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.

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.

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.

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.

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.

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.

Quantitative analysis validation for sclerotherapy treatment of lower limb telangiectasias.

BACKGROUND: The evaluation of sclerotherapy efficacy for lower limb telangiectasias, which is the standard treatment for such condition, is commonly assisted by scores based on before and after pictures. This method is marked by its subjectivity, which impairs the precision of studies on the subject, making it unfeasible to evaluate and compare different interventions. We hypothesize that a quantitative method for evaluating the effectiveness of sclerotherapy for lower limb telangiectasias may present more reproducible results. Reliable measurement methods and new technologies may become part of the clinical practice in the near future. METHODS: Before and after treatment photographs were analyzed using a quantitative method and compared with a validated qualitative method based on improvement scores. Reliability analysis of the methods was performed, applying the intraclass correlation coefficient (ICC) and kappa coefficient with quadratic weights (Fleiss Cohen), for analysis of inter-examiner and intra-examiner agreement in both evaluation methods. Convergent validity was evaluated by applying the Spearman test. To assess the applicability of the quantitative scale, the Mann-Whitney test was used. RESULTS: A better agreement between examiners is shown for the quantitative scale, with a mean kappa of .3986 (.251-.511) for qualitative analysis and a mean kappa of .788 (.655-.918) for quantitative analysis (P < .001 for all examiners). Convergent validity was achieved by correlation coefficients of .572 to .905 (P < .001). The quantitative scale results obtained between the specialists with different degrees of experience did not show statistical difference (seniors: 0.71 [-0.48/1.00] × juniors: 0.73 [-0.34/1.00]; P = .221). CONCLUSIONS: Convergent validity between both analyses has been achieved, but quantitative analysis has been shown to be more reliable and can be applied by professionals of any degree of experience. The validation of quantitative analysis is a major milestone for the development of new technology and automated, reliable, applications.

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.

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.

Transcutaneous Neuromodulation for Constipation and Fecal Incontinence in Children: A Systematic Review and Meta-Analysis.

INTRODUCTION: Constipation is a disorder with a multifactorial origin. Constipation has a varied clinical presentation, including infrequent defecation of bulky stools and episodes of retentive fecal incontinence. Neuromodulation has been used to treat many health problems, with promising results. OBJECTIVE: To conduct a systematic review of randomized clinical trials based on the effects of transcutaneous neuromodulation in treating constipation and retentive fecal incontinence in children and adolescents. METHODS: A systematic review of randomized clinical trials was performed. Medline (PubMed), PEDro, SciELO, Cochrane (CENTRAL), Embase, and Scopus databases were searched from March 2000 to August 2022. We included clinical trials evaluating transcutaneous neuromodulation in children with constipation and fecal incontinence compared or associated with other types of treatment. Two reviewers independently selected relevant studies, assessed the methodological quality, and extracted the data. RESULTS: Three studies with 164 participants were included in this review. Two meta-analyses were generated based on these studies. These analyses revealed that transcutaneous neuromodulation is an effective adjuvant treatment modality that improves children's constipation and retentive fecal incontinence. The methodological quality of the included studies was classified as high based on the assessment of the quality of evidence, with a high degree of confidence based on the GRADE system. CONCLUSIONS: Transcutaneous neuromodulation is an effective adjuvant treatment modality for children with constipation and retentive fecal incontinence.

Carcinoma espinocelular sobre cicatriz de fístula arteriovenosa: relato de caso / Squamous cell carcinoma on an arteriovenous fistula scar: case report

Resumo A fístula arteriovenosa (FAV) é o principal acesso para hemodiálise devido à sua patência superior e menores índices de complicação quando comparada aos demais acessos para hemodiálise. Relatamos o caso de uma paciente do sexo feminino, de 69 anos, com doença renal crônica dialítica secundária a nefroesclerose hipertensiva com FAV radio-cefálica no membro superior esquerdo realizada há 9 anos. Há 2 anos, foi submetida a transplante renal e fazia uso de imunossupressores. Evoluiu com aparecimento de lesão crostosa em antebraço esquerdo há 3 meses, foi submetida a biópsia excisional, e foi evidenciado carcinoma espinocelular bem diferenciado e superficialmente invasivo, com margens cirúrgicas laterais e profundas livres de neoplasia. No seguimento de 1 ano, a paciente não apresentava sinais de recidiva neoplásica.

Abstract 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.

Comparação das alterações angiográficas entre pacientes diabéticos e não diabéticos com doença arterial periférica / Comparative study of angiographic changes in diabetic and non-diabetic patients with peripheral arterial disease

Resumo Contexto Os diabéticos possuem risco de 5 a 15 vezes maior para o desenvolvimento de doença arterial periférica (DAP), e poucos estudos compararam fatores de risco e a distribuição e gravidade de alterações arteriais angiográficas entre diabéticos e não diabéticos. Objetivos Comparar alterações angiográficas entre pacientes diabéticos e não diabéticos com DAP avançada, correlacionando-as com demais fatores de risco. Métodos Trata-se de um estudo transversal retrospectivo de pacientes consecutivos submetidos a arteriografia de membros inferiores por DAP (Rutherford de 3 a 6), usando os escores angiográficos TASC II e de Bollinger et al. Os critérios de exclusão incluíram arteriografias de membros superiores, exames incompletos ou sem nitidez e cirurgias prévias. A análise estatística incluiu o teste do qui-quadrado ou exato de Fisher para variáveis discretas e o teste t para variáveis contínuas (significância: p < 0,05). Resultados Foram estudados 153 pacientes com idade média de 67 anos, sendo 50,9% do sexo feminino e 58,2% diabéticos. Um total de 91 pacientes (59%) tinha lesão trófica (Rutherford 5 ou 6), enquanto 62 (41%) tinham dor em repouso ou claudicação limitante (Rutherford 3 e 4). Entre os diabéticos, 81,7% eram hipertensos, 29,4% nunca fumaram e 14% tinham antecedente de infarto do miocárdio. Pelo escore de Bollinger et al., as artérias infrapoplíteas foram as mais comprometidas, em especial a tibial anterior (p = 0,005) nos diabéticos, enquanto a femoral superficial foi mais acometida nos não diabéticos (p = 0,008). Pelo TASC II, as alterações arteriográficas mais graves ocorreram no segmento fêmoro-poplíteo nos pacientes não diabéticos (p = 0,019). Conclusões Os setores infrapoplíteos foram os mais comprometidos nos diabéticos, enquanto o setor femoral foi o mais acometido nos não diabéticos.

Abstract 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.

Pós-processamento da mediana de escala de cinza (GSM), posterização e remapeamento de cores para ultrassonografia de carótidas / Grayscale median (GSM) post-processing, posterizing, and color mapping for carotid ultrasound

Resumo Fatores relativos à placa aterosclerótica podem indicar instabilidade como ulcerações, hemorragias intraplaca, núcleo lipídico, capa fibrosa delgada ou irregular e inflamação. A mediana de escala de cinza (GSM, de greyscale median) da placa é um dos métodos mais difundidos de estudo da placa aterosclerótica; nesse sentido, é importante criar uma padronização da pós-processamento de forma compreensível. O pós-processamento foi realizado no software Photoshop 23.1.1. A padronização da imagem foi alcançada com o ajuste de curvas do histograma de escalas de cinza definindo o ponto mais escuro do lúmen vascular (sangue) para zero e a adventícia distal para 190. A posterização e o remapeamento de cores foram realizados. Um método que apresenta o atual estado da arte da técnica de forma acessível e ilustrativa pode contribuir para disseminação da análise de GSM. Neste artigo, esse processo é demonstrado passo a passo.

Abstract 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.

Elastografia por cisalhamento (shear wave) para placas ateroscleróticas carotídeas extracranianas: princípios técnicos e como realizar / Shear wave elastography for extracranial carotid atherosclerotic plaques: technical principles and how to do it

Resumo Na esteira de estudos direcionados à placa aterosclerótica e em busca de variáveis quantificáveis que adicionem informações à tomada de decisão terapêutica, a avaliação a partir de elastografia shear wave (SWE) se apresenta como alternativa reprodutível e promissora. Utilizamos um único aparelho Logiq S8 (General Electric, Boston, Massachusetts, Estados Unidos) com um transdutor linear multifrequencial 8,5-11 MHz em 10 MHz em corte longitudinal. Consideramos critérios relevantes para a aquisição de imagem: adequada insonação longitudinal, diferenciação do complexo médio-intimal, delineamento de túnicas adventícias proximal e distal, lúmen vascular, boa visualização da placa aterosclerótica, ciclo em diástole ventricular e ausência de alterações incongruentes. A SWE é um método emergente e extremamente promissor no contexto da avaliação de placas carotídeas, podendo contribuir no futuro para a tomada de decisão terapêutica baseada em características relativas à placa aterosclerótica de forma reprodutível entre aparelhos e examinadores.

Abstract 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.

Evaluation of Biointegration and Inflammatory Response to Blood Vessels Produced by Tissue Engineering-Experimental Model in Rabbits.

Peripheral arterial disease (PAD) is the main cause of mortality in the western population and requires surgical intervention with the use of vascular substitutes, such as autologous veins or Dacron or PTFE prostheses. When this is not possible, it progresses to limb amputation. For cases where there is no autologous vascular substitute, tissue engineering with the production of neovessels may be a promising option. Previous experimental studies have shown in vitro that rabbit vena cava can be decellularized and serve as a scaffold for receiving mesenchymal stem cells (MSC), with subsequent differentiation into endothelial cells. The current study aimed to evaluate the behavior of a 3D product structure based on decellularized rabbit inferior vena cava (IVC) scaffolds seeded with adipose-tissue-derived stem cells (ASCs) and implanted in rabbits dorsally subcutaneously. We evaluated the induction of the inflammatory response in the animal. We found that stem cells were positive in reducing the inflammatory response induced by the decellularized scaffolds.

Urinary Bladder Patch Made with Decellularized Vein Scaffold Seeded with Adipose-Derived Mesenchymal Stem Cells: Model in Rabbits.

BACKGROUND: To evaluate tissue regeneration of the urinary bladder after the implantation of a decellularized vein sown with autologous adipose-derived mesenchymal stem cells (ASC) on luminal surfaces. METHODS: New Zealand rabbits (n = 10) were distributed in two groups: Group Bioscaffold alone (G1)-decellularized vena cava (1 cm2) was implanted, and Group Bioscaffold plus ACSs (G2)-decellularized vena cava (1 cm2) containing ASCs were implanted. ASCs were expanded, characterized, and maintained for one week in culture with a decellularized vein scaffold. The implants were performed under general anesthesia using a continuous suture pattern. Afterward, 21 d (day) specimens were collected and analyzed by hematoxylin and eosin (HE) histology and scanning electron microscopy (SEM). RESULTS: The integrity of the urinary bladder was maintained in both groups. A superior regenerative process was observed in the G2 group, compared to the G1 group. We observed a greater urothelial epithelialization and maturity of the mucosa and submucosa fibroblasts. Furthermore, SEM demonstrated a notable amount of urothelial villus in the G2 group. CONCLUSION: Decellularized vena cava scaffolds were able to maintain the integrity of the urinary bladder in the proposed model. In addition, ASCs accelerated the regenerative process development, observed primarily by the new urothelial epithelization and the maturity of mucosa and submucosa fibroblasts.