Amarilio Vieira de Macedo Neto

Tratamento agressivo com retalho muscular e/ou omentopexia nas infecções do esterno e mediastino anterior em pós-operatório de esternotomia

OBJECTIVE: To evaluate the impact of an aggressive treatment approach using muscle flaps or omentopexy in infections of the sternum and anterior mediastinum following sternotomy on mortality, as compared to that of a conservative treatment approach. METHODS: Data were collected prior to, during and after the surgical procedures. Group A (n = 44) included patients submitted to conservative treatment-debridement together with resuture or continuous irrigation with polyvinylpyrrolidone-iodine solutions, or even with second-intention wound healing (retrospective data). Group B (n = 9) included patients in whom infection was not resolved with conservative treatment, and who therefore underwent aggressive treatment (intermediate phase). Group C (n = 28) included patients primarily submitted to aggressive treatment (prospective data). RESULTS: Postoperative hospital stays were shorter in the patients submitted to aggressive treatment (p < 0.046). There were 7 deaths in group A, 1 in group B, and 2 in group C. However, the classical level of significance of α = 0.05 was not reached. CONCLUSION: Aggressive treatment also proved to be effective when the infection was not resolved with conservative treatment. These findings demonstrate that the proposed treatment provides excellent results.

Desenvolvimento de uma órtese de Dumon modificada para aplicações traqueais: um estudo experimental em cães

OBJECTIVE: To describe the development of a silicone stent and perform in vivo testing for biocompatibility/applicability in the normal canine trachea. METHODS: Four different densities were tested in order to obtain the silicone prototypes. The pressure required for compression considering a contact area of 1 cm2, and a 30% reduction in diameter was calculated for each density. The best density was 70-75 Shore A hardness. Powdered barium sulfate was added to the silicone to make the stent radiopaque and easily identifiable in radiological imaging. This novel stent presents a corrugated external surface with discontinuous and protruding arcs resembling the tracheobronchial rings (for intercalation and fixation in the lumen of the lower airways), a highly polished inner surface and smooth extremities (to prevent friction-related damage). The prototype considered most appropriate in terms of rigidity and flexibility was bronchoscopically implanted in normal canine tracheas. After eight weeks, the animals were euthanized, and the tracheas were removed for anatomopathological analysis. RESULTS: There were no postimplantation complications, and none had to be removed. After eight weeks, the devices were found to be well-positioned. Histopathology revealed a well-preserved epithelial basal membrane, foci of denuded epithelium, mild submucosal inflammatory infiltrate with scattered granulation tissue, vascular neoformation, and no microorganisms. CONCLUSIONS: The stent developed proved resistant to mechanical stress, biocompatible in the canine trachea and well-preserved at the study endpoint.

A correção das estenoses traqueobrônquicas mediante o emprego de órteses

O tratamento cirurgico do paciente com estenose traqueobronquica exige uma avaliacaoindividualizada em razao da complexidade de sua origem, sendo a traqueoplastia considerada amodalidade ideal. As causas mais comuns de estenose sao devidas a intubacao traqueal e aodesenvolvimento de neoplasias e estas condicoes sao justamente as que mais se beneficiam com otratamento endoscopico quando a correcao cirurgica nao esta indicada. Na atualidade, os meiosendoscopicos incluem a aplicacao de diversos tipos de

Combined Bone Marrow‐Derived Mesenchymal Stromal Cell Therapy and One‐Way Endobronchial Valve Placement in Patients with Pulmonary Emphysema: A Phase I Clinical Trial

One‐way endobronchial valves (EBV) insertion to reduce pulmonary air trapping has been used as therapy for chronic obstructive pulmonary disease (COPD) patients. However, local inflammation may result and can contribute to worsening of clinical status in these patients. We hypothesized that combined EBV insertion and intrabronchial administration of mesenchymal stromal cells (MSCs) would decrease the inflammatory process, thus mitigating EBV complications in severe COPD patients. This initial study sought to investigate the safety of this approach. For this purpose, a phase I, prospective, patient‐blinded, randomized, placebo‐controlled design was used. Heterogeneous advanced emphysema (Global Initiative for Chronic Lung Disease [GOLD] III or IV) patients randomly received either allogeneic bone marrow‐derived MSCs (108 cells, EBV+MSC) or 0.9% saline solution (EBV) (n = 5 per group), bronchoscopically, just before insertion of one‐way EBVs. Patients were evaluated 1, 7, 30, and 90 days after therapy. All patients completed the study protocol and 90‐day follow‐up. MSC delivery did not result in acute administration‐related toxicity, serious adverse events, or death. No significant between‐group differences were observed in overall number of adverse events, frequency of COPD exacerbations, or worsening of disease. Additionally, there were no significant differences in blood tests, lung function, or radiological outcomes. However, quality‐of‐life indicators were higher in EBV + MSC compared with EBV. EBV + MSC patients presented decreased levels of circulating C‐reactive protein at 30 and 90 days, as well as BODE (Body mass index, airway Obstruction, Dyspnea, and Exercise index) and MMRC (Modified Medical Research Council) scores. Thus, combined use of EBV and MSCs appears to be safe in patients with severe COPD, providing a basis for subsequent investigations using MSCs as concomitant therapy. Stem Cells Translational Medicine 2017;6:962–969

Fissure Integrity and Volume Reduction in Emphysema: A Retrospective Study

Background: One-way endobronchial valves (EBVs) relieve symptoms of emphysema, particularly in patients without collateral ventilation between the target and adjacent lobes. Pretreatment knowledge of fissure integrity could serve as an aid in indicating EBV interventions. Objective: This study aimed to investigate the relationship between software-measured lung fissure integrity and clinically relevant lung volume reduction (≥350 ml) in emphysema patients treated with one-way EBVs using a lobar exclusion strategy. Methods: Of 108 patients treated between March 2008 and July 2014, 38 had both baseline and follow-up computed tomography (CT) scans acquired following a specific protocol for quantitative CT analysis and were included in the study (total of 39 treatments, two lungs treated in 1 patient). Outcome measures were fissure integrity measured on baseline CT scans, difference between pre- and postoperative lung volume (considering the lowest measured postoperative volume), and correlation between fissure integrity and volume change. Results: Fissure integrity ≥75% correlated with volume reduction ≥350 ml (Spearman coefficient: -0.65; p < 0.01). The mean and median volume reductions were 1,223.96 ± 907.5 ml and 663 ml, respectively, for lungs with fissure integrity ≥75% (n = 31). The accuracy of fissure integrity ≥75% in predicting a volume reduction was 87.2%. The positive predictive value of fissure integrity ≥75% to predict a volume reduction ≥350 ml was 83.9%, and it was 70% for fissure integrity 75-90% and 90.5% for fissure integrity >90%. Conclusions: A target lobe volume reduction using EBVs is possible with lung fissure integrity ≥75%. For patients with fissure integrity between 75 and 90%, a further evaluation of interlobar ventilation should be performed. A clinically relevant volume reduction following treatment with EBVs is likely with any level of fissure integrity >90%.

Novel Silicone Stent to Treat Tracheobronchial Lesions: Results of 35 Patients

We describe a case series of 35 patients with either benign (14) or malignant (21) tracheal stenosis who were treated using a novel silicone stent, the HCPA-1, designed to prevent migration. Between March 2001 and September 2008, 13 women and 22 men received 41 HCPA-1 stents. The median duration of stenting in benign cases was 457 days (range, 4–2, 961 days). Successful stent removal with curative results was accomplished in 2 patients with tracheomalacia and 1 with post-intubation stenosis. In malignant cases, the median duration of stenting was 162 days (range, 1–1, 279 days). Five patients had tumor progression with obstruction requiring repeated laser resection, dilatation, or additional stents. Two patients died due to airway obstruction despite bronchoscopic intervention. Twelve patients with malignant lesions died with the stent in place. At the end of the study, 3 patients with malignant disease remained alive; 2 were lost to follow-up. The HCPA-1 stent proved to be safe, with no severe complications during the study period, and effective in improving quality of life with relief of dyspnea.

Modelo experimental de estenose traqueal mediante ressecção cirúrgica submucosa de anéis traqueais combinada com instilações de hidróxido de sódio

OBJECTIVE To experimentally develop tracheal stenosis and malacia to test new models of tracheal stents. METHODS We resected three cartilaginous rings from the cervical trachea of dogs in group A (n = 5) and six rings in group B (n = 4) to produce malacia. The mucosa of the region with malacia then received applications of a solution of sodium hydroxide (NaOH) at 23%, and the animals were accompanied with bronchoscopic examinations to observe the development of luminal narrowing of the airway. When the stenosis was of more than 50% or there were minimal signs of ventilatory failure, the animals were sacrificed. The segment of narrowed airway was then collected for histological analysis and calculation of the area of residual lumen in the tracheal segment with stenosis and malacia. RESULTS In histological analysis, fibrosis was found in the submucosa and adventitia, associated with granulomas in the mucosa. The average residual lumen of the segments with stenosis was 9% and 12% in groups A and B, respectively (p> 0.05). CONCLUSION The combination of resection of the cartilaginous rings and the application of 23% NaOH in the respiratory mucosa promoted severe tracheal stenosis, but was associated with loss of animals. Further studies are needed to verify that the isolated use of one of the techniques would be safer and more effective to develop tracheal stenosis.

Rejection and indirect revascularization of glycerin-preserved tracheal implant.

The objective of the following study was to evaluate antigenicity, malacia and revascularization in glycerin-preserved canine tracheal allografts. Trachea with six cartilage rings (2.4 to 3.1 cm) were distributed in three study groups: autograft (21), allograft (18) and glycerin-preserved (22). We implanted two segments from different groups in the greater omentum of dogs. After 28 days, latex was injected in the canine aorta before the segments were harvested. We evaluated number of sectors with functional vessels, number of vessels dyed in the submucosa, acute arteritis score, incidence of acute rejection, cartilage lesion score, and malacia. The autograft group had a larger number of dyed vessels than the glycerin-preserved group. The autograft group also had a higher average number of quadrants with functional vessels than the allograft group and the glycerin-preserved group. The allograft group had a higher mean score for acute arteritis than the autograft group and more acute rejection than the glycerin-preserved group. The cartilage lesion score did not show any significant difference between groups. Malacia was not observed in any tracheal segment. Overall, the glycerin-preserved tracheal implant had low antigenicity and good rigidity, but showed incomplete revascularization.

Polydimethylsiloxane/nano calcium phosphate composite tracheal stents: Mechanical and physiological properties: POLYDIMETHYLSILOXANE/NANOCALCIUM PHOSPHATE COMPOSITE TRACHEAL STENTS

In this study, we report the production and characterization of tracheal stents composed of polydimethylsiloxane/nanostructured calcium phosphate composites obtained by reactive synthesis. Tracheal stents were produced by transfer molding, and in vivo tests were carried out. PDMS was combined with H3 PO4 and Ca(OH)2 via an in situ reaction to obtain nanoparticles of calcium phosphate dispersed within the polymeric matrix. The incorporation of bioactive inorganic substances, such as calcium phosphates, improved biological properties, and the in situ reaction allowed tight coupling of particles to the matrix. Results showed the presence of the nanoparticles of DCPA and CDHA. The porosity generated during mixing decreased the tensile strength and tear properties. Composites presented higher values of cell viability compared with those for PDMS. In vivo tests indicated the presence of inflammatory tissue 30 days after implantation in both cases. Thus, the present biomaterial shows potential for application in tracheal disease, however further evaluation is needed.

Vascular endothelial growth factor gene therapy induces early re-establishment of canine bronchial circulation §,§§

OBJECTIVE To evaluate the usefulness of gene therapy with human vascular endothelial growth factor 165 (phVEGF(165)) to promote the early re-establishment of systemic arterial perfusion in canine bronchi deprived of bronchial circulation. METHODS To disrupt bronchial circulation, dogs were submitted to transversal bronchotomy dividing the left mainstem bronchus into a proximal and a distal portion. phVEGF(165) (VEGF group, n=8) or physiologic saline solution (control group, n=8) were then delivered to the left distal bronchus. After that, the airway was reconstituted with interrupted suture. On day 3, nine dogs (four VEGF and five controls) were euthanized and their left distal bronchi were harvested to evaluate VEGF(165) gene expression by reverse transcription-polymerase chain reaction. In the other dogs (four VEGF and three controls), a microvascular dye was injected through the canine aorta to verify the re-establishment of arterial blood supply to the distal bronchus. Additionally, VEGF immunohistochemistry was performed in distal airway specimens. RESULTS Microvascular dye was observed in 100% of specimens transfected with phVEGF(165) compared to none in controls. VEGF gene expression (p<0.01) and VEGF protein expression (p<0.05) were higher in VEGF(165)-treated bronchi. CONCLUSIONS Local transfection with phVEGF(165) promoted the early re-establishment of systemic arterial perfusion to bronchi previously deprived of bronchial circulation. Gene therapy with phVEGF(165) may be a useful tool to restore bronchial circulation by promoting early airway angiogenesis.