Deciphering Key microRNA Regulated Pathways in Tissue-Engineered Blood Vessels: Implications for Vascular Scaffold Production.

MicroRNAs (miRNAs) are non-coding RNAs involved in the regulation of gene expression associated with cell differentiation, proliferation, adhesion, and important biological functions such as inflammation. miRNAs play roles associated with the pathogenesis of chronic degenerative disorders including cardiovascular diseases. Understanding the influence of miRNAs and their target genes can effectively streamline the identification of key biologically active pathways that are important in the development of vascular grafts through the tissue engineering of blood vessels. To determine miRNA expression levels and identify miRNA target genes and pathways with biological roles in scaffolds that have been repopulated with adipose-derived stem cells (ASCs) generated through tissue engineering for the construction of blood vessels. miRNA quantification assays were performed in triplicate to determine miRNA expression in a total of 20 samples: five controls (natural inferior vena cava), five scaffolds recellularized with ASCs and differentiated into the endothelium (luminal layer), five samples of complete scaffolds seeded with ASCs differentiated into the endothelium (luminal layer) and smooth muscle (extraluminal layer), and five samples of ASC without cell differentiation. Several differentially expressed miRNAs were identified and predicted to modulate target genes with roles in key pathways associated with angiogenesis, vascular system control, and endothelial and smooth muscle regulation, including migration, proliferation, and growth. These findings underscore the involvement of these pathways in the regulatory mechanisms that are essential for vascular scaffold production through tissue engineering. Our research contributes to the knowledge of miRNA-regulated mechanisms, which may impact the design of vascular substitutes, and provide valuable insights for enhancing clinical practice. The molecular pathways regulated by miRNAs in tissue engineering of blood vessels (TEBV) allowed us to elucidate the main phenomena involved in cellular differentiation to constitute a blood vessel, with the main pathways being essential for angiogenesis, cellular differentiation, and differentiation into vascular smooth muscle.

Shear wave elastography for extracranial carotid atherosclerotic plaques: technical principles and how to do it.

In the wake of studies targeting atherosclerotic plaques and searching for quantifiable variables that contribute additional information to therapeutic decision-making, plaque assessment using Shear Wave Elastography (SWE) is emerging as a reproducible and promising alternative. We used a single Logiq S8 device (General Electric, Boston, Massachusetts, United States) with an 8.5-11MHz multifrequency linear transducer at 10MHz in longitudinal section. We considered relevant criteria for image acquisition: adequate longitudinal insonation, differentiation of the intima-media complex, delineation of proximal and distal tunica adventitia and the vascular lumen, good visualization of the atherosclerotic plaque, cardiac cycle in ventricular diastole, and absence of incongruous changes. SWE is an emerging and extremely promising method for assessment of carotid plaques that may contribute to therapeutic decision-making based on characteristics related to the atherosclerotic plaque, with inter-device and inter-examiner reproducibility.

Grayscale median (GSM) post-processing, posterizing, and color mapping for carotid ultrasound.

Factors related to atherosclerotic plaques may indicate instability, such as ulcerations, intraplaque hemorrhages, lipid core, thin or irregular fibrous cap, and inflammation. The grayscale median (GSM) value is one of the most widespread methods of studying atherosclerotic plaques and it is therefore important to comprehensively standardize image post-processing. Post-processing was performed using Photoshop 23.1.1.202. Images were standardized by adjusting the grayscale histogram curves, setting the darkest point of the vascular lumen (blood) to zero and the distal adventitia to 190. Posterization and color mapping were performed. A methodology that presents the current state of the art in an accessible and illustrative way should contribute to the dissemination of GSM analysis. This article describes and illustrates the process step by step.

Squamous cell carcinoma on an arteriovenous fistula scar: case report.

The main type of access used for hemodialysis is the arteriovenous fistula (AVF) because it offers superior patency and lower complication rates when compared to other hemodialysis accesses. We report the case of a 69-year-old female patient with chronic kidney disease on dialysis secondary to hypertensive nephrosclerosis with a radiocephalic AVF in the left upper limb created 9 years previously. Two years previously, she had undergone a kidney transplant and was taking immunosuppressants. A crusted lesion developed on her left forearm with onset 3 months before presentation and she underwent an excisional biopsy that revealed a well-differentiated and superficially invasive squamous cell carcinoma, with lateral and deep surgical margins free from neoplasia. At 1-year follow-up, the patient showed no signs of neoplastic recurrence.

Comparative study of angiographic changes in diabetic and non-diabetic patients with peripheral arterial disease.

Background: Diabetics are at 5-15 times greater risk of developing peripheral arterial disease (PAD) and few studies have compared risk factors and distribution and severity of arterial changes in diabetics compared with non-diabetics. Objectives: To compare angiographic changes between diabetic and non-diabetic patients with advanced PAD and correlate them with risk factors. Methods: A retrospective cross-sectional study was conducted of consecutive patients undergoing lower limb arteriography for PAD (Rutherford 3-6) using TASC II and Bollinger et al. angiographic scores. Exclusion criteria were upper limb angiographies, unclear images, incomplete laboratory test results, and previous arterial surgeries. Statistical analyses included chi-square tests, Fisher's test for discrete data, and Student's t test for continuous data (significance level: p < 0.05). Results: We studied 153 patients with a mean age of 67 years, 50.9% female and 58.2% diabetics. A total of 91 patients (59%) had trophic lesions (Rutherford 5 or 6) and 62 (41%) had resting pain or limiting claudication (Rutherford 3 and 4). Among diabetics, 81.7% were hypertensive, 29.4% had never smoked, and 14% had a history of acute myocardial infarction. According to the Bollinger et al. score, infra-popliteal arteries were more affected in diabetics, especially the anterior tibial artery (p = 0.005), while the superficial femoral artery was more affected in non-diabetics (p = 0.008). According to TASC II, the most severe angiographic changes in the femoral-popliteal segment occurred in non-diabetic patients (p = 0.019). Conclusions: The most frequently affected sectors were the infra-popliteal sectors in diabetics and the femoral sector in non-diabetics.

What to do when advanced thyroid cancer invades the carotid artery? Therapeutic challenge.

Of all thyroid cancers, anaplastic thyroid carcinoma (ATC) has the lowest incidence and worst prognosis. In this report, we describe a 64-year-old female patient who underwent total thyroidectomy and level VI neck dissection for papillary thyroid carcinoma. During follow-up, she showed signs of regional recurrence and underwent extended neck dissection and cervical esophagectomy. Intraoperatively, there was no cleavage plane between the tumor and the common carotid artery (CCA), so a carotid shunt was implanted and en bloc resection, including the affected CCA and esophagus segments was performed followed by vascular bypass with interposition of a great saphenous vein graft. A pathology review found evidence of anaplastic carcinoma. The patient underwent adjuvant treatment and has no signs of locoregional recurrence. Presented with the possibility of carrying out curative surgery with en bloc resection, the vascular surgeon must be prepared for the surgical options.

Polidocanol Plus Glucose Versus Glucose Alone for the Treatment of Telangiectasias: Triple Blind, Randomised Controlled Trial (PG3T).

OBJECTIVE: The aim of this study was to compare the effectiveness and safety of two sclerosing agents used to treat telangiectasias in the lower limbs: 0.2% polidocanol + 70% hypertonic glucose (HG) vs. 75% HG alone. METHODS: A prospective, randomised, triple blind, controlled, parallel group trial with patients randomly assigned in a 1:1 ratio between January and December 2015, with a two month follow up, from a single academic medical centre in Brazil, was carried out. Participants were women aged 18-65 years with telangiectasias on the lateral aspect of one thigh, classified as C1EpAsPn who underwent sclerotherapy in a single session with 0.2% polidocanol + 70% HG or 75% HG alone to treat the telangiectasias on an area limited by a rectangular template. The primary effectiveness endpoint was elimination of 75% of the telangiectasias within 60 days vs. the pre-treatment pattern. The length of vessels was measured on images obtained before and after treatment using ImageJ software. Safety outcomes were analysed immediately, 7 days, and 60 days after the treatment, and included pigmentation. RESULTS: A total of 115 patients were included, 98 of whom completed the study. Sclerotherapy with 0.2% polidocanol + 70% HG was significantly more effective than with 75% HG alone to treat telangiectasias in the target area (82.2% vs. 63.9%; p < .001); considering a minimum improvement of 75%, there was a 0.49 risk reduction (95% confidence interval 0.24-0.98; p = .047). No severe adverse events occurred in either group. Pigmentation was the most common minor adverse event and was significantly shorter in length in the group treated with 0.2% polidocanol + 70% HG (median 0 cm vs. 0.5 cm, respectively; p = .033). CONCLUSION: Polidocanol 0.2% plus 70% HG had better results than 75% HG alone in sclerosing telangiectasias. No severe adverse events occurred. Pigmentation occurred in both groups and was shorter in length in the group treated with 0.2% polidocanol + 70% HG.

Agenesis of the infra-hepatic segment of the inferior vena cava associated with recurrent deep venous thrombosis: case report.

Agenesis of the inferior vena cava (IVC) has been described in less than 1% of the population; a rare occurrence caused by embryonic abnormalities. Its correlation with deep vein thrombosis (DVT) is certainly underestimated, since this change is hard to detect using ultrasound. The aim of the article is to report the case of a 41-year-old female patient with pain and edema up to the top of the right thigh after plastic surgery. Bilateral venous duplex ultrasound revealed bilateral DVT involving iliac-femoral-popliteal and distal segments. Venous angiotomography was requested because the IVC was not visible on ultrasound, revealing thrombosis of the right lumbar plexus and iliofemoral segment bilaterally and agenesis of the infrahepatic segment of the inferior vena cava, with ectasia and compensatory tortuosity of paravertebral veins and the azygos-hemiazygos system, and bilateral pelvic varices. Systemic and oral anticoagulation were administered, with a satisfactory clinical response.

Endovascular treatment with aortic endoprostheses for subclavian artery aneurysm secondary to late traumatic axillary-axillary arteriovenous fistula.

Traumatic arteriovenous fistulas (AVFs) involving the axillary and subclavian vessels are uncommon and account for 5 to 10% of all arterial traumas. The complex anatomy of this region makes treatment of this segment challenging. In this therapeutic challenge, we describe the case of a 73-year-old man, referred for progressive edema and ulceration involving the right upper limb and with a history of gunshot wound to the right infraclavicular region about 50 years previously. Angiotomography was performed and an axillary-axillary AVF was found, associated with tortuosity and aneurysmatic dilation of the subclavian artery downstream. He underwent endovascular intervention and a conical (monoiliac) 26 × 14 × 90 mm Braile® endoprosthesis was used in the aneurysmatic subclavian artery, posterior to the exit of the right vertebral artery and a 16 × 16 × 95mm Excluder® monoiliac endoprosthesis was placed overlapping the first prosthesis, showing a satisfactory result. Therefore, the possibility of successfully using aortic endoprostheses in an unusual and exceptional situation is described.

True isolated deep femoral artery aneurysm associated with peripheral artery disease: case report.

True deep femoral artery aneurysms are extremely rare, accounting for about 0.5% of all peripheral aneurysms. In this report, we describe a 79-year-old male patient with a history of prior abdominal aortic aneurysm surgery via a conventional approach who was admitted to the vascular surgery service at the Hospital das Clínicas with intermittent claudication of the lower limbs. Arterial color-Doppler ultrasonography of the right lower limb was performed, revealing peripheral arterial disease of the femoral--popliteal and infrapatellar segments. Computed tomography angiography identified aortoiliac and bifurcated graft occlusion from the infrarenal segment of the aorta, in addition to a deep femoral artery aneurysm with diameters of 3.7 cm x 3.5 cm and length of 7 cm. Resection of the aneurysm was followed by revascularization of the deep femoral artery by interposition of a Dacron® graft and reimplantation of the superficial femoral artery into the graft. In cases of deep femoral artery aneurysms with concomitant peripheral arterial disease, it is important to ensure revascularization and adequate perfusion of the lower limb.

Endovascular treatment of portal hypertension and recurrent digestive hemorrhage secondary to arterioportal fistula syndrome: late complication of penetrating abdominal trauma.

The arterioportal fistula (APF) syndrome is a rare and reversible cause of pre-sinusoidal portal hypertension, caused by communication between a visceral artery and the portal venous system. Most patients are asymptomatic, but when they do develop symptoms, these are mainly related to gastrointestinal bleeding, ascites, congestive heart failure, and diarrhea. This therapeutic challenge presents a case of APF caused by a 20-year-old stabbing injury with unfavorable late clinical evolution, including significant malnutrition and severe digestive hemorrhages. The patient was treated using an endovascular procedure to occlude of the fistula.

Results of treatment of acute occlusions of limb arteries at a university hospital - retrospective study.

BACKGROUND: Acute arterial occlusions (AAO) in limbs have been increasing in parallel with population longevity. OBJECTIVE: To assess risk factors, limb salvage rates, and survival of patients with AAO treated at a University Hospital. METHODS: Retrospective cohort study of consecutive patients. Outcomes included: patency, symptoms, comorbidities, Rutherford category, arteries occluded, postoperative complications, and 30-day limb salvage and mortality rates. RESULTS: Medical records were evaluated from 105 patients, predominantly males (65.7%), with ages ranging from 46 to 91 years. Etiology: thrombotic (54.3%), embolic (35.2%), and undefined (10.5%). About 2/3 of the patients were assessed as Rutherford category II or III. Associated symptoms: pain (97.1%), coldness (89.5%), pallor (64.7%), sensory loss (44.7%), paralysis (30.5%), anesthesia (21.9%), edema (21.9%), and cyanosis (15.2%). Associated comorbidities: hypertension (65.0%), smoking (59.0%), arrhythmias (26.6%), dyslipidemia (24.0%), and diabetes (23.8%). The distal superficial femoral-popliteal segment was the most affected (80%). Thromboembolectomy with a Fogarty catheter was performed in 73.3% of cases (81.0% of embolic cases, 71.9% of thrombotic cases, and 54.5% of cases with undefined etiology) and was the only treatment used in 41 cases (39.05%), among which there were 11 reocclusion, 20 amputations, and 14 deaths. Arterial reocclusion was more frequent in thrombosis cases (12.9%, p = 0.054). Within 30 days of treatment, total mortality was 14.6%, and 19.8% of cases underwent major amputation, which was less frequent among Rutherford Class I patients (p = 0.0179). CONCLUSION: Treatment of AAO was primarily performed by thromboembolectomy with a Fogarty catheter, either alone or in combination with other treatments, achieving amputation and complication rates compatible with the best results in the literature and were progressively lower in less advanced Rutherford categories.

Photodynamic Therapy Versus Glucose for the Treatment of Telangiectasia: A Randomised Controlled Study in a Rabbit Ear Model.

OBJECTIVES: Telangiectasia is a common venous formation that mainly affects women and causes discomfort, including psychological distress. This study compared photodynamic therapy (PDT) with glucose for vessel sclerosis in a rabbit ear model. METHODS: Thirty-six ears of 18 rabbits were randomly divided into four groups: Group 1: only injection of Photogem (4 mg/mL); Group 2: only light (635 nm, 100 mW/cm2, 8 min, 48 J/cm2); Group 3: glucose 75% injection; Group 4: PDT procedure with injection of Photogem and illumination immediately after. Injections were made into the central ear artery. After injection or sham procedures, manual compression of the marginal vein was maintained for 8 min in all ears. Follow up was immediately after the procedures, and one and six days later. The percentage of length reduction of spider veins, the target vessels, was analysed in digital photographs with Image J software. Ear thermographs were made with a thermocamera device and average temperatures were collected for analysis. Ear biopsies were obtained after six days. Endothelium average, inflammation, fibrosis, necrosis, skin burn, and vascular thrombosis were assessed using a specific score. RESULTS: The mean vessel length reduction was 26% for Group 4, 2.4% for Group 3, .4% for Group 1, and 0 for Group 2, highlighting that in Group 4, the vessel lengths were significantly reduced compared with the other groups (p < .001). In the thermal analysis, in Group 3, the temperature was unchanged from the initial temperature and the central diameter vessel increased after six days, while, in Group 4, the temperature decreased and the vessels were not clearly detected, suggesting a reduction of the vessels and smaller infusion. Histology showed no difference among groups and one case of necrosis was found in Group 4. CONCLUSIONS: PDT was associated with significantly more target vessel sclerosis than glucose injection and controls.

Venous thromboembolism, can we do better? Profile of venous thromboembolism risk and prophylaxis in a University Hospital in the State of São Paulo.

BACKGROUND: Venous thromboembolism (VTE) is a silent and potentially lethal disease that affects a considerable proportion of hospitalized patients. It has high morbidity and mortality and is responsible for a heavy financial burden on healthcare systems. However, VTE can be prevented using prophylaxis measures that have been established in the literature. Nonetheless, in the real world, mean rates of appropriately administered VTE prophylaxis are lower than 50%. OBJECTIVES: To define the epidemiological profile of patients with VTE in a University Hospital and the rate of appropriately administered VTE prophylaxis at that service and to identify measures to improve the rate. METHODS: A cross-sectional, observational study was conducted with data collected from the medical records of patients who met the inclusion criteria. The rates of correct VTE prophylaxis prescribed to clinical and surgical patients were compared, assessed according to guidelines published by the Brazilian Society of Angiology and Vascular Surgery (SBACV), based on VTE risk classification. RESULTS: The overall rate of correctly-prescribed VTE prophylaxis was 42.1%, while 57.9% of patients were not managed correctly in this respect. Clinical patients had a 52.9% rate of appropriate prophylaxis, while the equivalent rate for surgical patients was 37.5%. CONCLUSIONS: Rates of correctly-prescribed VTE prophylaxis are still lower than they should be. Ongoing education, measures to encourage bedside risk stratification, and improvements to the electronic prescription system could increase appropriate VTE prophylaxis rates.

Results of One-Stage or Staged Amputations of Lower Limbs Consequent to Critical Limb Ischemia and Infection.

BACKGROUND: Amputations of lower limbs can be conducted as one-stage amputation (OSA) or staged amputation (SA) procedures. The objective of this study was to analyze technical success and mortality rates of both techniques, as well as factors that might influence outcomes in patients with critical limb ischemia (CLI). METHODS: A retrospective study of 185 consecutive patients with CLI who underwent amputations in the period 2004-2011. Primary end points were rates of technical success (healing without dehiscence or reintervention) and mortality. The influence on outcomes of demographic data, clinical status, and comorbidities was also analyzed by logistic regression. RESULTS: A total of 101 SA (91 patients) and 106 OSA (94 patients) were analyzed. SA had proportionally higher success rate (SA 77.2% vs. OSA 66.0%, P = 0.0253), lower perioperative mortality rate (SA, 10.9% vs. OSA, 20.7%, P = 0.0247), and lower 30-day mortality rate (SA, 12.2% vs. OSA, 23.8%, P = 0.0220) in spite of more cases with Rutherford classes 5 and 6 (SA, 87.1% vs. OSA, 72.6%, P = 0.0047), diabetes (71.2% vs. 55.6%, P = 0.0076), and infection (44.5% vs. 28.3%, P = 0.0061). Logistic regression demonstrated that in SA, success was more frequent in patients with diabetes who did not use insulin (P = 0.0072), in those with transfemoral amputations (P = 0.0392), with no coronary artery disease (P = 0.0053), and in foot infection (P = 0.0446), while for OSA success was more frequent in nondiabetic patients (P = 0.0077), limbs without infection (P = 0.0298), amputations at foot level (P = 0.0155), or transfemoral amputations (P = 0.0030). CONCLUSIONS: SA had a higher rate of technical success and lower mortality rates than OSA, even with greater number of patients with diabetes and more severe cases of ischemia and infection. However, prospective studies comparing both techniques are needed for further evidence.

Inferior gluteal artery pseudoaneurysm after fall from a bicycle: case report.

Pseudoaneurysms of gluteal arteries are rare, especially involving the inferior gluteal artery. They are mainly associated with penetrating trauma, infections, or pelvic fractures. A minority of cases are caused by blunt traumas, with only six cases reported in English. We present a case of pseudoaneurysm of the right inferior gluteal artery after a bicycle fall, presenting with a large hematoma in the gluteal region, observed during clinical examination, and significantly reduced hemoglobin. CT angiography revealed a large hematoma, with contrast extravasation and pseudoaneurysm formation. Angiography revealed that the origin of the lesion was in the right inferior gluteal artery. This artery was embolized with coils. After the procedure, the patient was referred to an intensive care unit, from where he was later transferred to a different hospital, with bleeding controlled. Endovascular treatment of these cases is a safe, fast and an effective option.

Morphofunctional characterization of decellularized vena cava as tissue engineering scaffolds.

Clinical experience for peripheral arterial disease treatment shows poor results when synthetic grafts are used to approach infrapopliteal arterial segments. However, tissue engineering may be an option to yield surrogate biocompatible neovessels. Thus, biological decellularized scaffolds could provide natural tissue architecture to use in tissue engineering, when the absence of ideal autologous veins reduces surgical options. The goal of this study was to evaluate different chemical induced decellularization protocols of the inferior vena cava of rabbits. They were decellularized with Triton X100 (TX100), sodium dodecyl sulfate (SDS) or sodium deoxycholate (DS). Afterwards, we assessed the remaining extracellular matrix (ECM) integrity, residual toxicity and the biomechanical resistance of the scaffolds. Our results showed that TX100 was not effective to remove the cells, while protocols using SDS 1% for 2h and DS 2% for 1h, efficiently removed the cells and were better characterized. These scaffolds preserved the original organization of ECM. In addition, the residual toxicity assessment did not reveal statistically significant changes while decellularized scaffolds retained the equivalent biomechanical properties when compared with the control. Our results concluded that protocols using SDS and DS were effective at obtaining decellularized scaffolds, which may be useful for blood vessel tissue engineering.

Tissue-engineered blood vessel substitute by reconstruction of endothelium using mesenchymal stem cells induced by platelet growth factors.

BACKGROUND: Cardiovascular diseases remain leaders as the major causes of mortality in Western society. Restoration of the circulation through construction of bypass surgical treatment is regarded as the gold standard treatment of peripheral vascular diseases, and grafts are necessary for this purpose. The great saphenous vein is often not available and synthetic grafts have their limitations. Therefore, new techniques to produce alternative grafts have been developed and, in this sense, tissue engineering is a promising alternative to provide biocompatible grafts. This study objective was to reconstruct the endothelium layer of decellularized vein scaffolds, using mesenchymal stem cells (MSCs) and growth factors obtained from platelets. METHODS: Fifteen nonpregnant female adult rabbits were used for all experiments. Adipose tissue and vena cava were obtained and subjected to MSCs isolation and tissue decellularization, respectively. MSCs were subjected to differentiation using endothelial inductor growth factor (EIGF) obtained from human platelet lysates. Immunofluorescence, histological and immunohistochemical analyses were employed for the final characterization of the obtained blood vessel substitute. RESULTS: The scaffolds were successfully decellularized with sodium dodecyl sulfate. MSCs actively adhered at the scaffolds, and through stimulation with EIGF were differentiated into functional endothelial cells, secreting significantly higher quantities of von Willebrand factor (0.85 µg/mL; P < .05) than cells cultivated under the same conditions, without EIGF (0.085 µg/mL). Cells with evident morphologic characteristics of endothelium were seen at the lumen of the scaffolds. These cells also stained positive for fascin protein, which is highly expressed by differentiated endothelial cells. CONCLUSIONS: Taken together, the use of decellularized bioscaffold and subcutaneous MSCs seems to be a potential approach to obtain bioengineered blood vessels, in the presence of EIGF supplementation.

Biocellulose-based hydrogel dressing as a strategy for the management of chronic arterial wounds.

PURPOSE: To evaluate using a biocellulose-based hydrogel as an adjuvant in the healing process of arterial ulcers. METHODS: A prospective single group quasi-experimental study was carried out with chronic lower limb arterial ulcer patients. These patients received biocellulose-based hydrogel dressings and outpatient guidance on dressing and periodic reassessments. The primary outcomes were the ulcer-healing rate and product safety, which were assessed by ulcer area measured in photographic records of pre-treatment and posttreatment after 7, 30, and 60 days. Secondary outcomes were related to clinical assessment by the quality-of-life scores (SF-36 and EQ-5D) and pain, evaluated by the visual analogue scale (VAS). RESULTS: Seventeen participants were included, and one of them was excluded. Six patients (37%) had complete wound healing, and all patients had a significant reduction in the ulcer area during follow-up (233.6mm2 versus 2.7mm2) and reduction on the score PUSH 3.0 (p < 0.0001). The analysis of the SF-36 and EQ-5D questionnaires showed a statistically significant improvement in almost all parameters analyzed and with a reduction of pain assessed by the VAS. CONCLUSIONS: The biocellulose-based hydrogel was safe and showed a good perspective to promoting the necessary conditions to facilitate partial or complete healing of chronic arterial ulcers within a 60-day follow-up. Quality of life and pain were positively affected by the treatment.

Nebulized enriched heparin improves respiratory parameters in patients with COVID-19: a phase I/II randomized and triple-blind clinical trial.

To evaluate the safety and the potential antiviral treatment of inhaled enriched heparin in patients with COVID-19. The specific objectives were to investigate the anticoagulation profile, antiviral and anti-inflammatory effects, and respiratory evolution of inhaled enriched heparin. We conducted a randomized, triple-blind, placebo-controlled Phase I/II clinical trial in hospitalized adults with COVID-19 receiving inhalation of enriched heparin or saline (placebo) every 4 h for 7 days. Among the 27 patients who completed the study, no changes in blood coagulation parameters were observed, indicating the safety of inhaled enriched heparin. The group receiving enriched heparin showed a significant reduction in the need for supplemental oxygen and improvement in respiratory parameters, such as the PaO2/FiO2 ratio. Inhalation of enriched heparin is shown to be safe and has also demonstrated potential therapeutic benefits for patients with COVID-19. These promising results justify the continuation of the study to the next phase, Phase II/III, to further evaluate the therapeutic efficacy of inhaled enriched heparin in the treatment of COVID-19-associated viral pneumonia.Trial registration: ClinicalTrials.gov. 08/02/2021. Identifier: NCT04743011.