Endothelium-Derived Extracellular Vesicles Expressing Intercellular Adhesion Molecules Reflect Endothelial Permeability and Sepsis Severity.

BACKGROUND: Currently, clinical indicators for evaluating endothelial permeability in sepsis are unavailable. Endothelium-derived extracellular vesicles (EDEVs) are emerging as biomarkers of endothelial injury. Platelet endothelial cell adhesion molecule (PECAM) and vascular endothelial (VE)-cadherin are constitutively expressed endothelial intercellular adhesion molecules that regulate intercellular adhesion and permeability. Herein, we investigated the possible association between EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) and endothelial permeability and sepsis severity. METHODS: Human umbilical vein endothelial cells (HUVECs) were stimulated with tumor necrosis factor alpha (TNF-α) directly or after pretreatment with permeability-modifying reagents such as angiopoietin-1, prostacyclin, or vascular endothelial growth factor (VEGF) to alter TNF-α-induced endothelial hyperpermeability. Endothelial permeability was measured using the dextran assay or transendothelial electrical resistance. Additionally, a prospective cross-sectional observational study was conducted to analyze circulating EDEV levels in patients with sepsis. EDEVs were examined in HUVEC culture supernatants or patient plasma (nonsepsis, n = 30; sepsis, n = 30; septic shock, n = 42) using flow cytometry. The Wilcoxon rank-sum test was used for comparisons between 2 groups. Comparisons among 3 or more groups were performed using the Steel-Dwass test. Spearman's test was used for correlation analysis. Statistical significance was set at P < .05. RESULTS: TNF-α stimulation of HUVECs significantly increased EDEV release and endothelial permeability. Pretreatment with angiopoietin-1 or prostacyclin suppressed the TNF-α-induced increase in endothelial permeability and inhibited the release of PECAM+ and VE-cadherin+ EDEVs. In contrast, pretreatment with VEGF increased TNF-α-induced endothelial permeability and the release of PECAM+ and VE-cadherin+ EDEVs. However, pretreatment with permeability-modifying reagents did not affect the release of EDEVs expressing inflammatory stimulus-inducible endothelial adhesion molecules such as E-selectin, intracellular adhesion molecule-1, or vascular cell adhesion molecule-1. The number of PECAM+ EDEVs on admission in the septic-shock group (232 [124, 590]/µL) was significantly higher (P = .043) than that in the sepsis group (138 [77,267]/µL), with an average treatment effect of 98/µL (95% confidence interval [CI], 2-270/µL), and the number of VE-cadherin+ EDEVs in the septic-shock group (173 [76,339]/µL) was also significantly higher (P = .004) than that in the sepsis group (81 [42,159]/µL), with an average treatment effect (ATE) of 79/µL (95% CI, 19-171/µL); these EDEV levels remained elevated until day 5. CONCLUSIONS: EDEVs expressing intercellular adhesion molecules (PECAM+ or VE-cadherin+ EDEVs) may reflect increased endothelial permeability and could be valuable diagnostic and prognostic markers for sepsis.

Giant cell myocarditis with prolonged cardiac standstill after drug-induced hypersensitivity syndrome: a case report.

Giant cell myocarditis (GCM) is a rare but fatal disease that can lead to cardiac failure. Survival with a cardiac standstill requires mechanical circulatory support or a biventricular assist device (BiVAD) and prolonged survival is extremely rare. Drug-induced hypersensitivity syndrome (DIHS) is a severe cutaneous adverse reaction. Some cases of DIHS are reportedly associated with the onset of GCM. We present a case of a 28-year-old woman who developed GCM during steroid tapering after DIHS. She went into continuous cardiac standstill but survived for 74 days under BiVAD support. Our case is noteworthy because the histopathologic specimens obtained on three occasions contributed to the diagnosis of this particular condition over time. We also reviewed previous literature on concomitant cases of GCM and DIHS. We found that two are potentially associated and most cases of GCM occur within 3 months of DIHS during steroid tapering.

ThelR547v1-An Asymmetric Dilated Convolutional Neural Network for Real-time Semantic Segmentation of Horticultural Crops.

Robust and automated image segmentation in high-throughput image-based plant phenotyping has received considerable attention in the last decade. The possibility of this approach has not been well studied due to the time-consuming manual segmentation and lack of appropriate datasets. Segmenting images of greenhouse and open-field grown crops from the background is a challenging task linked to various factors such as complex background (presence of humans, equipment, devices, and machinery for crop management practices), environmental conditions (humidity, cloudy/sunny, fog, rain), occlusion, low-contrast and variability in crops and pose over time. This paper presents a new ubiquitous deep learning architecture ThelR547v1 (Thermal RGB 547 layers version 1) that segmented each pixel as crop or crop canopy from the background (non-crop) in real time by abstracting multi-scale contextual information with reduced memory cost. By evaluating over 37,328 augmented images (aug1: thermal RGB and RGB), our method achieves mean IoU of 0.94 and 0.87 for leaves and background and mean Bf scores of 0.93 and 0.86, respectively. ThelR547v1 has a training accuracy of 96.27%, a training loss of 0.09, a validation accuracy of 96.15%, and a validation loss of 0.10. Qualitative analysis further shows that despite the low resolution of training data, ThelR547v1 successfully distinguishes leaf/canopy pixels from complex and noisy background pixels, enabling it to be used for real-time semantic segmentation of horticultural crops.

A case of myocardial infarction caused by obstruction of a drug-eluting stent during the perioperative period.

We report a patient who developed drug-eluting stent (DES) thrombosis induced by discontinuation of dual antiplatelet therapy (DAPT) and subsequently had a massive surgical site bleed caused by restarting heparin and DAPT during the perioperative period. An 85-year-old man visited a local hospital owing to complaints dyspnea. He was diagnosed with laryngeal cancer and was scheduled for a total laryngectomy. Preoperative examinations showed an anteroseptal myocardial infarction. A DES was placed at segment 6 of the coronary artery and DAPT was initiated 27 days before surgery. After admission to our hospital, DAPT was replaced with unfractionated heparin. On the operation day, heparin was discontinued, and a tracheotomy, total laryngectomy and right hemi-thyroidectomy were performed. While recovering from anesthesia, ischemic ST elevation appeared. Cardiac catheterization revealed complete obstruction of the DES by a white thrombus. After recanalization, heparin and DAPT were restarted, and bleeding occurred. The next day, total blood loss was 2755 mL and surgical hemostasis was performed. Because his serum creatine kinase value was elevated at the cessation of heparin, anticoagulation by unfractionated heparin could not have prevented platelet thrombosis. Therefore, we should performed the tracheostomy to secure the patient's airway under DAPT or only aspirin therapy a month after the DES implantation, and performed the laryngectomy and right hemi-thyroidectomy five months after the first surgery. This case is serious warnings of perioperative major adverse cardiac events induced by discontinuation of DAPT; unfractionated heparin was an insufficient safeguard against platelet thrombosis, and perioperative massive bleeding induced by restarting antiplatelet and anticoagulation therapy. In addition, a series of human errors, which the cardiologist chosen DES regardless of scheduled total larygectomy, the discontinuation of antiplatelet therapy shortly after a DES placement, and the surgical staffs failed to share the elevated serum CK and CK-MB values, caused life-threatening complications.