Abdominal Wall Transplantation: Indications and Outcomes

Abstract Purpose of Review This article aims to review published outcomes associated with full-thickness vascularized abdominal wall transplantation, with particular emphasis on advances in the field in the last 3 years. Recent Findings Forty-six full-thickness vascularized abdominal wall transplants have been performed in 44 patients worldwide. Approximately 35% of abdominal wall transplant recipients will experience at least one episode of acute rejection in the first year after transplant, compared with rejection rates of 87.8% and 72.7% for hand and face transplant respectively. Recent evidence suggests that combining a skin containing abdominal wall transplant with an intestinal transplant does not appear to increase sensitization or de novo donor-specific antibody formation. Summary Published data suggests that abdominal wall transplantation is an effective safe solution to achieve primary closure of the abdomen after intestinal or multivisceral transplant. However, better data is needed to confirm observations made and to determine long-term outcomes, requiring standardized data collection and reporting and collaboration between the small number of active transplant centres around the worl

NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods

Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submit- Avenue, Silver Spring, Maryland 20993; 22Glycoscience Research Laboratory, Genos, Borongajska cesta 83h, 10 000 Zagreb, Croatia; 23Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovacˇ ic´ a 1, 10 000 Zagreb, Croatia; 24Department of Chemistry, Georgia State University, 100 Piedmont Avenue, Atlanta, Georgia 30303; 25glyXera GmbH, Brenneckestrasse 20 * ZENIT / 39120 Magdeburg, Germany; 26Health Products and Foods Branch, Health Canada, AL 2201E, 251 Sir Frederick Banting Driveway, Ottawa, Ontario, K1A 0K9 Canada; 27Graduate School of Advanced Sciences of Matter, Hiroshima University, 1-3-1 Kagamiyama Higashi-Hiroshima 739–8530 Japan; 28ImmunoGen, 830 Winter Street, Waltham, Massachusetts 02451; 29Department of Medical Physiology, Jagiellonian University Medical College, ul. Michalowskiego 12, 31–126 Krakow, Poland; 30Department of Pathology, Johns Hopkins University, 400 N. Broadway Street Baltimore, Maryland 21287; 31Mass Spec Core Facility, KBI Biopharma, 1101 Hamlin Road Durham, North Carolina 27704; 32Division of Mass Spectrometry, Korea Basic Science Institute, 162 YeonGuDanji-Ro, Ochang-eup, Cheongwon-gu, Cheongju Chungbuk, 363–883 Korea (South); 33Advanced Therapy Products Research Division, Korea National Institute of Food and Drug Safety, 187 Osongsaengmyeong 2-ro Osong-eup, Heungdeok-gu, Cheongju-si, Chungcheongbuk-do, 363–700, Korea (South); 34Center for Proteomics and Metabolomics, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands; 35Ludger Limited, Culham Science Centre, Abingdon, Oxfordshire, OX14 3EB, United Kingdom; 36Biomolecular Discovery and Design Research Centre and ARC Centre of Excellence for Nanoscale BioPhotonics (CNBP), Macquarie University, North Ryde, Australia; 37Proteomics, Central European Institute for Technology, Masaryk University, Kamenice 5, A26, 625 00 BRNO, Czech Republic; 38Max Planck Institute for Dynamics of Complex Technical Systems, Sandtorstrasse 1, 39106 Magdeburg, Germany; 39Department of Biomolecular Sciences, Max Planck Institute of Colloids and Interfaces, 14424 Potsdam, Germany; 40AstraZeneca, Granta Park, Cambridgeshire, CB21 6GH United Kingdom; 41Merck, 2015 Galloping Hill Rd, Kenilworth, New Jersey 07033; 42Analytical R&D, MilliporeSigma, 2909 Laclede Ave. St. Louis, Missouri 63103; 43MS Bioworks, LLC, 3950 Varsity Drive Ann Arbor, Michigan 48108; 44MSD, Molenstraat 110, 5342 CC Oss, The Netherlands; 45Exploratory Research Center on Life and Living Systems (ExCELLS), National Institutes of Natural Sciences, 5–1 Higashiyama, Myodaiji, Okazaki 444–8787 Japan; 46Graduate School of Pharmaceutical Sciences, Nagoya City University, 3–1 Tanabe-dori, Mizuhoku, Nagoya 467–8603 Japan; 47Medical & Biological Laboratories Co., Ltd, 2-22-8 Chikusa, Chikusa-ku, Nagoya 464–0858 Japan; 48National Institute for Biological Standards and Control, Blanche Lane, South Mimms, Potters Bar, Hertfordshire EN6 3QG United Kingdom; 49Division of Biological Chemistry & Biologicals, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158–8501 Japan; 50New England Biolabs, Inc., 240 County Road, Ipswich, Massachusetts 01938; 51New York University, 100 Washington Square East New York City, New York 10003; 52Target Discovery Institute, Nuffield Department of Medicine, University of Oxford, Roosevelt Drive, Oxford, OX3 7FZ, United Kingdom; 53GlycoScience Group, The National Institute for Bioprocessing Research and Training, Fosters Avenue, Mount Merrion, Blackrock, Co. Dublin, Ireland; 54Department of Chemistry, North Carolina State University, 2620 Yarborough Drive Raleigh, North Carolina 27695; 55Pantheon, 201 College Road East Princeton, New Jersey 08540; 56Pfizer Inc., 1 Burtt Road Andover, Massachusetts 01810; 57Proteodynamics, ZI La Varenne 20–22 rue Henri et Gilberte Goudier 63200 RIOM, France; 58ProZyme, Inc., 3832 Bay Center Place Hayward, California 94545; 59Koichi Tanaka Mass Spectrometry Research Laboratory, Shimadzu Corporation, 1 Nishinokyo Kuwabara-cho Nakagyo-ku, Kyoto, 604 8511 Japan; 60Children’s GMP LLC, St. Jude Children’s Research Hospital, 262 Danny Thomas Place Memphis, Tennessee 38105; 61Sumitomo Bakelite Co., Ltd., 1–5 Muromati 1-Chome, Nishiku, Kobe, 651–2241 Japan; 62Synthon Biopharmaceuticals, Microweg 22 P.O. Box 7071, 6503 GN Nijmegen, The Netherlands; 63Takeda Pharmaceuticals International Co., 40 Landsdowne Street Cambridge, Massachusetts 02139; 64Department of Chemistry and Biochemistry, Texas Tech University, 2500 Broadway, Lubbock, Texas 79409; 65Thermo Fisher Scientific, 1214 Oakmead Parkway Sunnyvale, California 94085; 66United States Pharmacopeia India Pvt. Ltd. IKP Knowledge Park, Genome Valley, Shamirpet, Turkapally Village, Medchal District, Hyderabad 500 101 Telangana, India; 67Alberta Glycomics Centre, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 68Department of Chemistry, University of Alberta, Edmonton, Alberta T6G 2G2 Canada; 69Department of Chemistry, University of California, One Shields Ave, Davis, California 95616; 70Horva´ th Csaba Memorial Laboratory for Bioseparation Sciences, Research Center for Molecular Medicine, Doctoral School of Molecular Medicine, Faculty of Medicine, University of Debrecen, Debrecen, Egyetem ter 1, Hungary; 71Translational Glycomics Research Group, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Veszprem, Egyetem ut 10, Hungary; 72Delaware Biotechnology Institute, University of Delaware, 15 Innovation Way Newark, Delaware 19711; 73Proteomics Core Facility, University of Gothenburg, Medicinaregatan 1G SE 41390 Gothenburg, Sweden; 74Department of Medical Biochemistry and Cell Biology, University of Gothenburg, Institute of Biomedicine, Sahlgrenska Academy, Medicinaregatan 9A, Box 440, 405 30, Gothenburg, Sweden; 75Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Bruna Straket 16, 41345 Gothenburg, Sweden; 76Department of Chemistry, University of Hamburg, Martin Luther King Pl. 6 20146 Hamburg, Germany; 77Department of Chemistry, University of Manitoba, 144 Dysart Road, Winnipeg, Manitoba, Canada R3T 2N2; 78Laboratory of Mass Spectrometry of Interactions and Systems, University of Strasbourg, UMR Unistra-CNRS 7140, France; 79Natural and Medical Sciences Institute, University of Tu¨ bingen, Markwiesenstrae 55, 72770 Reutlingen, Germany; 80Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands; 81Division of Bioanalytical Chemistry, Amsterdam Institute for Molecules, Medicines and Systems, Vrije Universiteit Amsterdam, de Boelelaan 1085, 1081 HV Amsterdam, The Netherlands; 82Department of Chemistry, Waters Corporation, 34 Maple Street Milford, Massachusetts 01757; 83Zoetis, 333 Portage St. Kalamazoo, Michigan 49007 Author’s Choice—Final version open access under the terms of the Creative Commons CC-BY license. Received July 24, 2019, and in revised form, August 26, 2019 Published, MCP Papers in Press, October 7, 2019, DOI 10.1074/mcp.RA119.001677 ER: NISTmAb Glycosylation Interlaboratory Study 12 Molecular & Cellular Proteomics 19.1 Downloaded from https://www.mcponline.org by guest on January 20, 2020 ted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide communityderived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods. Molecular & Cellular Proteomics 19: 11–30, 2020. DOI: 10.1074/mcp.RA119.001677.L

Mandibular Reconstruction Using the Free Vascularized Fibula Graft: An Overview of Different Modifications

The reconstruction of the mandible is a complex procedure because various cosmetic as well as functional challenges must be addressed, including mastication and oral competence. Many surgical techniques have been described to address these challenges, including non-vascularized bone grafts, vascularized bone grafts, and approaches related to tissue engineering. This review summarizes different modifications of the free vascularized fibula graft, which, since its introduction by Hidalgo in 1989, has become the first option for mandibular reconstruction. The fibula free flap can undergo various modifications according to the individual requirements of a particular reconstruction. Osteocutaneous flaps can be harvested for reconstruction of composite defects. 'Double-barreling' of the fibula can, for instance, enable enhanced aesthetic and functional results, as well as immediate one-stage osseointegrated dental implantation. Recently described preoperative virtual surgery planning to facilitate neomandible remodeling could guarantee good results. To conclude, the free fibula bone graft can currently be regarded as the "gold standard" for mandibular reconstruction in case of composite (inside and outside) oral cavity defects as well as a way of enabling the performance of one-stage dental implantation

The Vascularized Fibular Graft in the Pediatric Upper Extremity: A Durable, Biological Solution to Large Oncologic Defects

Skeletal reconstruction after large tumor resection is challenging. The free vascularized fibular graft (FVFG) offers the potential for rapid autograft incorporation as well as growing physeal transfer in pediatric patients. We retrospectively reviewed eleven pediatric patients treated with FVFG reconstructions of the upper extremity after tumor resection. Eight male and three female patients were identified, including four who underwent epiphyseal transfer. All eleven patients retained a functional salvaged limb. Nonunion and graft fracture were the most common complications relating to graft site (27%). Peroneal nerve palsy occurred in 4/11 patients, all of whom received epiphyseal transfer. Patients receiving epiphyseal transplant had a mean annual growth of 1.7 cm/year. Mean graft hypertrophy index increased by more than 10% in all cases. Although a high complication rate may be anticipated, the free vascularized fibula may be used to reconstruct large skeletal defects in the pediatric upper extremity after oncologic resection. Transferring the vascularized physis is a viable option when longitudinal growth is desired

Facial Fractures in the Aging Population.

BACKGROUND: As the U.S. population ages and life expectancy increases, the number of elderly patients seeking trauma care and treatment for facial fractures will increase. Understanding age-related differences in the pattern, cause, and management of these fractures is essential for improving care. METHODS: A retrospective review of adults presenting to a Level I trauma center was performed to evaluate age-related differences in facial fractures. Descriptive statistics were used to compare fracture number, type, cause of injury, management, and adverse events between elderly (older than 64 years) and younger cohorts (aged 18 to 64 years). Logistic regression was used to evaluate the effect of age on fracture type while controlling for potential confounding variables. RESULTS: Two thousand twenty-three adult patients sustained a facial fracture from 2001 to 2011. Two hundred nine patients were elderly and 1814 were younger. Regarding cause of injury, older patients were more likely to fall and younger patients were more likely to be injured through assaults, motor vehicle collisions, or sports (p \u3c 0.0001). Elderly patients sustained a higher incidence of maxillary (16.3 percent versus 11.4 percent; p = 0.0401), nasal (54.1 percent versus 45.3 percent; p = 0.0156), and orbital floor fractures (28.2 percent versus 18.1 percent; p = 0.004) and a lower incidence of mandible fractures (10.1 percent versus 21.3 percent; p = 0.0001). The elderly had significantly less operative intervention (24.9 percent versus 43 percent; p \u3c 0.0001) and were less likely to experience complications (5.3 percent versus 10.5 percent; p = 0.0162). CONCLUSION: Elderly patients tend to suffer from less severe facial fractures, requiring less need for operative intervention, likely secondary to low-energy mechanisms of injury. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II

Transcardiopulmonary vs Pulmonary Arterial Thermodilution Methods for Hemodynamic Monitoring of Burned Patients.

The objective of this study was to validate a new method of transcardiopulmonary thermodilution for assessment of cardiac index (CI), stroke volume index (SVI), systemic vascular resistance index (SVRI) and additional parameters such as intrathoracic blood volume index and extravascular lung water index (EVLWI) by comparison with conventional pulmonary artery catheter values in a severely burned population. The pulmonary artery measurements were performed continuously with the Vigilance system, and the transcardiopulmonary thermodilution with the PiCCO(R) system. One hundred thirteen measurements with each system on up to six consecutive days were taken in 14 severely burned patients (average TBSA, 49.6%; average ABSI, 10.3), aged 21 to 61 years (mean, 42.2 years) and compared intraindividually. An excellent correlation between the two methods was shown for CI (r = 0.80) and its derived parameters SVI and SVRI in states of low to normal cardiac output. The correlation was poor for cardiac indices greater then 5.5 up to their maximum values (r = 0.46). No correlation between index of oxygenation (PaO2/FiO2) vs EVLW I was observed. There was no difference between survivors and nonsurvivors, and between patients with and without inhalation injury in EVLWI. The method of transcardiopulmonary thermodilution is suitable to assess SVI, CI and SVRI under the special pathophysiologic condition of a major burn for low to normal cardiac output states. It is less reliable when cardiac output is high. The lower cost and less invasive nature are the advantages of the system compared with use of the pulmonary artery catheter. The role of intrathoracic blood volume index and EVLWI in cardiopulmonary monitoring of severely burned patients remains to be further determined

ICA512 signaling enhances pancreatic beta-cell proliferation by regulating cyclins D through STATs

Changes in metabolic demands dynamically regulate the total mass of adult pancreatic beta-cells to adjust insulin secretion and preserve glucose homeostasis. Glucose itself is a major regulator of beta-cell proliferation by inducing insulin secretion and activating beta-cell insulin receptors. Here, we show that islet cell autoantigen 512 (ICA512)/IA-2, an intrinsic tyrosine phosphatase-like protein of the secretory granules, activates a complementary pathway for beta-cell proliferation. On granule exocytosis, the ICA512 cytoplasmic domain is cleaved and the resulting cytosolic fragment (ICA512-CCF) moves into the nucleus where it enhances the levels of phosphorylated STAT5 and STAT3, thereby inducing insulin gene transcription and granule biogenesis. We now show that knockdown of ICA512 decreases cyclin D1 levels and proliferation of insulinoma INS-1 cells, whereas beta-cell regeneration is reduced in partially pancreatectomized ICA512-/- mice. Conversely, overexpression of ICA512-CCF increases both cyclin D1 and D2 levels and INS-1 cell proliferation. Up-regulation of cyclin D1 and D2 by ICA512-CCF is affected by knockdown of STAT3 and STAT5, respectively, whereas it does not require insulin signaling. These results identify ICA512 as a regulator of cyclins D and beta-cell proliferation through STATs and may have implication for diabetes therapy