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Right neck swelling and pain occurred in a 49-year-old man. A Blood count showed a slight increase in platelet count without leukemoid reaction. After a biopsy of the cervical mass and bone marrow aspiration, a diagnosis of extramedullary blast crisis (EBC) of chronic myeloid leukemia (CML) was made. Fluorescence in situ hybridization (FISH) analysis showed a BCR-ABL1 fusion signal, but results of real-time polymerase chain reaction (RT-PCR) for major and minor BCR-ABL1 transcripts were negative. We identified a rare e1a 3 BCR-ABL1 fusion transcript. Administration of dasatinib resulted in disappearance of the extramedullary tumor. This is the first reported case of CML-EBC with e1a3 transcript. An aleukemic extramedullary tumor can be the initial presentation of CML.

Background: There are no reports on the effects of interventions, such as discontinuation and change and/or deescalation of carbapenems and anti-methicillin-resistant Staphylococcus aureus (MRSA) antibiotics by an antimicrobial stewardship team focusing on detailed patient outcomes. This study aimed to evaluate these effects. Methods: This retrospective cohort study was conducted at a tertiary care hospital from December 2018 to November 2019. Results: Favorable clinical responses were obtained in 165 of 184 cases (89.7%) in the intervention-accepted group, higher than those in the not accepted group (14/19 cases, 73.7%; P = .056). All-cause 30 day mortality was lower in the accepted group than in the not accepted group (1.1% and 10.5%, respectively; P = .045). The microbiological outcomes were similar between the two groups. Duration of carbapenem and anti-MRSA antibiotic use in the accepted group was significantly lower than that in the not accepted group (median [interquartile range]: 8 days [5-13] versus 14 days [8-15], respectively, P = .026 for carbapenem; 10 days [5.3-15] vs 15.5 days [13.8-45.3], respectively, P = .014 for anti-MRSA antibiotic). Conclusions: This is the first study to investigate the effects of interventions such as discontinuation and change and/ or de-escalation of antibiotics on detailed outcomes. Our intervention could reduce the duration of carbapenem and anti-MRSA antibiotic use without worsening clinical and microbiological outcomes. (c) 2021 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.

Hepatic sinusoidal obstruction syndrome (SOS)/veno-occlusive disease is a life-threatening complication after hematopoietic stem cell transplantation (HSCT). We previously reported the efficacy of the Hokkaido Ultrasonography (US)-based scoring system (HokUS-10) for US findings. To establish easier-to-use criteria, we retrospectively evaluated US findings from 441 patients, including 30 patients with SOS using the HokUS-10 scoring system. Using logistic regression analysis, we established the novel diagnostic criteria HokUS-6. In the presence of ascites, US diagnosis was made in the presence of two of the following 6 parameters: moderate amount of ascites, the appearance of a paraumbilical vein blood flow signal, gallbladder wall thickening, portal vein dilatation, portal vein velocity decrease, and hepatic artery resistive index increase. The AUC, sensitivity, and specificity of HokUS-6 were 0.974 (95% confidence interval 0.962-0.990), 95.2%, and 96.9%, respectively. The scores were significantly higher in patients with severe SOS than in those with non-severe SOS (p = 0.013). Furthermore, the scores before HSCT were significantly higher in patients who developed SOS than in controls (p = 0.001). The HokUS-6 is an easy and useful way to diagnose and identify the risk of SOS.

The constant development and improvement of microelectromechanical systems (MEMS) have been given a great opportunity to develop new reliable microsystems devices for biomedical research. This article presents a locally addressable 2-D arrayed indium–tin oxide microelectrode platform with integrated thin-film transistors (TFTs) for biological and chemical sensing. Microelectrode arrays (MEAs) using TFT have the advantage of being transparent with a high density of microelectrodes on a large surface. In vitro 2-D electrical measurements on 28 parallel-connected lines selected from a 22 500 MEA were successfully performed with heart cells for the first time. Observation of cell contraction was performed simultaneously with an inverted microscope. Voltammetry and amperometry measurements were also demonstrated using the transparent microelectrodes as working electrodes and an integrated Ag/AgCl reference electrode. Due to its unique features, we believe that the TFT platform can provide more understanding of the key communication between heart cells, and large-scale cardiovascular and nervous systems. As a result, the platform offers unique access to versatile lab-on-a-chip devices that integrate many measurement techniques on one chip for the study of cell cultures, tissues, and organoids.

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 10^7/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0–85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 10^9/L on day 60 was 80.6% (68.2–88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 10^9/L and platelets ≥ 50 × 10^9/L on day 100 were 75.8% (62.6–84.9%) and 72.6% (59.4–82.1%), respectively, with median time to platelets ≥ 20 × 10^9/L and platelets ≥ 50 × 10^9/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II–IV and III–IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.

Masafumi Yamamoto,1 Satoshi Konno,2 Hironi Makita,2,3 Katsuaki Nitta,4 Kaoruko Shimizu,2 Masaru Suzuki,2 Mutsumi Nishida,1 Junichi Sugita,1 Takanori Teshima,1 Masaharu Nishimura2,3 1Division of Laboratory and Transfusion Medicine, Hokkaido University Hospital, Sapporo, Hokkaido, Japan; 2Department of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Hokkaido, Japan; 3Hokkaido Institute of Respiratory Diseases, Sapporo, Hokkaido, Japan; 4Makita Hospital, Sapporo, Hokkaido, JapanCorrespondence: Masaharu NishimuraDepartment of Respiratory Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, N-15 W-7, Kita-Ku, Sapporo, 060-8638, JapanTel +81-11-706-5911Fax +81-11-706-7899Email ma-nishi@med.hokudai.ac.jpBackground: Generally, the maximal expiratory flow–volume (MEFV) curve must be measured for the diagnosis and staging of chronic obstructive pulmonary disease (COPD). As this test is effort dependent, international guidelines recommend that three acceptable trials are required for each test. However, no study has examined the magnitude and factors for the variability in parameters among three acceptable trials.Methods: We evaluated the intra-individual variations in several parameters among three acceptable MEFV curves obtained at one-time point in patients with COPD (n = 28, stage 1; n = 36, stage 2; n = 21, stages 3– 4). Next, the factors for such variations were examined using forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC).Results: The averages of coefficient of variation (CV) for FEV1 and FVC were 2.0% (range: 1.0– 3.0%) and 1.6% (0.9– 2.2%), respectively. Both parameters were significantly better than peak expiratory flow rate, forced expiratory flow at 50% of expired FVC, and forced expiratory flow at 75% of expired FVC (CVs: 5.0– 6.9%). A higher spirometric stage was significantly associated with higher CVs for FVC and FEV1, and older age was significantly correlated with a higher variation in FEV1 alone. Furthermore, a significantly inverse association was observed between emphysema severity, and the CVs for FEV1, but not that for FVC, regardless of spirometric stage.Conclusion: Both FVC and FEV1 are highly reproducible; nevertheless, older age, lower FEV1 at baseline, and non-emphysema phenotype are factors for a higher variability in FEV1 in patients with COPD.Keywords: chronic obstructive pulmonary disease, coefficient of variation, flow–volume curve, forced expiratory volume in 1 second, variability

Introduction: The Global Leadership Initiative on Malnutrition (GLIM) lacks reliable blood tests for evaluating the nutrition status. We retrospectively compared the GLIM criteria, Controlling Nutrition Status (CONUT) score, and Subjective Global Assessment (SGA) to establish effective malnutrition screening and provide appropriate nutritional interventions according to severity. Methods: We classified 177 patients into 3 malnutrition categories (normal/mild, moderate, and severe) according to the GLIM criteria, CONUT score, and SGA. We investigated the malnutrition prevalence, concordance of malnutrition severity, predictability of clinical outcome, concordance by etiology, and clinical outcome by inflammation. Results: The highest prevalence of malnutrition was found using the GLIM criteria (87.6%). Concordance of malnutrition severity was low between the GLIM criteria and CONUT score. Concordance by etiology was low in all groups but was the highest in the “acute disease” group. The area under the curve of clinical outcome and that of the “with inflammation group” were significantly higher when using the CONUT score versus using the other tools (0.679 and 0.683, respectively). Conclusion: The GLIM criteria have high sensitivity, while the CONUT score can effectively predict the clinical outcome of malnutrition. Their combined use can efficiently screen for malnutrition and patient severity in acute care hospitals.

Purpose Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a fatal complication after hematopoietic stem cell transplantation. We previously reported the usefulness of an ultrasonographical (US) scoring system, the Hokkaido US-based scoring system consisting of ten parameters (HokUS-10): (1) hepatomegaly in the left lobe and (2) right lobe, (3) dilatation of the main portal vein (PV), (4) hepatofugal flow in the main PV, (5) decreased velocity of the PV, (6) dilatation of the para-umbilical vein (PUV), (7) appearance of blood flow signal in the PUV, (8) gallbladder (GB) wall thickening, (9) ascites, and (10) increased resistive index of the hepatic artery, for the diagnosis of SOS/VOD. However, the reliability of this system among operators remains elusive. Therefore, we prospectively evaluated the reliability of HokUS-10. Methods Twenty-four healthy volunteers and 40 patients with liver dysfunction were enrolled. Inter- and intra-operator reliabilities were analyzed using three sonographers. Results The median concordance rate of HokUS-10 among three sonographers and intra-operator in 24 volunteers was 92% (95% CI: 73-98%) and 98% (95% CI: 92-100%), respectively. In all 64 cases, in terms of the reliability between two sonographers for three representative US parameters (amount of ascites, GB wall thickening, and appearance of PUV blood flow signal), the median concordance rate was more than 98% (95% CI: 86-106%). Conclusion The inter- and intra-reliabilities of HokUS-10 were excellent. Thus, US might be a reliable tool for SOS/VOD diagnosis.

Purpose Mycophenolate mofetil (MMF), a mycophenolic acid (MPA) prodrug, is used to prevent graft-versus-host disease (GVHD) in hematopoietic stem cell transplantation (HSCT). Although previous studies have reported that enterohepatic circulation (EHC) of MPA, which is usually observed in MMF-treated patients, does not occur in HSCT patients, it is unclear what happens in haploidentical–HSCT (haplo-HSCT) patients, who are using post-transplant cyclophosphamide. This study was conducted to investigate MPA pharmacokinetics in haplo-HSCT patients. Methods Seventeen haplo-HSCT patients, who received MMF for GVHD prophylaxis, were enrolled in this study. We collected blood samples on days 14 and 28, and plasma MPA concentrations were measured by high-performance liquid chromatography; pharmacokinetic parameters such as area under the curve (AUC), mean residence time (MRT), and apparent oral clearance (CL/F) were measured with moment analysis. We also evaluated EHC as AUC6-12h/AUC0-12h. Results There was no significant difference in MPA pharmacokinetic parameters between days 14 and 28. There was also no difference between the pharmacokinetic parameter changes and diarrhea. Additionally, varying plasma MPA concentrations suggested that MPA EHC did not occur. Conclusion In this study, we revealed the pharmacokinetics of MMF in Japanese haplo-HSCT recipients. Additionally, our study demonstrated that MPA EHC might not occur in Japanese haplo-HSCT recipients.

Antithymocyte globulin (ATG) reduces severe acute and chronic graft-versus-host disease (GVHD) in allogeneic peripheral blood stem cell transplantation (PBSCT). However, risk factors for severe acute GVHD in PBSCT using ATG remain to be determined. We conducted a single-center, retrospective study to analyze the association of acute GVHD requiring systemic corticosteroid (SC-aGVHD) with absolute lymphocyte counts (ALC) before the administration of ATG or conditioning in 53 patients with HLA-matched PBSCT using low-dose thymoglobulin (2 mg/kg) after myeloablative conditioning. The cumulative incidence of SC-aGVHD was 17.0% and ALC before ATG were significantly higher in patients with SC-aGVHD compared to that in patients without it (median, 0.15 x 10(9)/L vs 0.06 x 10(9)/L, P = 0.047). The cumulative incidence of SC-aGVHD was significantly higher in patients with high ALC before ATG (>= 0.15 x 10(9)/L) than in those with low ALC (38.5% vs 10.0%, P = 0.016). Non-relapse mortality (NRM) was also significantly higher in the high ALC before ATG group than the low ALC before ATG group (2-year NRM: 23.9% vs 6.0%, P = 0.048), leading to worse survival (2-year overall survival: 69.2% vs 83.5%, P = 0.039). Our study suggested that high ALC before ATG is a risk factor for SC-aGVHD.

Repeated hospitalization for heart failure (HF) is a strong predictor of mortality among HF patients. While recent cardiac electrical implantable devices (CIEDs) can detect worsening HF through remote monitoring1,2, there is no early detection system for HF progression in patients at home without a CIED. We therefore developed an artificial intelligence-based HF detection system that uses single-lead electrocardiograms (ECGs) recorded at home. Our convolutional neural network (CNN) model calculated a novel HF-index from the estimated NYHA grades as a quantitative indicator of HF severity. Retrospective data revealed a strong correlation between HF-indexes and plasma BNP levels (R=0.91).A prospective clinical study confirmed the accuracy of the HF severity judged from the estimated HF-index using a portable single-lead ECG monitor at home.We have thus successfully constructed a novel, at-home HF monitoring system for a portable single-lead ECG device, which enables early detection and early medical intervention in HF.

Maintaining a coordinated heart rhythm is essential for maintaining the heart's pumping function and blood circulation. Every heartbeat is generated by electrical impulse propagation that is passing through gap junctions, which are composed of connexin proteins. In mammalian hearts, Cx43, Cx40, Cx45, and Cx30.2 are expressed and regulated by post-translational modification. Cardiac macrophages account for only a small number of total heart cells, but they reside all around the heart. They are primarily established prenatally, and they arise from embryonic yolk sac progenitors. Recently, increasing attention has been directed toward novel roles for cardiac resident macrophages, especially in the heart's electrical impulse conduction. Here, we provide an overview of the recent findings on connexins, with a focus on the emerging function of cardiac macrophages, and we discuss the future directions of treatment for heart disease.

We prospectively compared the efficacy of PCR detection of SARS-CoV-2 between paired nasopharyngeal and saliva samples in nine COVID-19 patients. SARS-CoV-2 was detected in saliva in 8 of 9 (89%) patients and in all 11 samples taken within 2 weeks after disease onset. Viral load was equivalent at earlier time points but declined in saliva than nasopharyngeal samples. PCR negativity was also concordant in all 27 saliva samples from 24 patients between nasopharyngeal and saliva samples. These results suggest that saliva is a reliable noninvasive alternative to nasopharyngeal swabs and facilitate widespread PCR testing in the face of shortages of swabs and protective equipment without posing a risk to healthcare workers.

Acute graft-versus-host disease (aGVHD) is 1 of the critical complications that often occurs following allogeneic hematopoietic stem cell transplantation (HSCT). Thus far, various types of prediction scores have been created using statistical calculations. The primary objective of this study was to establish and validate the machine learning–dependent index for predicting aGVHD. This was a retrospective cohort study that involved analyzing databases of adult HSCT patients in Japan. The alternating decision tree (ADTree) machine learning algorithm was applied to develop models using the training cohort (70%). The ADTree algorithm was confirmed using the hazard model on data from the validation cohort (30%). Data from 26 695 HSCT patients transplanted from allogeneic donors between 1992 and 2016 were included in this study. The cumulative incidence of aGVHD was 42.8%. Of >40 variables considered, 15 were adapted into a model for aGVHD prediction. The model was tested in the validation cohort, and the incidence of aGVHD was clearly stratified according to the categorized ADTree scores; the cumulative incidence of aGVHD was 29.0% for low risk and 58.7% for high risk (hazard ratio, 2.57). Predicting scores for aGVHD also demonstrated the link between the risk of development aGVHD and overall survival after HSCT. The machine learning algorithms produced clinically reasonable and robust risk stratification scores. The relatively high reproducibility and low impacts from the interactions among the variables indicate that the ADTree algorithm, along with the other data-mining approaches, may provide tools for establishing risk score.

HLA-haploidentical stem cell transplantation using posttransplant cyclophosphamide has spread rapidly worldwide. This strategy was initially developed in the setting of bone marrow transplantation following nonmyeloablative conditioning. Recently, peripheral blood stem cell grafts and/or myeloablative conditioning regimen have been widely used. In Japan, prospective, multicenter, phase II studies have been conducted by the Japan Study Group for Cell Therapy and Transplantation to evaluate the safety and efficacy of HLA-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haploPBSCT). In the first such study (JSCT Haplo 13 study), we demonstrated that PTCy-haploPBSCT after busulfan-based reduced-intensity conditioning (RIC) enables stable donor engraftment and low incidences of both acute and chronic graft-versus-host disease (GVHD). In the second (JSCT Haplo 14 study), we showed that both myeloablative conditioning (MAC) and RIC are valid options for PTCy-haploPBSCT. Emerging evidence, including our findings, suggests that donor type (HLA-haploidentical donor versus HLA-matched related or unrelated donor) may no longer be a significant predictor of transplant outcome.

Chronic graft-versus-host disease (GVHD) profoundly affects the quality of life of long-term survivors of allogeneic hematopoietic stem cell transplantation (SCT). The eyes are frequently involved, and dry eye syndrome is the most common manifestation of ocular chronic GVHD. We explored the role of heat shock protein 47 (HSP47) in ocular GVHD and developed a novel antifibrotic topical therapy using vitamin A–coupled liposomes containing HSP47 small interfering RNA (siRNA) against HSP47 (VA-lip HSP47). In a mouse model of chronic GVHD, infiltration of HSP47+ fibroblasts and massive fibrosis surrounding the lacrimal ducts were observed after allogeneic SCT, leading to impaired tear secretion. After ocular instillation, VA-lip HSP47 was distributed to the lacrimal glands, knocked down HSP47 expression in fibroblasts, reduced collagen deposition, and restored tear secretion after allogeneic SCT. Ocular instillation of VA-lip HSP47 also ameliorated established lacrimal gland fibrosis and dry eye syndrome. VA-lip HSP47 eye drops are a promising prophylactic and therapeutic option against dry eye syndrome in chronic GVHD.

Cardiac arrhythmias are a primary contributor to sudden cardiac death, a major unmet medical need. Because right ventricular (RV) dysfunction increases the risk for sudden cardiac death, we examined responses to RV stress in mice. Among immune cells accumulated in the RV after pressure overload-induced by pulmonary artery banding, interfering with macrophages caused sudden death from severe arrhythmias. We show that cardiac macrophages crucially maintain cardiac impulse conduction by facilitating myocardial intercellular communication through gap junctions. Amphiregulin (AREG) produced by cardiac macrophages is a key mediator that controls connexin 43 phosphorylation and translocation in cardiomyocytes. Deletion of Areg from macrophages led to disorganization of gap junctions and, in turn, lethal arrhythmias during acute stresses, including RV pressure overload and β-adrenergic receptor stimulation. These results suggest that AREG from cardiac resident macrophages is a critical regulator of cardiac impulse conduction and may be a useful therapeutic target for the prevention of sudden death., Cardiac immune cells play various roles in the maintenance of homeostasis and diseases in the heart. Here the authors show that cardiac resident macrophages are a critical regulator of cardiac impulse conduction through amphiregulin production, contributing to the prevention of sudden death.

Antithymocyte globulin (ATG) has been shown to reduce chronic graft-versus-host disease (GVHD) particularly in allogeneic peripheral blood stem cell transplantation (PBSCT) from unrelated donors; however, anti-GVHD effects of lower doses of ATG remains to be elucidated. We conducted a nationwide retrospective study to compare the outcomes of unrelated PBSCT with or without rabbit ATG (thymoglobulin) in 287 patients. A median ATG dose was 2.0 mg/kg. The primary endpoint, the cumulative incidence of moderate-severe chronic GVHD at 2 years was 22.1% in the ATG group, which was significantly less than that in the non-ATG group (36.3%, P = 0.025). The ATG group had a higher incidence of immunosuppressant discontinuation, GVHD-free, relapse-free survival, and moderate-severe chronic GVHD-free, relapse-free survival at 2 years compared to the non-ATG group. The incidences of grade III-IV aGVHD and moderate-severe chronic GVHD were significantly higher in patients with high absolute lymphocyte count (ALC) before the administration of ATG, whereas relapse rate was significantly higher in patients with low ALC before ATG. In conclusion, low-dose ATG effectively suppresses chronic GVHD in unrelated PBSCT, and ALC before ATG may be a potential predictor for GVHD and relapse.

BackgroundThe rapid detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an urgent need for the prevention and containment of disease outbreaks in communities. Although the gold standard is polymerase chain reaction (PCR), antigen tests such as immunochromatographic assay (ICA) and chemiluminescent enzyme immunoassay (CLEIA) that can yield results within 30 minutes.MethodsWe evaluated performance of ICA and CLEIA using 34 frozen PCR-positive specimens (17 saliva and 17 nasopharyngeal swab) and 307 PCR-negative samples.ResultsICA detected SARS-CoV-2 in only 14 (41%) samples, with positivity of 24% in saliva and 59% in NPS. Notably, ICA detected SARS-CoV-2 in 5 (83%) of 6 samples collected within 4 days after symptom onset. CLEIA detected SARS-CoV-2 in 31 (91%) samples, with positivity of 82% in saliva and 100% in NPS. CLEIA was negative in 3 samples with low viral load by PCR.ConclusionsThese results suggest that use of ICA should be limited to earlier time after symptom onset and CLEIA is more sensitive and can be used in situations where quick results are required.

Convolutional neural networks (CNNs) applied to electrocardiograms (ECGs) have been showing utility for detecting left ventricular (LV) dysfunction1. Although early detection of reduced LV ejection fraction (rEF) could improve handling of heart failure (HF) with rEF (HFrEF), it is not sufficient to detect HF with preserved EF (HFpEF). Here we developed a CNN algorithm to classify the severity of HF based on single-lead ECG data, irrespective of EF. We trained a CNN using ECG data and the HF classification from 7,865 patients with HF. The CNN achieved an area under the receiver-operating characteristic curve (AUC) of 0.996 for distinguishing patients with HF of various severity from healthy controls. It is anticipated that early detection of HF and therapeutic management of HF patients can be improved by employing this CNN with a single-lead ECG device.

Background Coronavirus disease 2019 (COVID-19) has rapidly evolved to become a global pandemic, largely owing to the transmission of its causative virus through asymptomatic carriers. Detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of polymerase chain reaction testing. In addition, although self-collected saliva samples have significant logistical advantages in mass screening, their utility as an alternative specimen in asymptomatic persons is yet to be determined. Methods We conducted a mass screening study to compare the utility of nucleic acid amplification, such as reverse-transcription polymerase chain reaction testing, using nasopharyngeal swab (NPS) and saliva samples from each individual in 2 cohorts of asymptomatic persons: the contact-tracing cohort and the airport quarantine cohort. Results In this mass screening study including 1924 individuals, the sensitivities of nucleic acid amplification testing with NPS and saliva specimens were 86% (90% credible interval, 77%–93%) and 92% (83%–97%), respectively, with specificities >99.9%. The true concordance probability between the NPS and saliva tests was estimated at 0.998 (90% credible interval, .996–.999) given the recent airport prevalence of 0.3%. In individuals testing positive, viral load was highly correlated between NPS and saliva specimens. Conclusion Both NPS and saliva specimens had high sensitivity and specificity. Self-collected saliva specimens are valuable for detecting SARS-CoV-2 in mass screening of asymptomatic persons.

Rapid and simple point-of-care detection of SARS-CoV-2 is an urgent need to prevent pandemic. Reverse transcription loop-mediated isothermal amplification (RT-fLAMP) can detect SARS-CoV-2 more rapidly than RT-PCR. Saliva is non-invasive specimen suitable for mass-screening, but data comparing utility of nasopharyngeal swab (NPS) and saliva in RT-FLAMP test are lacking and it remains unclear whether SARS-CoV-2 could be detected by direct processing of samples without the need for prior RNA extraction saliva. In this study, we compared utility of saliva and NPS samples for the detection of SARS-CoV-2 by a novel RT-fluorescence LAMP (RT-fLAMP). The sensitivity and specificity of the RT-fLAMP with RNA extraction were 97% and 100%, respectively, with equivalent utility of NPS and saliva. However, sensitivity was decreased to 71% and 47% in NPS and saliva samples without RNA extraction, respectively, suggesting that RNA extraction process may be critical for the virus detection by RT-fLAMP.

Background: COVID-19 has rapidly evolved to become a global pandemic due largely to the transmission of its causative virus through asymptomatic carriers. Detection of SARS-CoV-2 in asymptomatic people is an urgent priority for the prevention and containment of disease outbreaks in communities. However, few data are available in asymptomatic persons regarding the accuracy of PCR testing. Additionally, although self-collected saliva has significant logistical advantages in mass screening, its utility as an alternative specimen in asymptomatic persons is yet to be determined. Methods: We conducted a mass-screening study to compare the utility of nucleic acid amplification, such as reverse transcriptase polymerase chain reaction (RT-PCR) testing, using NPS and saliva samples from each individual in two cohorts of asymptomatic persons: the contact tracing cohort and the airport quarantine cohort. Findings: In this mass-screening study including 1,924 individuals, the sensitivity of nucleic acid amplification testing with nasopharyngeal and saliva specimens were 86% (90%CI:77-93%) and 92% (90%CI:83-97%), respectively, with specificities greater than 99.9%. The true concordance probability between the nasopharyngeal and saliva tests was estimated at 0·998 (90%CI:0·996-0·999) on the estimated airport prevalence, 0·3%. In positive individuals, viral load was highly correlated between NPS and saliva. Interpretation: Both nasopharyngeal and saliva specimens had high sensitivity and specificity. Self-collected saliva is a valuable specimen to detect SARS-CoV-2 in mass screening of asymptomatic persons. Funding: Funded by Health, Labour and Welfare Policy Research Grant 20HA2002. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was approved by the Institutional Ethics Board (Hokkaido University Hospital Division of Clinical Research Administration Number: 020-0116) and informed consent was obtained from all individuals.

Proper resolution of inflammation is vital for repair and restoration of homeostasis after tissue damage, and its dysregulation underlies various noncommunicable diseases, such as cardiovascular and metabolic diseases. Macrophages play diverse roles throughout initial inflammation, its resolution, and tissue repair. Differential metabolic reprogramming is reportedly required for induction and support of the various macrophage activation states. Here we show that a long noncoding RNA (lncRNA),lncFAO, contributes to inflammation resolution and tissue repair in mice by promoting fatty acid oxidation (FAO) in macrophages.lncFAOis induced late after lipopolysaccharide (LPS) stimulation of cultured macrophages and in Ly6Chimonocyte-derived macrophages in damaged tissue during the resolution and reparative phases. We found thatlncFAOdirectly interacts with the HADHB subunit of mitochondrial trifunctional protein and activates FAO.lncFAOdeletion impairs resolution of inflammation related to endotoxic shock and delays resolution of inflammation and tissue repair in a skin wound. These results demonstrate that by tuning mitochondrial metabolism,lncFAOacts as a node of immunometabolic control in macrophages during the resolution and repair phases of inflammation.

The dynamical property of the heart bioelectrical system is closely associated with cardiac diseases. For this reason, there is a growing interest in the development of system analysis for studying the cardiac signaling network. In this article, extracellular potentials of cardiac muscle cells were measured on an array of microelectrodes using Thin-Film-Transistor (TFT) technology, and electrophysiological data was analyzed using a spike sorting technique. This study shows the possibility of extracting useful bioelectrical information from the extracellular signals recorded by TFT arrays.

International audience; The dynamical property of the heart bioelectrical system is closely associated with cardiac diseases. There is thus a growing interest in the development of system analysis for studying the cardiac signaling network. In this article, the electrical potentials of cardiac muscle cells have been measured on an array of microelectrodes using the Thin-Film-Transistor (TFT) technology, and electrophysiological data were analyzed. This study shows the possibility of obtaining and accurately analyzing extracellular signals measured on TFT arrays.

Sinusoidal obstruction syndrome (SOS)/hepatic veno-occlusive disease (VOD) is a well-documented complication after hematopoietic stem cell transplantation (HSCT). Transabdominal ultrasonography (US) enables the visualization of blood flow abnormalities and is therefore useful for the diagnosis of SOS/VOD. We herein prospectively evaluated accuracy of a novel US diagnostic scoring system of SOS/VOD based on US findings. We carried out US in 106 patients on day 14 and when SOS/VOD was suspected after allogeneic HSCT. Among 106 patients, 10 patients (9.4%) were diagnosed as SOS/VOD by Baltimore or Seattle criteria. According to univariate analysis of 17 US findings (US-17 screening), we established a novel scoring system (HokUS-10) consisting of 10 parameters, such as gallbladder wall thickening, ascites, and blood flow signal in the paraumbilical vein. The sensitivity and specificity were 100% and 95.8%, respectively. Diagnostic performance of the HokUS-10 was significantly better than US-17 screening. In 4 of 10 patients US detection of SOS/VOD preceded to clinical diagnosis. The HokUS-10 scoring system is useful in the diagnosis of SOS/VOD; however, our results should be validated in other cohorts.