Faculty Bibliography

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

BACKGROUND: Internalizing a strong medical professional identity (PI) is a critical part of medical education. Recent studies of medical students have documented that students' PI, measured by the Professional Identity Essay (PIE), a reflective writing assessment of PI based on Kegan's theory of adult development and Bebeau's developmental model of PI, vary and are impacted by education. Little is known about the PI of exemplary professional physicians. We sought to: 1) describe the PI of physicians who exemplify the highest principles of the medical profession, and 2) evaluate NYU faculty identified as professional exemplars by peers to provide data and demonstrate clear role models for learners METHODS: We elicited nominations for professional exemplar physicians from NYU faculty, chief residents, and 4th-year students, using the definition of professionalism developed by Colby and Damon (1992). Participants were recruited after receiving at least 3 nominations; select participants who received 1 or 2 nominations were also recruited to diversify the participants in terms of specialty, years of practice, gender and race.We also used snowball techniques to get nominations fromstudy participants. After consenting, faculty received the 11-question PIE. We analyzed demographic data of nominated faculty and completed a content analysis of the PIE.
RESULT(S): 206 individual faculty were nominated at least one time by 70 community members. 32 individuals were recruited to the study; to date 22 have completed the PIE. The 206 nominees/22 participants represent: 34/12 specialties, average years in practice 17.6/23.8, range of years in practice 62 for nominees/44 for participants. We identified 3 primary themes through the content analysis: (1) Response to Expectations, "Everything. The profession demands everything.As much as this profession takes fromme, it is dwarfed by what I have received in return." (2) Response to Failure: "I fail to live up to expectations every day. Some days thismotivatesme, other days I disappoint myself." (3) Learning from Others: "I view teaching as integral to medical professionalism." There was a range of developmental levels in the responses with some focusing more on external rather than internal motivations: "I can say that the [malpractice] process for me was very threatening, emotionally consuming and had the potential to alter professional behavior in the wrong way."
CONCLUSION(S): Nominated faculty represented a diverse group with respect to PI. Many participants demonstrated great professionalism and a sense of internal PI in responses to the PIE questions, while others focused onmore externalmotivations to drive their professional behaviors. Further analysis is needed to define the qualities of a true exemplary professional. The range of responses of the exemplars can both serve as role models for learners and provide multiple pathways for learners and faculty to strengthen their own professional identities

Trichorhinophalangeal syndrome type 1 (TRPS1; Online Mendelian Inheritance in Man #190350) is an autosomal dominant disorder caused by mutations in TRPS1. We report a Thai male with TRPS1 who carried a c.1842C>T (p.Arg615Ter) mutation. He had 15 supernumerary teeth, double mental foramina, hypoplastic mandibular condyles with slender condylar necks and unique ultrastructural hair findings. Body hair was absent. The hair in the area of a congenital melanocytic nevus had a greater number of hair cuticles than normal. Occipital hair had abnormal hair follicles and cuticles. The scale edges of the hair cuticles were detached and rolled up. Hypoplastic mandibular condyles with slender condylar necks, double mental foramina and the rolled up edges of hair cuticles have not been reported in patients with TRPS1.

PURPOSE/OBJECTIVE:The purpose of this study is to determine if the radiographic humerus union measurement (RHUM) is predictive of union in humeral shaft fractures treated nonoperatively. METHODS:All patients with long bone fracture nonunion presenting to a single surgeon were enrolled in a prospective registry. This registry was queried to identify patients with humeral shaft fractures treated nonoperatively and developed nonunion. The nonunion cohort was matched to a three to one gender- and age-matched control group that were treated nonoperatively for a humeral shaft fracture and achieved union. Two fellowship-trained orthopedic traumatologists blinded to eventual union scored radiographs obtained 12 weeks after injury using the RHUM. A binomial logistic regression determined the effect of the RHUM on the likelihood of developing union. RESULTS:Nine patients with humeral shaft fractures treated nonoperatively with radiographs 12 weeks after injury that developed nonunion were identified. These patients were matched to 27 controls. Logistic regression demonstrated the RHUM was a significant predictor of healing 12 weeks after humeral shaft fracture treated nonoperatively (p = 0.014, odds ratio 9.434, 95% CI for OR 1.586-56.098). All patients with RHUM below 7 went on to nonunion. All patients with RHUM above 8 healed. Three of seven patients (43%) with RHUM of 7 or 8 healed. CONCLUSION/CONCLUSIONS:The RHUM demonstrated an increased likelihood of achieving union 12 weeks after injury. Orthopedic surgeons can counsel patients that fractures with RHUM scores of 6 or below are in danger of developing nonunion and can target interventions appropriately.

OBJECTIVE:Ischemic complications (including in the lower extremity, visceral, spinal, and pelvic territories) following standard endovascular aortic repair (EVAR) are well recognized but fortunately uncommon. The incidence of such complications following fenestrated and branched aortic repair (F/BEVAR) has not been well defined in the literature. The objective of this study was to compare the incidence of ischemic complications between EVAR and F/BEVAR and to elucidate potential risk factors for these complications. METHODS:We identified all patients who underwent EVAR from 2003 to 2017 or F/BEVAR from 2012 to 2017 in the national Vascular Quality Initiative database. We assessed differences in perioperative ischemic outcomes with methods including logistic regression and inverse probability of treatment propensity score weighting, using a composite endpoint of lower extremity ischemia, intestinal ischemia, stroke, or new dialysis as the primary endpoint. RESULTS:The data comprised 35,379 EVAR patients and 3374 F/BEVAR patients. F/BEVAR patients were more likely to be female, have had previous aneurysm repairs, and be deemed unfit for open aneurysm repair; they were less likely to have ruptured aneurysms; and they had higher estimated blood losses, contrast volumes, and fluoroscopy and procedure times. The incidence of any ischemic event (7.7% vs 2.2%) as well as the incidences of the component endpoints of lower extremity ischemia (2.3% vs 1.0%), intestinal ischemia (2.7% vs 0.7%), stroke (1.5% vs 0.3%), and new hemodialysis (3.1% vs 0.4%) were all significantly increased (all P < .001) in F/BEVAR compared with standard EVAR. After propensity adjustment, F/BEVAR conferred increased odds of any ischemic complication (1.8), intestinal ischemia (2.0), lower extremity ischemia (1.3), new hemodialysis (10.2), and stroke (2.3). CONCLUSIONS:Rates of lower extremity ischemia, intestinal ischemia, new dialysis, and stroke each range from 0% to 1% for standard EVAR and 1% to 3% for F/BEVAR. The incidence of perioperative ischemic complications following F/BEVAR is significantly increased compared to EVAR. The real-world data in this study should help guide decision-making for surgeons and patients as well as serve as one metric for progress in device and technique development. Improvements in ischemic complications may come from continued technology development such as smaller sheaths, improved imaging to decrease procedure time and contrast volume, embolic protection, and increased operator skill with wire and catheter manipulation.

Electronic health record (EHR) technologies have improved the ease of access to structured clinical data. The standard means by which data are collected continues to be manual chart review. The authors compared the accuracy of manual chart review against modern electronic data warehouse queries. A manual chart review of the EHR was performed with medical record numbers and surgical admission dates for the 100 most recent inpatient venous thromboembolic events after total joint arthroplasty. A separate data query was performed with the authors' electronic data warehouse. Data sets were then algorithmically compared to check for matches. Discrepancies between data sets were evaluated to categorize errors as random vs systematic. From 100 unique patient encounters, 27 variables were retrieved. The average transcription error rate was 9.19% (SD, ±5.74%) per patient encounter and 11.04% (SD, ±21.40%) per data variable. The systematic error rate was 7.41% (2 of 27). When systematic errors were excluded, the random error rate was 5.79% (SD, ±7.04%) per patient encounter and 5.44% (SD, ±5.63%) per data variable. Total time and average time for manual data collection per patient were 915 minutes and 10.3±3.89 minutes, respectively. Data collection time for the entire electronic query was 58 seconds. With an error rate of 10%, manual chart review studies may be more prone to type I and II errors. Computer-based data queries can improve the speed, reliability, reproducibility, and scalability of data retrieval and allow hospitals to make more data-driven decisions. [Orthopedics. 2020;43(x):xx-xx.].

Stresses associated with disease may pathologically remodel the proteome by both increasing interaction strength and altering interaction partners, resulting in proteome-wide connectivity dysfunctions. Chaperones play an important role in these alterations, but how these changes are executed remains largely unknown. Our study unveils a specific N-glycosylation pattern used by a chaperone, Glucose-regulated protein 94 (GRP94), to alter its conformational fitness and stabilize a state most permissive for stable interactions with proteins at the plasma membrane. This "protein assembly mutation' remodels protein networks and properties of the cell. We show in cells, human specimens, and mouse xenografts that proteome connectivity is restorable by inhibition of the N-glycosylated GRP94 variant. In summary, we provide biochemical evidence for stressor-induced chaperone-mediated protein mis-assemblies and demonstrate how these alterations are actionable in disease.

ABC transporters facilitate the movement of diverse molecules across cellular membranes, but how their activity is regulated post-translationally is not well understood. Here we report the crystal structure of MlaFB from E. coli, the cytoplasmic portion of the larger MlaFEDB ABC transporter complex, which drives phospholipid trafficking across the bacterial envelope to maintain outer membrane integrity. MlaB, a STAS domain protein, binds the ABC nucleotide binding domain, MlaF, and is required for its stability. Our structure also implicates a unique C-terminal tail of MlaF in self-dimerization. Both the C-terminal tail of MlaF and the interaction with MlaB are required for the proper assembly of the MlaFEDB complex and its function in cells. This work leads to a new model for how an important bacterial lipid transporter may be regulated by small proteins, and raises the possibility that similar regulatory mechanisms may exist more broadly across the ABC transporter family.

Despite remarkable responses to cancer immunotherapy in a subset of patients, many patients remain resistant to therapies. It is now clear that elevated levels of tumor-infiltrating T cells as well as a systemic anti-tumor immune response are requirements for successful immunotherapies. However, the tumor microenvironment imposes an additional resistance mechanism to immunotherapy. We have developed a practical and improved strategy for cancer immunotherapy using an oncolytic virus and anti-OX40. This strategy takes advantage of a preexisting T cell immune repertoire in vivo, removing the need to know about present tumor antigens. We have shown in this study that the replication-deficient oncolytic Sindbis virus vector expressing interleukin-12 (IL-12) (SV.IL12) activates immune-mediated tumor killing by inducing OX40 expression on CD4 T cells, allowing the full potential of the agonistic anti-OX40 antibody. The combination of SV.IL12 with anti-OX40 markedly changes the transcriptome signature and metabolic program of T cells, driving the development of highly activated terminally differentiated effector T cells. These metabolically reprogrammed T cells demonstrate enhanced tumor infiltration capacity as well as anti-tumor activity capable of overcoming the repressive tumor microenvironment. Our findings identify SV.IL12 in combination with anti-OX40 to be a novel and potent therapeutic strategy that can cure multiple types of low-immunogenic solid tumors.

Homeostasis of neural firing properties is important in stabilizing neuronal circuitry, but how such plasticity might depend on alternative splicing is not known. Here we report that chronic inactivity homeostatically increases action potential duration by changing alternative splicing of BK channels; this requires nuclear export of the splicing factor Nova-2. Inactivity and Nova-2 relocation were connected by a novel synapto-nuclear signaling pathway that surprisingly invoked mechanisms akin to Hebbian plasticity: Ca²⁺-permeable AMPA receptor upregulation, L-type Ca²⁺ channel activation, enhanced spine Ca²⁺ transients, nuclear translocation of a CaM shuttle, and nuclear CaMKIV activation. These findings not only uncover commonalities between homeostatic and Hebbian plasticity but also connect homeostatic regulation of synaptic transmission and neuronal excitability. The signaling cascade provides a full-loop mechanism for a classic autoregulatory feedback loop proposed ∼25 years ago. Each element of the loop has been implicated previously in neuropsychiatric disease.