Reducing Peri-implant Capsule Thickness in Submuscular Rodent Model of Breast Reconstruction With Delayed Radiotherapy.

INTRODUCTION: Capsular contracture remains the most common complication following device-based breast reconstruction, occurring in up to 50% of women who also undergo adjuvant radiotherapy either before or after device-based reconstruction. While certain risk factors for capsular contracture have been identified, there remains no clinically effective method of prevention. The purpose of the present study is to determine the effect of coating the implant with the novel small molecule Met-Z2-Y12, with and without delayed, targeted radiotherapy, on capsule thickness and morphologic change around smooth silicone implants placed under the latissimus dorsi in a rodent model. METHODS: Twenty-four female Sprague Dawley rats each had 2 mL smooth round silicone breast implants implanted bilaterally under the latissimus dorsi muscle. Twelve received uncoated implants and twelve received implants coated with Met-Z2-Y12. Half of the animals from each group received targeted radiotherapy (20 Gray) on postoperative day ten. At three and 6 months after implantation, the tissue surrounding the implants was harvested for analysis of capsular histology including capsule thickness. Additionally, microCT scans were qualitatively analyzed for morphologic change. RESULTS: Capsules surrounding Met-Z2-Y12-coated implants were significantly thinner (P = 0.006). The greatest difference in capsule thickness was seen in the irradiated 6-month groups, where mean capsule thickness was 79.1 ± 27.3 µm for uncoated versus 50.9 ± 9.6 µm for Met-Z2-Y12-coated implants (P = 0.038). At the time of explant, there were no capsular morphologic differences between the groups either grossly or per microCT. CONCLUSIONS: Met-Z2-Y12 coating of smooth silicone breast implants significantly reduces capsule thickness in a rodent model of submuscular breast reconstruction with delayed radiotherapy.

Optimal Timing of Delayed Microvascular Breast Reconstruction after Radiation Therapy.

BACKGROUND: The purpose of this study was to determine the optimal timing of delayed microvascular breast reconstruction after completion of postmastectomy radiation therapy (PMRT). The authors evaluated whether the timing of reconstruction after PMRT completion affects the development of major postoperative complications. We hypothesize that delayed microvascular breast reconstruction can be safely performed within 12 months of PMRT completion. METHODS: A retrospective chart review of microvascular, autologous breast reconstructions at Brigham and Women's Hospital from 2007 to 2019 was performed. Logistic regression analysis and marginal estimation methods were used to estimate the probability of any major complication (flap compromise requiring operative intervention, hematoma formation requiring evacuation, infection requiring readmission, and flap necrosis requiring operative debridement) occurring in 2-month intervals after PMRT. Patients were classified as having undergone reconstruction 0 to 12 months after PMRT (group 1), 12 to 18 months after PMRT (group 2), or 18 to 50 months after PMRT (group 3). RESULTS: A total of 303 patients were identified. All patients received postmastectomy radiation (n = 143 group 1, n = 57 group 2, n = 103 group 3). Mean follow-up time was 71.4 ± 38 months. Patients in group 1 were significantly younger and more likely to have undergone neoadjuvant chemotherapy (p < 0.05). Major complications occurred in 10% of patients. There was no significant difference in the development of major complications between the three groups (p = 0.57). Although not statistically significant, the probability of any major complication peaked 2 to 6 months after PMRT completion. CONCLUSION: There was no significant difference in major complications among patients who underwent delayed, microvascular breast reconstruction within versus beyond 1 year of PMRT completion. These findings suggest that delayed microvascular breast reconstruction can be safely performed beginning 6 months after PMRT completion.

Scalp Nodules and Deformed Great Toes: Omens of Fibrodysplasia Ossificans Progressiva.

ABSTRACT: We report a case of fibrous scalp nodules and bilateral hallux valgus in an infant who one decade later was diagnosed with a rare life-threatening genetic disease.

Topical α-gal nanoparticles accelerate diabetic wound healing.

An inadequate response from macrophages, key orchestrators of the wound healing process, has been implicated in the pathophysiology of impaired healing in diabetes. This study explored the utility of nanoparticles presenting the α-gal (Galα1-3Galß1-4GlcNAc-R) epitope to induce anti-Gal antibody-mediated local transient recruitment of macrophages to accelerate wound closure and healing in a diabetic murine model. α1,3galactosyltrasferase knockout mice were stimulated to produce anti-Gal antibodies and subsequently diabetes was induced by streptozotocin-induced ß-cell destruction. Six mm full-thickness skin wounds were made and α-gal nanoparticles (AGN) were topically applied on postwounding days 0 and 1. Wounds were analysed histologically for macrophage invasion and markers of wound healing, including epithelialization, vascularization and granulation tissue deposition through postoperative day 12. We found that application of AGN transiently but significantly increased macrophage recruitment into the wounds of diabetic mice. Treated wounds demonstrated more rapid closure and enhanced wound healing as demonstrated by significantly accelerated rates of epithelialization, vascularization and granulation tissue deposition. Thus, topical treatment of full-thickness wounds in diabetic mice with α-gal nanoparticles induced a transient but significant increase in macrophage recruitment resulting in an accelerated rate of wound healing. Using α-gal nanoparticles as a topical wound healing adjunct is a simple, safe and effective means of augmenting dysregulated macrophage recruitment present in the diabetic state.

Evaluating Venous Drainage in Reverse Flow Pedicles: Available Evidence and Mechanisms.

BACKGROUND: The anatomy and physiology of venous drainage in the reversed flow vascular pedicle is controversial and there have been few well-designed, controlled studies to effectively evaluate the physiology. We evaluated the available evidence for venous drainage to synthesize the conclusions of these studies, and to identify areas in need of further research. METHODS: Electronic databases were searched for articles published from January 1, 1950 to November 1, 2017. A total of 316 citations were screened for inclusion. Fifty articles met inclusion criteria and underwent review, yielding 12 articles for final data analysis. Three principal study types were found: human cadaveric (7), animal (3), human clinical (1), and mixed (1). RESULTS: We identified two main theories regarding the mechanism of venous drainage in reverse flow flaps. The "avalvular bypass" theory is based on the findings of intact valves of the venae comitantes, and venous outflow through the crossover pattern of the communicating branches and bypass pattern of the collateral branches. Alternatively, the "valvular incompetence" theory implies that pedicle dissection, proximal ligation, and insetting of the flap cause physiologic changes, such as increased venous pressure, denervation, and simultaneous proximal and distal filling, which together result in valvular insufficiency. CONCLUSION: The mechanism by which retrograde venous outflow occurs in reverse flow flaps remains controversial. Nonetheless, a few well-designed studies have contributed to the understanding of venous anatomy and outflow. Most likely, the true mechanism is based on venous outflow that occurs via the "avalvular bypass" route initially and the "valvular incompetence" route later.

Advances in flap monitoring and impact of enhanced recovery protocols.

Recent advances in technology have shown promise in improving outcomes in microsurgery. Although vascular compromise and flap loss represent major complications, flap monitoring techniques have evolved to improve rates of salvage. Enhanced recovery protocols have also been adapted to expedite patient recovery and length of stay. Early studies have shown benefits such as decreased complications and costs and improved patient outcomes. This review examines the current literature on these topics in the setting of microsurgery.

Antigen-Mediated, Macrophage-Stimulated, Accelerated Wound Healing Using α-Gal Nanoparticles.

BACKGROUND: Macrophages are known to be crucial to timely and efficacious wound healing. They have been shown to modulate inflammation and the migration and proliferation of regenerative cells, promoting tissue deposition and wound closure. This study explored the use of the natural antigen Galα1-3Galß1-4GlcNAc-R (α-gal), present in lower mammals yet absent in Old World primates and humans, to induce a transiently enhanced macrophage response and thereby direct accelerated wound closure and healing in a standard murine model. METHODS: α1,3galactosyltransferase knockout mice were stimulated to produce anti-Gal antibodies at levels comparable with humans. α-Gal-containing micelle nanoparticles were generated and applied to full-thickness splinted wounds on the mice. At 1, 2, 3, 6, and 9 days postoperatively, mice were killed, and wounds were analyzed histologically for macrophage invasion, epithelialization, vascularization, and granulation tissue deposition. Flow cytometry of wound tissue was performed to quantify relative levels of proinflammatory M1 to anti-inflammatory M2 macrophage subtypes. RESULTS: Treatment of splinted full-thickness murine wounds with α-gal-containing nanoparticles led to accelerated wound healing and closure as demonstrated by accelerated rates of keratinization, vascular growth, and wound tissue deposition. Furthermore, treated wounds demonstrated early and enhanced macrophage invasion, as well as a lower M1-M2 ratio. CONCLUSION: Application of α-gal-containing nanoparticles to wounds stimulated a transiently increased inflammatory response, accelerating the rate of wound healing. Use of α-gal may be a simple and effective way to stimulate the wound healing response in both normal and pathologic wound beds.

In Search of a Murine Model of Radiation-Induced Periprosthetic Capsular Fibrosis.

INTRODUCTION: Capsular contracture after breast reconstruction is a morbid complication, occurring in 30.0% to 47.5% of patients undergoing postoperative radiotherapy. Although it is well known that radiation increases rate of capsular contracture, there are few well-established animal models that faithfully replicate standard-of-care clinical practice, that is, prosthesis placement at the time of mastectomy followed by delayed radiotherapy. To better recapitulate current clinical practice, we developed a murine model in which the implant sites were irradiated 10 days postoperatively, rather than at time of surgery. METHODS: Hemispherical implants were created from polydimethylsiloxane and implanted bilaterally in the subcutaneous dorsa of 20 C57Bl/6 mice. Mice were randomized to 5 treatment groups, differing in irradiation dose: 0 to 40 Gy. Ten days postoperatively, irradiation was performed using 250-kVp x-rays (XRAD225Cx, Precision X-ray, North Branford, Conn). In 1 mouse per group, dosimeters were placed subcutaneously to measure the delivered absorbed dose. Thirty-one days postoperatively, the mice were sacrificed and examined grossly, and periprosthetic tissues were removed for histologic analysis of periprosthetic capsule thickness and cellular deposition. RESULTS: Total radiation dose was calculated by the treatment planning software and confirmed by the in vivo dosimeters. Physical examination of the irradiated region demonstrated evidence of local radiation delivery, including circular patterns of hair blanching and thinning directly over the implants. Furthermore, histologic analysis of the irradiated epidermis demonstrated dose-dependent radiation changes including keratin whorls and patches of uneven epidermal thickness. There was no statistically significant difference in capsule thickness among the groups. Mice in the 30 and 40 Gy groups endured complications including shortness of breath, coagulopathy, and death, signs of systemic radiation poisoning. CONCLUSIONS: There was no evidence of increased periprosthetic capsule thickness with localized irradiation, irrespective of dose up to 20 Gy. These results differ from those previously published, which demonstrated increased capsule thickness with 10 Gy irradiation. Given the evidence of local radiation delivery, we believe that the lack of increase in capsule thickness observed in our experiment is a real phenomenon and demonstrate the difficulty in creating an easily reproducible rodent model that mimics the effects of postmastectomy implant-based reconstruction and irradiation.

Ventriculostomy-related infections: The performance of different definitions for diagnosing infection.

INTRODUCTION: Comparison of rates of ventriculostomy-related infections (VRIs) across institutions is difficult due to the lack of a standard definition. We sought to review published definitions of VRI and apply them to a test cohort to determine the degree of variability in VRI diagnosis. MATERIALS AND METHODS: We conducted a PubMed search for definitions of VRI using the search strings "ventriculostomy-related infection" and "ventriculostomy-associated infection." We applied these definitions to a test cohort of 18 positive cerebrospinal fluid (CSF) cultures taken from ventriculostomies at two institutions to compare the frequency of infection using each definition. RESULTS: We found 16 unique definitions of VRI. When the definitions were applied to the test cohort, the frequency of infection ranged from 22 to 94% (median 61% with interquartile range (IQR) 56-74%). The concordance between VRI diagnosis and treatment with VRI-directed antibiotics for at least seven days ranged from 56 to 89% (median: 72%, IQR: 71-78%). CONCLUSIONS: The myriad of definitions in the literature produce widely different frequencies of infection. In order to compare rates of VRI between institutions for the purposes of qualitative metrics and research, a consistent definition of VRI is needed.

Therapeutic temperature modulation for fever after intracerebral hemorrhage.

BACKGROUND: We sought to determine whether therapeutic temperature modulation (TTM) to treat fever after intracerebral hemorrhage (ICH) is associated with improved hospital complications and discharge outcomes. METHODS: We performed a retrospective case-control study of patients admitted with spontaneous ICH having two consecutive fevers ≥38.3 °C despite acetaminophen administration. Cases were enrolled from a prospective database of patients receiving TTM from 2006 to 2010. All cases received TTM for fever control with goal temperature of 37 °C with a shiver-control protocol. Controls were matched in severity by ICH score and retrospectively obtained from 2001 to 2004, before routine use of TTM for ICH. Primary outcome was discharge-modified Rankin score. RESULTS: Forty patients were enrolled in each group. Median admission ICH Score, ICH volume, and GCS were similar. TTM was initiated with a median of 3 days after ICH onset and for a median duration of 7 days. Mean daily T max was significantly higher in the control group over the first 12 days (38.1 vs. 38.7 °C, p ≤ 0.001). The TTM group had more days of IV sedation (median 8 vs. 1, p < 0.001) and mechanical ventilation (18 vs. 9, p = 0.003), and more frequently underwent tracheostomy (55 vs. 23 %, p = 0.005). Mean NICU length of stay was longer for TTM patients (15 vs. 11 days, p = 0.007). There was no difference in discharge outcomes between the two groups (overall mortality 33 %, moderate or severe disability 67 %). CONCLUSIONS: Therapeutic normothermia is associated with increased duration of sedation, mechanical ventilation, and NICU stay, but is not clearly associated with improved discharge outcome.

The Impact of Breast Implant Cohesivity on Rippling and Revision Procedures in 2-Stage Prepectoral Breast Reconstruction.

Background: Rippling remains one of the most common complications following prepectoral implant-based reconstruction (IBR). Objectives: The purpose of this study was to assess how implant cohesivity, a measure of elasticity and form stability, affects the incidence of rippling in prepectoral IBR. Methods: We performed a retrospective cohort study of 2-stage prepectoral IBR performed between January 2020 and June 2022 at the Brigham and Women's Hospital and Dana-Farber Cancer Institute, comparing outcomes in patients who received Allergan Natrelle least cohesive, moderately cohesive, and most cohesive silicone gel implants. Outcomes of interest were rippling and reoperation for fat grafting. Results: A total of 129 patients were identified, of whom 52 had the least cohesive implants, 24 had the moderately cohesive implants, and 53 patients had the most cohesive implants. The mean follow-up time was 463 (±220) days. A decreased incidence of rippling was seen with moderately cohesive (odds ratio [OR] 0.30, P < .05) and most cohesive (OR 0.39, P < .05) implants. Third stage reoperation for fat grafting was less frequent in patients with the most cohesive implant (OR 0.07, P < .05). In subgroup analyses, the patients with the most cohesive implant, who did not receive fat grafting at the time of initial implant placement, did not require reoperation for fat grafting (0%). Conclusions: The use of highly cohesive implants in prepectoral IBR is associated with decreased rippling and fewer reoperations for fat grafting.

The Neuroma Startle Sign: A Surgical Indicator of Proximity to an Injured Nerve.

During operative intervention for the treatment of symptomatic neuromas, the authors have observed a hypersensitive "startle" response to stimulation in proximity to the painful nerve. This physiologic sign is an indicator of the specific anatomic localization of the painful stimulus, commonly a symptomatic neuroma, that appears to be reproducible. The aim of this article is to describe this "neuroma startle sign," posit the underlying mechanism for this observation, and propose how this phenomenon could be clinically harnessed for innovation and optimization in both surgery and anesthesia for more effective symptomatic neuroma localization.

An Antifibrotic Breast Implant Surface Coating Significantly Reduces Periprosthetic Capsule Formation.

BACKGROUND: The body responds to prosthetic materials with an inflammatory foreign body response and deposition of a fibrous capsule, which may be deleterious to the function of the device and cause significant discomfort for the patient. Capsular contracture (CC) is the most common complication of aesthetic and reconstructive breast surgery. The source of significant patient morbidity, it can result in pain, suboptimal aesthetic outcomes, implant failure, and increased costs. The underlying mechanism remains unknown. Treatment is limited to reoperation and capsule excision, but recurrence rates remain high. In this study, the authors altered the surface chemistry of silicone implants with a proprietary anti-inflammatory coating to reduce capsule formation. METHODS: Silicone implants were coated with Met-Z2-Y12, a biocompatible, anti-inflammatory surface modification. Uncoated and Met-Z2-Y12-coated implants were implanted in C57BL/6 mice. After 21, 90, or 180 days, periprosthetic tissue was removed for histologic analysis. RESULTS: The authors compared mean capsule thickness at three time points. At 21, 90, and 180 days, there was a statistically significant reduction in capsule thickness of Met-Z2-Y12-coated implants compared with uncoated implants ( P < 0.05). CONCLUSIONS: Coating the surface of silicone implants with Met-Z2-Y12 significantly reduced acute and chronic capsule formation in a mouse model for implant-based breast augmentation and reconstruction. As capsule formation obligatorily precedes CC, these results suggest contracture itself may be significantly attenuated. Furthermore, as periprosthetic capsule formation is a complication without anatomical boundaries, this chemistry may have additional applications beyond breast implants, to a myriad of other implantable medical devices. CLINICAL RELEVANCE STATEMENT: Coating of the silicone implant surface with Met-Z2-Y12 alters the periprosthetic capsule architecture and significantly reduces capsule thickness for at least 6 months postoperatively in a murine model. This is a promising step forward in the development of a therapy to prevent capsular contracture.

Safety of DIEP Flap Reconstruction in Patients with Factor V Leiden: A Retrospective Cohort Study.

Background: Factor V Leiden (FVL) is the most common inherited thrombophilia in White people. Thrombotic complications resulting from free flap breast reconstruction in FVL patients have been studied to a limited degree. We evaluated whether patients heterozygous for a FVL mutation undergoing deep inferior epigastric perforator flap reconstruction had increased risk of micro- or macrovascular thrombotic complications compared with patients without a diagnosed thrombophilia. Methods: We performed a retrospective cohort study of deep inferior epigastric perforator flap reconstructions at Brigham and Women's Hospital (1/2015-12/2020) comparing patients diagnosed as FVL heterozygotes compared with matched controls without a diagnosed thrombophilia. Patients were matched using coarsened exact matching algorithm based on clinical characteristics. The primary outcomes were micro- (return to OR for flap compromise, flap loss) and macrovascular (venous thromboembolism) complications. Results: A total of 506 patients (812 flaps) were included in this study. Eleven patients (17 flaps) were FVL heterozygotes. After matching, 10 patients (16 flaps) with FVL were matched to 55 patients (94 flaps). The return to OR for flap compromise was 0% in the FVL cohort compared with 5% (n = 5/94, 3/94 flaps lost, P = 1.00) in the matched controls (1.9%, n = 15/795 in unmatched controls, 0.6%, n = 5/795 loss rate). There were zero venous thromboembolism events among FVL patients compared with 2% of controls (n = 1/55). Conclusions: FVL heterozygosity did not increase the risk of micro- or macrovascular complications in patients undergoing deep inferior epigastric perforator flap breast reconstruction. This study supports the safety of microvascular reconstruction in this group of patients when appropriate venous thromboembolism prophylaxis is given.

An Outcomes Review of 330 Sternal Wound Reconstructions: Timing of Closure Does Make a Difference.

BACKGROUND: Sternal wound infection and dehiscence following cardiac surgery remain difficult clinical problems with high morbidity. Older classification systems regarding timing to reconstruction do not take into account recent improvements in critical care, wound vacuum-assisted closure use, or next-generation antibiotic therapies, which may prolong time to reconstruction. METHODS: Records of patients undergoing sternal wound reconstruction performed by the senior author (J.A.A.) from 1996 to 2018 at a high-volume cardiac surgery center were reviewed. Indications included sternal wound infection or dehiscence. All patients underwent single-stage removal of hardware, débridement, and flap closure. Patients were divided into two groups based on timing of wound closure after cardiac surgery: less than 30 days or greater than or equal to 30 days. RESULTS: Of the 505 patients identified during the study period, 330 had sufficient data for analysis. Mean time to sternal wound surgery was 15.7 days in the early group compared to 64.4 days (p < 0.01) beyond 30 days. Postdébridement cultures were positive in 72 percent versus 62.5 percent of patients (p = 0.11), whereas rates of postoperative infection were significantly higher in the delayed group: 1.9 percent versus 9.5 percent (p < 0.01). Partial wound dehiscence rates were also higher after 30 days (1.9 percent versus 11.3 percent; p < 0.01), whereas total length of stay was decreased. Use of wound vacuum-assisted closure was significantly associated with reconstruction beyond 30 days (p < 0.01). CONCLUSIONS: Although performing sternal wound reconstruction more than 30 days after initial cardiac surgery was associated with a shorter overall hospital length of stay and higher extubation rates in the operating room, these patients also had elevated postoperative infection and wound complication rates. The authors thus recommend not delaying definitive surgical reconstruction when possible. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Webinar during COVID-19 Improves Knowledge of Changes to the Plastic Surgery Residency Application Process.

BACKGROUND: The COVID-19 pandemic has significantly impacted residency application process for all specialties, including plastic surgery residency. Almost all plastic surgery residency programs have suspended visiting sub-internship rotations. This study quantifies the impact of a webinar through an analysis of poll questions and a post-webinar survey sent to all registered participants. METHODS: A dedicated webinar was organized and held by the Harvard Plastic Surgery Residency Training Program. All attendees were asked several poll questions during the webinar. The 192 participants were also sent a post-webinar survey. RESULTS: The response rate was 68.2% (n = 131). Respondents were more confident about matching into a plastic surgery residency program at the end of the webinar compared with before the webinar (P < 0.001). Respondents who did not have a plastic surgery residency program at their home institution were less confident at the start of the webinar (P = 0.009). In addition, respondents who had not taken time off for research or for other endeavors during or after medical school were less confident about their chances to match at the start of the webinar (P = 0.034). CONCLUSIONS: An online webinar program increased confidence levels of medical students interested in applying for residency positions in plastic surgery. Residency programs should consider webinars as a method to inform and assist medical students during the upcoming application season.

Treatment of Infected Wounds in the Age of Antimicrobial Resistance: Contemporary Alternative Therapeutic Options.

As antibiotic resistance increases and antimicrobial options diminish, there is a pressing need to identify and develop new and/or alternative (non-antimicrobial-based) wound therapies. The authors describe the implications of antibiotic resistance on their current wound treatment paradigms and review the most promising non-antibiotic-based antimicrobial agents currently in research and development, with a focus on preclinical and human studies of therapeutic bacteriophages, antimicrobial peptides, cold plasma treatment, photodynamic therapy, honey, silver, and bioelectric dressings.