649 results on '"Raffoul, Wassim"'
Search Results
202. Body Taping for Contour Surgery
- Author
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Kalbermatten, Daniel Felix, primary, Wettstein, Reto, additional, Erba, Paolo, additional, Rieger, Ulrich Michael, additional, Pierer, Gerhard, additional, and Raffoul, Wassim, additional
- Published
- 2008
- Full Text
- View/download PDF
203. Importation ofAcinetobacter baumanniiInto a Burn Unit: A Recurrent Outbreak of Infection Associated With Widespread Environmental Contamination
- Author
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Zanetti, Giorgio, primary, Blanc, Dominique S., additional, Federli, Isabelle, additional, Raffoul, Wassim, additional, Petignat, Christiane, additional, Maravic, Philippe, additional, Francioli, Patrick, additional, and Berger, Mette M., additional
- Published
- 2007
- Full Text
- View/download PDF
204. Epidermolyse nécrosante suraiguë de Lyell ou toxic epidermal necrolysis
- Author
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Bigliardi, Paul L., primary, Raffoul, Wassim, additional, and Berger, Mette M., additional
- Published
- 2007
- Full Text
- View/download PDF
205. Ulnar Nerve Transposition at the Elbow under Local Anesthesia: A Patient Satisfaction Study.
- Author
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Roberti del Vecchio, Pietro M., Christen, Thierry, Raffoul, Wassim, and Erba, Paolo
- Subjects
ULNAR nerve ,DECOMPRESSION (Physiology) ,GENERAL anesthesia ,PATIENT satisfaction ,LOCAL anesthesia ,SURGERY - Abstract
Background Ulnar nerve decompression at the elbow traditionally requires regional or general anesthesia. We wished to assess the feasibility of performing ulnar nerve decompression and transposition at the elbow under local anesthesia. Methods We examined retrospectively the charts of 50 consecutive patients having undergone ulnar nerve entrapment surgery either under general or local anesthesia. Patients were asked to estimate pain on postoperative days 1 and 7 and satisfaction was assessed at 1 year. Results On day 1, pain was comparable among all groups. On day 7, pain scores were twice as high when transposition was performed under general anesthesia when compared with local anesthesia. Patient satisfaction was slightly increased in the local anesthesia group. These patients were significantly more willing to repeat the surgery. Conclusion Ulnar nerve decompression and transposition at the elbow can be performed under local anesthesia without added morbidity when compared with general anesthesia. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
- View/download PDF
206. Is There Really a Survival Benefit of SDD in Burns?
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Eggimann, Philippe, primary, Chiol??ro, Ren?? L., additional, Raffoul, Wassim, additional, Voirol, Pierre, additional, and Berger, Mette M., additional
- Published
- 2006
- Full Text
- View/download PDF
207. Increased Wnt signaling triggers oncogenic conversion of human breast epithelial cells by a Notch-dependent mechanism
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Ayyanan, Ayyakannu, primary, Civenni, Gianluca, additional, Ciarloni, Laura, additional, Morel, Catherine, additional, Mueller, Nathalie, additional, Lefort, Karine, additional, Mandinova, Anna, additional, Raffoul, Wassim, additional, Fiche, Maryse, additional, Dotto, Gian Paolo, additional, and Brisken, Cathrin, additional
- Published
- 2006
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208. A novel technique for the reconstruction of infected full-thickness chest wall defects
- Author
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Raffoul, Wassim, primary, Dusmet, Michael, additional, Landry, Michel, additional, and Ris, Hans-Beat, additional
- Published
- 2001
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- View/download PDF
209. Abnormal Balance between Proliferation and Apoptotic Cell Death in Fibroblasts Derived from Keloid Lesions
- Author
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Luo, Shengkang, primary, Benathan, Messod, additional, Raffoul, Wassim, additional, Panizzon, Renato G., additional, and Egloff, Daniel V., additional
- Published
- 2001
- Full Text
- View/download PDF
210. Anterolateral Thigh Fasciocutaneous Flap in the Difficult Perineogenital Reconstruction
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Luo, Shengkang, primary, Raffoul, Wassim, additional, Piaget, F., additional, and Egloff, Daniel V., additional
- Published
- 2000
- Full Text
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211. Anterolateral thigh flap: A review of 168 cases
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Luo, Shengkang, primary, Raffoul, Wassim, additional, Luo, Jinhui, additional, Luo, Lishen, additional, Gao, Jianhua, additional, Chen, Linfeng, additional, and Egloff, Daniel V., additional
- Published
- 1999
- Full Text
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212. Bilateral Silicone Granulomas Mimicking Breast Cancer Recurrence on 18F-FDG PET/CT.
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Fernandes Vieira, Victor, Dubruc, Estelle, Raffoul, Wassim, Prior, John O., and Meyer, Marie
- Published
- 2021
- Full Text
- View/download PDF
213. PALLIATIVE SURGICAL PROCEDURES TO RESTORE SHOULDER FUNCTION IN OBSTETRIC BRACHIAL PALSY
- Author
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Egloff, Daniel V., primary, Raffoul, Wassim, additional, Bonnard, Chantal, additional, and Stalder, Jean, additional
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- 1995
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214. Flux EXPLORER: a new high-speed laser Doppler imaging system for the assessment of burn injuries.
- Author
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Erba, Paolo, Espinoza, Daniel, Koch, Nathalie, Christen, Thierry, Serov, Alexandre, and Raffoul, Wassim
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SURGICAL excision ,SKIN grafting ,BURNS & scalds ,MEDICAL imaging systems ,PLASTIC surgery ,DEBRIDEMENT ,MINIATURE electronic equipment - Abstract
Background Deep burn assessment made by clinical evaluation has an accuracy varying between 60% and 80% and will determine if a burn injury will need tangential excision and skin grafting or if it will be able to heal spontaneously. Laser Doppler Imaging ( LDI) techniques allow an improved burn depth assessment but their use is limited by the time-consuming image acquisition which may take up to 6 min per image. Methods To evaluate the effectiveness and reliability of a newly developed full-field LDI technology, 15 consecutive patients presenting with intermediate depth burns were assessed both clinically and by FluxExplorer LDI technology. Comparison between the two methods of assessment was carried out. Results Image acquisition was done within 6 s. Flux EXPLORER LDI technology achieved a significantly improved accuracy of burn depth assessment compared to the clinical judgement performed by board certified plastic and reconstructive surgeons ( P < 0.05, 93% of correctly assessed burns injuries vs. 80% for clinical assessment). Conclusion Technological improvements of LDI technology leading to a decreased image acquisition time and reliable burn depth assessment allow the routine use of such devices in the acute setting of burn care without interfering with the patient's treatment. Rapid and reliable LDI technology may assist clinicians in burn depth assessment and may limit the morbidity of burn patients through a minimization of the area of surgical debridement. Future technological improvements allowing the miniaturization of the device will further ease its clinical application. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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215. Combination of Hyaluronan and Lyophilized Progenitor Cell Derivatives: Stabilization of Functional Hydrogel Products for Therapeutic Management of Tendinous Tissue Disorders.
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Laurent, Alexis, Porcello, Alexandre, Fernandez, Paula Gonzalez, Jeannerat, Annick, Peneveyre, Cédric, Abdel-Sayed, Philippe, Scaletta, Corinne, Hirt-Burri, Nathalie, Michetti, Murielle, de Buys Roessingh, Anthony, Raffoul, Wassim, Allémann, Eric, Jordan, Olivier, and Applegate, Lee Ann
- Subjects
PROGENITOR cells ,HYALURONIC acid ,PRODUCT management ,HYDROGELS ,REGENERATIVE medicine - Abstract
Cultured progenitor cells and derivatives have been used in various homologous applications of cutaneous and musculoskeletal regenerative medicine. Active pharmaceutical ingredients (API) in the form of progenitor cell derivatives such as lysates and lyophilizates were shown to retain function in controlled cellular models of wound repair. On the other hand, hyaluronan-based hydrogels are widely used as functional vehicles in therapeutic products for tendon tissue disorders. The aim of this study was the experimental characterization of formulations containing progenitor tenocyte-derived APIs and hyaluronan, for the assessment of ingredient compatibility and stability in view of eventual therapeutic applications in tendinopathies. Lyophilized APIs were determined to contain relatively low quantities of proteins and growth factors, while being physicochemically stable and possessing significant intrinsic antioxidant properties. Physical and rheological quantifications of the combination formulas were performed after hydrogen peroxide challenge, outlining significantly improved evolutive viscoelasticity values in accelerated degradation settings. Thus, potent effects of physicochemical protection or stability enhancement of hyaluronan by the incorporated APIs were observed. Finally, combination formulas were found to be easily injectable into ex vivo tendon tissues, confirming their compatibility with further translational clinical approaches. Overall, this study provides the technical bases for the development of progenitor tenocyte derivative-based injectable therapeutic products or devices, to potentially be applied in tendinous tissue disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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216. Hypoxic Incubation Conditions for Optimized Manufacture of Tenocyte-Based Active Pharmaceutical Ingredients of Homologous Standardized Transplant Products in Tendon Regenerative Medicine.
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Jeannerat, Annick, Peneveyre, Cédric, Armand, Florence, Chiappe, Diego, Hamelin, Romain, Scaletta, Corinne, Hirt-Burri, Nathalie, de Buys Roessingh, Anthony, Raffoul, Wassim, Applegate, Lee Ann, and Laurent, Alexis
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HOMOGRAFTS ,MANUFACTURING cells ,OSTEOINDUCTION ,EXTRACELLULAR matrix proteins ,PROTEIN expression ,REGENERATIVE medicine - Abstract
Human fetal progenitor tenocytes (hFPT) produced in defined cell bank systems have recently been characterized and qualified as potential therapeutic cell sources in tendon regenerative medicine. In view of further developing the manufacture processes of such cell-based active pharmaceutical ingredients (API), the effects of hypoxic in vitro culture expansion on key cellular characteristics or process parameters were evaluated. To this end, multiple aspects were comparatively assessed in normoxic incubation (i.e., 5% CO
2 and 21% O2 , standard conditions) or in hypoxic incubation (i.e., 5% CO2 and 2% O2 , optimized conditions). Experimentally investigated parameters and endpoints included cellular proliferation, cellular morphology and size distribution, cell surface marker panels, cell susceptibility toward adipogenic and osteogenic induction, while relative protein expression levels were analyzed by quantitative mass spectrometry. The results outlined conserved critical cellular characteristics (i.e., cell surface marker panels, cellular phenotype under chemical induction) and modified key cellular parameters (i.e., cell size distribution, endpoint cell yields, matrix protein contents) potentially procuring tangible benefits for next-generation cell manufacturing workflows. Specific proteomic analyses further shed some light on the cellular effects of hypoxia, potentially orienting further hFPT processing for cell-based, cell-free API manufacture. Overall, this study indicated that hypoxic incubation impacts specific hFPT key properties while preserving critical quality attributes (i.e., as compared to normoxic incubation), enabling efficient manufacture of tenocyte-based APIs for homologous standardized transplant products. [ABSTRACT FROM AUTHOR]- Published
- 2021
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217. Evolution of Diploid Progenitor Lung Cell Applications: From Optimized Biotechnological Substrates to Potential Active Pharmaceutical Ingredients in Respiratory Tract Regenerative Medicine.
- Author
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Laurent, Alexis, Abdel-Sayed, Philippe, Hirt-Burri, Nathalie, Scaletta, Corinne, Michetti, Murielle, de Buys Roessingh, Anthony, Raffoul, Wassim, and Applegate, Lee Ann
- Subjects
REGENERATIVE medicine ,PROGENITOR cells ,LUNGS ,COVID-19 ,CURRENT good manufacturing practices ,VACCINE trials - Abstract
The objective of this review is to describe the evolution of lung tissue-derived diploid progenitor cell applications, ranging from historical biotechnological substrate functions for vaccine production and testing to current investigations around potential therapeutic use in respiratory tract regenerative medicine. Such cell types (e.g., MRC-5 or WI-38 sources) were extensively studied since the 1960s and have been continuously used over five decades as safe and sustainable industrial vaccine substrates. Recent research and development efforts around diploid progenitor lung cells (e.g., FE002-Lu or Walvax-2 sources) consist in qualification for potential use as optimal and renewed vaccine production substrates and, alternatively, for potential therapeutic applications in respiratory tract regenerative medicine. Potentially effective, safe, and sustainable cell therapy approaches for the management of inflammatory lung diseases or affections and related symptoms (e.g., COVID-19 patients and burn patient severe inhalation syndrome) using local homologous allogeneic cell-based or cell-derived product administrations are considered. Overall, lung tissue-derived progenitor cells isolated and produced under good manufacturing practices (GMP) may be used with high versatility. They can either act as key industrial platforms optimally conforming to specific pharmacopoeial requirements or as active pharmaceutical ingredients (API) for potentially effective promotion of lung tissue repair or regeneration. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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218. Bilateral Silicone Granulomas Mimicking Breast Cancer Recurrence on 18F-FDG PET/CT
- Author
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Fernandes Vieira, Victor, Dubruc, Estelle, Raffoul, Wassim, Prior, John O., and Meyer, Marie
- Abstract
We report the case of a 45-year-old woman with a history of right breast reconstruction with silicone implant for breast cancer. An 18F-FDG PET/CT performed several years later revealed the presence of 18F-FDG–avid nodules at the periphery of the silicone implant, in the right internal mammary chain, and in the contralateral breast. Needle core biopsies were positive for bilateral silicone granulomas, without any sign of malignancy. This case displays intense 18F-FDG uptake in silicone granulomas affecting the contralateral breast after implant reconstruction.
- Published
- 2021
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219. Corrigendum to: Burn Center Organization and Cellular Therapy Integration: Managing Risks and Costs.
- Author
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Chemali, Michèle, Laurent, Alexis, Scaletta, Corinne, Waselle, Laurent, Simon, Jeanne-Pascale, Michetti, Murielle, Brunet, Jean-François, Flahaut, Marjorie, Hirt-Burri, Nathalie, Raffoul, Wassim, Applegate, Lee Ann, Roessingh, Anthony S de Buys, Abdel-Sayed, Philippe, and de Buys Roessingh, Anthony S
- Subjects
BURN care units ,CELLULAR therapy ,COST ,ORGANIZATION - Published
- 2021
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220. Optimized Manufacture of Lyophilized Dermal Fibroblasts for Next-Generation Off-the-Shelf Progenitor Biological Bandages in Topical Post-Burn Regenerative Medicine.
- Author
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Laurent, Alexis, Scaletta, Corinne, Abdel-Sayed, Philippe, Michetti, Murielle, Flahaut, Marjorie, Simon, Jeanne-Pascale, Roessingh, Anthony de Buys, Raffoul, Wassim, Hirt-Burri, Nathalie, and Applegate, Lee Ann
- Subjects
BIOLOGICAL dressings ,REGENERATIVE medicine ,TECHNICAL specifications ,FIBROBLASTS ,BIOMATERIALS - Abstract
Cultured fibroblast progenitor cells (FPC) have been studied in Swiss translational regenerative medicine for over two decades, wherein clinical experience was gathered for safely managing burns and refractory cutaneous ulcers. Inherent FPC advantages include high robustness, optimal adaptability to industrial manufacture, and potential for effective repair stimulation of wounded tissues. Major technical bottlenecks in cell therapy development comprise sustainability, stability, and logistics of biological material sources. Herein, we report stringently optimized and up-scaled processing (i.e., cell biobanking and stabilization by lyophilization) of dermal FPCs, with the objective of addressing potential cell source sustainability and stability issues with regard to active substance manufacturing in cutaneous regenerative medicine. Firstly, multi-tiered FPC banking was optimized in terms of overall quality and efficiency by benchmarking key reagents (e.g., medium supplement source, dissociation reagent), consumables (e.g., culture vessels), and technical specifications. Therein, fetal bovine serum batch identity and culture vessel surface were confirmed, among other parameters, to largely impact harvest cell yields. Secondly, FPC stabilization by lyophilization was undertaken and shown to maintain critical functions for devitalized cells in vitro, potentially enabling high logistical gains. Overall, this study provides the technical basis for the elaboration of next-generation off-the-shelf topical regenerative medicine therapeutic products for wound healing and post-burn care. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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221. Antimicrobial Peptide Dendrimers and Quorum-Sensing Inhibitors in Formulating Next-Generation Anti-Infection Cell Therapy Dressings for Burns.
- Author
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Jafari, Paris, Luscher, Alexandre, Siriwardena, Thissa, Michetti, Murielle, Que, Yok-Ai, Rahme, Laurence G., Reymond, Jean-Louis, Raffoul, Wassim, Van Delden, Christian, Applegate, Lee Ann, and Köhler, Thilo
- Subjects
CELLULAR therapy ,QUORUM sensing ,PROGENITOR cells ,MULTIDRUG resistance ,BIOTHERAPY ,BACTERIAL growth ,DENDRIMERS ,ANTIBIOTICS - Abstract
Multidrug resistance infections are the main cause of failure in the pro-regenerative cell-mediated therapy of burn wounds. The collagen-based matrices for delivery of cells could be potential substrates to support bacterial growth and subsequent lysis of the collagen leading to a cell therapy loss. In this article, we report the development of a new generation of cell therapy formulations with the capacity to resist infections through the bactericidal effect of antimicrobial peptide dendrimers and the anti-virulence effect of anti-quorum sensing MvfR (PqsR) system compounds, which are incorporated into their formulation. Anti-quorum sensing compounds limit the pathogenicity and antibiotic tolerance of pathogenic bacteria involved in the burn wound infections, by inhibiting their virulence pathways. For the first time, we report a biological cell therapy dressing incorporating live progenitor cells, antimicrobial peptide dendrimers, and anti-MvfR compounds, which exhibit bactericidal and anti-virulence properties without compromising the viability of the progenitor cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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222. Propionibacterium avidum infection following breast reduction: high morbidity from a low-virulence pathogen.
- Author
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di Summa, Pietro G., Yvon, Adrien, Larcher, Lorenz, Raffoul, Wassim, and Koch, Nathalie
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PROPIONIBACTERIUM ,REDUCTION mammaplasty ,ABSCESSES ,ULTRASONIC imaging ,AMOXICILLIN ,CLAVULANIC acid - Abstract
Propionibacterium avidum is a common inhabitant of sebaceous glands, traditionally considered to be of low virulence and generally found on implanted foreign material. We report a rare case of P. avidum breast abscess, causing severe morbidity following breast reduction surgery. A 36-year-old woman presented with a non-painful wound discharge 3 weeks postoperatively, and was treated conservatively. She was readmitted 7 weeks postoperatively with a red and tender breast. A purulent discharging abscesswas drained under ultrasound guidance. A 2-week intravenous course of amoxicillin--clavulanic acid, followed by oral replacement for a month resulted effective. Serial ultrasound imaging was useful in treatment decision-making. The infective potential of P. avidum may be underappreciated. Proximity of sutures to the axilla, tobacco smoking and the potential for resorbable sutures to host bacteria may predispose to infection, and should raise the clinician's awareness. [ABSTRACT FROM AUTHOR]
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- 2015
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223. Industrial Development of Standardized Fetal Progenitor Cell Therapy for Tendon Regenerative Medicine: Preliminary Safety in Xenogeneic Transplantation.
- Author
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Laurent, Alexis, Abdel-Sayed, Philippe, Grognuz, Anthony, Scaletta, Corinne, Hirt-Burri, Nathalie, Michetti, Murielle, de Buys Roessingh, Anthony S., Raffoul, Wassim, Kronen, Peter, Nuss, Katja, von Rechenberg, Brigitte, Applegate, Lee Ann, and Darwiche, Salim E.
- Subjects
CELLULAR therapy ,REGENERATIVE medicine ,PROGENITOR cells ,INDUSTRIALIZATION ,FETAL development - Abstract
Tendon defects require multimodal therapeutic management over extensive periods and incur high collateral burden with frequent functional losses. Specific cell therapies have recently been developed in parallel to surgical techniques for managing acute and degenerative tendon tissue affections, to optimally stimulate resurgence of structure and function. Cultured primary human fetal progenitor tenocytes (hFPT) have been preliminarily considered for allogeneic homologous cell therapies, and have been characterized as stable, consistent, and sustainable cell sources in vitro. Herein, optimized therapeutic cell sourcing from a single organ donation, industrial transposition of multi-tiered progenitor cell banking, and preliminary preclinical safety of an established hFPT cell source (i.e., FE002-Ten cell type) were investigated. Results underlined high robustness of FE002-Ten hFPTs and suitability for sustainable manufacturing upscaling within optimized biobanking workflows. Absence of toxicity or tumorigenicity of hFPTs was demonstrated in ovo and in vitro, respectively. Furthermore, a 6-week pilot good laboratory practice (GLP) safety study using a rabbit patellar tendon partial-thickness defect model preliminarily confirmed preclinical safety of hFPT-based standardized transplants, wherein no immune reactions, product rejection, or tumour formation were observed. Such results strengthen the rationale of the multimodal Swiss fetal progenitor cell transplantation program and prompt further investigation around such cell sources in preclinical and clinical settings for musculoskeletal regenerative medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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- View/download PDF
224. Human platelet lysate as a potential clinical-translatable supplement to support the neurotrophic properties of human adipose-derived stem cells.
- Author
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Palombella, Silvia, Guiotto, Martino, Higgins, Gillian C., Applegate, Laurent L., Raffoul, Wassim, Cherubino, Mario, Hart, Andrew, Riehle, Mathis O., and di Summa, Pietro G.
- Subjects
HUMAN stem cells ,GROWTH factors ,SCHWANN cells ,NERVE grafting ,AUTOTRANSPLANTATION ,CELL transplantation - Abstract
Background: The autologous nerve graft, despite its donor site morbidity and unpredictable functional recovery, continues to be the gold standard in peripheral nerve repair. Rodent research studies have shown promising results with cell transplantation of human adipose-derived stem cells (hADSC) in a bioengineered conduit, as an alternative strategy for nerve regeneration. To achieve meaningful clinical translation, cell therapy must comply with biosafety. Cell extraction and expansion methods that use animal-derived products, including enzymatic adipose tissue dissociation and the use of fetal bovine serum (FBS) as a culture medium supplement, have the potential for transmission of zoonotic infectious and immunogenicity. Human-platelet-lysate (hPL) serum has been used in recent years in human cell expansion, showing reliability in clinical applications. Methods: We investigated whether hADSC can be routinely isolated and cultured in a completely xenogeneic-free way (using hPL culture medium supplement and avoiding collagenase digestion) without altering their physiology and stem properties. Outcomes in terms of stem marker expression (CD105, CD90, CD73) and the osteocyte/adipocyte differentiation capacity were compared with classical collagenase digestion and FBS-supplemented hADSC expansion. Results: We found no significant differences between the two examined extraction and culture protocols in terms of cluster differentiation (CD) marker expression and stem cell plasticity, while hADSC in hPL showed a significantly higher proliferation rate when compared with the usual FBS-added medium. Considering the important key growth factors (particularly brain-derived growth factor (BDNF)) present in hPL, we investigated a possible neurogenic commitment of hADSC when cultured with hPL. Interestingly, hADSC cultured in hPL showed a statistically higher secretion of neurotrophic factors BDNF, glial cell-derived growth factor (GDNF), and nerve-derived growth factor (NFG) than FBS-cultured cells. When cocultured in the presence of primary neurons, hADSC which had been grown under hPL supplementation, showed significantly enhanced neurotrophic properties. Conclusions: The hPL-supplement medium could improve cell proliferation and neurotropism while maintaining stable cell properties, showing effectiveness in clinical translation and significant potential in peripheral nerve research. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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225. Application of Dermal Skin Substitutes for Hand and Finger Palmar Soft Tissue Loss.
- Author
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Lucas, Dominique, Di Rocco, Damien, Müller, Camillo T., Jurjus, Abdo R., Raffoul, Wassim, di Summa, Pietro G., and Watfa, William
- Published
- 2019
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226. Dermal Triangular Flaps to Prevent Pseudoptosis in Mastopexy Surgery: The Hammock Technique.
- Author
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Watfa, William, Zaugg, Patrice, Baudoin, Julien, Bramhall, Russell J., Raffoul, Wassim, and di Summa, Pietro G.
- Published
- 2019
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227. Importation of Acinetobacter baumanniiInto a Burn Unit: A Recurrent Outbreak of Infection Associated With Widespread Environmental Contamination
- Author
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Zanetti, Giorgio, Blanc, Dominique S., Federli, Isabelle, Raffoul, Wassim, Petignat, Christiane, Maravic, Philippe, Francioli, Patrick, and Berger, Mette M.
- Abstract
A burn patient was infected with Acinetobacter baumanniion transfer to the hospital after a terrorist attack. Two patients experienced cross-infection. Environmental swab samples were negative for A. baumannii. Six months later, the bacteria reemerged in 6 Patients. Environmental swab samples obtained at this time were inoculated into a minimal mineral broth, and culture results showed widespread contamination. No case of infection occurred after closure of the unit for disinfection.
- Published
- 2007
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228. Acute limb ischemia following perineal reconstruction in lithotomy position: take-home message for plastic surgeons.
- Author
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Sapino, Gianluca, Deglise, Sebastien, Raffoul, Wassim, and di Summa, Pietro G.
- Subjects
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PLASTIC surgeons , *LITHOTOMY , *COMPUTED tomography , *ABDOMINOPERINEAL resection , *PLASTIC surgery , *PERFORATOR flaps (Surgery) , *GYNECOLOGIC surgery - Abstract
Despite the extensive use of lithotomy position in several plastic surgery procedures, most reports regarding the related incidence of complications are presented in the urologic, gynecologic, and anesthesiologic fields. We present the case of a 54-year-old male patient. polytrauma patient who underwent internal iliac artery embolization leading to extensive gluteal necrosis requiring: debridement, abdominoperineal resection and composite anterolateral thigh flap reconstruction with prolonged lithotomy position. The patient presented lower limb ischemia briefly after surgical theater. A computed tomography scan revealed the obstruction of the left superficial femoral artery requiring emergency revascularization. Arterial thrombosis is a potentially devastating complication and plastic surgeons should be aware of the possible dangers when performing surgeries in prolonged lithotomy position. Preoperative detection of patients at high risks for developing complications should be performed in order to implement preventive measures and avoid potentially life-threatening sequelae. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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229. Biologicals and fetal cell therapy for wound healing and scar management
- Author
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Hirt-Burri, Nathalie, Ramelet, Albert-Adrien, Raffoul, Wassim, De Buys Roessingh, Anthony, Scaletta, Corinne, Pioletti, Dominique P., and Laurent-Applegate, Lee Ann
- Subjects
chronic ulcers ,scars ,wound healing ,cell therapy - Abstract
Few biopharmaceutical preparations developed from biologicals are available for tissue regeneration and scar management. When developing biological treatments with cellular therapy, selection of cell types and establishment of consistent cell banks are crucial steps in whole-cell bioprocessing. Various cell types have been used in treatment of wounds to reduce scar to date including autolog and allogenic skin cells, platelets, placenta and amniotic extracts. Experience with fetal cells show that they may provide an interesting cell choice due to facility of out-scaling and known properties for wound healing without scar. Differential gene profiling has helped to point to potential indicators of repair which include cell adhesion, extracellular matrix, cytokines, growth factors and development. Safety has been evidenced in Phase I & II clinical fetal cell use for burn and wound treatments with different cell delivery systems. Overall fetal cells present technical and therapeutic advantages compared to other cell types for effective cell-based therapy for wound and scar management.
230. Epiphyseal chondro-progenitors provide a stable cell source for cartilage cell therapy
- Author
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Darwiche, Salim Elias, Scaletta, Corinne, Raffoul, Wassim, Pioletti, Dominique, and Applegate, Lee
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Chondrocytes ,Cell banking ,Articular cartilage regeneration ,Progenitor cells - Abstract
Articular cartilage regeneration poses particularly tough challenges for implementing cell-‐based therapies. Many cell types have been investigated looking for a balanced combination of responsiveness and stability, yet techniques are still far from defining a gold standard. The work presented focuses on the reliable expansion and characterization of a clinical-‐grade human epiphyseal chondro-‐progenitor (ECP) cell bank from a single tissue donation. A parental human ECP cell bank was established which provides the seed material for master and working cell banks. ECPs were investigated at both low and high cumulative population doublings looking at morphology, monolayer expansion kinetics, resistance to cryogenic shock, colony forming efficiency and cell surface markers. Three dimensional micro-‐pellet assays were used to determine spontaneous extracellular matrix deposition at varying population doublings and monolayer 2D differentiation studies were undertaken to assess the propensity for commitment into other lineages and their stability. ECPs exhibited remarkable homogeneity in expansion with a steady proliferative potential averaging 3 population doublings over eight days. Surface marker analysis revealed no detectable contaminating subpopulations or population enrichment during prolonged culture periods. Despite a slight reduction in Sox9 expression levels at higher population doublings in monolayer, nuclear localization was equivalent both in monolayer and in micro-‐pellet format. Equally, ECPs were capable of depositing glycosaminoglycans, producing aggrecan, collagen I and collagen II in 3D pellets both at after low and high population doublings indicating a stable spontaneous chondrogenic potential. Osteogenic induction was differentially restricted in low and high population doublings as observed by Von Kossa staining of calcified matrix, with a notable collagen X, MMP13 and ADAMTS5 down-‐regulation. Rare adipogenic induction was seen as evidenced by cytoplasmic lipid accumulation detectable by Oil Red O staining. These findings highlight the reliability, stability and responsiveness of ECPs over prolonged culture, making them ideal candidates in defining novel strategies for cartilage regeneration.
231. Biomechanical Evaluation of Human Skin on Various Anatomical Sites (Semester Project)
- Author
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Darwiche, Salim Elias, Laurent-Applegate, Lee Ann, Raffoul, Wassim, and Pioletti, Dominique
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Mechanobiology ,finished ,integumentary system ,digestive, oral, and skin physiology - Abstract
Measures of skin elasticity, immediate retraction and distention as well as pigmentation and erythema will be conducted on various anatomical sites to compile a profile of skin properties.
232. A carpenter's hypothenar hammer syndrome.
- Author
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di Summa, Pietro Giovanni, Yvon, Adrien, Raffoul, Wassim, and Bollmann, Christof
- Published
- 2014
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233. Early detection of microcirculatory perfusion changes with a high resolution, real time laser doppler imaging camera - frostbite case study.
- Author
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Erba, Paolo, Harbi, Pascal, Thacher, Tyler, Pries, Axel, Ambrosio, Giuseppe, and Raffoul, Wassim
- Abstract
A 41-year-old male presented with severe frostbite that was monitored clinically and with a new laser Doppler imaging (LDI) camera that records arbitrary microcirculatory perfusion units (1-256 arbitrary perfusion units (APU's)). LDI monitoring detected perfusion differences in hand and foot not seen visually. On day 4-5 after injury, LDI showed that while fingers did not experience any significant perfusion change (average of 31±25 APUs on day 5), the patient's left big toe did (from 17±29 APUs day 4 to 103±55 APUs day 5). These changes in regional perfusion were not detectable by visual examination. On day 53 postinjury, all fingers with reduced perfusion by LDI were amputated, while the toe could be salvaged. This case clearly demonstrates that insufficient microcirculatory perfusion can be identified using LDI in ways which visual examination alone does not permit, allowing prognosis of clinical outcomes. Such information may also be used to develop improved treatment approaches. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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234. Cutaneous Cell Therapy Manufacturing Timeframe Rationalization: Allogeneic Off-the-Freezer Fibroblasts for Dermo-Epidermal Combined Preparations (DE-FE002-SK2) in Burn Care.
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Chen, Xi, Laurent, Alexis, Liao, Zhifeng, Jaccoud, Sandra, Abdel-Sayed, Philippe, Flahaut, Marjorie, Scaletta, Corinne, Raffoul, Wassim, Applegate, Lee Ann, and Hirt-Burri, Nathalie
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MANUFACTURING cells , *CELLULAR therapy , *SKIN grafting , *FIBROBLASTS , *TIME measurements , *BURN patients - Abstract
Autologous cell therapy manufacturing timeframes constitute bottlenecks in clinical management pathways of severe burn patients. While effective temporary wound coverings exist for high-TBSA burns, any means to shorten the time-to-treatment with cytotherapeutic skin grafts could provide substantial therapeutic benefits. This study aimed to establish proofs-of-concept for a novel combinational cytotherapeutic construct (autologous/allogeneic DE-FE002-SK2 full dermo-epidermal graft) designed for significant cutaneous cell therapy manufacturing timeframe rationalization. Process development was based on several decades (four for autologous protocols, three for allogeneic protocols) of in-house clinical experience in cutaneous cytotherapies. Clinical grade dermal progenitor fibroblasts (standardized FE002-SK2 cell source) were used as off-the-freezer substrates in novel autologous/allogeneic dermo-epidermal bilayer sheets. Under vitamin C stimulation, FE002-SK2 primary progenitor fibroblasts rapidly produced robust allogeneic dermal templates, allowing patient keratinocyte attachment in co-culture. Notably, FE002-SK2 primary progenitor fibroblasts significantly outperformed patient fibroblasts for collagen deposition. An ex vivo de-epidermalized dermis model was used to demonstrate the efficient DE-FE002-SK2 construct bio-adhesion properties. Importantly, the presented DE-FE002-SK2 manufacturing process decreased clinical lot production timeframes from 6–8 weeks (standard autologous combined cytotherapies) to 2–3 weeks. Overall, these findings bear the potential to significantly optimize burn patient clinical pathways (for rapid wound closure and enhanced tissue healing quality) by combining extensively clinically proven cutaneous cell-based technologies. [ABSTRACT FROM AUTHOR]
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- 2023
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235. Autologous and Allogeneic Cytotherapies for Large Knee (Osteo)Chondral Defects: Manufacturing Process Benchmarking and Parallel Functional Qualification.
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Philippe, Virginie, Jeannerat, Annick, Peneveyre, Cédric, Jaccoud, Sandra, Scaletta, Corinne, Hirt-Burri, Nathalie, Abdel-Sayed, Philippe, Raffoul, Wassim, Darwiche, Salim, Applegate, Lee Ann, Martin, Robin, and Laurent, Alexis
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MANUFACTURING defects , *MANUFACTURING processes , *CARTILAGE regeneration , *PARALLEL processing , *CELLULAR aging , *CELL transplantation , *KNEE , *ENDOCHONDRAL ossification - Abstract
Cytotherapies are often necessary for the management of symptomatic large knee (osteo)-chondral defects. While autologous chondrocyte implantation (ACI) has been clinically used for 30 years, allogeneic cells (clinical-grade FE002 primary chondroprogenitors) have been investigated in translational settings (Swiss progenitor cell transplantation program). The aim of this study was to comparatively assess autologous and allogeneic approaches (quality, safety, functional attributes) to cell-based knee chondrotherapies developed for clinical use. Protocol benchmarking from a manufacturing process and control viewpoint enabled us to highlight the respective advantages and risks. Safety data (telomerase and soft agarose colony formation assays, high passage cell senescence) and risk analyses were reported for the allogeneic FE002 cellular active substance in preparation for an autologous to allogeneic clinical protocol transposition. Validation results on autologous bioengineered grafts (autologous chondrocyte-bearing Chondro-Gide scaffolds) confirmed significant chondrogenic induction (COL2 and ACAN upregulation, extracellular matrix synthesis) after 2 weeks of co-culture. Allogeneic grafts (bearing FE002 primary chondroprogenitors) displayed comparable endpoint quality and functionality attributes. Parameters of translational relevance (transport medium, finished product suturability) were validated for the allogeneic protocol. Notably, the process-based benchmarking of both approaches highlighted the key advantages of allogeneic FE002 cell-bearing grafts (reduced cellular variability, enhanced process standardization, rationalized logistical and clinical pathways). Overall, this study built on our robust knowledge and local experience with ACI (long-term safety and efficacy), setting an appropriate standard for further clinical investigations into allogeneic progenitor cell-based orthopedic protocols. [ABSTRACT FROM AUTHOR]
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- 2023
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236. Bio-Enhanced Neoligaments Graft Bearing FE002 Primary Progenitor Tenocytes: Allogeneic Tissue Engineering & Surgical Proofs-of-Concept for Hand Ligament Regenerative Medicine.
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Jeannerat, Annick, Meuli, Joachim, Peneveyre, Cédric, Jaccoud, Sandra, Chemali, Michèle, Thomas, Axelle, Liao, Zhifeng, Abdel-Sayed, Philippe, Scaletta, Corinne, Hirt-Burri, Nathalie, Applegate, Lee Ann, Raffoul, Wassim, and Laurent, Alexis
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REGENERATIVE medicine , *TISSUE engineering , *TISSUE scaffolds , *THUMB , *LIGAMENT surgery , *LIGAMENTS , *PLASTIC surgery - Abstract
Hand tendon/ligament structural ruptures (tears, lacerations) often require surgical reconstruction and grafting, for the restauration of finger mechanical functions. Clinical-grade human primary progenitor tenocytes (FE002 cryopreserved progenitor cell source) have been previously proposed for diversified therapeutic uses within allogeneic tissue engineering and regenerative medicine applications. The aim of this study was to establish bioengineering and surgical proofs-of-concept for an artificial graft (Neoligaments Infinity-Lock 3 device) bearing cultured and viable FE002 primary progenitor tenocytes. Technical optimization and in vitro validation work showed that the combined preparations could be rapidly obtained (dynamic cell seeding of 105 cells/cm of scaffold, 7 days of co-culture). The studied standardized transplants presented homogeneous cellular colonization in vitro (cellular alignment/coating along the scaffold fibers) and other critical functional attributes (tendon extracellular matrix component such as collagen I and aggrecan synthesis/deposition along the scaffold fibers). Notably, major safety- and functionality-related parameters/attributes of the FE002 cells/finished combination products were compiled and set forth (telomerase activity, adhesion and biological coating potentials). A two-part human cadaveric study enabled to establish clinical protocols for hand ligament cell-assisted surgery (ligamento-suspension plasty after trapeziectomy, thumb metacarpo-phalangeal ulnar collateral ligamentoplasty). Importantly, the aggregated experimental results clearly confirmed that functional and clinically usable allogeneic cell-scaffold combination products could be rapidly and robustly prepared for bio-enhanced hand ligament reconstruction. Major advantages of the considered bioengineered graft were discussed in light of existing clinical protocols based on autologous tenocyte transplantation. Overall, this study established proofs-of-concept for the translational development of a functional tissue engineering protocol in allogeneic musculoskeletal regenerative medicine, in view of a pilot clinical trial. [ABSTRACT FROM AUTHOR]
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- 2023
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237. Primary Chondroprogenitors: Standardized & Versatile Allogeneic Cytotherapeutics.
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Laurent, Alexis, Jeannerat, Annick, Peneveyre, Cédric, Scaletta, Corinne, Philippe, Virginie, Abdel-Sayed, Philippe, Raffoul, Wassim, Martin, Robin, Hirt-Burri, Nathalie, and Applegate, Lee Ann
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BIOACTIVE glasses , *MANUFACTURING cells , *CELL transplantation , *REGENERATIVE medicine , *JOB qualifications , *PROGENITOR cells - Abstract
Definition: Primary chondroprogenitors obtained from standardized cell sources (e.g., FE002 clinical grade cell sources) may be cultured in vitro and may be cytotherapeutically applied in allogeneic musculoskeletal regenerative medicine. Multicentric translational research on FE002 human primary chondroprogenitors under the Swiss progenitor cell transplantation program has notably validated their robustness and high versatility for therapeutic formulation in clinically compatible prototypes, as well as a good safety profile in diverse in vivo preclinical models. Therein, stringently controlled primary cell source establishment and extensive cell manufacturing optimization have technically confirmed the adequation of FE002 primary chondroprogenitors with standard industrial biotechnology workflows for consistent diploid cell biobanking under GMP. Laboratory characterization studies and extensive qualification work on FE002 progenitor cell sources have elucidated the key and critical attributes of the cellular materials of interest for potential and diversified human cytotherapeutic uses. Multiple formulation studies (i.e., hydrogel-based standardized transplants, polymeric-scaffold-based tissue engineering products) have shown the high versatility of FE002 primary chondroprogenitors, for the obtention of functional allogeneic cytotherapeutics. Multiple in vivo preclinical studies (e.g., rodent models, GLP goat model) have robustly documented the safety of FE002 primary chondroprogenitors following implantation. Clinically, FE002 primary chondroprogenitors may potentially be used in various forms for volumetric tissue replacement (e.g., treatment of large chondral/osteochondral defects of the knee) or for the local management of chondral affections and pathologies (i.e., injection use in mild to moderate osteoarthritis cases). Overall, standardized FE002 primary chondroprogenitors as investigated under the Swiss progenitor cell transplantation program were shown to constitute tangible contenders in novel human musculoskeletal regenerative medicine approaches, for versatile and safe allogeneic clinical cytotherapeutic management. [ABSTRACT FROM AUTHOR]
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- 2023
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238. Thermo-Responsive Hyaluronan-Based Hydrogels Combined with Allogeneic Cytotherapeutics for the Treatment of Osteoarthritis.
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Porcello, Alexandre, Gonzalez-Fernandez, Paula, Jeannerat, Annick, Peneveyre, Cédric, Abdel-Sayed, Philippe, Scaletta, Corinne, Raffoul, Wassim, Hirt-Burri, Nathalie, Applegate, Lee Ann, Allémann, Eric, Laurent, Alexis, and Jordan, Olivier
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HYDROGELS , *HYALURONIC acid , *OSTEOARTHRITIS , *RHEOLOGY (Biology) , *RHEOLOGY , *TRIBOLOGY - Abstract
Thermo-responsive hyaluronan-based hydrogels and FE002 human primary chondroprogenitor cell sources have both been previously proposed as modern therapeutic options for the management of osteoarthritis (OA). For the translational development of a potential orthopedic combination product based on both technologies, respective technical aspects required further optimization phases (e.g., hydrogel synthesis upscaling and sterilization, FE002 cytotherapeutic material stabilization). The first aim of the present study was to perform multi-step in vitro characterization of several combination product formulas throughout the established and the optimized manufacturing workflows, with a strong focus set on critical functional parameters. The second aim of the present study was to assess the applicability and the efficacy of the considered combination product prototypes in a rodent model of knee OA. Specific characterization results (i.e., spectral analysis, rheology, tribology, injectability, degradation assays, in vitro biocompatibility) of hyaluronan-based hydrogels modified with sulfo-dibenzocyclooctyne-PEG4-amine linkers and poly(N-isopropylacrylamide) (HA-L-PNIPAM) containing lyophilized FE002 human chondroprogenitors confirmed the suitability of the considered combination product components. Specifically, significantly enhanced resistance toward oxidative and enzymatic degradation was shown in vitro for the studied injectable combination product prototypes. Furthermore, extensive multi-parametric (i.e., tomography, histology, scoring) in vivo investigation of the effects of FE002 cell-laden HA-L-PNIPAM hydrogels in a rodent model revealed no general or local iatrogenic adverse effects, whereas it did reveal some beneficial trends against the development of knee OA. Overall, the present study addressed key aspects of the preclinical development process for novel biologically-based orthopedic combination products and shall serve as a robust methodological basis for further translational investigation and clinical work. [ABSTRACT FROM AUTHOR]
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- 2023
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239. Process Optimization and Efficacy Assessment of Standardized PRP for Tendinopathies in Sports Medicine: Retrospective Study of Clinical Files and GMP Manufacturing Records in a Swiss University Hospital.
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Sebbagh, Patrick, Hirt-Burri, Nathalie, Scaletta, Corinne, Abdel-Sayed, Philippe, Raffoul, Wassim, Gremeaux, Vincent, Laurent, Alexis, Applegate, Lee Ann, and Gremion, Gerald
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SPORTS medicine , *TENDINOPATHY , *PROCESS optimization , *UNIVERSITY hospitals , *PLATELET-rich plasma , *PHYSICAL activity - Abstract
Platelet-rich plasma (PRP) preparations have recently become widely available in sports medicine, facilitating their use in regenerative therapy for ligament and tendon affections. Quality-oriented regulatory constraints for PRP manufacturing and available clinical experiences have underlined the critical importance of process-based standardization, a pre-requisite for sound and homogeneous clinical efficacy evaluation. This retrospective study (2013–2020) considered the standardized GMP manufacturing and sports medicine-related clinical use of autologous PRP for tendinopathies at the Lausanne University Hospital (Lausanne, Switzerland). This study included 48 patients (18–86 years of age, with a mean age of 43.4 years, and various physical activity levels), and the related PRP manufacturing records indicated a platelet concentration factor most frequently in the range of 2.0–2.5. The clinical follow-up showed that 61% of the patients reported favorable efficacy outcomes (full return to activity, with pain disappearance) following a single ultrasound-guided autologous PRP injection, whereas 36% of the patients required two PRP injections. No significant relationship was found between platelet concentration factor values in PRP preparations and clinical efficacy endpoints of the intervention. The results were in line with published reports on tendinopathy management in sports medicine, wherein the efficacy of low-concentration orthobiologic interventions appears to be unrelated to sport activity levels or to patient age and gender. Overall, this study confirmed the effectiveness of standardized autologous PRP preparations for tendinopathies in sports medicine. The results were discussed in light of the critical importance of protocol standardization for both PRP manufacturing and clinical administration to reduce biological material variability (platelet concentrations) and to enhance the robustness of clinical interventions (comparability of efficacy/patient improvement). [ABSTRACT FROM AUTHOR]
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- 2023
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240. Industrial Biotechnology Conservation Processes: Similarities with Natural Long-Term Preservation of Biological Organisms.
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Laurent, Alexis, Scaletta, Corinne, Abdel-Sayed, Philippe, Raffoul, Wassim, Hirt-Burri, Nathalie, and Applegate, Lee Ann
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TRANSPLANTATION of organs, tissues, etc. , *BIOTECHNOLOGY , *CELL transplantation , *PHASE transitions , *BIOLOGICAL adaptation , *COLD adaptation - Abstract
Cryopreservation and lyophilization processes are widely used for conservation purposes in the pharmaceutical, biotechnological, and food industries or in medical transplantation. Such processes deal with extremely low temperatures (e.g., −196 °C) and multiple physical states of water, a universal and essential molecule for many biological lifeforms. This study firstly considers the controlled laboratory/industrial artificial conditions used to favor specific water phase transitions during cellular material cryopreservation and lyophilization under the Swiss progenitor cell transplantation program. Both biotechnological tools are successfully used for the long-term storage of biological samples and products, with reversible quasi-arrest of metabolic activities (e.g., cryogenic storage in liquid nitrogen). Secondly, similarities are outlined between such artificial localized environment modifications and some natural ecological niches known to favor metabolic rate modifications (e.g., cryptobiosis) in biological organisms. Specifically, examples of survival to extreme physical parameters by small multi-cellular animals (e.g., tardigrades) are discussed, opening further considerations about the possibility to reversibly slow or temporarily arrest the metabolic activity rates of defined complex organisms in controlled conditions. Key examples of biological organism adaptation capabilities to extreme environmental parameters finally enabled a discussion about the emergence of early primordial biological lifeforms, from natural biotechnology and evolutionary points of view. Overall, the provided examples/similarities confirm the interest in further transposing natural processes and phenomena to controlled laboratory settings with the ultimate goal of gaining better control and modulation capacities over the metabolic activities of complex biological organisms. [ABSTRACT FROM AUTHOR]
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- 2023
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241. Primary Progenitor Tenocytes: Cytotherapeutics and Cell-Free Derivatives.
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Laurent, Alexis, Scaletta, Corinne, Abdel-Sayed, Philippe, Raffoul, Wassim, Hirt-Burri, Nathalie, and Applegate, Lee Ann
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CO-cultures , *CELL transplantation , *REGENERATIVE medicine , *TISSUE engineering , *PROGENITOR cells , *SYMPTOMS - Abstract
Definition: Primary progenitor tenocytes are diploid cells that may be cultured in vitro and therapeutically used for allogeneic musculoskeletal regenerative medicine. Firstly, technical aspects of cell banking, biotechnological manufacturing, and extensive preclinical characterization data have confirmed that FE002-Ten primary progenitor tenocytes may be safely considered for human cytotherapeutic use (e.g., in tissue engineering products, standardized transplants). Parallelly, lyophilized progenitor tenocyte extracts (e.g., stabilized cells or cell-free derivatives) were shown to optimally act as potent hyaluronan-based hydrogel functionalizing agents, useful for stability enhancement against oxidative product degradation. Therefore, primary progenitor tenocytes (e.g., FE002-Ten cell source) may potentially be used in diverse clinical presentations of tendon-related pathologies, ranging from volumetric tissue replacement (i.e., for the promotion of enhanced graft bio-integration) to local management of tissular inflammation and pain (i.e., ancillary action of the cellular extracts for the functional enhancement of injectable hyaluronan-based preparations). Overall, the primary progenitor tenocytes investigated under the Swiss progenitor cell transplantation program were shown to represent highly standardized biotechnological materials with a versatility of potential therapeutic uses after formulation into an array of cytotherapeutic preparations or cell-free devices. [ABSTRACT FROM AUTHOR]
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- 2023
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242. Current Status of PRP Manufacturing Requirements & European Regulatory Frameworks: Practical Tools for the Appropriate Implementation of PRP Therapies in Musculoskeletal Regenerative Medicine.
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Sebbagh, Patrick, Cannone, Alessandro, Gremion, Gerald, Gremeaux, Vincent, Raffoul, Wassim, Hirt-Burri, Nathalie, Michetti, Murielle, Abdel-Sayed, Philippe, Laurent, Alexis, Wardé, Nathalie, and Applegate, Lee Ann
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REGENERATIVE medicine , *MEDICAL offices , *CLINICS , *TECHNICAL specifications , *PHYSICIANS , *PLATELET-rich plasma , *CURRENT good manufacturing practices - Abstract
Providing accurate and up-to-date practical tools enabling oversight of platelet-rich plasma (PRP) legislation and of the appropriate standards to be implemented for its manufacture and use in Europe is a demanding task. This is due to rapid medico-technological advancements, slowness and disparity in legislation updates and enforcement between member states, and many reported gray-zone practices, notably for autologous PRP use. The levels of risk associated with blood manipulation processes generally dictate the manufacturing requirements for PRP preparations, which have gradually shifted toward good manufacturing practices (GMP) for standardization and overall quality enhancement. This work firstly outlines Western European and Swiss legislation for PRP products/preparations, providing key simplified information and recommendations for medical doctors seeking to implement this biological-based therapy for safe use in hospital settings, clinics, or private offices. This work secondly shows the importance of PRP-based product manufacturing standardization, which subsequently enables sound clinical evaluation of therapeutic interventions. Although the applicable legal bases provide guidelines for GMP manufacturing infrastructure and basic process design, paramount importance is set on the definition of workflows, technical specifications, and key parameters for PRP preparation and delivery. Overall, the development of simple and robust technologies and processes for PRP preparation is critical for guaranteeing the high therapeutic quality of the intervention, in collaboration with qualified GMP manufacturing platforms. Importantly, this work aims to serve as a practical tool for clinicians based in Western Europe who are willing to appropriately (i.e., administratively and technically) implement autologous PRP treatments in musculoskeletal regenerative medicine workflows, to ensure they make informed and optimal regulatory or process-based decisions. [ABSTRACT FROM AUTHOR]
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- 2023
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243. Lower limb soft tissue reconstruction using free ALT flaps: multimodal parameter analysis to predict the level of spontaneous reinnervation.
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Watfa, William, Sapino, Gianluca, Teatini, Francesco, Oranges, Carlo M., Cherubino, Mario, Guiller, David, Raffoul, Wassim, and di Summa, Pietro G.
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FREE flaps , *PERCEPTION testing , *SURFACE area , *TISSUES , *PRODUCT returns - Abstract
This work aims to assess lower limb free flaps spontaneous sensory recovery by comparing and analyzing a single standardized reconstructive procedure, namely the free noninnervated anterolateral thigh (ALT) flap in order to evaluate which flap or patient-related factors may predict flap reinnervation. Between January 2010 and March 2018 all nonreinnervated ALT flaps for lower limb coverage performed at our institution were screened. We excluded from the study flaps with less than 18 months of follow-up time, neurotized flaps, and those from patients who missed the last follow up. Sensory modalities that were evaluated included the two-point discrimination (2PD) test, measured in mm; and the Semmes–Weinstein monofilament (SWM) test, measured in gram. The sensory parameter results were compared and analyzed according to flap size (two groups; <160 cm2 vs. > 160 cm2), and post-op time of testing (two groups; <18–28 months vs. > 28 months). Twenty-one ALT free flaps were finally retained by this study. Our findings showed that flaps of smaller surface area showed a significantly better return in sensory discrimination 2PD and in sensory cutaneous pressure perception SWM testing. This work establishes for the first time some key quantitative data that can help predict free flap spontaneous reinnervation outcomes when using the same ALT flap. In our series, flaps surface remains the main discriminant value for a better sensory recovery. [ABSTRACT FROM AUTHOR]
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- 2023
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244. Lymphatic flow through (LyFT) ALT flap: an original solution to reconstruct soft tissue loss with lymphatic leakage or lower limb lymphedema.
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Guillier, David, Guiotto, Martino, Cherix, Stephane, Raffoul, Wassim, and di Summa, Pietro G.
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LYMPHOID tissue , *LYMPHEDEMA , *REOPERATION , *PATIENT satisfaction , *PERFORATOR flaps (Surgery) , *CELLULITIS - Abstract
The lympho-venous shunt using the distal vein of ALT flap pedicle allowed at the same time the coverage of the inguinal defects and to perform lymphovenous shunt into a run-in vein of the descending branch of the lateral circumflex femoral pedicle, draining the lymph through the flap pedicle. Surgical technique, complications and final outcomes (both clinical and lymphoscintigraphic) are reported. Five patients (45.8 y.o.[22–70]) with groin soft tissue loss with lymphatic leakage or lower limb lymphedema, benefited of the described technique. The ALT flap was used to cover the defect and, at the same time, we could perform a lymphovenous shunt between afferent lymphatics to the thigh and the descending branch of the lateral circumflex femoral pedicle, distal to the perforator nourishing the flap. Clinical and lymphoscintigraphic assessment of the limbs, cease of lymphorrhea or cellulitis/lymphangitis episodes, eventual downstaging of physiologic/physical therapy were recorded. LYMphatic Quality Of Life in leg (LYMQoLLeg) and patient satisfaction were evaluated. Average flap size was 88.8cm2 (range 84–126). The mean number of multi-lymphovenous anastomosis (MLVA) performed was 1.8 (range 1–3) per patient with 1–3 lymphatics shunted into each vein. Only one hemato-seroma requiring surgical revision. Mean improvement of perometer values was 48.2% (range 27.7–67.7) with an average follow-up of 13.6 months (range 12–17). Lymphoscintigraphy showed disappearing of the lymphatic leak and lymphedema with a high satisfaction of LYMQoL score. The combination of pedicle flap with lympho-venous bypass as lymphatic derivation concept, improving the chronic morbidity scenarios of lymphatic complications. [ABSTRACT FROM AUTHOR]
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- 2023
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245. Retrospectives on Three Decades of Safe Clinical Experience with Allogeneic Dermal Progenitor Fibroblasts: High Versatility in Topical Cytotherapeutic Care.
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Laurent, Alexis, Rey, Marina, Scaletta, Corinne, Abdel-Sayed, Philippe, Michetti, Murielle, Flahaut, Marjorie, Raffoul, Wassim, de Buys Roessingh, Anthony, Hirt-Burri, Nathalie, and Applegate, Lee Ann
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BIOLOGICAL dressings , *TOPICAL drug administration , *CELL transplantation , *GENE therapy , *CELLULAR therapy , *FIBROBLASTS - Abstract
Allogeneic dermal progenitor fibroblasts constitute cytotherapeutic contenders for modern cutaneous regenerative medicine. Based on advancements in the relevant scientific, technical, and regulatory fields, translational developments have slowly yet steadily led to the clinical application of such biologicals and derivatives. To set the appropriate general context, the first aim of this study was to provide a current global overview of approved cell and gene therapy products, with an emphasis on cytotherapies for cutaneous application. Notable advances were shown for North America, Europe, Iran, Japan, and Korea. Then, the second and main aim of this study was to perform a retrospective analysis on the various applications of dermal progenitor fibroblasts and derivatives, as clinically used under the Swiss progenitor cell transplantation program for the past three decades. Therein, the focus was set on the extent and versatility of use of the therapies under consideration, their safety parameters, as well as formulation options for topical application. Quantitative and illustrative data were summarized and reported for over 300 patients treated with various cell-based or cell-derived preparations (e.g., progenitor biological bandages or semi-solid emulsions) in Lausanne since 1992. Overall, this study shows the strong current interest in biological-based approaches to cutaneous regenerative medicine from a global developmental perspective, as well as the consolidated local clinical experience gathered with a specific and safe allogeneic cytotherapeutic approach. Taken together, these current and historical elements may serve as tangible working bases for the further optimization of local and modern translational pathways for the provision of topical cytotherapeutic care. [ABSTRACT FROM AUTHOR]
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- 2023
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246. Reduction of nosocomial pneumonia after major burns by trace element supplementation: aggregation of two randomised trials
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Berger, Mette, Eggimann, Philippe, Heyland, Daren, Chioléro, René, Revelly, Jean-Pierre, Day, Andrew, Raffoul, Wassim, and Shenkin, Alan
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Introduction Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia.Methods Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20.Results The patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023).Conclusion Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.
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- 2006
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247. Facial Fat Grafting (FFG): Worth the Risk? A Systematic Review of Complications and Critical Appraisal.
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Schiraldi, Luigi, Sapino, Gianluca, Meuli, Joachim, Maruccia, Michele, Cherubino, Mario, Raffoul, Wassim, and di Summa, Pietro G.
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LIPOSUCTION , *FAT , *CHILD patients - Abstract
Introduction: Autologous fat is ideal soft tissue filler. It is easily accessible, biocompatible, cheap, and it provides both volume augmentation and skin quality improvement. Fat grafting has been used since 1893, but it has only gained widespread popularity since the development of modern liposuction by Colemann and Illouz in the 1980s. Every year more than half a million facial fat grafting procedures are carried out worldwide and the trend is rapidly increasing. Overall, general complications associated with facial fat grafting are assumed to be around 2%. Is that true? Material and Methods: Until July 2021, a systematic search of the literature was performed interrogating PubMed search engines. The following algorithm was used for the research: (fat graft OR lipofilling) AND face AND complications. Exclusion criteria applied hierarchically were review articles, not reporting recipient site complications; not in English and paediatric population. Abstracts were manually screened by LS, GS, JM and PDS separately and subsequently matched for accuracy. Pertinent full-text articles were retrieved and analysed and data were extracted from the database. The flow chart of article selection is described following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: In total, 462 papers were identified by PubMed search. A total of 359 were excluded: 38 papers were not in English, 41 were review articles, 279 articles did not report recipient site complications and 1 was not on human subjects. Average complication rate ranged from 1.5% to 81.4%. A total of 298 adverse events were identified: 40 (13.4%) intravascular injections, 13 (4.3%) asymmetry, 57 (19.1%) irregularities, 22 (7.4%) graft hypertrophy, 21 (7%) fat necrosis, 73 (24.5%) prolonged oedema, 1 (0.3%) infection, 6 (2%) prolonged erythema, 15 (5%) telangiectasia and 50 (16.8%) cases of acne activation. Conclusions: FFG related side effects could be resumed in three categories: severe, moderate, and minor. Severe (13.4%) side effects such as intravascular injection or migration require neurological or neurosurgical management and often lead to permanent disability or death. Moderate (38.3%) side effects such as fat hypertrophy, necrosis, cyst formation, irregularities and asymmetries require a retouch operation. Minor (48.3%) side effects such as prolonged oedema or erythema require no surgical management. Despite the fact that the overall general complication rate of facial fat grafting is assumed to be around 2%, the real complication rate of facial fat grafting is unknown due to a lack of reporting and the absence of consensus on side effect definition and identification. More RCTs are necessary to further determine the real complication rate of this procedure. [ABSTRACT FROM AUTHOR]
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- 2022
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248. One-Stage Coverage of Leg Region Defects with STSG Combined with VAC Dressing Improves Early Patient Mobilisation and Graft Take: A Comparative Study.
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Sapino, Gianluca, Lanz, Loise, Roesti, Aurore, Guillier, David, Deglise, Sebastien, De Santis, Giorgio, Raffoul, Wassim, and di Summa, Pietro
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SKIN grafting , *POSTOPERATIVE care , *POSTOPERATIVE period , *SURGICAL dressings , *COMPARATIVE studies , *BONE grafting - Abstract
Lower limb skin defects are very common and can result from a wide range of aetiologies. Split thickness skin graft (STSG) is a widely used method to address these problems. The role of postoperative dressing is primary as it permits one to apply a uniform pressure over the grafted area and promote adherence. Focusing on lower limb reconstruction, our clinical study compares the application of V.A.C. (Vacuum Assisted Closure) Therapy vs. conventional dressing in the immediate postoperative period following skin grafting. We included in the study all patients who received skin grafts on the leg region between January 2015 and December 2018, despite the aetiology of the defect. Only reconstructions with complete preoperative and postoperative follow-up data were included in the study. Patients were divided into two groups depending on if they received a traditional compressive dressing or a VAC dressing in the immediate postoperative period. We could retain 92 patients, 23 in the No VAC group and 69 in the VAC group. The patients included in the VAC group showed a statistically significant higher rate of graft take together with a lower immobilisation time (p < 0.05). Moreover, a lower rate of postoperative infection was recorded in the VAC group. This study represents the largest in the literature to report in detail surgical outcomes comparing the use of VAC therapy vs. conventional dressing after STSG in the postoperative management of lower limb reconstruction using skin grafts. VAC therapy was used to secure the grafts in the leg region, increasing the early graft take rate while at the same time improving patient mobilisation. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
249. Biotechnology and Cytotherapeutics: The Swiss Progenitor-Cell Transplantation Program.
- Author
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Laurent, Alexis, Scaletta, Corinne, Abdel-Sayed, Philippe, Michetti, Murielle, de Buys Roessingh, Anthony, Raffoul, Wassim, Hirt-Burri, Nathalie, and Applegate, Lee Ann
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REGENERATIVE medicine , *MANUFACTURING cells , *BIOMATERIALS , *BIOTECHNOLOGY , *PROGENITOR cells - Abstract
Definition: Historically, primary human progenitor cells (e.g., WI-38 and MRC-5 diploid-cell sources) have been industrially applied in research and in manufacturing processes for vaccines and for biologicals. Furthermore, tissue-specific primary progenitor-cell banks have recently been developed and exploited for the provision of safe, consistent, and effective cellular active pharmaceutical ingredients (API) in homologous allogeneic regenerative medicine applications. Notably, the modern legal and regulatory frameworks for novel therapeutic products and for progenitor-cell therapy development have been iteratively optimized to guarantee utmost product safety, quality, and efficacy. Over 50 years of global technical hindsight around progenitor-cell biotechnological substrates and over 30 years of in-house clinical experience around the therapeutic uses of standardized progenitor-cell sources in Switzerland have demonstrated the importance of such biological materials for public health. The aim of this entry work was to summarize the evolution of the industrial applications of selected primary progenitor-cell sources, ranging from the use as robust biotechnological substrates to standardized cellular API manufacture and their clinical uses in highly specialized regenerative medicine. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
250. Back to the Cradle of Cytotherapy: Integrating a Century of Clinical Research and Biotechnology-Based Manufacturing for Modern Tissue-Specific Cellular Treatments in Switzerland.
- Author
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Laurent, Alexis, Abdel-Sayed, Philippe, Scaletta, Corinne, Laurent, Philippe, Laurent, Elénie, Michetti, Murielle, de Buys Roessingh, Anthony, Raffoul, Wassim, Hirt-Burri, Nathalie, and Applegate, Lee Ann
- Subjects
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MEDICAL research , *CELL transplantation , *CELLULAR therapy , *REGENERATIVE medicine , *PROGENITOR cells - Abstract
Empirically studied by Dr. Brown-Séquard in the late 1800s, cytotherapies were later democratized by Dr. Niehans during the twentieth century in Western Switzerland. Many local cultural landmarks around the Léman Riviera are reminiscent of the inception of such cell-based treatments. Despite the discreet extravagance of the remaining heirs of "living cell therapy" and specific enforcements by Swiss health authorities, current interest in modern and scientifically sound cell-based regenerative medicine has never been stronger. Respective progress made in bioengineering and in biotechnology have enabled the clinical implementation of modern cell-based therapeutic treatments within updated medical and regulatory frameworks. Notably, the Swiss progenitor cell transplantation program has enabled the gathering of two decades of clinical experience in Lausanne for the therapeutic management of cutaneous and musculoskeletal affections, using homologous allogeneic cell-based approaches. While striking conceptual similarities exist between the respective works of the fathers of cytotherapy and of modern highly specialized clinicians, major and important iterative updates have been implemented, centered on product quality and risk-analysis-based patient safety insurance. This perspective article highlights some historical similarities and major evolutive differences, particularly regarding product safety and quality issues, characterizing the use of cell-based therapies in Switzerland over the past century. We outline the vast therapeutic potential to be harnessed for the benefit of overall patient health and the importance of specific scientific methodological aspects. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
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