This study aims to review the available literature pertinent to vascular complications in COVID-19. A systematic search was performed using PubMed and Google Scholar to identify all relevant studies based on our study objective. Multiple studies have reported widespread systemic inflammation and procoagulant/hypercoagulable state in COVID-19, including thrombotic microangiopathy, endothelial dysfunction, bleeding disorder, and thrombosis. However, large specialised studies on vascular complications are lacking despite current evidence indicating dysfunctional coagulation pathways. Furthermore, there are no clear and definitive recommendations regarding thromboprophylaxis or full therapeutic anticoagulation in COVID-19. Several studies have reported hypercoagulability and vascular complications as important predictors of patient outcome in COVID-19. Therefore, it is important to understand the pathogenesis, epidemiology, management, and outcomes of patients who develop venous or arterial thrombosis and those with a pre-existing thrombotic disease who contract COVID-19 for risk stratification, thromboprophylaxis, optimal antithrombotic therapy during active infection and long-term anticoagulation following discharge or recovery.

/pdf/a-comprehensive-review-of-vascular-complications-in-covid-19-12l8878ghb.pdf

A comprehensive review of vascular complications in COVID-19.

Although intensive care medicine (ICM) is a relatively young discipline, it has rapidly developed into a full-fledged and highly specialized specialty covering several fields of medicine. The COVID-19 pandemic led to a surge in intensive care unit demand and also bring unprecedented development opportunities for this area. Multiple new technologies such as artificial intelligence (AI) and machine learning (ML) were gradually being applied in this field. In this study, through an online survey, we have summarized the potential uses of ChatGPT/GPT-4 in ICM range from knowledge augmentation, device management, clinical decision-making support, early warning systems, and establishment of intensive care unit (ICU) database. 

/pdf/artificial-intelligence-in-intensive-care-medicine-toward-a-17u2uhom.pdf

Artificial Intelligence in Intensive Care Medicine: Toward a ChatGPT/GPT-4 Way?

Purpose Extracorporeal membrane oxygenation (ECMO) is employed to support critically ill COVD-19 patients. The occurrence of ischemic stroke and intracranial hemorrhage (ICH), as well as the implementation of anticoagulation strategies under the dual influence of ECMO and COVID-19 remain unclear. We conducted a systematic review and meta-analysis to describe the ischemic stroke, ICH and overall in-hospital mortality in COVID-19 patients receiving ECMO and summarize the anticoagulation regimens. Methods EMBASE, PubMed, Cochrane, and Scopus were searched for studies examining ischemic stroke, ICH, and mortality in COVID-19 patients supported with ECMO. The outcomes were incidences of ischemic stroke, ICH, overall in-hospital mortality and anticoagulation regimens. We calculated the pooled proportions and 95% confidence intervals (CIs) to summarize the results. Results We analyzed 12 peer-reviewed studies involving 6039 COVID-19 patients. The incidence of ischemic stroke had a pooled estimate of 2.2% (95% CI: 1.2%–3.2%). The pooled prevalence of ICH was 8.0% (95% CI: 6.3%–9.6%). The pooled estimate of overall in-hospital mortality was 40.3% (95% CI: 33.1%–47.5%). The occurrence of ICH was significantly higher in COVID-19 patients supported with ECMO than in other respiratory ECMO [relative risk=1.75 (95% CI: 1.00–3.07)]. Unfractionated heparin was the most commonly used anticoagulant, and anticoagulation monitoring practice varied among centers. Conclusions Ischemic stroke and ICH were common under the double “hit” of COVID-19 and ECMO. The prevalence of ICH was significantly higher in COVID-19 patients supported with ECMO than non-COVID-19 patients requiring ECMO. Individualized anticoagulation regimens may be a good choice to balance thrombosis and bleeding. More detailed research and further exploration are needed to clarify the underlying mechanism and clinical management decisions.

Ischemic stroke and intracranial hemorrhage in extracorporeal membrane oxygenation for COVID-19: A systematic review and meta-analysis

Adiponectin, a key metabolic hormone, is secreted into the circulation by fat cells where it enhances insulin sensitivity and stimulates glucose and fatty acid metabolism. Adiponectin receptors are highly expressed in the taste system; however, their effects and mechanisms of action in the modulation of gustatory function remain unclear. We utilized an immortalized human fungiform taste cell line (HuFF) to investigate the effect of AdipoRon, an adiponectin receptor agonist, on fatty acid-induced calcium responses. We showed that the fat taste receptors (CD36 and GPR120) and taste signaling molecules (Gα-gust, PLCβ2, and TRPM5) were expressed in HuFF cells. Calcium imaging studies showed that linoleic acid induced a dose-dependent calcium response in HuFF cells, and it was significantly reduced by the antagonists of CD36, GPR120, PLCβ2, and TRPM5. AdipoRon administration enhanced HuFF cell responses to fatty acids but not to a mixture of sweet, bitter, and umami tastants. This enhancement was inhibited by an irreversible CD36 antagonist and by an AMPK inhibitor but was not affected by a GPR120 antagonist. AdipoRon increased the phosphorylation of AMPK and the translocation of CD36 to the cell surface, which was eliminated by blocking AMPK. These results indicate that AdipoRon acts to increase cell surface CD36 in HuFF cells to selectively enhance their responses to fatty acids. This, in turn, is consistent with the ability of adiponectin receptor activity to alter taste cues associated with dietary fat intake.

/pdf/adiponectin-enhances-fatty-acid-signaling-in-human-taste-235fju0t.pdf

Adiponectin Enhances Fatty Acid Signaling in Human Taste Cells by Increasing Surface Expression of CD36

Dementia is a detrimental neuropathologic condition with considerable physical, mental, social, and financial impact on patients and society. Patients with metabolic syndrome (MetS), a group of diseases that occur in tandem and increase the risk of neurologic diseases, have a higher risk of dementia. The ratio between muscle and adipose tissue is crucial in MetS, as these contain many hormones, including myokines and adipokines, which are involved in crosstalk and local paracrine/autocrine interactions. Evidence suggests that abnormal adipokine and myokine synthesis and release may be implicated in various MetS, such as atherosclerosis, diabetic mellitus (DM), and dyslipidemia, but their precise role is unclear. Here we review the literature on adipokine and myokine involvement in MetS-induced dementia via glucose and insulin homeostasis regulation, neuroinflammation, vascular dysfunction, emotional changes, and cognitive function. 

Pharmacological and physiological roles of adipokines and myokines in metabolic-related dementia.

ECMO support for COVID-19: a balancing act.

Deep hypothermic circulatory arrest (DHCA) can induce systemic inflammatory response syndrome, including neuroinflammation. Finding suitable compounds is necessary for attenuating neuroinflammation and avoiding cerebral complications following DHCA. In the present study, we established DHCA rat models and monitored the vital signs during the surgical process. After surgery, we found significantly increased proinflammatory cytokines (IL-6, IL-1β, and TNF-α) in DHCA rats. Quantitative proteomics analysis was performed for exploring the differentially expressed proteins in hippocampus of DHCA rats and the data showed the adiponectin receptor 1 protein was upregulated. More importantly, administration of AdipoRon, a small-molecule adiponectin receptor agonist, could improve the basic vital signs and attenuate the increased IL-6, IL-1β, and TNF-α in DHCA rats. Furthermore, AdipoRon inhibits the activation of microglia (M1 state) and promotes their transition to an anti-inflammatory state, via promoting the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), and downregulating nuclear factor kappa B (NF-κB) in DHCA rats. Consistently, we used LPS-treated BV2 cells to mimic the neuroinflammatory condition and found that AdipoRon dose-dependently decreased cytokines, along with increased phosphorylation of AMPK and downregulated NF-κB. In conclusion, our present data supported that AdipoRon inhibited DHCA-induced neuroinflammation via activating the hippocampal AMPK/NF-κB pathway.

/pdf/adiporon-inhibits-neuroinflammation-induced-by-deep-e6i2i1hf.pdf

AdipoRon Inhibits Neuroinflammation Induced by Deep Hypothermic Circulatory Arrest Involving the AMPK/NF-κB Pathway in Rats

Deep hypothermic circulatory arrest (DHCA) is routinely applied during surgeries for complex congenital heart disease and aortic arch disease. The present study aims to provide a method for establishing DHCA in rats. To evaluate the impact of the DHCA process on vital signs, a normal temperature cardiopulmonary bypass (CPB) rat model without circulatory arrest was used as a control. As expected, DHCA led to a significant decrease in body temperature and mean arterial blood pressure. The blood gas analysis indicated that DHCA increased lactic acid levels but did not influence the blood pH and the concentrations of hemoglobin, hematocrit, Na+, Cl-, K+, and glucose. Furthermore, compared with the normal temperature CPB rats, the results of the transmission electron microscopy showed a mild increase in hippocampal autophagosomes in the DHCA rats.

Establishment of Deep Hypothermic Circulatory Arrest in Rats.

A transfusion risk stratification score to facilitate quality management in cardiopulmonary bypass.

BACKGROUND
Extracorporeal membrane oxygenation (ECMO) has salvaged many people's life during global pandemics. However, ECMO is associated with a high incidence of hemostatic complications. This study aims to explore the effects of the ECMO system on the coagulation system in the healthy ovine ECMO model.


METHODS
Ten healthy male sheep were included. Five received the veno-arterial ECMO and five received the veno-venous ECMO. Heparin was infused for systemic anticoagulation and was adjusted according to the activated clotting time. Blood routine tests, coagulation factors, anticoagulation proteins, and fibrinolysis markers were tested at the baseline and every 24 hours. After weaning, the pump heads were dissected to explore thrombosis.


RESULTS
Platelets decreased in the first 72 hours and returned to the baseline at the 120th hour. The neutrophils increased in the first 24 hours and returned to the baseline at the 48th hour. Factors II, VII, and X decreased in the first 24 hours and gradually increased, while factors VIII, IX, XI, and XII decreased in the first 24 hours and remained at a low level. The baseline antithrombin was 73.2 ± 14.4% and reduced to 42.6 ± 9.9% at the 168th hour. Pathology showed seven sheep developed thrombus, but no clinically relevant bleeding or thrombosis events occurred.


CONCLUSIONS
The study explored hemostatic alterations during ECMO in healthy animal models, which eliminated the confounding under critically ill conditions. The study may provide insights into ECMO hemostatic disorders and aid the design of optimal therapeutic strategies.

Bingyang Ji

Papers

ECMO support for COVID-19: a balancing act.

AdipoRon Inhibits Neuroinflammation Induced by Deep Hypothermic Circulatory Arrest Involving the AMPK/NF-κB Pathway in Rats

Establishment of Deep Hypothermic Circulatory Arrest in Rats.

A transfusion risk stratification score to facilitate quality management in cardiopulmonary bypass.

Hemostatic alterations during extracorporeal membrane oxygenation in ovine veno-venous and veno-arterial models.