Postoperative Interventions in Pediatric Digital Replantation: A Tertiary Referral Center Case Review.

PURPOSE: Although a few case series have been published describing the excellent outcomes of replantation and revascularization operations in children, there has been limited study of the hospital course that these patients experience and the number of potentially harmful interventions and treatments that occur. The purpose of this study was to detail the results of various postoperative interventions, including anticoagulation, transfusion, leeching, sedation, and additional anesthetic exposures. METHODS: Twenty-nine patients aged less than 18 years had 34 digital revascularizations or replantations performed between January 2000 and May 2020. The details of each patient's presentation, surgery, and postoperative care were analyzed. RESULTS: Nine of 29 children underwent repeat anesthetics, including 6 revision amputations. No demographic, surgical, or postoperative variables consistently preceded revision amputation or additional anesthetic procedures. Only 5 patients had >1 hemoglobin (Hb) measurement. Two patients received blood transfusions; the average drop in Hb was 3.5 g/dL from before surgery to the lowest after surgery. Four patients underwent leech therapy. Only patients receiving leech therapy required postoperative transfusions. Anticoagulation regimens were prescribed on the basis of demographic and surgical factors, although no medication or regimen seemed to affect outcomes. CONCLUSIONS: Although the experience of digital replantation is essentially the same in pediatric patients as adults, there may be different ramifications for children. Specifically, postoperative management of pediatric digital replantation or revascularization can involve multiple interventions that carry their risks. Parents should be counseled about the risks of anticoagulants, transfusions, and repeat anesthetics, and clinicians should monitor Hb closely when using leech therapy. TYPE OF STUDY/LEVEL OF EVIDENCE: Case series, Therapeutic IV.

Dispose with dish soap: A simple and convenient method to increase proper opioid disposal in postoperative pediatric patients.

BACKGROUND: The opioid abuse crisis is rampant in the United States. Children and adolescents are unique risk groups in this crisis; age-specific concerns include accidental ingestion and association with high-risk behaviors. Studies aimed at disposal are limited in pediatric patients. Our study aimed to determine whether an educational brochure detailing a simple opioid disposal method using dish soap could enhance disposal in postoperative pediatric patients. METHODS: A prospective survey study of pediatric plastic surgery patients at the St. Louis Children's Hospital was performed from January to December 2020. Patients were assigned into two groups: those who received the educational brochure at the time of surgery and those who did not. In clinic, patient caretakers completed anonymous preoperative and/or postoperative surveys regarding opioid use and disposal. RESULTS: Surveys of 326 patients were analyzed (188 preoperative, 120 pre/postoperative, and 18 postoperative). Prescribed opioids were all consumed in 19% of patients. Receiving the educational brochure significantly increased the opioid disposal of leftover medications: 78% versus 35% (OR 6.52, 95% CI [2.03, 21.37], p < 0.001). Although not statistically significant owing to small sample size (p = 0.09), 71.4% of families with excess opioids in the home preoperatively retained unused postoperative opioids versus 31.6% without preoperative opioids. CONCLUSIONS: Postoperative opioids are overprescribed for most pediatric plastic surgery patients. A simple brochure significantly increases proper postoperative opioid disposal, representing a cost-effective, convenient, risk-free method to decrease opioid misuse and accumulation in our communities.

Re-Endothelialization of Decellularized Liver Scaffolds: A Step for Bioengineered Liver Transplantation.

Bioengineered livers (BELs) are an attractive therapeutic alternative to address the donor organ shortage for liver transplantation. The goal of BELs technology aims at replacement or regeneration of the native human liver. A variety of approaches have been proposed for tissue engineering of transplantable livers; the current review will highlight the decellularization-recellularization approach to BELs. For example, vascular patency and appropriate cell distribution and expansion are critical components in the production of successful BELs. Proper solutions to these components of BELs have challenged its development. Several strategies, such as heparin immobilization, heparin-gelatin, REDV peptide, and anti-CD31 aptamer have been developed to extend the vascular patency of revascularized bioengineered livers (rBELs). Other novel methods have been developed to enhance cell seeding of parenchymal cells and to increase graft functionality during both bench and in vivo perfusion. These enhanced methods have been associated with up to 15 days of survival in large animal (porcine) models of heterotopic transplantation but have not yet permitted extended survival after implantation of BELs in the orthotopic position. This review will highlight both the remaining challenges and the potential for clinical application of functional bioengineered grafts.

A Simple Brochure Improves Disposal of Unused Opioids: An Observational Cross-Sectional Study.

BACKGROUND: We evaluated the effectiveness of a simple, low-cost educational brochure in improving disposal rates of unused opioids after outpatient upper extremity surgery. METHODS: This cross-sectional study enrolled eligible adult patients from a peripheral nerve clinic between November 2017 and September 2018. Patients either received or did not receive the educational brochure, which outlined a simple method to dispose of unused opioids and completed a survey at 2 weeks after surgery. We compared the proportion of patients who disposed of unused opioids after surgery between the group that had received the brochure and the group that had not. Categorical data were analyzed with χ2 test, proportions data with binomial tests, and numerical data with Mann-Whitney U test, all with a significance level of P < .05. RESULTS: There were 339 survey respondents. Nineteen patients who did not meet inclusion criteria were excluded. Of the 320 remaining patients, 139 received the brochure and 181 did not. An additional 55 patients were excluded due to preoperative opioid use. Overall, 35.3% of recipients and 38.3% of those who did not receive the brochure used all of their prescribed opioid medication (P = .625; confidence interval = -14.6%-8.8%). Among patients with unused opioid medication, a significantly higher proportion of brochure recipients disposed of the medicine compared with those who did not receive the brochure (46.7% vs 19.6%, P < .001). CONCLUSIONS: Distribution of an educational brochure significantly improved disposal of unused opioids after surgery. This easily implemented intervention can improve disposal of unused opioids and ultimately decrease excess opioids available for diverted use in the community.

The Effects of Intraoperative Electrical Stimulation on Regeneration and Recovery After Nerve Isograft Repair in a Rat Model.

Background: Therapeutic electrical stimulation (ES) applied to repaired nerve is a promising treatment option to improve regeneration. However, few studies address the impact of ES following nerve graft reconstruction. The purpose of this study was to determine if ES applied to a nerve repair using nerve isograft in a rodent model could improve nerve regeneration and functional recovery. Methods: Adult rats were randomized to 2 groups: "ES" and "Control." Rats received a tibial nerve transection that was repaired using a tibial nerve isograft (1.0 cm length), where ES was applied immediately after repair in the applicable group. Nerve was harvested 2 weeks postrepair for immunohistochemical analysis of axon growth and macrophage accumulation. Independently, rats were assessed using walking track and grid-walk analysis for up to 21 weeks. Results: At 2 weeks, more robust axon regeneration and greater macrophage accumulation was observed within the isografts for the ES compared to Control groups. Both walking track and grid-walk analysis revealed that return of functional recovery was accelerated by ES. The ES group demonstrated improved functional recovery over time, as well as improved recovery compared to the Control group at 21 weeks. Conclusions: ES improved early axon regeneration into a nerve isograft and was associated with increased macrophage and beneficial M2 macrophage accumulation within the isograft. ES ultimately improved functional recovery compared to isograft repair alone. This study supports the clinical potential of ES to improve the management of nerve injuries requiring a nerve graft repair.

Limited Expansion of Human Hepatocytes in FAH/RAG2-Deficient Swine.

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes. Therefore, we engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application. Immunodeficient swine were engineered by knockout of the recombinase-activating gene 2 (RAG2) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. Human albumin was measured as a marker of engraftment. Cytotoxicity against ihHCs was measured in transplanted piglets and control swine. We initially detected higher levels of human albumin in cord blood of newborn FAH/RAG2-deficient (FR) pigs compared with immunocompetent controls (196.26 ng/dL vs. 39.29 ng/dL, p = 0.008), indicating successful engraftment of ihHCs after IUCT and adaptive immunity in the fetus. Although rare hepatocytes staining positive for human albumin were observed, levels of human albumin did not rise after birth, but declined, suggesting rejection of xenografted ihHCs. Cytotoxicity against ihHCs increased after birth by 3.8% (95% CI: [2.1%-5.4%], p < 0.001) and inversely correlated with declining levels of human albumin (p = 2.1 × 10-5, R2 = 0.17). Circulating numbers of T cells and B cells were negligible in FR pigs. However, circulating natural killer (NK) cells exerted cytotoxicity against ihHCs. NK cell activity was lower in immunodeficient piglets after IUCT than in naive controls (30.4% vs. 40.1%, p = 0.011, 95% CI for difference [2.7%-16.7%]). In conclusion, ihHCs were successfully engrafted in FR swine after IUCT. NK cells were a significant barrier to expansion of hepatocytes. New approaches are needed to overcome this hurdle and allow large-scale expansion of human hepatocytes in immunodeficient swine. Impact statement There is currently a need for robust expansion of human hepatocytes. We describe an immunodeficient swine model into which we engrafted immature human hepatocytes (ihHCs). We identified the mechanism of the eventual graft rejection by the intact NK cell population, which has not been previously shown to have a significant role in xenograft rejection. By both improving engraftment and reducing NK cell-mediated cytotoxicity toward the graft through intrauterine cell transfer, we confirmed the presence of residual adaptive immunity in this model of immunodeficiency and the ability to induce hyposensitization in the NK cell population by taking advantage of the fetal microenvironment.

Efficacy of SARS-CoV-2 wastewater surveillance for detection of COVID-19 at a residential private college.

Many colleges and universities utilized wastewater surveillance testing for SARS-CoV-2 RNA as a tool to help monitor and mitigate the COVID-19 pandemic on campuses across the USA during the 2020-2021 academic year. We sought to assess the efficacy of one such program by analyzing data on relative wastewater RNA levels from residential buildings in relation to SARS-CoV-2 cases identified through individual surveillance testing, conducted largely independent of wastewater results. Almost 80% of the cases on campus were associated with positive wastewater tests, resulting in an overall positive predictive value of 79% (Chi square 48.1, Df = 1, P < 0.001). However, half of the positive wastewater samples occurred in the two weeks following the return of a student to the residence hall following the 10-day isolation period, and therefore were not useful in predicting new infections. When these samples were excluded, the positive predictive value of a positive wastewater sample was 54%. Overall, we conclude that the continued shedding of viral RNA by patients past the time of potential transmission confounds the identification of new cases using wastewater surveillance, and decreases its effectiveness in managing SARS-CoV-2 infections on a residential college campus.

Fumarylacetoacetate hydrolase gene as a knockout target for hepatic chimerism and donor liver production.

A reliable source of human hepatocytes and transplantable livers is needed. Interspecies embryo complementation, which involves implanting donor human stem cells into early morula/blastocyst stage animal embryos, is an emerging solution to the shortage of transplantable livers. We review proposed mutations in the recipient embryo to disable hepatogenesis, and discuss the advantages of using fumarylacetoacetate hydrolase knockouts and other genetic modifications to disable hepatogenesis. Interspecies blastocyst complementation using porcine recipients for primate donors has been achieved, although percentages of chimerism remain persistently low. Recent investigation into the dynamic transcriptomes of pigs and primates have created new opportunities to intimately match the stage of developing animal embryos with one of the many varieties of human induced pluripotent stem cell. We discuss techniques for decreasing donor cell apoptosis, targeting donor tissue to endodermal structures to avoid neural or germline chimerism, and decreasing the immunogenicity of chimeric organs by generating donor endothelium.

Cell-Mediated Therapies to Facilitate Operational Tolerance in Liver Transplantation.

Cell therapies using immune cells or non-parenchymal cells of the liver have emerged as potential treatments to facilitate immunosuppression withdrawal and to induce operational tolerance in liver transplant (LT) recipients. Recent pre-clinical and clinical trials of cellular therapies including regulatory T cells, regulatory dendritic cells, and mesenchymal cells have shown promising results. Here we briefly summarize current concepts of cellular therapy for induction of operational tolerance in LT recipients.

Women in Leadership and Their Influence on the Gender Diversity of Academic Plastic Surgery Programs.

BACKGROUND: Women seldom reach the highest leadership positions in academic plastic surgery. Contributing factors include lack of female role models/mentors and lack of gender diversity. Studies show that female role models and mentors are critical for recruiting and retaining female surgeons and that gender diversity within organizations more strongly influences women's career choices. The authors therefore sought to determine the current gender diversity of academic plastic surgery programs and investigate influences of gender and leadership on program gender composition. METHODS: A cross-sectional study of U.S. plastic surgery residency programs was performed in December of 2018. Genders of the leadership were collected, including medical school dean, department of surgery chair, department/division of plastic surgery chair/chief, plastic surgery program director, plastic surgery faculty, and plastic surgery residents. Gender relationships among these groups were analyzed. RESULTS: Ninety-nine residency programs were identified (79 integrated with or without independent and 20 independent). Women represented a smaller proportion of academic plastic surgeons in more senior positions (38 percent residents, 20 percent faculty, 13 percent program directors, and 8 percent chairs). Plastic surgery chair gender was significantly correlated with program director gender, and plastic surgery faculty gender was significantly associated with plastic surgery resident gender. Although not statistically significant, female plastic surgery chair gender was associated with a 45 percent relative increase in female plastic surgery residents. CONCLUSIONS: Women in leadership and gender diversity influence the composition of academic plastic surgery programs. Gender disparity exists at all levels, worsening up the academic ladder. Recruitment, retention, and promotion of women is critical, as such diversity is required for continued progress in innovation and problem-solving within plastic surgery.

Successful management and technical aspects of major liver resection in children: A retrospective cohort study.

ABSTRACT: Optimal treatment of patients with various types of liver tumors or certain liver diseases frequently demands major liver resection, which remains a clinical challenge especially in children.Eighty seven consecutive pediatric liver resections including 51 (59%) major resections (resection of 3 or more hepatic segments) and 36 (41%) minor resections (resection of 1 or 2 segments) were analyzed. All patients were treated between January 2010 and March 2018. Perioperative outcomes were compared between major and minor hepatic resections.The male to female ratio was 1.72:1. The median age at operation was 20 months (range, 0.33-150 months). There was no significant difference in demographics including age, weight, ASA class, and underlying pathology. The surgical management included functional assessment of the future liver remnant, critical perioperative management, enhanced understanding of hepatic segmental anatomy, and bleeding control, as well as refined surgical techniques. The median estimated blood loss was 40 ml in the minor liver resection group, and 90 ml in major liver resection group (P < .001). Children undergoing major liver resection had a significantly longer median operative time (80 vs 140 minutes), anesthesia time (140 vs 205 minutes), as well as higher median intraoperative total fluid input (255 vs 450 ml) (P < .001 for all). Fourteen (16.1%) patients had postoperative complications. By Clavien-Dindo classification, there were 8 grade I, 4 grade II, and 2 grade III-a complications. There were no significant differences in complication rates between groups (P = .902). Time to clear liquid diet (P = .381) and general diet (P = .473) was not significantly different. There was no difference in hospital length of stay (7 vs 7 days, P = .450). There were no 90-day readmissions or mortalities.Major liver resection in children is not associated with an increased incidence of postoperative complications or prolonged postoperative hospital stay compared to minor liver resection. Techniques employed in this study offered good perioperative outcomes for children undergoing major liver resections.

Median to radial nerve transfer after traumatic radial nerve avulsion in a pediatric patient.

This case report describes an isolated radial nerve avulsion in a pediatric patient, treated by combination sensory and motor median to radial nerve transfers. After traumatic avulsion of the proximal radial nerve, a 12-year-old male patient underwent end-to-end transfer of median nerve branches to flexor carpi radialis and flexor digitorum superficialis to the posterior interosseous nerve and extensor carpi radialis nerve, respectively. He underwent end-to-side sensory transfer of the superficial radial sensory to the median sensory nerve. Pronator teres to extensor carpi radialis brevis tendon transfer was simultaneously performed to power short-term wrist extension. Within months after surgery, the patient had regained 9-10/10 sensation in the hand and forearm. In the following months and years, he regained dexterity, independent fine-finger and thumb motions, and 4-5/5 strength in all extensors except the abductor pollicis longus muscle. He grew 25 cm without extremity deformity or need for secondary orthopedic procedures. In appropriate adult and pediatric patients with proximal radial nerve injuries, nerve transfers have advantages over tendon transfers, including restored independent fine finger motions, regained sensation, and reinnervation of multiple muscle groups with minimal donor sacrifice.

The accumulation of T cells within acellular nerve allografts is length-dependent and critical for nerve regeneration.

Repair of traumatic nerve injuries can require graft material to bridge the defect. The use of alternatives to bridge the defect, such as acellular nerve allografts (ANAs), is becoming more common and desired. Although ANAs support axon regeneration across short defects (<3 cm), axon regeneration across longer defects (>3 cm) is limited. It is unclear why alternatives, including ANAs, are functionally limited by length. After repairing Lewis rat nerve defects using short (2 cm) or long (4 cm) ANAs, we showed that long ANAs have severely reduced axon regeneration across the grafts and contain Schwann cells with a unique phenotype. But additionally, we found that long ANAs have disrupted angiogenesis and altered leukocyte infiltration compared to short ANAs as early as 2 weeks after repair. In particular, long ANAs contained fewer T cells compared to short ANAs. These outcomes were accompanied with reduced expression of select cytokines, including IFN-γ and IL-4, within long versus short ANAs. T cells within ANAs did not express elevated levels of IL-4, but expressed elevated levels of IFN-γ. We also directly assessed the contribution of T cells to regeneration across nerve grafts using athymic rats. Interestingly, T cell deficiency had minimal impact on axon regeneration across nerve defects repaired using isografts. Conversely, T cell deficiency reduced axon regeneration across nerve defects repaired using ANAs. Our data demonstrate that T cells contribute to nerve regeneration across ANAs and suggest that reduced T cells accumulation within long ANAs could contribute to limiting axon regeneration across these long ANAs.

Gender Imbalance at Academic Plastic Surgery Meetings.

BACKGROUND: Participation in scientific meetings yields multiple benefits, yet participation opportunities may not be equally afforded to men and women. The authors' primary goal was to evaluate the representation of men and women at five major academic plastic surgery meetings in 2017. Secondarily, the authors used bibliometric data to compare academic productivity between male and female physician invited speakers or moderators. METHODS: The authors compiled information regarding male and female invited speakers from meeting programs. Bibliometric data (h-index, m-value) and metrics of academic productivity (numbers of career publications, publications in 2015 to 2016, career peer-reviewed publications, first and senior author publications) for invited speakers were extracted from Scopus and analyzed. RESULTS: There were 282 academic physician invited speakers at the five 2017 meetings. Women constituted 14.5 percent. Univariate analysis showed no differences in h-index, m-value, or numbers of total career publications or first and last author publications at the assistant and associate professor ranks, but higher values for men at the professor level. A model of academic rank based on bibliometric and demographic variables showed male gender significantly associated with increased probability of holding a professor title, even when controlling for academic achievement markers (OR, 2.17; 95 percent CI, 1.61 to 2.92). CONCLUSIONS: Although the impact of women's published work was no different than that of men among junior and midcareer faculty, women constitute a minority of invited speakers at academic plastic surgery meetings. Sponsorship is imperative for achieving gender balance within plastic surgery and to ultimately create more diverse and effective teams to improve patient care.

Empowering Post-Surgical Patients to Improve Opioid Disposal: A Before and After Quality Improvement Study.

BACKGROUND: Our country is in the midst of an opioid epidemic. Although the problem is multifactorial, one issue is the presence of excess prescription opioid medications circulating in our communities. Our objective was to determine whether dissemination of an educational brochure would improve the disposal of unused opioids after surgery. STUDY DESIGN: Eligible surgery patients from an upper extremity/peripheral nerve clinic were enrolled into this prospective before and after study between February 2017 and September 2017. Patients who reported opioid use preoperatively were excluded from this study. The same survey was administered to the group of patients who did not receive the intervention and to those who did receive the intervention. Our primary endpoint was the proportion of patients who disposed of unused opioid medications. RESULTS: A total of 334 patients were studied: 164 who did not receive the brochure and 170 who received the brochure. Seventy-six patients were excluded for preoperative opioid use. After dissemination of the brochure, there was a significant increase in the proportion of patients who disposed of their unused opioids (11% vs 22%, p = 0.02). Of those who disposed of their opioids, there was no significant difference in the proportion of patients from each group who disposed in a manner that was recommended by the brochure (43% vs 64%, p = 0.19). CONCLUSIONS: Dissemination of the educational brochure improved disposal of unused opioids after surgery. This low-cost, easily implemented intervention can improve disposal of unused opioids and ultimately, decrease the amount of excess opioids circulating in our communities.