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1.
J Plast Reconstr Aesthet Surg ; 80: 4-12, 2023 05.
Article in English | MEDLINE | ID: mdl-36931006

ABSTRACT

BACKGROUND: There is a mounting body of evidence that underscores the worldwide and US national need for increased plastic surgery recruitment of trainees. Thus, plastic surgery must attract more applicants while maintaining the high-level qualifications of residency candidates. METHODS: A total of 250 (w = 197) medical students rated the prototypical plastic surgeon (PS), general practitioner (GP), and craniomaxillofacial surgeon (CMF) with respect to traits derived from a literature review on the general perception of surgery, favorability, and their intention to pursue a respective career. RESULTS: Factor analysis yielded two overarching dimensions of prototype perception in addition to femininity and resilience, one reflecting a coldhearted, narcissistic, competitive character (status primacy; SP), and one reflecting role-model-like traits (hard-working, healthy, admired, and empathetic). Prototypical PSs scored significantly higher on SP than GPs (t(249) = 18.72, p < 0.001, d = 1.26) and CMFs (t(249) = 5.73, p < 0.001, d = 0.36), while receiving significantly less positive evaluations (GP: t(249) = -9.93, p < 0.001, d = -0.63; CMF: t(249) = -3.52, p < 0.001, d = -0.22). The higher participants rated PSs on SP, the more likely a career in plastic surgery was excluded (OR = 0.71, p = 0.03). An opposite relationship with femininity approached significance (OR = 1.32, p = 0.06). CONCLUSIONS: Given the growing need for PSs, worldwide and US national task fields have to overcome the outdated traits and highlight the field's pro-bono engagement. Furthermore, plastic surgery should further expand its leading role in promoting female trainees.


Subject(s)
Plastic Surgery Procedures , Students, Medical , Surgery, Plastic , Female , Humans , Factor Analysis, Statistical , Perception
2.
J Plast Reconstr Aesthet Surg ; 75(2): 586-604, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34895853

ABSTRACT

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.


Subject(s)
Vascularized Composite Allotransplantation , Animals , Graft Rejection/prevention & control , Humans , Immunomodulation , Immunosuppressive Agents/pharmacology , Immunosuppressive Agents/therapeutic use , Rats , Skin , Tacrolimus/therapeutic use
3.
J Craniofac Surg ; 32(8): e728-e735, 2021.
Article in English | MEDLINE | ID: mdl-34172684

ABSTRACT

OBJECTIVES: Mandible fractures can be treated with different plate systems, that is, miniplates or three-dimensional (3D) plates. This systematic review describes the effectiveness and clinical outcomes of 3D plates used in fractures of the mandible and aims to critically evaluate its risks and benefits. MATERIALS AND METHODS: A comprehensive electronic search was conducted without date but with restriction to articles written in English. Studies in humans, including randomized or quasi-randomized controlled trials and retrospective studies, were included. The outcome parameters measured were number of patients, fracture classification, results, follow-up period, postoperative complications, and mean age of patients. Major complications were defined as those needing additional surgical intervention, for example, malocclusion, infection or plate fracture. Accordingly, complications not needing additional surgical intervention were defined as minor (ie, dehiscence, trismus). RESULTS: Guided by the PRISMA statement and the Cochrane Handbook for Systematic Reviews of Interventions, the authors identified 44 publications with a total of 1790 patients. Among the articles selected for the final review, there were 32 reported prospective studies, 12 reported retrospective studies. Regarding the evaluation of quality, 8 studies showed a low value of the risk of bias, 17 a moderate risk, and 19 a high risk. There were statistically significant advantages for 3D plates in mandibular fractures in terms of postoperative complications, for example, wound dehiscences or plate fracture. CONCLUSIONS: The 3D plate is an effective treatment modality for mandibular fractures, with low incidence of major complications, decreased length of operation time, and increased stability of osteosynthesis.


Subject(s)
Mandibular Fractures , Bone Plates , Fracture Fixation, Internal , Humans , Mandibular Fractures/surgery , Prospective Studies , Retrospective Studies , Treatment Outcome
4.
Plast Reconstr Surg ; 148(1): 194-202, 2021 Jul 01.
Article in English | MEDLINE | ID: mdl-34181616

ABSTRACT

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.


Subject(s)
Cytomegalovirus Infections/epidemiology , Donor Selection/statistics & numerical data , Hepatitis C/epidemiology , Vascularized Composite Allotransplantation/statistics & numerical data , Adolescent , Adult , Aged , Cytomegalovirus/isolation & purification , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/diagnosis , Cytomegalovirus Infections/transmission , Donor Selection/standards , Female , Hepacivirus/isolation & purification , Hepatitis C/blood , Hepatitis C/diagnosis , Humans , Male , Middle Aged , Retrospective Studies , Time Factors , Vascularized Composite Allotransplantation/standards , Waiting Lists , Young Adult
5.
Am J Transplant ; 21(10): 3472-3480, 2021 10.
Article in English | MEDLINE | ID: mdl-34033210

ABSTRACT

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.


Subject(s)
Composite Tissue Allografts , Graft Rejection , Female , Graft Rejection/etiology , Humans , Reoperation , Transplantation, Homologous
8.
Plast Reconstr Surg ; 147(3): 722-727, 2021 03 01.
Article in English | MEDLINE | ID: mdl-33620943

ABSTRACT

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.


Subject(s)
Composite Tissue Allografts/diagnostic imaging , Facial Transplantation/adverse effects , Graft Rejection/diagnosis , Maxillary Sinus/diagnostic imaging , Respiratory Mucosa/transplantation , Adult , Composite Tissue Allografts/pathology , Female , Graft Rejection/etiology , Graft Rejection/pathology , Graft Rejection/prevention & control , Humans , Male , Maxillary Sinus/pathology , Middle Aged , Respiratory Mucosa/pathology , Retrospective Studies , Tomography, X-Ray Computed , Treatment Outcome , Young Adult
9.
J Plast Reconstr Aesthet Surg ; 74(5): 1031-1040, 2021 05.
Article in English | MEDLINE | ID: mdl-33436337

ABSTRACT

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.


Subject(s)
Free Tissue Flaps , Limb Salvage/methods , Lower Extremity/surgery , Peripheral Vascular Diseases/surgery , Plastic Surgery Procedures/methods , Vascular Surgical Procedures/methods , Aged , Comorbidity , Female , Humans , Lower Extremity/blood supply , Male , Microsurgery/methods , Middle Aged , Propensity Score , United States
10.
J Plast Reconstr Aesthet Surg ; 74(2): 327-335, 2021 02.
Article in English | MEDLINE | ID: mdl-33229219

ABSTRACT

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.


Subject(s)
Graft Rejection/prevention & control , Immunosuppression Therapy/methods , Immunosuppressive Agents/administration & dosage , Tacrolimus/administration & dosage , Vascularized Composite Allotransplantation , Animals , Humans , Immunosuppressive Agents/therapeutic use , Rats , Swine , Tacrolimus/therapeutic use , Treatment Outcome
11.
Transplantation ; 105(8): 1869-1880, 2021 08 01.
Article in English | MEDLINE | ID: mdl-33148976

ABSTRACT

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.


Subject(s)
Facial Transplantation/adverse effects , Adult , Facial Transplantation/psychology , Female , Graft Rejection , Humans , Immunosuppressive Agents/therapeutic use , Infections/etiology , Male , Middle Aged , Quality of Life , Research Design , Transplantation, Homologous
12.
Mil Med ; 185(11-12): e2004-e2012, 2020 12 30.
Article in English | MEDLINE | ID: mdl-33377496

ABSTRACT

INTRODUCTION: Hypothermic ex-situ machine perfusion (MP) has been shown to be a promising alternative to static cold storage (SCS) for preservation of solid organs for transplantation and vascularized composite allotransplantation. Perfusion with blood-based perfusion solutions in austere environments is problematic due to their need for appropriate storage and short shelf life, making it impractical for military and emergency use. Acellular perfusion has been shown to be effective, but the ideal perfusate solution for MP of amputated limbs is yet to be determined. The purpose of this study is to evaluate the efficacy of alternative perfusate solutions, such as dextran-enriched Phoxilium, Steen, and Phoxilium in ex-vivo hypothermic MP of amputated limbs in a porcine model. MATERIALS AND METHODS: Amputated forelimbs from Yorkshire pigs (n = 8) were preserved either in SCS (n = 2) at 4°C for 12 hours or machine-perfused at 10°C for 12 hours with oxygenated perfusion solutions (n = 6) at a constant flow rate. The perfusates used include modified Steen-solution, Phoxilium (PHOX), or Phoxilium enriched with dextran-40 (PHODEX). The perfusate was exchanged after 1 and 6 hours of perfusion. Machine data were recorded continuously. Perfusate samples for clinical chemistry, blood gas analysis, and muscle biopsies were procured at specific timepoints and subsequently analyzed. In this semi in-vivo study, limb replantation has not been performed. RESULTS: After amputation, every limb was successfully transferred and connected to our perfusion device. The mean total ischemia time was 77.5 ± 5.24 minutes. The temperature of the perfusion solution was maintained at 10.18 ± 2.01°C, and perfusion pressure at 24.48 ± 10.72 mmHg. Limb weight increased by 3% in the SCS group, 36% in the PHODEX group, 25% in the Steen group, and 58% in the PHOX group after 12 hours. This increase was significant in the PHOX group compared with the SCS group. All perfusion groups showed a pressure increase of 10.99 mmHg over time due to edema. The levels of HIF-1a decreased over time in all groups except the Steen and the PHODEX group. The biomarkers of muscle injury in the perfusate samples, such as creatine kinase and lactate-dehydrogenase, showed a significant difference between groups, with highest values in the PHODEX group. No significant differences were found in the results of the blood gas analysis. CONCLUSION: With the exception of significantly higher levels of creatine kinase and lactate dehydrogenase, MP with dextran-enriched Phoxilium provides similar results as that of the commercially available perfusates such as Steen, without the need for cold storage, and at circa 5% of the cost of the Steen solution. Further large-scale replantation studies are necessary to evaluate the efficacy of dextran-enriched Phoxilium as an alternate perfusate solution.


Subject(s)
Extremities/surgery , Amputation, Surgical , Animals , Organ Preservation , Perfusion , Replantation , Swine
13.
Plast Reconstr Surg Glob Open ; 8(8): e3038, 2020 Aug.
Article in English | MEDLINE | ID: mdl-32983791

ABSTRACT

Supplemental Digital Content is available in the text.

14.
Surgery ; 167(6): 991-998, 2020 06.
Article in English | MEDLINE | ID: mdl-32113580

ABSTRACT

BACKGROUND: Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation. METHODS: Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed. RESULTS: The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6-8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient's death 10 years after transplantation. CONCLUSION: This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy.


Subject(s)
Facial Transplantation , Skin/pathology , Transplant Recipients , Allografts , CD4 Antigens/metabolism , Carcinoma, Hepatocellular/virology , Follow-Up Studies , Glomerular Filtration Rate , Hepatitis C, Chronic/complications , Humans , Immunosuppressive Agents/therapeutic use , Interleukin-17/metabolism , Liver Neoplasms/virology , Male , Middle Aged , Skin/metabolism , T-Lymphocytes/metabolism , Tumor Necrosis Factor-alpha/metabolism
15.
Transplantation ; 104(9): e260-e270, 2020 09.
Article in English | MEDLINE | ID: mdl-32168040

ABSTRACT

BACKGROUND: Machine perfusion (MP) has evolved as a promising approach for the ex situ preservation in organ transplantation. However, the literature on the use of MP in human vascularized composite allografts is scarce. The aim of this study was to evaluate the effects of hypothermic MP with an acellular perfusate in human upper extremities and compare with the current gold standard of static cold storage (SCS). METHODS: Six upper extremities were assigned to either MP (n = 3) or SCS (n = 3) conditions for 24 h. MP-extremities were perfused with oxygenated Steen solution at a constant pressure of 30 mm Hg and 10°C. RESULTS: Median total ischemia time was 213 min (range, 127-222 min). Myoglobin, creatine-kinase (CK) showed increased levels at the start of MP (medians: myoglobin: 4377 ng/mL, CK: 1442 U/L), peaking 6 h after perfusate exchange (medians: myoglobin: 9206 ng/mL, CK: 3995 U/L) at timepoint 24. Lactate levels decreased from a median of 6.9-2.8 mmol/L over time. Expression of hypoxia-inducible factor 1-alpha peaked in the SCS-group after 8 h, followed by a decrease. Increased hypoxia-inducible factor 1-alpha expression in the MP group was delayed until 20 h. Perfusion pressure, temperature, and circuit flow were maintained at median of 30.88 mm Hg, 9.77°C, and 31.13 mL/min, respectively. Weight increased 1.4% in the SCS group and 4.3% in the MP group over 24 h. CONCLUSIONS: Hypothermic ex situ perfusion with an oxygenated acellular Steen solution may extend the allowable extracorporeal preservation time by a factor of 4-6 compared to SCS and holds promise to be beneficial for vascularized composite allograft recipients and victims of traumatic major limb amputation.


Subject(s)
Extremities/blood supply , Organ Preservation/methods , Perfusion/methods , Replantation/methods , Adult , Allografts , Cold Temperature , Cytokines/analysis , Extremities/surgery , Female , Humans , Male , Middle Aged , Organ Preservation Solutions , Warm Ischemia
16.
Transplantation ; 104(12): 2616-2624, 2020 12.
Article in English | MEDLINE | ID: mdl-32053572

ABSTRACT

BACKGROUND: Facial vascularized composite allotransplantation (fVCA) presents an established approach to restore form and function of patients with catastrophic facial defects. Skin is one of the target tissues of the rejection process, and due to its easy accessibility has become the gold standard in the diagnosis of rejection. Mucosal rejection frequently occurs; however, the added value of mucosal rejection assessment for patient management is unknown. METHODS: We conducted a systematic review of manuscripts listed in the MEDLINE/PubMed and GoogleScholar databases to identify articles that provide data on mucosal rejection following fVCA. For inclusion, papers had to be available as full-text and written in English. Non-VCA studies and animal studies were excluded. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: We included 17 articles that described changes in allotransplanted mucosa of fVCAs. These articles yielded data on 168 BANFF graded biopsies of corresponding skin and mucosa biopsies. Rejection grades were consistently higher in mucosal biopsies. Concordance between allograft skin and mucosa biopsy grades increased with an increasing skin-BANFF grade. Mucosa rejection grades were on average lower in the early stages of the posttransplant period (postoperative mo 12). CONCLUSIONS: The mucosa of facial allotransplants is one of the primary targets of rejection. The data indicates that higher-grade skin rejection does not occur in absence of mucosal rejection. Further investigations are needed to elucidate the exact role of mucosal biopsies for fVCA patient management.


Subject(s)
Composite Tissue Allografts/transplantation , Facial Transplantation/adverse effects , Graft Rejection/immunology , Mucous Membrane/transplantation , Skin Transplantation/adverse effects , Skin/immunology , Vascularized Composite Allotransplantation/adverse effects , Adult , Biopsy , Composite Tissue Allografts/immunology , Composite Tissue Allografts/pathology , Female , Graft Rejection/pathology , Graft Rejection/therapy , Graft Survival , Humans , Male , Middle Aged , Mucous Membrane/immunology , Mucous Membrane/pathology , Skin/pathology , Treatment Outcome
17.
Front Immunol ; 10: 2771, 2019.
Article in English | MEDLINE | ID: mdl-31849957

ABSTRACT

Background: There is unmet need for non-invasive immunomonitoring to improve diagnosis and treatment of acute rejection in vascularized composite allotransplantation (VCA). Circulating matrix metalloproteinase 3 (MMP3) was described as a candidate non-invasive biomarker to predict treatment response to acute rejection in clinical VCA. However, larger validation studies are yet to be reported to allow for more definitive conclusions. Methods: We retrospectively measured MMP3 levels using ELISA in a total of 140 longitudinal serum samples from six internal and three external face transplant recipients, as well as three internal and seven external upper extremity transplant recipients. The control groups comprised serum samples from 36 kidney transplant recipients, 14 healthy controls, and 38 patients with autoimmune skin disease. A linear mixed model was used to study the effect of rejection state (pre-transplant, no-rejection, non-severe rejection (NSR), and severe rejection) on MMP3 levels. Results: In VCA, MMP3 levels increased significantly (p < 0.001) between pre- and post-transplant no-rejection states. A further increase occurred during severe rejection (p < 0.001), while there was no difference in MMP3 levels between non-severe and no-rejection episodes. A threshold of 5-fold increase from pre-transplant levels could discriminate severe from NSR with 76% sensitivity and 81% specificity (AUC = 0.79, 95% CI = 0.65-0.92, p < 0.001). In kidney transplantation, the MMP3 levels were significantly (p < 0.001) elevated during antibody-mediated rejection but not during T-cell mediated rejection (TCMR) (p = 0.547). MMP3 levels in healthy controls and autoimmune skin disease patients were comparable with either pre-transplant or no-rejection/NSR episodes of VCA patients. Conclusion: The results of this study suggest that serum MMP3 protein is a promising marker for stratifying patients according to severity of rejection, complementary to biopsy findings.


Subject(s)
Biomarkers , Graft Rejection/etiology , Graft Rejection/metabolism , Matrix Metalloproteinase 3/metabolism , Skin Transplantation , Vascularized Composite Allotransplantation , Adult , Autoimmunity , Female , Graft Rejection/diagnosis , Humans , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Severity of Illness Index
18.
J Craniofac Surg ; 30(8): e799-e802, 2019.
Article in English | MEDLINE | ID: mdl-31633669

ABSTRACT

OBJECTIVES: The aim of the study was to investigate the association between meningioma volume and the occurrence of clinic-radiologic signs of tumor aggressiveness. For volumetric approximation, the authors evaluated the method of semiautomatic image segmentation at hand of high-resolution MRI-image sequences. METHODS: ITK-SNAP was utilized for semiautomatic image segmentation of 58 gadolinium-contrast enhanced T1-weighted thin-slice MRI datasets for volumetric analysis. Furthermore, multimodal imaging datasets (including T2, FLAIR, T1) were evaluated for radiological biomarkers of aggressiveness and growth potential. Thereby generated data was checked for association with retrospectively collected data points. RESULTS: Location (P = 0.001), clinical disease manifestation (P = 0.033), peritumoral edema (P = 0.038), tumor intrinsic cystic degeneration (P = 0.007), three-dimensional complexity (P = 0.022), and the presence of meningioma mass effect (P = 0.001) were statistically associated with higher tumor volumes. There was no association between higher tumor volumes and histopathological tumor grade. CONCLUSION: The size of a meningioma does not seem to reliably predict tumor grade. Growth potential seems to be influenced by tumor location. Higher tumor volumes were significantly associated with the occurrence of clinical symptoms.


Subject(s)
Meningeal Neoplasms/diagnostic imaging , Meningioma/diagnostic imaging , Adult , Aged , Female , Humans , Intraoperative Period , Magnetic Resonance Imaging/methods , Male , Meningeal Neoplasms/pathology , Meningioma/pathology , Middle Aged , Multimodal Imaging , Neoplasm Grading , Retrospective Studies , Tumor Burden
19.
Burns ; 45(6): 1300-1310, 2019 09.
Article in English | MEDLINE | ID: mdl-31176508

ABSTRACT

BACKGROUND: Unintentional and intentional burn injuries vary across age groups, gender, income, and global region. In high-income countries, the trend over the last several years has been a reduction in burn incidence, burn severity, length of hospital stay, and mortality rate. However, there is a lack of data on predictors of the health-related quality of life (HRQoL) of major burn survivors extending beyond a follow-up period of 10 years. PATIENTS AND METHODS: This single-center cross-sectional study is considering 42 long-term severe burn survivors with deep partial thickness burns and an affected total body surface area (TBSA) of ≥20%. For study eligibility design a minimum follow-up of 10 years was obligatory. Entitled individuals were asked to fill in the generic Short Form 36 (SF-36) questionnaire. The physical (PCS) and mental (MCS) component scores of the SF-36 were used as the primary outcome variables. Putative predictor variables were drawn from medical records. Burn-specific functionality and scar tissue quality were assessed using the Burn Specific Health Scale-Brief (BSHS-B) questionnaire and the Patient and Observer Scar Assessment Scale (POSAS), respectively. Correlation between putative predictor variables and SF-36 norm scores were evaluated by Pearson- and Point-Biserial correlation as well as multivariate linear regression. The SF-36 norm scores were compared to the general German population. RESULTS: Mean follow-up was 14 (±3) years with a minimum and maximum of 10 and 28 years, respectively. Mean age at the time of the incident was 37 (±17) years. The majority of individuals were male (74%). The mean burn size was 39 (±17) % (TBSA) with 76% of the individuals showing a full thickness burn. SF-36 norm scores were not statistically different from the general population. Statistically significant independent predictor variables of the physical summary score were: age at the time of the injury (-0.381), time since injury (-0.466), length of hospital stay (-0.356), limb amputation (-0.318), unemployment (-0.433), work (0.593), hand function (0.601), body image (0.518), affect (0.355), simple abilities (0.602), burns involving the hands (-0.339) and back (-0.343), POSAS patient- (-0.521) and observer scores (-0.483). In multivariate analysis, work (4.315), the POSAS Score (-2.082) and the age at the time of the incident (-0.242) were statistically significant predictors. Statistically significant independent predictor variables of the mental summary score were: duration of mechanical ventilation (-0.459), hand function (0.415), body image (0.502), sexual activity (0.625), social support (0.542), burns involving the back (-0.315) and affect (0.692). In multivariate analysis, affect (13.844) and the length of mechanical ventilation (-0.115) were statistically significant independent predictor variables. CONCLUSION: Ten years after the burn incident, the quality of life was on average comparable to the one in the general population. Multiple variables seem to influence the physical and mental long-term outcome. Herein presented data may support in adapting and designing follow-up strategies tailored to a patient's burn-specific circumstances.


Subject(s)
Burns/physiopathology , Quality of Life , Adult , Affect , Age Factors , Amputation, Surgical/statistics & numerical data , Body Surface Area , Burns/psychology , Cicatrix/physiopathology , Cicatrix/psychology , Employment/statistics & numerical data , Female , Follow-Up Studies , Hand Injuries/physiopathology , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Prognosis , Respiration, Artificial/statistics & numerical data , Social Support , Survivors , Young Adult
20.
J Craniofac Surg ; 30(3): e213-e216, 2019.
Article in English | MEDLINE | ID: mdl-30845093

ABSTRACT

INTRODUCTION: Microsurgical interposition of vein grafts is an extraordinarily filigree surgical technique, which requires both sound theoretical knowledge and solid manual skills. Although there are a large number of training models, the majority of these are either relatively expensive, technically complex, or employ synthetic materials with poor resemblance to human tissue. The authors' model allows training of ex vivo vein graft interposition on gradually thawed cryopreserved vessels and it, therefore, is cost-efficient and readily available when needed. Furthermore, it respects the 3R-principle (Reduce-Refine-Replace), as it is based on rat cadaveric vessels. METHODS: Three trainees with basic microsurgical experience, but without prior performance of vein graft interpositioning, were chosen to perform 20 femoral vein graft (5 mm) interpositions into femoral artery defects. The patency and leakage rate served as qualitative variable and operation time as a quantitative variable for efficiency control. RESULTS: For the first half of trials, the trainees had a patency failure rate of 50% and for the second half a rate of 13.3%. The leakage rate noticeably decreased from 44.4% in the first half of trials to 10% in the second half. Although the trainees needed 60 minutes on average for their first 10 trials, they improved to 51 minutes for their last 10 anastomoses. CONCLUSION: The authors' microsurgical model offers a simple, low-cost simulation training, specifically designed for learning of vein graft interposition into arterial defects. The model is associated with a high learning curve, based on an objective control of the anastomoses by assessment of the patency, leakage, and operation time.


Subject(s)
Cryopreservation , Microsurgery/education , Vascular Grafting/education , Animals , Femoral Artery/physiology , Femoral Artery/surgery , Femoral Vein/physiology , Femoral Vein/transplantation , Humans , Models, Educational , Rats
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