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1.
Crit Care ; 25(1): 381, 2021 11 08.
Article in English | MEDLINE | ID: covidwho-1506432

ABSTRACT

BACKGROUND: COVID-19 is primarily a respiratory disease; however, there is also evidence that it causes endothelial damage in the microvasculature of several organs. The aim of the present study is to characterize in vivo the microvascular reactivity in peripheral skeletal muscle of severe COVID-19 patients. METHODS: This is a prospective observational study carried out in Spain, Mexico and Brazil. Healthy subjects and severe COVID-19 patients admitted to the intermediate respiratory (IRCU) and intensive care units (ICU) due to hypoxemia were studied. Local tissue/blood oxygen saturation (StO2) and local hemoglobin concentration (THC) were non-invasively measured on the forearm by near-infrared spectroscopy (NIRS). A vascular occlusion test (VOT), a three-minute induced ischemia, was performed in order to obtain dynamic StO2 parameters: deoxygenation rate (DeO2), reoxygenation rate (ReO2), and hyperemic response (HAUC). In COVID-19 patients, the severity of ARDS was evaluated by the ratio between peripheral arterial oxygen saturation (SpO2) and the fraction of inspired oxygen (FiO2) (SF ratio). RESULTS: Healthy controls (32) and COVID-19 patients (73) were studied. Baseline StO2 and THC did not differ between the two groups. Dynamic VOT-derived parameters were significantly impaired in COVID-19 patients showing lower metabolic rate (DeO2) and diminished endothelial reactivity. At enrollment, most COVID-19 patients were receiving invasive mechanical ventilation (MV) (53%) or high-flow nasal cannula support (32%). Patients on MV were also receiving sedative agents (100%) and vasopressors (29%). Baseline StO2 and DeO2 negatively correlated with SF ratio, while ReO2 showed a positive correlation with SF ratio. There were significant differences in baseline StO2 and ReO2 among the different ARDS groups according to SF ratio, but not among different respiratory support therapies. CONCLUSION: Patients with severe COVID-19 show systemic microcirculatory alterations suggestive of endothelial dysfunction, and these alterations are associated with the severity of ARDS. Further evaluation is needed to determine whether these observations have prognostic implications. These results represent interim findings of the ongoing HEMOCOVID-19 trial. Trial registration ClinicalTrials.gov NCT04689477 . Retrospectively registered 30 December 2020.


Subject(s)
COVID-19/physiopathology , Intensive Care Units/trends , Microvessels/physiopathology , Respiratory Care Units/trends , Respiratory Distress Syndrome/physiopathology , Severity of Illness Index , Adult , Aged , Brazil/epidemiology , COVID-19/diagnosis , COVID-19/epidemiology , Female , Humans , Male , Mexico/epidemiology , Microcirculation/physiology , Middle Aged , Muscle, Skeletal/blood supply , Muscle, Skeletal/physiopathology , Prospective Studies , Respiratory Distress Syndrome/diagnosis , Respiratory Distress Syndrome/epidemiology , Spain/epidemiology
2.
Hip Int ; 30(6): 718-724, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-1455854

ABSTRACT

OBJECTIVES: The posterior approach in total hip arthroplasty (THA) often requires dissection of the short external rotators (SERs), which could increase the postoperative dislocation rate. The reattachment of the dissected SERs has been reported to reduce the dislocation rate, while such repair generally causes progression of muscle atrophy. 1 of the suggested causes of atrophy is reduced blood flow to the repaired SERs. The present study aimed to measure the blood flow of the SERs before dissection (pre-tenotomy) and after reattachment (post-reattachment) during the posterior approach in THA. METHODS: This prospective study included 26 patients who underwent THA via the posterior approach. A laser-Doppler rheometer was used to measure the blood flow in the following SERs at the time of pre-tenotomy and post-reattachment: the piriformis muscle (PM), superior gemellus (SG), inferior gemellus (IG), obturator internus (OI), and subcutaneous tissue as a control. RESULTS: The average pre-tenotomy and post-reattachment blood flows (mL/minutes/100 g) were: 1.90 ± 0.28 and 1.92 ± 0.40 in the PM, 1.94 ± 0.20 and 1.99 ± 0.39 in the SG, 1.91 ± 0.21 and 1.94 ± 0.30 in the IG, 1.93 ± 0.22 and 1.98 ± 0.36 in the OI, and 1.94 ± 0.24 and 1.87 ± 0.38 in the subcutaneous tissue. The pre-tenotomy and post-reattachment blood flows did not show significant difference in any muscle. CONCLUSIONS: Laser-Doppler blood flow measurements showed that the blood flow is preserved, even when the SERs are dissected and reattached in THA via the posterior approach.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Hip Dislocation/surgery , Hip Joint/surgery , Muscle, Skeletal/surgery , Regional Blood Flow/physiology , Tenotomy/methods , Aged , Aged, 80 and over , Female , Hip Joint/blood supply , Humans , Male , Middle Aged , Muscle, Skeletal/blood supply , Postoperative Period , Prospective Studies
3.
Mol Ther ; 29(10): 3042-3058, 2021 10 06.
Article in English | MEDLINE | ID: covidwho-1331299

ABSTRACT

Reprogramming non-cardiomyocytes (non-CMs) into cardiomyocyte (CM)-like cells is a promising strategy for cardiac regeneration in conditions such as ischemic heart disease. Here, we used a modified mRNA (modRNA) gene delivery platform to deliver a cocktail, termed 7G-modRNA, of four cardiac-reprogramming genes-Gata4 (G), Mef2c (M), Tbx5 (T), and Hand2 (H)-together with three reprogramming-helper genes-dominant-negative (DN)-TGFß, DN-Wnt8a, and acid ceramidase (AC)-to induce CM-like cells. We showed that 7G-modRNA reprogrammed 57% of CM-like cells in vitro. Through a lineage-tracing model, we determined that delivering the 7G-modRNA cocktail at the time of myocardial infarction reprogrammed ∼25% of CM-like cells in the scar area and significantly improved cardiac function, scar size, long-term survival, and capillary density. Mechanistically, we determined that while 7G-modRNA cannot create de novo beating CMs in vitro or in vivo, it can significantly upregulate pro-angiogenic mesenchymal stromal cells markers and transcription factors. We also demonstrated that our 7G-modRNA cocktail leads to neovascularization in ischemic-limb injury, indicating CM-like cells importance in other organs besides the heart. modRNA is currently being used around the globe for vaccination against COVID-19, and this study proves this is a safe, highly efficient gene delivery approach with therapeutic potential to treat ischemic diseases.


Subject(s)
Cellular Reprogramming/genetics , Genetic Therapy/methods , Ischemia/therapy , Muscle, Skeletal/blood supply , Myocardial Infarction/therapy , Neovascularization, Physiologic/genetics , Regeneration/genetics , Transfection/methods , Animals , Animals, Newborn , Cells, Cultured , Disease Models, Animal , Female , Fibroblasts/metabolism , Humans , Male , Mice , Mice, Knockout, ApoE , Myocytes, Cardiac/metabolism , RNA, Messenger/genetics
5.
J Clin Monit Comput ; 35(3): 661-662, 2021 May.
Article in English | MEDLINE | ID: covidwho-649924

ABSTRACT

OBJECTIVE: Objective of this case report is to draw attention to a less known thrombotic complication associated with COVID-19, i.e., thrombosis of both radial arteries, with possible (long-term) consequences. THE CASE: In our COVID-19 ICU a 49-year-old male patient was admitted, with past medical history of obesity, smoking and diabetes, but no reported atherosclerotic complications. The patient had been admitted with severe hypoxemia and multiple pulmonary emboli were CT-confirmed. ICU-treatment included mechanical ventilation and therapeutic anticoagulation. Preparing the insertion of a new radial artery catheter for invasive blood pressure measurement and blood sampling, we detected that both radial arteries were non-pulsating and occluded: (a) Sonography showed the typical anatomical localization of both radial and ulnar arteries. However, Doppler-derived flow-signals could only be obtained from the ulnar arteries. (b) To test collateral arterial supply of the hand, a pulse-oximeter was placed on the index finger. Thereafter, the ulnar artery at the wrist was compressed. This compression caused an immediate loss of the finger's pulse-oximetry perfusion signal. The effect was reversible upon release of the ulnar artery. (c) To test for collateral perfusion undetectable by pulse-oximetry, we measured regional oxygen saturation (rSO2) of the thenar muscle by near-infrared spectroscopy (NIRS). Confirming our findings above, ulnar arterial compression demonstrated that thenar rSO2 was dependent on ulnar artery flow. The described development of bilateral radial artery occlusion in a relatively young and therapeutically anticoagulated patient with no history of atherosclerosis was unexpected. CONCLUSIONS: Since COVID-19 patients are at increased risk for arterial occlusion, it appears advisable to meticulously check for adequacy of collateral (hand-) perfusion, avoiding the harm of hand ischemia if interventions (e.g., catheterizations) at the radial or ulnar artery are intended.


Subject(s)
Arterial Occlusive Diseases/diagnostic imaging , Arterial Occlusive Diseases/etiology , COVID-19/complications , Radial Artery , SARS-CoV-2 , Arterial Occlusive Diseases/physiopathology , COVID-19/diagnostic imaging , COVID-19/physiopathology , Hand/blood supply , Hand/diagnostic imaging , Humans , Male , Middle Aged , Muscle, Skeletal/blood supply , Muscle, Skeletal/metabolism , Netherlands , Oximetry , Oxygen Consumption , Pandemics , Radial Artery/diagnostic imaging , Radial Artery/physiopathology , Regional Blood Flow , Spectroscopy, Near-Infrared , Ulnar Artery/diagnostic imaging , Ultrasonography, Doppler
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