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Solid organ and vascularized composite allograft transplantation are pivotal in enhancing both life expectancy and quality of life. However, the significant risk of donor tissue ...rejection requires lifelong immunosuppressive therapy. Tacrolimus, a common component of immunosuppressive regimens, offers effectiveness in preventing organ rejection but poses challenges due to its narrow therapeutic window and toxicity, making it essential to carefully monitor its concentration. Tacrolimus trough levels are currently measured in blood, requiring frequent blood draws from patients, and results are available after 3 to 6 h. To address the need for a fast, minimally-invasive, and simple method to monitor tacrolimus concentrations, we have assessed a new device for at-home analysis, the Immunosuppressant Drug Monitor (IDM) that can extract, identify and quantify tacrolimus in saliva within 15 min. We included males and females hospitalized at Massachusetts General Hospital Transplant Unit, between the ages of 21 and 65 years, and treated with Tacrolimus. Informed consent, demographic and treatment data were collected. Each subject was asked to provide a 5 mL saliva sample that was de-identified and processed by the IDM, while a 5 mL blood sample was drawn and supplied to the MGH clinical lab for analysis by the current standard, immunoassays. The predicted tacrolimus concentration found in saliva was compared to the blood trough level results. 62 samples from 31 different patients were obtained. The male to female ratio and ethnicity distribution were well balanced. The majority of patients were within 30 days of initiating tacrolimus treatment. After IDM calibration and exclusion, 21 samples were measured by the IDM. Using an exponential function fit, the IDM showed a correlation of R2 = 0.39 between the saliva Test Line absorption and the measured tacrolimus concentration in blood, with an average absolute error of 1.8 ng/mL. Our results demonstrate a clear correlation between blood and saliva measurements. The IDM provided promising results to monitor immunosuppressant drug concentrations in patients after transplantation. Future larger studies will further develop the correlation, and the IDM’s potential impact on patient outcomes.
The current gold standard for preserving vascularized composite allografts (VCA) is 4°C static cold storage (SCS), albeit muscle vulnerability to ischemia can be described as early as after 2 h of ...SCS. Alternatively, machine perfusion (MP) is growing in the world of organ preservation. Herein, we investigated the outcomes of oxygenated acellular subnormothermic machine perfusion (SNMP) for 24-h VCA preservation before allotransplantation in a swine model. Six partial hindlimbs were procured on adult pigs and preserved
for 24 h with either SNMP (
= 3) or SCS (
= 3) before heterotopic allotransplantation. Recipient animals received immunosuppression and were followed up for 14 days. Clinical monitoring was carried out twice daily, and graft biopsies and blood samples were regularly collected. Two blinded pathologists assessed skin and muscle samples. Overall survival was higher in the SNMP group. Early euthanasia of 2 animals in the SCS group was linked to significant graft degeneration. Analyses of the grafts showed massive muscle degeneration in the SCS group and a normal aspect in the SNMP group 2 weeks after allotransplantation. Therefore, this 24-h SNMP protocol using a modified Steen solution generated better clinical and histological outcomes in allotransplantation when compared to time-matched SCS.
Hemorrhage is an uncommon complication of liposuction that may be trauma-induced by the cannula on the subcutaneous perforators. It usually resolves spontaneously with external compression and ...results in mild to moderate ecchymosis on the liposuction site. However, in sporadic cases, active bleeding may persist and require urgent intervention for hemostasis.
We report the case of a 60-year-old White female who developed a massive hematoma in the hour following liposuction of the right internal thigh, with active bleeding in the subcutaneous plane reported on contrast-enhanced computed tomography. The initial angiogram was conducted in the right common femoral artery and showed active bleeding from a profunda artery perforator. After careful selective catheterization of the feeding artery using a 2.0-French microcatheter, 0.3 mL of Onyx 34 was injected. Control angiography showed no immediate complication and confirmed the exclusion of the pseudoaneurysm. No postoperative event occurred. Blood pressure and hemoglobin levels remained stable throughout the episode.
Although liposuction is a very common procedure in plastic surgery, hemorrhagic complications may occur and require urgent hemostasis. This case suggests a vital place for interventional radiology in the management of hemorrhagic complications after liposuction.
Vascularized composite allografts (VCAs) can restore fully functional anatomic units in patients with limb amputations or severe facial tissue loss. However, acute rejection of the skin is frequently ...observed and underscores the importance of developing tolerance induction protocols. In this study, we have characterized the skin immune system in VCAs. We demonstrate infiltration of recipient leukocytes, regardless of rejection status, and in tolerant mixed hematopoietic chimeras, the co‐existence of these cells with donor leukocytes in the absence of rejection. Here we characterize the dermal T cell and epidermal Langerhans cell components of the skin immune system in our porcine model of VCA tolerance, and the kinetics of cutaneous chimerism in both of these populations in VCAs transplanted to tolerant and nontolerant recipients, as well as in host skin. Furthermore, in biopsies from the first patient to receive a hand transplant in our program, we demonstrate the presence of recipient T cells in the skin of the transplanted limb in the absence of clinical or histological evidence of rejection.
The authors show that recipient leukocytes infiltrate the skin of vascularized composite allografts and, in tolerant large animal recipients and in an immunosuppressed hand recipient, coexist with donor leukocytes without evidence of rejection.
Enzymes are commonly used as a biochemical means to liberate cells from a host of tissues for use in in vitro studies and/or in vivo transplantations. However, very little understanding exists of the ...biological and functional effects that enzymes have on cells during the process of releasing the native cells from a given tissue. One specific reason for this is that no technology has existed as a nonenzymatic control to compare baseline biology and function for a given processed tissue. We have developed a sterile, onetime use, disposable system (referred to as the AuxoCell Processing System or AC:Px®) that allows for processing of solid tissue in a closed, standardized system using mechanical means to liberate cells without the need and/or use of any biochemical, enzymatic digestion. In this report, for the first time, we directly compare the cellular outputs derived from processing the same umbilical cord tissue (UCT) in the presence and absence of collagenase. In the presence of collagenase, we observed on average, approximately a 2.7-fold reduction in native mesenchymal stem/stromal cell (MSC) yields and a reduction in MSC-specific markers CD90, CD29, CD105, CD73, CD44, CD36, CD49b, CD49a, CD146, CD295, and CD166 and in endothelial marker CD31. These data directly exhibit that the use of collagenase to process UCT to release cells impacts cell recovery with respect to number and cell surface marker expression and, hence, could affect the in vivo function of the recovered native cellular population.
Microsurgical free tissue transfer may be the only reconstructive option for lower extremity limb salvage. However, the functional and aesthetic results following free tissue transfer after initial ...salvage may be suboptimal, thus requiring secondary surgeries to facilitate definitive wound healing and/or refinement.
A multi-institutional retrospective cohort study was performed including patients who underwent lower extremity free tissue transfer from January 2002 to December 2020. Our primary outcome variable was the presence of secondary surgery after free tissue transfer for lower extremity reconstruction. Independent variables (wound etiology, flap, donor type, recipient, co-morbidities, etc.) were collected. Secondary surgery was categorized as (1) procedures for definitive wound closure and (2) refinement procedures. Multivariable logistic regression was performed to determine which variables were independently associated with the outcome.
Four-hundred-and-twenty free tissue transfers for lower extremity reconstruction were identified. Secondary surgery was performed in over half (57%) of the patients. Presence of diabetes (OR: 2.0, p: 0.01, 95% CI: 1.2-3.5) and use of a latissimus dorsi donor (OR: 2.4, p: 0.037, 95% CI: 1.1-5.4) were predictors of wound closure procedures. Fasciocutaneous (OR 3.6, p: <0.001, 95% CI 1.8-7.2) and myocutaneous (OR: 3.0, p=0.005, 95% CI 1.5-9.9) flaps were predictors of refinement procedures when compared to muscle-only flaps with skin grafts.
The majority of lower extremity free tissue reconstructions required secondary procedures to provide definitive wound closure and/or refinement. Overall, this study provides predictors of secondary surgery that will help formulate patients' expectations of lower extremity limb salvage.
Gender affirmation in trans men requires multiple staged procedures. The final masculinizing step involves phalloplasty or metoidioplasty and further incorporation of penile and testicular ...prostheses. However, these are functionally suboptimal and associated with high complication rates. Therefore, we sought to investigate the anatomical feasibility of one-stage genitourinary vascularized composite allotransplantation (GUVCA) for such gender-affirming surgeries.
Twenty fresh cadaveric dissections were performed to delineate the neurovascular anatomy of the proposed GUVCA. Specifically, in donors (n = 14), besides the penis and scrotum, the GUVCA included an inferior bladder patch with the urinary sphincter, prostate, seminal vesicles, as well as a strip of the pubic bone. In trans men recipients, osteotomies of the pubic bone to match that of the donor GUVCA were required. Five cadaveric GUVCA transplants were then performed to simulate one-stage gender affirmation surgery.
The GUVCA required (1) vascular anastomoses between the recipient's deep inferior epigastric, external pudendal, and superficial circumflex iliac (or superficial inferior epigastric) vessels to the donor's internal pudendal, external pudendal and genitofemoral vessels respectively; (2) neurosynthesis between the recipient pudendal and dorsal clitoral nerves to the donor pudendal and genitofemoral nerves; and (3) urinary bladder anastomosis at the bladder neck, upstream of the urinary sphincter. Average donor measurements (length (cm), diameter (mm)) were: external pudendal artery (2.5, 2.0) and vein (2.0, 3.5), internal pudendal artery (15.0, 4.0), pudendal (15.0, 3.0) and genitofemoral nerves (8.0, 2.0).
We have described the anatomical basis for a one-stage GUVCA in trans masculine genitourinary reconstruction.
Autologous fat transplantation -i.e., lipofilling- has become a promising and popular technique in aesthetic and reconstructive surgery with several application such as breast reconstruction, facial ...and hand rejuvenation. However, the use of this technology is still limited due to an unpredictable and low graft survival rate (which ranges from 25%-80%). A systematic literature review was performed by thoroughly searching 12 terms using the PubMed database. The objective of this study is to present the current evidence for the efficacy of adjuvant regenerative strategies and cellular factors, which have been tested to improve fat graft retention. We present the main results (fat retention rate, histological analysis for pre-clinical studies and satisfaction/ complication for clinical studies) obtained from the studies of the three main fat grafting enrichment techniques: platelet-rich plasma (PRP), the stromal vascular fraction (SVF) and adipose-derived stem cells (ADSCs) and discuss the promising role of recent angiogenic cell enrichment that could induce early vascularization of fat graft. All in all, adding stem or progenitor cells to autologous fat transplantation might become a new concept in lipofilling. New preclinical models should be used to find mechanisms able to increase fat retention, assure safety and transfer these technologies to a good manufacturing practice (GMP) compliant facility, to manufacture an advanced therapy medicinal product (ATMP).
Vascularized composite allotransplantations are complex procedures with substantial functional impact on patients. Extended preservation of VCAs is of major importance in advancing this field. It ...would result in improved donor-recipient matching as well as the potential for ex vivo manipulation with gene and cell therapies. Moreover, it would make logistically feasible immune tolerance induction protocols through mixed chimerism. Supercooling techniques have shown promising results in multi-day liver preservation. It consists of reaching sub-zero temperatures while preventing ice formation within the graft by using various cryoprotective agents. By drastically decreasing the cell metabolism and need for oxygen and nutrients, supercooling allows extended preservation and recovery with lower ischemia-reperfusion injuries. This study is the first to demonstrate the supercooling of a large animal model of VCA. Porcine hindlimbs underwent 48 h of preservation at - 5 °C followed by recovery and normothermic machine perfusion assessment, with no issues in ice formation and favorable levels of injury markers. Our findings provide valuable preliminary results, suggesting a promising future for extended VCA preservation.
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