafting.

Background: This single-center retrospective analysis investigated the number of days required for postoperative 6-minute walk distance (6MWD) to recover to preoperative values after coronary artery bypass grafting (CABG) and the factors influencing this recovery. Methods and Results: The 6MWD was measured in 101 patients (median age 69 years; 18 women) before and every day after CABG. Univariate and multivariate analyses were performed to identify factors affecting 6MWD recovery to preoperative values after CABG. The median number of days required for recovery of 6MWD after CABG was 9 (interquartile range 7-11 days). Patients were divided into 2 groups based on the median number of days required for recovery of 6MWD; there were 60 patients in the early recovery group (<9 days) and 41 in the "non-early" recovery group (38 who recovered after the median 9 days, and 3 who did not recover during hospitalization). Using univariate logistic regression analysis, diabetes (P=0.01), stroke (P=0.26), left ventricular ejection fraction (P=0.27), and grip strength (P=0.13) were selected for multivariate analysis. Multivariate logistic regression analysis revealed that diabetes (odds ratio 2.955; 95% confidence interval 1.208-7.229; P=0.02) was the only independent predictor of 6MWD recovery. Conclusions: Diabetes was the single factor influencing the recovery of postoperative 6MWD in patients undergoing CABG.