Socioeconomic Disparities in Postoperative Outcomes of Osteocutaneous Fibula Free Flaps for Head and Neck Reconstruction.

BACKGROUND: Osteocutaneous fibula free flaps (FFFs) are a fundamental component of reconstructive surgery in the head and neck region, particularly after traumatic injuries or oncologic resections. Despite their utility, FFFs are associated with various postoperative complications, such as infection, flap failure, and donor site morbidity, impacting up to 54% of cases. This study aimed to investigate the influence of socioeconomic variables, with a particular focus on median household income (MHI), on the incidence of postoperative complications in FFF reconstruction for head and neck cancer. METHODS: A retrospective analysis of 80 patients who underwent FFF reconstruction for head and neck cancer at a single center from 2016 to 2022 was conducted. Demographic and patient characteristics, including race, MHI, insurance type, history of radiation therapy, and TNM (tumor, node, metastasis) cancer stage, were evaluated. Logistic regression, controlling for comorbidities, was used to assess the impact of MHI on 30-, 90-, and 180-day postoperative complications. RESULTS: The patient population was predominantly male (n = 51, 63.8%) and White (n = 63, 78.8%), with the majority falling within the $55,000 to $100,000 range of MHI (n = 51, 63.8%). Nearly half of the patients had received neoadjuvant radiation treatment (n = 39, 48.75%), and 36.25% (n = 29) presented with osteoradionecrosis. Logistic regression analysis revealed that the $55,000-$100,000 MHI group had significantly lower odds of developing complications in the 0- to 30-day postoperative period when compared with those in the <$55,000 group (odds ratio [OR], 0.440; 95% confidence interval [CI], 0.205-0.943; P = 0.035). This trend persisted in the 31- to 90-day period (OR, 0.136; 95% CI, 0.050-0.368; P < 0.001) and was also observed in the likelihood of flap takeback. In addition, the $100,000-$150,000 group had significantly lower odds of developing complications in the 31- to 90-day period (OR, 0.182; 95% CI, 0.035-0.940; P = 0.042). No significant difference was found in the >$150,000 group. CONCLUSIONS: Median household income is a significant determinant and potentially a more influential factor than neoadjuvant radiation in predicting postoperative complications after FFF reconstruction. Disparities in postoperative outcomes based on income highlight the need for substantial health care policy shifts and the development of targeted support strategies for patients with lower MHI.

Complications Following Tissue Expander-Based Reconstruction in Pediatric Burn Injuries: A Retrospective Analysis.

BACKGROUND: Tissue expansion has been widely used to reconstruct soft tissue defects following burn injuries in pediatric patients, allowing for satisfactory cosmetic and functional outcomes. Factors impacting the success of tissue expander (TE)-based reconstruction in these patients are poorly understood. Herein, we aim to determine the risk factors for postoperative complications following TE-based reconstruction in pediatric burn patients. METHODS: A retrospective review of pediatric patients who underwent TE placement for burn reconstruction from 2006 to 2019 was performed. Primary outcomes were major complications (TE explantation, extrusion, replacement, flap necrosis, unplanned reoperation, readmission) and wound complications (surgical site infection and wound dehiscence). Descriptive statistics were calculated. The association between primary outcomes, patient demographics, burn characteristics, and TE characteristics was assessed using the chi-squared, Fisher's exact, and Mann-Whitney U tests. RESULTS: Of 28 patients included in the study, the median [interquartile range (IQR)] age was 6.5 (3.3-11.8) years, with a follow-up of 12 (7-32) months. The majority were males [n = 20 (71%)], Black patients [n = 11 (39%)], and experienced burns due to flames [n = 78 (29%)]. Eleven (39%) patients experienced major complications, most commonly TE premature explantation [n = 6 (21%)]. Patients who experienced major complications, compared to those who did not, had a significantly greater median (IQR) % total body surface area (TBSA) [38 (27-52), 10 (5-19), P = 0.002] and number of TEs inserted [2 (2-3), 1 (1-2), P = 0.01]. Ten (36%) patients experienced wound complications, most commonly surgical site infection following TE placement [n = 6 (21%)]. Patients who experienced wound complications, compared to those who did not, had a significantly greater median (IQR) %TBSA [35 (18-45), 19 (13-24), P = 0.02]. CONCLUSION: Pediatric burn injuries involving greater than 30% TBSA and necessitating an increasing number of TEs were associated with worse postoperative complications following TE-based reconstruction.

Optimal Treatment Order With Fibula-Free Flap Reconstruction, Oncologic Treatment, and Dental Implants: A Systematic Review and Meta-Analysis.

Head and neck cancer (HNC) patients benefit from craniofacial reconstruction, but no clear guidance exists for rehabilitation timing. This meta-analysis aims to clarify the impact of oncologic treatment order on implant survival. An algorithm to guide placement sequence is also proposed in this paper. PubMed, Embase, and Web of Science were searched for studies on HNC patients with ablative and fibula-free flap (FFF) reconstruction surgeries and radiotherapy (RTX). Primary outcomes included treatment sequence, implant survival rates, and RTX dose. Of 661 studies, 20 studies (617 implants, 199 patients) were included. Pooled survival rates for implants receiving >60 Gy RTX were significantly lower than implants receiving < 60 Gy (82.8% versus 90.1%, P=0.035). Placement >1 year after RTX completion improved implant survival rates (96.8% versus 82.5%, P=0.001). Implants receiving pre-placement RTX had increased survival with RTX postablation versus before (91.2% versus 74.8%, P<0.001). One hundred seventy-seven implants were placed only in FFF with higher survival than implants placed in FFF or native bone (90.4% versus 83.5%, P=0.035). Radiotherapy is detrimental to implant survival rates when administered too soon, in high doses, and before tumor resection. A novel evidence-based clinical decision-making algorithm was presented for utilization when determining the optimal treatment order for HNC patients. The overall survival of dental prostheses is acceptable, reaffirming their role as a key component in rehabilitating HNC patients. Considerations must be made regarding RTX dosage, timing, and implant location to optimize survival rates and patient outcomes for improved functionality, aesthetics, and comfort.

Cervicofacial Pediatric Tissue Expansion: Aesthetic Unit-Based Algorithm.

BACKGROUND: Tissue expansion is a powerful tool for reconstruction of pediatric soft-tissue pathologies, but complication rates for children have been reported as high as 40%. Infection and implant extrusion lead to premature removal and delays in reconstruction. Expanding the head and neck is uniquely challenging because the confluence of facial aesthetic units must be respected. These challenges have prompted the senior author's creation of an aesthetic-unit based algorithm. METHODS: A retrospective study of pediatric patients who underwent cervicofacial tissue expander placement by the senior author (R.J.R) was performed over a 17-year period. Predictor variables included age, sex, race, indication, number of expanders placed at each operation, serial expansion, expander type, expander size, home versus clinic inflation, and prophylactic antibiotics. Univariate and multivariate analyses were performed to identify risk factors for complications. RESULTS: An aesthetic-unit based reconstructive algorithm is proposed. Forty-eight pediatric patients had 111 cervicofacial tissue expanders placed. Twenty expanders were associated with complications (18%) for surgical site-infection (12.6%), extrusion (4.5%), and expander deflation (6.3%). Expanders placed for congenital nevi (p=0.042) and use of textured expander (p=0.027) were significantly associated with decreased complications. When controlling for covariates, serial expansion of the same site was associated with increased rates of readmission (p=0.027) after having just one prior expander. Iatrogenic ectropion occurred in 13.5% of the study population; expanders with at least one complication during tissue expansion were significantly associated with incidence of iatrogenic ectropion (p=0.026). CONCLUSION: By using an aesthetic-unit based algorithm, reconstructive outcomes can be optimized for pediatric cervicofacial tissue expansion.

Therapy of Mycobacterium abscessus Infections in Solid Organ Transplant Patients.

Mycobacterium abscessus complex (MABC), a rapidly growing Mycobacterium, is one of the most common causes of non-tuberculous mycobacteria (NTM) infections in the United States of America, and it has been associated with a wide spectrum of infections in immunocompetent and immunosuppressed individuals. Eradicating MABC is very challenging, even with prolonged combination therapies. The management of MABC infections in solid organ transplant (SOT) patients is usually complex given their net state of immunosuppression, associated comorbidities, and potential drug-drug interactions, among other things. In this manuscript, we discussed the antimicrobial management of pulmonary and extrapulmonary MABC infections. In addition, we reviewed promising novel therapies such as clofazimine, omadacycline, bedaquiline, and inhaled tigecycline that could join the existing antimicrobial armamentarium to fight this infection associated with significant morbidity and mortality. However, further studies are needed, especially among the immunocompromised host.

Draft genome sequence of Metabacillus indicus strain EGFCL74 isolated from spontaneously fermented apple cider.

Here, we report the draft genome and annotations for Metabacillus indicus strain EGFCL74, a bacterium isolated from spontaneously fermented apples. This 4.10-Mb genome adds to the limited existing data on a potential spoilage organism in natural cider ferments.

Causes and Clinical Presentation of Drug-Induced Dermatomyositis: A Systematic Review.

Importance: While several medications are known to induce dermatomyositis (DM), most existing studies are case reports or small case series from a single institution. There is also limited information on DM induced by immune checkpoint inhibitors, which are increasingly used in oncologic therapy. Objective: To characterize causes and clinical presentation of drug-induced DM based on the current literature. Evidence Review: A systematic review was performed in PubMed according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines, from inception to August 22, 2022. Articles meeting preestablished inclusion criteria (written in English and classified as original articles, case reports, literature reviews, and observation letters) were selected and data abstracted. Articles that met the scope of the review were also added from reference lists. When possible, study results were quantitatively combined. Findings: In 134 studies (114 from the literature search and 20 additional studies pulled from reference lists) describing 165 cases, 88 patients (53.3%) were female, and the median (IQR) age was 61 (49-69) years. Among the cases of drug-induced DM, the most common associated medications were hydroxyurea (50 [30.3%]), immune checkpoint inhibitors (27 [16.4%]), statins (22 [13.3%]), penicillamine (10 [6.1%]), and tumor necrosis factor inhibitors (10 [6.1%]). Histopathologic testing, when undertaken, helped establish the diagnosis. There was a median (IQR) of 60 (21-288) days between drug initiation and drug-induced DM onset. History of cancer was reported in 85 cases (51.6%). Conclusions and Relevance: In this systematic review, drug-induced DM was associated with multiple types of medications, including chemotherapies and immunotherapies. It is essential that dermatologists promptly recognize and diagnose drug-induced DM so that they can guide management to minimize interruption of therapy when possible.

Skull and Scalp En-Bloc Harvest Protects Calvarial Perfusion: A Cadaveric Study.

BACKGROUND: Calvarial defects are severe injuries that can result from a wide array of etiologies. Reconstructive modalities for these clinical challenges include autologous bone grafting or cranioplasty with biocompatible alloplastic materials. Unfortunately, both approaches are limited by factors such as donor site morbidly, tissue availability, and infection. Calvarial transplantation offers the potential opportunity to address skull defect form and functional needs by replacing "like-with-like" tissue but remains poorly investigated. METHODS: Three adult human cadavers underwent circumferential dissection and osteotomy to raise the entire scalp and skull en-bloc. The vascular pedicles of the scalp were assessed for patency and perfused with color dye, iohexol contrast agent for computed tomography (CT) angiography, and indocyanine green for SPY-Portable Handheld Imager assessment of perfusion to the skull. RESULTS: Gross changes were appreciated to the scalp with color dye, but not to bone. CT angiography and SPY-Portable Handheld Imager assessment confirmed perfusion from the vessels of the scalp to the skull beyond midline. CONCLUSION: Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes.

Lower Extremity Pediatric Tissue Expansion: A Single Surgeon's 16-Year Experience.

BACKGROUND: Tissue expansion is a well-established approach to soft tissue reconstruction in the pediatric population for lower extremity pathologies. Unfortunately, complication rates range from 19% to 40% in literature, including infection and implant extrusion, leading to delays in reconstruction. These challenges have prompted investigation toward categorizing risk factors for lower extremity tissue expander placement. METHODS: A retrospective study of pediatric patients who underwent lower extremity tissue expander placement by the senior author (R.J.R.) was performed over a 16-year period. Patient charts were reviewed to categorize baseline and operative characteristics. Primary outcome variables were surgical-site infection, expander extrusion, and expander deflation. Univariate and multivariate logistic regressions were performed ( α < 0.05). RESULTS: There were 59 tissue expanders in our cohort. The overall complication rate was 27.1% with a 77.2% successful reconstruction rate. Greater number of expanders placed during 1 operation is associated with 2.5 increased odds of having any complication and is associated with 0.4 decreased odds of having a successful reconstruction. Incisions made in scar tissue for expander placement appear to be associated with a greater than 7 times increased odds of readmission. CONCLUSIONS: Reconstruction of soft tissue pathologies using lower extremity tissue expanders in the pediatric population is an effective yet challenging technique. This study identified that the number of expanders inserted during 1 operation, incisions made over scar tissue, and expanders placed in the anterior thigh were correlated with having a negative impact on reconstructive outcomes. Extra care should be taken with patients who require multiple expanders during 1 operation and with choosing the location and incision of expander placement.

Penile Transplantation in Gender Affirmation Surgery: A Theoretical Feasibility Study.

BACKGROUND: It can be argued that individuals in the transgender and gender nonbinary (TGNB) community suffer from a similar impact on quality of life in the face of gender dysphoria, with psychosocial and physical consequences. Indications for penile allotransplantation for patients wishing to undergo gender affirmation surgery have yet to be elucidated, but technical lessons for feasibility can be gleaned from penis transplants that have already been performed on cisgender males to date. METHODS: This study investigates the theoretical feasibility for penile-to-clitoral transplantation, prior penile transplants, and current multidisciplinary gender affirmation health care modalities. RESULTS: Penile allotransplantation offers a potential solution for individuals in the TGNB community for a more aesthetic penis, improved erectile function without the need of a prosthesis, optimal somatic sensation, and improved urethral outcomes. CONCLUSION: Questions remain about ethics, patient eligibility, and immunosuppressive sequelae. Before these issues are addressed, feasibility of this procedure must be established.

Expanding indications for urogenital transplantation: congenital and oncologic defects, and gender affirmation.

PURPOSE OF REVIEW: Penile transplantation has become an emerging option for patients with severe genital defects. Only transplantation restores anatomy, sexual, and reproductive function of the penis. However, penile transplantation comes with important technical, psychosocial, ethical, and surgical challenges that must be considered for successful implementation. Indications for penile transplantation have yet to be clearly elucidated. RECENT FINDINGS: Since 2006, only five penile transplants have been performed globally. Four of the five transplants have been performed following traumatic defects, and one was performed following a total penectomy from squamous cell carcinoma. Only two of the five penile transplants remain intact. However, long-term outcomes are encouraging with optimal surgical planning, patient selection, and immunologic compliance. Clinical implications and ethical considerations are discussed. SUMMARY: Penile transplantation is a novel solution for penile defects not amenable to traditional reconstructive approaches. With an evidence-based surgical technique, potential advantages include improved urinary function, sensation, and cosmesis. While patient selection is challenging, there is an ongoing effort to identify potential candidates. Indications are discussed in this article.

Understanding Barriers and Facilitators to High-Quality Cancer Care Among Veterans With Lung Cancer: A Qualitative Study.

PURPOSE: Veteran populations have higher lung cancer incidence and worse overall survival compared with non-Veteran populations. Although recent clinical advancements have reduced lung cancer death rates, these advances are not routinely received among Veteran populations because of multilevel factors, including Veterans' complex comorbidities, limited health literacy, and other economic and social disadvantages. This study aimed to assess Veterans' perspectives regarding their lung cancer care with a specific focus on identifying modifiable barriers to evidence-based care delivery. METHODS: We conducted 1:1 semistructured interviews with 24 Veterans diagnosed with lung cancer at the Veterans Affairs Palo Alto Health Care System. All interviews were recorded, transcribed, and analyzed using the constant comparative method of qualitative analysis. RESULTS: Four themes emerged. These included (1) social and economic disadvantages can prevent routine delivery of evidence-based cancer care; (2) fragmented care contributes to worsening patient mental and emotional well-being; (3) lack of health system interventions to address limited health literacy inhibits patient engagement in shared decision making regarding diagnosis, genomic and molecular testing, targeted and other treatments, and end-of-life care; and (4) deep appreciation for care and VA trustworthiness facilitates adherence to cancer care recommendations. CONCLUSION: This study revealed critical gaps in lung cancer care delivery and the role of institution-engendered trust in overcoming barriers in the VA system. Targeted solutions should address the identified barriers to routine, evidence-based lung cancer care delivery among Veterans.

The impact of COVID-19 pandemic on free tissue transfer outcomes: A NSQIP analysis.

BACKGROUND: The COVID-19 pandemic significantly impacted hospital resources and patient care, although its effect on free tissue transfer procedures is poorly understood. We conducted the current study to investigate the potential impact of COVID-19 and its accompanying system shut-downs on the surgical outcomes of patients undergoing free flap procedures. METHODS: Patients undergoing free tissue transfer procedures were identified from the National Surgical Quality Improvement Program (NSQIP) database from 2016 to 2020. We used 2016-2019 as baseline (pre-pandemic) data to compare with 2020 (peri-pandemic). We divided the patients into the following 3 groups: all patients undergoing free tissue transfer, breast reconstruction free tissue transfer, and non-breast free tissue transfer cases. Outcomes of interest included patient morbidity/mortality, time to surgery, time to takeback, and length of hospital stay. We used Pearson's chi-square and Fisher's exact tests to assess categorical variables. Wilcoxon's ranked sign tests and ANOVA tests were used for non-parametric and parametric continuous variables, respectively. Significance was set at alpha < 0.05. RESULTS: When comparing peri-pandemic to pre-pandemic rates, patient morbidity and mortality and unplanned primary or secondary takeback operations were both significantly higher in all 3 groups peri-pandemic. Median time to primary or secondary takeback operation was also significantly greater peri-pandemic. CONCLUSION: Patients undergoing flap procedures peri-pandemic had an overall increase in median morbidity and mortality, unplanned primary or secondary takebacks, and median number of days to takebacks compared to the pre-pandemic period. This is concerning given that any future protocols instituted can have detrimental effects on patients who receive a free tissue transfer procedure.

Socioeconomic Status Diversity of Trainees and Faculty in Residency Programs: A Pilot Study in Plastic Surgery.

INTRODUCTION: The socioeconomic diversity of residents, fellows, and faculty members in any medical or surgical specialty is currently unknown making it difficult to understand socioeconomic status (SES) disparities and create programs to improve diversity. Additionally, the career trajectories of residents and faculty members who come from different SES backgrounds have not been explored. We have performed a survey-based research study to understand the SES composition and career trajectories of residents and faculty members within U.S. Plastic and Reconstructive Surgery (PRS) residency programs. METHODS: An anonymous online survey was administered to 754 recipients within plastic surgery residency programs in the United States. Self-reported SES information such as household income prior to age 18 and parental education level was collected. Data regarding career trajectories was obtained through questions about away rotations and research productivity. RESULTS: A total of 196 fellows, and faculty members participated in the study, with an estimated survey respondent rate of 25.9%. Only 9.9% (10 of 101) of residents and fellows reported a childhood (under age 18) family income less than $40,000. When analyzing parental education and occupation (EO-status), 42.6% (43 of 101) of residents and fellows had at least 1 parent in an executive, managerial, or professional position with a doctorate/professional degree. Low-income and low EO-status were associated with increased utilization of federal and state assistance programs (p = 0.0001) and approval for AAMC's Fee Assistance Program (FAP) (p = 0.0001). Residents and fellows who identified as White were not as likely to be from low EO-status households as those who identified as Asian (OR 0.3 and p = 0.015 vs. OR 2.9 and p = 0.038). Residents and fellows from low EO-status backgrounds were more likely to take a gap in education (87% vs. 65.4%, p = 0.047) compared to their high EO-status peers. Notably, more current residents and fellows performed away rotations and had first-author publications during or before medical school compared to full professors (p = 0.0001). CONCLUSION: Understanding the backgrounds and career trajectories of trainees and faculty in medicine is essential, yet it has not been performed at the resident or faculty level. This survey is the first to demonstrate the lack of socioeconomic diversity in a specialty (PRS) and identifies variation in career trajectories among those from different SES backgrounds. Large-scale research efforts are necessary to understand current SES diversity and barriers encountered by trainees and educators from low-SES backgrounds in all medical and surgical specialties.

Treatment Delays in Nonsyndromic Craniosynostosis: A 30-Year Retrospective Case-Control Analysis of the Impact of Socioeconomic and Family Status on Access to Care.

BACKGROUND: Patients with nonsyndromic craniosynostosis (NSC) generally undergo corrective surgery before 1 year of age to the mitigate morbidities and risks of delayed repair. The cohort of patients who receive primary corrective surgery after 1 year and factors associated with their gaps to care is poorly characterized in literature. METHODS: A nested case-control study was conducted for NSC patients who underwent primary corrective surgery at our institution and affiliates between 1992 and 2022. Patients whose surgery occurred after 1 year of age were identified and matched 1:1 by surgical date to standard-care control subjects. Chart review was conducted to gather patient data regarding care timeline and sociodemographic characteristics. RESULTS: Odds of surgery after 1 year of age were increased in Black patients (odds ratio, 3.94; P < 0.001) and those insured by Medicaid (2.57, P = 0.018), with single caregivers (4.96, P = 0.002), and from lower-income areas (+1% per $1000 income decrease, P = 0.001). Delays associated with socioeconomic status primarily impacted timely access to a craniofacial provider, whereas caregiver status was associated with subspecialty level delays. These disparities were exacerbated in patients with sagittal and metopic synostosis, respectively. Patients with multisuture synostosis were susceptible to significant delays related to familial strain (foster status, insurer, and English proficiency). CONCLUSIONS: Patients from socioeconomically strained households face systemic barriers to accessing optimal NSC care; disparities may be exacerbated by the diagnostic/treatment complexities of specific types of craniosynostosis. Interventions at primary care and craniofacial specialist levels can decrease health care gaps and optimize outcomes for vulnerable patients.

Do Racial and Ethnic Disparities Exist in Management of Pediatric Mandible Fractures? A 30-Year Outcome Analysis.

BACKGROUND: Mandibular fractures are the most common of pediatric facial fractures. The effect of race on management/outcomes in these injuries has not been previously studied. Given the significant association between race and healthcare outcomes in many other pediatric conditions, an in-depth study of race as related to mandibular fractures in the pediatric patient population is warranted. METHODS: This was a 30-year retrospective, longitudinal study of pediatric patients who presented to a single institution with mandibular fractures. Patient data were compared between patients of different races and ethnicities. Demographic variables, injury characteristics, and treatment variables were analyzed to find predictors of surgical treatment and posttreatment complications. RESULTS: One hundred ninety-six patients met inclusion criteria, of whom 49.5% were White, 43.9% were Black, 0.0% were Asian, and 6.6% were classified as "other." Black and "other" patients were more likely than their White counterparts to be injured as pedestrians (P = 0.0005). Black patients were also more likely than White patients or "other" patients to be injured by assault than by sports-related injuries or animal-related accidents (P = 0.0004 and P = 0.0018, respectively). Race or ethnicity were not found to be a predictor of receiving surgical treatment (ORIF) or of posttreatment complications. The posttreatment rates for all the complications observed were comparable among all race and ethnic groups. Higher mandible injury severity score (odds ratio [OR], 1.25), condyle fracture (OR, 2.58), and symphysis fracture (OR, 3.20) were positively correlated with receiving ORIF as treatment. Mandible body fracture (OR, 0.36), parasymphyseal fracture (OR, 0.34), bilateral mandible fracture (OR, 0.48), and multiple mandibular fractures (OR, 0.34) were negatively correlated with receiving ORIF as treatment. Only high mandible injury severity score (OR, 1.10) was identified as an independent predictor of posttreatment complications. Lastly, Maryland's transition to an all-payer model in 2014 also had no impact on treatment modality; treatment of fractures among race and ethnicity were not significantly different pre- and post-2014. CONCLUSIONS: There is no difference in how patients are treated (surgically vs nonsurgically) and no difference in outcomes for patients based on race at our institution. This could be due to institutional ideology, services provided by a tertiary care center, or simply the more diverse patient population at baseline.

Skull and Scalp En-Bloc Harvest Protects Calvarial Perfusion: A Cadaveric Study.

BACKGROUND: Calvarial defects are severe injuries that can result from a wide array of etiologies. Reconstructive modalities for these clinical challenges include autologous bone grafting or cranioplasty with biocompatible alloplastic materials. Unfortunately, both approaches are limited by factors such as donor site morbidly, tissue availability, and infection. Calvarial transplantation offers the potential opportunity to address skull defect form and functional needs by replacing "like-with-like" tissue but remains poorly investigated. METHODS: Three adult human cadavers underwent circumferential dissection and osteotomy to raise the entire scalp and skull en-bloc. The vascular pedicles of the scalp were assessed for patency and perfused with color dye, iohexol contrast agent for computed tomography (CT) angiography, and indocyanine green for SPY-Portable Handheld Imager assessment of perfusion to the skull. RESULTS: Gross changes were appreciated to the scalp with color dye, but not to bone. CT angiography and SPY-Portable Handheld Imager assessment confirmed perfusion from the vessels of the scalp to the skull beyond midline. DISCUSSION/CONCLUSION: Calvarial transplantation may be a technically viable option for skull defect reconstruction that requires vascularized composite tissues (bone and soft tissue) for optimal outcomes.

Blocking muscle wasting via deletion of the muscle-specific E3 ligase MuRF1 impedes pancreatic tumor growth.

Cancer-induced muscle wasting reduces quality of life, complicates or precludes cancer treatments, and predicts early mortality. Herein, we investigate the requirement of the muscle-specific E3 ubiquitin ligase, MuRF1, for muscle wasting induced by pancreatic cancer. Murine pancreatic cancer (KPC) cells, or saline, were injected into the pancreas of WT and MuRF1-/- mice, and tissues analyzed throughout tumor progression. KPC tumors induces progressive wasting of skeletal muscle and systemic metabolic reprogramming in WT mice, but not MuRF1-/- mice. KPC tumors from MuRF1-/- mice also grow slower, and show an accumulation of metabolites normally depleted by rapidly growing tumors. Mechanistically, MuRF1 is necessary for the KPC-induced increases in cytoskeletal and muscle contractile protein ubiquitination, and the depression of proteins that support protein synthesis. Together, these data demonstrate that MuRF1 is required for KPC-induced skeletal muscle wasting, whose deletion reprograms the systemic and tumor metabolome and delays tumor growth.

Hickman Catheter Use for Long-Term Vascular Access in a Preclinical Swine Model.

Central venous catheters (CVCs) are invaluable devices in large animal research as they facilitate a wide range of medical applications, including blood monitoring and reliable intravenous fluid and drug administration. Specifically, the tunneled multi-lumen Hickman catheter (HC) is commonly used in swine models due to its lower extrication and complication rates. Despite fewer complications relative to other CVCs, HC-related morbidity presents a significant challenge, as it can significantly delay or otherwise negatively impact ongoing studies. The proper insertion and maintenance of HCs is paramount in preventing these complications, but there is no consensus on best practices. The purpose of this protocol is to comprehensively describe an approach for the insertion and maintenance of a tunneled HC in swine that mitigates HC-related complications and morbidity. The use of these techniques in >100 swine has resulted in complication-free patent lines up to 8 months and no catheter-related mortality or infection of the ventral surgical site. This protocol offers a method to optimize the lifespan of the HC and guidance for approaching issues during use.

Polycomb Ezh1 maintains murine muscle stem cell quiescence through non-canonical regulation of Notch signaling.

Organismal homeostasis and regeneration are predicated on committed stem cells that can reside for long periods in a mitotically dormant but reversible cell-cycle arrest state defined as quiescence. Premature escape from quiescence is detrimental, as it results in stem cell depletion, with consequent defective tissue homeostasis and regeneration. Here, we report that Polycomb Ezh1 confers quiescence to murine muscle stem cells (MuSCs) through a non-canonical function. In the absence of Ezh1, MuSCs spontaneously exit quiescence. Following repeated injuries, the MuSC pool is progressively depleted, resulting in failure to sustain proper muscle regeneration. Rather than regulating repressive histone H3K27 methylation, Ezh1 maintains gene expression of the Notch signaling pathway in MuSCs. Selective genetic reconstitution of the Notch signaling corrects stem cell number and re-establishes quiescence of Ezh1-/- MuSCs.