The Ethics of Hand Transplantation: A Systematic Review

SCIENTIFIC ARTICLE

The Ethics of Hand Transplantation: A Systematic Review Carisa M. Cooney, MPH,* Charalampos Siotos, MD,* Jeffrey W. Aston, BS,* Ricardo J. Bello, MD, MPH,* Stella M. Seal, MLS,† Damon S. Cooney, MD, PhD,* Jaimie T. Shores, MD,* Gerald Brandacher, MD,* W. P. Andrew Lee, MD*

Purpose We conducted a systematic review to document ethical concerns regarding human upper extremity (UE) allotransplantation and how these concerns have changed over time. Methods We performed a systematic review of 5 databases to find manuscripts addressing ethical concerns related to UE allotransplantation. Inclusion criteria were papers that were on the topic of UE allotransplantation, and related ethical concerns, written in English. We extracted and categorized ethical themes under the 4 principles of bioethics: Autonomy, Beneficence, Nonmaleficence, and Justice. We assessed theme frequency by publication year using Joinpoint regression, analyzing temporal trends, and estimating annual percent change. Results We identified 474 citations; 49 articles were included in the final analysis. Publication years were 1998 to 2015 (mean, 3 publications/y; range, 0e7 publications/y). Nonmaleficence was most often addressed (46 of 49 papers; 94%) followed by autonomy (36 of 49; 74%), beneficence (35 of 49; 71%), and justice (31 of 49; 63%). Of the 14 most common themes, only “Need for More Research/Data” (nonmaleficence) demonstrated a significant increase from 1998 to 2002. Conclusions Upper extremity transplantation is an appealing reconstructive option for patients and physicians. Its life-enhancing (vs life-saving) nature and requirement for long-term immunosuppression have generated much ethical debate. Availability of human data has influenced ethical concerns over time. Our results indicate that discussion of ethical issues in the literature increased following publication of UE transplants and outcomes as well as after meetings of national societies and policy decisions by regulatory agencies. Clinical relevance Because UE transplantation is not a life-saving procedure, much ethical debate has accompanied its evolution. It is important for UE surgeons considering referring patients for evaluation to be aware of this discussion to fully educate patients and help them make informed treatment decisions. (J Hand Surg Am. 2017;-(-):1.e1-e15. Copyright Ó 2017 by the American Society for Surgery of the Hand. All rights reserved.) Key words Ethics, hand transplantation, VCA, composite tissue allotransplantation, upper extremity allotransplantation.

From the *Department of Plastic and Reconstructive Surgery; and the †Welch Medical Library, Johns Hopkins University School of Medicine, Baltimore, MD. Received for publication August 19, 2016; accepted in revised form August 2, 2017. No benefits in any form have been received or will be received related directly or indirectly to the subject of this article.

Corresponding author: Carisa M. Cooney, MPH, Department of Plastic and Reconstructive Surgery, Johns Hopkins University School of Medicine, 601 N. Caroline St., JHOC 8163, Baltimore, MD 21287; e-mail: [email protected]. 0363-5023/17/---0001$36.00/0 http://dx.doi.org/10.1016/j.jhsa.2017.08.004

Ó 2017 ASSH

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HAND TRANSPLANT ETHICS: A SYSTEMATIC REVIEW

extremity (UE) allotransplantation and whether it should be performed in human subjects have evolved over the past 25 years. Open discussions were initiated at the 1991 conference on the clinical use of composite tissue allotransplantation. Held in conjunction with the Rehabilitation Research & Development Service of the Department of Veterans Affairs in Washington, DC, this conference’s determination was that more preclinical data were needed prior to being able to ethically perform hand transplants in human subjects.1 In November 1997, the conversation continued at the First International Symposium on composite tissue allotransplantation held in Louisville, KY. A controversial conclusion there was that it was time to “just do it” (human hand transplantation).2 Outside ethicist-observer Mark Siegler, MD, agreed, stating that, based on data presented at the meeting and preparatory steps taken by presenting programs, it was “ethically defensible” to perform cadaveric human hand transplantation under an institutional review boardeapproved research protocol.3 Within the next 2 years, the first 2 human patients were transplanted: the first in Lyon, France (1998),4 and the second in Louisville, KY (1999).5 Following the publication of data from these and 2 other early patients, which included the amputation of the first patient’s graft 28 months after transplant,4e9 the International Federation of Societies for Surgery of the Hand and the American Society for Surgery of the Hand (ASSH) released their position statement in 2001 strongly advising caution on the further expansion of hand transplantation until more human data were available.10 Whereas the hand transplant community heeded the call to return to the laboratory to conduct more basic research into rejection mechanisms and improved immunosuppression,11e13 clinical UE transplants continued in parallel. In 2002, the International Registry on Hand and Composite Tissue Transplantation (IRHCTT) was established to facilitate pooled reporting of outcomes on the world experience.14 In 2003, the ASSH revisited its position statement, maintaining its strong cautionary stance. However, transplants continued and the hand transplantation community was widely encouraged to publish or share all data available on patient outcomes.10e12,14,15 In the meantime, advances in solid organ transplantation immunosuppression protocols were being made, which some researchers thought could improve hand transplantation.16e18 By 2009, these experimental strategies were successfully adopted by the University of Pittsburgh Medical Center for hand/UE

transplantation, enabling vascularized composite allotransplantation (VCA) to be performed and maintained on a single-drug immunosuppression regimen, thus further favoring the risk-benefit ratio for hand transplant recipients.19 Inspired by these advances, several other academic institutions across the United States including the University of California Los Angeles, Harvard Medical School/Massachusetts General and Brigham and Women’s Hospital, University of Pennsylvania, Emory University, Duke University, and others, established active hand transplantation programs.20 The data regarding improved methods of immunosuppression appeared to have disseminated into the hand surgery community during the next several years. In 2009, Mathes et al21 published an article on North American hand surgeons’ attitudes toward hand transplantation. Their study found that 78% of respondents thought that bilateral amputation and 32% that dominant hand amputation were appropriate indications for hand transplantation, whereas only 16% were in favor of performing transplants with the immunosuppression regimen available at the time.21 Importantly, 71% of respondents believed hand transplantation was an ethical procedure when performed in carefully selected patients.21 Bertrand et al22 revisited this topic in 2014 and opinions were slightly more favorable toward hand transplantation—80% of respondents stated that bilateral amputation and 36% that dominant hand amputation were appropriate indications. Opinions were much more favorable when considering its required immunosuppression: 56% of respondents stated they were in favor of performing transplants with the currently available immunosuppression.22 Despite potential selection bias, this change in opinion may have been influenced by the ASSH’s 2013 revised position on hand transplantation23 in which the procedure is acknowledged as an alternative to prosthetics but should be undertaken only by experienced centers and in carefully selected patients. This was followed by the implementation of the U.S. Department of Health and Human Services (DHHS) Organ Procurement and Transplantation Network Final Rule (42 CFR part 121) which included vascularized composite allografts as covered human organs effective July 3, 2014, and subjected programs to minimum membership requirements.24 Hand/UE transplant programs continue to be established in the United States and worldwide. Currently, 15 U.S. programs are listed on the American Society for Reconstructive Transplantation Web site.20 However, concerns regarding the ethics of the

PINIONS ON THE ETHICS OF UPPER

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IdenƟficaƟon

HAND TRANSPLANT ETHICS: A SYSTEMATIC REVIEW

Records identified through database searching (n = 474)

Additional records identified through other sources (n = 7)

Included

Eligibility

Screening

Records after duplicates removed (n = 313)

Records screened (n = 313)

Full-text articles assessed for eligibility (n = 86)

Records excluded (n = 227)

Full-text articles excluded (n = 37) Language other than English (n = 9) Abstract only (n = 4) Did not include ethical themes (n = 19) Not about hand transplant (n = 2) Duplicate (n = 3)

Studies included in qualitative synthesis (n = 49)

FIGURE 1: Flow chart summarizes the results of the screening process and final article selection.

procedure remain and new issues have emerged as the field evolves. We performed a systematic review of the literature to summarize these concerns using 4 pillars of bioethical principles, autonomy, beneficence, nonmaleficence, and justice, and to study how ethical concerns have changed over time.25

(the physician’s obligation to respect patients’ decisions on the care they receive, after being accurately informed), Beneficence (the obligation to act in benefit of the patient), Nonmaleficence (the Hippocratic obligation of “do not harm”), and Justice (the obligation to respect laws and patients’ rights, and to promote fair distribution of health care resources).25 The frequency of themes by publication year was assessed. The Joinpoint regression program (National Cancer Institute, Calverton, MD) was used to analyze temporal trends in ethical themes and to estimate annual percentage change (APC, used to evaluate changes in rates and trends over time) for the most common ethical themes. Level of significance was set at P less than .05.

MATERIALS AND METHODS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and with the assistance of a medical library informationist, we conducted a literature search in 5 databases (PubMed, Embase, Cochrane, Web of Science, and Scopus) from inception to June 10, 2016. Inclusion criteria consisted of articles on hand/UE allotransplantation and the ethical concerns relating to it, written in the English language (Appendix A for search strategy; available on the Journal’s Web site at www.jhandsurg.org). Two reviewers (C.M.C., C.S.) performed the title/abstract screening and full-article review. Any disagreements regarding articles to be included were resolved by discussion. Ethical themes were extracted qualitatively and categorized as applicable under the 4 principles of bioethics: Autonomy J Hand Surg Am.

RESULTS The search revealed 474 citations; after removing 168 duplicates, 306 unique citations remained. Following title/abstract review, 79 articles were eligible for full-text review; hand searching of references yielded 7 additional articles (n ¼ 86). Following full-article review, 49 articles were eligible and included in the final data extraction and analysis (Fig. 1). r

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7

ASSH releases posi on statement opposing hand transplant; 1st hand transplant amputated

6

5

IRHCTT established; renewed efforts in basic science

2nd hand transplant performed (Louisville, KY; USA)

# of Publications

4

1st bilateral hand, 1st pediatric hand transplants performed

3

2

ASSH affirms posi on statement on hand transplanta on

Hand transplant immunosuppression minimiza on protocol ini ated (Pi sburgh, PA)

1st hand transplant performed (Lyon, France)

6 pa ents received hand transplants in the USA

Announcement that VCA will be regulated under OPTN; ASSH revises posi on statement on hand transplant

1st combined hand/face transplant pa ent dies (Paris, France)

1

0 1998

1999

2000

2001

2002

2003

2004

2005

2006

2007

2008

2009

2010

2011

2012

2013

2014

2015

Year of Publica on

FIGURE 2: Number of papers (n ¼ 49) addressing ethical themes published by year from 1998 to 2015 with notes regarding some pivotal hand transplant/VCA events. OPTN, Organ Procurement and Transplantation Network.

Publication years were 1998 through 2015. The number of papers published per year varied from 0 in 2004 to 7 in 2011; the average number published per year was 3 (Fig. 2). Among the 4 pillars of bioethics, Nonmaleficence was the most often addressed with themes included in 46 of 49 papers (94%). This was followed by Autonomy (36 of 49; 74%), Beneficence (35 of 49; 71%), and Justice (31 of 49; 63%). The most commonly addressed themes and when they appeared in the literature are summarized in Figure 3. To summarize top concerns, nonmaleficence included risks of long-term immunosuppression (n ¼ 35; 76%),3,10,15,21,22,26e55 patient selection (n ¼ 21; 46%),* ensuring benefits justify risks (n ¼ 18; 39%),† and need for additional research (n ¼ 12; 26%).‡ Autonomy included informed consent/decision making (n ¼ 31; 86%),§ recipient’s right/ability to choose (n ¼ 18; 50%),k and role of patient advocate/ family in decision making (n ¼ 5; 14%).33,35,43,58,64

Beneficence included restoration of function/body integrity/aesthetics (n ¼ 20; 57%),{ improved quality of life (n ¼ 11; 31%),# recovery of sensation (n ¼ 4; 11%),29,48,49,56 and professional/social reintegration (n ¼ 4; 11%)47,48,50,52 Justice included burden to donors/donor families/ impact on solid organ transplantation (n ¼ 11; 35%),** appropriate patient selection (n ¼ 11; 35%),†† and cost considerations (n ¼ 6; 19%).30,49,52,53,61,66 All themes may be viewed in Table 1; all papers and information on bioethical pillars addressed may be viewed in Appendix B (available on the Journal’s Web site at www.jhandsurg.org). The APC trends were calculated for the previously listed 14 primary themes (Table 2). Seven themes decreased in frequency over time [APC, < (e)1] whereas 4 themes increased [APC, > (þ)1]. Five themes did not change (APC ranged from e1 to þ1). Only the theme of “Need for more research/data” under the principle of

*

{

†

#

References 22,26,30,32,34,35,37e39,43,45,46,49,50,52,53,56e60. References 9,11,15,21,26,27,29,31,32,35,39,43,46,49,52e54,61. ‡ References 15,21,28,30,31,33e36,38,50,51. § References 3,9e11,15,26,27,29,30,32,33,36,38e40,42e45,47e50,52,53,55e58,62,63. k References 3,9,11,15,26,29,30,35,38,40,45,48e50,52,53,62,63.

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References 1,10,15,22,27,29,32e36,44,47,49,52,53,56,59,60,63. References 3,33e36,39,40,45,56,62,63. ** References 26,27,30,35,36,40,43,47,50,58,65. †† References 1,10,33,34,36,37,43,48,57,60,63.

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AUTONOMY

BENEFICENCE

Informed consent/decision (n = 31) Recipient's right/ability to choose (n = 18) Role of paent/advocate, family in decision making (n = 5) 7

7

6

6

5

5

4

4

3

3

2

2

1

1

0 1996

1998

2000

2002

2004

2006

2008

2010

2012

2014

Body integrity/aesthecs/funcon (n = 20) Recovery of sensaon (n = 4)

0 1996

2016

1998

2000

2002

NONMALEFICENCE

6

5

5

4

4

3

3

2

2

1

1

1998

2000

2002

2004

2006

2008

2010

2012

2014

2008

2010

2012

2014

2016

2014

2016

Donor/donor family ethical issues/impact on SOT (n = 11) Appropriate paent selecon (n = 11) Cost consideraons (n = 6)

7

6

0 1996

2006

JUSTICE

Immunosuppression (n = 35) Paent selecon (i.e., psychosocial issues, compliance) (n = 21) Risk/benefit rao (n = 18) Need for more research/data (n = 12)

7

2004

Improvement in QOL (n = 11) Professional/social integraon (n = 4)

2016

0 1996

1998

2000

2002

2004

2006

2008

2010

2012

FIGURE 3: Most frequent ethical themes and their appearance in the peer-reviewed literature from 1998 to 2015 categorized by the 4 principles of bioethics. QOL, quality of life; SOT, solid organ transplantation.

nonmaleficence demonstrated a statistically significant increase over time from 1998 to 2002 (APC ¼ 61; 95% confidence interval, 5e147; P < .05).

Concerns peaked in 2002, following the unfavorable outcomes resulting from the first patient’s noncompliance with immunosuppression and subsequent explantation 28 months after transplant.7,68 These results caused many individuals to advise a reevaluation of the risk-benefit ratio of UE allotransplantation and to consider a moratorium on performing additional transplants until more research had been done and human data from currently transplanted human subjects published.10,11,68 Interestingly, ethical themes from the other 3 pillars also peaked in 2002, the most published of which related to “body integrity/aesthetics/function” under the pillar of beneficence. This coincided with published data on all other patients to date, indicating that outcomes in compliant patients were better than anticipated.8,11,12,15,33,35 These realizations seem to feed back into the theme of “careful patient selection,” which was addressed under the pillars of both nonmaleficence (physician cause-noharm by selecting candidates most likely to benefit from the procedure)32,34,35 and justice (programs have the responsibility to make the procedure available to

DISCUSSION Hand and UE allotransplantation has become a reconstructive option for the treatment of major amputations of the upper limb. It is valued by its advocates for its ability to reconstruct “like with like” without creating autologous donor site morbidity21,34,67,68 and its ability to restore function and quality of life at least as well as analogous replants.15,53,62 Its critics continue to emphasize concerns pertaining to the risks of long-term immunosuppression and the justifications for such risks for a nonelife-saving procedure, the challenges of selecting appropriate patients, and the costs.10,15,30,66 Our study found that themes related to the principle of nonmaleficence were the most commonly addressed, appearing in over 93% of included papers. These were followed by themes relating to autonomy (74%), beneficence (71%), and justice (63%). J Hand Surg Am.

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TABLE 1.

Recurring Themes Identified From 49 Hand Transplant Articles Addressing Ethical Concerns

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Beneficence (n ¼ 35)

Non-Maleficence (n ¼ 46)

Justice (n ¼ 31)

Most common themes (frequency n, %)

 Informed consent/decision making (31, 86)  Recipient’s right/ability to choose (18, 50)  Role of patient advocate/family in decision-making (5, 14)

 Restoration of function/body integrity/aesthetics (20, 57)  Improved QOL (11, 31)  Recovery of sensation (4, 11)  Professional/social reintegration (4, 11)

 Risks of long-term immunosuppression (35, 76)  Patient selection (21, 46)  Risk-benefit ratio (18, 39)  Need for additional research (12, 26)

 Appropriate patient selection (11, 35)  Burden to donors/donor families/impact on SOT (11, 35)  Cost considerations (6, 19)

Less common themes

     

 Improved immunosuppression/tolerance  Double effect  Phantom limb phenomenon  Patient selection  Intimacy  VCA team characteristics  Human trials  Cadaveric tissue (no donor site)  Welfare of patient  Cost-benefit ratio  Openly publicized intent  Altruism by donors  Benefit to the blind  Informed consent

   

       

Donor’s right to choose Selecting appropriate candidates Filming informed consent Realistic expectations Religious and cultural sensitivity Unique individual experience

IEC, institutional ethics committee; IRB, institutional review board; SOT, solid organ transplantation.

        

Cost Transplant team Religious/cultural concerns Objective measurement of impact Patient autonomy Donor’s rights Compromise of SOT donation Need for oversight (IRB, IEC) Appropriate length of followup Informed consent Overzealous team Realistic expectations Invasive interest of press

Organ availability (scarcity)/organ trafficking Public disclosure Availability of long-term immunosuppression Need for oversight (IRB, IEC) Cultural and social considerations Need for additional research VCA team characteristics Identity

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TABLE 2.

Joinpoint Analysis of Number of Papers Addressing Ethical Themes From 1998 to 2015 Start of Trend

End of Trend

APC

95% CI

P Value

Informed consent/decision

1998

2015

e3.1

e8.4 to 2.6

NS

Recipient’s right/ability to choose

1998

2015

e1.9

e6.9 to 3.4

NS

Role of patient advocate, family in decision making

1998

2015

e0.6

e4.6 to 3.5

NS

Body integrity/aesthetics/function

1998

2015

e0.4

e8.1 to 7.9

NS

Improvement in QOL

1998

2015

e3.9

e8.6 to 1.2

NS

Principle Autonomy

Beneficence

Nonmaleficence

Justice

Total

Theme

Recovery of sensation

1998

2015

e0.7

e3.6 to 2.4

NS

Professional/social integration

1998

2015

3.3

e0.2 to 7.0

NS

Immunosuppression

1998

2015

0

e6.3 to 6.7

NS

Patient Selection (ie, psychosocial issues, compliance)

1998

2015

0.2

e6.2 to 7.1

NS

Risk-benefit ratio

1998

2015

e1.4

e7.7 to 5.4

NS

Need for more research/data

1998

2002

60.9

2002

2006

e36.8

4.9 to 146.9 e67.9 to 24.4

< .05 NS

2006

2015

5.5

e6.8 to 19.3

NS

Appropriate patient selection

1998

2015

e2.2

e7.8 to 3.8

NS

Donor/donor family ethical issues/ impact on SOT

1998

2015

e1.9

e6.5 to 2.9

NS

Cost considerations

1998

2015

2.8

e1.8 to 7.5

NS

-

1998

2015

e0.6

e6.8 to 5.9

NS

95% CI, 95% confidence interval; NS, not significant; QOL, quality of life; SOT, solid organ transplantation.

those patients most likely to benefit).10,33,34 The field remained sensitive to the importance and meaning of “informed consent” (under autonomy), which consistently appeared as a concern throughout the period studied for this high-risk research procedure.10,15,32,33 In comparing the change between years, the 2002 publications showed an increase in ethical concerns in 8 of the 14 most commonly addressed areas (APC range, 3e61). Only 2 themes trended down between 2001 and 2002: “recipient’s right/ability to choose (their treatment)” addressed under the pillar of autonomy and “cost considerations” under justice. Although smaller than the 2002 peak, 2 additional increases in ethical concerns occurred in 2011 and 2014. The 2011 increase in publications (n ¼ 7)46e48,63e66 may have been in response to the increase in UE transplants in the United States from late 2009 through 2010 and the 2010 publication of patient data by the IRHCTT.69 Although thematic increases occurred in 8 of the 14 most commonly addressed themes, no theme was raised more than 3 times and this peak seems to be a continuation of the general discussion pertaining to ongoing considerations relevant to program development and patient selection. J Hand Surg Am.

Five papers contributed to the 2014 increase in concerns affecting 7 of the 14 most common themes affecting all ethical pillars.22,51e53,61 This was likely in response to 2 significant events that occurred in 2013: the revision of the ASSH position statement acknowledging UE transplantation as a treatment option that should be undertaken only by experienced centers and in carefully selected patients23 and the July 3, 2013, announcement of the DHHS Final Rule stating that vascularized composite allografts would be regulated under the Organ Procurement and Transplantation Network starting in 2014.70 Although a desirable outcome, the Final Rule decision brought with it many uncertainties regarding exactly how regulation would be implemented. Under such circumstances, it seems reasonable that the VCA community became more cognizant of opportunities to openly discuss program obligations to ensure coverage (“cost considerations”) for the procedure and, perhaps more importantly, for the long-term immunosuppression required for posttransplant graft maintenance.52,53,61 It seems the public attention provided a similar opportunity for the reassertion of concerns regarding long-term immunosuppression,22,51e53 the procedure’s risk-benefit ratio,52,53,61 the importance of r

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informed consent,52,53 the patient’s right to choose the procedure,52,53 the beneficial effects UE transplant can have on body integrity and function,22,52,53 and the vital role of appropriate patient selection in contributing to favorable long-term outcomes and success.22,52,53 In reviewing our results, it is not surprising that the majority of the discussion has focused on risks (nonmaleficence) rather than benefits. In his 1998 paper, Dr. Siegler3 pointed out that the area of bioethics arose, in part, as a response to a series of past, unacceptable occurrences in human experimentation. In working to ensure that such events did not recur, bioethics has taken a more conservative role with the burden of proof relying on demonstrations of beneficence. The struggle to realize medical advances begins at the intersection between implementation of a potentially beneficial, cutting-edge technology and the inability to absolutely know all possible risks. Our study has limitations. Although we identified 49 eligible papers, primary themes represented relatively small sample sizes for meaningful analyses of changes over time when stratified by year. This small sample size could also explain the wide 95% confidence interval for the only statistically significant outcome (“Need for More Research/Data” from 1998 to 2002). Although years of publication could have been condensed into broader time frames, we chose to display these data separately by year because ethical concerns have closely followed clinical outcomes published in the literature and regulatory changes. In addition, extraction of ethical themes is a subjective process and subsequent attempts to reproduce this study may yield different results. We cannot hope, through this study, to end the ethical debate regarding implementation of hand/UE allotransplantation. Instead, we hope that by highlighting the work and discussions that have taken place during the past 25 years, we may further advance the discussion. Indeed, the field has survived many changes: from the early days when bilateral, distal forearm amputees were considered the only ethical candidates for transplantation1,28,57 to current, encouraging results demonstrated by proximal, aboveelbow unilateral amputees67,71; from initial views on immunosuppression, which considered it impossible to manage VCA on regimens equivalent to those of kidney transplant patients7,10,29,68 to the implementation of immunosuppression minimization protocols that have made it possible to maintain allograft survival up to 7 years or more without evidence of longterm renal or other toxicity.53,72,73 Such advancements have shifted the risk-benefit ratio. Regardless, the J Hand Surg Am.

ethical debate continues because ongoing discussion of issues is critical to the development of the field and delivery of high-quality patient-centered care. REFERENCES 1. Herndon JH. Composite-tissue transplantation—a new frontier. N Engl J Med. 2000;343(7):503e505. 2. Barker JH, Jones JW, Breidenbach WC. Closing remarks. Transplant Proc. 1998;30(6):2787. 3. Siegler M. Ethical issues in innovative surgery: should we attempt a cadaveric hand transplantation in a human subject? Transplant Proc. 1998;30(6):2779e2782. 4. Dubernard JM, Owen E, Herzberg G, et al. Human hand allograft: report on first 6 months. Lancet. 1999;353(9161):1315e1320. 5. Jones JW, Gruber SA, Barker JH, Breidenbach WC. Successful hand transplantation. One-year follow-up. Louisville Hand Transplant Team. N Engl J Med. 2000;343(7):468e473. 6. Francois CG, Breidenbach WC, Maldonado C, et al. Hand transplantation: comparisons and observations of the first four clinical cases. Microsurgery. 2000;20(8):360e371. 7. Hettiaratchy S, Butler PE, Lee WP. Lessons from hand transplantations. Lancet. 2001;357(9255):494e495. 8. Lanzetta M, Nolli R, Borgonovo A, et al. Hand transplantation: ethics, immunosuppression and indications. J Hand Surg Br. 2001;26(6):511e516. 9. Meyer VE. Hand transplantation. J Hand Surg Br. 2001;26(6): 509e510. 10. Cooney WP, Hentz VR, American Society for Surgery of the Hand. Hand transplantation—primum non nocere. J Hand Surg Am. 2002;27(1):165e168. 11. Manske PR. Hand transplantation. J Hand Surg Am. 2001;26(2): 193e195. 12. Margreiter R, Brandacher G, Ninkovic M, Steurer W, Kreczy A, Schneeberger S. A double-hand transplant can be worth the effort! Transplantation. 2002;74(1):85e90. 13. Lee WP. Composite tissue transplantation: more science and patience needed. Plast Reconstr Surg. 2001;107(4):1066e1070. 14. Lanzetta M, Petruzzo P, Margreiter R, et al. The International Registry on Hand and Composite Tissue Transplantation. Transplantation. 2005;79(9):1210e1214. 15. Jones NF. Concerns about human hand transplantation in the 21st century. J Hand Surg Am. 2002;27(5):771e787. 16. Starzl TE, Murase N, Abu-Elmagd K, et al. Tolerogenic immunosuppression for organ transplantation. Lancet. 2003;361(9368): 1502e1510. 17. Ciancio G, Miller J, Garcia-Morales RO, et al. Six-year clinical effect of donor bone marrow infusions in renal transplant patients. Transplantation. 2001;71(7):827e835. 18. Cirocco RE, Carreño MR, Mathew JM, et al. FoxP3 mRNA transcripts and regulatory cells in renal transplant recipients 10 years after donor marrow infusion. Transplantation. 2007;83(12):1611e1619. 19. Schneeberger S, Gorantla VS, Brandacher G, et al. Upper-extremity transplantation using a cell-based protocol to minimize immunosuppression. Ann Surg. 2013;257(2):345e351. 20. The American Society for Reconstructive Transplantation. National Directory of VCA Centers. Available at: http://www.a-s-r-t.com/ NationalDirectoryofVCACenters.html. Accessed July 14, 2016. 21. Mathes DW, Schlenker R, Ploplys E, Vedder N. A survey of North American hand surgeons on their current attitudes toward hand transplantation. J Hand Surg Am. 2009;34(5):808e814. 22. Bertrand AA, Sen S, Otake LR, Lee GK. Changing attitudes toward hand allotransplantation among North American hand surgeons. Ann Plast Surg. 2014;72(Suppl 1):S56eS60. 23. The American Society for Surgery of the Hand Council. ASSH Position Statement on Hand Transplantation 2013. J Hand Surg Am. 2013;38(11):2234e2235.

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24. Organ Procurement and Transplantation Network. Policies. Available at: https://optn.transplant.hrsa.gov/governance/policies/. U.S. Department of Health and Human Services. Accessed July 1, 2016. 25. Beauchamp TL, Childress JF. Principles of Biomedical Ethics. New York: Oxford University Press; 1973. 26. Caplan AL. Wearing your organ transplant on your sleeve. Hastings Cent Rep. 1999;29(2):52. 27. Dickenson D, Hakim NS. Ethical issues in limb transplants. Postgrad Med J. 1999;75(887):513e515. 28. Tamai S. Reflections on human hand allografts. J Orthop Sci. 1999;4(5):325e327. 29. Simmons PD. Ethical considerations in composite tissue allotransplantation. Microsurgery. 2000;20(8):458e465. 30. Dickenson D, Widdershoven G. Ethical issues in limb transplants. Bioethics. 2001;15(2):110e124. 31. Hatrick NC, Tonkin MA. Hand transplantation: a current perspective. ANZ J Surg. 2001;71(4):245e251. 32. Benatar D, Hudson DA. A tale of two novel transplants not done: the ethics of limb allografts. BMJ. 2002;324(7343):971e973. 33. Breidenbach WC III, Tobin GR II, Gorantla VS, Gonzalez RN, Granger DK. A position statement in support of hand transplantation. J Hand Surg Am. 2002;27(5):760e770. 34. Brenner MJ, Tung TH, Jensen JN, Mackinnon SE. The spectrum of complications of immunosuppression: is the time right for hand transplantation? J Bone Joint Surg Am. 2002;84-A(10):1861e1870. 35. Lees VC, McCabe SJ. The rationale for hand transplantation. Transplantation. 2002;74(6):749e753. 36. Agich GJ. Extension of organ transplantation: some ethical considerations. Mt Sinai J Med. 2003;70(3):141e147. 37. Hausman MR, Masters J, Panozzo A. Hand transplantation: current status. Mt Sinai J Med. 2003;70(3):148e153. 38. Lübbe AS. Successful hand transplantation or too early to tell? Transplantation. 2003;75(11):1916e1917. 39. Tobin GR, Breidenbach WC, Klapheke MM, Bentley FR, Pidwell DJ, Simmons PD. Ethical considerations in the early composite tissue allograft experience: a review of the Louisville Ethics Program. Transplant Proc. 2005;37(2):1392e1395. 40. Lanzetta M, Nolli R, Vitale G, et al. Hand transplantation: the Milan experience. Polski Przegl Chir. 2007;79(12):1379e1397. 41. Tobin GR, Breidenbach WC III, Pidwell DJ, Ildstad ST, Ravindra KV. Transplantation of the hand, face, and composite structures: evolution and current status. Clin Plast Surg. 2007;34(2):271e278, ixex. 42. Gorantla VS, Breidenbach WC. Hand transplantation: the Louisville experience. In: Hewitt CW, Lee WPA, eds. Transplantation of Composite Tissue Allografts. New York: Springer; 2008:215e233. 43. Hartman RG. Ethical and policy concerns of hand/face transplantation. In: Hewitt CW, Lee WPA, eds. Transplantation of Composite Tissue Allografts. New York: Springer; 2008:429e442. 44. Gordon CR, Siemionow M. Clinical Experience with hand transplantation. In: Siemionow M, Eisenmann-Klein M, eds. Plastic and Reconstructive Surgery. London: Springer-Verlag; 2010:729e749. 45. Shores JT, Brandacher G, Schneeberger S, Gorantla VS, Lee WP. Composite tissue allotransplantation: hand transplantation and beyond. J Am Acad Orthop Surg. 2010;18(3):127e131. 46. Amer H, Carlsen BT, Dusso JL, Edwards BS, Moran SL. Hand transplantation. Minn Med. 2011;94(5):40e43. 47. Badoiu SC, Stefanescu O. Ethical aspects in hand transplantation. Rev Rom Bioet. 2011;9(4):102e108. 48. Chang J, Mathes DW. Ethical, financial, and policy considerations in hand transplantation. Hand Clin. 2011;27(4):553e560, xi. 49. Errico M, Metcalfe NH, Platt A. History and ethics of hand transplants. JRSM Short Rep. 2012;3(10):74. 50. Kay S, Wilks D. Invited comment: vascularized composite allotransplantation: an update on medical and surgical progress and

J Hand Surg Am.

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52. 53. 54.

55.

56. 57. 58. 59. 60. 61. 62. 63.

64.

65. 66. 67.

68. 69.

70.

71.

72.

73.

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remaining challenges. J Plast Reconstr Aesthet Surg. 2013;66(11): 1456e1457. Koulmanda M, Pomahac B, Fan Z, Murphy GF, Strom TB. Hand transplants and the mandate for tolerance. Curr Opin Organ Transplant. 2014;19(6):545e551. MacKay BJ, Nacke E, Posner M. Hand transplantation—a review. Bull Hosp Jt Dis (2013). 2014;72(1):76e88. Nassimizadeh M, Nassimizadeh AK, Power D. Hand transplant surgery. Ann R Coll Surg Engl. 2014;96(8):571e574. Brügger U, Plessow R, Hess S, et al. The health technology assessment of the compulsory accident insurance scheme of hand transplantation in Switzerland. J Hand Surg Eur Vol. 2015 Nov;40(9): 914e923. Jowsey-Gregoire SG, Kumnig M, Morelon E, Moreno E, Petruzzo P, Seulin C. The Chauvet 2014 Meeting Report: psychiatric and psychosocial evaluation and outcomes of upper extremity grafted patients. Transplantation. 2016;100(7):1453e1459. Lundborg G. Hand transplantation. Scand J Plast Reconstr Surg Hand Surg. 1999;33(4):369e371. Germann G. Bilateral hand transplantationeindication and rationale. J Hand Surg Br. 2001;26(6):521. Carosella ED, Pradeu T. Transplantation and identity: a dangerous split? Lancet. 2006;368(9531):183e184. Slatman J, Widdershoven GAM. Hand transplants and bodily integrity. Body & Society. 2010;16(3):69e92. Breidenbach WC. Hand transplantation. Med J Aust. 2013;199(4): 228e229. Muramatsu K, Taguchi T. Human hand transplants and challenges for adaptation in Japan. Microsurgery. 2014;34(4):335e336. Schneeberger S, Zelger B, Ninkovic M, Margreiter R. Transplantation of the hand. Transplant Rev. 2005;19(2):100e107. Carty MJ, Bueno E, Lehmann LS, Pomahac B. A position paper in support of hand transplantation in the blind. Plast Reconstr Surg. 2011;128(5):510ee515e. Siemionow MZ, Rampazzo A, Gharb BB. Addressing religious and cultural differences in views on transplantation, including composite tissue allotransplantation. Ann Plast Surg. 2011;66(4): 410e415. McDiarmid SV, Azari KK. Donor-related issues in hand transplantation. Hand Clin. 2011;27(4):545e552, xexi. Shores JT, Imbriglia JE, Lee WP. The current state of hand transplantation. J Hand Surg Am. 2011;36(11):1862e1867. Shores JT, Brandacher G, Lee WP. Hand and upper extremity transplantation: an update of outcomes in the worldwide experience. Plast Reconstr Surg. 2015;135(2):351ee360e. Lee WP, Mathes DW. Hand transplantation: pertinent data and future outlook. J Hand Surg Am. 1999;24(5):906e913. Petruzzo P, Lanzetta M, Dubernard JM, et al. The International Registry on Hand and Composite Tissue Transplantation. Transplantation. 2010;90(12):1590e1594. Department of Health and Human Services. 42 CFR Part 121, RIN 0906-AA73, Organ Procurement and Transplantation Network. Fed Reg. Vol. 78, No. 128, Wednesday, July 3, 2013; Rules and Regulations. Available at: https://www.gpo.gov/fdsys/pkg/FR-2013-0703/pdf/2013-15731.pdf. Accessed July 1, 2016. Kanitakis J, Petruzzo P, Badet L, et al. Chronic rejection in human vascularized composite allotransplantation (hand and face recipients): an update. Transplantation. 2016;100(10):2053e2061. Brandacher G, Lee WP, Schneeberger S. Minimizing immunosuppression in hand transplantation. Expert Rev Clin Immunol. 2012;8(7):673e683. Gorantla VS, Brandacher G, Schneeberger S, et al. Favoring the riskbenefit balance for upper extremity transplantation—the Pittsburgh Protocol. Hand Clin. 2011;27(4):511e520, ixex.

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APPENDIX A. Search Strategies PubMed ((((((“Hand Transplantation”[Mesh]) OR “Hand/transplantation”[Mesh] OR (hand [mh] AND (transplantation [sh])) OR “hand transplant” OR “hand transplants” OR “hand transplantation” OR “hand allotransplantation”)) OR ((“arm/transplantation”[Mesh] OR (arm [mh] AND (transplantation [sh] OR transplantation [mh])) OR “arm transplant” OR “arm transplants” OR “arm transplantation”)) OR ((“upper extremity/transplantation”[Mesh] OR (upper extremity [mh] AND (transplantation [sh] OR transplantation [mh])) OR “upper extremity transplant” OR “upper extremity transplants” OR “upper extremity transplantation”))) AND (“Ethics”[Mesh] OR “ethics” [Subheading] OR ethic* [tiab] OR moral* [tiab] OR nonmaleficence [tiab] OR justice [tiab] OR autonomy [tiab] OR beneficence [tiab]) Searched 06102016 89 citations retrieved Embase

No.

Query

Results

#3

(‘hand transplantation’/exp OR (‘arm’/exp AND ‘transplantation’/exp) OR ((hand OR arm OR ‘upper limb’ OR ‘upper limbs’ OR arms OR hands OR ‘upper extremity’ OR ‘upper extremities’) NEAR/3 transplant*):ab,ti) AND (‘medical ethics’/exp OR ‘beneficence’/exp OR ‘justice’/exp OR ‘personal autonomy’/exp OR ‘morality’/exp OR ethic*:ab,ti OR beneficen*:ab,ti OR autonomy:ab,ti OR justice:ab,ti OR nonmaleficen:ab,ti)

209

June 10, 2016

#2

‘medical ethics’/exp OR ‘beneficence’/exp OR ‘justice’/ exp OR ‘personal autonomy’/exp OR ‘morality’/exp OR ethic*:ab,ti OR beneficen*:ab,ti OR autonomy:ab,ti OR justice:ab,ti OR nonmaleficen:ab,ti

295,234

June 10, 2016

#1

‘hand transplantation’/exp OR (‘arm’/exp AND ‘transplantation’/exp) OR ((hand OR arm OR ‘upper limb’ OR ‘upper limbs’ OR arms OR hands OR ‘upper extremity’ OR ‘upper extremities’) NEAR/3 transplant*):ab,ti

11,834

June 10, 2016

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Date

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Cochrane Search Name: hand transplantation ethics Last Saved: 10/06/2016 16:57:37.550 Description:

ID

Search

#1

MeSH descriptor: [Hand Transplantation] explode all trees

#2

MeSH descriptor: [Hand] explode all trees

#3

MeSH descriptor: [Upper Extremity] explode all trees

#4

MeSH descriptor: [Arm] explode all trees

#5

(#2 or #3 or #4 or hand* or “upper extremity” or “upper extremities” or arm*) near/3 transplant*

#6

#1 or #5

#7

MeSH descriptor: [Ethics] explode all trees

#8

MeSH descriptor: [Morals] explode all trees

#9

#7 or #8 or ethic* or moral* or beneficen* or autonomy or justice or nonmaleficen*

#10

#6 and #9

7

Total results

6

Cochrane reviews

1

Trial

Web of Science TOPIC: ((arm* OR hand* OR “upper extremity” OR “upper extremities”) NEAR/3 transplant*) AND TOPIC: (ethic* OR moral* OR justice OR autonomy OR beneficen* OR nonmaleficen*) Timespan: All years. Indexes: SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, ESCI, CCR-EXPANDED, IC. Searched 06/10/2016 71 citations Scopus ( TITLE-ABS-KEY ( ( arm* OR hand* OR “upper extremity” OR “upper extremities” ) W/3 transplant* ) AND TITLE-ABS-KEY ( ethic* OR moral* OR beneficen* OR nonmaleficen* OR justice OR autonomy ) ) Searched 06/10/2016 98 citations

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APPENDIX B.

List of Citations (n [ 49) and the Pillars of Bioethics They Address Sorted by Year of Publication

Citation Number

Year Published

E1

1998

E2

Author(s)

r

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Autonomy

Beneficence

Nonmaleficence

Justice

Siegler

Ethical issues in innovative surgery: should we attempt a cadaveric hand transplantation in a human subject?

X

X

X

-

1999

Caplan

Wearing your organ transplant on your sleeve

X

-

X

X

E3

1999

Dickenson & Hakim

Ethical issues in limb transplants

X

X

X

X

E4

1999

Lundborg

Hand transplantation

X

X

X

-

E5

1999

Tamai

Reflections on human hand allografts

-

-

X

-

E6

2000

Herndon

Composite-tissue transplantation—a new frontier

-

X

-

X

E7

2000

Simmons

Ethical considerations in composite tissue allotransplantation

X

X

X

X

E8

2001

Dickenson & Widdershoven

Ethical issues in limb transplants

X

-

X

X

E9

2001

Germann

Bilateral hand transplantation–indication and rationale

X

X

X

X

E10

2001

Hatrick & Tonkin Hand transplantation: a current perspective

-

-

X

X

E11

2001

Manske

Hand transplantation

X

X

X

-

E12

2001

Meyer

Hand transplantation

X

-

X

-

E13

2002

Benatar & Hudson

A tale of two novel transplants not done: the ethics of limb allografts

X

X

X

-

E14

2002

Breidenbach et al A position statement in support of hand transplantation

X

X

X

X

E15

2002

Brenner et al

The spectrum of complications of immunosuppression: is the time right for hand transplantation?

-

X

X

X

E16

2002

Cooney & Hentz

Hand transplantation—primum non nocere

X

X

X

X

E17

2002

Jones

Concerns about human hand transplantation in the 21st century

X

X

X

X

E18

2002

Lees & McCabe

The rationale for hand transplantation

X

X

X

X

E19

2003

Agich

Extension of organ transplantation: some ethical considerations

X

X

X

X

E20

2003

Hausman et al

Hand transplantation: current status

-

-

X

X

E21

2003

Lubbe

Successful hand transplantation or too early to tell?

X

-

X

-

E22

2005

Schneeberger et al Transplantation of the hand

X

X

X

-

E23

2005

Tobin et al

X

X

X

-

Ethical considerations in the early composite tissue allograft experience: a review of the Louisville Ethics Program

(Continued)

HAND TRANSPLANT ETHICS: A SYSTEMATIC REVIEW

J Hand Surg Am.

Title

APPENDIX B.

List of Citations (n [ 49) and the Pillars of Bioethics They Address Sorted by Year of Publication (Continued)

Citation Number

Year Published

E24

2006

Carosella & Pradeu

E25

2007

E26

2007

E27

Author(s)

Title

r

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Beneficence

Nonmaleficence

Justice

Transplantation and identity: a dangerous split?

X

X

X

X

Lanzetta et al

Hand transplantation: the Milan experience

X

X

X

X

Tobin et al

Transplantation of the hand, face, and composite structures: evolution and current status

-

-

X

-

2008

Gorantla & Breidenbach

Hand transplantation: the Louisville experience

X

X

X

-

E28

2008

Hartman

Ethical and policy concerns of hand/face transplantation

X

X

X

X

E29

2009

Mathes et al

A survey of North American hand surgeons on their current attitudes toward hand transplantation

-

X

X

-

E30

2010

Gordon & Siemionow

Clinical experience with hand transplantation

X

X

X

-

E31

2010

Shores et al

Composite tissue allotransplantation: hand transplantation and beyond

X

X

X

-

E32

2010

Slatman & Widdershoven

Hand transplants and bodily integrity

X

X

X

-

E33

2011

Amer et al

Hand transplantation

-

-

X

-

E34

2011

Badoiu & Stefanescu

Ethical aspects in hand transplantation

X

X

X

X

E35

2011

Carty et al

Transplantation of the hand

X

X

-

X

E36

2011

Chang & Mathes

Ethical, financial, and policy considerations in hand transplantation

X

X

X

X

E37

2011

Siemionow et al

Addressing religious and cultural differences in views on transplantation, including composite tissue allotransplantation

X

-

X

-

E38

2011

McDiarmid & Azari

Donor-related issues in hand transplantation

X

X

X

X

E39

2011

Shores et al

The current state of hand transplantation

-

-

-

X

E40

2012

Errico et al

History and ethics of hand transplants

X

X

X

X

E41

2013

Breidenbach

Hand transplantation

-

X

X

X

E42

2013

Kay & Wilks

Invited comment: vascularized composite allotransplantation: an update on medical and surgical progress and remaining challenges

X

X

X

X

1.e13

(Continued)

HAND TRANSPLANT ETHICS: A SYSTEMATIC REVIEW

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Autonomy

1.e14

HAND TRANSPLANT ETHICS: A SYSTEMATIC REVIEW

-

X

X

E1. Siegler M. Ethical issues in innovative surgery: should we attempt a cadaveric hand transplantation in a human subject? Transplant Proc. 1998;30(6):2779e2782. E2. Caplan AL. Wearing your organ transplant on your sleeve. Hastings Cent Rep. 1999;29(2):52. E3. Dickenson D, Hakim NS. Ethical issues in limb transplants. Postgrad Med J. 1999;75(887):513e515. E4. Lundborg G. Hand transplantation. Scand J Plast Reconstr Surg Hand Surg. 1999;33(4):369e371. E5. Tamai S. Reflections on human hand allografts. J Orthop Sci. 1999;4(5):325e327. E6. Herndon JH. Composite-tissue transplantationea new frontier. N Engl J Med. 2000;343(7):503e505. E7. Simmons PD. Ethical considerations in composite tissue allotransplantation. Microsurgery. 2000;20(8):458e465. E8. Dickenson D, Widdershoven G. Ethical issues in limb transplants. Bioethics. 2001;15(2):110e124. E9. Germann G. Bilateral hand transplantationeindication and rationale. J Hand Surg Br. 2001;26(6):521. E10. Hatrick NC, Tonkin MA. Hand transplantation: a current perspective. ANZ J Surg. 2001;71(4):245e251. E11. Manske PR. Hand transplantation. J Hand Surg Am. 2001;26(2): 193e195. E12. Meyer VE. Hand transplantation. J Hand Surg Br. 2001;26(6): 509e510. E13. Benatar D, Hudson DA. A tale of two novel transplants not done: the ethics of limb allografts. BMJ. 2002;324(7343):971e973. E14. Breidenbach WC 3rd, Tobin GR 2nd, Gorantla VS, Gonzalez RN, Granger DK. A position statement in support of hand transplantation. J Hand Surg Am. 2002;27(5):760e770. E15. Brenner MJ, Tung TH, Jensen JN, Mackinnon SE. The spectrum of complications of immunosuppression: is the time right for hand transplantation? J Bone Joint Surg Am. 2002;84-A(10): 1861e1870. E16. Cooney WP, Hentz VR. American Society for Surgery of the Hand. Hand transplantationeprimum non nocere. J Hand Surg Am. 2002;27(1):165e168. E17. Jones NF. Concerns about human hand transplantation in the 21st century. J Hand Surg Am. 2002;27(5):771e787. E18. Lees VC, McCabe SJ. The rationale for hand transplantation. Transplantation. 2002;74(6):749e753. E19. Agich GJ. Extension of organ transplantation: some ethical considerations. Mt Sinai J Med. 2003;70(3):141e147. E20. Hausman MR, Masters J, Panozzo A. Hand transplantation: current status. Mt Sinai J Med. 2003;70(3):148e153. E21. Lübbe AS. Successful hand transplantation or too early to tell? Transplantation. 2003;75(11):1916e1917. E22. Schneeberger S, Zelger B, Ninkovic M, Margreiter R. Transplantation of the hand. Transplantation Reviews. 2005;19(2): 100e107. E23. Tobin GR, Breidenbach WC, Klapheke MM, Bentley FR, Pidwell DJ, Simmons PD. Ethical considerations in the early composite tissue allograft experience: a review of the Louisville Ethics Program. Transplant Proc. 2005;37(2): 1392e1395. E24. Carosella ED, Pradeu T. Transplantation and identity: a dangerous split? Lancet. 2006;368(9531):183e184. E25. Lanzetta M, Nolli R, Vitale G, et al. Hand transplantation: The Milan experience. Pol Przegl Chir. 2007;79(12):1379e1397. E26. Tobin GR, Breidenbach WC 3rd, Pidwell DJ, Ildstad ST, Ravindra KV. Transplantation of the hand, face, and composite structures: evolution and current status. Clin Plast Surg. 2007;34(2):271e278. ix-x. E27. Gorantla VS, Breidenbach WC. Hand transplantation: The Louisville experience. In: Hewitt CW, Lee WPA, eds. Transplantation of Composite Tissue Allografts. New York: Springer; 2008:215e233.

X, area addressed in publication; -, area not addressed in publication.

X The Chauvet 2014 Meeting Report: psychiatric and psychosocial evaluation and outcomes of upper extremity grafted patients Jowsey-Gregoire et al 2016 E49

X The health technology assessment of the compulsory accident insurance scheme of hand transplantation in Switzerland 2015 E48

Brugger et al

X X X X Hand transplant surgery 2014 E47

Nassimizadeh et al

X

X X

X -

X X

X Human hand transplants and challenges for adaptation in Japan

Hand transplantation—a review

2014 E46

Muramatsu & Taguchi

2014 E45

MacKay et al

X X X Hand transplants and the mandate for tolerance 2014 E44

Koulmanda et al

X X X Changing attitudes toward hand allotransplantation among North American hand surgeons 2014 E43

Bertrand et al

Beneficence Autonomy Title Author(s) Year Published Citation Number

APPENDIX B.

List of Citations (n [ 49) and the Pillars of Bioethics They Address Sorted by Year of Publication (Continued)

Nonmaleficence

Justice

REFERENCES

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HAND TRANSPLANT ETHICS: A SYSTEMATIC REVIEW

E39. Shores JT, Imbriglia JE, Lee WP. The current state of hand transplantation. J Hand Surg Am. 2011;36(11):1862e1867. E40. Errico M, Metcalfe NH, Platt A. History and ethics of hand transplants. JRSM Short Rep. 2012;3(10):74. E41. Breidenbach WC. Hand transplantation. Med J Aust. 2013;199(4): 228e229. E42. Kay S, Wilks D. Invited comment: Vascularized composite allotransplantation: an update on medical and surgical progress and remaining challenges. J Plast Reconstr Aesthet Surg. 2013;66(11): 1456e1457. E43. Bertrand AA, Sen S, Otake LR, Lee GK. Changing attitudes toward hand allotransplantation among North American hand surgeons. Ann Plast Surg. 2014;72 Suppl 1:S56eS60. E44. Koulmanda M, Pomahac B, Fan Z, Murphy GF, Strom TB. Hand transplants and the mandate for tolerance. Curr Opin Organ Transplant. 2014;19(6):545e551. E45. MacKay BJ, Nacke E, Posner M. Hand transplantationea review. Bull Hosp Jt Dis (2013). 2014;72(1):76e88. E46. Muramatsu K, Taguchi T. Human hand transplants and challenges for adaptation in Japan. Microsurgery. 2014;34(4):335e336. E47. Nassimizadeh M, Nassimizadeh AK, Power D. Hand transplant surgery. Ann R Coll Surg Engl. 2014;96(8):571e574. E48. Brügger U, Plessow R, Hess S, et al. The health technology assessment of the compulsory accident insurance scheme of hand transplantation in Switzerland. J Hand Surg Eur Vol. 2015;40(9): 914e923. E49. Jowsey-Gregoire SG, Kumnig M, Morelon E, Moreno E, Petruzzo P, Seulin C. The Chauvet 2014 Meeting Report: Psychiatric and Psychosocial Evaluation and Outcomes of Upper Extremity Grafted Patients. Transplantation. 2016;100(7): 1453e1459.

E28. Hartman RG. Ethical and policy concerns of hand/face transplantation. In: Hewitt CW, Lee WPA, eds. Transplantation of Composite Tissue Allografts. New York: Springer; 2008: 429e442. E29. Mathes DW, Schlenker R, Ploplys E, Vedder N. A survey of North American hand surgeons on their current attitudes toward hand transplantation. J Hand Surg Am. 2009;34(5):808e814. E30. Gordon CR, Siemonow M. Clinical Experience with Hand Transplantation. In: Siemionow M, Eisenmann-Klein M, eds. Plastic and Reconstructive Surgery. Godalming, Surrey, England: SpringerVerlag London Ltd; 2010:729e749. E31. Shores JT, Brandacher G, Schneeberger S, Gorantla VS, Lee WP. Composite tissue allotransplantation: hand transplantation and beyond. J Am Acad Orthop Surg. 2010;18(3):127e131. E32. Slatman J, Widdershoven GAM. Hand transplants and bodily integrity. Body & Society. 2010;16(3):69e92. E33. Amer H, Carlsen BT, Dusso JL, Edwards BS, Moran SL. Hand transplantation. Minn Med. 2011;94(5):40e43. E34. Badoiu SC, Stefanescu O. Ethical aspects in hand transplantation. Rev Rom Bioet. 2011;9(4):102e108. E35. Carty MJ, Bueno E, Lehmann LS, Pomahac B. A position paper in support of hand transplantation in the blind. Plast Reconstr Surg. 2011;128(5):510ee515e. E36. Chang J, Mathes DW. Ethical, financial, and policy considerations in hand transplantation. Hand Clin. 2011;27(4):553e560. xi. E37. Siemionow MZ, Rampazzo A, Gharb BB. Addressing religious and cultural differences in views on transplantation, including composite tissue allotransplantation. Ann Plast Surg. 2011;66(4): 410e415. E38. McDiarmid SV, Azari KK. Donor-related issues in hand transplantation. Hand Clin. 2011;27(4):545e552. x-xi.

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