137 results on '"Paolo Macchiarini"'
Search Results
2. Publisher Correction: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Johannes C. Haag, Greg Lemon, Philipp Jungebluth, Silvia Baiguera, Cristian Ibarra, Paolo Macchiarini, Rainer Heuchel, Karolina Kublickiene, Doris A. Taylor, Peter Damberg, Bertrand Joseph, Alessandra Bianco, Domenico Ribatti, Antonio B. Rodriguez, Ylva Gustafsson, Miguel Angel Burguillos, Sebastian Sjöqvist, Mei Ling Lim, Costantino Del Gaudio, Alexander Sotnichenko, Ying Zhao, Heike Kielstein, and Henrik Ullman
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medicine.medical_specialty ,Science ,Myocytes, Smooth Muscle ,MEDLINE ,General Physics and Astronomy ,General Biochemistry, Genetics and Molecular Biology ,Orthotopic transplantation ,Esophagus ,Medicine ,Animals ,Regeneration ,Multidisciplinary ,Tissue engineered ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Published Erratum ,General surgery ,Correction ,Cell Differentiation ,Mesenchymal Stem Cells ,General Chemistry ,Rats ,business ,Immunocompetence - Abstract
A tissue-engineered oesophageal scaffold could be very useful for the treatment of pediatric and adult patients with benign or malignant diseases such as carcinomas, trauma or congenital malformations. Here we decellularize rat oesophagi inside a perfusion bioreactor to create biocompatible biological rat scaffolds that mimic native architecture, resist mechanical stress and induce angiogenesis. Seeded allogeneic mesenchymal stromal cells spontaneously differentiate (proven by gene-, protein and functional evaluations) into epithelial- and muscle-like cells. The reseeded scaffolds are used to orthotopically replace the entire cervical oesophagus in immunocompetent rats. All animals survive the 14-day study period, with patent and functional grafts, and gain significantly more weight than sham-operated animals. Explanted grafts show regeneration of all the major cell and tissue components of the oesophagus including functional epithelium, muscle fibres, nerves and vasculature. We consider the presented tissue-engineered oesophageal scaffolds a significant step towards the clinical application of bioengineered oesophagi.
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- 2018
3. Uniportal Videothoracoscopic Surgery: Our Indications and Limits
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Massimo Osvaldo Jaus, Paolo Macchiarini, Natalia Battisti, Alessandro Gonfiotti, Daniel Barale, and Domenico Viggiano
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Adult ,Lung Diseases ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,Operative Time ,Young Adult ,medicine ,Humans ,Thoracic Wall ,Aged ,Retrospective Studies ,Pain, Postoperative ,Solitary pulmonary nodule ,Thoracic Surgery, Video-Assisted ,business.industry ,Pneumothorax ,Solitary Pulmonary Nodule ,Retrospective cohort study ,General Medicine ,Middle Aged ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Cardiothoracic surgery ,Operative time ,Cardiology and Cardiovascular Medicine ,business ,Neurilemmoma ,Thoracic wall - Abstract
Objective We present our experience with uniportal videothoracoscopic surgery (VATS-U), examining its indications, limits, and results. Methods Since January 2009, 66 patients underwent VATS-U for the following indications: pneumothorax (n = 25), lung nodule (n = 15; n = 10 with preoperative radiolocalization), wedge biopsy (n = 15), hyperhidrosis (n = 10), and chest wall schwannoma (n = 1). The conversion rate to conventional video-assisted thoracic surgery (VATS), postoperative pain, complications, residual paraesthesia, and hospitalization were analyzed. Operative time, postoperative pain, and paraesthesia were retrospectively compared with a cohort of 172 cases of conventional multiportal VATS, performed in the same period. Results Conversion to traditional VATS was necessary in two cases (pulmonary nodule, n = 1; pneumothorax, n = 1). The mean pain score was 0.8, the mean operation time was 42 minutes, and 10 patients had postoperative paraesthesia that lasted a mean of 7 days. No postoperative complications were reported, and the mean postoperative hospital stay was 3 days (range, 1–6 days). The comparison between the VATS-U and the standard multiportal VATS group showed in the VATS-U group a lower but not statistically significant pain score and paraesthesia as well as a lower and statistically significant operative time. Conclusions Uniportal videothoracoscopic surgery has a wide range of indications: lung apex resections and pleurodesis for spontaneous pneumothorax treatment; pulmonary nodule assessment with or without preoperative localization; lung biopsy for interstitial diseases; unilateral or bilateral sympathectomy to treat hyperhidrosis; benign chest wall tumor evaluation. The limits of this technique are linked to pleural adhesions or lung nodules in difficult positions. In our experience, VATS-U results in minimal postoperative pain, allowing for fast functional recovery and a consequent short hospital stay; thus, we suggest that VATS-U is a valid alternative to traditional multiportal VATS for indications beyond cosmetic benefits. Prospective randomized trials are necessary to validate the advantages of uniportal VATS.
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- 2015
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4. Retraction Note: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Silvia Baiguera, Johannes C. Haag, Henrik Ullman, Bertrand Joseph, Paolo Macchiarini, Alessandra Bianco, Doris A. Taylor, Karolina Kublickiene, Costantino Del Gaudio, Mei Ling Lim, Domenico Ribatti, Ying Zhao, Ylva Gustafsson, Philipp Jungebluth, Heike Kielstein, Cristian Ibarra, Antonio Beltrán Rodríguez, Alexander Sotnichenko, Rainer Heuchel, Peter Damberg, Greg Lemon, Miguel Angel Burguillos, and Sebastian Sjöqvist
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0301 basic medicine ,Pathology ,medicine.medical_specialty ,Multidisciplinary ,Tissue engineered ,business.industry ,Science ,General Physics and Astronomy ,General Chemistry ,General Biochemistry, Genetics and Molecular Biology ,Retraction ,03 medical and health sciences ,030104 developmental biology ,Orthotopic transplantation ,Medicine ,business - Abstract
Nature Communications 5: Article number: 3562 (2014); Published 15 April 2014; Updated 21 March 2017 This Article is retracted by the authors. Nature Communications previously issued an Editorial Expression of Concern (http://www.nature.com/articles/ncomms13310) related to this Article, following the publication of a report commissioned by The Karolinska Institute and prepared by the Expert Group for Misconduct in Research at the Swedish Central Ethical Review Board.
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- 2017
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5. Tracheal tissue engineering in rats
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Philipp Jungebluth, Paolo Macchiarini, Greg Lemon, Johannes C. Haag, Ivar Dehnisch, Alessandra Bianco, Per Uhlén, Mei Ling Lim, Silvia Baiguera, Antonio Beltrán Rodríguez, Ylva Gustafsson, Costantino Del Gaudio, and Sebastian Sjöqvist
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Decellularization ,Tissue Engineering ,Tissue Scaffolds ,Guided Tissue Regeneration ,business.industry ,Settore ING-IND/22 - Scienza e Tecnologia dei Materiali ,Cellular differentiation ,Regeneration (biology) ,Rat model ,Nanofibers ,General Biochemistry, Genetics and Molecular Biology ,Biomechanical Phenomena ,Rats ,Trachea ,Orthotopic transplantation ,Tissue engineering ,Electrospun nanofibers ,Animals ,Medicine ,Colorimetry ,Viability assay ,business ,Biomedical engineering - Abstract
Tissue-engineered tracheal transplants have been successfully performed clinically. However, before becoming a routine clinical procedure, further preclinical studies are necessary to determine the underlying mechanisms of in situ tissue regeneration. Here we describe a protocol using a tissue engineering strategy and orthotopic transplantation of either natural decellularized donor tracheae or artificial electrospun nanofiber scaffolds into a rat model. The protocol includes details regarding how to assess the scaffolds' biomechanical properties and cell viability before implantation. It is a reliable and reproducible model that can be used to investigate the crucial aspects and pathways of in situ tracheal tissue restoration and regeneration. The model can be established in
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- 2014
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6. Ethics of bioengineering organs and tissues
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Doris A. Taylor, Paolo Macchiarini, and Arthur L. Caplan
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Pharmacology ,Clinical Trials as Topic ,medicine.medical_specialty ,Tissue Engineering ,Ethical issues ,business.industry ,Clinical Biochemistry ,Alternative medicine ,Bioengineering ,Bioethics ,Clinical Practice ,Clinical trial ,Organ Culture Techniques ,Drug Discovery ,medicine ,Humans ,Engineering ethics ,business - Abstract
Tissue-engineered medical products are now entering the clinical testing phase of development. Therefore, an open discussion is warranted regarding ethical issues that may arise as these novel 'combination' products move forward, such as when to conduct clinical trials, how to regulate such trials, when and how to responsibly introduce these strategies into clinical practice and how to maintain a positive public perception of the tissue-engineering field as a whole. These issues are discussed, and recommendations are provided for conducting first-in-human clinical studies.
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- 2014
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7. RETRACTED: Airway Transplantation
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Philipp Jungebluth and Paolo Macchiarini
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Pulmonary and Respiratory Medicine ,Transplantation ,medicine.medical_specialty ,business.industry ,medicine ,Surgery ,business ,Airway - Published
- 2014
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8. The first tissue-engineered airway transplantation: 5-year follow-up results
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Camilla E. Comin, Oriol Sibila, Paolo Macchiarini, Alessandro Gonfiotti, Silvia Baiguera, Federico Lavorini, Philipp Jungebluth, Giovanni Rombolà, Daniel Barale, Massimo Osvaldo Jaus, and Giovanni A. Fontana
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Cough reflex ,General Medicine ,Anastomosis ,medicine.disease ,Malacia ,Surgery ,Transplantation ,Bronchoscopy ,medicine ,Respiratory function ,Teratoma ,business ,Airway - Abstract
Summary Background In 2008, the first transplantation of a tissue-engineered trachea in a human being was done to replace an end-staged left main bronchus with malacia in a 30-year-old woman. We report 5 year follow-up results. Methods The patient was followed up approximately every 3 months with multidetector CT scan and bronchoscopic assessment. We obtained mucosal biopsy samples every 6 months for histological, immunohistochemical, and electron microscopy assessment. We also assessed quality of life, respiratory function, cough reflex test, and production and specificity of recipient antibodies against donor human leucocyte antigen. Findings By 12 months after transplantation, a progressive cicatricial stenosis had developed in the native trachea close to the tissue-engineered trachea anastomosis, which needed repeated endoluminal stenting. However, the tissue-engineered trachea itself remained open over its entire length, well vascularised, completely re-cellularised with respiratory epithelium, and had normal ciliary function and mucus clearance. Lung function and cough reflex were normal. No stem-cell-related teratoma formed and no anti-donor antibodies developed. Aside from intermittent bronchoscopic interventions, the patient had a normal social and working life. Interpretation These clinical results provide evidence that a tissue-engineering strategy including decellularisation of a human trachea, autologous epithelial and stem-cell culture and differentiation, and cell-scaffold seeding with a bioreactor is safe and promising. Funding European Commission, Knut and Alice Wallenberg Foundation, Swedish Research Council, ALF Medicine.
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- 2014
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9. The development of the bioartificial lung
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Fatemeh Ajalloueian, Greg Lemon, Paolo Macchiarini, and Mei Ling Lim
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Lung Diseases ,Pathology ,medicine.medical_specialty ,medicine.medical_treatment ,Models, Biological ,Artificial lung ,Tissue engineering ,medicine ,Humans ,Lung transplantation ,Computer Simulation ,Progenitor cell ,Lung ,Bioartificial Organs ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,General Medicine ,respiratory system ,Embryonic stem cell ,respiratory tract diseases ,medicine.anatomical_structure ,Lung disease ,Chronic Disease ,Stem cell ,business ,Lung Transplantation ,Stem Cell Transplantation - Abstract
The incidence of chronic lung disease is increasing worldwide due to the spread of risk factors and ageing population. An important advance in treatment would be the development of a bioartificial lung where the blood-gas exchange surface is manufactured from a synthetic or natural scaffold material that is seeded with the appropriate stem or progenitor cells to mimic the functional tissue of the natural lung.Articles relating to bioartificial lungs were sourced through PubMed and ISI Web of Knowledge.There is a consensus that advances in bioartificial lung engineering will be beneficial to patients with chronic lung failure. Ultimate success will require the concerted efforts of researchers drawn from a broad range of disciplines, including clinicians, cell biologists, materials scientists and engineers.As a source of cells for use in bioartificial lungs it is proposed to use human embryonic stem cells; however, there are ethical and safety concerns regarding the use of these cells.There is a need to identify the optimum strategies for differentiating progenitor cells into functional lung cells; a need to better understand cell-biomaterial/ECM interactions and a need to understand how to harness the body's natural capacity to regenerate the lung.Biomaterial technologies for recreating the natural lung ECM and architecture need further development. Mathematical modelling techniques should be developed for determining optimal scaffold seeding strategies and predicting gas exchange performance.
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- 2013
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10. Tracheal replacement for primary tracheal cancer
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Johannes C. Haag, Paolo Macchiarini, and Philipp Jungebluth
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medicine.medical_specialty ,Bioartificial Organs ,Tissue Engineering ,business.industry ,medicine.medical_treatment ,Mesenchymal stem cell ,Tracheal cancer ,Immunosuppression ,Clinical method ,Surgery ,Trachea ,Neovascularization ,Otorhinolaryngology ,Tissue engineering ,Clinical investigation ,medicine ,Humans ,Tracheal Neoplasms ,medicine.symptom ,business ,Allotransplantation - Abstract
Purpose of review To summarize the so far applied clinical methods of tracheal replacement, comparing pros and cons of conventional and tissue-engineered approaches. Recent findings Several strategies have been most recently described to replace the trachea-like aortic homografts, allotransplantation, and tissue engineering. Allotransplantation requires lifelong immunosuppression and this may be ethically questioned being not a lifesaving procedure. Tissue-engineered tracheal transplantation has been clinically applied using biological or bioartificial tubular or bifurcated scaffolds reseeded with mesenchymal stromal cells, and bioactive molecules boosting regeneration and promoting neovascularization. Summary Tracheal tissue engineering may be a promising alternative to conventional allotransplantation in adults and children. Different methods have been developed and are currently under active clinical investigation, and await long-term results.
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- 2013
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11. Diverse applications of nanomedicine
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Philipp Jungebluth, Ali Khademhosseini, Xian-En Zhang, Yuzhou Wu, Tai Hyun Park, Christian Dullin, Helmuth Möhwald, Neus Feliu, Mahmoud Soliman, Michael D. George, Nicholas A. Kotov, Buddhisha Udugama, Paul Mulvaney, Ramon A. Alvarez-Puebla, Warren C. W. Chan, Kazunori Kataoka, Sumaira Ashraf, Beatriz Pelaz, Xingyu Jiang, Yury Gogotsi, Naomi J. Halas, Yuliang Zhao, Arnold Grünweller, Laura Ballerini, Jose Oliveira, Ben Zhong Tang, Sebastian Sjöqvist, Susanna Bosi, Andre G. Skirtach, Anne M. Andrews, Teruo Okano, Daxiang Cui, Shuming Nie, Maurizio Prato, Qian Zhang, Patrick Hunziker, Alberto Escudero, Xin Zhou, Qiang Zhang, Huan Meng, Claus-Michael Lehr, Christoph Alexiou, Youqing Shen, Wolfgang J. Parak, Luis M. Liz-Marzán, Lajos P. Balogh, Ji Jian, Andre E. Nel, Molly M. Stevens, Xiaowei Ma, Paul S. Weiss, Zhao Yue, Rainer Tietze, Xiaodong Chen, Raymond E. Schaak, Zhongwei Gu, Chunying Chen, Hsing-Wen Sung, Jindřich Kopeček, Xing-Jie Liang, Alessandra Bestetti, Lily Yang, Harald F. Krug, Paolo Macchiarini, Mei Ling Lim, Vincent M. Rotello, Mónica Carril, Tanja Weil, Zhen Cheng, Pranav Kadhiresan, J. Scott VanEpps, Roland K. Hartmann, Mark C. Hersam, Xiaoyuan Chen, Itamar Willner, Mingyuan Gao, Dong Soo Lee, Amila Samarakoon, Peter Nordlander, Norbert Hampp, Víctor F. Puntes, Cornelia Brendel, Reginald M. Penner, Kam W. Leong, Jianzhong Du, Frauke Alves, Helmholtz-Institute for Pharmaceutical Research Saarland (HIPS),Saarland 9 University, 66123 Saarbrücken, Germany., Pelaz, Beatriz, Alexiou, Christoph, Alvarez Puebla, Ramon A., Alves, Frauke, Andrews, Anne M., Ashraf, Sumaira, Balogh, Lajos P., Ballerini, Laura, Bestetti, Alessandra, Brendel, Cornelia, Bosi, Susanna, Carril, Monica, Chan, Warren C. W., Chen, Chunying, Chen, Xiaodong, Chen, Xiaoyuan, Cheng, Zhen, Cui, Daxiang, Du, Jianzhong, Dullin, Christian, Escudero, Alberto, Feliu, Neu, Gao, Mingyuan, George, Michael, Gogotsi, Yury, Grünweller, Arnold, Gu, Zhongwei, Halas, Naomi J., Hampp, Norbert, Hartmann, Roland K., Hersam, Mark C., Hunziker, Patrick, Jian, Ji, Jiang, Xingyu, Jungebluth, Philipp, Kadhiresan, Pranav, Kataoka, Kazunori, Khademhosseini, Ali, Kopeček, Jindřich, Kotov, Nicholas A., Krug, Harald F., Lee, Dong Soo, Lehr, Claus Michael, Leong, Kam W., Liang, Xing Jie, Ling Lim, Mei, Liz Marzán, Luis M., Ma, Xiaowei, Macchiarini, Paolo, Meng, Huan, Möhwald, Helmuth, Mulvaney, Paul, Nel, Andre E., Nie, Shuming, Nordlander, Peter, Okano, Teruo, Oliveira, Jose, Park, Tai Hyun, Penner, Reginald M., Prato, Maurizio, Puntes, Victor, Rotello, Vincent M., Samarakoon, Amila, Schaak, Raymond E., Shen, Youqing, Sjöqvist, Sebastian, Skirtach, Andre G., Soliman, Mahmoud G., Stevens, Molly M., Sung, Hsing Wen, Tang, Ben Zhong, Tietze, Rainer, Udugama, Buddhisha N., Vanepps, J. Scott, Weil, Tanja, Weiss, Paul S., Willner, Itamar, Wu, Yuzhou, Yang, Lily, Yue, Zhao, Zhang, Qian, Zhang, Qiang, Zhang, Xian En, Zhao, Yuliang, Zhou, Xin, Parak, Wolfgang J., German Academic Exchange Service, Chinese Academy of Sciences, National Natural Science Foundation of China, National Basic Research Program (China), European Commission, Ministerio de Economía y Competitividad (España), Generalitat de Catalunya, Swiss National Science Foundation, Julian Schwinger Foundation, Claude Leon Foundation, National Science Foundation (US), Canadian Institutes of Health Research, Natural Sciences and Engineering Research Council of Canada, Alexander von Humboldt Foundation, Lars Hierta Memorial Foundation, Eusko Jaurlaritza, Research Grants Council (Hong Kong), National Cancer Institute (US), Junta de Andalucía, Research Foundation - Flanders, and German Research Foundation
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Technology ,Chemistry, Multidisciplinary ,neurons ,General Physics and Astronomy ,02 engineering and technology ,Settore BIO/09 - Fisiologia ,01 natural sciences ,Engineering (all) ,Drug Delivery Systems ,Imaging tools ,Neoplasms ,Medicine and Health Sciences ,Nanotechnology ,General Materials Science ,Diverse applications ,nanomaterials ,Wearable technology ,Drug Carriers ,Chemistry, Physical ,General Engineering ,021001 nanoscience & nanotechnology ,Wearable devices ,3. Good health ,Chemistry ,Nanomedicine ,Physical Sciences ,QUANTUM-DOT BARCODES ,Science & Technology - Other Topics ,Medicine ,Materials Science (all) ,0210 nano-technology ,Nano Focus ,Materials science ,Materials Science ,Physics and Astronomy (all) ,Materials Science, Multidisciplinary ,010402 general chemistry ,MESENCHYMAL STEM-CELLS ,Vaccine development ,TARGETED DRUG-DELIVERY ,LABEL-FREE DETECTION ,MESOPOROUS SILICA NANOPARTICLES ,High throughput screening ,MD Multidisciplinary ,Animals ,Humans ,SURFACE-PLASMON RESONANCE ,Nanoscience & Nanotechnology ,Particle Size ,cell physiology ,FIELD-EFFECT TRANSISTOR ,Biomedicine ,Science & Technology ,carbon nanotubes ,business.industry ,COATED GOLD NANOPARTICLES ,neurology ,IRON-OXIDE NANOPARTICLES ,Biology and Life Sciences ,Data science ,nanomedicine, neurology, nanomaterials, carbon nanotubes, cell physiology, neurons ,0104 chemical sciences ,Physics and Astronomy ,Targeted drug delivery ,Nanoscale size ,Nanoparticles ,ENHANCED RAMAN-SCATTERING ,Drug Delivery ,business - Abstract
The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic., This work was supported by the Deutscher Akademischer Austauschdienst (DAAD to Philipps Universität Marburg and Zhejiang University, Hangzhou), the Chinesisch Deutsches Zentrum für Wissenschaftsförderung (“CDZ” to Z.G. and W.J.P.), and the Chinese Academy of Science (CAS). Part of this work was supported by the National Natural Science Foundation (51390481, 81227902, 81625011), National Basic Research Program (2014CB931900) of China (to Y.S.), by the European Commission grant Futurenanoneeds (to V.P. and W.J.P.), by the Spanish Ministerio de Economia y Competitividad (CTQ2011-23167 and CTQ2014-59808R to R.A.A.P.), the Generalitat of Catalunya (2014-SGR-612 to R.A.A.P.), the Deutsche Forschungsgemeinschaft (DFG) (AL552/8-1 to R.T.), the Swiss National Science Foundation (NRP62 to P.H.), the Claude & Julianna Foundation (grant to P.H.), the National Science Foundation (NSF) grants CHE-1306928 (to R.P.) and ECS-0601345; CBET 0933384; CBET 0932823; and CBET 1036672 (to N.A.K.), Canadian Institute of Health Research (grant to W.C.W.C.), and Natural Sciences and Engineering Research Council of Canada (grant to W.C.W.C.). S.A. and B.P. acknowledge a fellowship from the Alexander von Humboldt Foundation. N.F. acknowledges the Lars Hiertas Minne Foundation. M.C. acknowledges Ikerbasque for a Research Fellow position. X.C. acknowledges the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). B.Z.T. acknowledges the Innovation and Technology Commission of Hong Kong (ITC-CNERC14SC01). The Pancreatic Cancer research of A.E.N. and H.M. was funded by the U.S. National Cancer Institute, NIH grant # U01CA198846. A.E. acknowledges Junta de Andalucía (Spain) for a Talentia Postdoc Fellowship, co-financed by the European Union's Seventh Framework Programme, grant agreement no 267226. A.G.S. acknowledges support by BOF (UGent) and FWO (Research Foundation Flanders). Part of this work was supported by the National Natural Science Foundation of China.
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- 2017
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12. Recommendations for the management of subsolid pulmonary nodules detected at CT: a statement from the Fleischner Society
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David P. Naidich, Paolo Macchiarini, Massimo Pistolesi, Christian J. Herold, Alexander A. Bankier, William D. Travis, James D. Crapo, Cornelia M. Schaefer-Prokop, John H. M. Austin, Jin Mo Goo, and Heber MacMahon
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Clinical Practice ,Pediatrics ,medicine.medical_specialty ,Clinical history ,business.industry ,medicine ,Radiology, Nuclear Medicine and imaging ,Medical physics ,Aetiology, screening and detection [ONCOL 5] ,business - Abstract
Item does not contain fulltext This report is to complement the original Fleischner Society recommendations for incidentally detected solid nodules by proposing a set of recommendations specifically aimed at subsolid nodules. The development of a standardized approach to the interpretation and management of subsolid nodules remains critically important given that peripheral adenocarcinomas represent the most common type of lung cancer, with evidence of increasing frequency. Following an initial consideration of appropriate terminology to describe subsolid nodules and a brief review of the new classification system for peripheral lung adenocarcinomas sponsored by the International Association for the Study of Lung Cancer (IASLC), American Thoracic Society (ATS), and European Respiratory Society (ERS), six specific recommendations were made, three with regard to solitary subsolid nodules and three with regard to multiple subsolid nodules. Each recommendation is followed first by the rationales underlying the recommendation and then by specific pertinent remarks. Finally, issues for which future research is needed are discussed. The recommendations are the result of careful review of the literature now available regarding subsolid nodules. Given the complexity of these lesions, the current recommendations are more varied than the original Fleischner Society guidelines for solid nodules. It cannot be overemphasized that these guidelines must be interpreted in light of an individual's clinical history. Given the frequency with which subsolid nodules are encountered in daily clinical practice, and notwithstanding continuing controversy on many of these issues, it is anticipated that further refinements and modifications to these recommendations will be forthcoming as information continues to emerge from ongoing research.
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- 2013
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13. Editorial Expression of Concern: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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Paolo Macchiarini, Ylva Gustafsson, Silvia Baiguera, Cristian Ibarra, Domenico Ribatti, Greg Lemon, Miguel Angel Burguillos, Alessandra Bianco, Sebastian Sjöqvist, Karolina Kublickiene, Heike Kielstein, Bertrand Joseph, Peter Damberg, Costantino Del Gaudio, Philipp Jungebluth, Alexander Sotnichenko, Doris A. Taylor, Rainer Heuchel, Ying Zhao, Johannes C. Haag, Henrik Ullman, Antonio B. Rodriguez, and Mei Ling Lim
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0301 basic medicine ,Multidisciplinary ,Tissue engineered ,business.industry ,Science ,digestive, oral, and skin physiology ,General Physics and Astronomy ,General Chemistry ,digestive system ,digestive system diseases ,General Biochemistry, Genetics and Molecular Biology ,Addendum ,03 medical and health sciences ,surgical procedures, operative ,030104 developmental biology ,Orthotopic transplantation ,otorhinolaryngologic diseases ,Cancer research ,Medicine ,business - Abstract
Editorial Expression of Concern: Experimental orthotopic transplantation of a tissue-engineered oesophagus in rats
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- 2016
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14. RETRACTED: Development and Validation of a New Outcome Score in Subglottic Stenosis
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Paolo Macchiarini, Massimo Pistolesi, Massimo Osvaldo Jaus, Alessandro Gonfiotti, Leonardo Polizzi, Philipp Jungebluth, Daniel Barale, Silvia Baiguera, and Matteo Paoletti
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Univariate analysis ,Multivariate analysis ,business.industry ,Mortality rate ,Subglottic stenosis ,Anastomosis ,medicine.disease ,Surgery ,Stenosis ,medicine ,Etiology ,Stage (cooking) ,Cardiology and Cardiovascular Medicine ,business - Abstract
Background. We prospectively evaluated a clinical and endoscopic score, the tracheal endoscopic clinical score (TECS), developed as a disease-specified outcome measure in adult patients undergoing operation for subglottic stenosis. We also performed a retrospective chart review to identify preoperative and intraoperative risk factors for worse TECS. Methods. The TECS includes endoscopic (vocal cord and glottic function, anastomotic healing, and patency) and interview (respiration, voice, swallow) variables, and was administered at 6-month follow-up. Endoscopic and subjective domains were weighted to obtain a continuous TECS index ranging from 0 (best) to 1 (worse). The TECS and preoperative variables relationships were evaluated by univariate and multivariate analysis. Results. We collected data (January 2009 to December 2010) from 30 patients (mean age, 48.3 19 years) undergoing subglottic resection and primary reconstruction. Stenosis etiology was postintubation (n 8), idiopathic (n 2), tracheostomy (n 18), and malignant (n 2). Surgery included Pearson operation with (n 7) or without (n 23) a Liberman-Mathisen cricoplasty. Mean length of resected trachea was 30.5 13.5 mm, and mean hospital stay was 7.4 days. Mortality rate was 1 patient (3.3%). The univariate analysis showed positive correlation between 6-month TECS and degree of stenosis (McCaffrey and Cotton scale 0 to 4) stage 4, tracheostomy or T-tube at surgery, bottleneck-type transition stenosis, and resection length. At multivariate analysis, the presence of tracheostomy, bottleneck-type transition stenosis and resection length were indicators of worse postoperative functional result. Conclusions. The TECS seems to be a valid and simple instrument to identify preoperative variables predicting worse results and to assess postoperative outcome. Validation on larger series is necessary. (Ann Thorac Surg 2012;94:1065‐72) © 2012 by The Society of Thoracic Surgeons
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- 2012
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15. The pumpless extracorporeal lung membrane provides complete respiratory support during complex airway reconstructions without inducing cellular trauma or a coagulatory and inflammatory response
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Philipp Jungebluth, David Sánchez-Lorente, Alberto Rodríguez, Manuela Iglesias, and Paolo Macchiarini
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Adult ,Male ,Pulmonary and Respiratory Medicine ,ARDS ,medicine.medical_specialty ,Cardiac output ,medicine.medical_treatment ,Extracorporeal ,law.invention ,Intraoperative Period ,law ,medicine ,Cardiopulmonary bypass ,Intubation ,Humans ,Prospective Studies ,Airway Management ,Lung ,Respiratory Distress Syndrome ,Haptoglobins ,L-Lactate Dehydrogenase ,business.industry ,Equipment Design ,Middle Aged ,Plastic Surgery Procedures ,Thoracic Surgical Procedures ,medicine.disease ,Surgery ,medicine.anatomical_structure ,Anesthesia ,Breathing ,Feasibility Studies ,Airway ,business ,Respiratory Insufficiency ,Cardiology and Cardiovascular Medicine - Abstract
ObjectiveOur objective was to investigate the capacity of a pumpless extracorporeal lung membrane (iLA) (Novalung; Novalung GmbH, Hechingen, Germany) to provide adequate respiratory support and the impact on morbidity/mortality during complex airway reconstruction.MethodsOnly patients unable to be ventilated via conventional intubation were eligible for the study. A larynx mask or orotracheal tubes were placed above the airway defect and the iLA was attached via femoral vessels (arteriovenous), providing extracorporeal gas exchange, apneic hyperoxygenation, and total tubeless airway reconstruction. Haptoglobulin, plasmin–antiplasmin complex, P-selectin activation, and interleukin 6 were measured before, during, and after iLA use and 72 hours postoperatively.ResultsFifteen consecutive patients (age, 42 ± 17 years) underwent elective (n = 7) or emergency (n = 8) reconstruction of the airway owing to a variety of disorders or defects. The iLA was left in place for 185 ± 61 minutes, diverted 1.70 ± 0.48 L/min of the cardiac output, and provided an arteriovenous carbon dioxide removal and oxygen transfer of 173 ± 94 and 144 ± 83 mL/min, respectively. The arterial oxygen tension/inspired oxygen fraction (314 ± 31 mm Hg), and arterial carbon dioxide tension (40 ± 6 mm Hg) remained stable throughout the entire operations. The following procedures were performed: redo slide tracheoplasties (n = 3), redo tracheoesophageal fistula repair (n = 1), sleeve lobectomies (n = 2), main carina reconstructions (n = 7), and anastomotic stenting and myocutaneous coverages (n = 2). Three patients required prolonged (9 ± 2 days) postoperative iLA support. Two (13%) patients died during the hospital stay. The use of iLA was associated with significant (P
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- 2012
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16. Superior Vena Cava and Innominate Vein Reconstruction in Thoracic Malignancies: Cryopreserved Graft Reconstruction
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Massimo Osvaldo Jaus and Paolo Macchiarini
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Vena Cava, Superior ,Locally advanced ,Blood Vessel Prosthesis Implantation ,Young Adult ,Blood vessel prosthesis ,Superior vena cava ,medicine ,Humans ,Transplantation, Homologous ,Neoplasm Invasiveness ,Innominate vein ,Aged ,Brachiocephalic Veins ,Bioprosthesis ,Cryopreservation ,Lung ,business.industry ,Patient Selection ,Operative mortality ,General Medicine ,Middle Aged ,Plastic Surgery Procedures ,Thoracic Neoplasms ,Thoracic Surgical Procedures ,Blood Vessel Prosthesis ,Surgery ,Transplantation ,Treatment Outcome ,medicine.anatomical_structure ,Cardiothoracic surgery ,Female ,Radiology ,Cardiology and Cardiovascular Medicine ,business - Abstract
Recent technical advances in the domains of anesthesia, cardiovascular and thoracic surgery, and synthetic materials manufacturing coupled with more oncological extended tumor indications have unlocked the door to the surgical treatment of pulmonary, mediastinal, or other rare tumors involving intrathoracic vessels. In 1987, Dartevelle et al1 first described a consecutive and large series of patients with mediastinal or lung malignancies and superior vena cava (SVC) involvement treated with SVC resection by using polytetrafluoroethylene tubular grafts for reconstruction. Open surgery requires a high level of technical expertise and vigilant attention to patient selection and perioperative management to minimize complications, which are reported even in highly specialized centers.1,2 During the past decade, operative mortality for these procedures has ranged between 0% and 7.7%, with long-term patency rates of about 70%-100%.3-9 However, proper patient selection is critical for clinical success. We will outline the role of surgery for selected patients with locally advanced but completely resectable non-small cell lung cancers (NSCLC) or mediastinal tumors (MT) involving invading the SVC and/or the innominate vein (IV).
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- 2011
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17. Tissue-Engineered Airway: A Regenerative Solution
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Silvia Baiguera, Paolo Macchiarini, Guido Moll, and Philipp Jungebluth
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Pharmacology ,Tissue engineered ,Tissue Engineering ,Tissue Scaffolds ,Polymers ,business.industry ,Cellular differentiation ,Tissue protection ,Regenerative Medicine ,Regenerative medicine ,Hematopoietic Stem Cell Mobilization ,Cell biology ,Trachea ,Tissue engineering ,Tissue scaffolds ,Immunology ,Animals ,Humans ,Medicine ,Pharmacology (medical) ,Stem cell ,business - Abstract
The use of synthetic degradable or permanent polymers and biomaterials has not yet helped to achieve successful clinical whole-airway replacement. A novel, clinically successful approach involves tissue engineering (TE) replacement using three-dimensional biologic scaffolds composed of allogeneic extracellular scaffolds derived from nonautologous sources and recellularized with autologous stem cells or differentiated cells. In this paper, we discuss this novel approach and review information that can lead to a better understanding of stem cell recruitment and/or mobilization and site-specific tissue protection, which can be pharmacologically boosted in humans.
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- 2011
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18. Airway tissue engineering
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Paolo De Coppi, Martin A. Birchall, Martin J. Elliott, Jonathan Fishman, Anthony Atala, and Paolo Macchiarini
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medicine.medical_specialty ,Clinical Biochemistry ,Cell Culture Techniques ,Organ function ,Regenerative Medicine ,Autologous tissue ,Regenerative medicine ,Laryngeal Diseases ,Tissue Culture Techniques ,Bioreactors ,Cell transplantation ,Tissue engineering ,Drug Discovery ,medicine ,Animals ,Humans ,Intensive care medicine ,Cells, Cultured ,Pharmacology ,Tracheal Diseases ,Bioartificial Organs ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Regeneration (biology) ,Surgery ,Trachea ,Transplantation ,Larynx ,business ,Airway - Abstract
Prosthetic replacements, autologous tissue transfer and allografts have so far failed to offer functional solutions for the treatment of long circumferential tracheal defects and loss of a functioning larynx. Interest has therefore turned increasingly to the field of tissue-engineering which applies the principles and methods of bioengineering, material science, cell transplantation and life sciences in an effort to develop in vitro biological substitutes able to restore, maintain or improve tissue and organ function.This article gives an overview of the tissue-engineering approach to airway replacement and will describe the encouraging results obtained so far in tracheal regeneration. The recent advances in the field of tissue-engineering have provided a new attractive approach towards the concept of functional substitutes and may represent an alternative to the shortage of suitable grafts for reconstructive airway surgery. We summarize fundamental questions, as well as future directions in airway tissue engineering.The replacement of active movement, as would be necessary to replace an entire larynx introduces another order of magnitude of complexity, although progress in this area is starting to bear fruit. In addition, the stem cell field is advancing rapidly, opening new avenues for this type of therapy.
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- 2011
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19. Interactive Role of Trauma Cytokines and Erythropoietin and Their Therapeutic Potential for Acute and Chronic Wounds
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Paolo Macchiarini, Katrin Lorenz, Anja Richter, Shibashish Giri, Sabine Ebert, Katja Scheffler, Maria Behrens, Augustinus Bader, Hans-Günther Machens, Larissa Kern, and Ulf Dornseifer
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Adult ,Male ,Aging ,Pharmacology ,Inhibitory postsynaptic potential ,Flow cytometry ,Sequence Analysis, Protein ,hemic and lymphatic diseases ,Receptors, Erythropoietin ,medicine ,Humans ,Receptor ,Erythropoietin ,Cells, Cultured ,Aged ,Cell Proliferation ,medicine.diagnostic_test ,business.industry ,Stem Cells ,Regeneration (biology) ,Drug Synergism ,Dermis ,Middle Aged ,Flow Cytometry ,Phenotype ,Child, Preschool ,Acute Disease ,Chronic Disease ,Immunology ,Cytokines ,Wounds and Injuries ,Female ,Tumor necrosis factor alpha ,Geriatrics and Gerontology ,Stem cell ,Wound healing ,business ,Biomarkers ,medicine.drug - Abstract
If controllable, stem cell activation following injury has the therapeutic potential for supporting regeneration in acute or chronic wounds. Human dermally-derived stem cells (FmSCs) were exposed to the cytokines interleukin-6 (IL-6), IL-1β, and tumor necrosis factor-α (TNF-α) in the presence of erythropoietin (EPO). Cells were cultured under ischemic conditions and phenotypically characterized using flow cytometry. Topical EPO application was performed in three independent clinical wound healing attempts. The FmSCs expressed the receptor for EPO. EPO had a strong inhibitory effect on FmSC growth in the absence of IL-6 and TNF-α. With IL-6, the EPO effects were reversed to that of growth stimulation. TNF-α had the strongest stimulatory effect. In contrast, IL-1β had an inhibitory effect. Topically applied EPO considerably enhanced wound healing and improved wound conditions of acute and chronic wounds. Site specificity of stem cell activation is mediated by IL-6 and TNF-α. In trauma, EPO ceases its inhibitory role and reverts to a clinically relevant boosting function. EPO may be an important therapeutic tool for the topical treatment of acute and chronic wounds.
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- 2011
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20. Both epithelial cells and mesenchymal stem cell–derived chondrocytes contribute to the survival of tissue-engineered airway transplants in pigs
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Paolo Macchiarini, Martin A. Birchall, Helmut Ostertag, Sara Mantero, Tetsuhiko Go, Augustinus Bader, Philipp Jungebluth, Adelaide Asnaghi, Silvia Baiguero, and Jaume Martorell
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Pulmonary and Respiratory Medicine ,Cell type ,Pathology ,medicine.medical_specialty ,Swine ,Chondrocyte ,Tissue culture ,Bioreactors ,Chondrocytes ,Tissue engineering ,Animals ,Medicine ,Tissue Engineering ,business.industry ,Graft Survival ,Mesenchymal stem cell ,Epithelial Cells ,Mesenchymal Stem Cells ,Epithelium ,Trachea ,Transplantation ,medicine.anatomical_structure ,Surgery ,Stem cell ,Cardiology and Cardiovascular Medicine ,business - Abstract
ObjectiveWe sought to determine the relative contributions of epithelial cells and mesenchymal stem cell–derived chondrocytes to the survival of tissue-engineered airway transplants in pigs.MethodsNonimmunogenic tracheal matrices were obtained by using a detergent-enzymatic method. Major histocompatibility complex–unmatched animals (weighing 65 ± 4 kg) were divided into 4 groups (each n = 5), and 6 cm of their tracheas were orthotopically replaced with decellularized matrix only (group I), decellularized matrix with autologous mesenchymal stem cell–derived chondrocytes externally (group II), decellularized matrix with autologous epithelial cells internally (group III), or decellularized matrix with both cell types (group IV). Autologous cells were recovered, cultured, and expanded. Mesenchymal stem cells were differentiated into chondrocytes by using growth factors. Both cell types were seeded simultaneously with a dual-chamber bioreactor. Animals were not immunosuppressed during the entire study. Biopsy specimens and blood samples were taken from recipients continuously, and animals were observed for a maximum of 60 days.ResultsMatrices were completely covered with both cell types within 72 hours. Survival of the pigs was significantly affected by group (P < .05; group I, 11 ± 2 days; group II, 29 ± 4 days; group III, 34 ± 4 days; and group IV, 60 ± 1 days). Cause of death was a combination of airway obstruction and infection (group I), mainly infection (group II), or primarily stenosis (group III). However, pigs in group IV were alive, with no signs of airway collapse or ischemia and healthy epithelium. There were no clinical, immunologic, or histologic signs of rejection despite the lack of immunosuppression.ConclusionsWe confirm the clinical potential of autologous cell– and tissue-engineered tracheal grafts, and suggest that the seeding of both epithelial and mesenchymal stem cell–derived chondrocytes is necessary for optimal graft survival.
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- 2010
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21. Structural and morphologic evaluation of a novel detergent–enzymatic tissue-engineered tracheal tubular matrix
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Philipp Jungebluth, Adelaide Asnaghi, Jaume Martorell, Maria Teresa Conconi, Silvia Bellini, Luca Urbani, Tetsuhiko Go, Paolo Macchiarini, Chiara Calore, Helmut Ostertag, and Sara Mantero
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,RESECTION ,Swine ,PIG MODEL, TRANSPLANTATION, ALLOGRAFTS, CRYOPRESERVATION, REPLACEMENT, GENERATION, RESECTION ,medicine.medical_treatment ,PIG MODEL ,Cryopreservation ,Mice ,Random Allocation ,Tissue culture ,Antigen ,In vivo ,Animals ,Transplantation, Homologous ,Medicine ,Saline ,Bioprosthesis ,Decellularization ,Tissue Engineering ,TRANSPLANTATION ,ALLOGRAFTS ,business.industry ,CRYOPRESERVATION ,REPLACEMENT ,Trachea ,Transplantation ,Surgery ,Stress, Mechanical ,Cardiology and Cardiovascular Medicine ,business ,Immunostaining ,GENERATION - Abstract
ObjectiveWe sought to bioengineer a nonimmunogenic tracheal tubular matrix of 6 cm in length and test its structural, functional, and immunologic properties in vitro and in vivo.MethodsTwelve-centimeter tracheal segments were harvested from Yorkshire boars. Half of each segment was subjected to a detergent–enzymatic method (containing sodium deoxycholate/DNase lavations) of decellularization for as many cycles as needed, and the other half was stored in phosphate-buffered saline at 4°C as a control. Bioengineered and control tracheas were then implanted in major histocompatibility complex–unmatched pigs (allograft) or mice (xenograft) heterotopically for 30 days. Structural and functional analysis and immunostaining were performed after each detergent–enzymatic method cycle and transplantation.ResultsCompared with control tracheas, bioengineered matrices displayed no major histocompatibility complex class I and II antigens after 17 detergent–enzymatic method cycles, without significant (P > .05) differences in their strain ability (rupture force, 56.1 ± 3.3 vs 55.5 ± 2.4 N; tissue deformation at 203% ± 13% vs 200% ± 8% or 12.2 ± 0.8 vs 12 ± 0.5 cm; and applied maximum force, 173.4 ± 3.2 vs 171.5 ± 4.6 N). Thirty days after implantation, significantly (P < .01) smaller inflammatory reactions (392 vs 15 macrophages/mm2 and 874 vs 167 T lymphocytes/mm2) and P-selectin expressions (1/6 vs 6/6) were observed in both the xenograft and allograft models with bioengineered matrices compared with those seen with control tracheas. There was no development of anti-pig leukocyte antigen antibodies or increase in both IgM and IgG content in mice implanted with bioengineered tracheas.ConclusionsBioengineered tracheal matrices displayed similar structural and mechanical characteristics to native tracheas and excite no immune response to 30 days when implanted as allografts or xenografts. This method holds great promise for the future of tissue-engineered airway replacement.
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- 2009
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22. Tratamiento quirúrgico en pacientes con hipertensión pulmonar tromboembólica crónica
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Paolo Macchiarini and David Lorente
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Extracorporeal circulation ,Transesophageal echocardiogram ,Extracorporeal ,Surgery ,Transplantation ,medicine.anatomical_structure ,Internal medicine ,Pulmonary angiography ,medicine ,Vascular resistance ,Cardiology ,business ,Contraindication ,Endarterectomy - Abstract
Chronic thromboembolic pulmonary hypertension (CTEPH), which has a natural history with low long-term survival, is increasingly being diagnosed. Pulmonary endarterectomy (PE) is the treatment of choice, which can be curative. This technique consists of a true endarterectomy through a midline sternotomy with extracorporeal circulation and periods of hypothermic circulatory arrest. The following procedures should be performed before surgery: transesophageal echocardiogram, ventilation-perfusion pulmonary scintigraphy, right cardiac catheterism, pulmonary angiography and helicoidal computed tomography. Surgery should be indicated in CTEPH as soon as the diagnosis is made, before arteriopathy develops in the non-obstructed regions and CTEPH becomes severe. The only absolute contraindication to PE is the presence of obstructive or restrictive, severe underlying pulmonary disease. There are no inaccessible grades of embolic obstruction, or grade of right ventricular failure or level of pulmonary vascular resistance (PVR) that are inoperable. However, prognosis worsens with greater preoperative pulmonary pressure and greater postoperative PVR. Mortality in PE is 4-10% and the main cause of postoperative death is the persistence of high pulmonary pressures and PVR, followed by reperfusion edema, which requires prolongation of mechanical ventilation, the use of pulmonary vasodilators and, sometimes, extracorporeal respiratory support. In the long-term, 75% of patients undergoing PE show good functional results and half recover adequate exercise tolerance. Pulmonary transplantation is an alternative for patients unsuitable for PE, although with worse results and greater mortality.
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- 2009
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23. Cryopreserved Arterial Allograft Reconstruction After Excision of Thoracic Malignancies
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Axel Haverich, Jose Louis Pomar, Paolo Macchiarini, Abel Gómez-Caro, David Sanchez, Jaume Martorell, Alberto Rodríguez, Wolfgang Harringer, Elisabeth Martinez, and Josep Maria Gimferrer
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Adult ,Graft Rejection ,Male ,Pulmonary and Respiratory Medicine ,Thorax ,medicine.medical_specialty ,Vena Cava, Superior ,medicine.medical_treatment ,Aorta, Thoracic ,Pulmonary Artery ,Revascularization ,Risk Assessment ,Cohort Studies ,medicine.artery ,medicine ,Humans ,Transplantation, Homologous ,Neoplasm Invasiveness ,Aged ,Retrospective Studies ,Aged, 80 and over ,Cryopreservation ,Aorta ,Cardiopulmonary Bypass ,Lung ,business.industry ,Graft Survival ,Arteries ,Middle Aged ,Plastic Surgery Procedures ,Thoracic Neoplasms ,medicine.disease ,Survival Analysis ,Vascular Neoplasms ,Surgery ,Treatment Outcome ,medicine.anatomical_structure ,Pulmonary artery ,Female ,Sarcoma ,Cardiology and Cardiovascular Medicine ,business ,Vascular Surgical Procedures ,Subclavian vein ,Follow-Up Studies ,Artery - Abstract
Background The purpose of this study was to evaluate the long-term clinical and immunologic outcome of cryopreserved arterial allograft (CAA) revascularization of intrathoracic vessels invaded by malignancies. Methods Since January 2002, consecutive patients whose intrathoracic vessels were invaded by malignancies were operated on and revascularizion made using human lymphocyte antigen (HLA)– and ABO-mismatched CAAs. Immunologic studies were performed preoperatively, and 1, 3, 6, 12, and 24 months postoperatively. Postoperative oral anticoagulation therapy was not given. Results Twenty-six patients aged 53.1 ± 15 years with a nonsmall-cell lung cancer (n = 10), invasive mediastinal tumors (n = 7), pulmonary artery sarcoma (n = 3), laryngeal (n = 2), or other rare lung neoplasms (n = 4) underwent operation. Cardiopulmonary bypass was used in 10 cases (38%), and all resections were pathologically complete. Revascularization was either for venous (n = 12) or arterial (n = 14) vessels, and a total of 30 allografts revascularized the superior vena cava (n = 6), pulmonary artery (n = 7), innominate vein (n = 3) or artery (n = 2), ascendent (n = 4) or descending (n = 1) aorta, and subclavian vein (n = 3) or artery (n = 4). Hospital morbidity and mortality were 50% (n = 13) and 3.8% (n = 1), respectively, all CAA unrelated. With a median follow-up of 18 months (range, 3 to 60+), 5-year survival and allograft patency were 84% and 95%, respectively. Preoperative anti-HLA antibodies were detected in 2 patients (7.7%) and a postoperative anti-HLA antibody response, clinically irrelevant, in 1 of 24 patients (4%). Conclusions Revascularization of intrathoracic venous and arterial vessels in patients with malignancies using HLA- and ABO-mismatched CAA is technically feasible and clinically attractive because of no infection risk and postoperative anticoagulation, and excellent long-term survival, patency, and nonimmunogeneicity.
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- 2008
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24. Optimal Positive End-Expiratory Pressure During Pumpless Extracorporeal Lung Membrane Support
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Manuela Iglesias, Paolo Macchiarini, Tetsuhiko Go, Philipp Jungebluth, and Oriol Sibila
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Lung ,Respiratory rate ,business.industry ,medicine.medical_treatment ,Biomedical Engineering ,Medicine (miscellaneous) ,Hemodynamics ,Bioengineering ,General Medicine ,respiratory system ,Extracorporeal ,respiratory tract diseases ,Biomaterials ,medicine.anatomical_structure ,Anesthesia ,Breathing ,Extracorporeal membrane oxygenation ,medicine ,business ,Tidal volume ,Positive end-expiratory pressure - Abstract
The aim of this study was to determine the optimal positive end-expiratory pressure (PEEP) required during extracorporeal lung membrane support (interventional lung assist [iLA]; Novalung GmbH, Hechingen, Germany). Twenty healthy pigs were initially (4 h) mechanically ventilated with a tidal volume (V(T)) of 10 mL/Kg, respiratory rate (RR) of 20 breaths/min, PEEP of 5 cm H(2)O, and fraction of inspired O(2) (FiO(2)) of 1.0. Thereafter, the iLAs were placed arteriovenously transfemorally and settings reduced to reach near static ventilation (V(T) 12 cm H(2)O, and this without hemodynamical imbalance. This study suggests that the iLA may provide adequate gas exchange during static ventilation only with PEEP levels > 10 cm H(2)O, and this without pulmonary or systemic hemodynamic imbalance.
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- 2008
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25. An Experimental Animal Model of Postobstructive Pulmonary Hypertension
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Helmut Ostertag, Paolo Macchiarini, and Philipp Jungebluth
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Male ,Hypertension, Pulmonary ,medicine.medical_treatment ,Hemodynamics ,Pulmonary Artery ,medicine.artery ,medicine ,Animals ,Ligature ,Ligation ,business.industry ,Respiratory disease ,Left pulmonary artery ,medicine.disease ,Pulmonary hypertension ,Rats ,Pulmonary embolism ,Disease Models, Animal ,medicine.anatomical_structure ,Rats, Inbred Lew ,Anesthesia ,Pulmonary artery ,Vascular resistance ,Vascular Resistance ,Surgery ,Pulmonary Embolism ,business - Abstract
A small experimental animal model of postobstructive pulmonary hypertension (PH) providing insights in the physiopathology of this disease was developed.Male Lewis rats were anesthetized and aleatory manipulated via a left thoracotomy with (group I, n = 10) or without (group II, n = 10) ligation of the left pulmonary artery. Animals were followed for 2 weeks and then sacrificed. Hemodynamic parameters and blood gases were recorded at baseline and 2 weeks after surgical procedure.Group I animals developed a significant (P0.01) PH (mean pulmonary artery pressure, 32 +/- 6 versus 16 +/- 2 mm Hg; pulmonary vascular resistance, 46 +/- 3 versus 21 +/- 2 mm Hg/mL/min; reduction of cardiac output, 75 +/- 3 versus 105 +/- 4 mL/min), compared to group II animals, and had a significant (P0.01) worse gas exchange (partial arterial pressure of O(2): 91 +/- 3 versus 439 +/- 24 mm Hg; partial arterial pressure of CO(2): 54 +/- 3 versus 42 +/- 2 mm Hg, on a fraction of inspired oxygen of 1.0), right ventricle hypertrophy (ventricle to left ventricle/septum ratio, 0.56 +/- 0.04 versus 0.45 +/- 0.04, P0.02) and less tolerance test (immobility time, 123 +/- 11 versus 61 +/- 8 s, P0.01) than group II animals. Histologically, ligated lungs showed postobstructive pulmonary vasculopathic abnormalities and bronchial-pulmonary artery hypertrophy, and the contralateral lung had initial signs of small vessel arteriopathy.The experimental model generated here successfully reproduced a PH morphologically and functionally similar to clinical postembolic PH and might be used for evaluating the physiopathology of postobstructive PH.
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- 2008
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26. Airway Transplantation: A Debate Worth Having?
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Martin A. Birchall and Paolo Macchiarini
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Transplantation ,medicine.medical_specialty ,Tissue Engineering ,business.industry ,medicine.medical_treatment ,Tracheal transplantation ,Pharyngeal Neoplasms ,Immunosuppression ,respiratory system ,Surgery ,Trachea ,Clinical trial ,medicine.anatomical_structure ,Quality of Life ,medicine ,Recurrent laryngeal nerve ,Animals ,Humans ,Larynx ,Intensive care medicine ,Airway ,business ,Allotransplantation ,Reinnervation - Abstract
Laryngeal and tracheal transplantation have been proposed as treatments for irreversible airway disease for many years. Despite much research, there has only been one true laryngeal transplant reported. Although this was in many ways a success, several barriers remain before full clinical trials. There are issues over patient selection, reinnervation, immunosuppression, and cost-benefit. For the trachea, where finely tuned neuromuscular activity is not an issue, tissue-engineering probably represents the future. This overview discusses the arguments for and against laryngeal and tracheal transplantation and suggests ways of overcoming these barriers.
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- 2008
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27. Allgemeine Aspekte der chirurgischen Therapie des nichtkleinzelligen Bronchialkarzinoms
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Paolo Macchiarini, Matthias Richter, and W. Harringer
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Pulmonary and Respiratory Medicine ,Gynecology ,medicine.medical_specialty ,business.industry ,Medicine ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
Das Bronchialkarzinom ist eine der haufigsten Krebserkrankungen in den Industrie landern, vorrangig bei Mannern, in zunehmendem Mase jedoch auch bei Frauen. Die einzig kurative Therapie besteht in der kompletten chirurgischen Resektion des Tumors. Hierbei sind die prazise praoperative Diagnostik mit moglichst exaktem Tumorstaging sowie die interdisziplinare Diskussion und Festlegung der weiteren individuellen Therapie essenziell fur ein modernes Therapiekonzept. Die operative Therapie des Bronchialkarzinoms ist heute stadienabhangig haufig in adjuvante und neoadjuvante Therapieschemata eingebunden und bedarf einer regen Kommunikation mit Pneumologen, Onkologen und Strahlentherapeuten. Chirurgische Uber legungen zur Therapie der einzelnen Tumorstadien werden prasentiert und die daraus resultierenden Operationsindikationen beschrieben. Daruber hinaus erlautert der Beitrag sowohl die invasiven Stagingtechniken als auch die praoperative Evaluation der Lungenfunktion.
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- 2008
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28. Extrapulmonary Ventilation for Unresponsive Severe Acute Respiratory Distress Syndrome After Pulmonary Resection
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Paolo Macchiarini, Manuela Iglesias, Elisabeth Martinez, and Joan Ramon Badia
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Adult ,Male ,Pulmonary and Respiratory Medicine ,ARDS ,Lung Neoplasms ,Respiratory rate ,Critical Illness ,medicine.medical_treatment ,Risk Assessment ,Sensitivity and Specificity ,Severity of Illness Index ,Extracorporeal Membrane Oxygenation ,Postoperative Complications ,Fraction of inspired oxygen ,medicine ,Humans ,Pneumonectomy ,Tidal volume ,Aged ,Retrospective Studies ,Mechanical ventilation ,Respiratory Distress Syndrome ,Lung ,Pulmonary Gas Exchange ,business.industry ,Respiratory disease ,Middle Aged ,medicine.disease ,Survival Rate ,Treatment Outcome ,medicine.anatomical_structure ,Anesthesia ,Breathing ,Feasibility Studies ,Female ,Surgery ,Cardiology and Cardiovascular Medicine ,business ,Follow-Up Studies - Abstract
The purpose of this study was to evaluate the feasibility of integrating an artificial, pumpless extracorporeal membrane ventilator (Novalung) to near static mechanical ventilation and its efficacy in patients with severe postresectional acute respiratory distress syndrome (ARDS) unresponsive to optimal conventional treatment.Indications were severe postresectional and unresponsive acute respiratory distress syndrome, hemodynamic stability, and no significant peripheral arterial occlusive disease or heparin-induced thrombocytopenia. Management included placement of the arteriovenous femoral transcutaneous interventional lung-assist membrane ventilator, lung rest at minimal mechanical ventilator settings, and optimization of systemic oxygen consumption and delivery.Among 239 pulmonary resections performed between 2005 and 2006, 7 patients (2.9%) experienced, 4 +/- 0.8 days after 5 pneumonectomies and 2 lobectomies, a severe (Murray score, 2.9 +/- 0.3) acute respiratory distress syndrome unresponsive to 4 +/- 2 days of conventional therapy. The interventional lung-assist membrane ventilator was left in place 4.3 +/- 2.5 days, and replaced only once for massive clotting. During this time, 29% +/- 0.3% or 1.4 +/- 0.36 L/min of the cardiac output perfused the device, without hemodynamic impairment. Using a sweep gas flow of 10.7 +/- 3.8 L/min, the device allowed an extracorporeal carbon dioxide removal of 255 +/- 31 mL/min, lung(s) rest (tidal volume, 2.7 +/- 0.8 mL/kg; respiratory rate, 6 +/- 2 beats/min; fraction of inspired oxygen, 0.5 +/- 0.1), early (24 hours) significant improvement of respiratory function, and reduction of plasmatic interleukin-6 levels (p0.001) and Murray score (1.25 +/- 0.1; p0.003). All but 1 patient (14%) who died of multiorgan failure were weaned from mechanical ventilation 8 +/- 3 days after removal of the interventional lung-assist membrane ventilator, and all of them were discharged from the hospital.The integration of this device to near static mechanical ventilation of the residual native lung(s) is feasible and highly effective in patients with severe and unresponsive acute respiratory distress syndrome after pulmonary resection.
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- 2008
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29. Right Carinal Lobectomy and Pneumonectomy
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Paolo Macchiarini
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Pulmonary and Respiratory Medicine ,Pneumonectomy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,medicine ,Surgery ,respiratory system ,Cardiology and Cardiovascular Medicine ,business - Published
- 2007
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30. Orthotopic transplantation of a tissue engineered diaphragm in rats
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Philipp Jungebluth, S. S. Dzhimak, Geoanna Bautista, Konstantin A. Danilenko, Sergei N. Chvalun, I. S. Gumenyuk, I. V. Gilevich, Mei Ling Lim, Paolo Macchiarini, Mark J. Holterman, E. A. Gubareva, Timofei E. Grigoriev, Greg Lemon, Doris A. Taylor, Antonio Beltrán Rodríguez, Sebastian Sjöqvist, E. V. Kuevda, A. S. Sotnichenko, Alexander G. Pokhotko, Ylva Gustafsson, Vladimir M. Pokrovsky, R. Z. Nakokhov, Neus Feliu, A. A. Basov, and S. V. Krasheninnikov
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0301 basic medicine ,Male ,Pathology ,medicine.medical_specialty ,Transplantation, Heterotopic ,Diaphragm ,Biophysics ,Diaphragmatic breathing ,Neovascularization, Physiologic ,Transplants ,Bioengineering ,Mesenchymal Stem Cell Transplantation ,Biomaterials ,03 medical and health sciences ,0302 clinical medicine ,Bioreactors ,Tissue engineering ,Absorbable Implants ,medicine ,Cell Adhesion ,Animals ,Wound Healing ,Decellularization ,Tissue Engineering ,Tissue Scaffolds ,business.industry ,Electromyography ,Regeneration (biology) ,Macrophages ,Mesenchymal stem cell ,Graft Survival ,Cell Differentiation ,Allografts ,Diaphragm (structural system) ,Rats ,Transplantation ,Radiography ,030104 developmental biology ,medicine.anatomical_structure ,Mechanics of Materials ,Rats, Inbred Lew ,030220 oncology & carcinogenesis ,Ceramics and Composites ,Bone marrow ,business ,Hernias, Diaphragmatic, Congenital - Abstract
The currently available surgical options to repair the diaphragm are associated with significant risks of defect recurrence, lack of growth potential and restored functionality. A tissue engineered diaphragm has the potential to improve surgical outcomes for patients with congenital or acquired disorders. Here we show that decellularized diaphragmatic tissue reseeded with bone marrow mesenchymal stromal cells (BM-MSCs) facilitates in situ regeneration of functional tissue. A novel bioreactor, using simultaneous perfusion and agitation, was used to rapidly decellularize rat diaphragms. The scaffolds retained architecture and mechanical properties and supported cell adhesion, proliferation and differentiation. Biocompatibility was further confirmed in vitro and in vivo. We replaced 80% of the left hemidiaphragm with reseeded diaphragmatic scaffolds. After three weeks, transplanted animals gained 32% weight, showed myography, spirometry parameters, and histological evaluations similar to native rats. In conclusion, our study suggested that reseeded decellularized diaphragmatic tissue appears to be a promising option for patients in need of diaphragmatic reconstruction.
- Published
- 2015
31. Pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension: is deep hypothermia required?☆
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Hiroyuki Kamiya, Michael Winterhalter, Matthias Karck, Joan Albert Barberà, José L. Pomar, Paolo Macchiarini, Christian Hagl, and Axel Haverich
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Hypertension, Pulmonary ,Hemodynamics ,Endarterectomy ,Pulmonary Artery ,Body Temperature ,law.invention ,Hypothermia, Induced ,law ,medicine ,Cardiopulmonary bypass ,Humans ,Prospective Studies ,Aged ,Postoperative Care ,Intraoperative Care ,Vascular disease ,business.industry ,Respiratory disease ,General Medicine ,Middle Aged ,Hypothermia ,medicine.disease ,Pulmonary hypertension ,Pulmonary embolism ,medicine.anatomical_structure ,Anesthesia ,Chronic Disease ,Vascular resistance ,Female ,Surgery ,medicine.symptom ,Pulmonary Embolism ,Cardiology and Cardiovascular Medicine ,business - Abstract
OBJECTIVE To investigate whether deep (
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- 2006
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32. Extended pulmonary resections of advanced thoracic malignancies with support of cardiopulmonary bypass
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Hassina Baraki, Paolo Macchiarini, K Wiebe, and Axel Haverich
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Adult ,Male ,Pulmonary and Respiratory Medicine ,Thorax ,medicine.medical_specialty ,Lung injury ,law.invention ,Intraoperative Period ,law ,medicine ,Cardiopulmonary bypass ,Humans ,Pneumonectomy ,Lung cancer ,Respiratory Distress Syndrome ,Lung cancer surgery ,Cardiopulmonary Bypass ,business.industry ,Respiratory disease ,Sarcoma ,General Medicine ,Middle Aged ,Thoracic Neoplasms ,medicine.disease ,Surgery ,Great vessels ,Female ,Epidemiologic Methods ,Tomography, X-Ray Computed ,Cardiology and Cardiovascular Medicine ,Complication ,business - Abstract
Objective: Complete resection of advanced pulmonary malignancies infiltrating the heart or the great vessels may require the application of cardiopulmonary bypass (CPB). Extracorporal circulation, however, is known to cause lung injury and may be harmful especially in pneumonectomies. Methods: Over a period of 10 years extended pulmonary resections requiring cardiopulmonary bypass were analyzed in a retrospective study. Results: From August 1993 to August 2003, 13 patients underwent an extended pulmonary resection for curative indications, requiringsupportbyCPB.Underlyingdiseasesweresarcomas(n = 8),non-smallcelllungcarcinomas(n = 3),andothers(n = 2).Pneumonectomies were performed in nine and lobectomies in four cases. In the majority of cases, several cardiac structures, predominantly the left atrium (n = 9), were affected. In four patients (31%), the indication for a CPB-supported procedure was not electively planned, but made intraoperatively. Complete en-bloc resection (R0) was achieved in 12 of 13 cases (92%). The 30-day mortality rate was 15% (n = 2). Major complications observed were acute lung injury (n = 4), right heart failure (n = 1), and multi-organ failure (n = 1). The cumulative survival at 1, 3, and 5 years in patients presenting with sarcomas was 62.5% compared to 33%, 0%, and 0%, respectively, in patients with non-small cell carcinoma (n = 3). Conclusions: Our results encourage the application of CPB in extended pulmonary resections to achieve complete resections. In carefully selected patients, especially those with sarcomas, the radical surgical procedure associated with increased pulmonary complications allows for significantly prolonged survival and quality of life. # 2005 Elsevier B.V. All rights reserved.
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- 2006
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33. Primary tracheal tumours
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Paolo Macchiarini
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medicine.medical_specialty ,Survival ,business.industry ,Incidence ,medicine.medical_treatment ,Brachytherapy ,Perioperative ,Tracheal Adenoid Cystic Carcinoma ,Prognosis ,medicine.disease ,Surgery ,Diagnosis, Differential ,Radiation therapy ,Tracheal tumor ,Debridement ,Oncology ,Tracheal Neoplasm ,Epidemiology ,Humans ,Medicine ,Stents ,Tracheal Neoplasms ,Differential diagnosis ,business - Abstract
Primary tumours of the trachea can be benign or malignant and account for fewer than 0.1% of tumours. However, they are a diagnostic and therapeutic challenge. Benign tumours are usually misdiagnosed as asthma or chronic lung disease, and can delay diagnosis for months or years. Because of their rapid growth and onset of haemoptysis, malignant tumours are often diagnosed earlier than benign tumours and patients thus often present with locally advanced disease. Inappropriate treatment is an equally frustrating issue. Modern techniques for tracheal surgery-laryngotracheal, tracheal, or carinal resection-combined with radiotherapy, can be offered curatively with low perioperative risks. Nevertheless, the low numbers of patients undergoing resection and the associated poor survival in epidemiological studies over the past two decades have shown that surgery is rarely considered outside referral centres, with radiotherapy or another form of local treatment (eg, endotracheal stents, debridement, brachytherapy) generally preferred. The liberal use of these other techniques should be avoided because surgery has the potential to cure all patients with benign and low-grade tumours and most patients with malignant primary tracheal tumours, and other techniques are usually palliative at best.
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- 2006
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34. Experimental generation of a tissue-engineered functional and vascularized trachea
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Fred Hofmann, Bettina Giere, Johanna Schanz, Heike Mertsching, Thorsten Walles, Michael Hofmann, Paolo Macchiarini, and Publica
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Pulmonary and Respiratory Medicine ,Pathology ,medicine.medical_specialty ,Swine ,Myocytes, Smooth Muscle ,Matrix (biology) ,Chondrocyte ,Tissue culture ,Tissue engineering ,Animals ,Medicine ,Viability assay ,Progenitor cell ,Cells, Cultured ,Bioartificial Organs ,Tissue Engineering ,business.industry ,Stem Cells ,Immunohistochemistry ,Trachea ,Endothelial stem cell ,medicine.anatomical_structure ,Respiratory epithelium ,Surgery ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objective We sought to grow in vitro functional smooth muscle cells, chondrocytes, and respiratory epithelium on a biologic, directly vascularized matrix as a scaffold for tracheal tissue engineering. Methods Ten- to 15-cm–long free jejunal segments with their own vascular pedicle were harvested and acellularized from donor pigs (n = 10) and used as a vascular matrix. Autologous costal chondrocytes, smooth muscle cells, and respiratory epithelium and endothelial progenitor cells were first cultured in vitro and then disseminated on the previously acellularized vascular matrix. Histologic, immunohistologic, molecular imaging, and Western blotting studies were then performed to assess cell viability. Results The endothelial progenitor cells re-endothelialized the matrix to such an extent that endothelial cell viability was uniformly documented through 2-(18F)-fluoro-2′-deoxyglucose positron emission tomography. This vascularized scaffold was seeded with functional (according to Western blot analysis) smooth muscle cells and successfully reseeded with viable ciliated respiratory epithelium. Chondrocyte growth and production of extracellular cartilaginous matrix was observed as soon as 2 weeks after their culture. Conclusions The fundamental elements for a bioartificial trachea were successfully engineered in vitro in a direct vascularized 10- to 15-cm–long bioartificial matrix. Future experimental work will be directed to give them a 3-dimensional aspect and a biomechanical profile of a functioning trachea.
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- 2004
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35. Regenerating the Respiratory Tract
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Paolo Macchiarini, Alexandra B. Firsova, E. V. Kuevda, Neus Feliu, Philipp Jungebluth, and Mei Ling Lim
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education.field_of_study ,business.industry ,Mesenchymal stem cell ,Population ,Regenerative medicine ,Cell biology ,Cell therapy ,medicine.anatomical_structure ,Tissue engineering ,Medicine ,Stem cell ,Progenitor cell ,business ,education ,Respiratory tract - Abstract
The ultimate target of regenerative medicine approaches (tissue engineering and cell therapy) for irreversible diseases of the respiratory tract is to replace or restore tissues or organ function. In this chapter we will describe the basic developmental biology of the respiratory system, and highlight the endogenous and exogenous stem or progenitor cells that are involved in tissue regeneration and homeostasis in the respiratory tract. We will also review the different therapeutic approaches to understand how a reconstituted complex whole tissue or organ can remodel, regenerate, and repair via specific mechanisms. We describe a mesenchymal stem-cell-like mucoepidermoid tumor cell population (MEi cells) in the human respiratory tract; and provide an overview of the innovative applications that nanotechnology can offer to accelerate the field of TE and cell therapy.
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- 2015
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36. Tissue Engineering of the Esophagus
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Paolo Macchiarini and Sebastian Sjöqvist
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medicine.medical_specialty ,business.industry ,Stomach ,Mucosal cell ,Cancer ,Esophageal Disorder ,medicine.disease ,Regenerative medicine ,Surgery ,medicine.anatomical_structure ,Tissue engineering ,Small animal ,Medicine ,Esophagus ,business - Abstract
Tissue engineering has the potential to help many adults and children affected by esophageal disorders such as cancer, Barrett’s esophagus, malformations, trauma, etc. Current surgical treatment is a complex procedure where the esophagus is replaced with either colon or stomach. Related mortality and morbidity is high, and functional outcomes are poor. A tissue-engineered graft could eliminate the need to use the patients’ own tissue and could result in a better clinical outcome. Tissue engineering approaches are also used to facilitate mucosal and submucosal healing after endoscopic removal of superficial cancer or precancerous lesions. This chapter describes the anatomy, physiology, and pathology of the esophagus, and summarizes the efforts made so far in the world of tissue engineering of the esophagus. We describe the use of biological and synthetic scaffolds and discuss results from many large and small animal publications. Lastly, we present two clinical studies that have been published to date, where either extra cellular matrix or oral mucosal cell sheets were transplanted to the wound bed after interventional endoscopy. In conclusion, the field of regenerative medicine and tissue engineering has the potential to save many lives, but much effort still needs to be made.
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- 2015
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37. Regenerative Medicine for Diseases of the Respiratory System
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Mei Ling Lim, Paolo Macchiarini, and Philipp Jungebluth
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business.industry ,Regeneration (biology) ,Organ dysfunction ,Context (language use) ,Disease ,Bioinformatics ,Regenerative medicine ,Cell therapy ,Tissue engineering ,Immunology ,medicine ,medicine.symptom ,Stem cell ,business - Abstract
Regenerative medicine is a promising and growing field for the treatment of both acute and chronic diseases affecting the respiratory tract. It focuses on the repair, replacement, or regeneration of cells, tissues, or organ dysfunction, which can be a result of many causes, including congenital defects, disease, trauma, and aging. This can be applied as a multidisciplinary approach to create and/or restore functional three-dimensional tissues or organs, which uses a combination of stem cells, scaffolds, and signaling molecules (tissue engineering), or direct application of cells to the site of injury or disorder (cell therapy). Tissue engineering might not be an ideal system for treating highly complex and multifunctional organ like the lung when targeting clinical application. Hence, cell therapy may be a more suitable treatment option because this can be applied by local or systemic administration combining with or without bioactive molecules such as erythropoietin. In this chapter, in the context of respiratory diseases, we will review the current research and clinical outcomes that involve the different approaches.
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- 2015
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38. Simplified anastomotic technique for end-to-side bronchial reimplantation onto the trachea or contralateral main bronchus after complex tracheobronchial resections
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Tetsuhiko Go, Paolo Macchiarini, and Gaetano Di Rienzo
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Male ,Pulmonary and Respiratory Medicine ,Surgical resection ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Bronchi ,Anastomosis ,Surgical anastomosis ,Main Bronchus ,Recurrence ,medicine ,Humans ,Aged ,Bronchus ,business.industry ,Anastomosis, Surgical ,Length of Stay ,Middle Aged ,respiratory system ,respiratory tract diseases ,Surgery ,Trachea ,Treatment Outcome ,medicine.anatomical_structure ,Replantation ,Female ,Cardiology and Cardiovascular Medicine ,business ,Airway ,End to side anastomosis ,Follow-Up Studies - Abstract
Recent anesthetic and surgical advances have remarkably reduced the frequency of airway complications after tracheobronchial resections, yet the end-to-side reimplantation of a main, lobar, or intermedius bronchus onto the trachea or the side of the contralateral main bronchus still represents a major technical challenge with high anastomotic morbidity and procedure-related mortality.1 We present the results of a simplified anastomotic technique for end-to-side reimplantation of the lobar or intermedius bronchus onto the trachea or contralateral main bronchus after extensive bronchial sleeve resections or carinal lobectomy.
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- 2002
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39. Characterization of Stem-Like Cells in Mucoepidermoid Tracheal Paediatric Tumor
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Jianri Lim, Paolo Macchiarini, Silvia Baiguera, Antonio Beltrán Rodríguez, Greg Lemon, Brandon Nick Sern Ooi, Tom Luedde, Lars Ährlund-Richter, Magnus Nordenskjöld, Evren Alici, Ivan Vassiliev, Ylva Gustafsson, Agne Liedén, José Inzunza, Iyadh Douagi, Johannes C. Haag, Philipp Jungebluth, Duncan Baker, Alina Popova, I. V. Gilevich, Sebastian Sjöqvist, Christian Unger, Mei Ling Lim, Isabell Hultman, and Jurate Asmundsson
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Male ,Pathology ,Microarrays ,Cellular differentiation ,lcsh:Medicine ,Cell Separation ,Cell Fate Determination ,Pediatrics ,Mice ,Animal Cells ,Molecular Cell Biology ,Medicine and Health Sciences ,lcsh:Science ,Child ,Stem cell transplantation for articular cartilage repair ,Multidisciplinary ,Stem Cells ,Amniotic stem cells ,Cell Differentiation ,Genomics ,3. Good health ,Mucoepidermoid Tumor ,medicine.anatomical_structure ,Bioassays and Physiological Analysis ,Oncology ,Neoplastic Stem Cells ,Female ,Stem cell ,Cellular Types ,Research Article ,medicine.medical_specialty ,Research and Analysis Methods ,Cancer stem cell ,medicine ,Animals ,Humans ,business.industry ,Gene Expression Profiling ,Mesenchymal stem cell ,lcsh:R ,Biology and Life Sciences ,Computational Biology ,Mesenchymal Stem Cells ,Cell Biology ,Pediatric Oncology ,lcsh:Q ,Tracheal Neoplasms ,Bone marrow ,business ,Developmental Biology - Abstract
Stem cells contribute to regeneration of tissues and organs. Cells with stem cell-like properties have been identified in tumors from a variety of origins, but to our knowledge there are yet no reports on tumor-related stem cells in the human upper respiratory tract. In the present study, we show that a tracheal mucoepidermoid tumor biopsy obtained from a 6 year-old patient contained a subpopulation of cells with morphology, clonogenicity and surface markers that overlapped with bone marrow mesenchymal stromal cells (BM-MSCs). These cells, designated as MEi (mesenchymal stem cell-like mucoepidermoid tumor) cells, could be differentiated towards mesenchymal lineages both with and without induction, and formed spheroids in vitro. The MEi cells shared several multipotent characteristics with BM-MSCs. However, they displayed differences to BM-MSCs in growth kinectics and gene expression profiles relating to cancer pathways and tube development. Despite this, the MEi cells did not possess in vivo tumor-initiating capacity, as proven by the absence of growth in situ after localized injection in immunocompromised mice. Our results provide an initial characterization of benign tracheal cancer-derived niche cells. We believe that this report could be of importance to further understand tracheal cancer initiation and progression as well as therapeutic development.
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- 2014
40. Extracorporeal membrane oxygenation-assisted esophagectomy
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Paolo Macchiarini, Stefano Romagnoli, Fulvio Pinelli, and Sergio Bevilacqua
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Mechanical ventilation ,Adult ,Male ,medicine.medical_specialty ,Cardiac output ,business.industry ,medicine.medical_treatment ,Remifentanil ,Cannula ,Surgery ,Esophagectomy ,Anesthesiology and Pain Medicine ,Extracorporeal Membrane Oxygenation ,Anesthesia ,Jugular vein ,medicine ,Extracorporeal membrane oxygenation ,Humans ,Thoracotomy ,Cardiology and Cardiovascular Medicine ,business ,medicine.drug - Abstract
CASE REPORTA 41-year-old man required an esophagectomy due to multipleareas of stenoses. His past surgical history included multiple esoph-ageal surgeries and dilation procedures in his childhood due toesophageal atresia and, later, tracheobronchial reconstruction for aniatrogenic trachea-esophageal fistula. His medical history was otherwisenoncontributory. To allow right lung collapse and to enable surgicalaccess to the esophagus via a right thoracotomy, one-lung ventilation(OLV) traditionally is required. However, OLV obtained via conven-tional measures (double-lumen endobronchial tube or bronchialblocker) was not feasible given the past surgical modification of histracheobronchial bifurcation. Moreover, the complex anatomic relation-ship between the airway and digestive tract required the availability oftotal extracorporeal ventilatory support if needed (ie, if surgicalcircumstances would not allow for mechanical ventilation). Ultra-lowtidal volume ventilation and VV- ECMO assistance via the rightinternal jugular vein was then planned, and a written informed consentto perform the surgery in this manner was obtained from the patient.Anesthesia was induced with 3 mg/kg of propofol and 1 μg/kg ofsufentanil. After the administration of 0.9 mg/kg of rocuronium, thetrachea was intubated under fiberoptic guidance with a 6.5-mm(internal diameter) oral-tracheal tube, with the tip positioned just belowthe vocal cords. Anesthesia was maintained with 4-to-6 mg/kg/h ofpropofol and 0.1-to-0.2 μg/kg/min of remifentanil; 0.1-0.3 mg/kg/hr ofrocuronium was administered according to the train-of-four monitoring.The American Society of Anesthesiologists standard monitoring wasimplemented with MostCare (Vygon, Vytech, Padova, Italy), a pulsecontour-based system for cardiac output estimation that received itsarterial waveform via the left radial artery with a standard pressuretransducer. The MostCare system provides hemodynamic data byanalyzing the arterial waveform at high sampling rate (1000 Hz) and,therefore, is not influenced by the VV-ECMO. In fact, the VV-ECMOdrains and injects blood into the right side of the cardiovascular systemwithout modifying, at steady state, right and left ventricular preload. A27-Fr double-lumen Avalon (Avalon Labs, Rancho Dominguez, CA)ECMO cannula was inserted into the right internal jugular vein undertransthoracic echography guidance using the subcostal approach. Afterthe administration of 5,000 IU of unfractionated heparin and radiologicconfirmation of proper placement, the cannula was connected to anheparin-coated ECMO circuit (Rotaflow System, Maquet Cardiopul-monary AG; GmbH & Co. KG; Rastatt, Germany) and primed withlactated Ringer’s solution. Activated partial thromboplastin time wastargeted to 50 to 70 seconds, and no further heparin administration wasnecessary throughout the case. During the thoracic portion of thesurgery, the mean pump flow was 2.06 L/min (SD 0.1; range 1.96-2.24). Mean inspired oxygen fraction (F
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- 2014
41. Primary Tracheal Tumors
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Paolo Macchiarini and Francesco Sammartino
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medicine.medical_specialty ,Primary (chemistry) ,business.industry ,Epidemiology ,Medicine ,business ,Airway ,Intensive care medicine - Published
- 2014
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42. Understanding Hyperacute Rejection of the Lung: Is This a Special Case?
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Richard N. Pierson, Paolo Macchiarini, and Agnes Azimzadeh
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Transplantation ,medicine.medical_specialty ,Lung ,medicine.anatomical_structure ,business.industry ,medicine ,Special case ,Intensive care medicine ,business - Published
- 2001
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43. Partial cricoidectomy with primary thyrotracheal anastomosis for postintubation subglottic stenosis
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Jean-Philippe Verhoye, Alain Chapelier, Philippe Dartevelle, Elie Fadel, and Paolo Macchiarini
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Adolescent ,Subglottic stenosis ,Tracheoesophageal fistula ,Anastomosis ,Cricoid Cartilage ,Surgical anastomosis ,Cricoid cartilage ,Intubation, Intratracheal ,medicine ,Humans ,Child ,Aged ,Retrospective Studies ,Cricoidectomy ,business.industry ,Anastomosis, Surgical ,Laryngostenosis ,Middle Aged ,medicine.disease ,Surgery ,Survival Rate ,Trachea ,Stenosis ,medicine.anatomical_structure ,Child, Preschool ,Thyroid Cartilage ,Cuff ,Female ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objective: We describe a Pearson-type technique and evaluate its results for postintubation subglottic stenosis. Methods: Forty-five patients underwent a partial cricoidectomy with primary thyrotracheal anastomosis, and 5 underwent simultaneous repair of a tracheoesophageal fistula as well. Twenty-four (53%) patients were referred to us after initial conservative (n = 21) or operative (n = 3) management. There were 27 cuff lesions, 7 stomal lesions, and 11 at both levels. The upper limit of the stenosis was 1.5 cm (range, 1-2.5 cm) below the cords, and the subglottic diameter was reduced by 60% in 38 (84%) of the patients. The length of airway resection ranged from 2 to 6 cm (median, 3 cm). Despite 23 thyrohyoid or suprahyoid releases, 8 anastomoses were under tension. Results: Thirty-seven (82%) patients were extubated after the operation (n = 30) or within 24 hours (n = 7). Six patients required postoperative airway stenting (median, 5.5 days). Early (
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- 2001
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44. USE OF EMBRYONIC HUMAN TRACHEA GROWN IN NUDE MICE TO PATCH-REPAIR CONGENITAL TRACHEAL STENOSIS1
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Vincent Thomas de Montpréville, Philippe Coullin, Karine Duprez-angio˙i, Philippe Dartevelle, Jean-Jacques Candelier, Nadia Guerra, Rafael Oriol, and Paolo Macchiarini
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Transplantation ,Pathology ,medicine.medical_specialty ,biology ,business.industry ,Ratón ,medicine.medical_treatment ,Respiratory disease ,Immunosuppression ,In situ hybridization ,respiratory system ,medicine.disease ,biology.organism_classification ,Tracheal Stenosis ,Stenosis ,Tissue culture ,Nude mouse ,medicine ,business - Abstract
Background. Long congenital tracheal stenosis is a life-threatening condition, and the available surgical treatments do not give satisfactory long-term results. Methods. Human embryonic tracheas were implanted in the abdominal cavities of nude mice until their differentiation was completed. These differentiated tracheas were used to patch-repair surgically induced tracheal stenosis in piglets. The human, mouse, or pig origin, of all the cells in the two successive xenotransplants in the nude mouse and the pig, was determined on tissue sections by in situ hybridization with species-specific DNA probes. Results. The transplanted pigs thrived and reached normal adulthood, irrespective of the administration of immunosuppressive treatment. The human tracheal tissue developed in nude mice conserved human structures, with the exception of feeding capillaries, which were of mouse origin. The tracheal patch in the adult healthy pigs comprised only pig cells organized into a fibrous scar, which was covered by normal pig epithelium. Conclusions. Results suggest that human embryonic trachea grown in nude mice can be successfully used as patch tracheoplasty for long congenital tracheal stenosis without conventional immunosuppression.
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- 2000
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45. Surgical treatment of pulmonary aspergilloma: Current outcome
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Gerard Babatasi, Elie Fadel, Paolo Macchiarini, Philippe Dartevelle, Andre Khayat, Massimo Massetti, and Alain Chapelier
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Lung Diseases ,Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,medicine.medical_treatment ,Lung abscess ,Asymptomatic ,Pneumonectomy ,Postoperative Complications ,medicine ,Aspergillosis ,Humans ,Settore MED/23 - CHIRURGIA CARDIACA ,Tomography ,Survival rate ,Retrospective Studies ,Lung Diseases, Fungal ,business.industry ,Patient Selection ,Retrospective cohort study ,medicine.disease ,Empyema ,X-Ray Computed ,Surgery ,Survival Rate ,Fungal ,Treatment Outcome ,Respiratory failure ,Female ,medicine.symptom ,Tomography, X-Ray Computed ,business ,Cardiology and Cardiovascular Medicine ,Aspergilloma - Abstract
Objective: This retrospective study was designed to confirm that aggressive pulmonary resection can provide effective long-term palliation of disease for patients with pulmonary aspergilloma. Methods and results: From 1959 to 1998, 84 patients underwent a total of 90 operations for treatment of pulmonary aspergilloma in the Marie-Lannelongue Hospital. The mean follow-up period was 9 years, and 83% of the patients were followed up for 5 years or until death, if the latter occurred earlier. The median age was 44 years. The most common indications were hemoptysis (66%) and sputum production (15%). Fifteen patients (18%) had no symptoms. Tuberculosis and lung abscess were the most common underlying causes of lung disease (65%). The procedures were 70 lobar or segmental resections, 8 cavernostomies, and 7 pneumonectomies. Five thoracoplasties were required after lobectomy (3 patients) or pneumonectomy (2 patients). The operative mortality rate was 4%. The major complications were bleeding (23 patients), prolonged air leak (31 patients), respiratory failure (10 patients), and empyema (5 patients). The actuarial survival curve showed 84% survival at 5 years and 74% survival at 10 years. During the first 2 years, death was related to the surgical procedure and the underlying disease. In contrast, 85% of the survivors had a good late result. Conclusion: Lobar resection in both the symptomatic and the asymptomatic patients was conducted in low-risk settings. For patients whose condition is unfit for pulmonary resection, cavernostomy may need to be undertaken despite the high operative risk. The better survival rate in this study may have been due to the selection of patients with better lung function and localized pulmonary disease. (J Thorac Cardiovasc Surg 2000;119:906-12)
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- 2000
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46. Evaluation and outcome of different surgical techniques for postintubation tracheoesophageal fistulas
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Jean-Philippe Verhoye, Elie Fadel, Paolo Macchiarini, Philippe Dartevelle, and Alain Chapelier
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Colon ,Fistula ,medicine.medical_treatment ,Tracheoesophageal fistula ,Anastomosis ,Esophagus ,Tracheotomy ,Intubation, Intratracheal ,medicine ,Humans ,Intubation ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Esophageal disease ,Anastomosis, Surgical ,Middle Aged ,medicine.disease ,Surgery ,Tracheal Stenosis ,Survival Rate ,Trachea ,Treatment Outcome ,medicine.anatomical_structure ,Esophagoplasty ,Female ,Cardiology and Cardiovascular Medicine ,business ,Tracheoesophageal Fistula - Abstract
Objective: We evaluated the outcome of different surgical techniques for postintubation tracheoesophageal fistula. Methods: Thirty-two consecutive patients aged 51 ± 23 years had tracheoesophageal fistulas resulting from a median of 30 days of mechanical ventilation via endotracheal (n = 12) or tracheostomy (n = 20) tubes. Tracheoesophageal fistulas were 2.5 ± 1.2 cm long and were associated with a tracheal (n = 10) or subglottic (n = 3) stenosis in 13 patients. Results: All but 3 patients were weaned from respirators before repair. All operations were done through cervical incisions and included direct division and closure (n = 9), esophageal diversion (n = 3), muscle interposition (n = 6), or, more recently, tracheal or laryngotracheal resection and anastomosis with primary esophageal closure (n = 14). Nine thyrohyoid and two supralaryngeal releases reduced anastomotic tension. Twenty-three patients (74%) were extubated after the operation (n = 16) or within 24 hours (n = 7), and 7 required a temporary tracheotomy tube. One postoperative death (3%) was associated with recurrent tracheoesophageal fistula. Seven complications (22%) included recurrent tracheoesophageal fistula (n = 1), delayed tracheal stenosis (n = 2), dysphagia (n = 2), and recurrent nerve palsy (n = 2). Complications necessitated reoperation (n = 1), dilation (n = 2), definitive tracheostomy (n = 1), Montgomery T tubes (n = 1), and Teflon injection of the vocal cords (n = 1). Twenty-nine patients (93%) had excellent (n = 24) or good (n = 5) anatomic and functional long-term results. Complications have been less common (7% vs 38%) and long-term results better (93% vs 65%) recently with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure as compared with previous procedures. Conclusions: Postintubation tracheoesophageal fistula is usually best treated with tracheal or laryngotracheal resection and anastomosis with primary esophageal closure even in the absence of tracheal damage. (J Thorac Cardiovasc Surg 2000;119:268-76)
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- 2000
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47. Revascularised laryngeal allografts in a pig model: experimental technique
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Paolo Macchiarini, Mick Bailey, and MA Birchall
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Pathology ,medicine.medical_specialty ,Otorhinolaryngology ,business.industry ,medicine ,Pig model ,business ,Surgery - Published
- 1999
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48. Clamshell or sternotomy for double lung or heart-lung transplantation?1
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Philippe Dartevelle, Jacques Cerrina, Elie Fadel, Alain Chapelier, Paolo Macchiarini, and François Le Roy Ladurie
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Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung ,business.industry ,medicine.medical_treatment ,Bronchiolitis obliterans ,General Medicine ,Anastomosis ,medicine.disease ,Pulmonary hypertension ,Surgery ,Transplantation ,medicine.anatomical_structure ,Median sternotomy ,Anesthesia ,Deformity ,Medicine ,Lung transplantation ,medicine.symptom ,Cardiology and Cardiovascular Medicine ,business - Abstract
Objective: To evaluate the influence of either incision on the lungs and chest wall. Methods: Ninety-two double lung (DLT) or heartlung (HLT) transplantations were done since January 1990. There were 22 (24%) hospital deaths, leaving 70 patients with complete data for evaluation. We did 38 DLT and 32 HLT for end-stage chronic respiratory failure (n = 22) and primary (n = 34) or secondary (n = 14) pulmonary hypertension, using 37 fourth or fifth interspace clamshell incisions and 33 median sternotomies. Results: The clamshell group included a higher percentage of DLTs (73 vs. 33%, P = 0.001) but recipient age, gender, preoperative diagnosis, bronchial anastomotic complications, number of cytomegalovirus infection, episode of acute rejection per patient-months and incidence of bronchiolitis obliterans were not statistically different between the two groups. At a follow-up time of 3.7 ∠ 2 years, the overall 5-year survival of 57% was not influenced by the type of incision. The clamshell incision caused sternal over-riding in 12 (32%) patients, and eight surgical clamshell revision were necessary as compared with one median sternotomy (P = 0.02). The clamshell incision was associated with a significantly higher incidence of postoperative chronic pain (27 vs. 6%, P = 0.02). Postoperative mechanical properties of the chest wall were significantly (P , 0.0001) worse in the clamshell-group patients while the intrinsic properties of the airways were not different. Conclusions: The clamshell incision results in more postoperative deformity, chronic pain, and impaired function as compared with median sternotomy. A bilateral anterolateral thoracotomy without division of the sternum is proposed for the sequential bilateral lung transplantation technique. © 1999 Elsevier Science B.V. All rights reserved.
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- 1999
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49. Technique to Avoid Innominate Artery Ligation and Perform an Anterior Mediastinal Tracheostomy for Residual Trachea of Less Than 5 cm
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Abel Gómez-Caro, Paolo Macchiarini, and Josep Maria Gimferrer
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Male ,Pulmonary and Respiratory Medicine ,Thorax ,medicine.medical_specialty ,Fistula ,medicine.medical_treatment ,Surgical Flaps ,Tracheostomy ,Tracheotomy ,medicine.artery ,Brachiocephalic artery ,medicine ,Humans ,Ligature ,Ligation ,Brachiocephalic Trunk ,business.industry ,Mediastinum ,Middle Aged ,medicine.disease ,Surgery ,Laryngectomy ,medicine.anatomical_structure ,Radiology ,Cardiology and Cardiovascular Medicine ,business ,Artery - Abstract
A 47-year-old man was admitted with recurrent autolimited bleeding arising from a cervical tracheostoma made 2 years earlier during a total laryngectomy. Stomal recurrence of the past laryngeal cancer invading the neighboring innominate artery was diagnosed by angiographic computer tomography and bronchoscopic biopsies. The malignant tracheostoma-innominate fistula was approached through an extended transversal supraclavicular incision, bilateral hemiclaviculectomy, and manubriectomy. It was treated with an anterior mediastinal tracheostomy with omental major transposition, right latissimus dorsi myocutaneous flap for tissue coverage, and brachiocephalic artery rerouting with cadaveric homograft. The patient was discharged on postoperative day 14 after an uneventful postoperative course.
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- 2007
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50. Thrombo-endartériectomie pulmonaire sous vidéo-angioscopie et arrêt circulatoire: une alternative à la transplantation cardiopulmonaire dans l'hypertension artérielle pulmonaire postembolique
- Author
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G. Simonneau, Philippe Dartevelle, François Parquin, Paolo Macchiarini, F Simonneau, Jacques Cerrina, M Humbert, E. Fadel, François Leroy-Ladurie, F. Parent, and Alain Chapelier
- Subjects
Gynecology ,medicine.medical_specialty ,business.industry ,medicine ,Surgery ,business - Abstract
Resume La principale cause d'echec des thrombo-endarteriectomies pulmonaires est l'insuffisance de la desobstruction des branches distales des arteres pulmonaires. Le but de cette etude est de souligner l'interet de l'angioscopie videoassistee comme aide a une endarteriectomie plus etendue et plus efficace. L'intervention est faite par sternotomie mediane, sous circulation extracorporelle en hypothermie profonde, et la dissection est limitee a la mobilisation totale de la veine cave superieure. L'endarteriectomie, toujours bilaterale, est faite a travers une arteriotomie longitudinale des arteres pulmonaires droite et gauche. Un endoscope rigide de 5 mm de diametre, introduit dans l'artere pulmonaire, guide l'endarteriectomie des branches les plus distales inaccessibles a la vue. De janvier 1996 a decembre 1997, 48 patients atteints d'hypertension arterielle pulmonaire postembolique grave sur le plan fonctionnel (deux stade II de la NYHA, 28 stade III et 18 stade IV) et sur le plan hemodynamique (pression arterielle pulmonaire moyenne: 53 ± 13 mmHg, index cardiaque: 2,16 ± 0,5 L/min/m 2 , resistances vasculaires pulmonaires totales: 1152 ± 414 dynes·s −1 ·cm 5 ) ont beneficie de cette intervention. Dans les suites operatoires, six patients sont decedes: quatre du fait d'une endarteriectomie insuffisante, un par hemorragie alveolaire et un par arret cardiaque hypoxique. Les 42 patients vivants ont eu une amelioration significative des parametres hemodynamiques (pression arterielle pulmonaire moyenne: 30 ± 9 mmHg, index cardiaque: 2,78 ± 0,5 L/min/m 2 , resistances vasculaires pulmonaires totales: 484 ± 159 dynes·s −1 cm 5 ). Quarante patients ont eu un excellent resultat fonctionnel postoperatoire (24 stade I et 16 stade II). Deux patients n'ont pas ete ameliores et sont restes au stade III, l'un d'eux est en attente de transplantation. La videoangioscopie a permis d'ameliorer la qualite de la thromboendarteriectomie et d'elargir les indications de cette chirurgie restauratrice aux patients les plus graves qui etaient auparavant candidats a une transplantation cardiopulmonaire.
- Published
- 1998
- Full Text
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