Skeletal Muscle Mass Assessment in Pediatric Patients: Development of a Normative Equation and Assessment of Factors Associated With a Low Skeletal Muscle Mass in PICU Patients.

OBJECTIVES: To develop an equation for defining a low skeletal muscle mass (SMM) in children and to investigate risk factors and outcomes associated with low SMM in critically ill pediatric patients. DESIGN: Single-center retrospective pediatric cohorts, 2011-2018. SETTING: Tertiary Emergency and Critical Care Center of Kyushu University Hospital in Japan. PATIENTS: We studied two cohorts of pediatric patients 1-15 years old who underwent abdominal CT at the level of the third lumbar vertebra (L3). First a cohort of trauma patients presented to the emergency department in whom we developed an SMM regression equation. Second, a cohort of patients who had undergone abdominal CT within 3 days of PICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The equation for estimating normal SMM used sex, age, and weight. Low SMM was defined as less than 80% of normal. In the 112 patients in the PICU cohort, median (range) age was 68 (13-191) months, and 83 (74.1%) had underlying disease. There was low SMM in 54 patients (48.2%). Regarding associations, using odds ratio (OR) and 95% CI, we found that low dietary intake (OR 4.33 [95% CI, 1.37-13.70]; p = 0.013) and the presence of underlying disease (OR 7.44 [95% CI, 2.10-26.30]; p = 0.002) were independently associated with greater odds of low SMM. Low SMM, compared with normal SMM, was also associated with longer hospital stays (42.5 d vs. 20.5 d; p = 0.007; ß, 1.59; 95% CI, 1.09-2.33; p = 0.016). CONCLUSIONS: In this retrospective PICU cohort from a single center in Japan, we found that low SMM at PICU admission was present in almost half the cases. Low SMM, as defined by being less than 80% of the normal, was associated with greater odds of low dietary intake and underlying chronic disease. Furthermore, low SMM was associated with longer hospital stays.

Emphysematous pyelonephritis with ST elevation accompanied by reciprocal changes mimicking acute coronary syndrome.

Patients with infectious diseases including sepsis can develop ST segment changes on an electrocardiogram (ECG) in the absence of coronary artery disease. However, ST elevation with "reciprocal ST segment depression (RSTD)", which is recognized as a specific finding for ST-elevated myocardial infarction, is rare in such patients. Although a small number of cases have reported ST-segment elevation in gastritis, cholecystitis, and sepsis, regardless of coronary artery disease, none presented with reciprocal changes. Here, we describe a rare case of a patient with emphysematous pyelonephritis complicating septic shock who developed ST elevation accompanied by reciprocal changes with no coronary occlusion. Emergency physicians should consider the possibility of acute coronary syndrome mimicking, and choose non-invasive diagnostic procedures when investigating the causes of ECG abnormalities associated with critically ill patients.

2.5-mm articulated endoluminal forceps using a compliant mechanism.

PURPOSE: Gastrointestinal cancer can be treated using a flexible endoscope through a natural orifice. However, treatment instruments with limited degrees of freedom (DOFs) require a highly skilled operator. Articulated devices useful for endoluminal procedures, such as endoscopic submucosal dissection and biopsy, have been developed. These devices enable dexterous operation in a narrow lumen; however, they suffer from limitations such as large size and high cost. To overcome these limitations, we developed a 2.5-mm articulated forceps that can be inserted into a standard endoscope channel based on a compliant mechanism. METHODS: The compliant mechanism allows the device to be compact and affordable, which is possible due to its monolithic structure. The proposed mechanism consists of two segments, 1-DOF grasping and 2-DOF bending, that are actuated by tendon-sheath mechanisms. A prototype was designed based on finite element analysis results. RESULTS: To confirm the effectiveness of the proposed mechanism, we fabricated the prototype using a 3D printer. A series of mechanical performance tests on the prototype revealed that it achieved the following specifications: (1) DOF: 1-DOF grasping + 2-DOF bending, (2) outer diameter: 2.5 mm, (3) length of the bending segment: 30 mm, and (4) range of motion: [Formula: see text] to [Formula: see text] (grasping) and [Formula: see text] to [Formula: see text] (bending). Finally, we performed a tissue manipulation test on an excised porcine colon and found that a piece of mucous membrane tissue was successfully resected using an electric knife while being lifted with the developed forceps. CONCLUSION: The results of the evaluation experiment demonstrated a positive feasibility of the proposed mechanism, which has a simpler structure compared to those of other conventional mechanisms; furthermore, it is potentially more cost-effective and is disposable. The mechanical design, prototype implementation, and evaluations are reported in this paper.

Impact of Antithrombin Activity Levels Following Recombinant Antithrombin Gamma Therapy in Patients with Sepsis-Induced Disseminated Intravascular Coagulation.

Recombinant antithrombin gamma (rAT) is reported as an effective drug for patients with disseminated intravascular coagulation (DIC) in Japan. As the appropriate dose and targeted AT activity remain unknown, this study aimed to determine these aspects for sepsis-induced DIC. Thirty-one patients with septic shock and DIC with AT levels <70% were treated with rAT between May 2018 and December 2020. The recovery rates from DIC were 32.2% and 63.3% on day 3 and 5 post administration, respectively. Recovery and survival rates were significantly higher in patients who achieved AT activity ≥70% or 80% on day 3 post administration. Receiver operating characteristic curve analysis revealed that the cutoff values of post-treatment AT activity on day 3 for 28-day survival and 5-day recovery from DIC were 79.5% and 81.5%, respectively. Patients who did not achieve AT activity ≥80% on day 3 presented a lower base level of AT activity and lower dose supplementation. Our results suggest that targeted AT activity should be at least 70%, and ideally 80%, and sufficient doses to maintain this activity are required to achieve better outcomes.

Prediction of intracranial lesions in patients with consciousness disturbance by ultrasonography in the intensive care unit.

OBJECTIVE: This study was performed to evaluate the correlation between parameters measured by bedside ultrasonography and detection of intracranial organic lesions in patients with impaired consciousness in an intensive care unit (ICU) setting. METHODS: We retrospectively reviewed the medical records of patients who were admitted to our ICU from April 2017 to July 2019. Patients who underwent computed tomography or magnetic resonance imaging examination and measurement of the flow velocity of the carotid and intracranial arteries and the optic nerve sheath diameter by ultrasonography were selected for analysis. RESULTS: In total, 64 patients were analyzed in this study. Of these, intracranial lesions were detected by computed tomography or magnetic resonance imaging in 17 (27%) patients. The left:right ratio of the end-diastolic velocity of the bilateral common carotid artery (CCA-ED ratio) and the pulsatility index of the middle cerebral artery (MCA-PI) were significantly higher in patients with than in those without intracranial lesions. The cut-off value of the CCA-ED ratio was 1.55 (sensitivity, 66.7%; specificity, 81.6%), and that of the MCA-PI was 1.21 (sensitivity, 57.1%; specificity, 76.7%). CONCLUSION: Bedside ultrasonography is useful for predicting intracranial lesions requiring therapeutic intervention in ICU patients with impaired consciousness.

Noninvasive Diagnosis of the Mitochondrial Function of Doxorubicin-Induced Cardiomyopathy Using In Vivo Dynamic Nuclear Polarization-Magnetic Resonance Imaging.

Doxorubicin (DOX) induces dose-dependent cardiotoxicity via oxidative stress and abnormal mitochondrial function in the myocardium. Therefore, a noninvasive in vivo imaging procedure for monitoring the redox status of the heart may aid in monitoring diseases and developing treatments. However, an appropriate technique has yet to be developed. In this study, we demonstrate a technique for detecting and visualizing the redox status of the heart using in vivo dynamic nuclear polarization-magnetic resonance imaging (DNP-MRI) with 3-carbamoyl-PROXYL (CmP) as a molecular imaging probe. Male C57BL/6N mice were administered DOX (20 mg/kg) or saline. DNP-MRI clearly showed a slower DNP signal reduction in the DOX group than in the control group. Importantly, the difference in the DNP signal reduction rate between the two groups occurred earlier than that detected by physiological examination or clinical symptoms. In an in vitro experiment, KCN (an inhibitor of complex IV in the mitochondrial electron transport chain) and DOX inhibited the electron paramagnetic resonance change in H9c2 cardiomyocytes, suggesting that the redox metabolism of CmP in the myocardium is mitochondrion-dependent. Therefore, this molecular imaging technique has the potential to monitor the dynamics of redox metabolic changes in DOX-induced cardiomyopathy and facilitate an early diagnosis of this condition.

Radiation Emergency Medical Preparedness in Japan: A Survey of Nuclear Emergency Core Hospitals.

OBJECTIVE: Based on experiences following the Great East Japan Earthquake and nuclear power plant accident in 2011, Nuclear Emergency Core Hospitals (NECHs) were designated as centers for radiation disaster management in Japan. This study aimed to investigate their current status and identify areas for improvement. METHODS: This cross-sectional study was conducted in October 2018. Demographic data were collected by a questionnaire with free text responses about attitudes toward NECHs. Considerations regarding risk communications during a radiation disaster were analyzed using qualitative text mining analysis. RESULTS: A total of 36 hospitals participated in this study. Only 31% of NECHs anticipated a radiation disaster. The importance of business continuity plans and risk communications was shown. Text analysis identified 7 important categories for health care workers during a radiation disaster, including media response, communications to hospital staff, risk communications, radiation effects on children, planning for a radiation disaster in the region, rumors, and the role in the region. CONCLUSION: The radiation disaster medical system and NECHs in Japan were surveyed. The importance of risk communications, planning for a radiation disaster in each region, and the role in the region are identified as issues that need to be addressed.

In Vivo Dynamic Nuclear Polarization Magnetic Resonance Imaging for the Evaluation of Redox-Related Diseases and Theranostics.

Significance:In vivo molecular and metabolic imaging is an emerging field in biomedical research that aims to perform noninvasive detection of tissue metabolism in disease states and responses to therapeutic agents. The imbalance in tissue oxidation/reduction (Redox) states is related to the onset and progression of several diseases. Tissue redox metabolism provides biomarkers for early diagnosis and drug treatments. Thus, noninvasive imaging of redox metabolism could be a useful, novel diagnostic tool for diagnosis of redox-related disease and drug discovery. Recent Advances:In vivo dynamic nuclear polarization magnetic resonance imaging (DNP-MRI) is a technique that enables the imaging of free radicals in living animals. DNP enhances the MRI signal by irradiating the target tissue or solution with the free radical molecule's electron paramagnetic resonance frequency before executing pulse sequence of the MRI. In vivo DNP-MRI with redox-sensitive nitroxyl radicals as the DNP redox contrast agent enables the imaging of the redox metabolism on various diseases. Moreover, nitroxyl radicals show antioxidant effects that suppress oxidative stress. Critical Issues: To date, considerable progress has been documented preclinically in the development of animal imaging systems. Here, we review redox imaging of in vivo DNP-MRI with a focus on the recent progress of this system and its uses in patients with redox-related diseases. Future Directions: This technique could have broad applications in the study of other redox-related diseases, such as cancer, inflammation, and neurological disorders, and facilitate the evaluation of treatment response as a theranostic tool. Antioxid. Redox Signal. 36, 172-184.

Reflectance spectra analysis for mucous assessment.

This review report represents an overview of research and development on medical hyperspectral imaging technology and its applications. Spectral imaging technology is attracting attention as a new imaging modality for medical applications, especially in disease diagnosis and image-guided surgery. Considering the recent advances in imaging, this technology provides an opportunity for two-dimensional mapping of oxygen saturation (SatO2) of blood with high accuracy, spatial spectral imaging, and its analysis and provides detection and diagnostic information about the tissue physiology and morphology. Multispectral imaging also provides information about tissue oxygenation, perfusion, and potential function during surgery. Analytical algorithm has been examined, and indication of accurate map of relative hemoglobin concentration and SatO2 can be indicated with preferable resolution and frame rate. This technology is expected to provide promising biomedical information in practical use. Several studies suggested that blood flow and SatO2 are associated with gastrointestinal disorders, particularly malignant tumor conditions. The use and analysis of spectroscopic images are expected to potentially play a role in the detection and diagnosis of these diseases.

Efficacy of thromboelastography in the management of anticoagulation for veno-venous extracorporeal membrane oxygenation in a coronavirus disease 2019 patient: A case report.

RATIONALE: In coronavirus disease 2019 (COVID-19) patients with acute respiratory distress syndrome refractory to optimal conventional management, we should consider the indication for veno-venous extracorporeal membrane oxygenation (V-V ECMO). Growing evidence indicates that COVID-19 frequently causes coagulopathy, presenting as hypercoagulation and incidental thrombosis. For these reasons, a multifactorial approach with several anticoagulant markers should be considered in the management of anticoagulation using heparin in COVID-19 patients on V-V ECMO. PATIENT CONCERNS: A 48-year-old man was infected with COVID-19 with a worsening condition manifesting as acute respiratory distress syndrome. DIAGNOSES: He was refractory to conventional therapy, thus we decided to introduce V-V ECMO. We used heparin as an anticoagulant therapy for V-V ECMO and adjusted the doses of heparin by careful monitoring of the activated clotting time (ACT) and activated partial thromboplastin time (APTT) to avoid both hemorrhagic and thrombotic complications. We controlled the doses of heparin in the therapeutic ranges of ACT and APTT, but clinical hemorrhaging and profound elevation of coagulant marker became apparent. INTERVENTIONS: Using thromboelastography (TEG; Haemonetics) in addition to ACT and APTT, we were able to clearly detect not only sufficient coagulability of COVID19 on V-V ECMO (citrated rapid thromboelastography-R 0.5 min, angle 75.5°, MA 64.0 mm, citrated functional fibrinogen-MA 20.7 mm) but also an excessive effect of heparin (citrated kaolin -R 42.7 min, citrated kaolin with heparinase 11.7 min). OUTCOMES: Given the TEG findings indicating an excessive heparin effect, the early withdrawal of ECMO was considered. After an evaluation of the patient's respiratory capacity, withdrawal from V-V ECMO was achieved and then anticoagulation was stopped. The hemorrhagic complications and elevated thrombotic marker levels dramatically decreased. LESSONS: TEG monitoring might be a useful option for managing anticoagulation in COVID-19 patients on V-V ECMO frequently showing a hypercoagulative state and requiring massive doses of heparin, to reduce both hemorrhagic and thrombotic complications.

Development of 20 cm sample bore size dynamic nuclear polarization (DNP)-MRI at 16 mT and redox metabolic imaging of acute hepatitis rat model.

Tissue redox metabolism is involved in various diseases, and an understanding of the spatio-temporal dynamics of tissue redox metabolism could be useful for diagnosis of progression and treatment. In in vivo dynamic nuclear polarization (DNP)-MRI, electron paramagnetic resonance (EPR) irradiation at the resonance frequency of nitroxyl radicals administered as a redox probe for induction of DNP, increases the intensity of MRI signals. For electron spin, it is necessary to apply a resonant frequency 658 times higher than that required for nuclear spin because of the higher magnetic moment of unpaired electrons. Previous studies using a disease model of small animals and in vivo DNP-MRI have revealed that an abnormal redox status is involved in many diseases, and that it could be used to visualize the dynamics of alterations in redox metabolism. To use the current methods in clinical practice, the development of a prototype DNP-MRI system for preclinical examinations of large animals is indispensable for clarifying the problems peculiar to the increase in size of the DNP-MRI device. Therefore, we developed a in vivo DNP-MRI system with a sample bore size of 20 cm and a 16-mT magnetic field using a U-shaped permanent magnet. Because the NMR frequency is very low, we adopted a digital radiofrequency transmission/reception system with excellent filter and dynamic range characteristics and equipped with a digital eddy current compensation system to suppress large eddy currents. The pulse sequence was based on the fast spin-echo sequence, which was improved for low frequency and large-eddy current equipment. The in vivo DNP-MRI system developed was used to non-invasively image the redox reaction of a carbamoyl-PROXYL probe in the livers of large rats weighing 800 g. Furthermore, DNP-MRI analysis was able to capture significant changes in redox metabolism in hepatitis-model rats.

Wireless Light-emitting Marker Using Magnetic Field Resonance for Laparoscopic Gastrointestinal Surgery.

BACKGROUND: In laparoscopic gastrointestinal surgery, the location of the tumor is identified mainly with marking methods, such as ink tattooing and intraoperative gastrointestinal endoscopy and marking with a metal clip followed by confirmation with intraoperative x-ray fluoroscopy. Each method has disadvantages, such as complexity, instability of ink sticks, and radiation exposure. Thus, a simple and less-invasive marking method is needed. METHODS: We developed a wireless light-emitting marker with a miniature light-emitting diode that uses a magnetic field resonance mechanism. It emits 4 individual colors-red, blue, green, and white. We confirmed the usefulness of this marker system in ex vivo and in vivo animal experiments. RESULTS: In the ex vivo experiment in porcine intestines, use of the wireless marker was successful, as each color of emitted light was recognized from outside the intestine. In the live animal experiment, it was confirmed that the light emitted by the marker system was visible in the porcine intestinal tract during laparoscopic surgery. The light emitted by the wireless marker in the intestinal tract was confirmed with a laparoscope in a simulated animal surgery. CONCLUSION: We have developed an innovative, radiation-free and reliable light-emitting marker system that uses a magnetic field resonance mechanism that emits four colors of light during laparoscopic surgery.

Use of venovenous extracorporeal membrane oxygenation for perioperative management of acute respiratory distress syndrome caused by fat embolism syndrome: A case report and literature review.

INTRODUCTION: Fat embolism syndrome (FES) is a known complication of long bone fracture and can affect multiple organs. The organ most commonly affected with FES is the lung. Severe cases of FES from long bone fracture can cause acute respiratory distress syndrome (ARDS). Although the treatment of ARDS remains challenging, it is reported that a lung protection strategy and prone positioning are effective. In addition, early fixation is reported to be beneficial in respiratory failure due to FES, though it may exacerbate respiratory failure during the perioperative period. We report the use of venovenous extracorporeal membrane oxygenation (VV-ECMO) for the successful perioperative management of a patient diagnosed with ARDS due to FES. PATIENT CONCERNS: A 24-year-old man injured in a traffic accident was brought to our emergency department due to shock and consciousness disorder. DIAGNOSIS: After examining the patient, we noted bilateral pneumothorax, liver and spleen injuries, and multiple long bone fractures. Four days after admission, he was diagnosed with FES due to a prolonged consciousness disorder, progressive hypoxia with diffuse lung damage, and cutaneous and mucosal petechiae. INTERVENTION: As respiratory failure progressed, VV-ECMO was initiated on the 6th day. To improve the respiratory failure caused by ARDS, prone position therapy was necessary. Thus, we performed osteosynthesis on the 9th day under ECMO. Prone position therapy was started after surgery. OUTCOMES: Subsequently, his respiratory condition and chest radiographs improved steadily. VV-ECMO was discontinued on the 17th day and the ventilator was removed on the 28th day. His consciousness levels improved without residual central nervous system complications. CONCLUSION: Our study reveals the successful improvement of FES-induced ARDS by osteosynthesis and prone positioning under VV-ECMO. This strategy prioritizes supportive treatment over pharmacologic interventions.

Histidine-Rich Glycoprotein Alleviates Liver Ischemia/Reperfusion Injury in Mice With Nonalcoholic Steatohepatitis.

Hepatic ischemia/reperfusion injury (IRI) is a major complication of liver surgery and transplantation, especially in patients with nonalcoholic steatohepatitis (NASH). The mechanism of NASH susceptibility to IRI has not been fully clarified. We investigated the role of liver-produced histidine-rich glycoprotein (HRG) in NASH IRI. A NASH mouse model was established using C57BL/6J mice fed a methionine-choline-deficient diet (MCDD) for 6 weeks. The MCDD and standard diet groups were exposed to 60 minutes of partial hepatic ischemia/reperfusion (I/R). We further evaluated the impact of HRG in this context using HRG knockdown (KD) mice. IRI increased HRG expression in the standard diet group, but not in the MCDD group after I/R. HRG expression was inversely correlated with neutrophil infiltration and the formation of neutrophil extracellular traps (NETs). HRG KD mice showed severe liver injury with neutrophil infiltration and the formation of NETs. Pretreatment with supplementary HRG protected against I/R with the inhibition of neutrophil infiltration and the formation of NETs. In vitro, hepatocytes showed that the expression of HRG was upregulated under hypoxia/reoxygenation conditions, but not in response to oleic acid-treated hepatocytes. The decrease in HRG expression in fatty hepatocytes was accompanied by decreased farnesoid X receptor and hypoxia inducible factor 2 alpha subunit expression. HRG is a hepatoprotective factor during hepatic IRI because it decreases neutrophil infiltration and the formation of NETs. The decrease in HRG is a cause of susceptibility to IRI in steatotic livers. Therefore, HRG is a new therapeutic target for minimizing liver damage in patients with NASH.

Free radical imaging of endogenous redox molecules using dynamic nuclear polarization magnetic resonance imaging.

Redox reactions accompanied by the oxidation-reduction of endogenous molecules play important roles in maintaining homeostasis in living organisms. In humans, numerous endogenous molecules that contribute toward maintaining physiological conditions form free radicals via electron transfer. A typical example of this is the mitochondrial electron transport chain, which is involved in energy production. If free radicals derived from endogenous molecules could be visualized and exploited as biological and functional probes, redox reactions mediated by endogenous molecules could be detected non-invasively. We succeeded in visualizing the free radicals derived from endogenous molecules using an in vivo dynamic nuclear polarization (DNP) magnetic resonance imaging (MRI) system. In this review, we describe the visualization of endogenous redox molecules, such as flavins and ubiquinones, which are mitochondrial electron carriers, as well as vitamin E and vitamin C (ascorbate). In addition, we describe the application of melanin free radicals for the in vivo visualization of metabola without using probes via in vivo DNP-MRI.

Prognostic factors for the short-term mortality of patients with rheumatoid arthritis admitted to intensive care units.

BACKGROUND: Patients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs). METHODS: This was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU. RESULTS: Upon admission, the median age was 70 (range, 33-96) years, and RA duration was 10 (range, 0-61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson's comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission. CONCLUSION: Our study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.

Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells.

BACKGROUND: Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. METHODS: Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection. RESULTS: The administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs. CONCLUSION: ADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.

Development of a novel molecular probe for the detection of liver mitochondrial redox metabolism.

Redox status influences the course of the inflammatory, metabolic, and proliferative liver diseases. Oxidative stress is thought to play a crucial and sustained role in the pathological progression of early steatosis to severe hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Oxidative stress induced by reactive oxygen species which are generated in the mitochondria can lead to chronic organelle damage in hepatocytes. Currently, the diagnosis of liver disease requires liver biopsy, which is invasive and associated with complications. The present report describes the development of a novel molecular probe, EDA-PROXYL, with higher reactivity and mitochondrial selectivity than standard carboxyl-PROXYL and carbamoyl-PROXYL probes. The membrane permeability of our probe improved in aqueous environments which led to increased accumulation in the liver and interaction of EDA-PROXYL with the carnitine transporter via the amine (NH3+) group further increased accumulation. This increased mitochondrial sensitivity and enhanced accumulation highlight the potential of EDA-PROXYL as a molecular probe for determining metabolic reactions of the mitochondria. Thus, this novel probe could be a tool for the evaluation of redox status of the mitochondria to assess the degree of liver injury and, ultimately, the response to pharmacological therapy.

Clinical improvement in a patient with severe coronavirus disease 2019 after administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate.

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.