Racial Disparities Following Reconstructive Flap Procedures.

BACKGROUND: Prior reports have highlighted disparities in healthcare access, environmental conditions, and food insecurity between Black and White populations in the United States. However, limited studies have explored racial disparities in postoperative complications, particularly reconstructive flap surgeries. METHODS: Cases of flap reconstruction based on named vascular pedicles were identified in the American College of Surgeons National Surgical Quality Improvement Program database and grouped into 3 time periods: 2005 to 2009, 2010 to 2014, and 2015 to 2019. Logistic regression was used to compare rates of postoperative complications between White and Black patients within each time period while controlling for comorbidities. Data for flap failure was only available from 2005 to 2010. RESULTS: A total of 56,116 patients were included in the study, and 6293 (11.2%) were Black. Black patients were significantly younger than White patients and had increased rates of hypertension, smoking, and diabetes across all years ( P <0.01). Black patients had significantly higher rates of sepsis compared to White patients in all time periods. From 2005 to 2009, Black patients had a significantly higher incidence of flap failure (aOR=2.58, P <0.01), return to the operating room (aOR=1.53, P =0.01), and having any complication (aOR=1.48, P <0.01). From 2010 to 2019, White patients had a higher incidence of superficial surgical site infection. CONCLUSIONS: Surgical complication rates following flap reconstruction based on a named vascular pedicle were higher for Black patients. Limited data on this topic currently exists, indicating that additional research on the drivers of racial disparities is warranted to improve plastic surgery outcomes in Black patients.

The Current State of Neoadjuvant Therapy in Resectable Advanced Stage Melanoma.

The advent of effective immunotherapy and targeted therapy has significantly improved outcomes in advanced-stage resectable melanoma. Currently, the mainstay of treatment of malignant melanoma is surgery followed by adjuvant systemic therapies. However, recent studies have shown a potential role for neoadjuvant therapy in the treatment of advanced-stage resectable melanoma. Mechanistically, neoadjuvant immunotherapy may yield a more robust response than adjuvant immunotherapy, as the primary tumor serves as an antigen in this setting rather than only micrometastatic disease after the index procedure. Additionally, targeted therapy has been shown to yield effective neoadjuvant cytoreduction, and oncolytic viruses may also increase the immunogenicity of primary tumors. Effective neoadjuvant therapy may serve to decrease tumor size and thus reduce the extent of required surgery and thus morbidity. It also allows for assessment of pathologic response, facilitating prognostication as well as tailoring future therapy. The current literature consistently supports that neoadjuvant therapy, even as little as one dose, is associated with improved outcomes and is well-tolerated. Some patients with a complete pathological response may even avoid surgery completely. These results challenge the current paradigm of a surgery-first approach and provide further evidence supporting neoadjuvant therapy in advanced-stage resectable melanoma. Further research into the optimal treatment schedule and dose timing is warranted, as is the continued investigation of novel therapies and combinations of therapies.

How Consistent are International Rotations Between Plastic Surgery Training Programs?

Institutional partnerships between plastic surgery residency programs in the United States and providers in low- and middle-income countries can serve as bilateral and longitudinal capacity-building relationships. In the United States, obtaining approval for international rotations by a home institution and national review committee is highly encouraged but not required before resident international engagement. Acquiring approval at the institutional level is the first step to allow trainees to participate in international rotations on elective time rather than on vacation time. National approval through the American Council of Graduate Medical Education and American Board of Plastic Surgery allows cases to count toward the resident's yearly case log. Methods: All 101 integrated and independent plastic surgery program directors/coordinators were asked to participate. The survey identified the requirements and details of existing international rotations. Results: In total, 57 programs responded (56% response rate) to the survey. An estimated 54% of all programs offered international rotations to their residents, and 94% of these programs obtained institutional approval. Additionally, 69% of these programs have received national approval. Conclusions: Institutional requirements for programs to provide international rotations vary significantly across institutions, which results in disparate experiences for residents and poses potential risks to international partners. This study will help promote transparency regarding international rotation requirements and better equip faculty to enhance international rotations that cater to the needs of the institution, residents, and most importantly, the host countries.

Clinical and histopathologic characterization of SETD2-mutated colorectal cancer.

With the advent of next-generation sequencing (NGS), identifying and better understanding genetic mutations in cancer pathways has become more feasible. A mutation now commonly reported in NGS panels is the SETD2 gene (H3K36 trimethyltransferase). However, its contributions to colorectal cancer (CRC) are not well described. In this study, we describe the clinicopathologic characteristics of SETD2-mutated CRC, determine common mutation sites on the SETD2 gene, and correlate these mutations with the loss of H3K36 trimethylation and the aberrant expression of beta-catenin. By searching pathology reports at our institution which included the 161-gene NGS panel from 2019 to 2021, we identify 24 individuals with SETD2-mutated CRC. All samples were evaluated for microsatellite status, H3K36 trimethylation, and beta-catenin via immunohistochemistry. In this cohort of 24 SETD2-mutated CRC individuals (a median age of 62.4 years [interquartile range: 49.1-73.6]), 10 (41.7%) patients presented at American Joint Committee on Cancer (AJCC) tumor stage II, seven (29.2%) at stage III, six (25%) at stage IV, and one (4.2%) at stage I. Most tumors studied were adenocarcinomas with no further specification (22, 92%), and most tumors were microsatellite stable (18, 82.5%). Thirty-three mutation locations were represented by 24 patients, with one patient having six mutations in the SETD2 gene and two patients having three mutations. The dominant mutation type is missense mutations (N = 29, 87.9%), and no mutation hotspots were found. Only two samples lost trimethylation of histone H3K36, both from individuals with multiple SETD2 mutations and aberrant nuclear beta-catenin expression. SETD2-mutated CRC is similar in clinical and histologic presentation to other commonly reported CRC. SETD2 mutations were missense dominantand showed no hotspots, and multiple mutations are likely necessary for loss of H3K36 trimethylation. These results warrant further study on determining a role of SETD2-histone H3K36 pathway in CRC.

Vascularized Medial Femoral Condyle Periosteal Flaps With Allograft Bone for Distal Radius Giant Cell Tumors: A Case Report.

CASE: Distal radius reconstruction after giant cell tumor (GCT) resection is typically performed with free fibular flaps when a vascularized bone is needed. However, vascularized fibular flaps are contraindicated in patients with peroneal artery variants. We present 2 patients with GCTs of the radius and bilateral peronea arteria magna who underwent resection with wrist fusion using an allograft bone and vascularized free medial femoral condyle periosteal flaps. Both patients had excellent outcomes with minimal postoperative morbidity. CONCLUSION: Allograft bone with vascularized medial femoral condyle periosteal flaps is an effective option for reconstructing distal radius defects after GCT resection when conventional methods fail.

How Important Are Dedicated Research Years and Global Health to Applicants in Plastic Surgery?

Applicant preferences for required research and global surgery experiences during plastic surgery training have not been previously studied. Methods: An anonymous survey was sent to integrated plastic surgery applicants from consecutive residency application cycles (2018-2020). Research and global health experiences before residency were elicited, along with the interest to continue these activities. Data were analyzed using frequency distributions and chi-square test of independence. Results: Seventy-eight former plastic surgery applicants responded to the survey (15.7% response rate). Most participants (65%) viewed time for research as important when evaluating residency programs. Fewer respondents (10%) ranked programs with a required research year higher, whereas 47% ranked those programs lower and 43% did not factor it into their decision-making. Less than one-third of respondents (28%) reported prior global health experience, yet 44% viewed international opportunities as an important factor when ranking programs, and the majority (72%) stated plans to participate in global surgery during residency. Past experience on a global health trip predicted a strong preference for longer rotations (P = 0.003) and willingness to use vacation time to participate during residency (P < 0.001). Conclusions: Research was an important consideration in residency selection, but a few preferred a residency program with a dedicated research year. Although applicants had limited experience with global surgery, the majority intended to get involved during residency. Understanding factors that influence applicants' interests in residency programs may better equip programs with information to create enriching experiences and attract the most qualified applicants.

Bullous Scabies in an Immunocompromised Host.

A 40-year-old woman with a history of poorly controlled HIV presented to a district referral hospital in rural Botswana for a generalized skin rash of several months duration. The highly pruritic rash predominantly involved her hands and feet and was associated with bullae that were present for days at a time before rupturing without drainage or discharge. The patient endorsed night sweats, periodic fevers, occasional cough productive of blood-tinged sputum, fatigue, and weight loss. On admission, CD4 count was 46 cells/mm3 and viral load was >750000 copies/mL. Pulmonary tuberculosis testing via sputum was negative twice. A blood count demonstrated eosinophilia. Oral acyclovir was started empirically for disseminated herpes virus infection, with topical beclomethasone and intravenous antibiotics for possible superinfected bullous dermatosis. With inadequate response to treatment, a skin biopsy was obtained and microscopic examination demonstrated scabies mites. The absence of skin burrows, the presence of bullae, and working in a low-resource setting without direct access to microscopic examination delayed diagnosis. The patient was initiated on topical permethrin. Oral ivermectin was not available in country and was obtained from overseas shipment, delaying treatment initiation. Drastic improvement was seen after the patient initiated ivermectin. A local nurse in the patient's village visited her community and found multiple individuals with active scabies infection. The patient's discharge was delayed until these community members were treated successfully with topical permethrin. This case describes an atypical presentation of scabies in an under-resourced setting, demonstrating unique diagnostic, therapeutic, and public health challenges.

The Current State of Cleft Care in Sub-Saharan Africa: A Narrative Review.

OBJECTIVE: To identify practices and limitations of cleft care in sub-Saharan Africa (SSA). DESIGN: A retrospective narrative nonsystematic literature review was performed. SETTING: Literature exploring the management practices of cleft lip and/or palate across regions in SSA was included. PARTICIPANTS: Full text case reports, retrospective studies, prospective studies, clinical trials, and review articles written and published in English between 1966 and February 1, 2021, were included in this analysis utilizing PubMed, MEDLINE, EMBASE, and Google scholar databases. MAIN OUTCOME MEASURES: Qualitative themes identified in analysis were clinical practice patterns, current infrastructure and limitations of cleft repair, training and interdisciplinary teams, economic analyses, and international partnerships. RESULTS: Significant barriers to care identified in SSA include lack of hospital resources, craniofacial training, access to multidisciplinary specialists, and public awareness. These problems make the entire care journey difficult for patients. Increasing public education has the power to diminish late presentations to hospitals. Providing adequate hospital resources and craniofacial training through international and organizational partnerships can ensure that more patients will receive care. Increasing the availability and number of multidisciplinary specialists is crucial to follow up care which aims at improving functional outcomes. CONCLUSION: This narrative review highlights current practices and limitations in cleft care, emphasizing the importance of effective and timely repair of clefts in SSA. Targeted efforts aimed at establishing sustainable infrastructure for cleft care in SSA can have significant individual and community health and economic benefits.

Supramolecular Exchange among Assemblies of Opposite Charge Leads to Hierarchical Structures.

Hierarchical assemblies of proteins into fibrillar structures occur in both physiologic and pathologic extracellular spaces and often involve interactions between oppositely charged peptide domains. However, the interplay between tertiary structure dynamics and quaternary hierarchical structure formation remains unclear. In this work, we investigate supramolecular mimics of these systems by mixing one-dimensional assemblies of small alkylated peptides bearing opposite charge and varying in peptide sequence. We found that assemblies with weak cohesive interactions readily create fibrous superstructures of bundled filaments as molecules redistribute upon mixing. Low cohesion allows molecules to escape from the original assemblies and exchange dynamics help them reassemble into electrostatically stable bundles. However, we also found that kinetic barriers can be encountered in these systems and limit formation of the hierarchical structures at pH values where charge densities are high. Increasing intermolecular cohesion using longer peptide sequences that form stable ß-sheets was found to suppress superstructure formation. Our findings suggest that low internal cohesion in protein systems could facilitate the conformational rearrangements required to create hierarchical structures.

Reversible self-assembly of superstructured networks.

Soft structures in nature, such as protein assemblies, can organize reversibly into functional and often hierarchical architectures through noncovalent interactions. Molecularly encoding this dynamic capability in synthetic materials has remained an elusive goal. We report on hydrogels of peptide-DNA conjugates and peptides that organize into superstructures of intertwined filaments that disassemble upon the addition of molecules or changes in charge density. Experiments and simulations demonstrate that this response requires large-scale spatial redistribution of molecules directed by strong noncovalent interactions among them. Simulations also suggest that the chemically reversible structures can only occur within a limited range of supramolecular cohesive energies. Storage moduli of the hydrogels change reversibly as superstructures form and disappear, as does the phenotype of neural cells in contact with these materials.