Label-free optical metabolic imaging of adipose tissues for prediabetes diagnosis.

Rationale: Prediabetes can be reversed through lifestyle intervention, but its main pathologic hallmark, insulin resistance (IR), cannot be detected as conveniently as blood glucose testing. In consequence, the diagnosis of prediabetes is often delayed until patients have hyperglycemia. Therefore, developing a less invasive diagnostic method for rapid IR evaluation will contribute to the prognosis of prediabetes. Adipose tissue is an endocrine organ that plays a crucial role in the development and progression of prediabetes. Label-free visualizing the prediabetic microenvironment of adipose tissues provides a less invasive alternative for the characterization of IR and inflammatory pathology. Methods: Here, we successfully identified the differentiable features of prediabetic adipose tissues by employing the metabolic imaging of three endogenous fluorophores NAD(P)H, FAD, and lipofuscin-like pigments. Results: We discovered that 1040-nm excited lipofuscin-like autofluorescence could mark the location of macrophages. This unique feature helps separate the metabolic fluorescence signals of macrophages from those of adipocytes. In prediabetes fat tissues with IR, we found only adipocytes exhibited a low redox ratio of metabolic fluorescence and high free NAD(P)H fraction a1. This differential signature disappears for mice who quit the high-fat diet or high-fat-high-sucrose diet and recover from IR. When mice have diabetic hyperglycemia and inflamed fat tissues, both adipocytes and macrophages possess this kind of metabolic change. As confirmed with RNA-seq analysis and histopathology evidence, the change in adipocyte's metabolic fluorescence could be an indicator or risk factor of prediabetic IR. Conclusion: Our study provides an innovative approach to diagnosing prediabetes, which sheds light on the strategy for diabetes prevention.

Plasma riboflavin fluorescence as a diagnostic marker of mesenteric ischemia-reperfusion injury in rats.

Due to the delayed and vague symptoms, it is difficult to early diagnose mesenteric ischemia injuries in the dynamics of acute illness, leading to a 60-80 % mortality rate. Here, we found plasma fluorescence spectra can rapidly assess the severity of mesenteric ischemia injury in animal models. Ischemia-reperfusion damage of the intestine leads to multiple times increase in NADH, flavins, and porphyrin auto-fluorescence of blood. The fluorescence intensity ratio between blue-fluorophores and flavins can reflect the occurrence of shock. Using liquid chromatography and mass spectroscopy, we confirm that riboflavin is primarily responsible for the increased flavin fluorescence. Since humans absorb riboflavin from the intestine, its increase in plasma may indicate intestinal mucosa injury. Our work suggests a self-calibrated and reagent-free approach to identifying the emergence of fatal mesenteric ischemia in emergency departments or intensive care units.

Noninvasive assessment of liver function reserve with fluorescent dosimetry of indocyanine green.

Using in vivo multiphoton fluorescent dosimetry, we demonstrate that the clearance dynamics of Indocyanine Green (ICG) in the blood can quickly reveal liver function reserve. In normal rats, the ICG retention rate was below 10% at the 15-minute post-administration; While in the rat with severe hepatocellular carcinoma (HCC), the 15-minute retention rate is over 40% due to poor liver metabolism. With a 785 nm CW laser, the fluorescence dosimeter can evaluate the liver function reserve at a 1/10 clinical dosage of ICG without any blood sampling. In the future, this low-dosage ICG 15-minute retention dosimetry can be applied for the preoperative assessment of hepatectomy or timely perioperative examination.

Feasibility and Safety of Using Supraglottic Airway Devices for Pediatric Patients Undergoing Magnetic Resonance Imaging: A Case Series of High-Risk Patients.

BACKGROUND: General anesthesia or sedation is commonly required for pediatric patients undergoing magnetic resonance imaging (MRI) scans, and airway management during the procedure is the highest concern for anesthesiologists owing to the limited access to the patient in the MRI unit. The use of supraglottic airway devices (SADs) has recently become more popular than endotracheal tubes; however, the feasibility of using SADs for children in MRI suites was reported only in a few studies that involved healthy patients. METHODS: We present a successful case series of 30 pediatric patients, and the majority are high-risk patients, including patients with aromatic L-amino acid decarboxylase (AADC) deficiency, mitochondrial disease, and tuberous sclerosis, using either i-gel or laryngeal masks for airway maintenance during MRI examination. RESULTS: A total of 38 MRI exams were conducted; the patients' median age was 4 (range 1.6-17.0 years), and the mean examination time was 50.87 minutes. No patient experienced oxygen desaturation, and only 1 patient with AADC deficiency had an episode of hypotension. The MRI scans were completed without interruption with an adequate image quality according to a specialized radiologist. CONCLUSION: From the clinical point of view, this case series demonstrated a broader application of SADs for airway maintenance during MRI scans for pediatric patients with a high risk during anesthesia rather than only for a healthy patient population.

Effects of high-flow nasal oxygen during prolonged deep sedation on postprocedural atelectasis: A randomised controlled trial.

BACKGROUND: Atelectasis is common in patients undergoing prolonged deep sedation outside the operating theatre. High-flow nasal oxygen (HFNO) produces positive airway pressure which, hypothetically, should improve lung atelectasis, but this has not been investigated. OBJECTIVE: We investigated whether HFNO ameliorates postprocedural atelectasis and compared the influences of HFNO and facial oxygen by mask on postprocedural outcomes. DESIGN: A single-blind, open-label single-institution randomised controlled trial. SETTING: A single university hospital, from February 2017 to July 2019. PATIENTS: A total of 59 patients undergoing computed tomography (CT)-guided hepatic tumour radiofrequency ablation were randomly allocated to two groups. INTERVENTION: These patients randomly received HFNO (oxygen flow 10 l min before sedation and 50 l min during the procedure) or a conventional oxygen face mask (oxygen flow 10 l min) during the procedure. MAIN OUTCOME MEASURES: Changes in the area of lung atelectasis calculated on the basis of chest CT images and also recovery profiles were compared between the two groups. RESULTS: The two groups had comparable procedural profiles, but the HFNO group exhibited less postprocedural atelectasis than the face mask group (median [IQR] 7.4 [3.9 to 11.4%] vs. 10.5 [7.2 to 14.6%]; P = 0.0313). However, the numbers of patients requiring oxygen supplementation in the recovery room and during transport from the recovery room to the ward did not differ significantly between groups (24.1 vs. 50.0%; P = 0.0596). CONCLUSION: Our results suggested that HFNO ameliorates lung atelectasis after prolonged deep sedation in patients receiving CT-guided hepatic tumour radiofrequency ablation. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03019354.

Role of neutrophil extracellular traps following injury.

Neutrophil extracellular traps (NETs), which consist of neutrophil DNA and cytoplasmic proteins, have been shown to be involved in various infectious, inflammatory, and autoimmune diseases. Neutrophil extracellular traps are abundant at the site of infection and acute inflammation. Neutrophil extracellular trap formation can occur through various intracellular signaling pathways, including peptidylarginine deiminase 4, Raf-MEK-ERK, nitric oxide, Toll-like receptor 4, high mobility group box 1, pentraxin 3, and mammalian targets of rapamycin. A growing body of evidence indicates that NETs may play an important role in injury, and decreases in NETs could reduce tissue injury. Neutrophil extracellular traps are believed to modulate the inflammatory and immune responses of individuals after injury. In this review, the role of NETs in injury, including traumatic injury, ischemia-reperfusion-induced injury, and sepsis, as well as the potential markers and therapeutic targets of NET-related injury will be discussed.

Albumin acts like transforming growth factor ß1 in microbubble-based drug delivery.

Unlike lipid-shelled microbubbles (MBs), albumin-shelled microbubbles (MBs) have not been reported to be actively targeted to cells without the assistance of antibodies. Recent studies indicate that the albumin molecule is similar to transforming growth factor ß (TGF-ß) both structurally and functionally. The TGF-ß superfamily is important during early tumor outgrowth, with an elevated TGF-ß being tumor suppressive; at later stages, this switches to malignant conversion and progression, including breast cancer. TGF-ß receptors I and II play crucial roles in both the binding and endocytosis of albumin. However, until now, no specific albumin receptor has been found. On the basis of the above-mentioned information, we hypothesized that non-antibody-conjugated albumin-shelled MBs can be used to deliver drugs to breast cancer cells. We also studied the possible roles of TGF-ß1 and radiation force in the behavior of cells and albumin-shelled MBs. The results indicate that albumin-shelled MBs loaded with paclitaxel (PTX) induce breast cancer cell apoptosis without the specific targeting produced by an antibody. Applying either an acoustic radiation force or cavitation alone to cells with PTX-loaded albumin MBs increased the apoptosis rate to 23.2% and 26.3% (p < 0.05), respectively. We also found that albumin-shelled MBs can enter MDA-MB-231 breast cancer cells and remain there for at least 24 h, even in the presence of PTX loading. Confocal micrographs revealed that 70.5% of the breast cancer cells took up albumin-shelled MBs spontaneously after 1 d of incubation. Applying an acoustic radiation force further increased the percentage to 91.9% in our experiments. However, this process could be blocked by TGF-ß1, even with subsequent exposure to the radiation force. From these results, we conclude that TGF-ß1 receptors are involved in the endocytotic process by which albumin-shelled MBs enter breast cancer cells. The acoustic radiation force increases the contact rate between albumin-shelled MBs and tumor cells. Combining a radiation force and cavitation yields an apoptosis rate of 31.3%. This in vitro study found that non-antibody-conjugated albumin-shelled MBs provide a useful method of drug delivery. Further in vivo studies of the roles of albumin MBs and TGF-ß in different stages of cancer are necessary.

Combining radiation force with cavitation for enhanced sonothrombolysis.

The use of acoustic radiation force has been suggested for enhancing the delivery of therapeutic substances, whereas sonothrombolysis has been developed for years as treatment by itself, or in combination with thrombolytic agents or ultrasound contrast agents. We have examined the efficacy of using acoustic radiation force to enhance the targeting of microbubbles in cavitation-induced sonothrombolysis in a flow phantom system. A clot was targeted by microbubbles using avidin-biotin binding, and the process was observed using a confocal microscope. We found that the experimental group in which radiation force was combined with cavitation showed an additional 3% to 9% weight reduction of the thrombus relative to the cavitation group. We also found that the fluorescence intensity of the clot increased with the microbubble concentration at each acoustic setting. Microbubbles traveled 10 to 20 µm further than the control group after being exposed to radiation force, cavitation, or both. These observations confirm that radiation force helps microbubbles to distribute into a clot (as does cavitation). Therefore, combining radiation force with cavitation would provide additional thrombolysis effects (based on clot weight measurements) relative to cavitation alone. A local delivery method based on acoustic radiation force has the potential to improve the safety and efficacy of sonothrombolysis.

Effects of ultrasound-induced inertial cavitation on enzymatic thrombolysis.

Cavitation induced by ultrasound enhances enzymatic fibrinolysis by increasing the transport of reactants. However, the effects of cavitation need to be fully understood before sonothrombolysis can be applied clinically. In order to understand the underlying mechanisms, we examined the effects of combining ultrasound, microbubbles and thrombolytic enzymes on thrombolysis. First, we evaluated the relations between inertial cavitation and the reduction in the weight of a blood clot. Inertial cavitation was varied by changing the amplitude and duration of the transmitted acoustic wave as well as the concentration of microbubbles used to induce cavitation. Second, we studied the combined effects of streptokinase and inertial cavitation on thrombolysis. The results show that inertial cavitation increases the weight reduction of a blood clot by up to 33.9%. With linear regression fitting, the measured differential inertial cavitation dose and the weight reduction had a correlation coefficient of 0.66. Microscopically, enzymatic thrombolysis effects manifest as multiple large cavities within the clot that are uniformly distributed on the side exposed to ultrasound. This suggests that inertial cavitation plays an important role in producing cavities, while microjetting of the microbubbles induces pits on the clot surface. These observations preliminarily demonstrate the clinical potential of sonothrombolysis. The use of the differential inertial cavitation dose as an indicator of blood clot weight loss for controlled sonothrombolysis is also possible and will be further explored.

In vitro evaluation of ultrasound-assisted thrombolysis using a targeted ultrasound contrast agent.

A thrombus-targeted ultrasound contrast agent bound with tirofiban - a glycoprotein (GP) IIb/IIIa antagonist that can specifically bind to activated platelets in the thrombus - was designed to enhance both the image contrast and thrombolysis effect. In this study, we used 76 canine thrombi for investigation. The targeting ability to thrombi was confirmed by microphotography and high-frequency ultrasound (40 MHz) imaging. The effect of the targeted microbubbles on thrombolysis enhancement was investigated using an in vitro flow system: targeted and nontargeted microbubbles flowed through the clot for 30 seconds with a washing step; the microbubbles remained on the clot that were then cavitated by ultrasound (frequency = 1 MHz, MI = 1.2). The extent of thrombolysis was evaluated by weight reduction and histology analysis. The targeted microbubbles reduced the weight of thrombi by a factor of 1.7 times that of the nontargeted microbubbles. (clot weight reduction: 23.1 +/- 5.3% versus 13.6 +/- 4.9%, p < 0.01 between targeted and nontargeted group), and the signal enhancement was 3.34 +/- 0.30 dB (mean +/- SD, p < 0.01 compared to control). We conclude that targeted microbubbles are applicable not only for molecular imaging of thrombi but also for improving the effectiveness of ultrasound-assisted thrombolysis.

Spleen rupture after mitral valve replacement for infective endocarditis.

We present a case of splenic rupture as the cause of a sudden drop in blood pressure soon after mitral valve surgery for infective endocarditis. This case suggests that, in addition to more common causes of unstable vital signs after valvular surgery, such as cardiac tamponade or bleeding at the operation site, splenic rupture, although rare, should be considered in the differential diagnosis. This is particularly important in the case of infective endocarditis.

Two different anesthetic managements of a patient with von Gierke's disease.

Von Gierke's disease, a form of glycogen storage disturbance, is a rare metabolic disorder with important implications for anesthesiologists. It is caused by the lack of the glucose-6-phosphatase, which is necessary for the liver to convert glycogen to glucose. To avoid severe hypoglycemia, it is crucial to keep oral feeding at intervals 2-3 hr for maintaining a normal blood sugar level. The metabolic derangements of von Gierke's disease may result in serious complications in patients undergoing surgery and anesthesia. We report the anesthetic managements of a patient with von Gierke's disease in two operations with different encounters.