Advancing vascularized composite allotransplantation: essential factors for upper extremity transplant program development.

Vascularized Composite Allotransplantation (VCA) offers a unique option to restore form and function after limb loss or facial trauma that cannot be satisfactorily accomplished through traditional prosthetics or reconstructions. Establishing a successful Upper Extremity Transplantation (UET) program requires strong leadership and a structured surgical team, and extensive interdisciplinary collaboration. We conducted a qualitative study among 12 health care professionals and patients. Informed consent was obtained per protocol, and semi-structured interviews were conducted online and recorded. Participants reported their perceptions of factors that either favored or hindered a successful outcome, including functional status before and after surgery, preparation for transplant, shared decision-making, rehabilitation, and psychosocial support. Thematic analysis revealed that it is essential to establish a team comprising various disciplines well before performing VCA procedures. Defining a common goal and choosing a defined leader is a key factor in procedural success and requires open collaboration beyond what is typical. Primary described categories are interdisciplinary collaboration and skills of the VCA team, building and leading a VCA team, pre-transplant procedures, post-transplant course, and factors to consider when establishing a program. The basic roles of team science play an outsized role in establishing a VCA program. Transplantation medicine involves various overlapping scientific and medical categories requiring health professionals to consciously work together to establish complex vertical and horizontal communication webs between teams to obtain positive outcomes. In addition to medical considerations, patient-specific factors such as transparent communication, therapy plan establishment, plan adherence, and continual follow-up are significant factors to overall success.

Case Report: Post-transplant lymphoproliferative disorder as a serious complication of vascularized composite allotransplantation.

Vascularized composite allotransplantation (VCA) is an emerging field in transplant surgery. Despite overall positive outcomes, VCA confers risk for multiple complications related to the procedure and subsequent immunosuppression. Post-transplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoproliferative disorders occurring after solid organ and hematopoietic stem cell transplant. A patient with PTLD after bilateral upper extremity transplantation is presented as well as a review of all known cases of PTLD after VCA, with a focus on the unique epidemiology, presentation, and treatment in this population.

Outcomes of Dermal Regeneration Templates in Irradiated and Nonirradiated Scalp Defects.

OBJECTIVES: Dermal regeneration templates (DRTs) are frequently used to treat scalp defects. The aim was to compare the time course of healing for DRTs in scalp defects with and without preoperative radiation. METHODS: The authors conducted a retrospective cohort study of DRT-based scalp reconstruction at 2 academic medical centers between 2013 and 2022. Information was collected on demographic variables, comorbidities, medication use, history of radiation, and DRT outcomes. The primary outcome was DRT loss, defined as exposed calvarium or DRT detachment based on postoperative follow-up documentation. Kaplan-Meier survival analysis and multivariable Cox proportional-hazard regressions were used to compare DRT loss in irradiated and nonirradiated defects. Multivariable logistic regressions were used to compare 30-day postoperative complications (infection, hematoma, or seroma) in irradiated and nonirradiated defects. RESULTS: In total, 158 cases were included. Twenty-eight (18%) patients had a preoperative history of radiation to the scalp. The mean follow-up time after DRT placement was 2.6 months (SD: 4.5 mo). The estimated probability of DRT survival at 2 months was 91% (95% CI: 83%-100%) in nonirradiated patients and 65% (95% CI: 48%-88%) in irradiated patients. In the 55 patients with a bony wound base, preoperative head radiation was associated with a higher likelihood of DRT loss (hazard ratio: 11). Half the irradiated defects experienced uncomplicated total wound closure using Integra Wound Matrix Dressing with or without second-stage reconstruction. CONCLUSIONS: Dermal regeneration template can offer durable coverage in nonirradiated scalp defects. Although DRT loss is more likely in irradiated scalp defects, successful DRT-based reconstruction is possible in select cases.

Long-term outcomes analysis of flap-based perineal reconstruction.

BACKGROUND: High-risk patients undergoing abdominoperineal resection and pelvic exenteration may benefit from immediate flap reconstruction. However, there is currently no consensus on the ideal flap choice or patient for whom this is necessary. This study aimed to evaluate the long-term outcomes of using pedicled gracilis flaps for pelvic reconstruction and to analyze predictors of postoperative complications. METHODS: This was a retrospective review of a single reconstructive surgeon's cases between January 2012 and June 2021 identifying patients who underwent perineal reconstruction secondary to oncologic resection. Preoperative and outcome variables were collected and analyzed to determine the risk of developing minor and major wound complications. RESULTS: A total of 101 patients were included in the study with most patients (n = 88) undergoing unilateral gracilis flap reconstruction after oncologic resection. The mean follow-up period was 75 months. Of 101 patients, 8 (7.9%) developed early major complications, and an additional 13 (12.9%) developed late major complications. Minor complications developed in 33 patients (32.7%) with most cases being minor wound breakdown requiring local wound care. Most patients (n = 92, 91.1%) did not develop donor site complications. Anal cancer was significantly associated with early major complications, whereas younger age and elevated body mass index were significant predictors of developing minor wound complications. CONCLUSIONS: This study builds on our previous work that demonstrated the long-term success rate of gracilis flap reconstruction after large pelvic oncologic resections. A few patients developed donor site complications, and perineal complications were usually easily managed with local wound care, thus making the gracilis flap an attractive alternative to abdominal-based flaps.

Banff 2022 Vascularized Composite Allotransplantation Meeting Report: Diagnostic criteria for vascular changes.

As more data become available, the Banff 2007 working classification of skin-containing vascularized composite allograft (VCA) pathology is expected to evolve and develop. This report represents the Banff VCA Working Group's consensus on the first revision of the 2007 scoring system. Prior to the 2022 Banff-CanXadian Society of Transplantation Joint Meeting, 83 clinicians and/or researchers were invited to a virtual meeting to discuss whether the 2007 Banff VCA system called for a revision. Unanimously, it was determined that the vascular changes were to be included in the first revision. Subsequently, 2 international online surveys, each followed by virtual discussions, were launched. The goals were (1) to identify which changes define severe rejection, (2) to grade their importance in the evaluation of severe rejection, and (3) to identify emerging criteria to diagnose rejection. A final hybrid (in-person and virtual) discussion at the Banff/Canadian Society of Transplantation Joint Meeting finalized the terminology, the definition, a scoring system, and a reporting system of the vascular changes. This proposal represents an international consensus on this topic and establishes the first revision of the Banff 2007 working classification of skin-containing vascularized composite allograft pathology.

Phototherapy Restores Deficient Type I IFN Production and Enhances Antitumor Responses in Mycosis Fungoides.

Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8+ T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.

The Nuances of Hand Transplantation After Sepsis.

Vascularized composite allotransplantation (VCA) of the upper extremity is an established restorative procedure for selected patients with acquired upper limb loss. The majority of upper limb VCAs performed worldwide have been for victims of various forms of trauma. However, in the developed world, amputation following severe sepsis seems to be an increasingly common indication for referral to hand transplant programs. Unlike trauma patients with isolated limb injuries, patients with amputations as a complication of sepsis have survived through a state of global tissue hypoperfusion and multisystem organ failure with severe, enduring effects on the entire body's physiology. This article reviews the unique considerations for VCA candidacy in postsepsis patients with upper limb amputation. These insights may also be relevant to postsepsis patients undergoing other forms of transplantation or to VCA patients requiring additional future solid organ transplants.

Quadriceps tendon malalignment is an independent anatomical deformity which is the primary abnormality associated with lateral facet patellofemoral joint osteoarthritis.

PURPOSE: The purposes of this study are to, firstly, develop techniques to accurately identify extensor mechanism malalignment by measuring the alignment of the quadriceps tendon (QTA) with computerized tomography (CT) scans. Secondly, to investigate correlations between QTA and lower limb bony anatomical variations within a representative normal population. Lastly, to evaluate the clinical significance of QTA by establishing its potential connection with lateral facet patellofemoral joint osteoarthritis (LFPFJOA). METHOD: CT scans were orientated to a mechanical axis reference frame and three techniques developed to measure the alignment of the quadriceps tendon. Multiple measurement of bony alignment from the hip to the ankle were performed on each scan. A series of 110 cadaveric CT scans were measured to determine normal values, reproducibility, and correlations with bony anatomy. Secondly, a comparison between 2 groups of 25 patients, 1 group with LFPFJOA and 1 group with isolated medial OA and no LFPFJOA. RESULTS: From the cadaveric study, it was determined that the alignment of the quadriceps tendon is on average 4.3° (SD 3.9) varus and the apex of the tendon is 9.1 mm (SD 7.7 mm) lateral to the trochlear groove and externally rotated 1.9° (SD 12.4°) from the centre of the femoral shaft. There was no association between the quadriceps tendon alignment and any other bony measurements including tibial tubercle trochlear groove distance (TTTG), coronal alignment, trochlear groove alignment and femoral neck anteversion. A lateralized QTA was significantly associated with LFPFJOA. QTA in the LFPFJOA group was 9.6° varus (SD 2.8°), 21.3 mm (SD 6.6) lateralised and 17.3° ER (SD 11°) compared to 5.5° (SD 2.3°), 10.7 mm (SD 4.9) and 3.3° (SD 7.2°), respectively, in the control group (p < 0.001). A significant association with LFPFJOA was also found for TTTG (17.2 mm (SD 5.7) vs 12.1 mm (SD 4.3), p < 0.01). Logistic regression analysis confirmed the QTA as having the stronger association with LFPFJOA than TTTG (AUC 0.87 to 0.92 for QTA vs 0.79 for TTTG). CONCLUSION: These studies have confirmed the ability to accurately determine QTA on CT scans. The normal values indicate that the QTA is highly variable and unrelated to bony anatomy. The comparative study has determined that QTA is clinically relevant and a lateralised QTA is the dominant predictor of severe LFPFJOA. This deformity should be considered when assessing patella maltracking associated with patella osteoarthritis, patella instability and arthroplasty. LEVEL OF EVIDENCE: III (retrospective cohort study).

Prevalence of Moral Injury, Burnout, Anxiety, and Depression in Healthcare Workers 2 Years in to the COVID-19 Pandemic.

ABSTRACT: COVID-19 has led to marked increases in healthcare worker distress. Studies of these phenomena are often limited to a particular element of distress or a specific subset of healthcare workers. We administered the Moral Injury Symptom Scale for Healthcare Professionals, Copenhagen Burnout Inventory, Patient Health Questionnaire-9, and Generalized Anxiety Disorder-7 via online survey to 17,000 employees of a large academic medical center between December 2021 and February 2022. A total of 1945 participants completed the survey. Across all roles, the prevalence of moral injury, burnout, depression, and anxiety were 40.9%, 35.3%-60.6%, 25.4%, and 24.8%, respectively. Furthermore, 8.1% had been bothered by thoughts that they would be better off dead or of hurting themselves for "several days" or more frequently. Healthcare workers across all roles and practice settings are experiencing unsustainable levels of distress, with 1 in 12 regularly experiencing thoughts of self-harm.

Psychosocial Risk Stratification in Upper Extremity Transplantation Candidates.

BACKGROUND: Candidate selection for upper extremity transplantation remains an inherently subjective process. This work evaluated the effect that psychosocial factors have on outcomes, both to standardize evaluation of potential candidates and in optimizing these factors prior to transplantation. Our goal was to measure and quantify the risk that various psychosocial factors have on transplant outcomes. METHODS: Given that we do not have sufficient post-transplant patients to examine specific factors, we chose to have experts in the field evaluate hypothetical patients based on their experience. We used a Generalized Estimating Equation to estimate and compare surgical candidacy scores using patient scenario vignettes based on the presence or absence of permutations of the following: (1) depression; (2) participation in occupational therapy (OT); (3) expectation of post-transplant function; (4) punctuality; and (5) family support were given to experts in the field. RESULTS: This work suggests there is a decrease in predicted success with increasing numbers of negative factors with participation in OT and realistic expectations of outcomes being most important. An increase in the summarizing risk score from 0 to 1.7 was associated with a decrease in the outcome surgical candidacy score from 8.6 to 5.3, meaning candidates with 2 risk factors would often observe a large drop in surgical candidacy score. CONCLUSIONS: Focusing on optimizing psychosocial variables in transplant candidates may help improve hand transplant success.

Long-Term Follow-Up of the Roux-Goldthwait Patellar Stabilization Procedure in a Predominantly Adult Population.

Background The Roux-Goldthwait patellar stabilisation (R-G) involves the medial transfer of the distal attachment of the lateral half of the patellar tendon. This paper reviews the long-term results of the R-G in a predominantly adult population. Methodology This is a retrospective study looking at patients with recurrent patellar instability who were treated with an R-G technique by a single surgeon over a 36-year period from 1976 to 2012. The primary outcomes measured were further patella instability and further knee surgical procedures. Results A total of 202 knees in 170 patients were analysed in this study. Patients between the ages of 9 and 70 years old (average 21 years old) were included in this study. The operative procedure changed during the study period. Initially, patients did not undergo concurrent arthroscopy. Early patients were likely to have additional lateral releases and open medial reefing procedures. More recent patients were more likely to undergo an isolated R-G procedure via a minimally invasive incision. The most common further operative procedure was arthroscopy of the knee for chondral pathology at 13.9%. These were more common early in the study period when patients did not have an initial arthroscopy. Recurrent dislocation was reported at 12.9%, with 5.9% of patients having revision stabilisation surgery, at a mean of 5.58 years (range = 1-15 years) postoperatively. Conclusions The R-G procedure is effective in treating recurrent patellar instability in both the paediatric and adult population. It can be performed as an isolated and minimally invasive procedure which is technically simple and has low morbidity.

COVID-19 pandemic impacts on mental health, burnout, and longevity in the workplace among healthcare workers: A mixed methods study.

To explore the mental health impacts of the COVID-19 pandemic on healthcare workers in Massachusetts and identify potential strategies to maintain the healthcare workforce we conducted a sequential exploratory mixed methods study. Fifty-two individuals completed interviews from April 22nd - September 7th, 2021; 209 individuals completed an online survey from February 17th - March 23rd, 2022. Interviews and surveys asked about the mental health impacts of working in healthcare during the COVID-19 pandemic, burnout, longevity in the workplace, and strategies for reducing attrition. Interview and survey participants were predominantly White (56%; 73%, respectively), female (79%; 81%) and worked as physicians (37%; 34%). Interviewees indicated high stress and anxiety levels due to frequent exposure to patient deaths from COVID-19. Among survey respondents, 55% reported worse mental health than before the pandemic, 29% reported a new/worsening mental health condition for themselves or their family, 59% reported feeling burned out at least weekly, and 37% intended to leave healthcare in less than 5 years. To decrease attrition, respondents suggested higher salaries (91%), flexible schedules (90%), and increased support to care for patients (89%). Healthcare workers' experiences with death, feeling unvalued, and overworked resulted in unprecedented rates of burnout and intention to leave healthcare.

Breakthrough treatments for accelerated wound healing.

Skin injuries across the body continue to disrupt everyday life for millions of patients and result in prolonged hospital stays, infection, and death. Advances in wound healing devices have improved clinical practice but have mainly focused on treating macroscale healing versus underlying microscale pathophysiology. Consensus is lacking on optimal treatment strategies using a spectrum of wound healing products, which has motivated the design of new therapies. We summarize advances in the development of novel drug, biologic products, and biomaterial therapies for wound healing for marketed therapies and those in clinical trials. We also share perspectives for successful and accelerated translation of novel integrated therapies for wound healing.

Augmented Reality Navigation Can Achieve Accurate Coronal Component Alignment During Total Knee Arthroplasty.

Background Computer-navigated knee arthroplasty has been shown to improve accuracy over conventional instruments. The next generation of computer assistance is being developed using augmented reality. The accuracy of augmented reality navigation has not been established. Methods From April 2021 to October 2021, a prospective, consecutive series of 20 patients underwent total knee arthroplasty utilising an augmented reality-assisted navigation system (ARAN). The coronal and sagittal alignment of the femoral and tibial bone cuts was measured using the ARAN and the final position of the components was measured on postoperative CT scans. The absolute difference between the measurements was recorded to determine the accuracy of the ARAN. Results Two cases were excluded due to segmentation errors, leaving 18 cases for analysis. The ARAN produced a mean absolute error of 1.4°, 2.0°, 1.1° and 1.6° for the femoral coronal, femoral sagittal, tibial coronal and tibial sagittal alignments, respectively. No outliers (absolute error of >3°) were identified in femoral coronal or tibial coronal alignment measurements. Three outliers were identified in tibial sagittal alignment, with all cases demonstrating less tibial slope (by 3.1°, 3.3° and 4°). Five outliers were identified in femoral sagittal alignment and in all cases, the component was more extended (3.1°, 3.2°, 3.2°, 3.4° and 3.9°). The mean operative time significantly decreased from the first nine augmented reality cases to the final nine cases by 11 minutes (p<0.05). There was no difference in the accuracy between the early and late ARAN cases. Conclusion Augmented reality navigation can achieve accurate alignment of total knee arthroplasty with a low rate of component malposition in the coronal plane. Acceptable and consistent accuracy can be achieved from the initial adoption of this technique, however, some sagittal outliers were identified and there is a clear learning curve with respect to operating time. The level of evidence was IV.

Psychosocial predictors in upper-extremity vascularized composite allotransplantation: A qualitative study of multidimensional experiences including patients, healthcare professionals, and close relatives.

Background: The impact of patient-specific psychosocial factors on functional outcomes after upper-extremity (UE) vascularized composite allotransplantation (VCA) is poorly understood. The objective of this study was to identify relevant psychosocial predictors for success or failure of UE VCA in an Austrian cohort. Methods: A qualitative study was undertaken consisting of semi-structured interviews with UE VCA staff, transplanted patients, and close relatives. Participants were asked about their perceptions of factors that either favored or hindered a successful transplant outcome, including functional status before surgery, preparation for transplant, decision-making, rehabilitation and functional outcome after surgery, and family and social support. Interviews were conducted online and recorded with the consent of interviewees. Results: Four bilateral UE VCA patients, 7 healthcare professionals, and a sister of a patient participated in the study. Thematic analysis revealed the importance of an expert interdisciplinary team with adequate resources for patient selection. Psychosocial aspects of prospective candidates are crucial to evaluate as they contribute to success. Both patients and providers may be impacted by public perceptions of UE VCA. Functional outcomes are optimized with a life-long commitment to rehabilitation as well as close, ongoing provider involvement. Conclusion: Psychosocial factors are important elements in the assessment and follow-up care for UE VCA. To best capture psychosocial elements of care, protocols must be individualized, patient-centered, and interdisciplinary. Investigating psychosocial predictors and collecting outcomes is, thus, critical to justifying UE VCA as a medical intervention and to providing accurate and salient information to prospective candidates.

Identifying Health-Related Quality of Life Domains After Upper Extremity Transplantation.

OBJECTIVE: To identify the most important health-related quality of life (HRQOL) domains and patient-reported outcomes after upper extremity transplantation (UET) in individuals with upper extremity amputation. DESIGN: Verbatim audio-recordings of individual interviews and focus groups were analyzed using qualitative, grounded theory-based methods to identify important domains of HRQOL and provide guidance for outcomes measurement after UET. SETTING: Individual interviews were conducted by phone. Focus groups were conducted at 5 upper extremity vascularized composite allotransplantation (VCA) centers in the US and at an international conference of VCA experts. PARTICIPANTS: Individual phone interviews were conducted with 5 individuals with lived experience of UET. Thirteen focus groups were conducted with a total of 59 clinical professionals involved in UET. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Not applicable. RESULTS: Twenty-eight key HRQOL domains were identified, including physical functioning and medical complications, positive and negative emotional functioning, and social participation, relations, and independence. We identified key constructs for use in evaluation of the potentially substantial physical, medical, social, and emotional effects of UET. CONCLUSIONS: This study provides an overview of the most important issues affecting HRQOL after UET, including several topics that are unique to individuals with UET. This information will be used to establish systematic, comprehensive, and longitudinal measurement of post-UET HRQOL outcomes.