Transplant vasculopathy has not been systematically investigated in composite tissue allotransplantation (CTA). The impact of multiple acute rejections (ARs) on long-term graft outcomes in reconstructive transplantation remains unknown. This study in a rat hind-limb allotransplantation model systematically analyzes vasculopathy and tissue-specific pathological changes secondary to multiple AR episodes. LEW rats were transplanted with BN rat hind limbs and treated as follows: Group 1 (Iso): isografts. Group 2 (CsA): Cyclosporine (CsA) qd; Group 3 (mult AR): CsA and dexamethasone only when AR was observed. No AR was observed in Groups 1 and 2. Multiple AR were observed in Group 3, and each episode was completely reversed (clinically) with pulsed CsA + dexamethasone treatment. Group 3 animals demonstrated significant vascular lesions along with skin and muscle atrophy, upregulation of profibrotic gene expression and fibrosis when compared to Groups 1 and 2. In addition, allograft bone was sclerotic, weak and prone to malunion and nonunion. Interestingly, vasculopathy was a late finding, whereas muscle atrophy with macrophage infiltration was seen early, after only a few AR episodes. Taken together, multiple AR episodes lead to vasculopathy and tissue-specific pathology in CTA. This is the first evidence of 'composite tissue vasculopathy and degeneration (CTVD)' in CTA.

Background: The year 2017 marked the first year women comprised a majority of U.S. medical school matriculants. While more women are pursuing surgical training, within plastic surgery, there is a steady attrition of women advancing in leadership roles. The authors report the current status of women in academic plastic surgery, from trainees to chairwomen and national leadership positions. Methods: The Electronic Residency Applications Service, San Francisco Match, National Resident Matching Program, Association of American Medical Colleges, American Council of Academic Plastic Surgeons, Plastic Surgery Education Network, and professional websites for journals and national societies were accessed for demographic information from 2007 to 2017. Results: The number of female integrated pathway applicants remained stable (30 percent), with an increased proportion of female residents from 30 percent to 40 percent. There was an increase in female faculty members from 14.6 percent to 22.0 percent, an increase of less than 1 percent per year. Twelve percent of program directors and 8.7 percent of department heads were women. Nationally, major professional societies and administrative boards demonstrated a proportion of female members ranging from 19 percent to 55 percent (average, 27.7 percent). The proportion of female committee leaders ranged from 0 percent to 50 percent (average, 21.5 percent). Only six societies have had female presidents. No major journal had had a female editor-in-chief. The proportion of female editorial board members ranged from 1 percent to 33 percent (average, 16.1 percent). Conclusions: The authors’ study shows a leak in the pipeline at all levels, from trainees to faculty to leadership on the national stage. This report serves as a starting point for investigating reasons for the underrepresentation of talented women in plastic surgery leadership.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line–derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 μm2) compared to autograft (4.62 ± 3.99 μm2) and PCL/Empty (4.52 ± 5.16 μm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

Summary:Glomus tumors are benign, painful growths originating from glomus bodies and comprise just 1% of tumors arising in the hand, with fewer than 10% in the volar pulp of digits. Hallmark symptoms of glomus tumors include hypersensitivity to cold, heightened pinprick sensitivity, and paroxysmal pain. We report a 72-year-old, right-hand dominant man who presented with pain in the left middle finger, localized to the tip. The fingertip was incredibly sensitive to touch, and his pain increased at night. He reported no recollection of trauma. Palpation of the finger revealed no mass, although it did indicate a focal point of pain within the distal pulp of the digit. Magnetic resonance imaging of the left hand revealed a round 7.0 × 4.0 × 6.0-mm soft tissue lesion along the volar ulnar aspect of the distal third digit. An incision was made in the mid-axial plane, circumscribing and removing the mass bluntly. It was a tan-yellow, soft tissue nodule of 0.8-cm in diameter without stalk or adherences to joints. Pathology revealed the mass was a glomus tumor. Symptoms improved on removal, and he healed without complication. Glomus tumors in the volar digital pulp can be difficult to diagnose. However, the presence of localized pain in the fingertip was reason to consider glomus tumor and proceed with treatment. Complete surgical removal of a glomus tumor is necessary to resolve symptoms and prevent recurrence.

BackgroundVascularized composite allotransplantation opens new possibilities in reconstructive transplantation such as hand or face transplants. Lifelong immunosuppression and its side-effects are the main drawbacks of this procedure. Mesenchymal stem cells (MSCs) have clinically useful immunomodulatory effects and may be able to reduce the burden of chronic immunosuppression. Herein, we assess and compare characteristics and immunomodulatory capacities of bone marrow- and adipose tissue-derived MSCs isolated from the same human individual across defined human leukocyte antigen (HLA) barriers.Materials and methodsSamples of omental (o.) adipose tissue, subcutaneous (s.c.) adipose tissue, and bone marrow aspirate from 10 human organ donors were retrieved and MSCs isolated. Cells were characterized by flow cytometry and differentiated in three lineages: adipogenic, osteogenic, and chondrogenic. In mixed lymphocyte reactions, the ability of adipose-derived mesenchymal stem cells (ASCs) and bone marrow-derived mesenchymal stem cells (BMSCs) to suppress the immune response was assessed and compared within individual donors. HLA mismatched or mitogen stimulations were analyzed in co-culture with different MSC concentrations. Supernatants were analyzed for cytokine contents.ResultsAll cell types, s.c.ASC, o.ASC, and BMSC demonstrated individual differentiation potential and cell surface markers. Immunomodulating effects were dependent on dose and cell passage. Proliferation of responder cells was most effectively suppressed by s.c.ASCs and combination with BMSC resulted in highly efficient immunomodulation. Immunomodulation was not cell contact-dependent and cells demonstrated a specific cytokine secretion.ConclusionWhen human ASCs and BMSCs are isolated from the same individual, both show effective immunomodulation across defined HLA barriers in vitro. We demonstrate a synergistic effect when cells from the same biologic system were combined. This cell contact-independent function underlines the potential of clinical systemic application of MSCs.