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Over the past 25 years, we have demonstrated the feasibility of airway bioengineering using stented aortic matrices experimentally then in a first-in-human trial (n = 13). The present TRITON-01 study analyzed all the patients who had airway replacement at our center to confirm that this innovative approach can be now used as usual care. For each patient, the following data were prospectively collected: postoperative mortality and morbidity, late airway complications, stent removal and status at last follow-up on November 2, 2021. From October 2009 to October 2021, 35 patients had airway replacement for malignant (n = 29) or benign (n = 6) lesions. The 30-day postoperative mortality and morbidity rates were 2.9% (n = 1/35) and 22.9% (n = 8/35) respectively. At a median follow-up of 29.5 months (range 1-133 months), 27 patients were alive. There have been no deaths directly related to the implanted bioprosthesis. Eighteen patients (52.9%) had stent-related granulomas requiring a bronchoscopic treatment. Ten among 35 patients (28.6%) achieved a stent free survival. The actuarial 2- and 5-year survival rates (Kaplan-Meier estimates) were respectively 88% and 75%. The TRITON-01 study confirmed that airway replacement using stented aortic matrices can be proposed as usual care at our center. Clinicaltrials.gov Identifier: NCT04263129.
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Estenosis de la Válvula Aórtica , Bioprótesis , Prótesis Valvulares Cardíacas , Adulto , Humanos , Estenosis de la Válvula Aórtica/cirugía , Estudios de Seguimiento , Complicaciones Posoperatorias , Stents , Resultado del TratamientoRESUMEN
Aims: Long noncoding RNAs (lncRNAs) play key roles in the pathophysiology of DKD involving actions of microRNAs (miRNAs). The aims of the study were to establish the involvement of selected lncRNAs in the epigenetic mechanisms of podocyte damage and tubular injury in DKD of type 2 diabetes mellitus (DM) patients in relation to a particular miRNAs profile. Methods: A total of 136 patients with type 2 DM and 25 healthy subjects were assessed in a cross-sectional study concerning urinary albumin: creatinine ratio (UACR), eGFR, biomarkers of podocyte damage (synaptopodin, podocalyxin) and of proximal tubule (PT) dysfunction (Kidney injury molecule-1-KIM-1, N-acetyl-D-glucosaminidase-NAG), urinary lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), nuclear-enriched abundant transcript 1 (NEAT1), myocardial infarction-associated transcript (MIAT), taurine-upregulated gene 1 (TUG1), urinary miRNA21, 124, 93, 29a. Results: Multivariable regression analysis showed that urinary lncMALAT1 correlated directly with urinary synaptopodin, podocalyxin, KIM-1, NAG, miRNA21, 124, UACR, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.727); urinary lncNEAT1 correlated directly with synaptopodin, KIM-1, NAG, miRNA21, 124, and negatively with eGFR, miRNA93, 29a (p<0.0001; R2=0.702); urinary lncMIAT correlated directly with miRNA93 and 29a, eGFR (p<0.0001; R2=0.671) and negatively with synaptopodin, KIM-1, NAG, UACR, miRNA21, 124 (p<0.0001; R2=0.654); urinary lncTUG1 correlated directly with eGFR, miRNA93, 29a, and negatively with synaptopodin, podocalyxin, NAG, miRNA21, 124 (p<0.0001; R2=0.748). Conclusions: In patients with type 2 DM lncRNAs exert either deleterious or protective functions within glomeruli and PT. LncRNAs may contribute to DKD through modulating miRNAs expression and activities. This observation holds true independently of albuminuria and DKD stage.
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Diabetes Mellitus Tipo 2/complicaciones , Nefropatías Diabéticas/genética , Túbulos Renales Proximales/fisiopatología , Podocitos/fisiología , ARN Largo no Codificante/metabolismo , Adulto , Anciano , Biomarcadores/metabolismo , Biomarcadores/orina , Estudios Transversales , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatología , Diabetes Mellitus Tipo 2/orina , Nefropatías Diabéticas/fisiopatología , Nefropatías Diabéticas/orina , Femenino , Regulación de la Expresión Génica/fisiología , Humanos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Factores Protectores , ARN Largo no Codificante/orina , Factores de Riesgo , Adulto JovenRESUMEN
Cannabis sativa L. (hemp) is a plant used in the textile industry and green building material industry, as well as for the phytoremediation of soil, medical treatments, and supplementary food products. The synergistic effect of terpenes, flavonoids, and cannabinoids in hemp extracts may mediate the biogenic synthesis of metal nanoparticles. In this study, the chemical composition of aqueous leaf extracts of three varieties of Romanian hemp (two monoecious, and one dioecious) have been determined by Fourier-Transformed Infrared spectroscopy (FT-IR), high-performance liquid chromatography, and mass spectrometry (UHPLC-DAD-MS). Then, their capability to mediate the green synthesis of silver nanoparticles (AgNPs) and their pottential antibacterial applications were evaluated. The average antioxidant capacity of the extracts had 18.4 ± 3.9% inhibition determined by 2,2-diphenyl-1-picrylhydrazyl (DPPHâ¢) and 78.2 ± 4.1% determined by 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS™) assays. The total polyphenolic content of the extracts was 1642 ± 32 mg gallic acid equivalent (GAE) L-1. After this, these extracts were reacted with an aqueous solution of AgNO3 resulting in AgNPs, which were characterized by UV-VIS spectroscopy, FT-IR, scanning electron microscopy (SEM-EDX), and dynamic light scattering (DLS). The results demonstrated obtaining spherical, stable AgNPs with a diameter of less than 69 nm and an absorbance peak at 435 nm. The mixture of extracts and AgNPs showed a superior antioxidant capacity of 2.3 ± 0.4% inhibition determined by the DPPH⢠assay, 88.5 ± 0.9% inhibition as determined by the ABTSâ¢+ assay, and a good antibacterial activity against several human pathogens: Escherichia coli, Klebsiella pneumoniae, Pseudomonas fluorescens, and Staphylococcus aureus.
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Antibacterianos/química , Cannabis/química , Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Extractos Vegetales/química , Antioxidantes/química , Hojas de la Planta/química , Polifenoles/análisis , Plata/químicaRESUMEN
We report for the first time on the antimicrobial activity of MgB2 powders produced via the Reactive Liquid Infiltration (RLI) process. Samples with MgB2 wt.% ranging from 2% to 99% were obtained and characterized, observing different levels of grain aggregation and of impurity phases. Their antimicrobial activity was tested against Staphylococcus aureus ATCC BAA 1026, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. A general correlation is observed between the antibacterial activity and the MgB2 wt.%, but the sample microstructure also appears to be very important. RLI-MgB2 powders show better performances compared to commercial powders against microbial strains in the planktonic form, and their activity against biofilms is also very similar.
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Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial. Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices. Design, Setting, and Participants: Uncontrolled single-center cohort study including 20 patients with end-stage tracheal lesions or with proximal lung tumors requiring a pneumonectomy. The study was conducted in Paris, France, from October 2009 through February 2017; final follow-up for all patients occurred on November 2, 2017. Exposures: Radical resection of the lesions was performed using standard surgical techniques. After resection, airway reconstruction was performed using a human cryopreserved (-80°C) aortic allograft, which was not matched by the ABO and leukocyte antigen systems. To prevent airway collapse, a custom-made stent was inserted into the allograft. In patients with proximal lung tumors, the lung-sparing intervention of bronchial transplantation was used. Main Outcomes and Measures: The primary outcome was 90-day mortality. The secondary outcome was 90-day morbidity. Results: Twenty patients were included in the study (mean age, 54.9 years; age range, 24-79 years; 13 men [65%]). Thirteen patients underwent tracheal (n = 5), bronchial (n = 7), or carinal (n = 1) transplantation. Airway transplantation was not performed in 7 patients for the following reasons: medical contraindication (n = 1), unavoidable pneumonectomy (n = 1), exploratory thoracotomy only (n = 2), and a lobectomy or bilobectomy was possible (n = 3). Among the 20 patients initially included, the overall 90-day mortality rate was 5% (1 patient underwent a carinal transplantation and died). No mortality at 90 days was observed among patients who underwent tracheal or bronchial reconstruction. Among the 13 patients who underwent airway transplantation, major 90-day morbidity events occurred in 4 (30.8%) and included laryngeal edema, acute lung edema, acute respiratory distress syndrome, and atrial fibrillation. There was no adverse event directly related to the surgical technique. Stent removal was performed at a postoperative mean of 18.2 months. At a median follow-up of 3 years 11 months, 10 of the 13 patients (76.9%) were alive. Of these 10 patients, 8 (80%) breathed normally through newly formed airways after stent removal. Regeneration of epithelium and de novo generation of cartilage were observed within aortic matrices from recipient cells. Conclusions and Relevance: In this uncontrolled study, airway bioengineering using stented aortic matrices demonstrated feasibility for complex tracheal and bronchial reconstruction. Further research is needed to assess efficacy and safety. Trial Registration: clinicaltrials.gov Identifier: NCT01331863.
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Aorta/trasplante , Bioingeniería/métodos , Bronquios/cirugía , Neoplasias Pulmonares/cirugía , Stents , Tráquea/cirugía , Enfermedades de la Tráquea/cirugía , Adulto , Anciano , Autoinjertos , Estudios de Factibilidad , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Neumonectomía , Procedimientos de Cirugía Plástica/métodos , Tráquea/patología , Enfermedades de la Tráquea/patología , Estenosis Traqueal/cirugíaRESUMEN
OBJECTIVE: We aimed to assess the feasibility and diagnostic performance of ultrasound-guided bone biopsies at the bedside of diabetic patients admitted for suspected foot osteitis not requiring surgery. RESEARCH DESIGN AND METHODS: In this retrospective monocentric study, we compared the performance of ultrasound-guided (n = 29 consecutive patients, Dec.2020-Oct.2022) versus surgical (n = 24 consecutive patients, Jan.2018-Nov.2020) bone biopsies at confirming or ruling out diabetic foot osteitis (primary outcome). RESULTS: Patient characteristics were similar in the two intervention groups, including arteritis prevalence (62.3 %), SINBAD score, and wound location (phalanges 36 %, metatarsus 43 %, and calcaneus 21 %). However, the ultrasound-guided group was older (67 ± 11 versus 60 ± 13 years respectively, P = 0.047) and had more type 2 diabetes (97 % versus 75 %, P = 0.038). Diagnostic performance (i.e., capacity to confirm or rule out suspected osteitis) was similar for ultrasound-guided (28/29 cases: 25 confirmations, 3 invalidations) and surgical (24 confirmations/24) biopsies, P = 0.358. No biopsy-related side effect or complication was observed for either intervention, even for patients on antiaggregation and/or anticoagulation therapy. The mean (± standard deviation) time necessary to perform the biopsy was shorter in the ultrasound-guided group (2.6 ± 3.0 versus 7.2 ± 5.8 days, respectively, P < 0.001) and wound evolution at three months was more favorable (83.3 versus 41.2 %, P = 0.005) (94.4 % versus 66.7 %, respectively, patients with new surgical procedure within six months excluded; P = 0.055). Even though not statistically significant, healing rates in terms of wound and osteitis at six months were also better in the ultrasound-guided group (wound: 40.9 % versus 36.8 %; P = 0.790, and osteitis: 81.8 vs 55.6 % P = 0.071). CONCLUSION: In diabetic patients with suspected foot osteitis not requiring surgery, bedside ultrasound-guided bone biopsies may constitute a promising alternative to surgical biopsies. This intervention provided excellent tolerance and microbiological documentation, short lead-times, and more favorable wound prognosis.
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Pie Diabético , Biopsia Guiada por Imagen , Humanos , Pie Diabético/diagnóstico por imagen , Masculino , Femenino , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Biopsia Guiada por Imagen/métodos , Osteítis , Ultrasonografía Intervencional/métodos , Huesos/patología , Huesos/diagnóstico por imagenRESUMEN
Lung cancer represents the most lethal cancer worldwide. Surgery is the treatment of choice for early-stage non-small cell lung cancer, with an overall survival that can reach 90% at 5 years, but its detection is difficult to achieve due to the lack of symptoms. Screening programs are crucial to identify small cancer. Minimally invasive surgery has modified the therapeutical approach of these tumors, becoming the standard of care, with an important clinical yield in terms of reduction of postoperative pain and length of hospital stay. The aim of this mini-review is to explore and describe two important and innovative aspects in the context of "growing opportunities in minimally invasive thoracic surgery": the clinical application of augmented reality and its advantages for patient and surgeon, and the pedagogical issue through simulation-based training.
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Layered zinc hydroxynitrate (ZHN), with the chemical formula Zn5 (OH)8 (NO3)2·2H2O, exhibits a range of special properties such as anion-exchange and intercalation capacity, as well as biocompatibility, making it attractive for a large variety of applications in fields from nanotechnology to healthcare and agriculture. In this study nanocrystalline ZHN doped with 1,000 ppm Mn2+ was prepared by two synthesis methods (coprecipitation and solid state reaction) using similar environment-friendly precursors. The complex morpho-structural [X-ray diffraction, scanning and transmission electron microscopy, textural analysis] and spectroscopic [Fourier transform infrared and electron paramagnetic resonance (EPR)] characterization of the two ZHN nanopowders showed similar crystalline structures with Mn2+ ions localized in the nanocrystals volume, but with differences in their morphological and textural characteristics, as well as in the doping efficiency. ZHN obtained by coprecipitation consists of larger nanoplatelets with more than two times larger specific surface area and pore volume, as well as a dopant concentration than in the ZHN sample obtained by solid state reaction. The thermal stability and the on-set of the structural phase transformation have been investigated at atomic scale with high accuracy by EPR, using Mn2+ as paramagnetic probes. The on-set of the ZHN structural phase transformation toward ZnO was observed by EPR to take place at 110°C and 130°C for the samples prepared by coprecipitation and solid state reaction, respectively, evidencing a manganese induced local decrease of the transformation temperature. Our results contribute to the selection of the most appropriate ZHN synthesis method for specific applications and in the development of new green, cost-effective synthesis routes for Mn2+ doped nano-ZnO.
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Objective: Recent studies have demonstrated the feasibility and favorable long-term results of tracheobronchial replacement using stented cryopreserved aortic allografts. We propose to investigate the outcomes of this emerging technique in the subgroup of patients with extensive tracheal cancer. Methods: This study was based on 13 patients with primary extensive tracheal cancer extracted from the prospective registry TRITON-01 (ClinicalTrials.gov Identifier: NCT04263129), which included 40 patients in total. We analyzed early and late outcomes in this subset of patients. Results: From March 2019 to September 2022, 13 patients were included in the study. There were 9 female and 4 male patients, with a mean age of 53.9 years [36-71 years]. They had tracheal replacement for extended adenoid cystic carcinoma (n = 11), squamous cell carcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). A venovenous extracorporeal membrane oxygenation was used in the 6 last cases. The mean length of resection was 81 mm [50-120 mm]. There was no 30-day postoperative mortality. A complete resection (R0) was achieved in 11 patients. The main late complications consisted of tracheal granulomas related to the stent and requiring repeated bronchoscopies (n = 9), pneumonia (n = 3), airway infection (n = 1), bronchoesophageal fistula (n = 1), mechanical stent obstruction requiring change (n = 2), and mediastinitis treated by antibiotics, drainage, and omentoplasty (n = 1). With a maximal follow-up of 3 years and 7 months, cancer recurrence was observed in 2 patients. All patients were alive at last follow-up except 2 (84.6%). Conclusions: Airway replacement using stented CAA represents a feasible and promising solution for extensive tracheal cancer.
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Introduction: The novel Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARSCoV-2), has spread rapidly to become a major global public health emergency since March 2020. Laryngotracheal stenosis (LTS) has been observed more frequently since the onset of the COVID-19 pandemic. Methods: All patients referred to our 24/7 Airway Diseases Center for laryngotracheal post-intubation/tracheostomy stenosis from May 2020 to May 2021were evaluated retrospectively. Patient data on comorbidities, diagnosis, type of procedures, lengths of ICU stay and invasive mechanical ventilation, medical treatment, and the severity of illness were recorded. Results: This case series included nine patients (five women and four men), with a mean age of 52.9 years, most with a BMI >30, all with a severe illness revealed by the Simplified Acute Physiology Score (SAPS) II >31. From May 2020 to May 2021, 21 procedures were performed on seven patients, consisting of bronchoscopic rigid interventions, T-tube Montgomery tracheostomy, and one cricotracheal resection with end-to-end anastomosis. Histologic examination of tracheal biopsies showed an inflammatory state of the airway mucosa. Two patients only had medical therapy. Discussion and Conclusions: Pneumonia caused by SARSCoV-2 can lead to severe acute respiratory distress syndrome (ARDS) requiring invasive mechanical ventilation. The time of intubation, the drugs used, the prone position, comorbidities (diabetes, obesity), and the inflammatory state of the upper airways linked to the viral infection, predispose to an increased tendency to stenosis and its recurrence. A conservative approach with medical and endoscopic treatment should be preferred in case of persistence of local airways inflammation. Further studies with a larger sample of patients will help to a better understanding of the disease, reduce the prevalence, and improve its treatment.
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BACKGROUND: Surgical lung biopsy is essential in the diagnostic algorithm of interstitial lung disease (ILD) of unknown cause. Safety concerns have been recently reiterated. This study prospectively assessed the yield of diagnosis and safety of video-assisted thoracoscopic surgical lung biopsy (VATS-LB) for ILD diagnosis. METHODS: This prospective study, conducted in 6 ILD-referral Paris hospitals, included 103 patients with ILD. VATS-LB was proposed after initial multidisciplinary discussion. A final diagnosis was made after the procedure, during a second multidisciplinary discussion. The main outcome was to determine the final diagnoses and their proportion after VATS-LB. Other outcomes were the percentage of change in diagnosis and treatment propositions after VATS-LB and adverse events during 3 months after the operation, postoperative pulmonary function, quality of life, and pain. RESULTS: A definite diagnosis was reached in 87 patients (84.4%), and 16 remained unclassifiable (15.6%). After VATS-LB, the hypothesized diagnosis changed in 65 patients (63.1%) and treatment changed in 41 patients (39.8%). One patient died of acute exacerbation. In-hospital complications were predicted by a shorter preoperative 6-minute walking test distance and by forced vital capacity lower than 77%. Postoperative quality of life was not modified at 3 months, whereas forced vital capacity decreased slightly. Postoperative neuropathic pain was revealed in 5% of patients at 1 month and in 2% at 3 months. CONCLUSIONS: VATS-LB dramatically changed preoperative hypothetical diagnoses and treatment in ILD of unknown cause, with good patient survival in ILD referral centers.
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Enfermedades Pulmonares Intersticiales , Cirugía Torácica Asistida por Video , Humanos , Estudios Prospectivos , Cirugía Torácica Asistida por Video/efectos adversos , Estudios Retrospectivos , Enfermedades Pulmonares Intersticiales/diagnóstico , Enfermedades Pulmonares Intersticiales/cirugía , Biopsia/métodos , Pulmón/patologíaRESUMEN
Lung transplantation is still the only curative treatment for end-stage pulmonary diseases. The results remain poor, however, because of the limited availability of lung donors, chronic rejection, and complications related to immunosuppressive therapy. The use of a bioartificial lung generated from autologous cells could offer a solution. We have demonstrated that in vivo epithelial and cartilage regeneration of the airways is feasible with the use of an aortic tissue matrix. Other studies show that in vitro and in vivo airway regeneration, respectively, can be obtained by using bio-engineering and heterotopic allograft implantation. A more complex challenge is the creation of an artificial lung Indeed, this would require the use of an elastic matrix that can promote regeneration of the different lung components (airways, alveoli, vessels) over a large surface area, thus allowing ventilation, blood perfusion and gas exchanges. Recent studies have demonstrated the possibility of in vitro and in vivo regeneration of lung tissue from autologous cells, and especially stem cells. This emerging research field is currently dominated by the use of decellularized lung matrices and autologous epithelial and endothelial cells. Implantation of such a recellularized matrix in animals has proved the feasibility of a functional bio-artificial lung. The first human transplantation of a bio-artificial lung should be possible within 10-20 years.
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Órganos Bioartificiales , Pulmón/fisiología , Regeneración , Trasplante de Células Madre , Diferenciación Celular/fisiología , Humanos , Pulmón/citología , Trasplante de PulmónRESUMEN
Goethite based nanocomposites with a different composition such as 6FeO(OH)·MnO(OH)·0.5H2O (Mn-composite), xFeO(OH)·M(OH)2·yH2O (Co-composite (M: Co, x = 12, y = 3), Ni-composite (M: Ni, x = 7, y = 2)) and xFeO(OH)·MO·yH2O (Cu-composite (M: Cu, x = 5.5, y = 3), Zn-composite (M: Zn, x = 6, y = 1.5)) have been prepared by a soft chemical synthesis consisting in acetate hydrolysis. The data provided by Fourier transform infrared (FTIR), ultraviolet-visible-near infrared (UV-Vis-NIR), electron paramagnetic resonance (EPR) and Mössbauer spectra account for a slight modification of all composites' physicochemical properties compared to the starting material. Powder X-ray diffraction and transmission electron microscopy (TEM) investigations revealed the secondary phase nature and presence along with that of goethite. The TEM data are also consistent with a nano rod-like morphology with a 5-10 nm width and an average length of 40 nm. The catalytic oxidation of cyclooctene with O2 using isobutyraldehyde as reductant and acetonitrile as a solvent was performed in batch conditions for 5 h at room temperature. The selectivity for the epoxide was higher than 99% for all tested solids. The conversion of cyclooctene decreased from 55% to 4% following the same order of variance as the base/acid sites ratio: Mn-composite > Fe-composite > Co-composite > Ni-composite > Zn-composite > Cu-composite. The 6FeO(OH)·MnO(OH)·0.5H2O (Mn-composite) exhibited the most promising catalytic activity in cyclooctene oxidation, which can be correlated with the redox ability of Mn(iii) combined with the increased base character of this solid. The catalytic activity of this sample decreases by 10% after several successive reaction cycles.
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Background Pulmonary inflammatory pseudotumors are rare lesions that remain problematic in several aspects, especially regarding the therapeutic strategy. The goal of this study was to evaluate long-term survival in a multicenter series of patients who required surgery for pulmonary inflammatory pseudotumors. Methods Thirty-six cases of pulmonary inflammatory pseudotumors, operated on in 3 French thoracic surgery departments between 1989 and 2015, were studied retrospectively. We recorded pre-, peri- and postoperative data for each patient, and long-term survival was analyzed. Results There were 22 men and 14 women. Mean age was 53.5 years (range 14-81 years). Three pneumonectomies, 1 bilobectomy, 19 lobectomies, 2 segmentectomies, 10 wedge resections, and 1 biopsy were performed. Complete resection was carried out in 32 (88.8%) patients. Median follow-up was 76 months. Five-year and 10-year survival rates were respectively 86.8% and 81.7% (96% and 90% for patients with R0 resection). Conclusions Long-term survival was excellent for patients with pulmonary inflammatory pseudotumors who benefited from surgery, especially when surgical resection was complete. These results confirm that surgical resection must be proposed as the first-line treatment for patients with pulmonary inflammatory pseudotumors.
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Granuloma de Células Plasmáticas del Pulmón/cirugía , Neumonectomía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Francia , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Granuloma de Células Plasmáticas del Pulmón/diagnóstico por imagen , Granuloma de Células Plasmáticas del Pulmón/mortalidad , Neumonectomía/efectos adversos , Neumonectomía/mortalidad , Estudios Retrospectivos , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Airway transplantation remains a major challenge in thoracic surgery. Based on our previous laboratory work, we developed the techniques required to bioengineer a tracheal substitute in vivo using cryopreserved aortic allografts as biological matrices (Replacement of the Airways and/or the Pulmonary Vessels Using a Cryopreserved Arterial Allograft [TRACHEOBRONCART] Study, NCT01331863). We present here 2 patients who had a definitive tracheostomy for complex laryngotracheal stenoses refractory to conventional therapy. METHODS: According to our protocol, a stented gender-mismatched -80°C cryopreserved aortic allograft was used for airway reconstruction. Follow-up assessments were done at regular intervals using clinical, imaging, and endoscopic evaluations. Immunohistochemical and XX/XY chimerism studies were performed at time of stent removal using graft biopsy specimens. Chemotactic and angiogenic properties of implanted matrices were also investigated. RESULTS: At a maximal follow-up of 5 years and 7 months, the patients were breathing and speaking normally, without tracheostomy or stent. Regeneration of cartilage within the aortic grafts was demonstrated by positive immunodetection of type II collagen and markers specific for Sox9. Chimerism study from samples of neotissues demonstrated that regenerated cartilage came from recipient cells. The remaining viable matrix cells released a functionally relevant amount of proangiogenic, chemoattractant, proinflammatory/immunomodulatory cytokines, and growth factors. CONCLUSIONS: This report documents the feasibility of in vivo tissue engineering for long-term functional airway transplantation in humans.
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Aorta/trasplante , Enfermedades de la Laringe/cirugía , Ingeniería de Tejidos/métodos , Tráquea/fisiología , Estenosis Traqueal/cirugía , Adulto , Criopreservación , Femenino , Humanos , Masculino , Persona de Mediana Edad , Stents , Tráquea/citología , Tráquea/cirugía , Trasplante HomólogoRESUMEN
After more than 50 years of research, airway transplantation remains a major challenge in the fields of thoracic surgery and regenerative medicine. Five principal types of tracheobronchial substitutes, including synthetic prostheses, bioprostheses, allografts, autografts and bioengineered conduits have been evaluated experimentally in numerous studies. However, none of these works have provided a standardized technique for the replacement of the airways. More recently, few clinical attempts have offered encouraging results with ex vivo or stem cell-based engineered airways and tracheal allografts implanted after heterotopic revascularization. In 1997, we proposed a novel approach: the use of aortic grafts as a biological matrix for extensive airway reconstruction. In vivo regeneration of epithelium and cartilage were demonstrated in animal models. This led to the first human applications using cryopreserved aortic allografts that present key advantages because they are available in tissue banks and do not require immunosuppressive therapy. Favorable results obtained in pioneering cases have to be confirmed in larger series of patients with extensive tracheobronchial diseases.
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Medicina Regenerativa , Tráquea/trasplante , Animales , Aorta/fisiología , Humanos , Ingeniería de Tejidos , Andamios del Tejido/químicaRESUMEN
Anterior mediastinal tracheostomy (AMT) is a rare but challenging operation associated with a high morbidity and mortality rate mainly related to the invasiveness of the procedure. In order to provide a more conservative technique with a lower risk of major postoperative complications, we proposed: (1) to reduce the extent of chest wall resection to only a trapezoidal segment of the manubrium; (2) to use a simple pedicle pectoralis major flap instead of myocutaneous or omental flaps; and (3) to perform a simple relocation of the residual trachea (RT) below the brachiocephalic artery instead of artery ligation, percutaneous stent placement or replacement by cadaveric allograft. This technique was used in a patient with cancer recurrence at the cervical stoma after total laryngectomy. Despite a short 2.5-cm RT, it was possible to perform AMT without any tension at the mediastinal stoma. Postoperative course showed only regressive minor complications. There was no late complication related to the procedure with a one-year follow-up. This more conservative technique for AMT could be used as an alternative to previously described procedures in order to reduce postoperative complications and mortality rate after sub-total resection of the trachea.
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Carcinoma de Células Escamosas/cirugía , Neoplasias Laríngeas/cirugía , Laringectomía , Recurrencia Local de Neoplasia , Tráquea/cirugía , Traqueostomía/métodos , Adulto , Carcinoma de Células Escamosas/patología , Francia , Humanos , Neoplasias Laríngeas/patología , Laringectomía/efectos adversos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos , Músculos Pectorales/cirugía , Reoperación , Colgajos Quirúrgicos , Técnicas de Sutura , Tomografía Computarizada por Rayos X , Tráquea/diagnóstico por imagen , Traqueostomía/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: Pneumonectomies for lung cancer are associated with a high postoperative mortality, especially when right-sided, after neoadjuvant radiochemotherapy, and in patients over 70 years of age. Preliminary studies in our laboratory have shown that aortic grafts could be valuable airway substitutes. We report the first human bronchial transplantation of a cryopreserved aortic allograft used as a biologic airway substitute to prevent a pneumonectomy for lung cancer. METHODS: The procedure was performed in a high-risk 78-year old patient with an extensive right bronchopulmonary malignant tumor pretreated with chemotherapy. After a complete resection of the lung cancer using an upper bilobectomy with lymph node removal, mobilization procedures did not allow for a primary end-to-end bronchial anastomosis. A stent-supported cryopreserved aortic allograft from a certified tissue bank was interposed to restore the bronchial continuity with sparing of the lower lobe. RESULTS: The postoperative course was eventful for a supraventricular arrhythmia leading to mild pulmonary edema that resolved using standard medical therapy, and a right lower lobe atelectasis with bacterial colonization that required fiberoptic bronchoscopies in addition to antibiotic treatment. A 1-year postoperative evaluation found a well-functioning reimplanted lower lobe with no complications related to the cryopreserved aortic allograft or the stent. The patient recovered to his baseline activity with a satisfying health-related quality of life. CONCLUSIONS: We demonstrate the feasibility of this surgical innovation to prevent the high-risk procedure of pneumonectomy in a single case. If confirmed in larger series of selected patients, it could bring new perspectives in conservative lung cancer surgery.
Asunto(s)
Aorta/trasplante , Bronquios/cirugía , Materiales Biocompatibles Revestidos , Neoplasias Pulmonares/cirugía , Neumonectomía/métodos , Stents , Trasplante de Tejidos/métodos , Anciano , Criopreservación , Estudios de Seguimiento , Humanos , Masculino , Diseño de PrótesisRESUMEN
BACKGROUND: Pneumonectomy is well known for a high risk of postoperative death. The alternative, sleeve lobectomy, is sometimes technically inaccessible, and is associated with locoregional recurrence. In certain situations, the use of a bronchial substitute would allow longer bronchial resections with better security margins. Previous experiments demonstrated that aortic grafts are valuable tracheal and carinal substitutes. The present study evaluated bronchial replacement with arterial allografts. METHODS: Fifteen female sheep underwent a left bilobectomy with replacement of the bronchus intermedius with arterial allografts: 5 received a fresh graft (group 1) and 10 received cryopreserved (group 2). A bronchial silicone stent was used to confer rigidity. Evaluation was conducted on clinical and histologic criteria at regular intervals up to 18 months. RESULTS: There were no perioperative deaths. Atelectasis, the only early postoperative complication (n = 2), was successfully treated by fiberscopic aspiration. The late postoperative period was uneventful in 12 sheep. Complications included 1 bronchopneumonia, 1 pulmonary abscess, and 1 distortion of the bronchial stent. Fiberscopic examination revealed 3 sheep with granuloma formation. The bronchial stent was removed in 3 sheep, 1 at 9 months and 2 at 12 months, without clinical complications or stenosis of the graft. Histologic analysis showed regeneration of new bronchial tissue, comprising epithelium and cartilage. CONCLUSIONS: This study confirmed that an arterial allograft could be a valuable bronchial substitute. The use of a bronchial substitute offers new perspectives in surgical resection of lung cancer because it would avoid pneumonectomy in some patients.