Terumo (Japan)

Predicting optimal coagulation control using heparin in intensive care units (ICUs) remains a significant challenge. This study aimed to develop a machine learning (ML) model to predict activated partial thromboplastin time (aPTT) in ICU patients receiving unfractionated heparin for anticoagulation and to identify key predictive factors. Data were obtained from the Tokushukai Medical Database, covering six hospitals with ICUs in Japan, collected between 2018 and 2022. The study included 945 ICU patients who received unfractionated heparin. The dataset comprised both static and dynamic features, which were used to construct and train ML models. Models were developed to predict aPTT following initial and multiple heparin doses. Model performance was evaluated using the area under the receiver operating characteristic curve (ROC AUC), area under the precision-recall curve (PR AUC), precision, recall, F1 score, and accuracy. SHAP analysis was conducted to determine key predictive factors. The random forest model demonstrated the highest predictive performance, with ROC AUC values of 0.707 for the first infusion and 0.732 for multiple infusions. Corresponding PR AUC values were 0.539 and 0.551. Despite moderate overall predictive performance, the model exhibited high precision (0.585 for the first infusion and 0.589 for multiple infusions), indicating effectiveness in correctly identifying true positive cases. However, recall and F1 scores were lower, suggesting that some cases, particularly in sub-therapeutic and supra-therapeutic ranges, may have been missed. Incorporating time-series data, such as vital signs, provided only marginal improvements in performance. ML models demonstrated moderate performance in predicting aPTT following heparin infusion in ICU patients, with the random forest model achieving the highest classification accuracy. Although the models effectively identified true positive cases, their overall predictive performance remained limited, necessitating further refinement. The inclusion of static and dynamic features did not significantly enhance model accuracy. Future studies should explore additional factors to improve predictive models for optimizing individualized anticoagulation management in ICUs.

Introduction: mRNA has great potential to provide new medical innovations in the treatment of heart failure. Lipid nanoparticles (LNPs) are an established and effective mRNA delivery system. However, effectively delivering LNPs to the heart remains a significant challenge. We evaluated the efficacy of transcatheter intracoronary (IC) administration compared to intravenous (IV) and intramyocardial (IM) administration as methods for delivering. Methods: Normal rabbits were used to examine each route of administration. Fluorescence (ATTO 700)-labeled LNP encapsulating Firefly Luciferase (FLuc) mRNA (25 ug/kg) were used to confirm the in vivo mRNA-LNP dynamics. The LNP accumulation and FLuc expression were verified using an in vivo imaging system (IVIS) 4 hours post-administration, followed by immunohistochemical analysis. The same experiments were conducted in an ischemia-reperfusion (I/R) model. Results: In the normal model, IVIS spectrum data showed that LNPs accumulated in the order of IM, IC and IV groups, with FLuc expression significantly higher in the IC group than in the IV group and comparable to the IM group (A). Histological analysis revealed that FLuc-expressing cells were mainly found in troponin T-positive cardiomyocytes at the injection site in the IM group and throughout the heart in the IC group (B). In the I/R model, LNP accumulation and FLuc expression were increased in the IV group compared to the normal model, whereas, in the IC and IM groups LNP accumulation and FLuc expression levels were similar to those in the normal model (C). Histological analysis revealed more FLuc-expressing cells in the infarcted area in all groups, but higher FLuc expression was observed in remote areas in the IC group (D). Conclusions: IC administration effectively delivered mRNA-LNPs not only to the damaged area but also to the remote area (non-damaged area) in the diseased heart, suggesting a safe and useful method for delivery to a wider range of cardiomyocytes in the heart.

BackgroundThe detection rate of superficial non-ampullary duodenal epithelial tumors (SNADETs) has recently been increasing. Large tumors may contain malignant lesions and early therapeutic intervention is recommended. Endoscopic mucosal dissection (ESD) is considered a feasible treatment modality, however, the anatomical and physiological characteristics of the duodenum create a risk of postoperative perforation after ESD.MethodsTo explore whether myoblast sheet transplantation could prevent delayed perforation after ESD, a first-in-human (FIH) clinical trial of laparoscopic autologous myoblast sheet transplantation after duodenal ESD was launched. Autologous myoblast sheets fabricated from muscle tissue obtained seven weeks before ESD were transplanted laparoscopically onto the serous side of the ESD. The primary endpoints were the onset of peritonitis due to delayed perforation within three days after surgery and all adverse events during the follow-up period.ResultsThree patients with SNADETs ≥ 20 mm in size underwent transplantation of a myoblast sheet onto the serous side of the duodenum after ESD. In case 1, The patient’s postoperative course was uneventful. Endoscopy and abdominal computed tomography revealed no signs of delayed perforation. Despite incomplete mucosal closure in case 2, and multiple micro perforations during ESD in case 3, cell sheet transplantation could prevent the postoperative massive perforation after ESD, and endoscopy on day 49 after transplantation revealed no stenosis.ConclusionsThis clinical trial showed the safety, efficacy, and procedural operability of this novel regenerative medicine approach involving transplanting an autologous myoblast sheet laparoscopically onto the serosa after ESD in cases with a high risk of delayed perforation. This result indicates the potential application of cell sheet medicine in treating various abdominal organs and conditions with minimal invasiveness in the future.Trial registrationjRCT, jRCT2073210094. Registered November 8 2021,https://jrct.niph.go.jp/latest-detail/jRCT2073210094.

Currently, in regenerative medicine, cell processing is performed manually, which is labor intensive and expensive. Recently, automatic cell culture apparatuses equipped with a vertical articulated robot have been proposed to improve the efficiency of cell-processing tasks. However, most of them automate all the cell-processing tasks, which complicate the system. This study aimed to develop a simple and rational cell-processing system by combining the tasks performed by a robot and human. In a previous study, we proposed a method to improve the efficiency of the media changing process and implemented prototypes that improve the efficiency of discarding and injecting tasks. Herein, we developed and evaluated a simpler discarding robot than the previous model. The proposed discarding robot fulfilled its basic functions. Using the robot, the operator does not need to worry about the liquid-dripping effect during the discarding task. Moreover, the device is equipped with human error countermeasures. Further, as this device is sufficiently small to be used in a safety cabinet, it can be integrated into current culture methods.

PurposeStent flexibility can influence clinical outcome, especially in bifurcation lesions. For instance, an overly rigid stent can impose mechanical stress on the artery at the stent edges and alter both arterial geometry and blood flow dynamics in bifurcations. This study investigated the influence of stent flexibility on vessel geometry, histology, wall stress, and blood flow dynamics in arterial bifurcations.Materials and MethodsWe compared arterial angulation, stenosis, histopathology, simulated wall shear stress (WSS), and simulated blood flow velocity distribution in swine coronary artery bifurcations following placement of the less flexible Multi-link 8 or more flexible Kaname stent (4.1 ± 0.5 vs 1.5 ± 0.1 mN, p < 0.05, t-test). Stents were implanted into six coronary artery bifurcations each using the single-stent crossover technique without side branch strut dilatation. Outcomes were examined after 28 days.ResultsImplantation of both stents significantly increased site angulation (Multi-link 8: 148° ± 8° to 172° ± 2°, p < 0.05, paired t-test; Kaname: 152° ± 5° to 164° ± 4°, p < 0.05, paired t-test), but the change tended to be greater after Multi-link 8 stent implantation (24° ± 15° vs 11° ± 7°, p = 0.1, t-test), suggesting greater straightening of the bifurcation. The Multi-link 8 stent induced greater neointimal thickness than the Kaname stent (0.53 ± 0.3 mm vs 0.26 ± 0.1 mm, p < 0.05, t-test). The distribution of neointimal hyperplasia following stent implantation as revealed by longitudinal histopathology matched the distribution of WSS simulated using computational fluid dynamics (CFD). The endothelium at low WSS areas exhibited aberrant cell morphology and leukocyte adhesion. A CFD model of a curved bifurcation suggested that the region of low WSS is expanded by artery straightening.ConclusionIn bifurcated lesions, stent flexibility influences not only mechanical stress on the artery but also WSS, which may induce local neointimal hyperplasia.

This study aimed to systematically investigate feasibility of radiofrequency intravascular ultrasound (RF-IVUS) analysis of blood signals for assessing functionally significant coronary stenosis. First, in-vivo human study was performed to evaluate 83 intermediate coronary lesions from 75 patients, using 40-MHz RF-IVUS, fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). Average blood integrated-backscatter (IB) values within lumen were measured at proximal and distal segments to the stenosis; ΔIB values between the two sites were calculated. Second, bench-test was performed to assess relationships of blood IB values to blood flow velocity and hematocrit using 40 and 60-MHz RF-IVUS. In in-vivo study, ΔIB values across the stenosis significantly correlated with both FFR (r = -.85, p < .0001) and iFR (r = -.65, p < .0001), which was confirmed in small minimum lumen area (MLA) lesions (MLA <2.0 mm2 ). Receiver operating characteristic curve analyses identified the best cut-off value as 10.06 of ΔIB values for predicting FFR ≤0.8 and iFR ≤0.89 (sensitivity 76.2 and 95.5%, specificity 100 and 82.0%, positive predictive value 100 and 65.6%, negative predictive value 80.4 and 98.0%, accuracy 92.9 and 92.8% for FFR and iFR). Bench-test study also identified that blood IB values exponentially changed as a function of blood flow velocity at any given hematocrit in both 40 and 60-MHz RF-IVUS. This study supports the potential utility of RF-IVUS analysis of blood signals to estimate functional ischemia, demonstrating relationships of blood ΔIB values to FFR and iFR, as well as relationships between blood IB values and flow velocity.

Intravenous catheters are widely used but are often removed due to complications associated with catheter sleeve formation. A catheter sleeve can develop from a thrombus, and catheter-induced vascular endothelium damage may be a critical factor for thrombus formation. We investigated the effect of catheter-induced mechanical stimulation on venous endothelial cells and catheter sleeve formation and the efficacy of anti-thrombogenic technology for preventing catheter sleeve formation in vivo. We surgically implanted poly(2-methoxyethyl acrylate)-coated and uncoated catheters with and without a stylet into the right external jugular vein of a rabbit model for 14 days. Catheter sleeve formation and the ratio of residual venous endothelial cells were compared using histological examination and immunostaining with an anti-CD31 antibody, respectively. Stiffening an uncoated catheter with a stylet induced catheter sleeve formation along more than two-thirds of the length of the catheter. The ratios of residual venous endothelial cells at the tip of uncoated catheters with and without a stylet were 3% and 36%, respectively. While poly(2-methoxyethyl acrylate) coating also reduced the ratio of venous endothelial cells at the tip of the stiffened catheter (12%), it prevented external thrombus and catheter sleeve formation. High levels of mechanical stimulation can affect catheter-related thrombosis and promote catheter sleeve formation, and anti-thrombogenic technology such as a poly(2-methoxyethyl acrylate) coating reduces thrombus formation and can prevent catheter sleeve formation on stiffened catheters. Further studies are required to determine the maximum degree of venous endothelial cell damage before catheter sleeve formation and to compare other anti-thrombogenic technologies with poly(2-methoxyethyl acrylate) for preventing catheter sleeve formation.

В.М.Гриняк 1 Владивостокский государственный университет экономики и сервиса Владивосток.Россия Т.М.Гриняк 2 ООО «Тера-Рекон» Токио, Япония Д.А.Акмайкин 3 Морской государственный университет им.адм.Г.И.Невельского Владивосток, Россия Планирование маршрута перехода морского судна с учетом параметров волненияСтатья посвящена проблеме обеспечения безопасного движения судов на морских акваториях.Особое место в рамках этой проблемы занимает задача планирования пути: траектории движения судна на локальной акватории и маршрута перехода от порта отправления к порту назначения.Целью планирования траектории судна на локальной акватории является обеспечение навигационной безопасности в условиях коллективного движения и географических особенностей акватории.Основная задача планирования маршрута перехода -оптимизация движения с различными критериями: кратчайший путь, кратчайшее время, минимальный расход топлива и т.п.В предлагаемой статье рассматривается задача планирования маршрута перехода с учётом опасности, которую представляет морское волнение при его воздействии на суда основных классов.В основу математической модели задачи положена интегральная оценка степени воздействия морского волнения на судно по пути следования судна к месту назначения