Assessment of Early and Late Management of Submental Gunshot Wounds.

Background: Management of submental gunshot wounds is becoming more common and requires complex surgical decisions. Objective: Compare outcomes of early and definitive reconstructive techniques following submental gunshot wounds. Methods: Retrospective chart review evaluated subjects who sustained a self-inflicted submental gunshot. The incidence of complications requiring unplanned operations was compared for early management techniques of skin/soft tissue, bone, and mucosal lining and definitive reconstructive techniques using Fisher's or Pearson Chi-square exact test with p ≤ 0.05 considered statistically significant. Results: The total of 27 patients were included. Early techniques included skin = primary soft tissue closure (n = 19) versus wound vacuum-assisted closure (n = 8); mandible = open reduction internal fixation (ORIF) (n = 19) versus external fixation (n = 8); and oral mucosal lining = primary mucosal closure (n = 20) versus dermal substitute (n = 7). Definitive management included ORIF (n = 10, 37%), ORIF with bone grafting (n = 8, 30%), and microvascular free-flap (n = 9, 33%). The incidence of complications requiring unplanned operation when using dermal substitutes for mucosal lining management was statistically higher than primary closure (p < 0.001); otherwise the complication rates of surgical techniques were equivalent. Conclusion: Several surgical decisions and techniques can be utilized at the time of early and definitive management of submental gunshot wounds. Only the use of dermal substitutes for mucosal lining is associated with a significantly higher rate of unplanned operation.

Amyand's Hernia: A Radiological Solution of a Surgical Dilemma.

Amyand's hernia is a rare condition whereby the appendix lies within the sac of an inguinal hernia; rarer still, the appendix can become inflamed (acute appendicitis) and is frequently misdiagnosed as a strangulated inguinal hernia. We report a case of Amyand's hernia complicated with acute appendicitis. In this case an accurate preoperative diagnosis was provided by a preoperative Computerised Tomography (CT) scan, permitting planning of treatment by a laparoscopic approach.

Comparing imaging biomarkers of cerebral edema after TBI in young adult male and female rats.

Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. Cerebral edema following TBI is known to play a critical role in injury severity and prognosis. In the current study we used multimodal magnetic resonance imaging (MRI) to assess cerebral edema 24 h after unilateral contusive TBI in male and female rats. We then directly quantified brain water content in the same subjectsex vivo.We found that both males and females had similarly elevated T2 values after TBI compared with sham controls. Apparent diffusion coefficient (ADC) was more variable than T2 and did not show significant injury effects in males or females. Brain water was elevated in male TBI rats compared with sham controls, but there was no difference between female TBI and sham groups. Notably, MRI biomarkers of edema were more closely correlated with brain water in male rats; female rats did not show any relationship between brain water and T2 or ADC. These observations raise questions about the interpretation of radiological findings traditionally interpreted as edema in female TBI patients. A better understanding of sex differences and similarities in the pathophysiology of post-traumatic edema is needed to help improve patient management and the development of effective treatment strategies for men and women.

Pediatric Odontogenic and Maxillofacial Bone Pathology: A Global Analysis.

BACKGROUND: Although pathology in the maxillary and mandibular bones is rare in young patients, the differential diagnosis is broad. The World Health Organization (WHO) updated its classification of maxillofacial bone pathology in 2017. Using these updated guidelines, a systematic review of common maxillofacial bone lesions in the pediatric population was performed. METHODS: A PubMed search was conducted capturing English language articles from inception to July 2020. Thirty-one articles were identified that described the frequency of maxillofacial bone pathology. Data were extracted and organized using the WHO 2017 classification of odontogenic and maxillofacial bone tumors. Prevalence data were analyzed among diagnostic categories and geographical regions. The SAS version 9.4 was used to complete statistical analyses. RESULTS: The articles included patients from birth to a maximum age of 14 to 19 years. The most common odontogenic cysts included radicular cyst (42.7%) and dentigerous cyst (39.0%) followed by odontogenic keratocyst (15.0%). Among odontogenic bone tumors, odontoma (49.3%) was most common followed by ameloblastoma (29.1%). The most common nonodontogenic bone tumor was fibrous dysplasia (42.4%), and the most common malignant bone tumor was osteosarcoma (75.0%). Significant variations were found by geographic region, with dentigerous cyst more common than radicular cyst, and ameloblastoma more common than odontoma in African and Asian countries (P < 0.0001). CONCLUSIONS: This systematic review uses the WHO 2017 guidelines to classify common odontogenic and nonodontogenic maxillofacial bone lesions around the world. Pathogenesis, presentation, and available treatment options for the most common maxillofacial bone lesions are reviewed.

Outcomes and Utility of Intracranial Free Tissue Transfer.

OBJECTIVE: Complications associated with intracranial vault compromise can be neurologically and systemically devastating. Primary and secondary repair of these deficits require an air and watertight barrier between the intracranial and extracranial environments. This study evaluated the outcomes and utility of using intracranial free tissue transfer as both primary and salvage surgical repair of reconstruction. METHODS: A retrospective review was performed of all subjects who underwent intracranial free tissue transfer as primary or salvage repair. RESULTS: A total of 13 intracranial free tissue transfers were performed on 11 subjects: osteocutaneous radial forearm free flaps (n = 6), partial myofascial rectus abdominis flaps (n = 5), temporoparietal fascia flap (n = 1), and serratus anterior myofascial flap (n = 1). Primary reconstruction was performed on 4 subjects with the remaining being salvage repair. Indications for surgery included neoplasm (n = 6 of 11), ballistic trauma (n = 3 of 11), motor vehicle accident (n = 1 of 11), and infection (n = 1 of 11). Three subjects required additional surgical repair for CSF leak and pneumocephalus, with 2 subjects requiring an additional free tissue transfer at a different site. CONCLUSION: In our experience, free tissue transfer is an effective primary and salvage surgical technique in the reconstruction of complex intracranial problems.

Anatomic Subunit Approach to Composite Reconstruction of Facial Gunshot Wounds.

ABSTRACT: With a rise in gun violence in the United States, surgeons are tasked with effectively managing penetrating facial trauma. The purpose of this study is to assess methods used for successful composite reconstruction of each anatomical facial subunit following penetrating trauma. A retrospective chart review was performed in subjects undergoing craniofacial reconstruction following penetrating trauma. Reconstructive methods were analyzed through operative reports. Subjects were categorized by anatomical subunit reconstructed (mandible, maxilla (malar complex and roof/palate), orbit, and cranium) and method of reconstruction (open reduction internal fixation only, bone graft, free flap, implant, and tissue expansion). Thirty-six subjects underwent reconstruction for penetrating facial trauma. Involved subunits include 24 mandible, 11 malar complex, 13 palate, 18 orbit, and 11 cranium. Predominate reconstruction method was open reduction internal fixation only for mandible (45.8%), bone grafting for malar complex (81.8%), implant for orbit (66.7%) and cranium (63.6%), and local tissue rearrangement for palate (84.6%). The predominate bone graft donor site was iliac for mandible (42.9%), rib for malar complex (36.3%) and orbit (40.0%), and frontal bone for cranium (42.8%). The predominate free flap was osteocutaneous for all mandible, orbit, and cranium and 7 of 10 (70.0%) palate reconstructions. Tissue expansion was used in all subunits except cranium. In conclusion, bone grafting, implants, free tissue transfer, and tissue expansion are all viable reconstruction options for penetrating trauma. There is no single approach to use, and decisions regarding definitive reconstruction method should be based upon anatomical subunit involved and the size/area of defects.

Giant Congenital Blue Nevus Presenting as Cutis Verticis Gyrata: A Case Report and Review of the Literature.

OBJECTIVES: Cerebriform intradermal nevus and giant congenital blue nevi are rarely reported melanocytic nevi with clinical and histopathologic similarities. Both are known to produce cutis verticis gyrata. We report a significantly large occipital scalp congenital blue nevus with secondary cutis verticis gyrata. The aim of this report is to increase clinical awareness of this entity, highlight histopathologic and mutational features of cerebriform intradermal nevi and giant congenital blue nevi, and stress the importance of clinicopathologic correlation for diagnosis. METHODS: Case report and review of the literature. RESULTS: A 20-year-old Asian male presented with a long-standing, large (20 cm × 30 cm), exophytic tumor at the occipital scalp and posterior neck. The skin overlying the lesion was arranged in thick folds resembling the surface of the brain, devoid of hair follicles, and discolored by salt-and-pepper pattern hyperpigmentation. After correlating the clinical and histopathologic findings, we diagnosed giant congenital blue nevus with secondary cutis verticis gyrata. Staged surgical excision was performed with subsequent treatment for hypertrophic scarring and occipital alopecia. CONCLUSIONS: Cerebriform intradermal nevus and giant congenital blue nevus have overlapping histologic and clinical features. Head and neck surgeons should be aware that nomenclature of these tumors is subjective and often imprecise. Diagnosis requires correlation of clinical findings, patient history, and histopathology. Surgical excision is advised due to rare malignant transformation potential.

Cartilage Grafting Outcomes in Intermediate and Definitive Cleft Rhinoplasty.

OBJECTIVE: To compare cartilage grafting outcomes in intermediate versus definitive cleft rhinoplasty. DESIGN: A retrospective chart review was conducted. The χ2 and Fisher exact tests were used for statistical analyses. Results were considered statistically significant at P < .05. PARTICIPANTS: All subjects who underwent revision cleft rhinoplasties between July 2011 and June 2019 were included. Subjects with syndromic conditions were excluded. RESULTS: A total of 46 subjects with a cleft nose deformity underwent 65 rhinoplasty procedures. The ages averaged 17 years (range 5-50) with 34 (73.9%) males and 12 (26.1%) females. In the intermediate group, 6 (28.6%) subjects required cartilage grafting as part of 6 cleft rhinoplasties, whereas 15 (71.4%) subjects underwent a total of 26 cleft rhinoplasties that did not require grafting. In the definitive group, 18 (76%) subjects required cartilage grafting over 21 cleft rhinoplasties, whereas 7 (24%) subjects underwent a total of 9 cleft rhinoplasties where cartilage grafting was not required. The difference between the number of subjects requiring cartilage grafting in the intermediate versus the definitive group was statistically significant (P = .007). Ear concha and nose were the most frequently used cartilage donor sites, with no observed complications. CONCLUSIONS: Cartilage grafting was significantly more common in the definitive rhinoplasty group. Intermediate cleft rhinoplasty during the 5- to 13-year age period was effective, with a low-risk profile. In our experience, ear concha and nose were the preferred cartilage donor sites, with effective results and an excellent safety profile.

Unrepaired decompressive craniectomy worsens motor performance in a rat traumatic brain injury model.

Decompressive craniectomy (DC) is often required to manage rising intracranial pressure after traumatic brain injury (TBI). Syndrome of the trephine (SoT) is a reversible neurologic condition that often occurs following DC as a result of the unrepaired skull. The purpose of the present study is to characterize neurological impairment following TBI in rats with an unrepaired craniectomy versus rats with a closed cranium. Long Evans male rats received a controlled cortical impact (CCI) over the caudal forelimb area (CFA) of the motor cortex. Immediately after CCI, rats received either a hemi-craniectomy (TBI Open Skull Group) or an immediate acrylic cranioplasty restoring cranial anatomy (TBI Closed Skull Group). Motor performance was assessed on a skilled reaching task on post-CCI weeks 1-4, 8, 12, and 16. Three weeks after the CCI injury, the TBI Closed Skull Group demonstrated improved motor performance compared to TBI Open Skull Group. The TBI Closed Skull Group continued to perform better than the TBI Open Skull Group throughout weeks 4, 8, 12 and 16. The protracted recovery of CFA motor performance demonstrated in rats with unrepaired skulls following TBI suggests this model may be beneficial for testing new therapeutic approaches to prevent SoT.

Manifestations of Apprehension and Anxiety in a Sprague Dawley Cranial Defect Model.

BACKGROUND: Syndrome of the trephined is a neurologic condition that commonly arises in patients who undergo craniectomy and have a prolonged cranial defect. Symptoms of this condition include headache, difficulties concentrating, diminished fine motor/dexterity skills, mood changes, and anxiety/apprehension. The authors hypothesize that an animal model demonstrating anxiety/apprehension in rats who undergo craniectomy is feasible utilizing standardized animal behavioral testing. METHODS: Sprague Dawley rats were the stratified to 1 of 2 groups for comparison of neurobehavioral outcomes. Group #1 (closed cranial group) had their cranial trephination immediately closed with acrylic to restore normal cranial anatomy and Group #2 (open cranial group) had their cranial trephination enlarged to represent a decompressive hemicraniectomy immediately. Anxiety/apprehension was studied using a standardized rodent open field test. Statistical comparison of differences among the 2 groups was performed. RESULTS: Ten rats were studied with 5 rats in each group. Standard rodent open field testing of anxiety demonstrated no difference among the 2 groups at 1 week. Rats in the "Open cranial group" demonstrated progressively more anxiety over the following 3-month period. Rats in the "Open cranial group" demonstrated increasing anxiety levels as compared with rats in the "Closed cranial group." At week 16, the "Open cranial group" anxiety levels were significantly greater than week 4 (t = 2.24, P = 0.04) demonstrating a significant linear trend over time (R = 0.99; P = 0.002). The "Closed cranial group" did not show this trend (R = 07; P = 0.74). CONCLUSION: Our study demonstrates that anxiety and apprehension are more prevalent in rats with an open, prolonged cranial defect in comparison to those with a closed cranium. This correlates with similar finds in humans with syndrome of the trephined.

Surgical Decision-Making in Microvascular Reconstruction of Composite Scalp and Skull Defects.

OBJECTIVES: Microvascular reconstruction of composite scalp and skull defects requires careful planning of both cranial bone and soft-tissue coverage. The current body of literature has yet to identify a "best practice" approach to achieve these goals. METHODS: A retrospective chart review was performed. Patients with composite defects who underwent combined microvascular surgery of the scalp and skull were included over a 6-year period. Reconstructions were classified by: microvascular flap, cranioplasty, timing of cranioplasty (primary or delayed), and exposure to radiation. RESULTS: Forty-five microvascular flaps were performed for 36 patients. Fasciocutaneous flaps were more likely to experience complications than other microvascular flaps (50.0% versus 8.6%, P = 0.008). Forty of the 50 patients (80%) underwent cranioplasty, including 19 autogenous and 21 alloplastic reconstructions. There were 8 total complications: partial flap loss with implant exposure (n = 5), cranioplasty infection (n = 2), and wound dehiscence (n = 1). Alloplastic implants experienced more frequent complications than autologous reconstructions (33.3% versus 5.3%, P = 0.046). Titanium implants demonstrated the higher rates of complications than other groups (P = 0.014). Titanium implants also had more complications relative to poly-ether-ether-ketone implants (60.0% versus 9.1%, P = 0.024). Immediate alloplastic cranioplasty was associated with a significant increase in complications relative to autogenous reconstruction (54.5% versus 5.5%, P = 0.027), and no significant difference in the delayed group (10% versus 0%, P = 0.740). CONCLUSION: According to authors' knowledge, myofascial flaps yield the lowest complication rate and when possible, autologous cranioplasty is preferred. When defects are too large to accommodate autogenous bone, the authors prefer delayed prefabricated poly-ether-ether-ketone implant reconstruction.

COVID-19 Pandemic and its Impact on Craniofacial Surgery.

In late 2019, a novel coronavirus strain, SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), also known as coronavirus disease 2019 (COVID-19), triggered a global pandemic as the virus spread from the Wuhan Province, China, across all continents. Although infrequent, severe respiratory infection and death caused by SARS-CoV-2 is disproportionately high amongst healthcare providers such as craniofacial surgeons who work in the head and neck region. Factors this impact SARS-CoV-2 transmission include: (1) high viral loads in the mucosa of the oral and nasopharynx, (2) limited and/or imprecise disease screening/confirmation testing, (3) access to and appropriate use of personal protective equipment (PPE).

Syndrome of the Trephined: Quantitative Functional Improvement after Large Cranial Vault Reconstruction.

BACKGROUND: Large decompressive craniectomies may be life-saving; however, they may also result in syndrome of the trephined. This postrecovery sequela is characterized by dizziness, fatigue, depression, weakness, speech slowing, gait disturbance, and impaired mentation. Because this entity is poorly understood, the authors attempted to quantify the functional improvement in patients with syndrome of the trephined after cranial vault reconstruction. METHODS: Patients with cranial vault defects (>50 cm) from trauma, meningioma, and hemorrhage were studied preoperatively and postoperatively (6 months) after cranial vault reconstruction using (1) the Cognistat Active Form and (2) the Functional Independence Measure instrument (n = 40). Cranial vault reconstructive techniques varied from split cranial bone to alloplastic implants (polyetheretherketone or titanium mesh). RESULTS: Of the 143 patients treated with decompressive craniectomies, 28 percent (n = 40) developed symptoms of syndrome of the trephined. A larger craniectomy defect size correlated with development of syndrome of the trephined. Time from craniectomy to presentation of symptoms was 4.5 months. Time from craniectomy to cranial vault reconstruction was 6.1 months. Time from cranial vault reconstruction to symptom improvement was 4.3 days. Complete functional recovery of syndrome of the trephined was seen in 70 percent. Type of cranial vault reconstruction included polyetheretherketone implant (57.5 percent), split calvarial graft (22.5 percent), and titanium mesh (20 percent), and was not a determinant of functional improvement. Cognistat assessment score noted improvement (from 38 to 69); likewise, the Functional Independence Measure measurement tool showed improvement (from 38 to 98). CONCLUSIONS: Syndrome of the trephined occurs more frequently than previously described in posttraumatic patients with large cranial vault defects. Cranial vault reconstruction leads to significant, quantifiable functional improvement in a large number of patients. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Thiolated bone and tendon tissue particles covalently bound in hydrogels for in vivo calvarial bone regeneration.

Bone regeneration of large cranial defects, potentially including traumatic brain injury (TBI) treatment, presents a major problem with non-crosslinking, clinically available products due to material migration outside the defect. Commercial products such as bone cements are permanent and thus not conducive to bone regeneration, and typical commercial bioactive materials for bone regeneration do not crosslink. Our previous work demonstrated that non-crosslinking materials may be prone to material migration following surgical placement, and the current study attempted to address these problems by introducing a new hydrogel system where tissue particles are themselves the crosslinker. Specifically, a pentenoate-modified hyaluronic acid (PHA) polymer was covalently linked to thiolated tissue particles of demineralized bone matrix (TDBM) or devitalized tendon (TDVT), thereby forming an interconnected hydrogel matrix for calvarial bone regeneration. All hydrogel precursor solutions exhibited sufficient yield stress for surgical placement and an adequate compressive modulus post-crosslinking. Critical-size calvarial defects were filled with a 4% PHA hydrogel containing 10 or 20% TDBM or TDVT, with the clinical product DBXⓇ being employed as the standard of care control for the in vivo study. At 12 weeks, micro-computed tomography analysis demonstrated similar bone regeneration among the experimental groups, TDBM and TDVT, and the standard of care control DBXⓇ. The group with 10% TDBM was therefore identified as an attractive material for potential calvarial defect repair, as it additionally exhibited a sufficient initial recovery after shearing (i.e., > 80% recovery). Future studies will focus on applying a hydrogel in a rat model for treatment of TBI. STATEMENT OF SIGNIFICANCE: Non-crosslinking materials may be prone to material migration from a calvarial bone defect following surgical placement, which is problematic for materials intended for bone regeneration. Unfortunately, typical crosslinking materials such as bone cements are permanent and thus not conducive to bone regeneration, and typical bioactive materials for bone regeneration such as tissue matrix are not crosslinked in commercial products. The current study addressed these problems by introducing a new biomaterial where tissue particles are themselves the crosslinker in a hydrogel system. The current study successfully demonstrated a new material based on pentenoate-modified hyaluronic acid with thiolated demineralized bone matrix that is capable of rapid crosslinking, with desirable paste-like rheology of the precursor material for surgical placement, and with bone regeneration comparable to a commercially available standard-of-care product. Such a material may hold promise for a single-surgery treatment of severe traumatic brain injury (TBI) following hemicraniectomy.

Outcomes of Head and Neck Microvascular Reconstruction in Hypercoagulable Patients.

BACKGROUND: Inherited coagulopathies and previous thrombotic events are often considered relative contraindications to microvascular reconstruction. We hypothesize that with planning, head and neck microvascular reconstruction can be successfully performed in hypercoagulable individuals. METHODS: A retrospective review was conducted of subjects with coagulopathies or previous thrombotic events who underwent microvascular head and neck reconstruction. Outcomes studied were "flap-related complications" (arterial/venous compromise or flap loss) and "patient-related complications" (hematoma, deep venous thrombosis, pulmonary embolism, infection, stroke, or death). RESULTS: One hundred thirty-four microvascular flaps were performed in 117 subjects. Twenty-four subjects (20.5%) had a preoperative hypercoagulable condition and underwent 28 microvascular reconstructions. Twenty-three of 24 subjects had a previous thrombotic event, with five subjects identified with an inherited or acquired coagulopathy. All microvascular reconstructions were successful; however, complications occurred in 12 of 28 reconstructions (42.9%). Complications were "flap related" in four reconstructions (14.3%), "patient related" in nine reconstructions (32.1%), and both in one reconstruction (3.6%). Flap-related complications included small partial flap loss (n = 2), arterial compromise (n = 1), and venous compromise (n = 1), with all undergoing successful salvage. Patient-related complications included hematoma (n = 3), pulmonary embolism (n = 2), infection (n = 2), deep venous thrombosis (n = 1), and death (n = 1). Statistical analysis demonstrated that complications were more common in subjects with inferior vena cava filters (p = 0.06) and hematomas were associated with the use of therapeutic heparin infusion (p = 0.04). CONCLUSION: Microvascular head and neck reconstruction can be successfully performed in hypercoagulable subjects. However, patient-related complications remain a concern in these subjects.

Comparison of Modern Rigid Fixation Plating Outcomes for Segmental Mandibular Microvascular Reconstruction.

OBJECTIVES/HYPOTHESIS: New advances in osseous microvascular mandibular rigid fixation are being employed at many institutions. These include standardized prebent/preformed reconstruction plates as well as computer-aided design/computer-aided manufacturing (CAD/CAM) custom plates that are patient specific. Our goal was to assess and compare the outcomes of both of these new technologies when utilized for mandibular microvascular reconstruction. STUDY DESIGN: Retrospective chart review. METHODS: Subjects were categorized into two groups according to their mandibular rigid fixation technique: group 1 = prebent/preformed plates and group 2 = CAD/CAM custom plates. Primary outcome measures were 1) perioperative complications (defined as deep tissue infection, wound dehiscence resulting in bone exposure, and/or plate exposure) and 2) reoperation rates for mandibular hardware failure/explantation. Statistical analysis consisted of χ2 , Fisher exact test, and multivariable regression models. RESULTS: A total of 142 subjects underwent microvascular mandibular reconstruction in a 6-year period. Eighty-nine subjects utilized prebent/preformed plates, and 53 employed CAD/CAM custom plates. Perioperative complications occurred in 32 of 89 (35.9%) subjects with prebent/preformed plates and 11 of 53 (20.7%) subjects using CAD/CAM custom plates. Reoperation requiring hardware explantation occurred in 18 of 89 (20.2%) subjects and three of 53 (5.6%) using CAD/CAM custom plates. Statistical comparison of perioperative complications between the two groups approached significance (P = .0556), and the rate of reoperation was significant favoring CAD/CAM implants (P = .0180). CONCLUSIONS: In our experience, CAD/CAM custom plates utilized for rigid fixation during microvascular mandibular reconstruction demonstrated fewer complications and statistically lower reoperation rates when compared with prebent/preformed plates. LEVEL OF EVIDENCE: 2c Laryngoscope, 129:1081-1086, 2019.

Identification and Management of Cranial Anomalies in Perinatology.

Neonatal skull and head shape anomalies are rare. The most common cranial malformations encountered include craniosynostosis, deformational plagiocephaly, cutis aplasia, and encephalocele. Improved prenatal imaging can diagnose morphologic changes as early as the second trimester. Prenatal identification also provides perinatologists and neonatologists with valuable information that helps to optimize care during and after delivery. Cranial anomalies require a multidisciplinary team approach and occasionally a lifetime of care. Today, care begins with the perinatologist as many cranial anomalies can be identified in utero with recent advances in prenatal testing.

Classification and Microvascular Flap Selection for Anterior Cranial Fossa Reconstruction.

BACKGROUND: Microvascular reconstruction of the anterior cranial fossa (ACF) creates difficult challenges. Reconstructive goals and flap selection vary based on the defect location within the ACF. This study evaluates the feasibility and reliability of free tissue transfer for salvage reconstruction of low, middle, and high ACF defects. METHODS: A retrospective review was performed. Reconstructions were anatomically classified as low (anterior skull base), middle (frontal bar/sinus), and high (frontal bone/soft tissue). Subjects were evaluated based on pathologic indication and goal, type of flap used, and complications observed. RESULTS: Eleven flaps in 10 subjects were identified and anatomic sites included: low (n = 5), middle (n = 3), and high (n = 3). Eight of 11 reconstructions utilized osteocutaneous flaps including the osteocutaneous radial forearm free flap (OCRFFF) (n = 7) and fibula (n = 1). Other reconstructions included a split calvarial graft wrapped within a temporoparietal fascia free flap (n = 1), latissimus myocutaneous flap (n = 1), and rectus abdominis myofascial flap (n = 1). All 11 flaps were successful without microvascular compromise. No complications were observed in the high and middle ACF defect groups. Two of five flaps in the low defect group using OCRFFF flaps failed to achieve surgical goals despite demonstrating healthy flaps upon re-exploration. Complications included persistent cerebrospinal fluid leak (n = 1) and pneumocephalus (n = 1), requiring flap repositioning in one subject and a second microvascular flap in the second subject to achieve surgical goals. CONCLUSION: In our experience, osteocutaneous flaps (especially the OCRFFF) are preferred for complete autologous reconstruction of high and middle ACF defects. Low skull base defects are more difficult to reconstruct, and consideration of free muscle flaps (no bone) should be weighed as an option in this anatomic area.

Survival and clinical outcomes of patients with melanoma brain metastasis in the era of checkpoint inhibitors and targeted therapies.

BACKGROUND: Melanoma brain metastasis is associated with an extremely poor prognosis, with a median overall survival of 4-5 months. Since 2011, the overall survival of patients with stage IV melanoma has been significantly improved with the advent of new targeted therapies and checkpoint inhibitors. We analyze the survival outcomes of patients diagnosed with brain metastasis after the introduction of these novel drugs. METHODS: We performed a retrospective analysis of our melanoma center database and identified 79 patients with brain metastasis between 2011 and 2015. RESULTS: The median time from primary melanoma diagnosis to brain metastasis was 3.2 years. The median overall survival duration from the time of initial brain metastasis was 12.8 months. Following a diagnosis of brain metastasis, 39 (49.4%), 28 (35.4%), and 24 (30.4%) patients were treated with anti-CTLA-4 antibody, anti-PD-1 antibody, or BRAF inhibitors (with or without a MEK inhibitor), with a median overall survival of 19.2 months, 37.9 months and 12.7 months, respectively. Factors associated with significantly reduced overall survival included male sex, cerebellar metastasis, higher number of brain lesions, and treatment with whole-brain radiation therapy. Factors associated with significantly longer overall survival included treatment with craniotomy, stereotactic radiosurgery, or with anti-PD-1 antibody after initial diagnosis of brain metastasis. CONCLUSIONS: These results show a significant improvement in the overall survival of patients with melanoma brain metastasis in the era of novel therapies. In addition, they suggest the activity of anti-PD-1 therapy specifically in the setting of brain metastasis.

Superior calvarial bone regeneration using pentenoate-functionalized hyaluronic acid hydrogels with devitalized tendon particles.

Traumatic brain injury (TBI) is a life-threatening condition defined by internal brain herniation. Severe TBI is commonly treated by a two-stage surgical intervention, where decompressive craniectomy is first conducted to remove a large portion of calvarial bone and allow unimpeded brain swelling. In the second surgery, spaced weeks to months after the first, cranioplasty is performed to restore the cranial bone. Hydrogels with paste-like precursor solutions for surgical placement may potentially revolutionize TBI treatment by permitting a single-stage surgical intervention, capable of being implanted with the initial surgery, remaining pliable during brain swelling, and tuned to regenerate calvarial bone after brain swelling has subsided. The current study evaluated the use of photocrosslinkable pentenoate-functionalized hyaluronic acid (PHA) and non-crosslinking hyaluronic acid (HA) hydrogels encapsulating naturally derived tissue particles of demineralized bone matrix (DBM), devitalized cartilage (DVC), devitalized meniscus (DVM), or devitalized tendon (DVT) for bone regeneration in critical-size rat calvarial defects. All hydrogel precursors exhibited a yield stress for placement and addition of particles increased the average material compressive modulus. The HA-DBM (4-30%), PHA (4%), and PHA-DVT (4-30%) groups had 5 (p < 0.0001), 3.1, and 3.2 (p < 0.05) times greater regenerated bone volume compared to the sham (untreated defect) group, respectively. In vitro cell studies suggested that the PHA-DVT (4-10%) group would have the most desirable performance. Overall, hydrogels containing DVT particles outperformed other materials in terms of bone regeneration in vivo and calcium deposition in vitro. Hydrogels containing DVT will be further evaluated in future rat TBI studies. STATEMENT OF SIGNIFICANCE: Traumatic brain injury (TBI) is a life-threatening condition characterized by severe brain swelling and is currently treated by a two-stage surgical procedure. Complications associated with the two-stage surgical intervention include the occurrence of the condition termed syndrome of the trephined; however, the condition is completely reversible once the secondary surgery is performed. A desirable TBI treatment would include a single surgical intervention to avoid syndrome of the trephined altogether. The first hurdle in reaching the overall goal is to develop a pliable hydrogel material that can regenerate the patient's bone. The development of a pliable hydrogel technology would greatly impact the field of bone regeneration for TBI application and other areas of bone regeneration.