All Publications


  • Career Trajectory After General Surgery Residency: Do Academic Program Graduates Pursue Academic Surgery? Annals of surgery Green, A., Sommer, E. R., Johnson, M. R., Gonzalez, H., Sia, T., Spain, D. A., Choi, J. 2024

    Abstract

    Determine the proportion of contemporary US academic general surgery residency program graduates who pursue academic careers and identify factors associated with pursuing academic careers.Many academic residency programs aim to cultivate academic surgeons, yet the proportion of contemporary graduates who choose academic careers is unclear. The potential determinants that affect graduates' decisions to pursue academic careers remain underexplored.We collected program and individual-level data on 2015 and 2018 graduates across 96 US academic general surgery residency programs using public resources. We defined those pursuing academic careers as faculty within US allopathic medical school-affiliated surgery departments who published two or more peer-reviewed publications as the first or senior author between 2020-2021. After variable selection using sample splitting LASSO regression, multivariable regression evaluated association with pursuing academic careers among all graduates, and graduates of top-20 residency programs. Secondary analysis using multivariable ordinal regression explored factors associated with high research productivity during early faculty years.Among 992 graduates, 166 (17%) were pursuing academic careers according to our definition. Graduating from a top-20 ranked residency program (OR[95%CI]: 2.34[1.40-3.88]), working with a longitudinal research mentor during residency (OR[95%CI]: 2.21[1.24-3.95]), holding an advanced degree (OR[95%CI]: 2.20[1.19-3.99]), and the number of peer-reviewed publications during residency as first or senior author (OR[95%CI]: 1.13[1.07-1.20]) were associated with pursuing an academic surgery career, while the number of peer-reviewed publications before residency was not (OR[95%CI]: 1.08[0.99-1.20]). Among top 20 program graduates, working with a longitudinal research mentor during residency (OR[95%CI]: 0.95[0.43-2.09]) was not associated with pursuing an academic surgery career. The number of peer-reviewed publications during residency as first or senior author was the only variable associated with higher productivity during early faculty years (OR[95%CI]: 1.12[1.07-1.18]).Our findings suggest programs that aim to graduate academic surgeons may benefit from ensuring trainees receive infrastructural support and demonstrate sustained commitment to research throughout residency. Our results should be interpreted cautiously as the impact of unmeasured confounders is unclear.

    View details for DOI 10.1097/SLA.0000000000006307

    View details for PubMedID 38652655

  • Does Recent COVID-19 Infection Impact Safety of Nasal Surgery? Facial plastic surgery & aesthetic medicine Wei, E. X., Green, A., Kandathil, C. K., Most, S. P. 2024

    View details for DOI 10.1089/fpsam.2023.0352

    View details for PubMedID 38530097

  • Rhinoplasty Outcomes in Patients with Symptoms of Body Dysmorphia. Aesthetic surgery journal Losorelli, S., Kimura, K. S., Wei, E. X., Abdelhamid, A. S., El Abany, A., Green, A., Karki, S., Stephanian, B. A., Kandathil, C. K., Most, S. P. 2024

    Abstract

    Patients with symptoms of body dysmorphia often seek consultation for aesthetic rhinoplasty. While body dysmorphic disorder is a formal psychiatric diagnosis, recent evidence indicates that patients with symptoms of this condition who seek rhinoplasty may experience increased satisfaction with their appearance following surgery.To determine the psychological impact of rhinoplasty in patients screened pre-/postoperatively with a body dysmorphia screening questionnaire.Retrospective chart review of patients who underwent aesthetic and/or functional rhinoplasty by a single surgeon (S.P.M.) from 6/2021- 4/2023. Adult patients with a complete pre- and postoperative body dysmorphic disorder-aesthetic surgery questionnaire (BDDQ-AS), Standardized Cosmesis and Health Nasal Outcomes Survey-Obstruction and Cosmesis (SCHNOS), and Visual Analog Scale (VAS) were included. Patient characteristics and outcomes were analyzed stratifying by BDDQ-AS screen.One-hundred fifteen patients (88% female) met criteria for inclusion. There was an 83% resolution rate in BDDQ-AS positive screening following rhinoplasty. Positive BDDQ-AS screening status pre- and postoperatively correlated with worse aesthetic satisfaction (all p<0.002). No patient reported outcome measures were indicative of which patients with a BDDQ-AS positive screen preoperatively would experience 'resolution' postoperatively.Body dysmorphia screening resolution following surgical intervention correlated with improved patient aesthetic satisfaction, pointing to a potential positive psychological impact of undergoing rhinoplasty.

    View details for DOI 10.1093/asj/sjae045

    View details for PubMedID 38452148

  • Increased Prevalence of Positive Body Dysmorphic Disorder Screening Among Rhinoplasty Consultations During the COVID-19 Era. Facial plastic surgery & aesthetic medicine Wei, E. X., Green, A., Kandathil, C. K., Most, S. P. 2023

    View details for DOI 10.1089/fpsam.2023.0262

    View details for PubMedID 38150506

  • Foreign Body Reaction Requiring Re-Exploration After Tympanoplasty With Porcine Small Intestinal Submucosa Reconstruction. The Annals of otology, rhinology, and laryngology Fullerton, Z. H., Wei, E. X., Green, A., Sajjadi, H. 2023: 34894231218900

    Abstract

    OBJECTIVE: We present the first published case of large foreign body reaction to Biodesign (Cook Medical, Bloomington, IN), an acellular otologic graft matrix derived from porcine small intestinal submucosa, after use in tympanoplasty surgery in a patient without previous exposure to meat products.METHODS: A single case report of a 39-year-old female who developed tinnitus, ear drainage, and large fibrotic mass in external auditory canal and extending into middle ear after Type I medial graft tympanoplasty with Biodesign Graft. Left endoscopic microdissection and resection of the tympanic membrane and middle ear fibrotic mass were performed.MAIN FINDINGS: Surgical excision of the fibrous mass required extensive microdissection to ensure preservation of the ossicles and chorda tympani. Postoperatively, hearing improved and otalgia and otorrhea resolved.CONCLUSIONS: We report the first case of post-tympanoplasty reaction with the use of Biodesign acellular porcine graft in a patient with no previous known exposure to meat products. Although this presentation appears to be rare, it reinforces the need for careful patient selection and counseling around the use of porcine or other foreign grafts.

    View details for DOI 10.1177/00034894231218900

    View details for PubMedID 38098236

  • Parosteal Lipoma Overlying an Osteochondroma of the Hyoid Bone: A Case Report and Literature Review. The Laryngoscope Green, A., Wei, E. X., Chang-Graham, A., Holmes, B., Smith, A., Sung, C. K. 2023

    Abstract

    Parosteal lipomas and osteochondromas of the head and neck are uncommon benign tumors, constituting a small fraction of lipoma and bone tumor cases. We present a unique case of a 66-year-old male with a parosteal lipoma overlying an osteochondroma in the anterior midline neck, causing dysphagia. Surgical excision confirmed the diagnosis, and a literature review revealed similar cases predominantly adjacent to the mandible or calvaria. This case emphasizes the need to have parosteal lipoma and osteochondroma on the differential diagnosis for patients presenting with a firm mass of the central neck, especially with a history of trauma. Laryngoscope, 2023.

    View details for DOI 10.1002/lary.31192

    View details for PubMedID 37965970

  • Prevalence and Characteristics Associated with Positive Body Dysmorphic Disorder Screening Among Patients Presenting for Cosmetic Facial Plastic Surgery. Facial plastic surgery & aesthetic medicine Wei, E. X., Kimura, K. S., Abdelhamid, A. S., Abany, A. E., Losorelli, S., Green, A., Kandathil, C. K., Most, S. P. 2023

    Abstract

    Background: Many patients with body dysmorphic disorder (BDD) seek out cosmetic surgery to alleviate their symptoms of distress related to a perceived defect in their appearance; however, the prevalence and risk factors for BDD among patients with cosmetic concerns have not been well characterized. Methods: We screened adult patients presenting to the clinic from June 2021 through September 2022 for BDD using the BDD Questionnaire-Aesthetic Surgery (BDDQ-AS) who were seen in consultation for rhinoplasty, aging face, and injectables. Results: Among 488 patients, the prevalence of screening positive for BDD was 41.0%. The prevalence of a positive BDD screen was highest among patients who were younger (p = 0.02), and those who had a positive self-reported psychiatric history (p = 0.02). Among rhinoplasty patients, those with aesthetic/cosmetic motivations, and those seeking revision rhinoplasty had higher rates of positive BDD screen. Higher scores on the Standardized Cosmesis and Health Nasal Outcomes Survey-Nasal Obstruction Score (SCHNOS-O) (p = 0.01) and Standardized Cosmesis and Health Nasal Outcomes Survey-Nasal Obstruction Score-Nasal Cosmesis Score (SCHNOS-C) (p < 0.0001) were predictive of a positive BDD screen, while question 5 of the SCHNOS was highly predictive of positive BDD screening (p < 0.0001). Conclusions: Our study characterizes relationships between positive BDD screening and age, gender, self-reported psychiatric history, and motivations for consultation, among patients seen for cosmetic surgery evaluation in a facial plastic and reconstructive surgery setting.

    View details for DOI 10.1089/fpsam.2023.0212

    View details for PubMedID 37930999

  • Evaluating the Effectiveness of Septoplasty for Nasal Valve Collapse: A Retrospective Study. Facial plastic surgery & aesthetic medicine Green, A., Wei, E. X., Kandathil, C. K., Youn, G. M., Shah, J. P., Most, S. P. 2023

    View details for DOI 10.1089/fpsam.2023.0218

    View details for PubMedID 37862050

  • Environmental Risk Factors for Pediatric Epistaxis vary by Climate Zone. The Laryngoscope Wei, E. X., Green, A., Chang, M. T., Hwang, P. H., Sidell, D. R., Qian, Z. J. 2023

    Abstract

    Prior studies have provided variable results regarding environmental risk factors for epistaxis. These studies were conducted in varying climate zones, which may explain discrepancies in results. The objective of this study is to investigate correlations between season, temperature, and humidity on frequency of pediatric epistaxis across climate zones.Children seen in the outpatient setting for epistaxis were identified from the 2007-2010 IBM MarketScan database. Climate zones were assigned according to International Energy Conservation Code (IECC) classification, where temperature zones in the United States and territories were assigned on an ordinal scale from 1 (tropical) to 8 (subarctic), and humidity zones were categorized as moist, dry, or marine. The control population was a sample of all well-child visits matched by age and county.We identified 184,846 unique children seen for epistaxis and 1,897,012 matched controls. Moderate temperature zones were associated with lower odds of epistaxis compared with the hottest and coldest zones. Humidity was associated inversely with epistaxis rates in moderate temperature zones but was not a significant predictor of epistaxis in climates with extreme heat. Additionally, summer was associated with lower odds of epistaxis compared to winter. Interestingly, however, there were significantly higher rates of cautery procedures during summer months, driven largely by increased procedures performed in clinic, as opposed to the operating room or emergency room.Environmental risk factors for epistaxis vary by climate zone. The model presented reconciles prior reports and may allow for more personalized clinical management based on regional climate.Level 3 Laryngoscope, 2023.

    View details for DOI 10.1002/lary.30961

    View details for PubMedID 37589269

  • Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells. Cancers Gerton, T. J., Green, A., Campisi, M., Chen, M., Gjeci, I., Mahadevan, N., Lee, C. A., Mishra, R., Vo, H. V., Haratani, K., Li, Z. H., Hasselblatt, K. T., Testino, B., Connor, T., Lian, C. G., Elias, K. M., Lizotte, P., Ivanova, E. V., Barbie, D. A., Dinulescu, D. M. 2023; 15 (16)

    Abstract

    High-grade serous ovarian cancer (HGSOC) is responsible for the majority of gynecology cancer-related deaths. Patients in remission often relapse with more aggressive forms of disease within 2 years post-treatment. Alternative immuno-oncology (IO) strategies, such as immune checkpoint blockade (ICB) targeting the PD-(L)1 signaling axis, have proven inefficient so far. Our aim is to utilize epigenetic modulators to maximize the benefit of personalized IO combinations in ex vivo 3D patient-derived platforms and in vivo syngeneic models. Using patient-derived tumor ascites, we optimized an ex vivo 3D screening platform (PDOTS), which employs autologous immune cells and circulating ascites-derived tumor cells, to rapidly test personalized IO combinations. Most importantly, patient responses to platinum chemotherapy and poly-ADP ribose polymerase inhibitors in 3D platforms recapitulate clinical responses. Furthermore, similar to clinical trial results, responses to ICB in PDOTS tend to be low and positively correlated with the frequency of CD3+ immune cells and EPCAM+/PD-L1+ tumor cells. Thus, the greatest response observed with anti-PD-1/anti-PD-L1 immunotherapy alone is seen in patient-derived HGSOC ascites, which present with high levels of systemic CD3+ and PD-L1+ expression in immune and tumor cells, respectively. In addition, priming with epigenetic adjuvants greatly potentiates ICB in ex vivo 3D testing platforms and in vivo tumor models. We further find that epigenetic priming induces increased tumor secretion of several key cytokines known to augment T and NK cell activation and cytotoxicity, including IL-6, IP-10 (CXCL10), KC (CXCL1), and RANTES (CCL5). Moreover, epigenetic priming alone and in combination with ICB immunotherapy in patient-derived PDOTS induces rapid upregulation of CD69, a reliable early activation of immune markers in both CD4+ and CD8+ T cells. Consequently, this functional precision medicine approach could rapidly identify personalized therapeutic combinations able to potentiate ICB, which is a great advantage, especially given the current clinical difficulty of testing a high number of potential combinations in patients.

    View details for DOI 10.3390/cancers15164128

    View details for PubMedID 37627156

    View details for PubMedCentralID PMC10452550

  • Inaugurating High-Throughput Profiling of Extracellular Vesicles for Earlier Ovarian Cancer Detection. Advanced science (Weinheim, Baden-Wurttemberg, Germany) Jo, A., Green, A., Medina, J. E., Iyer, S., Ohman, A. W., McCarthy, E. T., Reinhardt, F., Gerton, T., Demehin, D., Mishra, R., Kolin, D. L., Zheng, H., Cheon, J., Crum, C. P., Weinberg, R. A., Rueda, B. R., Castro, C. M., Dinulescu, D. M., Lee, H. 2023: e2301930

    Abstract

    Detecting early cancer through liquid biopsy is challenging due to the lack of specific biomarkers for early lesions and potentially low levels of these markers. The current study systematically develops an extracellular-vesicle (EV)-based test for early detection, specifically focusing on high-grade serous ovarian carcinoma (HGSOC). The marker selection is based on emerging insights into HGSOC pathogenesis, notably that it arises from precursor lesions within the fallopian tube. This work thus establishes murine fallopian tube (mFT) cells with oncogenic mutations and performs proteomic analyses on mFT-derived EVs. The identified markers are then evaluated with an orthotopic HGSOC animal model. In serially-drawn blood of tumor-bearing mice, mFT-EV markers increase with tumor initiation, supporting their potential use in early cancer detection. A pilot clinical study (n = 51) further narrows EV markers to five candidates, EpCAM, CD24, VCAN, HE4, and TNC. The combined expression of these markers distinguishes HGSOC from non-cancer with 89% sensitivity and 93% specificity. The same markers are also effective in classifying three groups (non-cancer, early-stage HGSOC, and late-stage HGSOC). The developed approach, for the first time inaugurated in fallopian tube-derived EVs, could be a minimally invasive tool to monitor women at high risk of ovarian cancer for timely intervention.

    View details for DOI 10.1002/advs.202301930

    View details for PubMedID 37485618

  • Sustained delivery of PARP inhibitor Talazoparib for the treatment of BRCA-deficient ovarian cancer FRONTIERS IN ONCOLOGY Yang, S., Green, A., Brown, N., Robinson, A., Senat, M., Testino, B., Dinulescu, D. M., Sridhar, S. 2023; 13: 1175617

    Abstract

    Ovarian cancer has long been known to be the deadliest cancer associated with the female reproductive system. More than 15% of ovarian cancer patients have a defective BRCA-mediated homologous recombination repair pathway that can be therapeutically targeted with PARP inhibitors (PARPi), such as Talazoparib (TLZ). The expansion of TLZ clinical approval beyond breast cancer has been hindered due to the highly potent systemic side effects resembling chemotherapeutics. Here we report the development of a novel TLZ-loaded PLGA implant (InCeT-TLZ) that sustainedly releases TLZ directly into the peritoneal (i.p.) cavity to treat patient-mimicking BRCA-mutated metastatic ovarian cancer (mOC).InCeT-TLZ was fabricated by dissolving TLZ and PLGA in chloroform, followed by extrusion and evaporation. Drug loading and release were confirmed by HPLC. The in vivo therapeutic efficacy of InCeT-TLZ was carried out in a murine Brca2-/-p53R172H/-Pten-/- genetically engineered peritoneally mOC model. Mice with tumors were divided into four groups: PBS i.p. injection, empty implant i.p. implantation, TLZ i.p. injection, and InCeT-TLZ i.p. implantation. Body weight was recorded three times weekly as an indicator of treatment tolerance and efficacy. Mice were sacrificed when the body weight increased by 50% of the initial weight.Biodegradable InCeT-TLZ administered intraperitoneally releases 66 μg of TLZ over 25 days. In vivo experimentation shows doubled survival in the InCeT-TLZ treated group compared to control, and no significant signs of toxicity were visible histologically in the surrounding peritoneal organs, indicating that the sustained and local delivery of TLZ greatly maximized therapeutic efficacy and minimized severe clinical side effects. The treated animals eventually developed resistance to PARPi therapy and were sacrificed. To explore treatments to overcome resistance, in vitro studies with TLZ sensitive and resistant ascites-derived murine cell lines were carried out and demonstrated that ATR inhibitor and PI3K inhibitor could be used in combination with the InCeT-TLZ to overcome acquired PARPi resistance.Compared to intraperitoneal PARPi injection, the InCeT-TLZ better inhibits tumor growth, delays the ascites formation, and prolongs the overall survival of treated mice, which could be a promising therapy option that benefits thousands of women diagnosed with ovarian cancer.

    View details for DOI 10.3389/fonc.2023.1175617

    View details for Web of Science ID 000992495000001

    View details for PubMedID 37228496

    View details for PubMedCentralID PMC10203577

  • Manganese dioxide nanosheets induce mitochondrial toxicity in fish gill epithelial cells NANOTOXICOLOGY Browning, C. L., Green, A., Gray, E. P., Hurt, R., Kane, A. B. 2021; 15 (3): 400-417

    Abstract

    The development and production of engineered 2D nanomaterials are expanding exponentially, increasing the risk of their release into the aquatic environment. A recent study showed 2D MnO2 nanosheets, under development for energy and biomedical applications, dissolve upon interaction with biological reducing agents, resulting in depletion of intracellular glutathione levels within fish gill cells. However, little is known concerning their toxicity and interactions with subcellular organelles. To address this gap, we examined cellular uptake, cytotoxicity and mitochondrial effects of 2D MnO2 nanosheets using an in vitro fish gill cell line to represent a target tissue of rainbow trout, a freshwater indicator species. The data demonstrate cellular uptake of MnO2 nanosheets into lysosomes and potential mechanisms of dissolution within the lysosomal compartment. MnO2 nanosheets induced severe mitochondrial dysfunction at sub-cytotoxic doses. Quantitative, single cell fluorescent imaging revealed mitochondrial fission and impaired mitochondrial membrane potential following MnO2 nanosheet exposure. Seahorse analyses for cellular respiration revealed that MnO2 nanosheets inhibited basal respiration, maximal respiration and the spare respiratory capacity of gill cells, indicating mitochondrial dysfunction and reduced cellular respiratory activity. MnO2 nanosheet exposure also inhibited ATP production, further supporting the suppression of mitochondrial function and cellular respiration. Together, these observations indicate that 2D MnO2 nanosheets impair the ability of gill cells to respond to energy demands or prolonged stress. Finally, our data demonstrate significant differences in the toxicity of the 2D MnO2 nanosheets and their microparticle counterparts. This exemplifies the importance of considering the unique physical characteristics of 2D nanomaterials when conducting safety assessments.

    View details for DOI 10.1080/17435390.2021.1874562

    View details for Web of Science ID 000612410000001

    View details for PubMedID 33502918

    View details for PubMedCentralID PMC8026737

  • Chemical and Colloidal Dynamics of MnO2 Nanosheets in Biological Media Relevant for Nanosafety Assessment SMALL Gray, E. P., Browning, C. L., Vaslet, C. A., Gion, K. D., Green, A., Liu, M., Kane, A. B., Hurt, R. H. 2020; 16 (21): e2000303

    Abstract

    Many layered crystal phases can be exfoliated or assembled into ultrathin 2D nanosheets with novel properties not achievable by particulate or fibrous nanoforms. Among these 2D materials are manganese dioxide (MnO2 ) nanosheets, which have applications in batteries, catalysts, and biomedical probes. A novel feature of MnO2 is its sensitivity to chemical reduction leading to dissolution and Mn2+ release. Biodissolution is critical for nanosafety assessment of 2D materials, but the timing and location of MnO2 biodissolution in environmental or occupational exposure scenarios are poorly understood. This work investigates the chemical and colloidal dynamics of MnO2 nanosheets in biological media for environmental and human health risk assessment. MnO2 nanosheets are insoluble in most aqueous phases, but react with strong and weak reducing agents in biological fluid environments. In vitro, reductive dissolution can be slow enough in cell culture media for MnO2 internalization by cells in the form of intact nanosheets, which localize in vacuoles, react to deplete intracellular glutathione, and induce cytotoxicity that is likely mediated by intracellular Mn2+ release. The results are used to classify MnO2 nanosheets within a new hazard screening framework for 2D materials, and the implications of MnO2 transformations for nanotoxicity testing and nanosafety assessment are discussed.

    View details for DOI 10.1002/smll.202000303

    View details for Web of Science ID 000520536700001

    View details for PubMedID 32191401

    View details for PubMedCentralID PMC7461694

  • Synthesis and characterization of iron nanoparticles on partially reduced graphene oxide as a cost-effective catalyst for polymer electrolyte membrane fuel cells MRS COMMUNICATIONS Green, A., Isseroff, R., Lin, S., Wang, L., Rafailovich, M. 2017; 7 (2): 166-172