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Aim Methods Results Conclusion Interprofessional collaboration between medical professionals is an essential aspect of caring for Japan's super‐aging population, but studies on the subject have been geographically limited in scope. Therefore, we aimed to determine the factors necessary for pharmacists to achieve interprofessional collaboration in home‐based care in Japan.Our online questionnaire survey was conducted from February 1, 2023 to February 15, 2023. The Japan Pharmaceutical Association introduced this survey to their membership, and survey letters were sent to hospitals and community pharmacies that were not included in this association.The study involved 1156 and 36 participants working in a community pharmacy and a hospital, respectively. These participants were divided into the collaboration group and the non‐collaboration group. Enough time for visiting patients and for preparing the first visiting plan was important to achieve interprofessional collaboration in home‐based care for a hospital pharmacist. More than 5 years of experience working in home‐based care and participation in pre‐visit conferences, discharge conferences, meetings with persons in charge of services were independent factors in collaborating with other medical staff for a community pharmacist.Hospital pharmacists with enough time to prepare and visit for home‐based care and community pharmacists working in home‐based care for more than 5 years and who share information on home‐based care with medical staff achieved interprofessional collaboration in home‐based care. Geriatr Gerontol Int 2024; ••: ••–••. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI), which occurs in association with sepsis, trauma, and coronavirus disease 2019 (COVID‐19), is a serious clinical condition with high mortality. Excessive platelet‐leukocyte aggregate (PLA) formation promotes neutrophil extracellular trap (NET) release and thrombosis, which are involved in various diseases, including ALI. Macrophage‐1 antigen (Mac‐1, CD11b/CD18), which is expressed on the surface of leukocytes, is known to promote NET formation. This study aimed to elucidate the role of Mac‐1 in extracellular histone‐induced ALI. Exogenous histones were administered to Mac‐1‐deficient mice and wild‐type (WT) mice with or without neutrophil or platelet depletion, and several parameters were investigated 1 h after histone injection. Depletion of neutrophils or platelets improved survival time and macroscopic and microscopic properties of lung tissues, and decreased platelet‐leukocyte formation and plasma myeloperoxidase levels. These improvements were also observed in Mac‐1−/− mice. NET formation in Mac‐1−/− bone marrow neutrophils (BMNs) was significantly lower than that in WT BMNs. In conclusion, our findings suggest that Mac‐1 is associated with exacerbation of histone‐induced ALI and the promotion of NET formation in the presence of activated platelets. [ABSTRACT FROM AUTHOR]

Aim: Multiple risk factors are involved in geriatric syndrome (GS) occurring in older adults. Although drug therapy often contributes to GS, the specific causes among older adults in Japan remain unclear. In this study, we examined the possible prescribing cascade rate among older outpatients eligible for Late‐stage Elderly Health Insurance and elucidated the differences between GS and GS associated with medication (GSAM) trends. Methods: This retrospective study enrolled patients from health insurance claims data in Japan between October 2018 and March 2019; hospitalized patients were excluded. Two groups were identified among the participants with GS: GS (no use of GS‐causing medications) and possible‐GSAM (p‐GSAM; use of GS‐causing medications). The collected data were analyzed using the Bell Curve for Excel, and statistical significance was set at P < 0.05. Results: In total, 137 781 outpatients were enrolled. Of the 32 259 outpatients who did not use GS‐causing medications, 7342 were classified into the GS group. Among 105 522 outpatients who used GS‐causing medications, 8347 were classified as having p‐GSAM. The mean number of prescriptions was significantly higher in the p‐GSAM group than in the GS group (P < 0.01). Furthermore, all GS symptoms showed significant differences, with impaired appetite being the most prevalent in the p‐GSAM group than in the GS group (P < 0.01). A possible prescribing cascade was suspected in 2826 (33.9%) of 8347 outpatients in the p‐GSAM group. Conclusion: Impaired appetite in patients taking GS‐causing medications might lead to prescribing cascades. Further studies are needed to prevent such prescribing cascades. Geriatr Gerontol Int 2024; 24: 61–67. [ABSTRACT FROM AUTHOR]

Naldemedine is structurally designed to prevent passage across the blood–brain barrier (BBB), resulting in the attenuation of opioid-induced constipation without interfering with the analgesic effects of opioids. However, the influence of brain metastasis (BM), as one indicator of BBB disruption, on the analgesic effects of opioids in patients treated with naldemedine remains unclear. To examine whether the analgesic effects of opioids following naldemedine treatment are lower in patients with BM than in those without BM, we surveyed inpatients with lung and breast cancers treated with naldemedine at Fujita Health University Hospital between April 2017 and March 2022. Changes in the numeric rating scale (NRS) scores, morphine milligram equivalents (MMEs), and the number of rescues were assessed as analgesia-related outcomes during the first 7 days of naldemedine treatment in patients with or without BM, matched by the propensity score. In total, 172 patients were enrolled. After propensity-score matching, 30 patients with BM and 60 patients without BM were included in the analysis. Changes in NRS scores, MMEs, and the number of rescues did not differ between patients with and without BM. In the linear mixed-effects model, the coefficient of interaction between patients with or without BM and the days for each outcome was not statistically significant. BM does not influence the analgesic effect of opioids in patients with lung and breast cancers treated with naldemedine. Naldemedine may be useful for treating BM. [ABSTRACT FROM AUTHOR]

Background: We developed a new sternal fixation device, Super FIXSORB WAVE®, a corrugated plate made of u-HA/PLLA, to improve sternal stability after sternotomy. This present study aimed to evaluate the new device clinically. Methods: This prospective, single-blinded, multicenter trial randomized 69 patients to either wire cerclage only (group C, n = 30) or wire cerclage plus Super FIXSORB WAVE® (group W, n = 39). The primary endpoint was a degree of sternal displacement at six months. Displacement of the sternal halves in the anteroposterior and lateral directions was measured using computed tomography horizontal section images at the third costal and fourth intercostal levels. The secondary endpoints were sternal pain and quality-of-life over 6 months. Results: Group W showed significantly reduced sternal anteroposterior displacement at both the third costal (0 [0–1.9] mm vs. 1.1 [0–2.1] mm; P = 0.014) and fourth intercostal (0 [0–1.0] mm) vs. 1.0 [0–1.8] mm; P = 0.015) levels than group C. In group W, lateral displacement was suppressed without a significant increase from 2 weeks to 6 months, while it increased in group C. There was no significant difference in postoperative sternal pain and quality-of-life between the two groups. No adverse events, such as infection, inflammation, or foreign body reaction, were observed with this device. Conclusions: Using Super FIXSORB WAVE®, sternal displacement was significantly suppressed in both the anteroposterior and lateral directions. The use of this device results in safe and easy sternal reinforcement without any adverse events, and sternal healing can be accelerated. Clinical trial registry number: This study was registered in the Japan Registry of Clinical Trials (February 21, 2019; jRCTs032180146). [ABSTRACT FROM AUTHOR]

Extracellular histones induce endothelial damage, resulting in lung haemorrhage; however, the underlying mechanism remains unclear. Factor XIII, as a Ca2+-dependent cross-linking enzyme in blood, mediates fibrin deposition. As another isozyme, transglutaminase 2 (TG2) has a catalytic activity distributing in most tissues. Herein, we investigated whether TG2 promotes fibrin deposition and mediates the adhesion of platelets to ECs in histone-induced acute lung injury (ALI). We evaluated the lung histology and the adhesion of platelets to endothelial cells (ECs) after injecting histones to wild-type (WT) C57BL/6J and TG2 knockout (TG2−/−) mice, and administered a TG2 inhibitor (NC9) to WT mice. Pulmonary haemorrhage was more severe in TG2−/− mice than that in WT mice. The area of fibrin deposition and the proportion of CD41+CD31+ cells were lower in TG2−/− mice than in WT mice. Pre-treatment of NC9 decreased the area of fibrin deposition and the proportion of CD41+CD31+ cells in WT mice. These results suggest that TG2 prevents from pulmonary haemorrhage in ALI by promoting the adhesion of platelets to ECs and the fibrin deposition. Role of transglutaminase 2 (TG2) in the adhesion of platelets to endothelial cells (ECs) and the deposition of fibrin. Extracellular histones induce severe pulmonary haemorrhage, resulting from endothelial barrier damage. To compensate for the loss of the endothelial barrier, TG2 mediates the adhesion of platelets to ECs and the deposition of fibrin. [Display omitted] • Transglutaminase 2 (TG2) did not directly affect platelet aggregation and coagulation abnormalities. • TG2 promoted the platelet adhesion to endothelial cells and the fibrin deposition as novel functions. • TG2 showed the protective contribution to extracellular histones induced-pulmonary haemorrhage. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES This study aimed to evaluate the outcomes of tricuspid annuloplasty with/without additional edge-to-edge plications in patients with functional tricuspid regurgitation (TR) and to clarify the impact of tethering on surgical outcomes. METHODS This retrospective observational study included patients with moderate or greater functional TR who underwent initial tricuspid valve repair between January 2008 and December 2021. The patients were divided into 2 groups based on whether they had tethering (preoperative tethering area ≥0.75 cm2). All patients underwent annuloplasty, and edge-to-edge plications were added at the regurgitant leakage site identified by saline tests. The surgical outcomes of each group and the effect of tethering on recurrent moderate or greater TR were evaluated. RESULTS One hundred and thirty-three patients were included in this study. During the follow-up period of 55.3 (standard deviation: 44.9) months, the 5-year survival rates were 78.4% in patients without tethering and 76.1% in patients with tethering (P  = 0.78). The 5-year cumulative incidence rates of readmission for heart failure and recurrent TR were 10.8% and 1.3% in patients without tethering and 23.0% and 29.5% in patients with tethering, respectively (P  = 0.12 and <0.001). Multivariable analyses revealed that the preoperative and predischarge tethering areas predicted recurrent TR. A large tethering area remained postoperatively in patients with tethering. CONCLUSIONS In patients without tethering, annuloplasty and additional edge-to-edge plications are effective in avoiding recurrent TR with satisfactory midterm clinical outcomes. However, in patients with tethering, these procedures resulted in residual tethering, which could be leading to recurrent TR. [ABSTRACT FROM AUTHOR]

We have developed novel cholesteric liquid crystal (Ch‐LC) films creating angle insensitive reflective colors. The wavy alignment formed by rapid change of the helical twisting power (HTP) enables the suppression of color shift with different incident angles. With this approach various decorative films for innovative applications can be created. [ABSTRACT FROM AUTHOR]

As cardiac implantable electronic devices, such as pacemakers, cardioverter defibrillators, and cardiac resynchronization therapies, have become more popular, device extraction has become more frequent. At our institution, individual treatment strategies are discussed at a heart team meeting. Transvenous lead extraction (TVLE) is a first-line treatment; however, surgical lead extraction (SLE) is sometimes selected as a primary choice to provide optimal treatment and maintain the medical safety policy. This study aimed to investigate the validity of this heart team decision-making. From 2013 to 2021, 384 consecutive patients underwent lead extraction at our institution. SLE was proposed as the primary intervention for 21 patients who had high risk of bleeding, difficult TVLE conditions, large vegetations, and other concomitant cardiac diseases. Of the 363 TVLE patients, 10 patients required surgical intervention; 5 had TVLE difficulty followed by SLE and 5 had excessive bleeding. SLE was performed in 26 patients, 19 of whom required valve surgery, and 8 required plication of the great veins. In 4 of the 17 hybrid procedures with SLE and TVLE, excessive bleeding occurred due to laceration of the superior vena cava and innominate vein. Operative mortality was not observed in SLE patients but was observed in 1 of the 4 TVLE patients who required emergent open-chest hemostasis. The heart team discussion was essential to provide optimal treatment and maintain medical safety policies for each patient. SLE should be selected for patients with high risk of TVLE or other cardiac complications such as tricuspid valve incompetence. Treatment strategy for cardiac electronic implantable devices. TVLE, transvenous lead extraction; SLE, surgical lead extraction; SVC, superior vena cava; pts., patients. [Display omitted] • Treatment strategies should be discussed for each patient in a heart team. • Decision-making made by a heart team can provide optimal treatment in each patient. • Surgical lead extraction (SLE) was required in 21 of the 384 patients. • Emergent open-chest hemostasis was required in 4 of the 363 transvenous patients. • Conversion to SLE is smoothly decided after heart team conferences. [ABSTRACT FROM AUTHOR]

Background: Antithrombogenicity of extracorporeal membrane oxygenation (ECMO) devices, particularly oxygenators, is a current problem, with numerous studies and developments underway. However, there has been limited progress in developing methods to accurately compare the antithrombogenicity of oxygenators. Animal experiments are commonly conducted to evaluate the antithrombogenicity of devices; however, it is challenging to maintain a steady experimental environment. We propose an innovative experimental animal model to evaluate different devices in a constant experimental environment in real‐time. Methods: This model uses two venous–arterial ECMO circuits attached to one animal (one by jugular vein and carotid artery, one by femoral vein and artery) and real‐time assessment of thrombus formation in the oxygenator by indocyanine green (ICG) fluorescence imaging. Comparison studies were conducted using three pigs: one to compare different oxygenators (MERA vs. CAPIOX) (Case 1), and two to compare antithrombotic properties of the oxygenator (QUADROX) when used under different hydrodynamic conditions (continuous flow vs. pulsatile flow) (Cases 2 and 3). Results: Thrombi, visualized using ICG imaging, appeared as black dots on a white background in each oxygenator. In Case 1, differences in the site of thrombus formation and rate of thrombus growth were observed in real‐time in two oxygenators. In Case 2 and 3, the thrombus region was smaller in pulsatile than in continuous conditions. Conclusions: We devised an innovative experimental animal model for comparison of antithrombogenicity in ECMO circuits. This model enabled simultaneous evaluation of two different ECMO circuits under the same biological conditions and reduced the number of sacrificed experimental animals. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES There are few reports on the rotational position of the aortic valve relative to the base of the left ventricle, and its influence on valve-sparing aortic root replacement (VSRR) has not been reported. Based on our experience with complications such as right atrial perforation and tricuspid valve injury, we investigated the cause of these complications in terms of morphological variations in the aortic root and its surrounding structures. METHODS The aortic valve rotation relative to the base of the left ventricle was assessed in 30 patients with tri-leaflet aortic valves who underwent VSRR. The influence of such anatomical variations on surgical procedures was investigated. RESULTS The aortic valve was positioned normally in 25 patients (83.3%), rotated counterclockwise in 4 (13.3%), and rotated clockwise in 1 patient (3.3%). In patients with a counterclockwise rotated aortic valve, the non-coronary sinus was the largest compared with other sinuses. This aortic valve rotation could be diagnosed by multidetector row computed tomography. In all patients who had difficulty in the external dissection of the right sinus of Valsalva, the aortic valve was counterclockwise rotated and forcible dissection had a risk of right atrial perforation and tricuspid valve injury. CONCLUSIONS Aortic valve rotation is an element that complicates VSRR. The rotational position of the aortic valve can be diagnosed preoperatively using multidetector row computed tomography and understanding the anatomy of the aortic valve related to rotational position help decide proper surgical decision-making in performing aortic root reconstruction procedure. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The goal of this study was to evaluate the outcomes of patients with subvalvular procedures for functional tricuspid regurgitation (TR) with severe leaflet tethering. METHODS Of 175 patients who had tricuspid valve surgery between June 2016 and June 2021, a total of 17 patients with functional TR with a preoperative tethering height ≥8 mm underwent subvalvular procedures (annular repositioning [An-Rep]) to reduce septal leaflet tethering, papillary muscle relocation to reduce anterior leaflet tethering, and/or papillary muscle bundling [PMB] to reduce anterior and posterior leaflet tethering along with ring annuloplasty at our institution. A single subvalvular procedure was performed in 9 patients (An-Rep in 5 patients, PMB in 4 patients; group S), and a combination of subvalvular procedures was performed in 8 patients (An-Rep and papillary muscle relocation in 5 patients, An-Rep and PMB in 3 patients; group C). RESULTS Predischarge TR grades and tethering height were significantly improved (3.2 ± 1.3–1.0 ± 0.5, p = 0.001; 9.9 ± 2.5 mm–5.5 ± 2.8 mm, p < 0.001, respectively). An-Rep and PMB significantly reduced the postoperative closing angles of the septal and anterior leaflets, respectively. During the 20.4 ± 19.5-month follow-up period, the rates of freedom from death and moderate TR at 2 years were 41.7% in group S, and 71.4% in group C (p = 0.39), respectively. In group C, TR recurrence was not observed at 2 years postoperatively. CONCLUSIONS Subvalvular procedures were effective in reducing the predischarge TR grades and tethering height. The combination of subvalvular procedures might be a durable strategy to prevent recurrent TR. [ABSTRACT FROM AUTHOR]

Background: The number of patients aged 80 years or older with diffuse large B-cell lymphoma (DLBCL) is increasing, and the incidence rate of the disease in this population group reaches up to 20%. The risk of infection is higher in older patients than in other patients. Although hypnotic drugs are frequently detected as potentially inappropriate medications, it is unclear whether hypnotic drugs affect the occurrence of infection during chemotherapy. Here, we investigated whether the use of hypnotic drugs is associated with infection during first-line chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) aged 80 years or older. Methods: Japanese patients aged 80 years or older with diffuse large B-cell lymphoma who had received first-line chemotherapy at Fujita Health University Hospital from January 2005 to March 2020 were enrolled in this retrospective cohort study. The primary study outcome was the identification of the risk factor for infection during first-line chemotherapy. Results: This study included 65 patients received first-line chemotherapy. The proportion of patients with National Comprehensive Cancer Network-international prognostic index ≥ 6 was higher in the infection group than in the non-infection group. The relative dose intensity of each anticancer drug (cyclophosphamide, adriamycin, and vincristine) and dose of prednisolone did not significantly differ between the two groups. Multivariate analysis showed that the use of benzodiazepines was a risk factor for infection (odds ratio, 4.131 [95% confidence interval: 1.225–13.94], P = 0.022). Conclusion: DLBCL patients using benzodiazepines should be monitored for infection symptoms during chemotherapy. [ABSTRACT FROM AUTHOR]

Purpose: Hybrid aortic arch repair (HAR) has been implemented for extended aortic arch and descending thoracic aortic disease since 2012 in our institution. This study aimed to estimate the early and mid-term efficacy and safety of HAR. Materials and Methods: From 2007 to 2019, 56 patients underwent HAR for extended aortic arch disease, and 75 patients underwent total arch replacement (TAR) for arch-limited disease. HAR comprises 3 procedures: replacement of the aorta, reconstruction of all arch vessels, and thoracic endovascular aortic repair (TEVAR) from zone 0 to the descending aorta after cardiopulmonary bypass is off in 1 stage. The type II-1 HAR procedure, in which the ascending aorta and aortic arch distal to the brachiocephalic artery are replaced, was the most frequently selected procedure (40/56 patients). The outcomes of the type II-1 HAR procedure were compared with those of TAR using the Cox regression analysis. Results: The median follow-up period was 36 months. In HAR, the operative mortality, in-hospital mortality, and postoperative permanent neurological deficits were not observed. The paraplegia rate was 1.8%. TEVAR-related complications occurred in 3 patients. Among the patients with non-ruptured atherosclerotic aortic arch aneurysm (31 type II-1 HAR patients and 36 TAR patients, the postoperative respiratory support time in those who underwent type II-1 HAR was quicker than in those who underwent TAR (p<0.01). The rate of 6 year freedom from all-cause death in type II-1 HAR (83.1%) was numerically higher than that in TAR (74.7%), and the rate of 6 year freedom from surgery-related complications in type II-1 HAR (90.3%) was numerically lower than that in TAR (96.9%) due to the occurrence of TEVAR-related complications, and the rate of 6 year freedom from reintervention to the descending thoracic aorta in type II-1 HAR (100%) seemed to be better than that in TAR (83.7%). However, Cox regression analysis did not reveal any statistical difference between the 2 procedures. Conclusions: HAR, especially the type II-1 procedure, can treat extended aortic arch disease with acceptable survival outcomes. The development of TEVAR technology will further improve the outcomes of HAR in the future. [ABSTRACT FROM AUTHOR]

Ventricular dilation after myocardial infarction can cause heart failure. Increasing strength and elasticity in the infarct region might prevent ventricular dilation. Because elastin provides strength, extensibility, and resilience to tissues and maintains tissue architecture, we studied the effect of elastin expression in the infarct on scar expansion and heart function. COS-7 cells transfected with a plasmid with an elastin gene fragment or a vector were seeded into a Gelfoam mesh and cultured. Mechanical stretch test (n = 5/group) showed that the elastin mesh was more elastic (P < 0.05) and tensile (P < 0.05) than the vector mesh. In an in vivo study in rats, 6 days after left anterior descending coronary artery ligation, COS-7 cells (Cell group, n = 7) or COS-7 cells with elastin gene (Elastin group, n = 9) or vector (Vector group, n = 9) were transplanted into the infarct; infarcted rats served as controls (n = 7). Over 8 wk the Cell group did not demonstrate effects on scar expansion and deterioration of heart function vs. controls. In contrast, infarct expansion was smaller and heart function was better maintained in the Elastin group vs. the Vector group (P < 0.05). At 8 wk after cell transplantation Langendorff data showed that the Elastin group had greater (P < 0.01) developed pressure and a smaller left ventricular volume than the Vector group. Western blot and histology showed accumulated elastin in the Elastin group infarct. Changing the extracellular matrix composition of a myocardial infarct by increasing elastin fragment content attenuated scar expansion, ventricular dilation, and onset of heart dysfunction. myocardial infarction; ventricular modulation; gene therapy; cell transplantation

Information on immune checkpoint inhibitor-induced vasculitides is limited, and predictors for this condition have not been identified. Therefore, we have examined the frequency of immune checkpoint inhibitor-induced vasculitides by analyzing the data recorded in the Japanese Adverse Drug Event Report database. Data from April 2004 to March 2020 were extracted, and vasculitides as an immune-related adverse event was defined according to the 2012 revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. Adverse event signals were recognized as significant when the reporting odds ratio estimates and lower limits of the corresponding 95% confidence intervals exceeded 1. The use of nivolumab showed a significant signal for vasculitides. Furthermore, significant signals of polymyalgia rheumatica were found when the patients were treated with nivolumab, pembrolizumab, and ipilimumab. In addition, the frequencies of nivolumab- and pembrolizumab-induced polymyalgia rheumatica were higher in patients aged ≥70 years and female patients, respectively. Polymyalgia rheumatica was reported in 38 patients treated with nivolumab; 31 (82%) of these were either in recovery or in remission. Further, polymyalgia rheumatica was reported in 17 patients treated with pembrolizumab; 13 (76%) of these were in recovery or remission, while three (18%) were not. Polymyalgia rheumatica was reported in 12 patients treated with ipilimumab; seven (58%) of these were in recovery or remission. Our study highlights that careful monitoring for the symptom of PMR (e.g., bilateral pain in shoulder and pelvic girdles) is required when the patients are aged >70 years and have been treated with nivolumab and when the patients are women and have been treated with pembrolizumab. [ABSTRACT FROM AUTHOR]

Background: Early detection and prediction of cisplatin-induced acute kidney injury (Cis-AKI) are essential for the management of patients on chemotherapy with cisplatin. This study aimed to evaluate the performance of a prediction model for Cis-AKI. Methods: Japanese patients, who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital, were enrolled in the study. The main metrics for evaluating the machine learning model were the area under the curve (AUC), accuracy, precision, recall, and F-measure. In addition, the rank of contribution as a predictive factor of Cis-AKI was determined by machine learning. Results: A total of 1,014 and 226 patients were assigned to the development and validation data groups, respectively. The current prediction model showed the highest performance in patients 65 years old and above (AUC: 0.78, accuracy: 0.77, precision: 0.38, recall: 0.70, F-measure: 0.49). The maximum daily cisplatin dose and serum albumin levels contributed the most to the prediction of Cis-AKI. Conclusion: Our prediction model for Cis-AKI performed effectively in older patients. [ABSTRACT FROM AUTHOR]

Acute lung injury (ALI) occurs in patients with severe sepsis and has a mortality rate of 40%–60%. Severe sepsis promotes the release of histones from dying cells, which can induce platelet aggregation, activate coagulation and cause endothelial cell (EC) death. We previously reported that the expression of membrane complement receptor type 1‐related gene Y (Crry)/p65, which plays a principal role in defence against abnormal activation of complement in the blood, is reduced in response to peritoneal mesothelial cell injury, and we hence hypothesized that a similar mechanism occurs in pulmonary ECs. In this study, we examined the role of Crry/p65 in histone‐mediated ALI using an experimental animal model. In ALI model mice, exposure to extracellular histones induces lung injury and results in a decrease in Crry/p65 expression. The levels of lactic acid dehydrogenase (LDH), a marker of cell damage, were significantly increased in the serum of ALI model compared with vehicle mice. The significant inverse correlation between the expression of Crry/p65 and LDH levels in plasma revealed an association between Crry/p65 expression and cell damage. The levels of complement component 3a (C3a) were also significantly increased in the serum of the ALI model compared with vehicle mice. Notably, a C3a receptor antagonist ameliorated lung injury induced by histones. We hypothesize that extracellular histones induce complement activation via down‐regulation of Crry/p65 and that C3a might serve as a therapeutic target for the treatment of ALI. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) plays an important role in the coronavirus disease 2019 (COVID‐19) pandemic. Management of thrombi in ECMO is generally an important issue; especially in ECMO for COVID‐19 patients who are prone to thrombus formation, the thrombus formation in oxygenators is an unresolved issue, and it is very difficult to deal with. To prevent thromboembolic complications, it is necessary to develop a method for early thrombus detection. We developed a novel method for detailed real‐time observation of thrombi formed in oxygenators using indocyanine green (ICG) fluorescence imaging. The purpose of this study was to verify the efficacy of this novel method through animal experiments. The experiments were performed three times using three pigs equipped with veno‐arterial ECMO comprising a centrifugal pump (CAPIOX SL) and an oxygenator (QUADROX). To create thrombogenic conditions, the pump flow rate was set at 1 L/min without anticoagulation. The diluted ICG (0.025 mg/mL) was intravenously administered at a dose of 10 mL once an hour. A single dose of ICG was 0.25mg. The oxygenator was observed with both an optical detector (PDE‐neo) and the naked eye every hour after measurement initiation for a total of 8 hours. With this dose of ICG, we could observe it by fluorescence imaging for about 15 minutes. Under ICG imaging, the inside of the oxygenator was observed as a white area. A black dot suspected to be the thrombus appeared 6‐8 hours after measurement initiation. The thrombus and the black dot on ICG imaging were finely matched in terms of morphology. Thus, we succeeded in real‐time thrombus detection in an oxygenator using ICG imaging. The combined use of ICG imaging and conventional routine screening tests could compensate for each other's weaknesses and significantly improve the safety of ECMO. [ABSTRACT FROM AUTHOR]