Download PDF
J Reconstr Microsurg 2022; 38(05): 420-428
DOI: 10.1055/s-0041-1733995
Original Article

Software-based Detection of Acute Rejection Changes in Face Transplant

Miguel I. Dorante  ‡   *
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
2   Department of Surgery, Division of Plastic and Reconstructive Surgery, Lahey Hospital and Medical Center, Burlington, Massachusetts
,
Branislav Kollar  ‡   *
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
3   Department of Plastic and Hand Surgery, University of Freiburg Medical Center, Medical Faculty of the University of Freiburg, Freiburg, Germany
,
Marian Bittner
4   VicarVision, Amsterdam, The Netherlands
,
Alice Wang 
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Yannick Diehm
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
5   Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
,
Sina Foroutanjazi
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Neil Parikh 
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
,
Valentin Haug
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
5   Department of Hand, Plastic and Reconstructive Surgery, Microsurgery, Burn Trauma Center, BG Trauma Center Ludwigshafen, University of Heidelberg, Ludwigshafen, Germany
,
Tim M. den Uyl
4   VicarVision, Amsterdam, The Netherlands
,
Bohdan Pomahac
1   Department of Surgery, Division of Plastic Surgery, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
6   Department of Surgery, Division of Plastic and Reconstructive Surgery, Yale New Haven Hospital, Yale School of Medicine, New Haven, Connecticut
› Author Affiliations Funding This study was granted funding to B.P. by the United States Department of Defense under their Reconstructive Transplant Research Program (#W81XWH-18–1-0702). The authors (M.I.D. and B.P.) received partial support from this award. A paid collaboration with VicarVision (Amsterdam, Netherlands) was paid for fully from this award with authors (M.B. and T.M.den U.) receiving support for their work. The Department of Defense had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. The opinions, interpretations, conclusions, and recommendations in this work are those of the authors and are not necessarily endorsed by the Department of Defense. B.K. was recipient of Plastic Surgery Foundation Research Fellowship Grant outside of submitted work. None of the authors have financial interests in any products or devices mentioned in this manuscript.
› Further Information
Also available at
    Permissions and Reprints

Abstract

Background An objective, non-invasive method for redness detection during acute allograft rejection in face transplantation (FT) is lacking.

Methods A retrospective cohort study was performed with 688 images of 7 patients with face transplant (range, 1 to 108 months post-transplant). Healthy controls were matched to donor age, sex, and had no prior facial procedures. Rejection state was confirmed via tissue biopsy. An image-analysis software developed alongside VicarVision (Amsterdam, Netherlands) was used to produce R, a measure of differences between detectable color and absolute red. R is inversely proportional to redness, where lower R values correspond to increased redness. Linear mixed models were used to study fixed effect of rejection state on R values. Estimated marginal means of fitted models were calculated for pairwise comparisons.

Results Of 688 images, 175, 170, 202, and 141 images were attributable to Banff Grade 0,1,2, and 3, respectively. Estimated change in R value of facial allografts decreased with increasing Banff Grade (p = 0.0001). The mean R value of clinical rejection (Banff Grade ⅔) (16.67, 95% Confidence Interval [CI] 14.79–18.58) was lower (p = 0.005) than non-rejection (Banff Grade 0/1) (19.38, 95%CI 17.43–21.33). Both clinical and non-rejection mean R values were lower (p = 0.0001) than healthy controls (24.12, 95%CI 20.96–27.28).

Conclusion This proof-of-concept study demonstrates that software-based analysis can detect and monitor acute rejection changes in FT. Future studies should expand on this tool's potential application in telehealth and as a screening tool for allograft rejection.

Keywords

vascularized composite allotransplantation - face transplant - rejection - software - facial recognition

* Miguel I. Dorante and Branislav Kollar have contributed equally to this manuscript.




Publication History

Received: 30 April 2021

Accepted: 19 July 2021

Article published online:
01 September 2021

© 2021. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 

  • References

  • 1 Shores JT, Brandacher G, Lee WPA. Hand and upper extremity transplantation: an update of outcomes in the worldwide experience. Plast Reconstr Surg 2015; 135 (02) 351e-360e
    CrossrefPubMedGoogle Scholar
  • 2 Shores JT, Malek V, Lee WPA, Brandacher G. Outcomes after hand and upper extremity transplantation. J Mater Sci Mater Med 2017; 28 (05) 72
    CrossrefPubMedGoogle Scholar
  • 3 Sosin M, Rodriguez ED. The Face Transplantation Update: 2016. Plast Reconstr Surg 2016; 137 (06) 1841-1850
    CrossrefPubMedGoogle Scholar
  • 4 Kollar B, Pomahac B. Facial restoration by transplantation. Surgeon 2018; 16 (04) 245-249
    CrossrefPubMedGoogle Scholar
  • 5 Fischer S, Lian CG, Kueckelhaus M. et al. Acute rejection in vascularized composite allotransplantation. Curr Opin Organ Transplant 2014; 19 (06) 531-544
    CrossrefPubMedGoogle Scholar
  • 6 Kueckelhaus M, Fischer S, Seyda M. et al. Vascularized composite allotransplantation: current standards and novel approaches to prevent acute rejection and chronic allograft deterioration. Transpl Int 2016; 29 (06) 655-662
    CrossrefPubMedGoogle Scholar
  • 7 Haug V, Kollar B, Obed D. et al. The Evolving Clinical Presentation of Acute Rejection in Facial Transplantation. JAMA Facial Plast Surg 2019; 21 (04) 278-285
    CrossrefPubMedGoogle Scholar
  • 8 Tasigiorgos S, Kollar B, Turk M. et al. Five-Year Follow-up after Face Transplantation. N Engl J Med 2019; 380 (26) 2579-2581
    CrossrefPubMedGoogle Scholar
  • 9 Petruzzo P, Sardu C, Lanzetta M. et al. Report (2017) of the International Registry on Hand and Composite Tissue Allotransplantation (IRHCTT). Curr Transpl Rep 2017; 4: 294-303
    CrossrefPubMedGoogle Scholar
  • 10 Schneider M, Cardones ARG, Selim MA, Cendales LC. Vascularized composite allotransplantation: a closer look at the banff working classification. Transpl Int 2016; 29 (06) 663-671
    CrossrefPubMedGoogle Scholar
  • 11 Kueckelhaus M, Fischer S, Lian CG. et al. Utility of sentinel flaps in assessing facial allograft rejection. Plast Reconstr Surg 2015; 135 (01) 250-258
    CrossrefPubMedGoogle Scholar
  • 12 Kollar B, Uffing A, Borges TJ. et al. MMP3 Is a Non-invasive Biomarker of Rejection in Skin-Bearing Vascularized Composite Allotransplantation: A Multicenter Validation Study. Front Immunol 2019; 10: 2771
    CrossrefPubMedGoogle Scholar
  • 13 Honeyman C, Stark H, Wang HC, Hester J, Issa F, Giele H. Biomarker and surrogate development in vascularised composite allograft transplantation: Current progress and future challenges. J Plast Reconstr Aesthet Surg 2021; 74 (04) 711-717
    CrossrefPubMedGoogle Scholar
  • 14 Logger JGM, de Jong EMGJ, Driessen RJB, van Erp PEJ. Evaluation of a simple image-based tool to quantify facial erythema in rosacea during treatment. Skin Res Technol 2020; 26 (06) 804-812
    CrossrefPubMedGoogle Scholar
  • 15 Fischer S, Diehm Y, Dorante MI. et al. Software-based video analysis of functional outcomes of face transplantation. Microsurgery 2019; 39 (01) 53-61
    CrossrefPubMedGoogle Scholar
  • 16 Dorante MI, Kollar B, Obed D, Haug V, Fischer S, Pomahac B. Recognizing Emotional Expression as an Outcome Measure After Face Transplant. JAMA Netw Open 2020; 3 (01) e1919247
    CrossrefPubMedGoogle Scholar
  • 17 Haug V, Kuang Y, Tasigiorgos S. et al. Circulating Donor-derived Cell-free DNA as a Biomarker in Vascularized Composite Allotransplantation?. Transplantation 2020; 104 (03) e79-e80
    CrossrefPubMedGoogle Scholar
  • 18 Kueckelhaus M, Imanzadeh A, Fischer S. et al. Noninvasive Monitoring of Immune Rejection in Face Transplant Recipients. Plast Reconstr Surg 2015; 136 (05) 1082-1089
    CrossrefPubMedGoogle Scholar
  • 19 Bettoni J, Balédent O, Petruzzo P. et al. Role of flow magnetic resonance imaging in the monitoring of facial allotransplantations: preliminary results on graft vasculopathy. Int J Oral Maxillofac Surg 2020; 49 (02) 169-175
    CrossrefPubMedGoogle Scholar
  • 20 Rabbani PS, Rifkin WJ, Kadle RL. et al. Noninvasive Monitoring of Allograft Rejection Using a Novel Epidermal Sampling Technique. Plast Reconstr Surg Glob Open 2019; 7 (08) e2368
    CrossrefPubMedGoogle Scholar
  • 21 Lalkhen AG, McCluskey A. Clinical tests: sensitivity and specificity. Contin Educ Anaesth Crit Care Pain 2008; 8 (06) 221-223
    CrossrefPubMedGoogle Scholar
  • 22 Kollar B, Pomahac B, Riella LV. Novel immunological and clinical insights in vascularized composite allotransplantation. Curr Opin Organ Transplant 2019; 24 (01) 42-48
    CrossrefPubMedGoogle Scholar
  • 23 Kollar B, Shubin A, Borges TJ. et al. Increased levels of circulating MMP3 correlate with severe rejection in face transplantation. Sci Rep 2018; 8 (01) 14915
    CrossrefPubMedGoogle Scholar
  • 24 Daneshgaran G, Stern CS, Garfein ES. Reporting Practices on Immunosuppression and Rejection Management in Face Transplantation: A Systematic Review. J Reconstr Microsurg 2019; 35 (09) 652-661
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Kanitakis J. The challenge of dermatopathological diagnosis of composite tissue allograft rejection: a review. J Cutan Pathol 2008; 35 (08) 738-744
    CrossrefPubMedGoogle Scholar
  • 26 Pomahac B, Pribaz J, Eriksson E. et al. Restoration of facial form and function after severe disfigurement from burn injury by a composite facial allograft. Am J Transplant 2011; 11 (02) 386-393
    CrossrefPubMedGoogle Scholar
  • 27 Robbins NL, Wordsworth MJ, Parida BK. et al. Is Skin the Most Allogenic Tissue in Vascularized Composite Allotransplantation and a Valid Monitor of the Deeper Tissues?. Plast Reconstr Surg 2019; 143 (04) 880e-886e
    CrossrefPubMedGoogle Scholar
  • 28 Sarhane KA, Tuffaha SH, Broyles JM. et al. A critical analysis of rejection in vascularized composite allotransplantation: clinical, cellular and molecular aspects, current challenges, and novel concepts. Front Immunol 2013; 4: 406
    CrossrefPubMedGoogle Scholar
  • 29 Yan D, Stokar E, Jacoby A, Gelb BE, Rodriguez ED, Meehan SA. A case of facial composite tissue allograft rejection. JAAD Case Rep 2020; 6 (09) 845-847
    CrossrefPubMedGoogle Scholar
  • 30 Kollar B, Rizzo NM, Borges TJ. et al. Accelerated chronic skin changes without allograft vasculopathy: A 10-year outcome report after face transplantation. Surgery 2020; 167 (06) 991-998
    CrossrefPubMedGoogle Scholar
  • 31 Kollar B, Kamat P, Klein HJ, Waldner M, Schweizer R, Plock JA. The Significance of Vascular Alterations in Acute and Chronic Rejection for Vascularized Composite Allotransplantation. J Vasc Res 2019; 56 (04) 163-180
    CrossrefPubMedGoogle Scholar
  • 32 Kaufman CL, Kanitakis J, Weissenbacher A. et al. Defining chronic rejection in vascularized composite allotransplantation-The American Society of Reconstructive Transplantation and International Society of Vascularized Composite Allotransplantation chronic rejection working group: 2018 American Society of Reconstructive Transplantation meeting report and white paper Research goals in defining chronic rejection in vascularized composite allotransplantation. SAGE Open Med 2020; 8: 2050312120940421 DOI: 10.1177/2050312120940421.
    Google Scholar
  • 33 Salehi PP, Torabi SJ, Lee YH, Azizzadeh B. Telemedicine Practices of Facial Plastic and Reconstructive Surgeons in the United States: The Effect of Novel Coronavirus-19. Facial Plast Surg Aesthet Med 2020; 22 (06) 464-470
    CrossrefPubMedGoogle Scholar
  • 34 Rifkin WJ, Manjunath A, Kimberly LL. et al. Long-distance care of face transplant recipients in the United States. J Plast Reconstr Aesthet Surg 2018; 71 (10) 1383-1391
    CrossrefPubMedGoogle Scholar
  • 35 Lambooy S, Krishnasamy R, Pollock A, Hilder G, Gray NA. Telemedicine for Outpatient Care of Kidney Transplant and CKD Patients. Kidney Int Rep 2021; 6 (05) 1265-1272
    CrossrefPubMedGoogle Scholar
  • 36 Chang JH, Diop M, Burgos YL. et al. Telehealth in outpatient management of kidney transplant recipients during COVID-19 pandemic in New York. Clin Transplant 2020; 34 (12) e14097
    CrossrefPubMedGoogle Scholar
  • 37 Wolfe EM, Najera-Sweeney G, Berman ZP. et al. Establishing Photographic Standards for Facial Transplantation: A Systematic Review of the Literature. Plast Reconstr Surg Glob Open 2020; 8 (05) e2834
    PubMedGoogle Scholar
  • 38 Liu X, Langsdon S, Holloway W. et al. The Ethics of Facial Allotransplantation: A Systematic Review. Plast Reconstr Surg Glob Open 2019; 7 (10) e2425
    CrossrefPubMedGoogle Scholar
  • 39 Kimberly LL, Ramly EP, Alfonso AR, Diep GK, Berman ZP, Rodriguez ED. Equity in access to facial transplantation. J Med Ethics . Published online October 15, 2020:medethics-2020–106129 DOI: 10.1136/medethics-2020-106129.
    CrossrefPubMedGoogle Scholar
  • 40 Shokri T, Saadi R, Wang W, Reddy L, Ducic Y. Facial Transplantation: Complications, Outcomes, and Long-Term Management Strategies. Semin Plast Surg 2020; 34 (04) 245-253
    Article in Thieme ConnectPubMedGoogle Scholar
  • 41 Baranoski GVG, Van Leeuwen SR, Chen TF. On the detection of peripheral cyanosis in individuals with distinct levels of cutaneous pigmentation. Annu Int Conf IEEE Eng Med Biol Soc 2017; 2017: 4260-4264
    PubMedGoogle Scholar
  • 42 Kauke M, Panayi AC, Tchiloemba B. et al. Face Transplantation in a Black Patient - Racial Considerations and Early Outcomes. N Engl J Med 2021; 384 (11) 1075-1076
    CrossrefPubMedGoogle Scholar
  • 43 Haider AH, Scott VK, Rehman KA. et al. Racial disparities in surgical care and outcomes in the United States: a comprehensive review of patient, provider, and systemic factors. J Am Coll Surg 2013; 216 (03) 482-92.e12
    CrossrefPubMedGoogle Scholar
  • 44 Ng Y-H, Pankratz VS, Leyva Y. et al. Does Racial Disparity in Kidney Transplant Waitlisting Persist After Accounting for Social Determinants of Health?. Transplantation 2020; 104 (07) 1445-1455
    CrossrefPubMedGoogle Scholar
  • 45 Kernodle AB, Zhang W, Motter JD. et al. Examination of Racial and Ethnic Differences in Deceased Organ Donation Ratio Over Time in the US. JAMA Surg 2021; 156 (04) e207083
    CrossrefPubMedGoogle Scholar
  • 46 Ramly EP, Berman ZP, Diep GK, Alfonso AR, Kimberly LL, Rodriguez ED. Vascularized Composite Allotransplantation in a Post-COVID-19 Pandemic World. Plast Reconstr Surg 2020; 146 (03) 394e-395e
    CrossrefPubMedGoogle Scholar
  • 47 Dorante MI, Wang A, Kollar B. et al. American Society for Reconstructive Transplantation Conference Abstracts 2020: Emotions after face transplant: first international face transplant cohort comparison. SAGE Open Med 2021; 9: 9
    PubMedGoogle Scholar
  • 48 Zarins U. Anatomy of Facial Expressions. 2018
    PubMedGoogle Scholar
  • 49 Guarin DL, Yunusova Y, Taati B. et al. Toward an Automatic System for Computer-Aided Assessment in Facial Palsy. Facial Plast Surg Aesthet Med 2020; 22 (01) 42-49
    CrossrefPubMedGoogle Scholar