BACKGROUND: Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowing VCA in humans. However, repeated rejection episodes are common, and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulatory approaches to improve allograft acceptance and minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field. METHODS: We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed databases. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging the survival of a skin-containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulatory strategies used in VCA preclinical research over a timeframe of 44 years. CONCLUSION: We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies.
- MeSH
- imunomodulace MeSH
- imunosupresiva farmakologie terapeutické užití MeSH
- krysa rodu rattus MeSH
- kůže MeSH
- lidé MeSH
- rejekce štěpu prevence a kontrola MeSH
- takrolimus terapeutické užití MeSH
- vaskularizovaná kompozitní alotransplantace * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- systematický přehled MeSH
BACKGROUND: Acute rejection remains a vexing problem in vascularized composite allotransplantation (VCA). Available immunosuppressive regimens are successful at minimizing alloimmune response and allowing VCA in humans. However, repeated rejection episodes are common, and systemic side effects of the current standard regimen (Tacrolimus, MMF, Prednisone) are dose limiting. Novel immunomodulatory approaches to improve allograft acceptance and minimize systemic toxicity are continuously explored in preclinical models. We aimed to systematically summarize past and current approaches to help guide future research in this complex field. METHODS: We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed databases. For inclusion, articles had to primarily investigate the effect of a therapeutic approach on prolonging the survival of a skin-containing preclinical VCA model. Non-VCA studies, human trials, anatomical and feasibility studies, and articles written in a language other than English were excluded. We followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. RESULTS: The search retrieved 980 articles of which 112 articles were ultimately included. The majority of investigations used a rat model. An orthotopic hind limb VCA model was used in 53% of the studies. Cell and drug-based approaches were investigated 58 and 52 times, respectively. We provide a comprehensive review of immunomodulatory strategies used in VCA preclinical research over a timeframe of 44 years. CONCLUSION: We identify a transition from anatomically non-specific to anatomical models mimicking clinical needs. As limb transplants have been most frequently performed, preclinical research focused on using the hind limb model. We also identify a transition from drug-based suppression therapies to cell-based immunomodulation strategies.
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND: Compromised lower limb perfusion due to vascular changes such as peripheral artery disease impedes wound healing and may lead to large-scale tissue defects and lower limb amputation. In such patients with defects and compromised or lacking recipient vessels, combined vascular reconstruction with free flap transfer is an option for lower extremity salvage. METHODS: By using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2018), we analyzed two patient cohorts undergoing (A) free flap lower limb reconstruction (LXTR) only and (B) combined (endo-)vascular reconstruction (vascLXTR). The preoperative variables assessed included demographic data and comorbidities, including smoking, diabetes mellitus, preoperative steroid use, and American Society of Anesthesiology (ASA) Physical Status Classification. Using a neighbor matching algorithm, we performed a 1:1 propensity score matching of 615 LXTR patients and 615 vascLXTR patients. Bivariate analysis for postoperative surgical and medical complications was performed for outcomes in the propensity-matched cohort. RESULTS: We identified 5386 patients who underwent microsurgical free flap reconstruction of the lower extremity. A total of 632 patients underwent a combined (endo-)vascular intervention and lower extremity free flap reconstruction. Diabetes and smoking were more prevalent in this group, with 206 patients having diabetes (32.6%) and 311 being smokers (49.2%). More patients returned to the operating room in the cohort that underwent a combined vascular intervention (24.4% versus 9.9%; p<0.0001). The 30-day mortality for patients undergoing a combined vascular procedure was 3.5%, compared with 1.3% with free tissue transfer only (p<0.0001). CONCLUSION: Despite the risks associated, the combined intervention decreases the very high mortality associated with limb amputation in severely sick patient populations. Careful preoperative assessment of modifiable risk factors may reduce complication rates while allowing limb salvage.
- MeSH
- dolní končetina krevní zásobení chirurgie MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- mikrochirurgie metody MeSH
- onemocnění periferních cév chirurgie MeSH
- senioři MeSH
- tendenční skóre MeSH
- volné tkáňové laloky * MeSH
- výkony cévní chirurgie metody MeSH
- záchrana končetiny metody MeSH
- zákroky plastické chirurgie metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké MeSH
BACKGROUND: Local immunosuppression in vascularized composite allotransplantation (VCA) aims to minimize immunosuppressant-related toxic and malignant side effects. Promising allograft survival data have been published by multiple workgroups. In this systematic review, we examine preclinical animal studies that investigated local immunosuppression in VCA. MATERIAL AND METHODS: We conducted a systematic review of manuscripts listed in the MEDLINE and PubMed database concerning preclinical VCA models. Papers included had to be available as full-text and written in English. Non-VCA studies, human trials, and studies using cell-based therapy strategies were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: Literature research retrieved 980 articles. Ten studies published between 2010 and 2019 met the inclusion and exclusion criteria. Seven out of ten articles demonstrated a significant prolongation of allograft survival by using local immunosuppression. Five articles employed tacrolimus (TAC) as the main immunosuppressive agent. Seven studies performed hind-limb VCA in a rat model. CONCLUSION: The easily accessible location of skin containing VCAs makes it an ideal candidate for local immunosuppression. Published preclinical data are very promising in terms of improved allograft survival and reduced systemic toxicity.
- MeSH
- imunosupresiva aplikace a dávkování terapeutické užití MeSH
- imunosupresivní léčba metody MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- prasata MeSH
- rejekce štěpu prevence a kontrola MeSH
- takrolimus aplikace a dávkování terapeutické užití MeSH
- vaskularizovaná kompozitní alotransplantace * MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
- MeSH
- COVID-19 epidemiologie MeSH
- lidé MeSH
- pandemie MeSH
- příjemce transplantátu * MeSH
- protilátky virové analýza MeSH
- SARS-CoV-2 imunologie MeSH
- senioři MeSH
- transplantace obličeje * MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
BACKGROUND: Facial vascularized composite allotransplantation (fVCA) represents a reconstructive approach that enables superior improvements in functional and esthetic restoration compared with conventional craniomaxillofacial reconstruction. Outcome reports of fVCA are usually limited to short-term follow-up or single-center experiences. We merge scientific literature on reported long-term outcome data to better define the risks and benefits of fVCA. METHODS: We conducted a systematic review of PubMed/MEDLINE databases in accordance with PRISMA guidelines. English full-text articles providing data on at least 1 unique fVCA patient, with ≥3 years follow-up, were included. RESULTS: The search yielded 1812 articles, of which 28 were ultimately included. We retrieved data on 23 fVCA patients with mean follow-up of 5.3 years. More than half of the patients showed improved quality of life, eating, speech, and motor and sensory function following fVCA. On average, the patients had 1 acute cell-mediated rejection and infectious episode per year. The incidence rates of acute rejection and infectious complications were high within first-year posttransplant but declined thereafter. Sixty-five percent of the patients developed at least 1 neoplastic or metabolic complication after transplantation. Chronic vascular rejection was confirmed in 2 patients, leading to allograft loss after 8 and 9 years. Two patient deaths occurred 3.5 and 10.5 years after transplant due to suicide and lung cancer, respectively. CONCLUSIONS: Allograft functionality and improvements in quality of life suggest a positive risk-benefit ratio for fVCA. Recurrent acute rejection episodes, chronic rejection, immunosuppression-related complications, and heterogeneity in outcome reporting present ongoing challenges in this field.
- MeSH
- dospělí MeSH
- homologní transplantace MeSH
- imunosupresiva terapeutické užití MeSH
- infekce etiologie MeSH
- kvalita života MeSH
- lidé středního věku MeSH
- lidé MeSH
- rejekce štěpu MeSH
- transplantace obličeje škodlivé účinky psychologie MeSH
- výzkumný projekt MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
There is limited experience with facial retransplantation (fRT). We report on the management of facial retransplantation in a facial vascularized composite allotransplant recipient following irreversible allograft loss 88 months after the first transplant. Chronic antibody-mediated rejection and recurrent cellular rejection resulted in a deteriorated first allograft and the patient underwent retransplantation. We summarize the events between the two transplantations, focusing on the final rejection episode. We describe the surgical technique of facial retransplantation, the immunological and psychosocial management, and the 6-month postoperative outcomes. Removal of the old allograft and inset of the new transplant were done in one operation. The donor and recipient were a good immunological match. The procedure was technically complex, requiring more proximal arterial anastomoses and an interposition vein graft. During the first and second transplantation, the facial nerve was coapted at the level of the branches. There was no hyperacute rejection in the immediate postoperative phase. Outcomes 6 months postoperatively are promising. We provide proof-of-concept that facial retransplantation is a viable option for patients who suffer irreversible facial vascularized composite allograft loss.
- MeSH
- homologní transplantace MeSH
- lidé MeSH
- rejekce štěpu * etiologie MeSH
- reoperace MeSH
- štěpy z kompozitní tkáně * MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- černoši nebo Afroameričané * MeSH
- imunosupresivní léčba MeSH
- kvalita života MeSH
- lidé MeSH
- pigmentace kůže * MeSH
- rejekce štěpu diagnóza MeSH
- senioři MeSH
- transplantace obličeje * MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
- Research Support, N.I.H., Extramural MeSH
SUMMARY: Skin is one of the target tissues of rejection in face transplants and, because of its easy accessibility, has become the gold standard in the diagnosis of rejection. The allograft contains deeper tissues where rejection can occur, but samples cannot be obtained because of difficult access. Deep tissue changes were monitored on computed tomographic scans of the midface in six face transplant recipients with the help of image segmentation. The maxillary sinus was identified as a dynamic anatomical compartment. Observed changes in volume of the aeration relative to the opacification (aeration coefficient) of the maxillary sinus were quantified with the help of image segmentation. Changes in the aeration coefficient as a surrogate of mucosal swelling were quantified and related to time, treatment, and skin rejection grade. Lower aeration coefficients were found only in patients with transplanted maxillary sinus mucosa. Pathologic changes were not observed in face transplant recipients with a native maxillary sinus. The data show that the aeration coefficient was significantly lower at the time of biopsy-proven allograft rejection. Neither mechanical, nor infectious, nor medication side effects sufficiently explain the findings presented herein. The authors' findings are important to consider for clinical management of face transplant patients who receive parts of the sinonasal tract. The authors identify a potential radiologic biomarker of deep tissue allograft rejection. In the future, the proposed methodology might prove useful in monitoring deeper dynamic tissue changes in vascularized composite allografts and might help in designing patient-specific, individualized treatment strategies.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- počítačová rentgenová tomografie MeSH
- rejekce štěpu diagnóza etiologie patologie prevence a kontrola MeSH
- respirační sliznice patologie transplantace MeSH
- retrospektivní studie MeSH
- sinus maxillaris diagnostické zobrazování patologie MeSH
- štěpy z kompozitní tkáně diagnostické zobrazování patologie MeSH
- transplantace obličeje škodlivé účinky MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Identifying a donor for facial vascularized composite allotransplant recipients can be a lengthy, emotionally challenging process. Little is known about the relative distribution of key donor characteristics among potential donors. Data on actual wait times of patients are limited, making it difficult to estimate wait times for future recipients. METHODS: The authors retrospectively reviewed charts of nine facial vascularized composite allotransplant patients and provide data on transplant wait times and patient characteristics. In addition, they analyzed the United Network for Organ Sharing database of dead organ donors. After excluding donors with high-risk characteristics (e.g., active cancer or risk factors for blood-borne disease transmission), the authors calculated the distribution of relevant donor-recipient matching criteria (i.e., ethnicity, body mass index, age, ABO blood group, cytomegalovirus, Epstein-Barr virus, hepatitis C virus) among 65,201 potential donors. RESULTS: The median wait time for a transplant was 4 months (range, 1 day to 17 months). The large majority of United Network for Organ Sharing-recorded deaths from disease were white (63 percent) and male (58 percent). Female donors of black, Hispanic, or Asian descent are underrepresented, with 7, 5, and 1 percent of all recorded deaths from disease, respectively. Potential donors show cytomegalovirus and Epstein-Barr virus seropositivity of 65 and 95 percent, respectively. The number of annual hepatitis C-positive donors increased over time. CONCLUSIONS: Actual facial vascularized composite allotransplant wait times vary considerably. Although most patients experience acceptable wait times, some with underrepresented characteristics exceed acceptable levels. Cytomegalovirus-seropositive donors present a large portion of the donor pool, and exclusion for seronegative patients may increase wait time. Hepatitis C-seropositive donors may constitute a donor pool for underrepresented patient groups in the future.
- MeSH
- časové faktory MeSH
- cytomegalovirové infekce krev diagnóza epidemiologie přenos MeSH
- Cytomegalovirus izolace a purifikace MeSH
- dospělí MeSH
- Hepacivirus izolace a purifikace MeSH
- hepatitida C krev diagnóza epidemiologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- retrospektivní studie MeSH
- senioři MeSH
- seznamy čekatelů MeSH
- vaskularizovaná kompozitní alotransplantace normy statistika a číselné údaje MeSH
- výběr dárců normy statistika a číselné údaje MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
