ABSTRACT
BACKGROUND: Currently, 2 predominant pathways exist for vascular surgery training: integrated and independent training pathways. We hypothesized that match rates would increase with time and be higher in the independent pathway than in the integrated pathway. METHODS: The National Resident Matching Program provided data from the Vascular Surgery Match (VSM) (2008-2021). Match rates were defined as the percentage of applicants who matched. Chi-squared tests were used to evaluate temporal trends and interpathway differences. RESULTS: Over the study period, the annual number of training positions increased for both the independent (119 to 129, 8% increase) and integrated (9 to 79, 778% increase) training pathways. From 2008 to 2021, the annual match rate was stable in the independent pathway (97% to 96%, P > 0.05). In the integrated pathway, the annual match rate increased from 29% to 44% (P < 0.001). During each year, match rates in the independent pathway exceeded those in the integrated pathway (P < 0.001). US allopathic graduates had higher match rates than non-US allopathic graduates in both the independent (92% vs. 82%, P < 0.001) and the integrated pathway (70% vs. 17%, P < 0.001). In the independent pathway, the percentage of applicants that matched at 1 of their top 3 choices decreased from 67% to 58% (P < 0.001). Over the study period, more training positions went unmatched in the Independent (n = 130, 8%) versus the Integrated (n = 17, 3%) pathway (P < 0.001). CONCLUSIONS: VSM match rates have increased for the integrated pathway and remains competitive especially for non-US allopathic graduates. More research is needed to understand applicant variables that modulate match rates.
Subject(s)
Internship and Residency , Specialties, Surgical , Humans , United States , Treatment Outcome , Specialties, Surgical/education , Education, Medical, Graduate , Vascular Surgical ProceduresABSTRACT
C-terminal binding proteins (CtBP1/2) are oncogenic transcriptional coregulators and dehydrogenases often overexpressed in multiple solid tumors, including breast, colon, and ovarian cancer, and associated with poor survival. CtBPs act by repressing expression of genes responsible for apoptosis (e.g., PUMA, BIK) and metastasis-associated epithelial-mesenchymal transition (e.g., CDH1), and by activating expression of genes that promote migratory and invasive properties of cancer cells (e.g., TIAM1) and genes responsible for enhanced drug resistance (e.g., MDR1). CtBP's transcriptional functions are also critically dependent on oligomerization and nucleation of transcriptional complexes. Recently, we have developed a family of CtBP dehydrogenase inhibitors, based on the parent 2-hydroxyimino-3-phenylpropanoic acid (HIPP), that specifically disrupt cancer cell viability, abrogate CtBP's transcriptional function, and block polyp formation in a mouse model of intestinal polyposis that depends on CtBP's oncogenic functions. Crystallographic analysis revealed that HIPP interacts with CtBP1/2 at a conserved active site tryptophan (W318/324; CtBP1/2) that is unique among eukaryotic D2-dehydrogenases. To better understand the mechanism of action of HIPP-class inhibitors, we investigated the contribution of W324 to CtBP2's biochemical and physiologic activities utilizing mutational analysis. Indeed, W324 was necessary for CtBP2 self-association, as shown by analytical ultracentrifugation and in vivo cross-linking. Additionally, W324 supported CtBP's association with the transcriptional corepressor CoREST, and was critical for CtBP2 induction of cell motility. Notably, the HIPP derivative 4-chloro-HIPP biochemically and biologically phenocopied mutational inactivation of CtBP2 W324. Our data support further optimization of W318/W324-interacting CtBP dehydrogenase inhibitors that are emerging as a novel class of cancer cell-specific therapeutic.
Subject(s)
Alcohol Oxidoreductases/chemistry , Alcohol Oxidoreductases/genetics , Antineoplastic Agents/pharmacology , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Enzyme Inhibitors/pharmacology , Intestinal Polyposis/drug therapy , Tryptophan/metabolism , Alcohol Oxidoreductases/antagonists & inhibitors , Animals , Antineoplastic Agents/chemistry , Catalytic Domain , Cell Line, Tumor , Cell Movement/drug effects , Cell Survival/drug effects , DNA-Binding Proteins/antagonists & inhibitors , Enzyme Inhibitors/chemistry , Epithelial-Mesenchymal Transition/drug effects , Gene Expression Regulation, Neoplastic/drug effects , HCT116 Cells , Humans , Hydroxylamines/chemistry , Hydroxylamines/pharmacology , Intestinal Polyposis/metabolism , Mice , Mutagenesis, Site-Directed , Phenylpropionates/chemistry , Phenylpropionates/pharmacology , Protein Multimerization/drug effects , Xenograft Model Antitumor AssaysABSTRACT
Histoplasmosis is a self-limiting and asymptomatic disease in immunocompetent individuals. Patients in an immunocompromised state are susceptible to disseminated disease. We present a case of a 60-year-old male with a history of psoriatic and rheumatoid arthritis treated with a tumor necrosis factor inhibitor (adalimumab), who presented with abdominal pain and was found to have gastrointestinal histoplasmosis as an obstructing ileocecal mass. Although gastrointestinal involvement is common in disseminating disease, symptomatic involvement is rare. This case presentation has implications in rheumatological patients on biologic medications.