Lymphatic regeneration after implantation of aligned nanofibrillar collagen scaffolds: Preliminary preclinical and clinical results.

BACKGROUND: We tested our hypothesis that implantation of aligned nanofibrillar collagen scaffolds (BioBridge™) can both prevent and reduce established lymphedema in the rat lymphedema model. Our authors report clinical cases that demonstrate new lymphatic formation guided by BioBridge™ as seen by near-infrared (NIR) fluoroscopy and magnetic resonance (MR) lymphography. METHODS: A rat lymphedema model was utilized. A prevention group received implantation of BioBridge™ immediately after lymphadenectomy. A lymphedema group received implantation of BioBridge™ with autologous adipose-derived stem cells (ADSC; treatment group) or remained untreated (control group). All subjects were observed for 4 months after lymphadenectomy. The hindlimb change was evaluated using computed tomography-based volumetric analysis. Lymphagiogenesis was assessed by indocyanine green (ICG) lymphography. RESULTS: Animals in the treatment group showed a reduction in affected limb volume. Animals in the prevention group showed no increase in the affected limb volume. ICG fluoroscopy demonstrated lymph flow and formation of lymphatics toward healthy lymphatics. CONCLUSIONS: In the rat lymphedema model, implantation of BioBridge™ at the time of lymph node removal prevents the development of lymphedema. Treatment of established lymphedema with the BioBridge™ and ADSC reduces lymphedema. New lymphatic vessels are demonstrated by NIR fluoroscopy and MR lymphography. These findings have implications for the treatment of lymphedema in human subjects.

Aesthetic Science of Rhinoplasty: Three Principles.

Aesthetic science is a rapidly growing discipline that involves plastic surgery as much or more than other disciplines of science. Fortunately, how and why the human brain responds to the visual world is better understood now than ever before. Of necessity plastic surgery is a part of that aesthetic science movement because it deals directly with the application of aesthetic principles. Therefore, it behooves the surgeon to be familiar with the principles of aesthetic science so as to both delineate and attain the aesthetic goal at the same time any functional goal is part of the operation. There are three important principles for rhinoplasty: (1) symmetry, (2) continuity and (3) persistence. This study provides examples of how they apply in the preop, intraop and postop phase of performing aesthetic rhinoplasty. A firm understanding of these principles can then guide the surgeon through the difficult maze of decision making, operative planning and surgical execution that arguably makes aesthetic rhinoplasty the most difficult aesthetic operation in plastic surgery. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Surgical Team Trips to Vietnam: Implementation of a Dedicated Cleft Palate Perioperative Program Improves Fistula Rates.

BACKGROUND: ReSurge International is a nongovernmental organization that organizes surgical team trips to low- and middle-income countries. Cleft palate repair is commonly performed on these trips. A comprehensive cleft care program was implemented to help reduce postoperative palatal fistula rates. METHODS: A retrospective review of all patients undergoing cleft palate repair surgery with ReSurge International in Vietnam from 2013 through 2019 was performed. The cleft care program was implemented in 2018. This intervention involved preoperative education of patients and close postoperative monitoring. Critically, this program also provided closer access to providers. Subsequent follow-up was performed by a ReSurge physician. Parent-reported outcomes were assessed preoperatively and postoperatively using 5-point Likert-like survey questions. RESULTS: Two hundred three patients underwent cleft palate repair. The patients were older and of higher Veau classification than is usually seen in the United States. The palatal fistula rate in the preintervention group was 37.5% and 14.3% in the intervention group (P = 0.014). Patients without fistulas demonstrated improvements on parent-reported outcomes compared with those with fistulas, with food less likely to go up their nose (P < 0.001), less difficulty eating (P < 0.001), and more understandable speech (P = 0.015). CONCLUSIONS: Implementation of a comprehensive cleft palate program reduced postoperative fistula rates by more than 50%. Improvements in parent-reported outcomes were observed after surgery among patients without fistulas. The blueprint for improved outcomes in these more complex patients includes enhanced perioperative patient counseling, close follow-up, and maintenance of communication with patients.

The versatile free medial sural artery perforator flap: An institutional experience for reconstruction of the head and neck, upper and lower extremities.

BACKGROUND: The medial sural artery perforator (MSAP) flap is an increasingly versatile and reliable flap for soft tissue reconstruction. This study investigates complication rates and long-term outcomes of the MSAP flap. METHODS: A retrospective review was performed on consecutive patients undergoing MSAP flap reconstruction at Chang Gung Memorial Hospital from 2006 through 2017. Patient demographics were assessed. Flap failure and wound complications were the outcome measures. RESULTS: In the cohort of 246 patients that underwent a total of 248 MSAP flap reconstructions were identified. The average age was 47.5 years (range 15-76). Of the 248 flaps, 170 were used for reconstruction of the head and neck, 48 for upper extremity reconstruction, and 30 for lower extremity reconstruction. The average MSAP flap size was 5.2 × 11.8 cm. 31 (12.5%) of the flaps developed arterial occlusion, venous insufficiency, or a hematoma postoperatively requiring re-exploration. Nineteen were successfully salvaged, yielding an overall failure rate of 4.8%. Minor complications included the need for flap debridement in 18 cases (7.3%) and need for donor site debridement in eight cases (3.2%). CONCLUSIONS: The MSAP flap can be used in a versatile fashion to reconstruct defects of the head and neck, upper extremity, and lower extremity with minimal complication rates.

Microsurgical Reconstruction of the Smile: A Critical Analysis of Outcomes.

BACKGROUND: Facial paralysis is a significant problem with functional, psychological, and esthetic consequences. Free muscle transfer for reanimation of the smile has been established as the preferred reconstructive method. However, little has been reported on the complications after this procedure. We sought to perform a critical analysis of these complications and their ultimate outcomes. METHODS: A retrospective review was performed on consecutive patients undergoing microsurgical reconstruction of the smile by the senior author from 2013 through 2017. Patient demographics including age, race, body mass index, and medical comorbidities were recorded. The cause of facial palsy and type of microsurgical reconstruction were assessed. Patient outcomes including complications and management of the complication were analyzed. All statistical analyses were performed using nonparametric analyses. RESULTS: We identified 17 patients who underwent microsurgical reconstruction of the smile, with 1 patient undergoing bilateral procedures, for a total of 18 microsurgical smile reanimation procedures performed. Sixteen of these were 1-stage reconstructions with the coaptation of the nerve to the masseter, whereas 2 were 2-stage reconstructions using cross-facial nerve grafts. The gracilis muscle was used as the donor muscle in all cases. The patients had a median age of 26.5 and a median follow-up of 1.04 years from surgery. There were no major early complications observed in our cohort. Eight (44.4%) reanimations developed a minor complication that required subsequent reoperation. The reoperations were performed at a median of 0.97 years after the microsurgical procedure. The most common indication for reoperation was lateral retraction of the insertion of the transplanted muscle, which occurred in 5 (62.5%) patients. One patient underwent surgical exploration for an abrupt loss of transplanted muscle function after trauma to the cheek. Another patient had less than expected transplanted muscle activity at 1 year postoperatively and underwent exploration of the cross-facial nerve graft and a neurorrhaphy revision. Lastly, 1 patient developed significant rhytids over the transplanted muscle secondary to tethering of the skin to the underlying muscle. This patient underwent 2 subsequent revisions, with placement of acellular dermal matrix between the muscle and skin and fat grafting. All patients had functional animation of the transplanted muscle postoperatively. CONCLUSIONS: Complications occurred in 44.4% of patients undergoing microsurgical reanimation of the smile. Most complications were minor in nature and were readily addressed with advancement of the transplanted muscle. All patients in our series had muscle function after the muscle transplantation.

Cost-Effectiveness Analysis of Humanitarian Hand Surgery Trips According to WHO-CHOICE Thresholds.

PURPOSE: Hand surgery outreach programs to low- and middle-income countries (LMICs) provide much-needed surgical care to the underserved populations and education to local providers for improved care. The cost-effectiveness of these surgical trips has not been studied despite a long history of such efforts. This study aimed to examine the economic impact of hand surgery trips to LMICs using data from the Touching Hands Project and ReSurge International. We hypothesized that hand surgery outreach would be cost-effective in LMICs. METHODS: We analyzed data on the cost of each trip and the surgical procedures performed. Using methods from the World Health Organization (WHO-Choosing Interventions That Are Cost-Effective [WHO-CHOICE]), we determined whether the procedures performed during the outreach trips would be cost-effective. RESULTS: For the 14 hand surgery trips, 378 patients received surgical treatment. Trips varied in the country where interventions were provided, the number of patients served, the severity of the conditions, and the total cost. The cost per disability-adjusted life-year averted ranged from United States (US)$222 to $1,525, all of which were very cost-effective according to WHO-CHOICE thresholds. The cost-effectiveness of global hand surgery was comparable to that of other medical interventions such as multidrug-resistant tuberculosis treatment in similar regions. We also identified a lack of standardized record keeping for these surgical trips. CONCLUSIONS: Hand surgeries performed in LMICs are cost-effective based on WHO-CHOICE criteria. However, a standardized record-keeping method is needed for future research and longitudinal comparison. Understanding the economic impact of hand surgery global outreach is important to the success and sustainability of these efforts, both to allocate resources effectively and to identify areas for improvement. TYPE OF STUDY/LEVEL OF EVIDENCE: Economic/Decision Analysis III.

Mastectomy Skin Necrosis After Breast Reconstruction: A Comparative Analysis Between Autologous Reconstruction and Implant-Based Reconstruction.

BACKGROUND: Mastectomy skin necrosis is a significant problem after breast reconstruction. We sought to perform a comparative analysis on this complication between patients undergoing autologous breast reconstruction and patients undergoing 2-stage expander implant breast reconstruction. METHODS: A retrospective review was performed on consecutive patients undergoing autologous breast reconstruction or 2-stage expander implant breast reconstruction by the senior author from 2006 through 2015. Patient demographic factors including age, body mass index, history of diabetes, history of smoking, and history of radiation to the breast were collected. Our primary outcome measure was mastectomy skin necrosis. Fisher exact test was used for statistical analysis between the 2 patient cohorts. The treatment patterns of mastectomy skin necrosis were then analyzed. RESULTS: We identified 204 patients who underwent autologous breast reconstruction and 293 patients who underwent 2-stage expander implant breast reconstruction. Patients undergoing autologous breast reconstruction were older, heavier, more likely to have diabetes, and more likely to have had prior radiation to the breast compared with patients undergoing implant-based reconstruction. The incidence of mastectomy skin necrosis was 30.4% of patients in the autologous group compared with only 10.6% of patients in the tissue expander group (P < 0.001). The treatment of this complication differed between these 2 patient groups. In general, those with autologous reconstructions were treated with more conservative means. Although 37.1% of patients were treated successfully with local wound care in the autologous group, only 3.2% were treated with local wound care in the tissue expander group (P < 0.001). Less than half (29.0%) of patients in the autologous group were treated with an operative intervention for this complication compared with 41.9% in the implant-based group (P = 0.25). CONCLUSIONS: Mastectomy skin necrosis is significantly more likely to occur after autologous breast reconstruction compared with 2-stage expander implant-based breast reconstruction. Patients with autologous reconstructions are more readily treated with local wound care compared with patients with tissue expanders, who tended to require operative treatment of this complication. Patients considering breast reconstruction should be counseled appropriately regarding the differences in incidence and management of mastectomy skin necrosis between the reconstructive options.

Complications After Two-Stage Expander Implant Breast Reconstruction Requiring Reoperation: A Critical Analysis of Outcomes.

BACKGROUND: Two-stage expander implant breast reconstruction is commonly performed after mastectomy. Salvage and long-term outcomes after development of complications have not been well described. We examined a single surgeon's experience to study the rate of reoperation secondary to complications after first-stage expander placement and to evaluate their outcomes. Better understanding of salvage techniques may help guide future management. METHODS: We performed a retrospective analysis of consecutive patients who underwent placement of a tissue expander (TE) for breast reconstruction between December 2006 and August 2015 with the senior author. Patient demographics including age, body mass index, medical comorbidities, history of smoking, and history of radiation to the breast were collected. Surgical factors including timing of reconstruction (immediate vs delayed) and location of TE (total submuscular vs with acellular dermal matrix) were recorded. Complications were analyzed, as were patients who underwent reoperation in the setting of developing a complication. RESULTS: We analyzed 282 patients who underwent 453 implant-based breast reconstructions. Of these, 39 patients and 45 breasts required a reoperation after development of a postoperative complication. Return to the operating room was associated with higher body mass index (29 vs 24, P < 0.001), higher TE initial fill volume (299 mL vs 169 mL, P < 0.001), and preoperative radiation (31% vs 13%, P = 0.001). Complications resulting in reoperation included infection (60%), mastectomy skin necrosis (27%), and TE extrusion through thin mastectomy skin (11%). The affected TE was removed and exchanged in 17 patients (38%), autologous flap reconstruction occurred in 16 patients (36%), and TE was explanted without replacement in 12 patients (27%). CONCLUSIONS: Infectious complications including cellulitis and abscess formation accounted for most cases requiring reoperation after TE placement for breast reconstruction. More than a quarter of patients who underwent a reoperation ultimately lost their implants. Patients undergoing two-stage expander implant breast reconstruction should be appropriately counseled regarding the possibility of requiring a reoperation in the setting of developing a complication.

The ReSurge Global Training Program: A Model for Surgical Training and Capacity Building in Global Reconstructive Surgery.

BACKGROUND: A paradigm shift is underway in the world of humanitarian global surgery to address the large unmet need for reconstructive surgical services in low- and middle-income countries (LMICs). Here, we discuss the ReSurge Global Training Program (RGTP), a model for surgical training and capacity building in reconstructive surgery in the developing world. The program includes an online reconstructive surgery curriculum, visiting educator trips, expert reconstructive surgeon involvement, trainee competency tracking system, and identification of local outreach partners to provide safe reconstructive surgery to the neediest of patients in the developing world. METHODS: A retrospective review of the components of the RGTP from July 2014 through June 2017 was performed. Trainee milestones scores were analyzed to observe trends toward competency in specific plastic surgery skill sets. RESULTS: There were a total of 38 visiting educator trips during the study period. The trips took place in 10 LMICs. A total of 149 trainees were evaluated in the context of the visiting educator trips with 377 distinct submodule evaluations. Four trainees had more than 10 submodule evaluations over 2 or more visiting educator trips. There was notable improvement in milestones ratings over time among the trainees in this program. CONCLUSIONS: The RGTP is a model of reconstructive surgical training and capacity building in LMICs. Trainees develop important skill sets in reconstructive surgery as a result of their involvement in the program. This comprehensive training approach addresses the disparity in access to care in the developing world by providing short- and long-term solutions to unmet reconstructive needs.

Practical Applications of Delayed-Immediate Autologous Breast Reconstruction: A Flexible and Safe Operative Strategy.

BACKGROUND: Timing is an important consideration in patients undergoing mastectomy for breast cancer. While immediate reconstruction results in superior aesthetic outcomes, the need for postmastectomy radiation can often only be ascertained after review of surgical pathology. Delayed-immediate autologous reconstruction (DIAR) is a reconstructive approach that consists of mastectomy with tissue expander placement in the first stage and flap-based breast reconstruction in the second stage. We describe our institution's experience with DIAR to characterize the reasons in which patients opt for this reconstructive approach and analyze its ultimate outcomes. METHODS: We conducted an institutional review board-approved retrospective chart review of all consecutive patients undergoing DIAR performed by the senior author from 2007 to 2016. Data gathered included demographics, operative techniques, and postoperative outcomes. RESULTS: In our study, 17 patients and 26 breasts underwent DIAR. Seven patients initially planned for and eventually underwent DIAR. Ten patients initially planned for implant-based reconstructions but ultimately underwent DIAR instead. Flap types included deep inferior epigastric perforator (n = 6), superficial inferior epigastric artery (n = 2), and muscle-sparing free transverse rectus abdominis myocutaneous (n = 18). The mean time between mastectomy and reconstruction was 208 days. Complications included tissue expander infection, vascular compromise, abscess formation, hematoma, and skin necrosis. CONCLUSIONS: The delayed-immediate approach allows for breast reconstruction with aesthetic and psychosocial benefits, while enabling postmastectomy radiation in patients with advanced disease. We describe modifications to DIAR, including use of a flap skin paddle and prolonged time between stages, which allow for broader applicability. We show that DIAR accommodates a range of patient preferences with few complications.

Analysis of Aesthetic Outcomes and Patient Satisfaction After Delayed-Immediate Autologous Breast Reconstruction.

BACKGROUND: Patients with breast cancer frequently opt to undergo breast reconstruction after mastectomy. The timing and aesthetic outcome of the breast reconstruction may be affected by the need for radiation therapy (RT). Delayed-immediate autologous reconstruction (DIAR) is a novel surgical approach for patients in whom the need for adjuvant RT after mastectomy is preoperatively unknown. AIM: We sought to evaluate the difference in clinical outcomes, patient satisfaction, and cosmetic results between DIAR and patients who underwent delayed autologous reconstruction. MATERIALS AND METHODS: A total of 19 DIAR and 19 delayed patients were retrospectively included.Patient demographics, surgical characteristics, and complications were obtained from patient files. Patients scored their satisfaction using the breast-Q questionnaire, and independent reviewers scored cosmetic outcomes, including skin quality/color, scar formation, symmetry, breast contour/size/position, and overall aesthetic outcome. The DIAR patients were matched to delayed patients based on age, body mass index, and unilateral or bilateral reconstruction. RESULTS: The median age in the delayed group was 48 years (range, 31-61 years) and 46 years (range, 29-64 years) in the DIAR group, with a median body mass index of 28.8 (range, 21.4-40.5) and 28.6 (range, 24-1.9), respectively.There were no significant differences in demographics between the two groups. In total, 16 patients underwent unilateral reconstruction and 22 patients bilateral reconstruction. Delayed-immediate autologous reconstruction was associated with a higher infection rate compared with delayed reconstruction, 8 and 1, respectively (P = 0.026). All infections in the DIAR group were tissue expander-related. The DIAR patients had significantly better breast contour/size/position and overall aesthetics compared with the delayed reconstruction group (P = 0.001). In addition, patients who did not receive RT had significant better cosmetic outcome (P < 0.001). There were no significant differences in patient satisfaction between the DIAR and delayed group. CONCLUSION: Delayed-immediate autologous reconstruction should be considered as an option for patients wanting autologous reconstruction when the need for RT remains unknown. Delayed-immediate autologous reconstruction demonstrates better breast contour/size/position and overall aesthetic outcome.

Leptin Is Produced by Parathyroid Glands and Stimulates Parathyroid Hormone Secretion.

OBJECTIVE: We asked if leptin and its cognate receptor were present in normal and diseased parathyroid glands, and if so, whether they had any functional effects on parathyroid hormone (PTH) secretion in parathyroid neoplasms. BACKGROUND: The parathyroid glands acting through PTH play a critical role in the regulation of serum calcium. Based on leptin's recently discovered role in bone metabolism, we hypothesized these glands were the sites of a functional interaction between these 2 hormones. METHODS: From July 2010 to July 2011, 96 patients were enrolled in a prospective study of leptin and hyperparathyroidism, all of whom were enrolled based on their diagnosis of hyperparathyroidism, and their candidacy for surgical intervention provided informed consent. Immediately after parathyroidectomy, 100 to 300 mg of adenomatous or hyperplastic diseased parathyroid tissue was prepared and processed according to requirements of the following: in situ hybridization, immunohistochemistry, immunofluorescence by conventional and spinning disc confocal microscopy, electron microscopy, parathyroid culture, whole organ explant, and animal model assays. RESULTS: Leptin, leptin receptor (long isoform), and PTH mRNA transcripts and protein were detected in an overlapping fashion in parathyroid chief cells in adenoma and hyperplastic glands, and also in normal parathyroid by in situ hybridization, qRT-PCR, and immunohistochemistry. Confocal microscopy confirmed active exogenous leptin uptake in cultured parathyroid cells. PTH secretion in explants increased in response to leptin and decreased with leptin receptor signaling inhibition by AG490, a JAK2/STAT3 inhibitor. Ob/ob mice injected with mouse leptin exhibited increased PTH levels from baseline. CONCLUSIONS: Taken together, these data suggest that leptin is a functionally active product of the parathyroid glands and stimulates PTH release.

Management of Mastectomy Skin Necrosis in Implant Based Breast Reconstruction.

BACKGROUND: Mastectomy skin necrosis is a significant problem after breast reconstruction. This complication may lead to poor wound healing and need for implant removal, which may delay subsequent oncologic treatment. We sought to characterize factors associated with mastectomy skin necrosis and propose a management algorithm. METHODS: A retrospective review was performed on consecutive patients undergoing implant-based breast reconstruction by the senior author from 2006 through 2015. Patient-level factors including age, race, body mass index, history of hypertension, history of diabetes, history of smoking, and history of radiation were collected. Surgical factors including type of mastectomy, location of implant placement, and immediate versus delayed reconstruction were collected. The incidence and treatment of mastectomy skin necrosis were analyzed. RESULTS: A total of 293 patients underwent either unilateral or bilateral implant-based breast reconstructions after mastectomy with a total of 471 reconstructed breasts. Mastectomy skin necrosis was observed in 8.1% of reconstructed breasts. Skin necrosis was not associated with age, hypertension, diabetes, prior radiation, or type of mastectomy. The incidence of skin necrosis was higher among smokers (17.9% vs 5.0%, P < 0.001), among patients with higher body mass index (11.4% vs 6.1%, P = 0.05), patients who underwent immediate reconstruction compared to delayed (9.6% vs 0%, P = 0.004), placement of expander under acellular dermal matrix compared with submuscular placement (12.0% vs 5.2%, P = 0.02), and use of higher initial expander fill volume compared with lower fill volume (11.4% vs 5.4%, P = 0.02).The median necrosis size was 8 cm. The median time to treatment was 15 days postoperatively. In 55% of patients minor necrosis was treated with clinic debridement, whereas 43% had larger areas of necrosis requiring operative debridement. The median size treated with clinic debridement was 5.5 cm, compared to 15 cm for operative debridement. All necrosis was treated in a timely fashion and did not delay adjuvant therapy. CONCLUSIONS: Mastectomy skin necrosis occurred in 8.1% of breasts after implant-based reconstruction. Necrosis less than 10 cm can be treated successfully with local debridement in the clinic setting. Timely and appropriate treatment of skin necrosis with debridement and primary closure expedites wound healing and facilitates tissue expander breast reconstruction.

Major bleeding in patients with mediastinitis: a heartbreaking series.

Deep sternal wound infection (DSWI) is a life-threatening complication that develops in 5% of patients undergoing median sternotomy. One feared complication is major bleeding, associated with up to 50% mortality. We characterized a series of patients who experienced major bleeding following DSWI. We included eight patients with DSWI who experienced major bleeding at our institution from 1990 to 2012. The median age was 70.9 (range, 47-81) and the cohort consisted of seven male patients and one female patient. All eight patients required emergent surgical repair for the bleeding and all survived past 30 days postoperatively from the repair.

Infantile hemangiomas exhibit neural crest and pericyte markers.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.

Arginine residues at internal positions in a protein are always charged.

Many functionally essential ionizable groups are buried in the hydrophobic interior of proteins. A systematic study of Lys, Asp, and Glu residues at 25 internal positions in staphylococcal nuclease showed that their pK(a) values can be highly anomalous, some shifted by as many as 5.7 pH units relative to normal pK(a) values in water. Here we show that, in contrast, Arg residues at the same internal positions exhibit no detectable shifts in pK(a); they are all charged at pH ≤ 10. Twenty-three of these 25 variants with Arg are folded at both pH 7 and 10. The mean decrease in thermodynamic stability from substitution with Arg was 6.2 kcal/mol at this pH, comparable to that for substitution with Lys, Asp, or Glu at pH 7. The physical basis behind the remarkable ability of Arg residues to remain protonated in environments otherwise incompatible with charges is suggested by crystal structures of three variants showing how the guanidinium moiety of the Arg side chain is effectively neutralized through multiple hydrogen bonds to protein polar atoms and to site-bound water molecules. The length of the Arg side chain, and slight deformations of the protein, facilitate placement of the guanidinium moieties near polar groups or bulk water. This unique capacity of Arg side chains to retain their charge in dehydrated environments likely contributes toward the important functional roles of internal Arg residues in situations where a charge is needed in the interior of a protein, in a lipid bilayer, or in similarly hydrophobic environments.

Hueston revisited: use of acellular dermal matrix following fasciectomy for the treatment of Dupuytren's disease.

Various surgical treatment modalities have been advocated for the treatment of Dupuytren's disease. However, recurrence following surgical treatment of Dupuytren's disease remains a common problem. Previous studies have demonstrated lower recurrence rates with use of a full-thickness skin graft. We therefore postulated that use of acellular dermal matrix may be associated with a similar outcome, based on the common inhibitory effect on underlying myofibroblasts. We performed a retrospective cohort study of 43 patients undergoing open fasciectomy for Dupuytren's disease from years 2005 to 2012 at our academic institution. Standard fasciectomies of the affected palmar and digital fascia were performed via Brunner incisions on all patients. Patients in the experimental group had a sheet of acellular dermal matrix (Alloderm; LifeCell, Bridgewater, NJ) sutured into the surgical bed with interrupted absorbable sutures before closure, whereas patients in the control group were not closed with acellular dermal matrix. Patients were then evaluated at follow-up for disease recurrence, defined as presence of Dupuytren's tissue in an area previously operated on with a contracture greater than that recorded following the surgical fasciectomy, or presence of contracture requiring surgery. Among our cohort of 43 patients, 23 (53.5%) were treated with acellular dermal matrix while 20 (46.5%) were not. The median age of our cohort was 66.5 years (range 54-91 years). The median follow-up was 1.8 years. During this follow-up period, recurrence of contracture was observed in 1 of 23 patients in the group receiving acellular dermal matrix, compared to 5 of 20 in the control group (P = 0.045). No differences in the incidence of minor wound complications were observed. Our novel technique of placement of acellular dermal matrix into the wound bed following fasciectomy for Dupuytren's disease may be an important surgical strategy to reduce recurrence rates in patients with Dupuytren's disease.

Development of a rat model of lymphedema and the implantation of a collagen-based medical device for therapeutic intervention.

Secondary lymphedema is a common condition among cancer survivors, and treatment strategies to prevent or treat lymphedema are in high demand. The development of novel strategies to diagnose or treat lymphedema would benefit from a robust experimental animal model of secondary lymphedema. The purpose of this methods paper is to describe and summarize our experience in developing and characterizing a rat hindlimb model of lymphedema. Here we describe a protocol to induce secondary lymphedema that takes advantage of micro computed tomography imaging for limb volume measurements and visualization of lymph drainage with near infrared imaging. To demonstrate the utility of this preclinical model for studying the therapeutic benefit of novel devices, we apply this animal model to test the efficacy of a biomaterials-based implantable medical device.

Use of hyaluronic acid filler for enhancement of nipple projection following breast reconstruction: An easy and effective technique.

BACKGROUND: Breast reconstruction improves the psychological well-being of patients with breast cancer. Patients who complete nipple-areolar reconstruction are even more satisfied with their final reconstructive result. Nipple flattening is a common complication. We hypothesized that injectable soft-tissue filler can be used to augment nipple projection in patients who underwent breast reconstruction. METHODS: This is a retrospective study of patients who underwent breast reconstruction and desired an enhanced postoperative nipple projection. The patients underwent a single session of injection with a hyaluronic acid filler as an outpatient. The filler was injected intradermally at the base of the nipple until the desired nipple projection was obtained. RESULTS: Twelve patients and 22 breasts were included in this study. Enhanced nipple projection was observed in all cases, with an average increase of 3.0 mm in nipple height (range 2.5-4.5 mm). All injected nipples remained soft to the touch. All results were stable at a median of 7.5 months follow-up. No complications were observed. CONCLUSIONS: The use of injectable fillers for enhanced nipple projection is a useful adjunct treatment in patients undergoing breast reconstruction. Advantages include the ability to obtain nipple projection in patients who opt to forgo nipple-areola reconstruction with local flaps, to augment reconstructed nipples in patients with thin mastectomy skin flaps especially following implant-based reconstruction, and to improve projection of the native nipple following nipple-sparing mastectomy. Another benefit of this adjunct treatment is that the injection is reversible. Filler injection is a safe and simple solution to the problem of insufficient nipple projection.

Economic Benefit of Hand Surgical Efforts in Low- and Middle-Income Countries: A Cost-Benefit Analysis.

BACKGROUND: Hand surgeons can alleviate the burden associated with various congenital anomalies, burn sequelae, and trauma that debilitate individuals in low- and middle-income countries. Because few surgeons in these areas have the necessary resources to perform complex hand surgery, surgical trips provide essential surgical care. The authors aimed to determine the economic benefit of hand surgical trips to low- and middle-income countries to comprehensively determine the economic implications of hand surgery trips in low-resource settings. METHODS: The authors collected data from two major global hand surgery organizations to analyze the economic benefit of hand surgery trips in low- and middle-income countries. The authors used both the human capital approach and the value of a statistical life-year approach to conduct this cost-benefit analysis. To demonstrate the economic gain, the authors subtracted the budgeted cost of each trip from the economic benefit. RESULTS: The authors analyzed a total of 15 trips to low- and middle-income countries. The costs of the trips ranged from $3453 to $87,434 (average, $24,869). The total cost for all the surgical trips was $373,040. The authors calculated a net economic benefit of $3,576,845 using the human capital approach and $8,650,745 using the value of a statistical life-year approach. CONCLUSIONS: The authors found a substantial return on investment using both the human capital approach and the value of a statistical life-year approach. In addition, the authors found that trips emphasizing education had a net economic benefit. Cost-benefit analyses have substantial financial implications and will aid policy makers in developing cost-reduction strategies to promote surgery in low- and middle-income countries.