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.

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.

Nebulized enriched heparin to treat no critical patients with Sars-Cov-2: Triple-blind clinical trial.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a viral respiratory disease that spreads rapidly, reaching pandemic status, causing the collapse of numerous health systems, and a strong economic and social impact. The treatment so far has not been well established and there are several clinical trials testing known drugs that have antiviral activity, due to the urgency that the global situation imposes. Drugs with specific mechanisms of action can take years to be discovered, while vaccines may also take a long time to be widely distributed while new virus variants emerge. Thus, drug repositioning has been shown to be a good strategy for defining new therapeutic approaches. Studies of the effect of enriched heparin in the replication of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) in vitro assays justify the advance for clinical tests. METHODS AND ANALYSIS: A phase I/II triple-blind parallel clinical trial will be conducted. Fifty participants with radiological diagnosis of grade IIA pneumonia will be selected, which will be allocated in 2 arms. Participants allocated in Group 1 (placebo) will receive nebulized 0.9% saline. Participants allocated in Group 2 (intervention) will receive nebulized enriched heparin (2.5 mg/mL 0.9% saline). Both groups will receive the respective solutions on a 4/4 hour basis, for 7 days. The main outcomes of interest will be safety (absence of serious adverse events) and efficacy (measured by the viral load).Protocols will be filled on a daily basis, ranging from day 0 (diagnosis) until day 8.

Quantification of adhesion of mesenchymal stem cells spread on decellularized vein scaffold.

PURPOSE: To evaluate methods that improve adipose-derived stem cells (ASCs) population in decellularized biological venous scaffold for tissue engineering in blood vessels, a model in rabbits. METHODS: The ASC was expanded until the third passage. Inferior vena cava (IVC) was submitted to the decellularization process using 1% sodium dodecyl sulfate (SDS) or 2% sodium deoxycholate (SD) to compose 12 study groups (G): pure SD or SDS, exposed or not to 1% TritonX-100 (TX-100) and exposed or not to poly-l'lysine and laminin (PL). Scaffolds were covered with 1 × 105 or 1 × 106 ASCs diluted in 10 µL Puramatrix™. The histological analysis was done by cell counting in hematoxylin and eosin (HE) and nuclei count in immunofluorescence (IF) with 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI). RESULTS: The study of groups in HE and IF showed similar results. For both analyses,IVC-SD-1 × 106 ASC and IVC-SD-PL-1 × 106 ASC provided the best results. The IF technique showed better sensitivity than HE, with a weak agreement between them. CONCLUSIONS: Decellularizing agent and the number of ASC influence scaffolds cellularization response and the best protocols as those ones using SD with or without the addition of PL.

Association between deep vein thrombosis and stent patency in symptomatic iliac vein compression syndrome: Systematic review and meta-analysis.

BACKGROUND: The study intended to evaluate stent primary patency rates for patients with iliac vein obstruction related with iliac vein compression syndrome according to clinic presentation. METHODS: A systematic review and meta-analysis was conducted of studies that compared: unexposed patients with nonthrombotic iliac vein lesion (NIVL, group 1) vs exposed patients with iliac acute deep vein thrombosis (DVT, group 2); and NIVL (group 1) vs exposed patients with iliac vein obstruction and post-thrombotic syndrome (PTS, group 3). The following databases were searched: EMBASE, PubMed, Web of Science, Scopus, SciELO, and LILACS. Two reviewers independently selected the potential studies and extracted data. The pooled odds ratio (OR) and 95% confidence interval (95% CI) are shown for each outcome. RESULTS: Five studies with a total of 1050 participants and 1169 lower limbs were included. Five hundred eighty-eight lower limbs presented NIVL (50.3%), 91 lower limbs presented acute DVT (7.7%), and 490 lower limbs presented PTS (42%). The endovascular technical success rate of stenting did not differ in any of the groups: 99.6% in NIVL, 94.5% in acute DVT, and 96.5% in PTS (P = .0632). The primary stent patency rates in the 6-month follow-up were 98.3% in NIVL vs 90.9% in PTS, with a statistical difference showing reduced stent patency rates in PTS (OR, 0.17; 95% CI, 0.06-0.48; P = .0008; I2 = 0%), and 100% in the NIVL group vs 91.6% in acute DVT, with no statistical difference (OR, 0.30; 95% CI, 0.06-2.32; P = .30; I2 = 0%). The primary stent patency rates in the 12-month follow-up were 94.6% in NIVL vs 84.1% in PTS, with a statistical difference showing decreases stent patency rates in the PTS group (OR, 0.29; 95% CI, 0.14-0.63; P = .0008; I2 = 0%), and 91.1% in NIVL vs 90.9% in acute DVT, with no statistical difference (OR, 1.03; 95% CI, 0.26-4.07; P = .96; I2 = 0%). CONCLUSIONS: There is no statistical difference for the stent primary patency rates when the treatment is conducted in NIVL as compared with acute DVT lower limbs (at 6 and 12 months); therefore, other criteria must be considered for the indication of this treatment in NIVL patients. However, because there were better results of stent primary patency rates for NIVL vs PTS patients, this finding favors the treatment of acute DVT instead of PTS in lower limbs, once PTS renders smaller stent patency rates at 6 and 12 months.

Quantification of adhesion of mesenchymal stem cells spread on decellularized vein scaffold

ABSTRACT Purpose: To evaluate methods that improve adipose-derived stem cells (ASCs) population in decellularized biological venous scaffold for tissue engineering in blood vessels, a model in rabbits. Methods: The ASC was expanded until the third passage. Inferior vena cava (IVC) was submitted to the decellularization process using 1% sodium dodecyl sulfate (SDS) or 2% sodium deoxycholate (SD) to compose 12 study groups (G): pure SD or SDS, exposed or not to 1% TritonX-100 (TX-100) and exposed or not to poly-l'lysine and laminin (PL). Scaffolds were covered with 1 × 105 or 1 × 106 ASCs diluted in 10 μL Puramatrix™. The histological analysis was done by cell counting in hematoxylin and eosin (HE) and nuclei count in immunofluorescence (IF) with 4',6-Diamidine-2'-phenylindole dihydrochloride (DAPI). Results: The study of groups in HE and IF showed similar results. For both analyses,IVC-SD-1 × 106 ASC and IVC-SD-PL-1 × 106 ASC provided the best results. The IF technique showed better sensitivity than HE, with a weak agreement between them. Conclusions: Decellularizing agent and the number of ASC influence scaffolds cellularization response and the best protocols as those ones using SD with or without the addition of PL.