Designing a Plastic and Reconstructive Surgery Virtual Curriculum: Assessment of Medical Student Knowledge, Surgical Skill, and Community Building.

BACKGROUND: The COVID-19 pandemic displaced medical students from their rotations and into virtual classrooms. The authors aimed to develop a virtual curriculum with the goals for students to gain knowledge in plastic surgery, to acquire technical skills, and to be able to promote community. METHODS: The authors developed a 4-week educational curriculum of topics in plastic surgery using the American Society of Plastic Surgeons Resident Education Curriculum and an online plastic surgery curriculum. Virtual flipped classroom case discussions and weekly surgical skills workshops were offered. Precourse and postcourse surveys were administered, and results were analyzed using IBM SPSS Statistics version 25.0. RESULTS: Three hundred three medical students and recent graduates enrolled in the course in June of 2020. One hundred eighty-two students completed the precourse survey (60 percent response rate), and of those, 50.0 percent ( n = 91) completed the postcourse survey for paired comparison. Students reported significant improvement in confidence discussing the relevant anatomy, workup, and surgical approaches to clinical cases, in addition to confidence in knowledge of all topic areas ( p < 0.001). Confidence in suturing and knot-tying techniques improved significantly among workshop participants ( p < 0.001). Students applying to residency programs this cycle felt significantly more prepared for subinternships ( p < 0.001) and significantly more connected to the community of applicants ( p < 0.001). CONCLUSIONS: The Plastic and Reconstructive Surgery Virtual Curriculum improved knowledge, surgical skills, and community in the field among medical student participants. This course may serve to provide a framework for structured virtual learning activities for students interested in plastic surgery and may have significant long-lasting utility for students interested in the field.

A Critical Assessment of the Transgender Health Care Workforce in the United States and the Capacity to Deliver Gender-Affirming Bottom Surgery.

BACKGROUND: Gender-affirming surgery is a critical component of transgender health care, but access information is limited. The study aim was to assess workforce capacity to perform gender affirming bottom surgeries (GABSs) in the United States. METHODS: A questionnaire was administered via email, phone call, or fax from February to May 2020 to 86 practices identified as performing GABS by searching 10 Web-based databases with standardized keywords. Questions assessed training capacity, surgical capacity, and surgeon experience. RESULTS: Thirty-two of 86 practices responded, 20 met the inclusion criteria. Practices were identified in 15 states, with an average 2.4 (SD, 1.3) surgeons performing GABS per year. States with the greatest number of total providers offering GABS were Illinois (n = 21), Texas (n = 10), and Massachusetts (n = 13). No significant correlation between number of GABS types offered and geographic population density (r = -0.40, P = 0.08), or between number of providers and geographic population density (r = 0.19, P = 0.44). Vaginoplasty was most frequently performed, with the longest waitlists and highest number of waitlist additions per month. Phalloplasty was the second most common procedure, and waitlist additions per month exceeded provider capacity to perform the procedure. Most surgeons performing GABS were plastic surgeons and urologists, whereas obstetricians/gynecologists performed the majority of hysterectomies. CONCLUSIONS: This study demonstrated a shortage of providers with requisite training and experience to provide GABS. Although more robust studies are needed to better characterize the relationship between the number of patients seeking GABS and available providers, these findings indicate a need for improved training.

Chaperone Use During Plastic Surgery Physical Examinations: Nationwide Provider Practices and Impact of Level of Training.

BACKGROUND: Medical chaperones often play an important role during physical examinations, providing patient comfort and serving as medicolegal witness. The purpose of this study was to evaluate and compare practices regarding chaperone use by plastic surgery attendings and trainees. METHODS: A voluntary survey was distributed to members of the American Council of Academic Plastic Surgeons. The survey included a standardized set of questions regarding physician demographics, nature of practice training, and current practices pertaining to chaperone use. Data were analyzed in a descriptive fashion. Ordinal logistic regression models were used to identify predictors of chaperone use. RESULTS: We received 167 responses, of which 107 (64.1%) were attendings and 60 (35.9%) were trainees. In total, 78.3% of the respondents were male and 21.7% were female. Routine use of chaperones was reported at 58.6%. Compared with plastic surgery trainees, attending surgeons were 12.8 times more likely to use a chaperone during sensitive examinations (P < 0.001). In addition, male respondents were 6.43 times more likely than their female counterparts to involve a chaperone during sensitive examinations (P < 0.001). Forty-eight percent of the trainees acknowledged receiving education regarding chaperone use, and this cohort was 7 times more likely to use a chaperone when compared with trainees who had not received chaperone instruction (P < 0.001). CONCLUSIONS: This study highlights the wide variability of chaperone use among plastic surgery attendings and trainees. Integration and standardization of chaperone education within plastic surgery training may be an effective technique to promote this practice and lead to improved patient-provider clinical experiences.

Opioid-sparing Strategies in Alloplastic Breast Reconstruction: A Systematic Review.

INTRODUCTION: Pain and discomfort are frequently experienced following mastectomy with concomitant breast implant- or tissue expander-based alloplastic breast reconstruction (AlBR). Unfortunately, postoperative opioids have decreased efficacy in AlBR, short-term complication profiles, and are fraught by long-term dependence. This systematic review aims to identify opioid-sparing pain management strategies in AlBR. METHODS: A systematic literature search of MEDLINE, Embase, Web of Science, and Cochrane Central Register was performed in September 2018. PRISMA guidelines were followed, and the review was prospectively registered in PROSPERO (CRD42018107911). The search identified 1184 articles. Inclusion criteria were defined as patients 18 years or older undergoing AlBR. RESULTS: Fourteen articles were identified assessing opioid-sparing strategies in AlBR. This literature included articles evaluating enhanced recovery protocols (two), intercostal blocks (two), paravertebral blocks (four), liposomal bupivacaine (three), diclofenac (one), and local anesthesia infusion pumps (two). The literature included five randomized trials and nine cohort studies. Study characteristics, bias (low to high risk), and reporting outcomes were extensively heterogeneous between articles. Qualitative analysis suggests reduced opioid utilization in enhanced recovery after surgery (ERAS) pathways, paravertebral blocks, and use of liposomal bupivacaine. CONCLUSIONS: A variety of opioid-sparing strategies are described for pain management in AlBR. Multimodal analgesia should be provided via ERAS pathways as they appear to reduce pain and spare opioid use. Targeted paravertebral blocks and liposomal bupivacaine field blocks appear to be beneficial in sparing opioids and should be considered as essential components of ERAS protocols. Additional prospective, randomized trials are necessary to delineate the efficacy of other studied modalities.

Assessment of Opioid-Prescribing Practices in Breast Augmentation: Future Directions for Prescribing Guidelines.

BACKGROUND: The United States (US) is in the mid of an opioid epidemic propagated, in part, by prescription opioids. With excess overprescribing documented in a variety of surgical procedures, several societies have recommended opioid-prescribing guidelines. Considering the scope and postoperative pain associated with aesthetic plastic surgery procedures, earnest evaluation into opioid-prescribing practices for breast augmentation was conducted. METHODS: Members of the American Society for Aesthetic Plastic Surgery were electronically surveyed on their opioid-prescribing patterns. The survey was distributed to 1709 plastic surgeons. Descriptive statistics were collated into percentages, deviations, and morphine milligram equivalents (MMEs), when appropriate. RESULTS: Two hundred twenty-nine American Society for Aesthetic Plastic Surgery members (13.4%) provided responses. A total of 91.2% of respondents prescribe opioids to patients undergoing breast augmentation. The most commonly prescribed agents included oxycodone/acetaminophen (Percocet, 47.0%) and hydrocodone/acetaminophen (Vicodin, 38.3%). On average, 165.3 ± 81.7 MMEs were dispensed (range, 25.0-600.0 MMEs; number tablets, 5-60). Prescribers felt that a lack of phone-in prescribing (52.4%) and the ease of preemptively prescribing opioids (52.4%) propagate opioid overprescribing. A total of 61.3% of respondents reported that they are or may be in favor of developing plastic surgery societal guidelines related to opioid prescribing. These respondents indicated support for guidelines on opioid-sparing pain management strategies (74.2%) and guidelines identifying the type (54.7%), duration of use (69.5%), and number of opioid tablets (61.7%) necessary for procedures. CONCLUSIONS: Considerable variability exists among prescribing patterns after breast augmentation. Societal guidelines aimed at providers and patients may serve a future role in opioid prescribing.

Single-Payer Health Care in the United States: Implications for Plastic Surgery.

Health care reform continues to be a topic of debate among lawmakers, politicians, physicians, and citizens of the United States. In recent years, proposed changes to the health care industry have grown in both granularity and popularity, with the possibility of adapting a single-payer health insurance system reaching an all-time high. The implications of such a policy are far-reaching and can be challenging to conceptualize, especially in isolation. The purpose of this article is to review some of the anticipated changes under this new system, specifically as they pertain to the field of plastic surgery.

The New 2019 Institutional Review Board Common Rule Update: Implications for Plastic Surgery Research.

Clinical research remains at the forefront of academic practice and evidence-based medicine. Unfortunately, history has shown that human subjects are vulnerable to experimentation without regard for their own dignity and informed decision-making. Subsequently, it is vital for research institutes to uphold safeguards and ethical conscientiousness toward human subjects. The establishment of federal regulations and the development of institutional review boards have set guidance on these processes. On January 21, 2019, final revisions to the Federal Policy for the Protection of Human Subjects (the "Common Rule") went into effect. The purpose of this article is to review changes to the Common Rule and discuss their impact on plastic surgery research.

Photographic and Video Deepfakes Have Arrived: How Machine Learning May Influence Plastic Surgery.

Advances in computer science and photography not only are pervasive but are also quantifiably influencing the practice of medicine. Recent progress in both software and hardware technology has translated into the design of advanced artificial neural networks: computer frameworks that can be thought of as algorithms modeled on the human brain. In practice, these networks have computational functions, including the autonomous generation of novel images and videos, frequently referred to as "deepfakes." The technological advances that have resulted in deepfakes are readily applicable to facets of plastic surgery, posing both benefits and harms to patients, providers, and future research. As a specialty, plastic surgery should recognize these concepts, appropriately discuss them, and take steps to prevent nefarious uses. The aim of this article is to highlight these emerging technologies and discuss their potential relevance to plastic surgery.

Are Prophylactic Postoperative Antibiotics Necessary after Masculinizing Mastectomy with Free Nipple Graft? A Single-institution Retrospective Review.

Antibiotic overuse, particularly in the postoperative period, has contributed substantially to increased rates of antibiotic resistance. Despite insufficient evidence to support prolonged prophylactic antibiotics following the majority of plastic surgery operations, and societal recommendations against the practice, many surgeons continue to perpetuate this cycle. Regarding "newer" operations, wherein minimal data pertaining to antibiotic use have been published, decision-making is often based on historical tradition. As such, continued communication of relevant data is essential to inform best practice guidelines. The aim of this case series was to report postoperative outcomes following chest masculinization with free nipple grafts performed according to a strict antibiotic protocol, which restricted prophylaxis to a single preoperative dose, in the absence of specific risk factors indicating a need for postoperative antibiotics. In this case series featuring 62 consecutive patients undergoing chest reconstruction with 124 free nipple grafts, there were no nipple losses or nipple graft infection events.

Surgical Approaches and 30-Day Complications of Velopharyngeal Insufficiency Repair Using American College of Surgeons National Surgical Quality Improvement Program-Pediatric.

BACKGROUND: This study aims to outline the 30-d complications of different velopharyngeal insufficiency (VPI) correction techniques using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric. METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program-Pediatric, VPI cases from 2012 to 2015 were identified. Patients were subdivided into two cohorts: (1) palatal procedures and (2) pharyngeal procedures, with the latter being subdivided into (1) pharyngeal flap and (2) sphincter pharyngoplasty. Patient characteristics and postoperative outcomes were compared using Pearson's chi-squared or Fischer's exact test for categorical variables and independent t-tests, Wilcoxon-Mann-Whitney, or analysis of variance for continuous variables. RESULTS: A total of 767 VPI cases were identified: 191 (24.9%) treated with palatal procedures and 576 (75.1%) with pharyngeal procedures, of which 444 were pharyngeal flap and 132 were sphincter pharyngoplasty. Patients who underwent palatal procedure had longer anesthesia (152.41 min) and operating time (105.72 min), whereas patients who underwent pharyngeal procedure had longer length of stay (1.66 d). There were no significant differences in outcomes between the two groups, nor were there significant differences in outcomes between pharyngeal flap and sphincter pharyngoplasty subgroups. Patients who experienced complications were younger, shorter, inpatient, and having a shorter operation time, longer anesthesia time, or longer length of stay. Plastic surgeons performed the majority of palatal procedures (62.3%), whereas pharyngeal procedures were most often performed by otolaryngologists (48.8%). CONCLUSIONS: As per national data, both palatal and pharyngeal procedures for repair can be performed with comparable 30-d complications. The chosen technique may be based on patient presentation and on the surgeon comfort level.

Opioid-Prescribing Practices in Plastic Surgery: A Juxtaposition of Attendings and Trainees.

BACKGROUND: The rates of opioid abuse and overdose in America have risen in parallel with the rates of opioid prescribing by physicians. As such, we sought to examine the prescribing practices among plastic surgery attendings and trainees to determine the need for more thorough education. METHODS: A survey was distributed to all ACGME-accredited plastic surgery residency programs and included questions regarding opioid-prescribing practices and self-rated ability pertaining to opioid management. Trends in prescribing practices based on prescriber position were analyzed using cumulative odds ordinal logistic regression with proportional odds and Chi-squared tests for ordinal and nominal variables, respectively. RESULTS: We received 78 responses with a wide geographical representation from plastic surgery residency programs: 59% of respondents were male and 39.7% female, 29.5% were attendings, 26.9% senior residents, 29.5% junior residents, and 14.1% interns. Compared with attendings, interns prescribe fewer pills (p < 0.05) and were significantly more likely to prescribe oxycodone (p < 0.03). Junior residents were 4.49 times more likely (p = 0.012) and senior residents 3.65 times more likely (p = 0.029) to prescribe additional opioids to avoid phone calls and follow-up visits. Interns and senior residents were significantly less comfortable than attendings in managing patients requesting additional opioids (p < 0.02). CONCLUSIONS: The results of this survey demonstrate that knowledge deficits do exist among trainees, and that trainees are significantly less comfortable than their attending counterparts with opioid prescribing and patient management. Therefore, the implementation of a thorough postoperative pain management education in residency may be a cogent strategy in mitigating the opioid crisis. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Evaluating unplanned readmission and prolonged length of stay following minimally invasive surgery for endometrial cancer.

OBJECTIVE: To evaluate risk factors for 30-day unplanned readmission and increased length of stay (LOS) following minimally invasive surgery (MIS) for endometrial cancer. METHODS: This was a retrospective, case-control study using the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP). Multivariable logistic regression was used to assess perioperative variables associated with readmission and increased LOS after MIS for endometrial cancer. RESULTS: The study population included 10,840 patients who met the criteria of having undergone MIS with a resultant endometrial malignancy confirmed on postoperative pathology. Common reasons for readmission included organ/space surgical site infection (65 cases), sepsis/septic shock (19 cases), and venous thromboembolism (20 cases). Notable risk factors for readmission included (Odds Ratio, Confidence Interval, p-value): dialysis dependence (6.77, 2.51-17.80, <0.01), increased length of stay (3.00, 2.10-4.10, <0.01), and preoperative weight loss (2.80, 1.06-7.17, 0.03); notable risk factors for increased LOS: ascites (8.51, 2.00-36.33, <0.01), operation duration >5 h (6.93, 5.29-9.25, <0.01), and preoperative blood transfusion (5.37, 2.05-14.04, <0.01). CONCLUSIONS: Identification of risk factors for adverse postoperative outcomes is necessary to inform and improve standards of care in MIS for endometrial cancer. Using nationally reported data from the ACS NSQIP, this study identifies independent risk factors for unplanned readmission and prolonged LOS, and in doing so, highlights potential avenues for quality improvement.

Does age or frailty have more predictive effect on outcomes following pedicled flap reconstruction? An analysis of 44,986 cases†.

The elderly population in the United States is expanding rapidly, and with advancements in modern medicine, the number of elderly patients undergoing surgery has risen in parallel. The aim of this study was to evaluate the effect of age and frailty on postoperative outcomes following pedicled flap reconstruction. The 2005-2016 ACS-NSQIP databases were queried to identify cases involving pedicled flaps based on CPT codes. Demographic data and postoperative complications were assessed using Chi-square and t-tests for analysis of categorical and continuous variables, respectively. A multivariable regression analysis was conducted to control for confounders. A total of 44,986 cases were included in our analysis. Patients in the 70-79year age group had the highest rates of all-cause (31.2%), mild systemic (25.3%) and severe systemic (7.4%) complications. Multivariable regression identified age as an independent risk factor for all-cause, severe systemic and wound complications. A score of 3+ on the 5-factor modified frailty index (mFI-5) was associated with all-cause, severe systemic and wound complications. When stratified by flap location, age was predictive of all-cause complications for breast, trunk, upper extremity and lower extremity flaps. Finally, mFI-5 score of 3+ was identified as an independent risk factor for all-cause complications in flaps of the head and neck, trunk and lower extremity. Although, increased age does contribute to risk of postoperative complications, the frailty index appears to hold much stronger predictive capacity. These findings stress the importance of optimizing preoperative comorbidities to reduce the risk of poor postoperative outcomes.

Epidemiologic Characteristics and Postoperative Complications following Augmentation Mammaplasty: Comparison of Transgender and Cisgender Females.

BACKGROUND: Breast augmentation in transgender women can be an important first step in addressing gender incongruence and improving psychosocial functioning. The aim of this study was to compare postoperative outcomes of augmentation mammoplasty in transgender and cisgender females. METHODS: We queried the American College of Surgeons National Surgical Quality Improvement Program database from 2006 to 2017 to establish 2 cohorts: (1) transgender females undergoing gender-affirming breast augmentation ("top surgery") and (2) cisgender females seeking cosmetic breast augmentation (CBA). Demographic characteristics and postoperative outcomes were compared between the 2 cohorts. Multivariable regression analysis was used to control for confounders. RESULTS: A total of 1,360 cases were identified, of which 280 (21%) were feminizing top surgeries and 1,080 (79%) were CBA cases. The transfeminine cohort was significantly older, had a higher average body mass index, and was more racially diverse than the CBA cohort. Transfeminine patients also had higher rates of smoking, diabetes, and hypertension. The rates of all-cause complications were low in both cohorts, and differences were not significant (1.6% transfeminine versus 1.8% CBA, P = 0.890) for the first 30-days after operation. After controlling for confounding variables, transfeminine patients had postoperative complication profiles similar to their cisgender counterparts. Multivariable regression analysis revealed no statistically significant predictors for all-cause complications. CONCLUSIONS: Transfeminine breast augmentation is a safe procedure that has a similar 30-day complication profile to its cisgender counterpart. The results of this study should reassure and encourage surgeons who are considering performing this procedure.

Mastectomy in Transgender and Cisgender Patients: A Comparative Analysis of Epidemiology and Postoperative Outcomes.

BACKGROUND: Mastectomy is a commonly requested procedure in the transmasculine population and has been shown to improve quality of life, although there is limited research on safety. The aim of this study was to provide a nationwide assessment of epidemiology and postoperative outcomes following masculinizing mastectomy and compare them with outcomes following mastectomy for cancer prophylaxis and gynecomastia correction in cisgender patients. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database from 2005 to 2017 was queried using International Classification of Diseases and Current Procedural Terminology codes to create cohorts of mastectomies for 3 indications: transmasculine chest reconstruction, cancer risk-reduction (CRRM), and gynecomastia treatment (GM). Demographic characteristics, comorbidities, and postoperative complications were compared between the 3 cohorts. Multivariable regression analysis was used to control for confounders. RESULTS: A total of 4,170 mastectomies were identified, of which 14.8% (n = 591) were transmasculine, 17.6% (n = 701) were CRRM, and 67.6% (n = 2,692) were GM. Plastic surgeons performed the majority of transmasculine cases (85.3%), compared with the general surgeons in the CRRM (97.9%) and GM (73.7%) cohorts. All-cause complication rates in the transmasculine, CRRM, and GM cohorts were 4.7%, 10.4%, and 3.7%, respectively. After controlling for confounding variables, transgender males were not at an increased risk for all-cause or wound complications. Multivariable regression identified BMI as a predictor of all-cause and wound complications. CONCLUSION: Mastectomy is a safe and efficacious procedure for treating gender dysphoria in the transgender male, with an acceptable and reassuring complication profile similar to that seen in cisgender patients who approximate either the natal sex characteristics or the new hormonal environment.

Reconstruction of Congenital Microtia and Anotia: Analysis of Practitioner Epidemiology and Postoperative Outcomes.

BACKGROUND: Microtia refers to a congenital malformation of the external ear that is associated with a range of functional, psychosocial, aesthetic, and financial burdens. The aim of this study was to analyze the epidemiology and postoperative complication profile of microtia reconstruction. METHODS: A retrospective review was conducted using data from the 2012-2017 the American College of Surgeons National Quality Improvement Program Pediatric databases. Patients with a diagnosis of microtia or anotia were identified using International Classification of Diseases codes. Demographics and postoperative complications were analyzed using Chi-square and t tests for categorical and continuous variables, respectively. Multivariable regression was performed to control for confounding variables. RESULTS: A total of 466 cases were analyzed, of which 290 (62.2%) were performed by plastic surgeons and 176 (37.8%) by otolaryngologists (ear, nose, and throat physicians [ENT]). Autologous reconstruction was the predominant approach [76.2% of cases (n = 355)] in this cohort. ENT physicians operated on a significantly younger patient population (mean age 8.4 ± 3.2 years versus 10.0 ± 3.2 years, P< 0.001) and had higher rates of concurrent atresia/middle ear repair [21.0% (n = 37) versus 3.7% (n = 17)] compared with plastic surgeons. The rate of all-cause complications was 5.9% (n = 17) in the plastic surgery cohort and 4.0% (n = 7) in the ENT cohort (P= 0.372). Multivariable regression did not reveal any statistically significant predictors for all-cause complications. CONCLUSIONS: Reconstruction of the external ear for patients with microtia/anotia is a safe procedure, with low rates of postoperative complications, readmissions, and reoperations. Autologous reconstruction remains the preferred modality for repair of the external ear and simultaneous atresiaplasty/middle ear repair does not increase the risk of complications.

Masculinizing Chest Reconstruction in Transgender and Nonbinary Individuals: An Analysis of Epidemiology, Surgical Technique, and Postoperative Outcomes.

BACKGROUND: Chest reconstruction ('top surgery') is an important component of transition in the transmasculine population that can substantially improve gender incongruence. The aim of this study was to evaluate the demographic characteristics, surgical technique, and postoperative outcomes following transmasculine chest surgery. METHODS: Using ICD codes, we identified all cases of gender-affirming transmasculine chest surgery from the ACS NSQIP database (2010-2017). CPT codes were used to categorize patients by reconstructive modality: reduction versus mastectomy (± free nipple grafting [FNG]). Univariate analysis was conducted to assess for differences in demographics, comorbidities, and postoperative complications. Multivariable regression analysis was used to control for confounders. RESULTS: A total of 755 cases were identified, of whom 591 (78.3%) were mastectomies and 164 (21.7%) were reductions. No significant differences were noted in terms of age or BMI. Mastectomies had shorter operative times, but similar length of stay compared to reductions. Rates of postoperative complications were low, with 4.7% (n = 28) of mastectomies and 3.7% (n = 6) of reductions experiencing at least one all-cause complications. Postoperative complication rates were not statistically different between mastectomy with (3.4%) and without (5.6%) FNG. After controlling for confounders, there was no difference in terms of risk of all-cause complications between reduction and mastectomy, with or without FNG. CONCLUSION: Mastectomy and reduction mammaplasty are both safe procedures for chest reconstruction in the transmasculine population. These results may be used to encourage shared decision making between patient and surgeon such that the reconstructive modality of choice best aligns with the desired aesthetic outcome. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Cypin: A novel target for traumatic brain injury.

Cytosolic PSD-95 interactor (cypin), the primary guanine deaminase in the brain, plays key roles in shaping neuronal circuits and regulating neuronal survival. Despite this pervasive role in neuronal function, the ability for cypin activity to affect recovery from acute brain injury is unknown. A key barrier in identifying the role of cypin in neurological recovery is the absence of pharmacological tools to manipulate cypin activity in vivo. Here, we use a small molecule screen to identify two activators and one inhibitor of cypin's guanine deaminase activity. The primary screen identified compounds that change the initial rate of guanine deamination using a colorimetric assay, and secondary screens included the ability of the compounds to protect neurons from NMDA-induced injury and NMDA-induced decreases in frequency and amplitude of miniature excitatory postsynaptic currents. Hippocampal neurons pretreated with activators preserved electrophysiological function and survival after NMDA-induced injury in vitro, while pretreatment with the inhibitor did not. The effects of the activators were abolished when cypin was knocked down. Administering either cypin activator directly into the brain one hour after traumatic brain injury significantly reduced fear conditioning deficits 5 days after injury, while delivering the cypin inhibitor did not improve outcome after TBI. Together, these data demonstrate that cypin activation is a novel approach for improving outcome after TBI and may provide a new pathway for reducing the deficits associated with TBI in patients.