Project description:Study objectivesThermistors, nasal cannulas, and respiratory inductance plethysmography (RIP) are the recommended reference sensors of the American Academy of Sleep Medicine (AASM) for the detection and characterization of apneas and hypopneas; however, these sensors are not well tolerated by patients and have poor scorability. We evaluated the performance of an alternative method using a combination of tracheal sounds (TSs) and RIP signals.MethodsConsecutive recordings of 70 adult patients from the Pays de la Loire Sleep Cohort were manually scored in random order using the AASM standard signals and the combination TS and RIP signals, without respiratory sensors placed on the patient's face. The TS-RIP scoring used the TS and RIP-flow signals for detection of apneas and hypopneas, respectively, and the suprasternal pressure and RIP belt signals for the characterization of apneas.ResultsSensitivity and specificity of the TS-RIP combination were 96.21% and 91.34% for apnea detection and 89.94% and 93.25% for detecting hypopneas, respectively, with a kappa coefficient of 0.87. For the characterization of apneas, sensitivity and specificity were 98.67% and 96.17% for obstructive apneas, 92.66% and 99.36% for mixed apneas, and 96.14% and 98.89% for central apneas, respectively, with a kappa coefficient of 0.94. The TS-RIP scoring revealed a high agreement for classifying obstructive sleep apnea into severity classes (none, mild, moderate, and severe obstructive sleep apnea) with a Cohen's kappa coefficient of 0.96.ConclusionsCompared with the AASM reference sensors, the TS-RIP combination allows reliable noninvasive detection and characterization of respiratory events with a high degree of sensitivity and specificity. TS-RIP combination could be used for diagnosis of obstructive sleep apnea in adults, either as an alternative to the AASM sensors or in combination with the recommended AASM sensors.
Project description:ObjectiveFace transplantation replaces substantial defects with anatomically identical donor tissues; preoperative vascular assessment relies on noninvasive imaging to separate and characterize the external carotid vessels and branches. The objective is to describe and illustrate vascular considerations for face transplantation candidates.MethodsNovel noninvasive imaging using computed tomography and magnetic resonance imaging over 3 spatial dimensions plus time was developed and tested in 4 face transplant candidates. Precontrast images assessed bones and underlying metal. Contrast media was used to delineate and separate arteries from veins. For computed tomography, acquisition over multiple time points enabled the computation of tissue perfusion metrics. Time-resolved magnetic resonance angiography was performed to separate arterial and venous phases.ResultsThe range of circulation times for the external carotid system was 6 to 14 seconds from arterial blush to loss of venous enhancement. Precontrast imaging provided a roadmap of bones and metal. Among the 4 patients, 3 had surgical clips, metal implants, or both within 1 cm of major vessels considered for surgery. Contrast-enhanced wide area detector computed tomographic data acquired in the axial mode separated these structures and provided arterial and venous images for planning the surgical anastomoses. Magnetic resonance imaging was able to distinguish between the large vessels from the external carotid systems.ConclusionsVascular imaging maps are challenging in face transplantation because of the rapid circulation times and artifact from the initial injury, prior reconstructive attempts, or both. Nevertheless, face transplant candidates require high spatial and temporal resolution vascular imaging to determine those vessels appropriate for surgical anastomoses.
Project description:The purpose of our study is to determine whether the current level of transplant fellow training is sufficient to meet the future demand for liver transplantation in the United States. Historical data from the Nationwide Inpatient Samples (NIS) for the years 1998 through 2003 were used to construct an estimate of the annual number of liver transplant procedures currently being performed in the United States, and the number projected for each year through 2020. Estimates for the current and future number of surgeons performing liver transplant procedures were also constructed using the same database. The NIS database was used because current national transplant registries do not include information on the number of surgeons performing liver transplant procedures. Using historical data derived from the NIS database, we project that the estimated number of liver transplant procedures per surgeon will remain relatively stable through 2020, with each surgeon performing an average of 12.9 procedures in 2020 compared to 12.9 currently. We conclude that the relationship between demand for liver transplantation in the United States and the supply of liver transplant surgeons will remain stable over the next 15 years.
Project description:Liver transplantation is currently the most effective method for treating end-stage liver disease. However, recipients still need long-term immunosuppressive drug treatment to control allogeneic immune rejection, which may cause various complications and affect the long-term survival of the recipient. Many liver transplant researchers constantly pursue the induction of immune tolerance in liver transplant recipients, immunosuppression withdrawal, and the maintenance of good and stable graft function. Although allogeneic liver transplantation is more tolerated than transplantation of other solid organs, and it shows a certain incidence of spontaneous tolerance, there is still great risk for general recipients. With the gradual progress in our understanding of immune regulatory mechanisms, a variety of immune regulatory cells have been discovered, and good results have been obtained in rodent and non-human primate transplant models. As immune cell therapies can induce long-term stable tolerance, they provide a good prospect for the induction of tolerance in clinical liver transplantation. At present, many transplant centers have carried out tolerance-inducing clinical trials in liver transplant recipients, and some have achieved gratifying results. This article will review the current status of liver transplant tolerance and the research progress of different cellular immunotherapies to induce this tolerance, which can provide more support for future clinical applications.
Project description:Importance:Limited quantitative data exist on the restoration of nonverbal communication via facial emotional expression after face transplant. Objective and noninvasive methods for measuring outcomes and tracking rehabilitation after face transplant are lacking. Objective:To measure emotional expression as an indicator of functional outcomes and rehabilitation after face transplant via objective, noninvasive, and nonobtrusive software-based video analysis. Design, Setting, and Participants:This single-center case-control study analyzed videos with commercially available video analysis software capable of detecting emotional expression. The study participants were 6 patients who underwent face transplant at Brigham and Women's Hospital between April 2009 and March 2014. They were matched by age, race/ethnicity, culture, and sex to 6 healthy controls with no prior facial surgical procedures. Participants were asked to perform either emotional expressions (direct evaluation) or standardized facial movements (indirect evaluation). Videos were obtained in a clinical setting, except for direct evaluation videos of 3 patients that were recorded at the patients' residences. Data analysis was performed from June 2018 to November 2018. Main Outcomes and Measures:The possibility of detecting the emotional expressions of happiness, sadness, anger, fear, surprise, and disgust was evaluated using intensity score values between 0 and 1, representing expressions that are absent or fully present, respectively. Results:Six patients underwent face transplant (4 men; mean [SD] age, 42 [14] years). Four underwent full face transplants, and 2 underwent partial face transplants of the middle and lower two-thirds of the face. In healthy controls, happiness was the only emotion reliably recognized in both indirect (mean [SD] intensity score, 0.92?[0.05]) and direct (mean [SD] intensity score, 0.91?[0.04]) evaluation. Indirect evaluation showed that expression of happiness significantly improved 1 year after transplant (0.04 point per year; 95% CI, 0.02 to 0.06 point per year; P?=?.002). Expression of happiness was restored to a mean of 43% (range, 14% to 75%) of that of healthy controls after face transplant. The expression of sadness showed a significant change only during the first year after transplant (-0.53 point per year; 95% CI, -0.82 to -0.24 point per year; P?=?.005). All other emotions were detectable with no significant change after transplant. Nearly all emotions were detectable in long-term direct evaluation of 3 patients, with expression of happiness restored to a mean of 26% (range, 5% to 59%) of that of healthy controls. Conclusions and Relevance:Partial restoration of facial emotional expression is possible after face transplant. Video analysis software may provide useful clinical information and aid rehabilitation after face transplant.
Project description:Facial transplantation (FT) has become a feasible reconstructive solution for patients with devastating facial injuries. Secondary revisions to optimize functional and aesthetic outcomes are to be expected, yet the optimal timing and approach remain to be determined. The purpose of this study was to analyze all facial allograft revisions reported to date, including the senior author's experience with 3 FTs.MethodsA literature review was performed, with 2 reviewers independently conducting title and abstract screening, followed by a full-text review. All articles mentioning FT revision surgeries were evaluated. The medical records of the senior author's 3 FT recipients were additionally reviewed.ResultsInitially, 721 articles were captured and 37 were included in the final analysis. Thirty-two FTs were reported to have involved posttransplant allograft revisions, with FT recipients undergoing a mean of 4.8 ± 4.6 revision procedures. The mean duration between FT and the first revision procedure was 149 ± 179 days. A wide spectrum of revisions was identified and categorized as involving the soft tissues, craniofacial skeleton, dentition, oronasal cavity, salivary glands, facial nerve, or ocular region. In the senior author's experience, when indicated, posttransplant occlusal changes and integrity of the donor-recipient intraoral interface were successfully addressed with secondary procedures without allograft compromise or loss.ConclusionsThe worldwide experience shows that secondary procedures are nearly ubiquitous after FT and can be safely performed at various timepoints. The authors thereby establish 5 distinct categories of facial allograft revisions and define 7 critical principles to optimize posttransplant procedures.
Project description:ObjectiveTo test the hypothesis that wide area detector face transplant surgical planning CT angiograms with simulated lower radiation dose and iterative reconstruction (AIDR3D) are comparable in image quality to those with standard tube current and filtered back projection (FBP) reconstruction.Materials and methodsThe sinograms from 320-detector row CT angiography of four clinical candidates for face transplantation were processed utilizing standard FBP, FBP with simulated 75, 62, and 50% tube current, and AIDR3D with corresponding dose reduction. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured at muscle, fat, artery, and vein. Image quality for each reconstruction strategy was assessed by two independent readers using a 4-point scale.ResultsCompared to FBP, the median SNR and CNR for AIDR3D images were higher at all sites for all 4 different tube currents. The AIDR3D with simulated 50% tube current achieved comparable SNR and CNR to FBP with standard dose (median muscle SNR: 5.77 vs. 6.23; fat SNR: 6.40 vs. 5.75; artery SNR: 43.8 vs. 45.0; vein SNR: 54.9 vs. 55.7; artery CNR: 38.1 vs. 38.6; vein CNR: 49.0 vs. 48.7; all p-values >0.19). The interobserver agreement in the image quality score was good (weighted κ = 0.7). The overall score and the scores for smaller arteries were significantly lower when FBP with 50% dose reduction was used. The AIDR3D reconstruction images with 4 different simulated doses achieved a mean score ranging from 3.68 to 3.82 that were comparable to the scores from images reconstructed using FBP with original dose (3.68-3.77).ConclusionsSimulated radiation dose reduction applied to clinical CT angiography for face transplant planning suggests that AIDR3D allows for a 50% reduction in radiation dose, as compared to FBP, while preserving image quality.
Project description:BackgroundIn the United States, no published guidelines promote exposure to technical variants (ie, living donor or split liver) during transplant fellowship. Simulation with hands-on liver models may improve training in transplantation. This pilot study addressed 3 overall goals (material and model creation tools, recruitment rates and assessment of workload, and protocol adherence).MethodsA patient-specific hands-on liver model was constructed from clinical imaging, and it needed to be resilient and realistic. Multiple types of materials were tested between January 2020 and August 2022. Participants were recruited stepwise. A left lateral segmentectomy simulation was conducted between August 2022 and December 2022 to assess protocol adherence.ResultsDigital anatomy 3-dimensional printing was considered the best option for the hands-on liver model. The recruitment rate was 100% and 47% for junior attendings and surgical residents, respectively. Ten participants were included and completed all the required surveys. Seven (70%) and 6 (60%) participants "agreed" that the overall quality of the model and the material were acceptable for surgical simulation. Five participants (50%) "agreed" that the training improved their surgical skills. Nine participants (90%) "strongly agreed" that similar sessions should be included in surgical training programs.ConclusionsThree-dimensional hands-on liver models have the advantage of tactile feedback and were rated favorably as a potential training tool. Study enrollment for further studies is possible with the support of leadership. Rigorous multicenter designs should be developed to measure the actual impact of 3-dimensional hands-on liver models on surgical training.
Project description:Rejection affects greater than 80% of face transplants, yet no diagnostic criteria for antibody-mediated rejection (AMR) following face transplantation have been established. Given that different treatment strategies are required to address AMR and T cell-mediated rejection (TCMR), there is a critical need to delineate the features that can differentiate these two alloimmune responses. Here, we report the longitudinal immunological examination of what we believe to be the first and only highly sensitized recipient of a crossmatch-positive face transplant up to 4 years following transplantation. We conducted gene expression profiling on allograft biopsies collected during suspected AMR and TCMR episodes as well as during 5 nonrejection time points. Our data suggest that there are distinctive molecular features in AMR, characterized by overexpression of endothelial-associated genes, including ICAM1, VCAM1, and SELE. Although our findings are limited to a single patient, these findings highlight the potential importance of developing and implementing molecular markers to differentiate AMR from TCMR to guide clinical management. Furthermore, our case illustrates that molecular assessment of allograft biopsies offers the potential for new insights into the mechanisms underlying rejection. Finally, our medium-term outcomes demonstrate that face transplantation in a highly sensitized patient with a positive preoperative crossmatch is feasible and manageable.
Project description:BACKGROUNDRejection is the primary barrier to broader implementation of vascularized composite allografts (VCAs), including face and limb transplants. The immunologic pathways activated in face transplant rejection have not been fully characterized.METHODSUsing skin biopsies prospectively collected over 9 years from 7 face transplant patients, we studied rejection by gene expression profiling, histology, immunostaining, and T cell receptor sequencing.RESULTSGrade 1 rejection did not differ significantly from nonrejection, suggesting that it does not represent a pathologic state. In grade 2, there was a balanced upregulation of both proinflammatory T cell activation pathways and antiinflammatory checkpoint and immunomodulatory pathways, with a net result of no tissue injury. In grade 3, IFN-γ-driven inflammation, antigen-presenting cell activation, and infiltration of the skin by proliferative T cells bearing markers of antigen-specific activation and cytotoxicity tipped the balance toward tissue injury. Rejection of VCAs and solid organ transplants had both distinct and common features. VCA rejection was uniquely associated with upregulation of immunoregulatory genes, including SOCS1; induction of lipid antigen-presenting CD1 proteins; and infiltration by T cells predicted to recognize CD1b and CD1c.CONCLUSIONOur findings suggest that the distinct features of VCA rejection reflect the unique immunobiology of skin and that enhancing cutaneous immunoregulatory networks may be a useful strategy in combatting rejection.Trial registrationClinicalTrials.gov NCT01281267.FUNDINGAssistant Secretary of Defense and Health Affairs, through Reconstructive Transplant Research (W81XWH-17-1-0278, W81XWH-16-1-0647, W81XWH-16-1-0689, W81XWH-18-1-0784, W81XWH-1-810798); American Society of Transplantation's Transplantation and Immunology Research Network Fellowship Research Grant; Plastic Surgery Foundation Fellowship from the American Society of Plastic Surgeons; Novo Nordisk Foundation (NNF15OC0014092); Lundbeck Foundation; Aage Bangs Foundation; A.P. Moller Foundation for the Advancement of Medical Science; NIH UL1 RR025758.