Due to the recent COVID-19 pandemic, patient care and medical education have faced many significant changes. The Association of American Medical Colleges and the American Council of Academic Plastic ...Surgery officially recommended halting all student rotations and interviews for the year. This change has unfortunately fallen squarely at the onset of a vital season for education and recruitment of plastic surgery subinterns. This article presents a curriculum for a single institution's virtual surgical subinternship to help inspire ideas and inspiration for programs developing their own virtual subinternships.
The goals for the virtual surgical subinternship are focused on student preparation for residency and remain similar to those outlined by the core competencies for in-person rotations. The first virtual subinternship in plastic surgery modeled after the curriculum presented was offered as a 2-week course starting May of 2020.
The components of the curriculum include a self-study syllabus, virtual case reviews, virtual suture laboratory, educational teleconferences, participation in research, and mentorship meetings. The 2-week course has approximately 25 hours of conferences and teaching, involving direct interaction with residents and faculty, and approximately 15 hours of self-directed learning.
To the authors' knowledge, this was the first virtual subinternship offered for rising fourth-year medical students. They strongly encourage other residency training programs to offer similar virtual learning opportunities for medical students, particularly for those without access to a home plastic surgery training program. The curriculum presented in this article is simply to provide ideas, inspiration, and a potential framework for programs wishing to create similar virtual learning opportunities.
T cells engineered to express a chimeric antigen receptor (CAR) against CD19 have recently been FDA approved for the treatment of relapsed or refractory large B-cell lymphoma. Despite the success and ...curative potential of CD19 CAR T cells, several reports describing disease relapse due to antigen loss are now emerging.
We developed a novel CAR construct directed against CD79b, a critical receptor for successful B-cell development that remains highly expressed in several subtypes of B-cell lymphoma, including mantle cell lymphoma (MCL). We tested CAR T cells directed against CD79b alone or in combination with CD19 targeting in a single construct, against cell line- and patient-derived xenograft models.
We demonstrate CAR79b antigen-specific recognition and cytotoxicity against a panel of cell lines and patient-derived xenograft models of MCL. Importantly, we show that downregulation of CD19 does not influence surface expression of CD79b and that anti-CD79b CAR T cells alone or arranged in a dual-targeting format with a CD19 single-chain variable fragment (scFv) are able to recognize and eliminate CD19
, CD19
, and mixed CD19
/CD19
B-cell lymphoma.
Our findings demonstrate that CAR T cells targeting CD79b alone or in combination have promise for treating and preventing CD19 antigen escape in B-cell lymphomas.
The authors studied the impact of a new, coordinated interview release date for integrated plastic surgery residencies.
A cross-sectional study of all 2020 integrated plastic surgery residencies and ...applicants was performed. Voluntary, anonymous surveys were administered following implementation of the interview policy.
Program response rates were 55.6% for the initial survey and 57.1% for the follow-up survey. Programs released an average of 2.1 (95% CI, 1.8 to 2.4) rounds of interview invitations and invited 39.0 (95% CI, 35.3 to 42.6) applicants to interview. Policy adherence was high (91.1%). Most programs believed the interview policy was an improvement for applicants (46.5% yes; 9.1% no) and programs (41.9% yes; 27.0% no). Median rank of matched candidates was 13, and 55.1% of programs matched candidates within the top quartile of their rank list. The average candidate applied to 72 programs, attended 11 interviews, and ranked 12 programs. Interview distribution was bimodal, with peaks at six and 15 total interview invitations. Applicants within the top fifth, tenth, and fifteenth percentile for total interview invites disproportionately accounted for 15.3%, 26.6%, and 36.5%, respectively, of all invitations received. Survey data suggested applicant satisfaction with travel planning, improved scheduling, and cost savings following implementation of the interview policy. Applicants were somewhat dissatisfied with interview distribution.
A coordinated interview release date is facile to adopt and does not adversely impact program interview trends or match rates. Applicants benefit from improved scheduling, travel planning, and cost savings; however, interview distribution continues to favor top-tier candidates.
Chimeric antigen receptor (CAR) T cells (CARTs) have shown tremendous potential for the treatment of certain B-cell malignancies, including patients with relapsed/refractory multiple myeloma (MM). ...Targeting the B-cell maturation antigen (BCMA) has produced the most promising results for CART therapy of MM to date, but not all remissions are sustained. Emergence of BCMA escape variants has been reported under the selective pressure of monospecific anti-BCMA CART treatment. Thus, there is a clinical need for continuous improvement of CART therapies for MM. Here, we show that a novel trimeric APRIL (a proliferation-inducing ligand)–based CAR efficiently targets both BCMA+ and BCMA− MM. Modeled after the natural ligand-receptor pair, APRIL-based CARs allow for bispecific targeting of the MM-associated antigens BCMA and transmembrane activator and CAML interactor (TACI). However, natural ligands as CAR antigen-binding domains may require further engineering to promote optimal binding and multimerization to adequately trigger T-cell activation. We found that using a trimeric rather than a monomeric APRIL format as the antigen-binding domain enhanced binding to BCMA and TACI and CART activity against MM in vitro and in vivo. Dual-specific, trimeric APRIL-based CAR are a promising therapeutic approach for MM with potential for preventing and treating BCMA escape.
•A trimeric extracellular moiety of APRIL has enhanced binding to BCMA and TACI compared with monomeric APRIL when incorporated into a CAR.•T cells transduced with a trimeric APRIL-based CAR are a promising approach for the treatment of MM.
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Genomic studies of the pediatric ocular tumor retinoblastoma are paving the way for development of targeted therapies. Robust model systems such as orthotopic xenografts are necessary for testing ...such therapeutics. One system involves bioluminescence imaging of luciferase-expressing human retinoblastoma cells injected into the vitreous of newborn rat eyes. Although used for several drug studies, the spatial and temporal development of tumors in this model has not been documented. Here, we present a new model to allow analysis of average luciferin flux (Formula: see text) through the tumor, a more biologically relevant parameter than peak bioluminescence as traditionally measured. Moreover, we monitored the spatial development of xenografts in the living eye. We engineered Y79 retinoblastoma cells to express a lentivirally-delivered enhanced green fluorescent protein-luciferase fusion protein. In intravitreal xenografts, we assayed bioluminescence and computed Formula: see text, as well as documented tumor growth by intraocular optical coherence tomography (OCT), brightfield, and fluorescence imaging. In vivo bioluminescence, ex vivo tumor size, and ex vivo fluorescent signal were all highly correlated in orthotopic xenografts. By OCT, xenografts were dense and highly vascularized, with well-defined edges. Small tumors preferentially sat atop the optic nerve head; this morphology was confirmed on histological examination. In vivo, Formula: see text in xenografts showed a plateau effect as tumors became bounded by the dimensions of the eye. The combination of Formula: see text modeling and in vivo intraocular imaging allows both quantitative and high-resolution, non-invasive spatial analysis of this retinoblastoma model. This technique will be applied to other cell lines and experimental therapeutic trials in the future.
Plastic surgery residencies are among the most competitive programs for graduate medical education. While board scores and research output are well-studied indicators of match success, no studies ...describe the association between an applicant's medical school ranking and subsequent residency ranking.
A cross-sectional study of integrated plastic surgery residents for the 2019 to 2020 academic year was performed. Integrated plastic surgery residency programs were ranked according to 2020 Doximity Residency Navigator. AAMC-affiliated allopathic medical schools were ranked according to US News & World Report 2020 Best Medical Schools. Multiple regression analysis was used to determine if academic pedigree predicted placement at highly competitive plastic surgery residency programs.
A total of 914 residents across 69 integrated plastic surgery residency programs were included. Ten medical schools accounted for 169 (18.4%) of all trainees. 159 (16.5%) matched at their home program for residency. Medical school ranking and medical school-affiliated integrated plastic surgery program ranking were significant predictors of match success and future residency competitiveness. The presence of an affiliated plastic surgery residency program predicted total number of medical school graduates who matriculated into plastic surgery residency (p < 0.0005). Graduates of top-ranked schools represented a disproportionate number of current plastic surgery residents (Top 10 program: 12.5%, Top 20: 24.1%, Top 40: 40.9%, Top 50: 49.1%).
Both medical school ranking and home plastic surgery program ranking appeared to influence match success and future residency training program competitiveness. This is the first study to demonstrate these associations.
Renal sympathetic denervation (RD) is a promising method of neuromodulation for the management of cardiac arrhythmia.
We tested the hypothesis that RD is antiarrhythmic in ambulatory dogs because it ...reduces the stellate ganglion nerve activity (SGNA) by remodeling the stellate ganglion (SG) and brain stem.
We implanted a radiotransmitter to record SGNA and electrocardiogram in 9 ambulatory dogs for 2 weeks, followed by a second surgery for RD and 2 months SGNA recording. Cell death was probed by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.
Integrated SGNA at baseline and 1 and 2 months after RD were 14.0 ± 4.0, 9.3 ± 2.8, and 9.6 ± 2.0 μV, respectively (P = .042). The SG from RD but not normal control dogs (n = 5) showed confluent damage. An average of 41% ± 10% and 40% ± 16% of ganglion cells in the left and right SG, respectively, were TUNEL positive in RD dogs compared with 0% in controls dogs (P = .005 for both). The left and right SG from RD dogs had more tyrosine hydroxylase-negative ganglion cells than did the left SG of control dogs (P = .028 and P = .047, respectively). Extensive TUNEL-positive neurons and glial cells were also noted in the medulla, associated with strongly positive glial fibrillary acidic protein staining. The distribution was heterogeneous, with more cell death in the medial than lateral aspects of the medulla.
Bilateral RD caused significant central and peripheral sympathetic nerve remodeling and reduced SGNA in ambulatory dogs. These findings may in part explain the antiarrhythmic effects of RD.
Regulatory T cells (Tregs) are key modulators of inflammation and are important for the maintenance of peripheral tolerance. Adoptive immunotherapy with polyclonal Tregs holds promise in organ ...transplantation, graft-versus-host disease, and autoimmune diseases, but may be enhanced by antigen-specific, long-lived Treg cells. We modified primary human Tregs with chimeric antigen-receptors (CARs) bearing different costimulatory domains and performed in vitro analyses of their phenotype and function. While neither the presence of a CAR nor the type of costimulation domain influenced Foxp3 expression in Tregs, the costimulation domain of the CARs affected CAR Treg surface phenotype and functions such as cytokine production. Furthermore, signaling from the CD28 costimulation domain maintained CAR Treg suppressor function, whereas 4-1B costimulation did not. In vivo, CAR Tregs accumulated at sites expressing target antigen, and suppressed antigen specific effector T cell responses; however, only CAR Tregs with CD28 signaling domains were potent inhibitors of effector T cell mediated graft rejection in vivo. Our findings support the use of CD28 based CAR-Tregs for tissue specific immune suppression in the clinic.
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