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Aim: 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. Methods: 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. Results: 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. Conclusion: 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; 24: 1008–1014. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. Objective: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. Methods: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. Results: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). Conclusions: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia. [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]

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]

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]

What is known and Objective: Hypertension (HTN) and chronic kidney disease (CKD) are recognized as silent killers because they are asymptomatic conditions that contribute to the burden of multiple comorbidities. The achievement of a blood pressure (BP) goal can dramatically reduce the risks of CKD. In this study, we aimed to assess the effectiveness of pharmacist intervention on BP control in patients with CKD and evaluate the usefulness of home‐based BP telemonitoring. Methods: The terms "chronic kidney disease," "pharmacist," "BP" and "randomized controlled trial (RCT)" were used five databases to search for information regarding pharmacist intervention on BP control in patients with CKD. The inclusion criteria were as follows: (a) studies for adult patients with uncontrolled HTN and (b) studies with adequate data for meta‐analysis. The primary outcome was an evaluation of achievement of BP goal in patients with CKD. The secondary outcome was usefulness of home‐based BP telemonitoring by pharmacists in patients with CKD. Results and discussion: Six RCTs were identified and included in the meta‐analysis with a total of 2573 patients (mean age 66.0 years and 63.9% male). Pharmacist interventions resulted in significantly better BP control vs usual care (OR = 1.53, 95% CI = 1.15‐2.04, P <.01). Pharmacist interventions using home‐based BP telemonitoring were significantly superior to control/usual care (OR = 2.03, 95% CI = 1.49‐2.77, P <.01), whereas pharmacist interventions without home‐based BP telemonitoring did not significantly improve BP control compared to that with control/usual care (OR = 1.30, 95% CI = 0.97‐1.75, P =.08). Home‐based BP telemonitoring supported team‐based care for HTN in these studies. In addition, patient self‐monitoring with telemedicine devices might enhance patients' abilities to manage their condition by pharmacist instruction. What is new and conclusion: The findings of this meta‐analysis showed that pharmacist interventions with home‐based BP telemonitoring improve BP control among adult patients with CKD. [ABSTRACT FROM AUTHOR]

Aim: To analyze the impact of clinical medication reviews (CMR) on reducing unplanned hospitalizations owing to polypharmacy among older adults using an intervention. Methods: Our meta‐analysis complied with PRISMA guidelines. The literature review comprised a search for articles published between January 1972 and March 2017 on MEDLINE and Google Scholar. We identified randomized controlled trials focusing on CMR that evaluated unplanned hospitalization and re‐hospitalization among older adults as a primary outcome. The keywords used were "CMR" or "medication review" in their titles, and the phrases "elderly" or "older adults" or "geriatric" and "polypharmacy." The randomized controlled trials selected were divided according to the three types of CMR to analyze the characteristics of each review. Results: We included nine randomized controlled trials that examined the impact of CMR of polypharmacy in older patients. Five trials corresponded to CMR type I (prescription only review) or II (adherence review), whereas four corresponded to type III (comprehensive clinical evaluation for disease management). Type I/II increased the number of unplanned hospitalizations (RR 1.22, 95% CI 1.07–1.38, P = 0.002), whereas type III decreased hospital admissions (RR 0.86, 95% CI 0.79–0.95, P = 0.001). Conclusions: The present findings show the need for an intervention standardization for CMR, particularly for type III in older adults with polypharmacy, to decrease hospitalizations. Geriatr Gerontol Int 2019; 19: 1275–1281. [ABSTRACT FROM AUTHOR]

Extracellular histones induce lethal thrombosis by promoting platelet aggregation, neutrophil migration, and cell injuries. Heparin, which has negative charges, can bind to extracellular histones; however, heparin strongly inhibits the activation of coagulation. Since chondroitin sulfate (CS) shows less effect on the coagulation system than heparin does, CS has the potential to become an effective drug for lethal thrombosis with high risk of bleeding. To elucidate the therapeutic mechanisms of CS in lethal thrombosis, we investigated the interaction between CS and extracellular histones. Mouse vascular endothelial cells were incubated with histones in the presence of heparin or CS, and the expression of caspase-3/7 was measured. The interactions between histones and heparin or CS were measured by surface plasmon resonance analysis. Vascular permeability, platelet counts, liver and renal functions, and coagulation times were evaluated in an in vivo assay. The apoptosis induced by histones was inhibited by treatment with heparin or CS. Heparin and CS showed strong binding to histones and inhibited vascular hyperpermeability. The platelet counts as well as liver and renal functions were not decreased by the treatment with heparin or CS. Moreover, CS showed less effect on the coagulation system than heparin did. These results suggested that CS can be a novel agent for lethal thrombosis with the risk for hemorrhage. Since vascular endothelial cell injuries occur at an early stage of lethal thrombosis, administration of CS might be a useful approach. [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]

Aim Polypharmacy is an extremely important problem, because it increases the risk of adverse drug reactions. The aim of the current study was to create a clinical medication review tool to detect inappropriate medication use, and assess this new method with elderly Japanese patients. Methods The new method involves optimizing prescription drugs from indications, based on the chronic disease-anatomical therapeutic class code list. The present study investigated the prevalence of potentially inappropriate medications in 5667 Japanese patients aged ≥65 years with polypharmacy (≥5 drugs) in comparison with the Beers criteria 2012. Results We propose a new method called the Mapping Approach for Pharmacotherapeutic Classifications: (i) identify the chronic disease-anatomical therapeutic class code assigned to the prescription drugs; (ii) identify the chronic disease-anatomical therapeutic class code corresponding to the patient's chronic disease; (iii) compare the prescription drug and patient's chronic disease chronic disease-anatomical therapeutic class codes; and (iv) identify the appropriateness of medication use based on the comparison (appropriate use is defined as matching codes). The mean number of potentially inappropriate medications detected was significantly different between the mapping approach and Beers criteria 2012 (3.1 ± 2.6 vs 0.6 ± 0.8 drugs, respectively; P < 0.001). Conclusions The Mapping Approach for Pharmacotherapeutic Classifications is highly dependent on the chronic condition. Pharmacists should confirm the chronic condition with the treating physician before reducing a patient's medications. We hope this process will further influence prescribing patterns, and decrease the inappropriate use of medications and associated adverse drug reactions in older adults. Geriatr Gerontol Int 2017; 17: 2025-2033. [ABSTRACT FROM AUTHOR]

Off-pump coronary artery bypass grafting (OPCAB) in patients with acute myocardial infarction (AMI) is difficult because of circulatory deterioration during displacement of the heart. At our institution, we performed minimally circulatory-assisted on-pump beating coronary artery bypass grafting (MICAB) in these patients. During MICAB, support flow was controlled at a minimal level to maintain a systemic blood pressure of approximately 100 mm Hg and a pulmonary arterial systolic pressure of <30 mm Hg, providing optimal pulsatile circulation for end-organ perfusion and prevention of heart congestion. From September 2006 to March 2012, MICAB was performed in 37 patients. Either emergent or urgent MICAB was performed in 27 patients following AMI because of hemodynamic instability during reconstruction. Elective MICAB was performed in the remaining 10 patients because of dilated left ventricle (LV) or small target coronary arteries. The details of bypass grafts, perioperative renal function, and early and mid-term morbidity and mortality were compared between the patients who received MICAB and the 37 consecutive patients who underwent OPCAB during the study period at our hospital. The assist flow indices (actual support flow/body surface area) during anastomosis to the left anterior descending artery, left circumflex artery, and right coronary artery were 0.95 ± 0.48 L/min/m2, 1.32 ± 0.53 L/min/m2, and 1.15 ± 0.47 L/min/m2, respectively, in the emergent and urgent patients following AMI, and 0.44 ± 0.39 L/min/m2, 1.25 ± 0.39 L/min/m2, and 1.14 ± 0.43 L/min/m2, respectively, in the elective patients with either dilated LVs or small target vessels. The lowest mixed venous oxygen saturation during pump support in the MICAB group was significantly higher than that in the OPCAB group (83.8 ± 10.8%, 71.6 ± 7.5%, P < 0.001). Comparing MICAB and OPCAB, the median number of distal bypass grafts for both groups was 4 (25th, 75th percentile: 3, 4) ( P = 0.558); the complete revascularization rates were 94.6 and 97.3%, respectively (not significant [NS]); the acute patency rates were 98.9 and 99.2%, respectively (NS); and the 30-day mortality rates were 2.7 and 0%, respectively (NS). No instances of either cerebrovascular complications or newly occurring postoperative renal failure were noted in either group. There were no statistically significant differences between the groups with respect to early and mid-term results (freedom from all-cause death: 82.9 vs. 86.5%, respectively, and freedom from cardiac events at 3 years: 96.4 vs. 96.4%, respectively). MICAB is a safe alternative to OPCAB, particularly in patients with AMI and dilated LV. MICAB is associated with high rates of complete revascularization and acute graft patency, adequate preservation of end-organ function, and early and mid-term results comparable with those observed following OPCAB. [ABSTRACT FROM AUTHOR]

Key Clinical Message We previously started pharmacist blood pressure ( BP) management programs using telemonitoring systems for monitoring side effects of antihypertensive drugs in a community pharmacy. The present case demonstrates that pharmacist BP management programs using telemonitoring systems are useful for monitoring side effects of antihypertensive drugs in a community pharmacy. [ABSTRACT FROM AUTHOR]

Background and Aims: Cisplatin-induced nephrotoxicity primarily occurs in the proximal tubules, and tubular injuries reduce glomerular filtration rates. Lower blood pressure causes renal hypoperfusion, which promotes ischemic acute kidney injury (AKI). Our study examined the relationship between lower blood pressure-induced renal hypoperfusion and cisplatin-induced nephrotoxicity. Methods: The relationship between cisplatin use and hypoalbuminemia is not clear. This study consisted of Japanese patients who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital from April 2006 to December 2012. Hypoalbuminemia was defined as serum albumin levels = 3.5 mg/dl. Results: Patients who experienced lower blood pressure during chemotherapy were included in the lower blood pressure group (n = 229), and those who did not were included in the normal blood pressure group (n = 743). Total cisplatin dose in the normal blood pressure and lower blood pressure groups was 58.9 ± 23.8 and 55.0 ± 20.4 mg/m², respectively. The rate of severe nephrotoxicity was higher and overall survival was shorter in the lower blood pressure group than in the normal blood pressure group. In a multivariable analysis, lower blood pressure significantly correlated with hypoalbuminemia. Conclusions: To prevent ischemic AKI, nutrition and cachexia controlling are important parts of cancer treatment. [ABSTRACT FROM AUTHOR]

The use of antimicrobial agents has increased in recent years as treatments have diversified and resistant bacteria have appeared. With increased use of antimicrobial agents, elderly patients are prone to adverse drug reactions (ADRs) as a result of factors such as drug-drug interactions, polypharmacy, long-term use, and over- or under-dosage. In particular, elderly patients using antimicrobials are at increased risk to develop drug-induced acute kidney injury (AKI), which is the most common severe ADR in such patients. AKI is a serious problem that is associated with mortality amongst hospitalized patients. Antimicrobial-induced AKI can be classified into three different types: acute tubular necrosis (ATN), acute interstitial nephritis (AIN), and renal tubule lumen obstruction. AKI can generally be prevented by proper maintenance of fluid balance. To design dosage regimens that ensure efficient drug excretion via the kidney, it is necessary to accurately estimate renal function; however, the kidney undergoes age-dependent structural and functional alterations over time. Therefore, proper management of antimicrobial agents by an antimicrobial stewardship team may lead to decreased incidence of AKI. This article reviews antimicrobial-induced AKI and discusses potential strategies for increasing awareness of AKI and mitigating its clinical effects. [ABSTRACT FROM AUTHOR]

Objectives: We reported that the KDIGO (Kidney Disease: Improving Global Outcomes) criteria could stratify the risk of mortality in acute kidney injury (AKI) caused by cisplatin. The purpose of this study was to investigate risk factors of severe cisplatin-induced AKI (CIA). Methods: From January 2006 to December 2012, we identified Japanese cancer patients who were treated with cisplatin as a first-line chemotherapy at Nagoya University Hospital. Serum creatinine levels were used to define CIA. Results: We evaluated 1,721 patients treated with cisplatin. In multivariable analysis, cisplatin dosages/m2 [odds ratio (OR) 1.019] or diagnosis of cancer stage 4 (OR 1.797) were risk factors of moderate CIA. History of diabetes mellitus (OR 3.454), history of cardiovascular disease (OR 3.612) or diagnosis of cancer stage 4 (OR 2.610) were risk factors of severe CIA. Conclusions: Diabetes mellitus, cardiovascular disease and advanced cancer increased the risk of severe CIA. As severe CIA shortens the survival period, we should consider whether the use of cisplatin benefits these patients. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate if KDIGO (Kidney Disease: Improving Global Outcomes) criteria could be a useful outcome predictor of cisplatin-induced acute kidney injury (CIA). Methods: In the period between January 2006 and December 2011, we identified Japanese patients who had been diagnosed with cancer and treated with cisplatin as a first-line chemotherapy at Nagoya University Hospital. The serum creatinine was used to define CIA and determine the KDIGO criteria of each patient after chemotherapy within 7 days. Results: Eighty-nine patients (5.4%) were classified as having acute kidney injury (AKI) going by the KDIGO criteria, and the numbers of patients classified into AKI stages 1, 2 and 3 were 65 (3.9%), 18 (1.1%) and 6 (0.4%), respectively. Overall survival times were significantly shorter in AKI stages 2 and 3 than in stage 1. The area under the receiver operating characteristic curve with all patients was 0.68, and that of patients who were diagnosed with cancer stage 4 was 0.80. Conclusion: These results suggest that KDIGO criteria can be a predictor of CIA mortality in patients with different primary cancers. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this study was to investigate if KDIGO (Kidney Disease: Improving Global Outcomes) criteria could be a useful outcome predictor of cisplatin-induced acute kidney injury (CIA). Methods: In the period between January 2006 and December 2011, we identified Japanese patients who had been diagnosed with cancer and treated with cisplatin as a first-line chemotherapy at Nagoya University Hospital. The serum creatinine was used to define CIA and determine the KDIGO criteria of each patient after chemotherapy within 7 days. Results: Eighty-nine patients (5.4%) were classified as having acute kidney injury (AKI) going by the KDIGO criteria, and the numbers of patients classified into AKI stages 1, 2 and 3 were 65 (3.9%), 18 (1.1%) and 6 (0.4%), respectively. Overall survival times were significantly shorter in AKI stages 2 and 3 than in stage 1. The area under the receiver operating characteristic curve with all patients was 0.68, and that of patients who were diagnosed with cancer stage 4 was 0.80. Conclusion: These results suggest that KDIGO criteria can be a predictor of CIA mortality in patients with different primary cancers. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background. Atrial natriuretic peptide (ANP) was recently reported to ameliorate fibrosis in the heart and experimental renal diseases and vascular thickening after balloon injury. Peritoneal fibrosis is an important complication of long-term peritoneal dialysis, and peritonitis is a factor in its onset. In the present study, we investigated the effects of ANP in a rat peritonitis-induced peritoneal fibrosis model. Methods. As pretreatment, an osmotic pump containing vehicle (saline) or ANP (0.15 or 0.3 μg/min) was inserted through the carotid vein in male Sprague–Dawley rats. ANP or saline was continuously infused using the osmotic pump. Three days after administration of ANP or saline, rats underwent peritoneal scraping in a blind manner and were sacrificed on Day 14. The effects of ANP were evaluated based on peritoneal thickness, immunohistochemistry and real-time polymerase chain reaction. In each experiment, we evaluated messenger RNA (mRNA) expression of the ANP receptor natriuretic peptide receptor A (NPR-A) in the peritoneum after scraping. The effects of ANP were also studied in cultured peritoneal fibroblasts and mesothelial cells. Results. We observed a significant increase in NPR-A mRNA in the peritoneum. Peritoneal thickness increased with time and peaked on Day 14, but ANP significantly reduced peritoneal thickness. Parameters such as number of macrophages and CD-31-positive vessels and expression of type III collagen/transforming growth factor-β/plasminogen activator inhibitor-1 (PAI-1)/connective tissue growth factor (CTGF) were significantly suppressed by ANP. In cultured peritoneal fibroblasts and mesothelial cells, ANP suppressed angiotensin II-induced upregulation of CTGF and PAI-1. Conclusions. Our results suggest that ANP is useful in preventing inflammation-induced peritoneal fibrosis. [ABSTRACT FROM AUTHOR]

Background. The peritoneal cavity is isolated from the outside and is usually a sterile environment. Patients on peritoneal dialysis (PD) have PD fluid (PDF) infused into the peritoneal cavity. We previously showed that unregulated complement activation could contribute to the development of peritoneal inflammation in yeast peritonitis in PD therapy. In that situation, suppression of local complement activation is essential to protect the host from further injury. The membrane complement regulators (CRegs), Crry, CD55 and CD59, are expressed in the rat peritoneum, especially along the mesothelial cell layer.Methods. We investigated CRegs’ functional roles in the peritoneal cavity using blocking mAb against each CReg and complement activation in different PDFs.Results. Blockade of any single CReg did not cause spontaneous peritoneal injury in rat. Combined blockade of Crry and CD59 induced focal peritoneal tissue injury and heavy accumulation of inflammatory cells with peritoneal edema at 24 h. Deposits of C3 and C5b-9 were found on the peritoneal surface after combined blocking of Crry and CD59. Systemic complement depletion by cobra venom factor abrogated these inflammatory changes. When combined blockade of Crry and CD59 was performed with PDF of different pH and glucose concentration in rats, the peritoneal injuries were enhanced with lower pH and higher glucose concentration. These results were confirmed by in vitro experiments using primary rat mesothelial cell culture.Conclusions. Rat CRegs, Crry and CD59, specifically collaborate to control complement activation in rat peritoneum. During PD, impairment of CReg might contribute to the development of severe peritoneal inflammation. [ABSTRACT FROM AUTHOR]

Abstract: Mural thrombus generation at sites of damaged vessel walls is essential for both physiological haemostasis and pathological intravascular thrombosis. While thrombi are established by the concerted action of platelet aggregation and blood coagulation, most previous in vitro coagulation assays have evaluated fibrin clot formation in a closed stirring situation that lacks blood cells including platelets. We describe here a modified flow chamber system, established originally for platelet functional studies, that enables real-time observation of intra-thrombus fibrin accumulation during platelet thrombogenesis under flow conditions. Analysis by confocal laser scanning microscopy during perfusion of whole blood anticoagulated to various extents revealed that the size and shape of mural thrombi can depend on the intra-thrombus fibrin development under high shear rate conditions. These observations were confirmed by perfusion of heparinized blood or blood from haemophilia patients with or without addition of activated factor VII. Thus, our experimental system provides visual evidence supporting the concept of “cell-based coagulation under whole blood flow”, which might be the most physiologically relevant model of comprehensive thrombogenicity in vivo to date. This system promises to help formulate strategies for haemostatic management of congenital coagulation disorders as well as for antithrombotic therapy targeting fatal arterial thrombosis. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Dual reflector antennas fed with a beam waveguide are widely used for base stations of satellite communication and for radio astronomy. When the antenna is used at several frequencies, it is effective to carry out diplexing with a frequency selective surface (FSS) in the beam waveguide. Traditionally, when an antenna containing an FSS on the reflector surface is designed, or its radiation characteristics are evaluated, it is assumed that the FSS is ideal and it is modeled by a metal plate or a transparent plate in order to derive the radiation characteristics of the antenna at the frequency range in which the FSS is used for transmission or reflection. Next, the return loss or transmission loss of the FSS alone is derived. This loss has been considered as gain reduction of the radiation characteristics of the antenna with an ideal FSS. However, since the reflection and transmission characteristics of the FSS differ depending on the angle of incidence and polarization angle of the wave incident on the FSS, the radiation pattern of the entire antenna system and that of the wave that is incident on the focusing reflector connected to the FSS are different from those obtained when using a focusing reflector modeled by an ideal FSS. Hence, for accurate design and evaluation of a dual reflector antenna fed by a beam waveguide using an FSS, the effect of the reflection and transmission characteristics of the FSS on the radiation characteristics must be considered in addition to the loss caused by the FSS. This paper studies the effect of the FSS on the radiation characteristics when a dual reflector fed by a beam waveguide with an FSS partially installed is excited by the fundamental mode (EH11) of the primary radiator. For calculation of the electromagnetic field in the beam-waveguide feed, the beam mode expansion method is used, so that the wave effect is taken into account. For calculation of the reflection and transmission characteristics of the FSS, a simple method is used in which the electromagnetic field scattered by the FSS is expanded in terms of Floquet modes and the electric field on the FSS is determined by the method of moments. Further, in order to reduce the effect on the radiation characteristics resulting from the difference in reflection phase at the metal part and at the FSS, the location of installation of the FSS is offset so that the phase difference of the reflected waves from two regions is compensated. This proposed method is found effective. © 2003 Wiley Periodicals, Inc. Electron Comm Jpn Pt 1, 86(5): 21–31, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/ecja.10041 [ABSTRACT FROM AUTHOR]

Objectives: Despite steadily improving outcomes, surgery for acute type A aortic dissection has several unresolved problems such as expansion of the residual false lumen in the descending aorta. We performed transaortic stented graft implantation into the descending aorta combined with the ascending aorta and aortic arch replacement for acute type A aortic dissection. We review the efficacy and outcomes of this procedure with respect to the residual false lumen and postoperative neurologic complications we encountered. Methods: Nine consecutive patients with acute type A aortic dissection underwent this procedure. The stented elephant trunk graft was implanted through the aortic arch under hypothermic circulatory arrest. The stented graft was 15 cm long in six patients, and 10 cm long in three patients. Enhanced computed tomography (CT) was performed 1 month after surgery and once each year after discharge to evaluate the postoperative time course of the residual false lumen. Results: Cardiopulmonary bypass (CPB) time was quite long because of slow cooling and re-warming [352±92 (mean±SD) min], and average lower-body arrest time was 54±10 min. The intima in one patient was injured at the time of implantation, and a small leak was created. One patient died of multiorgan failure postoperatively. One patient suffered cerebral injury, and two suffered spinal cord injury perioperatively. Average follow-up time was 40.4 months (range, 13–66 months). One patient died of cerebral infarction during follow up, and the other seven survived and remain well. Postoperative enhanced CT scans showed that the dissected descending aortas attached to the stented grafts and the aortas near the stented grafts returned to normal. In one patient with no re-entry, the false lumen completely closed with thrombi and the entire aorta returned to normal. The diameter of the descending aorta decreased or did not change in six of the seven patients (85.8%) and increased by only 2 mm in one of them (14.2%) during follow up. Conclusions: Implantation of a stented elephant trunk into the descending aorta combined with replacement of the ascending aorta and total arch for acute type A aortic dissection is effective in closing the residual false lumen of the descending aorta and in preventing expansion of the descending aorta. However, further technical modifications, such as using a short stented elephant trunk, eliminating aortic clamping, shortening CPB and spinal cord ischemic time, and reconstruction of left subclavian artery, are needed to prevent neurologic complications. [Copyright &y& Elsevier]

Blood pressure (BP) telemonitoring systems and pharmacist management programs were introduced into Haruka Community Pharmacy. A 22-year-old healthy male came to the community pharmacy, although he was not in a diseased state, he had been informed previously that he had a moderately high BP during a routine examination. He continued home BP telemonitoring for 28 days. A pharmacist intervention was conducted at 2 week intervals. His average nighttime systolic BP was higher than the daytime systolic BP. The pharmacist consulted a doctor based on the BP telemonitoring results, and ambulatory blood pressure monitoring (ABPM) was initiated. The doctor detected nocturnal hypertension based on the results of ABPM monitoring. BP telemonitoring systems have been introduced into a small percentage of pharmacies in Japan, and this is the first case report for the usefulness of these systems in a community pharmacy. Keywords: community pharmacy, management, ambulatory blood pressure monitoring. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the present study were to establish a population pharmacokinetic (PPK) model of cefazolin for adult patients undergoing cardiac surgery with cardiopulmonary bypass (CPB) and to assess the probability of target attainment (PTA) for the prophylaxis of surgical site infection (SSI) using cefazolin. Methods: Adult patients who underwent cardiac surgery with CPB were enrolled in the prospective study. Blood samples for plasma cefazolin assay were collected, and total and unbound drug concentrations were measured and analysed using the nonlinear mixed-effects modelling (NONMEM) software considering saturable plasma protein binding. Using the PPK model, plasma unbound cefazolin concentration-time courses with current prophylaxis protocols were simulated, and the PTA for common SSI pathogens was estimated. Results: A total of 199 blood samples were obtained from 27 patients. A one-compartment model with first-order elimination plus an on/off CPB compartment best described the data. The population mean for systemic drug clearance (CL) was reduced and that for the volume of distribution (V) was increased during CPB compared with the pre-CPB values. CPB-induced hypoalbuminemia was associated with reduced maximum protein binding (Bmax). The simulation studies suggested that the current dosing protocols are insufficient for attaining PTA > 0.9 throughout surgery against pathogens with minimum inhibitory concentrations (MICs) >8 mg/L. A new dosing protocol that achieves a PTA > 0.9 for pathogens with a MIC of 16 mg/L was proposed. Conclusion: PPK modelling with simulation may be valuable for devising a cefazolin prophylaxis protocol for patients undergoing cardiac surgery with CPB. [ABSTRACT FROM AUTHOR]

Introduction: For extended arch and thoracic descending aortic disease, open surgery is too invasive, but endovascular aortic arch repair with reconstruction of three arch vessels is still problematic. We aggressively apply single-stage hybrid arch repair (HAR) for those patients. Methods: Between 2007 and 2018, we treated 133 patients with aortic arch and descending thoracic aortic disease. In our typical single-stage HAR, the ascending aorta and partial arch are replaced with debranching of three arch vessels via sternotomy, and SGs are antegradely deployed via a graft branch from the replaced artificial graft to the descending aorta under good hemodynamic conditions after cardiopulmonary bypass is stopped. We assessed the results of our HAR. Results: HAR was performed in 41 patients, total arch replacement (TAR) in 69, frozen elephant trunk (FET) in 8, and left thoracotomy approach (LT) in 16. There was no overall operative mortality. In HAR, concomitant cardiac surgery was performed in 37.5% of patients, and 82.5% of the patients were extubated within 24 hours after surgery. No permanent neurological deficit was observed. The mean distal end of the SGs was located at Th 8.5 (Th7-11), and paraparesis was observed in 1 patient (the distal end of the SG was at Th10). The rates of freedom from all-cause death and freedom from aorta-related complications were 100% and 97.3% at 1 year and 88.0% and 83.4% at 5 years, respectively. In TAR, the rate of concomitant cardiac surgery was 41.8% with respiratory support needed within 24 hours in 62.7%, and permanent neurological deficit in 1 patient; the rates of freedom from all-cause death and aorta-related complications were 91.8% and 98.4% at 1 year and 82.6% and 98.4% at 5 years, respectively (statistically identical to HAR). The rate of spinal cord ischemia was significantly higher in FET (25%), and the duration of respiratory support in LT was significantly longer than in HAR and TAR. Conclusions: Our single-stage HAR can treat extended arch and thoracic descending aortic disease, while simultaneously reducing the duration of respiratory support, preventing stroke, and preventing spinal cord ischemia, with the same efficacy as for TEVAR. Our HAR effectively balances surgical invasiveness with improved postoperative outcomes. [ABSTRACT FROM AUTHOR]

Extracellular histones promote platelet aggregation and thrombosis; this is followed by induction of coagulation disorder, which results in exhaustion of coagulation factors. Complement component 5 (C5) is known to be associated with platelet aggregation and coagulation system activation. To date, the pathological mechanism underlying liver injury has remained unclear. Here, we investigated whether C5 promotes liver injury associated with histone-induced lethal thrombosis. C5-sufficient and C5-deficient mice received single tail vein injections of purified, unfractionated histones obtained from calf thymus (45-75 μg/g). Subsequently, the mice were monitored for survival for up to 72 h. Based on the survival data, the 45 μg/g dose was used for analysis of blood cell count, liver function, blood coagulation ability, and promotion of platelet aggregation and platelet/leukocyte aggregate (PLA) production by extracellular histones. C5-deficient mice were protected from lethal thrombosis and had milder thrombocytopenia, consumptive coagulopathy, and liver injury with embolism and lower PLA production than C5-sufficient mice. These results indicate that C5 is associated with coagulation disorders, PLA production, and embolism-induced liver injury. In conclusion, C5 promotes liver injury associated with histone-induced lethal thrombosis. [ABSTRACT FROM AUTHOR]

The aim of the study was to evaluate the disposition of plasma unbound cefazolin in patients undergoing cardiothoracic surgery with cardiopulmonary bypass (CPB). Adult patients undergoing cardiothoracic surgery with CPB were enrolled in the study. Cefazolin sodium was given intravenously before skin incision (1 g) and at the beginning of CPB (2 g). Thereafter, an additional dose (1 g) was given every 4 hours. Seven to ten blood samples were collected before and during surgery. Plasma total and unbound (ultrafiltrated) cefazolin concentrations were analyzed using an HPLC-UV method. Plasma protein binding was analyzed with the Langmuir model. Twenty-seven patients (aged 70 ± 12 years, body weight 62 ± 12 kg, mean ± SD) with GFR >30 mL min-1 completed the study. There was a significant (P < 0.001) increase in median plasma unbound fraction of cefazolin from 21% before skin incision to 45% during CPB (P < 0.001), which was accompanied by a significant (P < 0.001) reduction in median plasma albumin concentration from 36 to 27 g L-1. Plasma concentrations of unbound cefazolin exceeded the assumed target thresholds of 2 μg mL-1 in all samples and of 8 μg mL-1 in all but one of 199 samples. The increased plasma unbound fraction of cefazolin would be attributable to dilutional reduction of serum albumin at the beginning of CPB and to saturable plasma protein binding of cefazolin. These data reveal CPB may alter the plasma protein binding and possibly distribution of cefazolin. Further studies are warranted to reappraise the protocol of antimicrobial prophylaxis with cefazolin in patients undergoing surgery with CPB. [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]

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]

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]

Anti-endothelial cell antibodies (AECA) are frequently detected in patients with systemic lupus erythematosus (SLE), but their pathological role remains unclear. We recently developed a solubilized cell surface protein capture enzyme-linked immunosorbent assay (CSP-ELISA) to detect antibodies against membrane proteins involved in autoimmune reactions. In this study, sera from 51 patients with biopsy-proven lupus nephritis (LN), 25 with SLE without renal involvement (non-LN SLE), 42 disease control (DC) subjects, and 80 healthy control (HC) subjects were tested for IgG- and IgA-AECA for human umbilical vein endothelial cells (HUVEC) and human glomerular EC (HGEC) by using CSP-ELISA. IgG- and IgA-AECA titers were significantly higher in LN and non-LN SLE patients than in the DC or HC (P < 0.001) groups. IgG- and IgA-AECA titers for HUVEC corresponded well with those for HGEC. The IgA-AECA level correlated with the SLE disease activity index and with histological evidence of active lesions (cellular proliferations, hyaline thrombi and wire loops, leukocytic infiltration, and fibrinoid necrosis) in LN patients (P < 0.001). The sensitivity of IgA-AECA as a diagnostic test for histological evidence of active lesions in LN patients was 0.92, with a specificity of 0.70. The significant correlation of IgA-AECA with glomerular hypercellularity indicates that IgA-AECA are associated with endothelial damage in LN. [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]

Peritonitis and the rare sequela of encapsulating peritoneal sclerosis (EPS) are serious problems in patients on peritoneal dialysis therapy. Chronic and persistent peritoneal injuries may be a risk factor of EPS. We previously reported that a chronic, proliferative peritonitis developed when zymosan was administered intraperitoneally following scraping injury of rat peritoneum (Mizuno M, Ito Y, Hepburn N, Mizuno T, Noda Y, Yuzawa Y, Harris CL, Morgan BP, Matsuo S. J Immunol 183: 1403-1412, 2009). Peritoneal membrane complement regulators (CRegs), especially Crry and CD59, protected from injury by inhibiting local complement activation, suggesting that CRegs play important roles in maintaining homeostasis in rat peritoneum. Here, we investigated roles of complement in the development of EPS by neutralizing CReg function with monoclonal antibodies (MAbs). Proliferative peritonitis was induced by scraping the peritoneum, followed by daily intraperitoneal administration of zymosan. When either Crry or CD59 alone was neutralized by MAb, the tissue injuries were not significantly changed compared with rats without neutralizing MAb. When both Crry and CD59 were neutralized in this model, severe fibrin exudation was observed on the peritoneal surface on day 5, accompanied by inflammatory cell infiltration, resembling the early stages of development of EPS. Dense peritoneal deposition of C3 fragments and membrane attack complex were observed, along with the fibrin exudates. Intravenous administration of cobra venom factor, which profoundly activates complement, further enhanced these pathological changes. Our results show that complement activation in injured peritoneum drives peritoneal inflammation, and that enhancement of complement activation by inhibiting CReg and/or enhancing systemic activation contributes to the initiation of EPS; therefore, anti-complement agents might be of therapeutic value in humans for the treatment of EPS. [ABSTRACT FROM AUTHOR]

• The antiviral agent favipiravir (FVP) may cause hyperuricemia. • Factors associated with FVP use and hyperuricemia in COVID-19 were examined. • Serum FVP levels were significantly correlated with baseline uric acid (UA) levels. • Serum FVP and baseline UA levels were associated with the development of hyperuricemia. • Cut-off values for predicting hyperuricemia were 3.7 mg/dL (UA) and 46.14 μg/mL (FVP). Favipiravir is an antiviral that is being evaluated for the treatment of COVID-19. Use of favipiravir is associated with elevation of serum uric acid levels. Risk factors for the occurrence of hyperuricemia are unclear. Specimens from COVID-19 patients who received 10 days of favipiravir in a previous clinical trial (jRCTs041190120) were used. Serum favipiravir concentrations were measured by LC-MS. Factors associated with the development of hyperuricemia were investigated using logistic regression analysis. Optimal cut-off values for the baseline serum uric acid levels and steady-state serum favipiravir concentrations in predicting the occurrence of hyperuricemia were determined by ROC curve analysis. Among the 66 COVID-19 patients who were treated with favipiravir for 10 days, the steady-state serum favipiravir concentrations were significantly correlated with serum uric acid levels. High baseline serum uric acid levels and steady-state serum favipiravir concentrations during therapy were factors associated with the development of hyperuricemia. The cut‑off baseline serum uric acid level and steady-state serum favipiravir concentration during favipiravir administration determined to predict hyperuricemia were 3.7 mg/dL and 46.14 μg/mL, respectively. Patients with high baseline serum uric acid levels or who achieved high steady-state serum favipiravir concentrations during therapy were susceptible to hyperuricemia. [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]

Pump thrombosis induces significant complications and requires timely detection. We proposed real‐time monitoring of pump thrombus in a magnetically levitated centrifugal blood pump (mag‐lev pump) without using additional sensors, by focusing on the changes in the displacement of the pump impeller. The phase difference between the current and displacement of the impeller increases with pump thrombus. This thrombus detection method was previously evaluated through simulated circuit experiments using porcine blood. Evaluation of real‐time thrombus detection in a mag‐lev blood pump was performed using a porcine left ventricular assist circulation model in this study. Acute animal experiments were performed five times using five Japanese domestic pigs. To create thrombogenic conditions, fibrinogen coating that induces thrombus formation in a short time was applied to the inner surfaces of the pump. An inflow and an outflow cannula were inserted into the apex of the left ventricle and the carotid artery, respectively, by a minimally invasive surgical procedure that allowed minimal bleeding and hypothermia. Pump flow was maintained at 1 L/min without anticoagulation. The vibrational frequency of the impeller (70 Hz) and its vibrational amplitude (30 μm) were kept constant. The thrombus was detected based on the fact that the phase difference between the impeller displacement and input current to the magnetic bearing increases when a thrombus is formed inside a pump. The experiment was terminated when the phase difference increased by over 1° from the lowest value or when the phase difference was at the lowest value 12 hours after commencing measurements. The phase difference increased by over 1° in three cases. The pump was stopped after 12 hours in two cases. Pump thrombi were found in the pump in three cases in which the phase difference increased by over 1°. No pump thrombus was found in the other two cases in which the phase difference did not increase. We succeeded in real‐time thrombus monitoring of a mag‐lev pump in acute animal experiments. [ABSTRACT FROM AUTHOR]

A pole-type filter is proposed, in which the coaxial probe acts as a trap circuit in addition to the conventional filter operation, by adjusting the spacing between the coaxial probe and the waveguide backshort in a coaxial-coupled cutoff waveguide filter. Unlike the conventional coaxial-coupled filter, this filter has a coaxial probe located close to the resonator of the next stage. Therefore, the filter is designed by using a synthesis method in which the effects of the higher-order cutoff modes are taken into account. The numerical results and the experimental investigation of the transmission characteristics of the synthesized filter verify its usefulness. © 1998 Scripta Technica. Electron Comm Jpn Pt 2, 80(8): 53–61, 1997 [ABSTRACT FROM AUTHOR]

Although the magnetically levitated centrifugal blood pump (mag‐lev pump) is considered superior to other pumps in antithrombogenicity, thrombotic complications are still reported. Research into thrombus detection inside a mag‐lev pump is very important for solving this problem. Our research group has already proposed a method to detect a thrombus inside a mag‐lev pump in real time without an additional sensor, which is named the impeller vibration method. To efficiently advance our research with reproducibility, a preconditioning method to induce thrombus inside the pump was thought to be necessary. Therefore, this study aimed to develop a preconditioning method that induces thrombus formation. To verify this method, in vitro experiments for thrombus detection were performed. A mag‐lev pump developed at Tokyo Institute of Technology was used. A fibrinogen solution was coated on the inner surfaces of the bottom housing to induce thrombus formation at the target point inside the pump. The thrombus is detected by utilizing the phenomenon that the phase difference between the impeller displacement and input current to the magnetic bearing increases when a thrombus is formed inside a pump. Five hundred mL of porcine blood anticoagulated with heparin sodium was circulated in the mock circuit, and protamine sulfate was administered. Flow rate (1 L/min), impeller vibrational frequency (70 Hz), and vibrational amplitude (30 µm) were set to constant. The experiment was terminated when the phase difference increased by over 2° from the minimum value. The experiments were performed in fibrinogen‐coated (group F, n = 5) and non‐coated pumps (group N, n = 5). In group F, thrombus formation was observed at the fibrinogen‐coated point of the housing. In contrast, a relatively small thrombus was observed in varying locations such as the housing or the impeller in group N. Thrombus formation time (the time from when the phase difference takes the minimum value to when the experiment is terminated) was different between the two groups. The mean time was significantly shorter in group F (44 ± 29 minutes) than in group N (143 ± 38 minutes; p = 0.0019). Therefore, a preconditioning method that induced thrombus formation at the target point inside a blood pump was successfully developed. [ABSTRACT FROM AUTHOR]

A common renal disease, immunoglobulin A (IgA) nephropathy (IgAN), is associated with glomerular deposition of IgA1-containing immune complexes. IgA1 hinge region (HR) has up to six clustered O-glycans consisting of Ser/Thr-linked N-acetylgalactosamine with β1,3-linked galactose and variable sialylation. IgA1 glycoforms with some galactose-deficient (Gd) HR O-glycans play a key role in IgAN pathogenesis. The clustered and variable O-glycans make the IgA1 glycomic analysis challenging and better approaches are needed. Here, we report a comprehensive analytical workflow for IgA1 HR O-glycoform analysis. We combined an automated quantitative analysis of the HR O-glycopeptide profiles with sequential deglycosylation to remove all but Gd O-glycans from the HR. The workflow was tested using serum IgA1 from healthy subjects. Twelve variants of glycopeptides corresponding to the HR with three to six O-glycans were detected; nine glycopeptides carried up to three Gd O-glycans. Sites with Gd O-glycans were unambiguously identified by electron-transfer/higher-energy collision dissociation tandem mass spectrometry. Extracted ion chromatograms of isomeric glycoforms enabled quantitative assignment of Gd sites. The most frequent Gd site was T236, followed by S230, T233, T228, and S232. The new workflow for quantitative profiling of IgA1 HR O-glycoforms with site-specific resolution will enable identification of pathogenic IgA1 HR O-glycoforms in IgAN. [ABSTRACT FROM AUTHOR]

Complications due to pump thrombus remain the weak point of mechanical circulatory support (MCS), such as the use of a left ventricular assist device (LVAD) or extracorporeal membrane oxygenation, leading to poor outcomes. Hyperspectral imaging (HSI) is an effective imaging method using a hyperspectral (HS) camera, which comprises a spectrophotometer and a charge-coupled device camera to discriminate thrombus from whole blood. Animal experiments were conducted to analyze dynamic imaging of thrombus inside a prototype of a hydrodynamically levitated centrifugal blood pump using an HSI system. Six pigs were divided into a venous circulation group ( n = 3) and an arterial circulation group ( n = 3). Inflow and outflow cannulae were inserted into the jugular veins in the venous circulation group. The latter simulated an LVAD application. To create thrombogenic conditions, pump flow was maintained at 1 L/min without anticoagulation. An image of the bottom surface of the pump was captured by the HS camera every 4 nm over the wavelength range of 608-752 nm. Real-time dynamic images of the inside of the pump were displayed on the monitor. Appearance of an area displaying thrombus was detected within 24 h after the start of the circulation in every experiment. This imaging system also succeeded in determining the origins of pump thrombus: from inside the pump in two cases, and from outside in four cases. Two main possible sources of pump thrombus originating outside the pump were identified on autopsy: wedge thrombus around the inflow cannula; and string-like thrombus at the junction between the pump inlet and circuit tube. The results of this study from close observation of the changing appearance of pump thrombus may contribute to improvements in the safety of extracorporeal MCS. [ABSTRACT FROM AUTHOR]

Inflammation is recognized as an important contributor to lymphangiogenesis; however, in tubulointerstitial lesions in human chronic kidney diseases, this process is better correlated with the presence of myofibroblasts rather than macrophages. As little is known about the interaction between lymphangiogenesis and renal fibrosis, we utilized the rat unilateral ureteral obstruction model to analyze inflammation, fibrosis, lymphangiogenesis, and growth factor expression. Additionally, we determined the relationship between vascular endothelial growth factor-C (VEGF-C), an inducer of lymphangiogenesis, and the profibrotic factor, transforming growth factor-β1 (TGF-β1). The expression of both TGF-β1 and VEGF-C was detected in tubular epithelial and mononuclear cells, and gradually increased, peaking 14 days after ureteral obstruction. The kinetics and localization of VEGF-C were similar to those of TGF-β1, and the expression of these growth factors and lymphangiogenesis were linked with the progression of fibrosis. VEGF-C expression was upregulated by TGF-β1 in cultured proximal tubular epithelial cells, collecting duct cells, and macrophages. Both in vitro and in vivo, the induction of VEGF-C along with the overall appearance of lymphatics in vivo was specifically suppressed by the TGF-β type I receptor inhibitor LY364947. Thus, TGF-β1 induces VEGF-C expression, which leads to lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Background: Diabetic cardiomyopathy is a common cause of heart failure in diabetic patients, but current treatments do not directly improve ventricular function. Cell transplantation can prevent cardiac dilatation after injury, and may also prevent congestive heart failure in diabetic cardiomyopathy. Aim: This study evaluated the functional effects of smooth muscle cells (SMCs) implanted into the myocardium of insulin- and non insulin-treated diabetic rats. Methods: Four weeks after streptozotocin infusion, adult Wistar rats were implanted with BrdU-labelled SMCs or culture media (N =12/group). Six rats in each group were also treated with insulin. Echocardiograms were performed at 0, 4 and 8 weeks after streptozotocin injection, and histology and heart function were evaluated at 4 weeks after implantation. Results: Blood glucose levels decreased after insulin treatment. Among cell-injected rats, histology indicated that those that did not receive insulin retained fewer surviving BrdU+ SMCs, and a smaller volume of myocardial tissue positive for α-smooth muscle actin. Cardiac function was preserved in the insulin-treated groups relative to those that did not receive insulin. Among insulin-treated rats, the cell-injected group functioned better than the media-injected group. Conclusions: Diabetic cardiomyopathy is partially treatable with insulin; however, a combination of SMC transplantation and insulin treatment produced the best functional result. Cell transplantation may prevent the progression of diabetic cardiomyopathy in patients whose glucose levels are controlled with insulin. [Copyright &y& Elsevier]

A magnetically levitated (MagLev) centrifugal blood pump (CBP) with a disposable pump head has been designed to realize a safe, easy-to-handle, reliable, and low-cost extracorporeal blood pump system. It consisted of a radial magnetic-coupled driver with a magnetic bearing having a two-degree freedom control and a disposable pump head unit with a priming volume of 24 mL. The easy on–off disposable pump head unit was made into a three-piece system consisting of the top and bottom housings, and the impeller-rotor assembly. The size and weight of the disposable pump unit were 75 mm × 45 mm and 100 g, respectively. Because the structure of the pump head unit is easily attachable and removable, the gap between the electromagnets of the stator and the target material in the rotor increased to 1.8 mm in comparison to the original integrated bearing system of 1.0 mm. The pump performance, power requirements, and controllability of the magnetic bearing revealed that from 1400 to 2400 rpm, the pump performance remained fairly unchanged. The amplitudes of the X- and Y-axis rotor oscillation increased to ± 24 µm. The axial displacement of the rotor, 0.4 mm, toward the top housing was also observed at the pump rpm between 1400 and 2400. The axial and rotational stiffness of the bearing were 15.9 N/mm and 4.4 Nm/rad, respectively. The MagLev power was within 0.7 Watts. This study demonstrated the feasibility of a disposable, magnetically suspended CBP as the safe, reliable, easy-to-handle, low-cost extracorporeal circulation support device. [ABSTRACT FROM AUTHOR]