Building Blood Vessel Chips with Enhanced Physiological Relevance

Blood vessel chips are bioengineered microdevices, consisting of biomaterials, human cells, and microstructures, which recapitulate essential vascular structure and physiology and allow a well-controlled microenvironment and spatial-temporal readouts. Blood vessel chips afford promising opportunities to understand molecular and cellular mechanisms underlying a range of vascular diseases. The physiological relevance is key to these blood vessel chips that rely on bioinspired strategies and bioengineering approaches to translate vascular physiology into artificial units. Here, several critical aspects of vascular physiology are discussed, including morphology, material composition, mechanical properties, flow dynamics, and mass transport, which provide essential guidelines and a valuable source of bioinspiration for the rational design of blood vessel chips. The state-of-art blood vessel chips are also reviewed that exhibit important physiological features of the vessel and reveal crucial insights into the biological processes and disease pathogenesis, including rare diseases, with notable implications for drug screening and clinical trials. It is envisioned that the advances in biomaterials, biofabrication, and stem cells improve the physiological relevance of blood vessel chips, which, along with the close collaborations between clinicians and bioengineers, enable their widespread utility. © 2023 Wiley-VCH GmbH.

Physiological Behavior of COVID-19 Patients Using Wearable System and Markov Chains

This study seeks to continuously monitor key physiological parameters in progression and development in people infected with the COVID-19 virus. This will be developed through a wearable system where physiological and some hemodynamic data will be obtained. Based on this data collection, Markov chains will be applied in order to establish the probability of change in the progression of the disease. That is, the probability of complications from this condition or improvement of the infected patient. For the development of this study, a data collection system based mainly on MEMS-type sensors will be used, as well as the use of stochastic simulations to verify the development of Markov chains. It is important to mention that this is a study in development that seeks the rapid application for the monitoring of patients with this condition. © 2021 IEEE.

Orthostatic Intolerance in Adults Reporting Long COVID Symptoms Was Not Associated With Postural Orthostatic Tachycardia Syndrome.

In this observational cross-sectional study, we investigated predictors of orthostatic intolerance (OI) in adults reporting long COVID symptoms. Participants underwent a 3-min active stand (AS) with Finapres® NOVA, followed by a 10-min unmedicated 70° head-up tilt test. Eighty-five participants were included (mean age 46 years, range 25-78; 74% women), of which 56 (66%) reported OI during AS (OIAS). OIAS seemed associated with female sex, more fatigue and depressive symptoms, and greater inability to perform activities of daily living (ADL), as well as a higher heart rate (HR) at the lowest systolic blood pressure (SBP) point before the first minute post-stand (mean HRnadir: 88 vs. 75 bpm, P = 0.004). In a regression model also including age, sex, fatigue, depression, ADL inability, and peak HR after the nadir SBP, HRnadir was the only OIAS predictor (OR = 1.09, 95% CI: 1.01-1.18, P = 0.027). Twenty-two (26%) participants had initial (iOH) and 5 (6%) classical (cOHAS) orthostatic hypotension, but neither correlated with OIAS. Seventy-one participants proceeded to tilt, of which 28 (39%) had OI during tilt (OItilt). Of the 53 who had a 10-min tilt, 7 (13%) had an HR increase >30 bpm without cOHtilt (2 to HR > 120 bpm), but six did not report OItilt. In conclusion, OIAS was associated with a higher initial HR on AS, which after 1 min equalised with the non-OIAS group. Despite these initial orthostatic HR differences, POTS was infrequent (2%). ClinicalTrials.gov Identifier: NCT05027724 (retrospectively registered on August 30, 2021).

The GUIDE-HF trial of pulmonary artery pressure monitoring in heart failure: impact of the COVID-19 pandemic.

AIMS: During the coronavirus disease 2019 (COVID-19) pandemic, important changes in heart failure (HF) event rates have been widely reported, but few data address potential causes for these changes; several possibilities were examined in the GUIDE-HF study. METHODS AND RESULTS: From 15 March 2018 to 20 December 2019, patients were randomized to haemodynamic-guided management (treatment) vs. control for 12 months, with a primary endpoint of all-cause mortality plus HF events. Pre-COVID-19, the primary endpoint rate was 0.553 vs. 0.682 events/patient-year in the treatment vs. control group [hazard ratio (HR) 0.81, P = 0.049]. Treatment difference was no longer evident during COVID-19 (HR 1.11, P = 0.526), with a 21% decrease in the control group (0.536 events/patient-year) and no change in the treatment group (0.597 events/patient-year). Data reflecting provider-, disease-, and patient-dependent factors that might change the primary endpoint rate during COVID-19 were examined. Subject contact frequency was similar in the treatment vs. control group before and during COVID-19. During COVID-19, the monthly rate of medication changes fell 19.2% in the treatment vs. 10.7% in the control group to levels not different between groups (P = 0.362). COVID-19 was infrequent and not different between groups. Pulmonary artery pressure area under the curve decreased -98 mmHg-days in the treatment group vs. -100 mmHg-days in the controls (P = 0.867). Patient compliance with the study protocol was maintained during COVID-19 in both groups. CONCLUSION: During COVID-19, the primary event rate decreased in the controls and remained low in the treatment group, resulting in an effacement of group differences that were present pre-COVID-19. These outcomes did not result from changes in provider- or disease-dependent factors; pulmonary artery pressure decreased despite fewer medication changes, suggesting that patient-dependent factors played an important role in these outcomes. Clinical Trials.gov: NCT03387813.

Recommendations on anticoagulation strategies, prevention of complications due to venous thromboembolic disease and hematological dysfunction. (Pautas nacionales para la atenci..n de pacientes adultos con COVID-19.) [Spanish]

Current considerations on nutritional therapy (NT) in the ICU for patients with COVID-19 are based on indirect recommendations established in similar populations of critically ill patients;for example, in conditions such as acute respiratory distress syndrome (ARDS), sepsis, or acute kidney injury. From a practical point of view, it is appropriate that the NT strategy in these patients consider: (1) the phase of the disease, (2) the hemodynamic condition and (3) the type of respiratory support indicated for each individual patient. Therefore, patients with severe pneumonia or COVID-19 sepsis should be considered patients with high nutritional risk. On the other hand, it has been shown that an increased BMI is related to a poor prognosis, which supports a possible role of sarcopenic obesity in the survival of critically ill patients with COVID-19. Patients with sepsis due to COVID-19 and septic shock have no contraindication to start an EN, with the exception of vasopressor doses being increased, presenting elements of tissue dysoxia or acute gastrointestinal dysfunction with intolerance to EN.

Recommendations on nutritional strategies and metabolic management. (Pautas nacionales para la atenci..n de pacientes adultos con COVID-19.) [Spanish]

The aim of the article was to discuss current guidelines for metabolic management. Current considerations on nutritional therapy (NT) in the ICU for patients with COVID-19 are based on indirect recommendations established in similar populations of critically ill patients;for example, in conditions such as acute respiratory distress syndrome (ARDS), sepsis, or acute kidney injury. From a practical point of view, it is appropriate that the NT strategy in these patients consider: (1) the phase of the disease, (2) the hemodynamic condition and (3) the type of respiratory support indicated for each individual patient. Therefore, patients with severe pneumonia or COVID-19 sepsis should be considered patients with high nutritional risk. On the other hand, it has been shown that an increased BMI is related to a poor prognosis, which supports a possible role of sarcopenic obesity in the survival of critically ill patients with COVID-19. Patients with sepsis due to COVID-19 and septic shock have no contraindication to start an EN, with the exception of vasopressor doses being increased, presenting elements of tissue dysoxia or acute gastrointestinal dysfunction with intolerance to EN.

Recommendations on fluid therapy and pharmacological management of hemodynamic dysfunction and septic shock in COVID-19. (Pautas nacionales para la atenci..n de pacientes adultos con COVID-19.) [Spanish]

The aim of the article was to discuss haemodynamics and septic shock for COVID-19. Recommendations for the management of acute kidney injury and liver dysfunctionManagement of acute kidney injury associated with COVID-19. The etiology of acute kidney injury (AKI) associated with COVID-19 is multifactorial, involving factors specific to the disease itself (viral tropism, proinflammatory cytokines, coagulopathy with thrombotic microangiopathy, rhabdomyolysis), and nonspecific, linked to the treatment of critically ill patients. The diagnosis of AKI is made using the diagnostic criteria of the KDIGO definition, through frequent monitoring of creatinine and urinary output in order to carry out early detection of renal involvement. There are no specific measures for prevention and treatment of acute kidney injury associated with CO-VID-19, but immunomodulatory treatment (corticosteroids) and coagulopathy (heparin) could contribute to reducing its incidence and magnitude. Some of the measures to treat the non-specific factors involved in the development of acute kidney injury are also discussed in this study.

Left ventricular thrombus in multisystem inflammatory syndrome in children associated with COVID-19.

A 17-year-old adolescent with severe multisystem inflammatory syndrome in children (MIS-C) associated with coronavirus disease-2019 developed reduced left ventricular function and left ventricular thrombus. With treatment, his condition improved and the thrombus was dissolved. This case illustrates the risk of severe intra-cardiac thrombotic complications in patients with MIS-C.

Risk prediction in patients with COVID-19 based on haemodynamic assessment of left and right ventricular function.

AIMS: Cardiovascular involvement is common in COVID-19. We sought to describe the haemodynamic profiles of hospitalized COVID-19 patients and determine their association with mortality. METHODS AND RESULTS: Consecutive hospitalized patients diagnosed with COVID-19 infection underwent clinical evaluation using the Modified Early Warning Score (MEWS) and a full non-invasive echocardiographic haemodynamic evaluation, irrespective of clinical indication, as part of a prospective predefined protocol. Patients were stratified based on filling pressure and output into four groups. Multivariable Cox-Hazard analyses determined the association between haemodynamic parameters with mortality. Among 531 consecutive patients, 44% of patients had normal left ventricular (LV) and right ventricular (RV) haemodynamic status. In contrast to LV haemodynamic parameters, RV parameters worsened with higher MEWS stage. While RV parameters did not have incremental risk prediction value above MEWS, LV stroke volume index, E/e' ratio, and LV stroke work index were all independent predictors of outcome, particularly in severe disease. Patients with LV or RV with high filling pressure and low output had the worse outcome, and patients with normal haemodynamics had the best (P < 0.0001). CONCLUSION: In hospitalized patients with COVID-19, almost half have normal left and right haemodynamics at presentation. RV but not LV haemodynamics are related to easily obtainable clinical parameters. LV but not RV haemodynamics are independent predictors of mortality, mostly in patients with severe disease.

Haemodynamic characteristics of COVID-19 patients with acute respiratory distress syndrome requiring mechanical ventilation. An invasive assessment using right heart catheterization.

AIMS: Interstitial pneumonia due to coronavirus disease 2019 (COVID-19) is often complicated by severe respiratory failure. In addition to reduced lung compliance and ventilation/perfusion mismatch, a blunted hypoxic pulmonary vasoconstriction has been hypothesized, that could explain part of the peculiar pathophysiology of the COVID-19 cardiorespiratory syndrome. However, no invasive haemodynamic characterization of COVID-19 patients has been reported so far. METHODS AND RESULTS: Twenty-one mechanically-ventilated COVID-19 patients underwent right heart catheterization. Their data were compared both with those obtained from non-mechanically ventilated paired control subjects matched for age, sex and body mass index, and with pooled data of 1937 patients with 'typical' acute respiratory distress syndrome (ARDS) from a systematic literature review. Cardiac index was higher in COVID-19 patients than in controls [3.8 (2.7-4.5) vs. 2.4 (2.1-2.8) L/min/m2 , P < 0.001], but slightly lower than in ARDS patients (P = 0.024). Intrapulmonary shunt and lung compliance were inversely related in COVID-19 patients (r = -0.57, P = 0.011) and did not differ from ARDS patients. Despite this, pulmonary vascular resistance of COVID-19 patients was normal, similar to that of control subjects [1.6 (1.1-2.5) vs. 1.6 (0.9-2.0) WU, P = 0.343], and lower than reported in ARDS patients (P < 0.01). Pulmonary hypertension was present in 76% of COVID-19 patients and in 19% of control subjects (P < 0.001), and it was always post-capillary. Pulmonary artery wedge pressure was higher in COVID-19 than in ARDS patients, and inversely related to lung compliance (r = -0.46, P = 0.038). CONCLUSIONS: The haemodynamic profile of COVID-19 patients needing mechanical ventilation is characterized by combined cardiopulmonary alterations. Low pulmonary vascular resistance, coherent with a blunted hypoxic vasoconstriction, is associated with high cardiac output and post-capillary pulmonary hypertension, that could eventually contribute to lung stiffness and promote a vicious circle between the lung and the heart.

Haemodynamic monitoring and management in COVID-19 intensive care patients: an International survey.

PURPOSE: To survey haemodynamic monitoring and management practices in intensive care patients with the coronavirus disease 2019 (COVID-19). METHODS: A questionnaire was shared on social networks or via email by the authors and by Anaesthesia and/or Critical Care societies from France, Switzerland, Belgium, Brazil, and Portugal. Intensivists and anaesthetists involved in COVID-19 ICU care were invited to answer 14 questions about haemodynamic monitoring and management. RESULTS: Globally, 1000 questionnaires were available for analysis. Responses came mainly from Europe (n = 460) and America (n = 434). According to a majority of respondents, COVID-19 ICU patients frequently or very frequently received continuous vasopressor support (56%) and had an echocardiography performed (54%). Echocardiography revealed a normal cardiac function, a hyperdynamic state (43%), hypovolaemia (22%), a left ventricular dysfunction (21%) and a right ventricular dilation (20%). Fluid responsiveness was frequently assessed (84%), mainly using echo (62%), and cardiac output was measured in 69%, mostly with echo as well (53%). Venous oxygen saturation was frequently measured (79%), mostly from a CVC blood sample (94%). Tissue perfusion was assessed biologically (93%) and clinically (63%). Pulmonary oedema was detected and quantified mainly using echo (67%) and chest X-ray (61%). CONCLUSION: Our survey confirms that vasopressor support is not uncommon in COVID-19 ICU patients and suggests that different haemodynamic phenotypes may be observed. Ultrasounds were used by many respondents, to assess cardiac function but also to predict fluid responsiveness and quantify pulmonary oedema. Although we observed regional differences, current international guidelines were followed by most respondents.