Impact of deep phenotyping: high diagnostic yield in a diverse pediatric population of 172 patients through clinical whole-genome sequencing at a single center.

Background: Pediatric patients with undiagnosed conditions, particularly those suspected of having Mendelian genetic disorders, pose a significant challenge in healthcare. This study investigates the diagnostic yield of whole-genome sequencing (WGS) in a pediatric cohort with diverse phenotypes, particularly focusing on the role of clinical expertise in interpreting WGS results. Methods: A retrospective cohort study was conducted at Acibadem University's Maslak Hospital in Istanbul, Turkey, involving pediatric patients (0-18 years) who underwent diagnostic WGS testing. Clinical assessments, family histories, and previous laboratory and imaging studies were analyzed. Variants were classified and interpreted in conjunction with clinical findings. Results: The cohort comprised 172 pediatric patients, aged 0-5 years (62.8%). International patients (28.5%) were from 20 different countries. WGS was used as a first-tier approach in 61.6% of patients. The diagnostic yield of WGS reached 61.0%, enhanced by reclassification of variants of uncertain significance (VUS) through reverse phenotyping by an experienced clinical geneticist. Consanguinity was 18.6% of the overall cohort. Dual diagnoses were carried out for 8.5% of solved patients. Discussion: Our study particularly advocates for the selection of WGS as a first-tier testing approach in infants and children with rare diseases, who were under 5 years of age, thereby potentially shortening the duration of the diagnostic odyssey. The results also emphasize the critical role of a single clinical geneticist's expertise in deep phenotyping and reverse phenotyping, which contributed significantly to the high diagnostic yield.

Early Return of Motion in Patients With Intramedullary Screw Placement for Metacarpal and Phalangeal Fracture Fixation.

INTRODUCTION: Hand fractures are associated with significant morbidity. Current management standards often result in prolonged immobilization, stiffness, and delayed return to functional use. Intramedullary (IM) compression screws offer minimal soft tissue disruption and early postoperative active motion. In this study, we describe our outcomes after intraosseous fracture fixation using IM cannulated headless screws for a multitude of fracture patterns. METHODS: This study is a retrospective review of patients who underwent IM screw placement for fixation of metacarpal and phalangeal fractures by a single surgeon from 2017 to 2022. Data were collected to include patient demographics, fracture details, postoperative complications, and follow-up. Time to range of motion and return to unrestricted motion was recorded. RESULTS: There were 69 patients with 92 fractures (n = 54 metacarpal, n = 38 phalanx). The median patient age was 45 years (range, 18-89 years) with 75.4% males. Majority presented with a single fracture (n = 50, 72.5%), and 38 patients (55.1%) had open fractures. Small finger was the most affected digit (n = 35, 37.6%). The median time to allow range of motion from surgery was 8.7 days (interquartile range, 0-32) with 32 days (interquartile range, 10-62) for unrestricted use of the hand. Thirty-five patients (50.7%) were allowed controlled motion from the first postoperative day. One patient had loss of reduction requiring reintervention for hardware removal, and 1 patient had superficial skin infection managed with oral antibiotics. CONCLUSIONS: Our findings indicate that the IM screw provides reliable fixation for a wide variety of fracture patterns with a low complication rate and offers early return to functional use.

A Model to Study Wound Healing Over Exposed Avascular Structures in Rodents With a 3D-Printed Wound Frame.

BACKGROUND: Soft tissue defects with exposed avascular structures require reconstruction with well-vascularized tissues. Extensive research is ongoing to explore tissue engineered products that provide durable coverage. However, there is a lack of controlled and affordable testbeds in the preclinical setting to reflect this challenging clinical scenario. We aimed to address this gap in the literature and develop a feasible and easily reproducible model in rodents that reflects an avascular structure in the wound bed. METHODS: We created 20 × 20 mm full thickness wounds on the dorsal skin of Lewis rats and secured 0.5-mm-thick silicone sheets of varying sizes to the wound bed. A 3D-printed wound frame was designed to isolate the wound environment. Skin graft and free flap survival along with exposure of the underlying silicone was assessed. Rats were followed for 4 weeks with weekly dressing changes and photography. Samples were retrieved at the endpoint for tissue viability and histologic analysis. RESULTS: The total wound surface area was constant throughout the duration of the experiment in all groups and the wound frames were well tolerated. The portion of the skin graft without underlying silicone demonstrated integration with the underlying fascia and a histologically intact epidermis. Gradual necrosis of the portion of the skin graft overlying the silicone sheet was observed with varying sizes of the silicone sheet. When the size of the silicone sheet was reduced from 50% of the wound surface area, the portion surviving over the silicone sheet increased at the 4-week timepoint. The free flap provided complete coverage over the silicone sheet. CONCLUSION: We developed a novel model of rodent wound healing to maintain the same wound size and isolate the wound environment for up to 4 weeks. This model is clinically relevant to a complex wound with an avascular structure in the wound bed. Skin grafts failed to completely cover increasing sizes of the avascular structure, whereas the free flap was able to provide viable coverage. This cost-effective model will establish an easily reproducible platform to evaluate more complex bioengineered wound coverage solutions.

Machine Perfusion Deters Ischemia-Related Derangement of a Rodent Free Flap: Development of a Model.

INTRODUCTION: Machine perfusion can enable isolated support of composite tissues, such as free flaps. The goal of perfusion in this setting is to preserve tissues prior to transplantation or provide transient support at the wound bed. This study aimed to establish a rodent model of machine perfusion in a fasciocutaneous-free flap to serve as an affordable testbed and determine the potential of the developed support protocol to deter ischemia-related metabolic derangement. METHODS: Rat epigastric-free flaps were harvested and transferred to a closed circuit that provides circulatory and respiratory support. Whole rat blood was recirculated for 8 h, while adjusting the flow rate to maintain arterial-like perfusion pressures. Blood samples were collected during support. Extracellular tissue lactate and glucose levels were characterized with a microdialysis probe and compared with warm ischemic, cold ischemic, and anastomosed-free flap controls. RESULTS: Maintenance of physiologic arterial pressures (85-100 mmHg) resulted in average pump flow rates of 360-430 µL/min. Blood-based measurements showed maintained glucose and oxygen consumption throughout machine perfusion. Average normalized lactate to glucose ratio for the perfused flaps was 5-32-fold lower than that for the warm ischemic flap controls during hours 2-8 (P < 0.05). CONCLUSIONS: We developed a rat model of ex vivo machine perfusion of a fasciocutaneous-free flap with maintained stable flow and tissue metabolic activity for 8 h. This model can be used to assess critical elements of support in this setting as well as explore other novel therapies and technologies to improve free tissue transfer.

ChatGPT Is Equivalent to First-Year Plastic Surgery Residents: Evaluation of ChatGPT on the Plastic Surgery In-Service Examination.

BACKGROUND: ChatGPT is an artificial intelligence language model developed and released by OpenAI (San Francisco, CA) in late 2022. OBJECTIVES: The aim of this study was to evaluate the performance of ChatGPT on the Plastic Surgery In-Service Examination and to compare it to residents' performance nationally. METHODS: The Plastic Surgery In-Service Examinations from 2018 to 2022 were used as a question source. For each question, the stem and all multiple-choice options were imported into ChatGPT. The 2022 examination was used to compare the performance of ChatGPT to plastic surgery residents nationally. RESULTS: In total, 1129 questions were included in the final analysis and ChatGPT answered 630 (55.8%) of these correctly. ChatGPT scored the highest on the 2021 exam (60.1%) and on the comprehensive section (58.7%). There were no significant differences regarding questions answered correctly among exam years or among the different exam sections. ChatGPT answered 57% of questions correctly on the 2022 exam. When compared to the performance of plastic surgery residents in 2022, ChatGPT would rank in the 49th percentile for first-year integrated plastic surgery residents, 13th percentile for second-year residents, 5th percentile for third- and fourth-year residents, and 0th percentile for fifth- and sixth-year residents. CONCLUSIONS: ChatGPT performs at the level of a first-year resident on the Plastic Surgery In-Service Examination. However, it performed poorly when compared with residents in more advanced years of training. Although ChatGPT has many undeniable benefits and potential uses in the field of healthcare and medical education, it will require additional research to assess its efficacy.

Biodegradable Nerve Guide with Glial Cell Line-Derived Neurotrophic Factor Improves Recovery After Facial Nerve Injury in Rats.

Background: Bioengineered nerve guides with glial cell line-derived neurotrophic factor (GDNF) support recovery after facial nerve injury by acting as regenerative scaffolds. Objective: To compare functional, electrophysiological, and histological outcomes after repair of rat facial nerve transection in control, empty nerve guide, and nerve guide with GDNF conditions. Methods: Rats underwent transection and primary repair of the buccal branch of the facial nerve and were divided into (1) transection and repair only, (2) transection and repair augmented with empty guide, (3) transection and repair augmented with GDNF-guide groups. Weekly measurements of the whisking movements were recorded. At 12 weeks, compound muscle action potentials (CMAPs) at the whisker pad were assessed, and samples were collected for histomorphometric analysis. Results: Rats in GDNF-guide group displayed the earliest peak in normalized whisking amplitude. CMAPs were significantly higher after GDNF-guide placement. Mean fiber surface area of the target muscle, axonal count of the injured branch, and the number of Schwann cells were highest with GDNF guides. Conclusion: The biodegradable nerve guide containing double-walled GDNF microspheres enhanced recovery after facial nerve transection and primary repair.

Venous Thromboembolism Rates After Free Flap Reconstruction of the Head and Neck Region.

BACKGROUND: Venous thromboembolism (VTE) is a major concern for the postoperative hospitalized patient, especially after long and complex procedures. Cancer itself also contributes to the hypercoagulable state, further complicating the management of patients. Despite prophylaxis, breakthrough events can occur. We aimed to assess our institutional VTE and bleeding rates after free flap reconstruction of the head and neck (H&N) region and the factors associated with VTE events. METHODS: A retrospective review of the patients who underwent H&N free flap reconstruction at an academic center from 2012 to 2021 was performed from a prospectively maintained database. Data regarding patient demographics, medical history, surgical details, and overall outcomes were collected. Outcomes studied included postoperative 30-day VTE rates and major bleeding events. Patients who had a VTE event were compared with the rest of the cohort to identify factors associated with VTE. RESULTS: Free flap reconstruction of the H&N region was performed in 949 patients. Reconstruction after cancer extirpation for squamous cell carcinoma was the most common etiology (79%). The most common flap was thigh based (50%), followed by the fibula (29%). The most common postoperative VTE chemoprophylaxis regimen was enoxaparin 30 mg twice daily (83%). The VTE and bleeding rates over the 10-year period were 4.6% (n = 44) and 8.7% (n = 83), respectively. Body mass index (28.7 ± 5.8 vs 26.2 ± 6.6, P = 0.013) and pulmonary comorbidities were found to be significantly higher in patients who had a VTE event (43% vs 27%, P = 0.017). Patients with a VTE event had a prolonged hospital stay of 8 more days (19.2 ± 17.4 vs 11 ± 7, P = 0.003) and a higher incidence of bleeding events (27% vs 8%, P < 0.001). CONCLUSIONS: Postoperative VTE is a significant complication associated with increased length of hospitalization in patients undergoing free flap reconstruction of the H&N region. Institutional measures should be implemented on an individualized basis based on patient comorbidities to improve the postoperative VTE rates, while balancing the bleeding events.

Early Detection of Breast Cancer-Related Lymphedema: Accuracy of Indocyanine Green Lymphography Compared with Bioimpedance Spectroscopy and Subclinical Lymphedema Symptoms.

Introduction: The reported incidences of breast cancer-related lymphedema (LE) affecting the arms vary greatly. Reason for this variability includes different diagnostic techniques used across studies. In the current study, we compared the accuracy of indocyanine green lymphography (ICG_L) and bioimpedance spectroscopy (BIS) in detecting LE before presentation of clinical signs. Methods and Results: Patients with no initial detectable signs of clinical LE of their arms after axillary lymph node dissection or removal of >5 lymph nodes on sentinel lymph node biopsy were included. Subclinical LE was defined as BIS values outside the normal range [(≥7 units (or >10 units)] or a 7-unit (or 10 unit) change between two measurements. We tracked ICG_L and BIS measurements for 133 potentially affected arms (n = 123). ICG_L detected signs of lymphatic flow disruption in 63 arms (47%). Based on the BIS value of 7 units, 60 arms (45%) had values outside the normal range. When using ICG_L-identified LE cases as true positives, BIS had a 54% accuracy (area under the curve [AUC] = 0.54) in detecting LE. Accuracy was 61% for subclinical LE symptoms when compared with ICG_L (AUC = 0.62). Both BIS and subclinical LE symptoms had <0.70 AUC-receiver characteristic operator curve, suggesting that BIS and development of subclinical LE symptoms are not adequate for identifying patients with subclinical LE. Conclusion: ICG_L is a reliable diagnostic tool for detecting early signs of lymphatic flow disruption in subclinical LE. Utilizing ICG_L to diagnose subclinical LE followed by a personalized treatment plan may provide patients the best chance of preventing disease progression.

Intramuscular Nanofat Injection Promotes Inflammation-Induced Gastrocnemius Regeneration in a Syngeneic Rat Sciatic Nerve Injury Model.

BACKGROUND: Mechanical emulsification of adipose tissue to concentrate protein and stromal cell components (ie, nanofat) has gained considerable interest in clinical practice. Although the regenerative potential of nanofat has largely been used in aesthetic applications, these effects have considerable potential in reconstruction as well. Here, the authors investigated the therapeutic properties of nanofat injected directly into the denervated gastrocnemius after a sciatic nerve injury in Lewis rats. METHODS: Muscle denervation was induced by transecting and immediately repairing the sciatic nerve. Inguinal and subcutaneous adipose was harvested from donor rodents, processed into nanofat, and then injected intramuscularly into the gastrocnemius. Gait analysis was performed weekly. Rodents were euthanized at 9 and 12 weeks, after which tetanic contraction force was measured, and gene expression, histology, and cytokine multiplexing were performed. RESULTS: Intramuscular injection of nanofat significantly increased maximum tetanic force generation at 9 and 12 weeks. The forces of the nanofat-injected gastrocnemii were better correlated to their contralateral gastrocnemii relative to controls. Muscle repair-associated inflammatory gene expressions were significantly up-regulated in nanofat-injected gastrocnemii. Cytokines interleukin (IL)-1ß, IL-18, vascular endothelial growth factor, granulocyte-macrophage colony-stimulating factor, and tissue inhibitor of metalloproteinase-1 were significantly higher in nanofat-injected gastrocnemii relative to control gastrocnemii, and the tetanic force was linearly and significantly correlated to IL-1ß and IL-18 and their interacting effects. CONCLUSIONS: Intramuscular injection of emulsified adipose tissue (nanofat) significantly increased gastrocnemii contraction force after sciatic nerve injury, with prolonged reconstructive inflammation by means of CD68, inducible nitric oxide synthase, IL-1ß, and IL-18 all being potential mechanisms for this recovery. This application could potentially increase the therapeutic breadth of nanofat to include muscular recovery after nerve injury. CLINICAL RELEVANCE STATEMENT: The authors' study investigates a clinically translatable therapy to mitigate muscle atrophy after nerve injury.

Association between venous thromboembolism rates and different prophylactic anticoagulation regimens in patients undergoing free flap reconstruction of the head and neck region.

BACKGROUND: Venous Thromboembolism (VTE) is a serious complication after free tissue transfer to the head and neck (H&N). However, an optimal antithrombotic prophylaxis protocol is not defined in the literature. Enoxaparin 30 mg twice daily (BID) and heparin 5000 IU three times daily (TID) are among the most commonly used regimens for chemoprophylaxis. However, no studies compare these two agents in the H&N population. METHODS: A cohort study of patients who underwent free tissue transfer to H&N from 2012 to 2021 and received either enoxaparin 30 mg BID or Heparin 5000 IU TID postoperatively. Postoperative VTE and hematoma events were recorded within 30 days of index surgery. The cohort was divided into two groups based on chemoprophylaxis. VTE and hematoma rates were compared between the groups. RESULTS: Out of 895 patients, 737 met the inclusion criteria. The mean age and Caprini score were 60.6 [SD 12.5] years and 6.5 [SD 1.7], respectively. 234 [31.88%] were female. VTE and hematoma rates among all patients were 4.47% and 5.56%, respectively. The mean Caprini score between the enoxaparin (n = 664) and heparin (n = 73) groups was not statistically significant (6.5 ± 1.7 vs.6.3 ± 1.3, p = 0.457). The VTE rate in the enoxaparin group was significantly lower than in the heparin group (3.9% vs. 9.6%; OR: 2.602, 95% CI: 1.087-6.225). Hematoma rates were similar between the two groups (5.5% vs. 5.6%; OR: 0.982, 95% CI: 0.339-2.838). CONCLUSIONS: Enoxaparin 30 mg BID was associated with a lower VTE rate while maintaining a similar hematoma rate compared to heparin 5000 units TID. This association may support the use of enoxaparin over heparin for VTE chemoprophylaxis in H&N reconstruction.

Automated Decellularization of the Rodent Epigastric Free Flap: A Comparison of Sodium Dodecyl Sulfate-Based Protocols.

BACKGROUND: Free tissue transfer to cover complex wounds with exposed critical structures results in donor-site morbidity. Perfusion decellularization and recellularization of vascularized composite tissues is an active area of research to fabricate complex constructs without a donor site. Sodium dodecyl sulfate (SDS)-based protocols remain the predominant choice for decellularization despite the deleterious effects on tissue ultrastructure and capillary networks. We aimed to develop an automated decellularization process and compare different SDS perfusion times to optimize the protocol. METHODS: A three-dimensional-printed closed-system bioreactor capable of continuously perfusing fluid through the vasculature was used for decellularization. The artery and vein of rat epigastric fasciocutaneous free flaps were cannulated and connected to the bioreactor. Protocols had varying durations of 1% SDS solution (3, 5, and 10 days) followed by 1 day of 1% Triton X-100 and 1 day of 1x phosphate-buffered saline. The residual DNA was quantified. Microarchitecture of the constructs was assessed with histology, and the vascular network was visualized for qualitative assessment. RESULTS: The structural integrity and the microarchitecture of the extracellular matrix was preserved in the 3- and 5-day SDS perfusion groups; however, the subcutaneous tissue of the 10-day protocol lost its structure. Collagen and elastin structures of the pedicle vessels were not compromised by the decellularization process. Five-day SDS exposure group had the least residual DNA content (p < 0.001). Across all protocols, skin consistently had twice as much residual DNA over the subcutaneous tissues. CONCLUSION: A compact and integrated bioreactor can automate decellularization of free flaps to bioengineer regenerative constructs for future use in reconstruction of complex defects. A decellularization protocol with 5 days of 1% SDS exposure was the most successful to keep the residual DNA content at a minimum while preserving the structural integrity of the tissues.

Use of wound edge inversion (epibole) to generate recalcitrant and inflamed diabetic wounds.

Robust and predictive pre-clinical models of recalcitrant diabetic wounds are critical for advancing research efforts toward improving healing. Murine models have logistic and genetic benefits versus larger animals; however, native murine healing inadequately represents clinically recalcitrant wounds in humans. Furthermore, current humanization techniques employing devices, deleterious mutations or chemical agents each carry model-specific limitations. To better replicate human wounds in a mouse, we developed a novel wound-edge inversion (WEI) technique that mimics the architecture of epibole and mitigates contracture, epithelialization, and consequently wound closure. In this study, we evaluated the reliability and durability of the WEI model in wild-type and obese diabetic mice and compared to healing after (i) punch biopsy, (ii) mechanical/silicone stenting or (iii) exogenous oxidative stressors. In wild-type mice, WEI demonstrated favourable closure characteristics compared to both control and stented wounds, however, wounds progressed to closure by 4 weeks. In contrast, diabetic WEI wounds persisted for 6-10 weeks with reduced contracture and epithelialization. In both diabetic and wild-type mice, WEI sites demonstrated persistence of inflammatory populations, absence of epithelialization, and histologic presence of alpha-SMA positive granulation tissue when compared to controls. We conclude that the WEI technique is particularly valuable for modelling recalcitrant diabetic wounds with sustained inflammation and dysfunctional healing.

Evolution of the Push-2-Spin Fat Graft Processing Device: Enhancing Efficiency and Reducing Risk of Contamination.

Background: Small-volume fat graft efficiency is a critical determinant of the cost and material effectiveness of aesthetic fat grafting in the clinical space. Recent development of devices, such as the Push-2-Spin (P2S) system (Pittsburgh, PA), has improved upon the process by yielding a rapid, handheld, multi-use system to minimize operative time and mess. Objectives: In this study, the authors describe further technical innovations on the P2S prototype that improve operative ease of use, time, and safety. Methods: Abdominoplasty samples were obtained as discarded tissue. Lipoaspirate was collected utilizing a 3.0 mm liposuction cannula and processed through centrifugation (Coleman technique), gauze (telfa) rolling, mesh straining, the tabletop P2S device (prototype), or the P2S handheld (P2S-H) device. Operative processing time, spin time, oil fraction, stromal vascular fraction (SVF) yield and viability, and adipocyte viability were assessed to compare the efficacy and viability of each device/technique. Blood agar smears of lipoaspirate were performed to assess for risk of contamination. Results: The P2S-H device outperformed its prior iteration in rotary and processing speed and was significantly faster than each other technique assessed. Furthermore, the use of an inline system offered significant advantages over open-air techniques in terms of resistance to contamination. Serial use characteristics were assessed; under these conditions, oil yield as well as adipocyte and SVF number and viability was similar between all techniques. Conclusions: The technical advancements to the P2S system which enable single-unit, handheld operation significantly improve operative time and minimize space requirements. This operative quality of life improvement comes at no cost to the efficacy of oil extraction, cellular yield, or cell viability.

Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck.

Importance: Venous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile. Objective: To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID. Design, Setting, and Participants: This was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022. Main Outcomes and Measures: Outcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes. Results: Among the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701). Conclusions and Relevance: This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

Establishment of a Robust and Reproducible Model of Radiation-Induced Skin and Muscle Fibrosis.

Radiation-induced skin fibrosis (RISF) can result from a plethora of scenarios including cancer therapy, accidental exposure, or acts of terrorism. Radioactive beams can penetrate through the skin and affect the structures in their path including skin, muscles, and internal organs. Skin is the first structure to get exposed to radiation and is susceptible to develop chronic fibrosis, which is challenging to treat. Currently, limited treatment options show moderate efficacy in mitigating radiation-related skin fibrosis. A key factor hindering the development of effective countermeasures is the absence of a convenient and robust model that could allow for translation of the experimental findings to humans. Here, a robust and reproducible murine hind limb skin fibrosis model has been established for prophylactic and therapeutic evaluation of possible agents for functional and molecular recovery. The right hind limb was irradiated using a single dose of 40 (Gray) Gy to induce skin fibrosis. Subjects developed edema and dermatitis in the early stages proceeded by visible skin constriction. Irradiated limbs showed a significantly reduced limb range of motion in the following weeks. In late stages, acute side effects subsided, yet chronic fibrosis persisted. A gait index was performed as an additional functional assay, which demonstrated the development of functional impairment. These non-invasive methods demonstrated reliable measurements for tracing fibrosis progression, which is supported by histological analyses. The radiation dose, application, and post-irradiation analyses employed in this model offer a vigorous and reproducible method for studying radiation-induced skin fibrosis and testing the efficacy of therapeutical agents.

Standard Fixed Enoxaparin Dosing for Venous Thromboembolism Prophylaxis Leads to Low Peak Anti-Factor Xa Levels in Both Head and Neck and Breast Free Flap Patients.

BACKGROUND: Venous thromboembolism (VTE) is a serious complication, particularly in cancer patients undergoing free flap reconstruction. Subcutaneous enoxaparin is the conventional prophylaxis for VTE prevention, and serum anti-factor Xa (afXa) levels are being increasingly used to monitor enoxaparin activity. In this study, free flap patients receiving standard enoxaparin prophylaxis were prospectively followed to investigate postoperative afXa levels and 90-day VTE and bleeding-related complications. METHODS: Patients undergoing free tissue transfer during an 8-month period were identified and prospectively followed. Patients received standard fixed enoxaparin dosing at 30 mg twice daily in head and neck (H&N) and 40 mg daily in breast reconstructions. Target peak prophylactic afXa range was 0.2 to 0.5 IU/mL. The primary outcome was the occurrence of 90-day postoperative VTE- and bleeding-related events. Independent predictors of afXa level and VTE incidence were analyzed for patients that met the inclusion criteria. RESULTS: Seventy-eight patients were prospectively followed. Four (5.1%) were diagnosed with VTE, and six (7.7%) experienced bleeding-related complications. The mean afXa levels in both VTE patients and bleeding patients were subprophylactic (0.13 ± 0.09 and 0.11 ± 0.07 IU/mL, respectively). Forty-six patients (21 breast, 25 H&N) had valid postoperative peak steady-state afXa levels. Among these, 15 (33%) patients achieved the target prophylactic range: 5 (33%) H&N and 10 (67%) breast patients. The mean afXa level for H&N patients was significantly lower than for breast patients (p = 0.0021). Patient total body weight was the sole negative predictor of afXa level (R 2 = 0.47, p < 0.0001). CONCLUSION: Standard fixed enoxaparin dosing for postoperative VTE prophylaxis does not achieve target afXa levels for the majority of our free flap patients. H&N patients appear to be a particularly high-risk group that may require a more personalized and aggressive approach. Total body weight is the sole negative predictor of afXa level, supporting a role for weight-based enoxaparin dosing.

Facial Nerve Repair: Bioengineering Approaches in Preclinical Models.

Injury to the facial nerve can occur after different etiologies and range from simple transection of the branches to varying degrees of segmental loss. Management depends on the extent of injury and options include primary repair for simple transections and using autografts, allografts, or conduits for larger gaps. Tissue engineering plays an important role to create artificial materials that are able to mimic the nerve itself without extra morbidity in the patients. The use of neurotrophic factors or stem cells inside the conduits or around the repair site is being increasingly studied to enhance neural recovery to a greater extent. Preclinical studies remain the hallmark for development of these novel approaches and translation into clinical practice. This review will focus on preclinical models of repair after facial nerve injury to help researchers establish an appropriate model to quantify recovery and analyze functional outcomes. Different bioengineered materials, including conduits and nerve grafts, will be discussed based on the experimental animals that were used and the defects introduced. Future directions to extend the applications of processed nerve allografts, bioengineered conduits, and cues inside the conduits to induce neural recovery after facial nerve injury will be highlighted. Impact statement Recovery after facial nerve injury is a complex process, which involves different management options such as primary repair or the use of nerve grafts or conduits. Various tissue-engineered approaches are increasingly studied on preclinical models with limited, but promising, translation to the clinical setting. Herein, preclinical models focusing on different recovery methods after facial nerve injury are comprehensively reviewed based on the experimental animals used. The review provides key insights into current developments and future directions on this highly relevant topic to help researchers further expand the field of tissue engineering and facial nerve recovery.

Individually tailored approach to reconstruction of complex defects using versatility of the lateral circumflex femoral artery system-based pedicled flaps.

Lateral circumflex femoral artery (LCFA) system is one of the most versatile donor sites in the body. We present our experience with pedicled flaps from the LCFA system, including different components for a wide variety of etiologies and locations. Twenty-three consecutive pedicled flaps were performed on 22 patients (10 females and 12 males; age 4-71 years) between 2007 and 2015 by a single surgeon. Flap size, type, and composition were tailored according to the requirements of the defects, including (1) location; (2) surface area; (3) depth; (4) number of defects; (5) presence of exposed critical structures; (6) presence of exposed foreign bodies; (7) prior use of other options; (8) history of radiation; and (9) other comorbidities. Defect locations were 10 abdominal wall (including groin and pubis), 9 ischio-gluteo-trochanteric and 4 perineal. Defect sizes ranged from 6 × 6 to 30 × 35 cm. Maximum depth of wounds ranged between 7 and 18 cm. The flap sizes ranged from 9 × 6 to 38 × 20 cm. Two flaps were fasciocutaneous perforator, 4 were myocutaneous with "muscle sparing" vastus lateralis, 10 were myocutaneous with "segmental" vastus lateralis, 5 were myocutaneous "tri-muscle," 1 was "tri-muscle," and 1 was rectus femoris only. Donor sites were closed primarily in 20 cases and with split thickness skin grafting in 3 cases. All flaps survived completely without any partial loss or congestion. Pedicled flaps from the LCFA system can be tailored individually for a wide variety of etiologies and locations. Muscles can be harvested and used as "muscle sparing," "segmental," and "tri-muscle" to accommodate the requirements of the defects.

A Single Superior Gluteal Artery Perforator Flap in Reconstruction of Large Midline Sacral Defects: A Method for Practical Harvest and Safe Closure.

BACKGROUND: Large midline sacral defects are reconstructive challenges. Superior gluteal artery perforator (SGAP) flap provides enough tissue and versatility to cover large defects; however, a single flap may be insufficient. We present a technique to cover large defects using single SGAP flaps. METHODS: Large sacral defects (>100 cm2) reconstructed with single SGAP flaps were included. Angle of transposition (45°-60°) was determined based on the tissue laxity and mobility of gluteal area. Perforator identification, intramuscular dissection, or skeletonization was not performed. Outcomes were measured as achieving durable reconstruction, flap viability, and complications. RESULTS: There were 17 patients (12 male, 5 females; aged 25-72 years) with different etiologies. The mean flap surface area (136.1 ± 45.6 cm2, between 9 × 8 and 26 × 10 cm) was smaller than the mean defect surface area (211.1 ± 87.2 cm2, between 10 × 10 and 28 × 14 cm) (P < 0.001). All flaps survived with no partial or complete flap loss. Minor dehiscence in 4 patients (2 at donor site and 2 at recipient site) healed with dressing changes or using negative-pressure vacuum therapy. All patients had durable outcomes without any recurrence. CONCLUSION: Single unilateral SGAP flaps can be used to completely cover midline large sacral defects. It is important to design the flaps to have a joint side with the defect in the proximal part and use the intrinsic mobility of gluteal soft tissues for the closure. Flaps can be (1) planned to be smaller than the defects, (2) harvested with no intramuscular perforator dissection or pedicle skeletonization, and (3) transposed with an angle less than 60°.