Xiaoti Xu

Human Satellite Cell Transplantation and Regeneration from Diverse Skeletal Muscles

Summary Identification of human satellite cells that fulfill muscle stem cell criteria is an unmet need in regenerative medicine. This hurdle limits understanding how closely muscle stem cell properties are conserved among mice and humans and hampers translational efforts in muscle regeneration. Here, we report that PAX7 satellite cells exist at a consistent frequency of 2–4 cells/mm of fiber in muscles of the human trunk, limbs, and head. Xenotransplantation into mice of 50–70 fiber-associated, or 1,000–5,000 FACS-enriched CD56+/CD29+ human satellite cells led to stable engraftment and formation of human-derived myofibers. Human cells with characteristic PAX7, CD56, and CD29 expression patterns populated the satellite cell niche beneath the basal lamina on the periphery of regenerated fibers. After additional injury, transplanted satellite cells robustly regenerated to form hundreds of human-derived fibers. Together, these findings conclusively delineate a source of bona-fide endogenous human muscle stem cells that will aid development of clinical applications.

The current management of skin tears

Each year, there are more than 1 million skin tears among the elderly and disabled. Because of their fragile nature, management of skin tears can be very challenging. Methods of wound closure should minimize additional trauma to the skin and promote an optimal wound healing environment while minimizing the risk of infection. The current article reviews the etiology, risk factors, classification, and therapeutic options for treating skin tears. We also review preventive measures to help reduce the incidence of skin tears.

The importance of basic science and clinical research as a selection criterion for general surgery residency programs.

OBJECTIVE The selection criteria for surgical residents applying for residency differ among programs nationwide. Factors influencing this selection process have not been well defined, and research in particular has not been evaluated fully. This study aimed to evaluate the relative importance of basic science and clinical research in the selection criteria used by program directors (PDs). DESIGN A web-based survey consisting of 11 questions was sent to PDs using the list server of the Association of Program Directors in Surgery. Respondents were asked to rank selection factors using a 1-to-5 scoring system, with 5 as most important. Their responses were recorded and tabulated. SETTING University-based teaching hospital. PARTICIPANTS The survey went to 251 accredited general surgery residency programs in the United States. RESULTS Overall, 134 (53.3%) of the surveys were returned, representing 61 university-based programs, 57 community-based programs with university affiliation, and 16 community-based programs without university affiliation. In total, 120 PDs (89.5%) considered basic or clinical research almost always or all the time when evaluating applicants to their general surgery program. Another 73 PDs (54.5%) gave basic science and clinical research equal importance. Another 40 PDs (29.9%) rarely or never credited research unless it had been published as an abstract or paper. In ranking research, 11 (8.2%) respondents gave it the 5 score. Most respondents (n = 93; 69.4%) gave it the 3 score. An applicants interview and interest in surgery were the factors considered most important by 93 (69.4%) and 78 (58.2%), respectively, of the PDs. CONCLUSIONS Basic science and clinical research constituted an important but secondary criterion for resident selection by PDs into general surgery residency programs. PDs perceived the primary factors for residency selection to be the interview, demonstrated interest in surgery, AOA membership, letters of recommendation, and USMLE Step I scores.

Porcine wound healing in full-thickness skin defects using Integra™ with and without fibrin glue with keratinocytes.

BACKGROUND An artificial dermal matrix such as Integra (Integra Life Sciences Corporation, USA) provides a wound bed template for vascular and fibrocyte ingrowth as well as collagen remodelling. Dermal repair leads to epidermal and basement membrane regeneration. Burn wounds in particular have been shown to benefit from Integra by enhanced wound healing. OBJECTIVE To evaluate the effect of fibrin glue to modify the integration of Integra in large excised cutaneous wounds. It was hypothesized that applying fibrin glue on a wound bed would reduce the time needed for matrix vascularization and incorporation of Integra and take of the cultured keratinocytes. METHODS Four separate full-thickness wounds were created on the dorsum of two swine. Wound beds were randomly assigned to either application of fibrin glue or no application of fibrin glue before application of Integra. Full-thickness biopsies were performed at days 7, 14, 21, 29 and 35. On day 21, keratinocytes were applied either as sheets or aerosolized fibrin glue suspension. RESULTS Histological analysis revealed a wave of inflammatory cells and early granulation tissue ingrowth into the Integra from the fascia below on day 7. Only this initial phase was augmented by application of fibrin glue to the wound bed. By day 14, most and by day 21, all of the Integra thickness was incorporated. Accelerated dermal repair proceeded from the base with new collagen deposition in Integra spaces. There was no evidence of keratinocyte engraftment, although re-epithelialization occurred at wound edges extending onto the incorporated Integra. CONCLUSIONS It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension.

Perineal flap reconstruction following oncologic anorectal extirpation: an outcomes assessment.

Background: The poorly healing perineal wound is a significant complication of abdominoperineal resection. The authors examined criteria for immediate flap coverage of the perineum and long-term cross-sectional surgical outcomes. Methods: Patients who underwent abdominoperineal resection or pelvic exenteration for anorectal cancer were retrospectively analyzed. Demographic characteristics, premorbid and oncologic data, surgical treatment, reconstruction method, and recovery were recorded. Outcomes of successful wound healing, surgical complications necessitating intervention (admission or return to the operating room), and progression to chronic wounds were assessed. Results: The authors identified 214 patients who underwent this procedure from 1995 to 2013. Forty-seven patients received pedicled flaps and had higher rates of recurrence and reoperation, active smoking, Crohn disease, human immunodeficiency virus, and anal cancers, and had higher American Joint Committee on Cancer tumor stages. Thirty-day complication rates were equivalent in the two groups. There were no complete flap losses or reconstructive failures. Perineal wound complication rates were marginally but not significantly higher in the flap group (55 percent versus 41 percent; p = 0.088). Infectious complications, readmissions for antibiotics, and operative revision were more frequent in the flap cohort. A larger proportion of the primary closure cohort developed chronic draining perineal wounds (23.3 versus 8.5 percent; p = 0.025). Conclusions: Immediate flap coverage of the perineum was less likely to progress to a chronic draining wound, but had higher local infectious complication rates. The authors attribute this to increased comorbidity in the selected patient population, reflecting the surgical decision making in approaching these high-risk closures and ascertainment bias in diagnosis of infectious complications with multidisciplinary examination. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

The effects of immunosuppressive medications on outcomes in microvascular free tissue transfer.

Background: Reported 10-year patient survival after liver transplantation is nearing 70 percent, with similar trends seen for kidney transplantation. With increasing life expectancy, these patients have an increased need for posttransplant reconstructive surgery. Thus, plastic surgeons must know the effects of immunosuppressive medications on outcomes in microvascular reconstruction. Methods: A retrospective review was performed on all immunosuppressed solid-organ transplant patients who underwent subsequent free tissue transfer of all types, over an 8-year period. Patient demographics, type of solid organ transplant, immunosuppressive regimen, anticoagulation regimen, associated medical comorbidities, and complication rates were analyzed. Results: Twenty-four microvascular free tissue transfers were performed over an 8-year period on immunosuppressed patients, for head and neck and lower extremity reconstruction. Fifteen patients (63 percent) underwent prior kidney transplant, seven (29 percent) underwent prior liver transplant, and two (8 percent) underwent prior lung transplant. Prednisone (79 percent of patients), cyclosporine (33 percent), and tacrolimus (33 percent) were the most commonly used immunosuppressive medications. Complications included one total flap loss (4 percent), three intraoperative arterial thromboses (13 percent), and two postoperative venous thromboses (8 percent). Univariate analysis illustrated a statistically significant association between prednisone and overall complication rate (p = 0.032). Conclusions: Microvascular free tissue transfer is a challenge in immunosuppressed patients. Univariate analysis showed prednisone to correlate statistically with operative morbidity. Transplant patients receiving prednisone at the time of their elective free flap procedure will require additional care to lower the additional risk of delayed wound healing, partial flap loss, and anastomotic thrombosis. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic IV.

Mirror-image Trigger Thumb in Dichorionic Identical Twins

The congenital vs acquired etiology of pediatric trigger thumb is the subject of considerable debate. Existing case reports of bilateral presentation in identical twins and first-degree familial association support the congenital hypothesis. However, prospective studies have yet to report a neonate presenting with this anomaly at birth. This article describes the first known set of dichorionic, monozygotic identical twins with unilateral trigger thumbs, affecting contralateral (mirror-image) hands and with asynchronous age at presentation (11 months and 18 months, respectively).Pediatric trigger thumb is caused by a mismatch between the flexor pollicis longus tendon and its A1 synovial pulley. Four sets of twins have been previously reported in the literature with trigger thumb. Of these, 3 sets were monozygotic twins who had bilaterally affected thumbs. Together with the absence of trauma, a congenital etiology was suggested. The fact that pediatric trigger thumb is generally seen several months after birth was felt to be due to infants holding their thumbs clutched in their palms until 6 months. However, no confirmed cases of trigger thumb have been diagnosed at birth in several large prospective studies of newborns.In the current case, the asynchronous presentation of unilateral trigger thumbs in identical twins does not support a solely congenital cause. Furthermore, the mirror-image presentation contradicts current embryological understanding of the temporal course of twinning and the determination of laterality. Thus, a multifactorial etiology is supported with both a genetic and acquired component affecting the development of this condition.

Atypical fibroxanthoma in a young woman: An unusual case presentation

Atypical fibroxanthoma (AFX) is an uncommon neoplasm, identified as a spindle cell tumour that is generally found in elderly patients on sun-exposed areas. The majority of cases of AFX are benign, and metastasis is a rare phenomenon. The first case in the literature of AFX is described in a young woman with no previous risk factors who presented with a three-month history of an enlarging nodule of the left nasal alar. Excision showed the lesion to be composed of hyperchromatic, pleomorphic, vacuolated spindle cells and multinucleated giant cells. The tumour cells stained positive for macrophage-histiocyte antigen alpha(1)-antitrypsin, neurokinin-1, CD68 and alpha(1)-antichymotrypsin. The present case report highlights the importance of correct diagnosis for AFX with adequate excision and by considering the histopathology and immunohisto-chemistry of its clinical differential diagnosis.

Human Satellite Cell Isolation and Xenotransplantation

Satellite cells are mononucleated cells of the skeletal muscle lineage that exist beneath the basal lamina juxtaposed to the sarcolemma of skeletal muscle fibers. It is widely accepted that satellite cells mediate skeletal muscle regeneration. Within the satellite cell pool of adult muscle are skeletal muscle stem cells (MuSCs), also called satellite stem cells, which fulfill criteria of tissue stem cells: They proliferate and their progeny either occupies the adult MuSC niche during self-renewal or differentiates to regenerate mature muscle fibers. Here, we describe robust methods for the isolation of enriched populations of human satellite cells containing MuSCs from fresh human muscle, utilizing mechanical and enzymatic dissociation and purification by fluorescence-activated cell sorting. We also describe a process for xenotransplantation of human satellite cells into mouse muscle by injection into irradiated, immunodeficient, mouse leg muscle with concurrent notexin or bupivacaine muscle injury to increase engraftment efficiency. The engraftment of human MuSCs and the formation of human muscle can then be analyzed by histological and immunofluorescence staining, or subjected to in vivo experimentation.

Abstract: Cryptotia Correction Using Double Opposing Interpositional Advancement Flaps

Suday, O cber 8, 2017 METHODS: A systematic literature review of the National Library of Medicine (PubMed) database was performed by two independent reviewers. English and French-language studies involving the outcomes of autologous fat grafting to correct contour defects of the face were included. Extracted data included patient demographics, harvest and injection sites, graft harvesting and injection technique, mean injected volume, retained volume percentage, and complications.