Ines C. Lin

Trends in immediate breast reconstruction across insurance groups after enactment of breast cancer legislation.

To improve access to breast reconstruction for mastectomy patients, the United States enacted the Womens Health and Cancer Rights Act in January of 1999. The objective of the current study was to evaluate the impact of this legislation on patients with different insurance plans.

Dihydrotestosterone stimulates proliferation and differentiation of fetal calvarial osteoblasts and dural cells and induces cranial suture fusion.

Background: The higher prevalence of metopic and sagittal suture synostosis in male infants suggests a role for androgens in early craniofacial development. These experiments characterize the influence of androgen stimulation on growth and differentiation of fetal dural and calvarial bone cells and on cranial suture fusion. Methods: Primary murine fetal (E18) dural cells and calvarial osteoblasts were isolated and cultured. Cells were treated for 48 hours with 5&agr;-dihydrotestosterone (0 to 1000 nM). Cell proliferation was examined by nonradioactive proliferation assay; mRNA expression of alkaline phosphatase, transforming growth factor (TGF)-&bgr;1, and the bone matrix proteins osteopontin, osteocalcin, and type 1 collagen was determined by reverse-transcriptase polymerase chain reaction. In separate experiments, intact fetal calvariae were grown in tissue culture with 10 nM 5&agr;-dihydrotestosterone for 7 and 14 days and then examined histologically. Results: Androgen stimulation at 5 nM increased proliferation of fetal dural cells by 46.0 percent and of fetal calvarial osteoblasts by 20.5 percent. Dural expression of osteopontin, osteocalcin, and type 1 collagen was enhanced by 5&agr;-dihydrotestosterone, as was that of TGF-&bgr;1 and alkaline phosphatase. Androgen stimulation increased calvarial osteoblast expression of alkaline phosphatase and TGF-&bgr;1 but induced little change in expression of osteocalcin, osteopontin, and type 1 collagen. In tissue culture, 5&agr;-dihydrotestosterone stimulated osteoid formation and fusion of sagittal sutures. Conclusions: Androgen stimulation of dural cells and osteoblasts isolated from fetal calvaria promotes cell proliferation and osteoblastic differentiation and can induce cranial suture fusion. These results suggest that sex steroid hormone signaling may stimulate sutural osteogenesis by means of osteodifferentiation of dural cells, thus explaining the male prevalence of nonsyndromic craniosynostosis.

Nitric oxide stimulates proliferation and differentiation of fetal calvarial osteoblasts and dural cells.

Background: Infant dura mater plays a critical role in calvarial development. This investigation examines the expression of nitric oxide synthase isoforms in the craniofacial skeleton and the influence of nitric oxide signaling on the growth and differentiation of fetal dural and calvarial bone cells. Methods: Sections of fetal and adult calvaria were evaluated for endothelial and inducible nitric oxide synthase expression by immunohistochemistry. Primary fetal (E18) murine dural cell and calvarial osteoblast cultures were treated with 1 &mgr;M or 10 &mgr;M DETA-NONOate, a nitric oxide donor compound, or 1 mM NG-monomethyl-l-arginine (l-NMMA), a nitric oxide synthase inhibitor. Controls were left untreated. Cell proliferation was measured at 48 hours, and mRNA transcripts for Runx2, alkaline phosphatase, and osteopontin were measured by reverse transcription and quantitative real-time polymerase chain reaction at 2 to 18 days. Experiments were performed in triplicate. Results: Fetal, but not adult, dural cells express endothelial nitric oxide synthase. DETA-NONOate stimulated osteoblast mitogenesis by 16 percent (p < 0.05) but did not affect proliferation of dural cells. l-NMMA inhibited proliferation of dural cells and calvarial osteoblasts by 35 percent (p < 0.01) and 17 percent (p = 0.05), respectively. Exogenous nitric oxide increased dural cell transcription of Runx2, alkaline phosphatase (p = 0.03), and osteopontin (p = 0.09) and calvarial osteoblast transcription of Runx2 (p = 0.02) and osteopontin (p < 0.01). Fetal calvarial osteoblasts and dural cells treated with l-NMMA demonstrated reduced transcription of Runx2 and alkaline phosphatase (p < 0.05). Conclusions: Fetal dural cells and calvarial osteoblasts express endothelial nitric oxide synthase. Nitric oxide enhances proliferation and differentiation of fetal dural cells and calvarial osteoblasts. These results suggest that endothelial nitric oxide synthase–derived nitric oxide may play an important role in development of the fetal craniofacial skeleton.

Gender Authorship Trends of Plastic Surgery Research in the United States.

BACKGROUND An increasing number of women are entering the medical profession, but plastic surgery remains a male-dominated profession, especially within academia. As academic aspirations and advancement depend largely on research productivity, the authors assessed the number of articles authored by women published in the journal Plastic and Reconstructive Surgery. METHODS Original articles in Plastic and Reconstructive Surgery published during the years 1970, 1980, 1990, 2000, 2004, and 2014 were analyzed. First and senior authors with an M.D. degree and U.S. institutional affiliation were categorized by gender. Authorship trends were compared with those from other specialties. Findings were placed in the context of gender trends among plastic surgery residents in the United States. RESULTS The percentage of female authors in Plastic and Reconstructive Surgery increased from 2.4 percent in 1970 to 13.3 percent in 2014. Over the same time period, the percentage of female plastic surgery residents increased from 2.6 percent to 32.5 percent. By 2014, there were more female first authors (19.1 percent) than senior authors (7.7 percent) (p < 0.001). As a field, plastic surgery had fewer female authors than other medical specialties including pediatrics, obstetrics and gynecology, general surgery, internal medicine, and radiation oncology (p < 0.05). CONCLUSIONS The increase in representation of female authors in plastic surgery is encouraging but lags behind advances in other specialties. Understanding reasons for these trends may help improve gender equity in academic plastic surgery.

Immunolocalization of androgen receptor in the developing craniofacial skeleton.

Male predominance in metopic and sagittal craniosynostosis and in nonsynostotic plagiocephaly suggests a role for circulating androgens in early craniofacial development. Androgens have been documented to play an important role in postnatal skeletal growth, and the androgen receptor has been recently demonstrated in human and rat osteoblast-like cell lines and in human long bones. The purpose of this study was to describe the expression of androgen receptor in the fetal craniofacial skeleton. The heads of E18 fetal CD-1 male and female mice were fixed in 10% formalin, decalcified, and embedded in paraffin. Four- to 6-μm coronal and sagittal sections were stained with a monoclonal antibody specific to androgen receptor, which was detected by an avidinbiotin conjugate and peroxidase system. The sections were then examined for androgen receptor expression patterns. Strong androgen receptor immunoreactivity was observed in the dura mater of developing fetuses. Androgen receptor expression was also noted in cells lining the osteogenic fronts and in calvarial osteoblasts. Similar androgen receptor expression patterns were found in male and female mice. Androgen receptor is abundantly expressed in fetal dura mater and calvarial bone. This study confirms the presence of androgen receptor in the murine fetal craniofacial skeleton, suggesting a potential role for the anabolic effects of androgens in the developing craniofacial skeleton.

18-month outcomes of heterologous bilateral hand transplantation in a child: a case report

BACKGROUND Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant. METHODS 2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation. FINDINGS The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation. INTERPRETATION Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation. FUNDING The Childrens Hospital of Philadelphia.

Management of the ptotic or hypertrophic breast in immediate autologous breast reconstruction: a comparison between the wise and vertical reduction patterns for mastectomy.

Background The Wise pattern can be used in mastectomies to address the excess skin in the ptotic or hypertrophic breast; however, limitations include mastectomy flap necrosis (MFN) and poor shape. The vertical pattern can potentially reduce the amount of MFN with improved aesthetic results. This study compares the Wise and vertical mastectomy patterns in immediate, autologous breast reconstruction. Methods Thirty-three patients with grade 2 or 3 ptosis who elected to undergo immediate, autologous breast reconstruction were prospectively recruited into 2 nonrandomized cohorts. Of total, 17 patients (26 reconstructions) had Wise pattern and 16 (28 reconstructions) had vertical pattern. All patients were followed for MFN, time for wound healing, and postoperative complications. Patient and surgeon surveys rated the aesthetics of the reconstructions. Results The 2 groups did not differ in age, body mass index, smoking, or breast measurements. The Wise group had significantly larger areas of MFN, higher number of postoperative visits, and longer wound-healing periods, compared with the vertical group (P < 0.05). There was no difference in time to adjuvant therapy or additional procedures. Patient surveys rated both incisions with equal satisfaction, except for symmetry that rated better in the Wise group. Surgeon surveys showed better scores for the vertical incision. Conclusions The Wise pattern is associated with significantly more MFN and prolonged wound care. Despite this complication, patients rate their breast reconstructions favorably, regardless of the type of incision. Both the Wise and vertical patterns can be safely used in skin-sparing mastectomies with immediate, autologous breast reconstruction with good aesthetic outcomes. The authors recommend the vertical pattern because of less MFN and surgeon-preferred aesthetics.

Geographic Trends in the Plastic Surgery Match

BACKGROUND The integrated plastic surgery match is among the most competitive residency matches in recent years. Although previous studies have correlated applicant characteristics with successful match outcomes, none have comprehensively investigated the role of geography in the match. This study elucidates regional biases in the match. METHODS Plastic surgery residents who matched during 2011-2015 were eligible for study inclusion. Names of residents were obtained from official residency program websites and cross-referenced with data obtained from the Student Doctor Network. For each resident, region of residency program and medical school were compared. RESULTS From 67 programs, 622 residents were identified. Most graduated from US medical schools (97.9%). A total of 94 residents matched at a home institution (15.1%). Half of the residents matched in the same region as their medical school (48.9%). Programs in the South matched the greatest number of residents from the same region (60.8%), whereas West programs matched the least (30.8%, p < 0.001). No regional differences existed regarding residents matching at their home institution (p = 0.268). More women matched at West programs (43.1%) versus East programs (30.6%, p < 0.05). CONCLUSIONS A significant number of residents matched at their home institution. Roughly, half matched at a program in the same region as their medical school. Whether this regional phenomenon stems from applicant or program factors remains unknown. Yet, given the limited number of interviews and the high costs of interviewing, applicants and programs can use these data to help optimize the match process.

Timing of forearm arterial repair in the well-perfused limb.

The purpose of this study was to evaluate the difference in the outcomes of patients with a well-perfused hand who were taken to the operating room (OR) within 6 hours of forearm arterial injury vs patients who were treated in a semiurgent fashion. A review of 201 consecutive patients who were taken to the OR with forearm-level radial or ulnar arterial injury identified 26 patients who had a well-perfused hand at presentation in whom hemostasis was achieved within 15 minutes with manual pressure and no signs of hemodynamic instability. Outcomes of interest included short-version Disabilities of the Arm, Shoulder and Hand (quickDASH) scores and patient-reported cold intolerance. Of the 26 patients, group 1 included 17 patients who were taken to the OR within 6 hours and group 2 included 9 patients who were taken to the OR in a delayed fashion. Minimum follow-up in both groups was 13 months. Average quickDASH score was 24.5 and 14.1 for groups 1 and 2, respectively. Average time spent in the OR was significantly less in group 2 compared with group 1 (1.7 vs 2.8 hours). In the setting of forearm arterial injury with a well-perfused distal limb, there was no difference in functional outcome in patients taken to the OR emergently compared with those who underwent surgery in a delayed manner. With careful evaluation and monitoring, semiurgent operative repair is feasible and may improve certain aspects of patient care and hospital resource use. Outcome measures in this study support semiurgent treatment of these injuries.

Intermittent hydrostatic compression promotes nitric oxide production and osteodifferentiation of fetal dural cells

Purpose:The aim of these studies was to evaluate the biologic response of fetal dural cell cultures to compressive mechanical force. Methods:Primary cell cultures from the dura mater of E18 CD-1 mice were subjected to 2 PSI of intermittent hydrostatic compression (IHC) at a frequency of 0.5 Hz. Quantitative measures of the expression of Osterix (Osx), osteopontin (OP), endothelial nitric oxide synthase (eNOS) and Noggin were performed by RT-PCR following 3, 6, and 12 hours of exposure to IHC. Nitric oxide production was quantified through the measurement of NO metabolites following 6 hours of exposure to IHC. Results:IHC resulted in an increase in Osx, OP, and eNOS expression compared with controls at all time points. The expression of Noggin decreased at all time points. Exposure to IHC resulted in a significant increase in the production of NO metabolites at 6 hours when compared with controls. Conclusions:These experiments indicate that dural cell biology is significantly altered following exposure to IHC. Specifically, IHC promotes production of NO and osteodifferentiation in fetal dural cell cultures, with increases in the expression of osteoinductive genes and decreases in inhibitors of osteogenesis.