Otolaryngology Applicant Characteristics and Trends: Comparing OTO-HNS with Peer Specialties.

PURPOSE: To evaluate the recent Otolaryngology-Head and Neck Surgery (OTO-HNS) applicant characteristics, to identify which applicant characteristics are associated with successful match into OTO-HNS, and to compare OTO-HNS applicant trends and characteristics to that of peer surgical specialties (PS). MATERIALS AND METHODS: Data were obtained from official reports by the National Residency Matching Program (NRMP) for OTO-HNS, plastic and reconstructive surgery, orthopedic surgery, neurosurgery, and dermatology from 2006 to 2019. Alpha Omega Alpha (AOA) membership, United States Medical Licensing Examination (USMLE) scores, research productivity, graduation from a top-40 NIH-funded U.S. medical school, and additional graduate degree were recorded. Odds ratios (OR) were calculated to evaluate the relationship between applicant qualifications and match success. RESULTS: From 2014 to 2018, the OTO-HNS applicant pool shrunk from 443 to 333, representing the largest drop of all PS. Furthermore, OTO-HNS reported the most unfilled positions and highest match rates in 2017 (n = 14; 92.1%) and 2018 (n = 12; 94.6%) among any PS. Despite recent trends, 2019 NRMP data revealed a 38.74% increase in OTO-HNS applicant numbers compared to 2018. AOA membership (OR, 7.3; P = .030), USMLE Step 2 scores between 241 and 260 (OR, 6.5; P = .009), and research productivity (OR, 5.6; P = .005) significantly increased the odds of matching into OTO-HNS. CONCLUSIONS: Despite recent fluctuations in application trends, OTO-HNS continues to successfully match highly qualified applicants, including applicants with AOA membership, high Step 2 scores, and high research productivity. An understanding of the qualifications used to evaluate residency applicants may be helpful to both applicants and residency programs of OTO-HNS.

Friend or foe? Lactobacillus in the context of autoimmune disease.

Over the last decade, the interplay between the gut microbiota, the consortium of intestinal microbes that colonizes intestinal mucosal barriers, and its host immune system has been increasingly better understood. Disruption of the delicate balance between beneficial and pathogenic commensals, known as dysbiosis, contributes to a variety of chronic immunologic and metabolic diseases. Complicating this paradigm are bacterial strains that can operate paradoxically both as instigators and attenuators of inflammatory responses, depending on host background. Here, we review the role of several strains in the genus Lactobacillus within the context of autoimmune and other chronic disorders with a predominant focus on L. reuteri. While strains within this species have been shown to provide immune health benefits, they have also been demonstrated to act as a pathobiont in autoimmune-prone hosts. Beneficial functions in healthy hosts include competing with pathogenic microbes, promoting regulatory T cell development, and protecting the integrity of the gut barrier. On the other hand, certain strains can also break through a dysfunctional gut barrier, colonize internal tissues such as the spleen or liver and promote inflammatory responses in host tissues that lead to autoimmune disease. This review summarizes the manifold roles that these commensals play in the context of health and disease.

Mechanisms and consequences of gut commensal translocation in chronic diseases.

Humans and other mammalian hosts have evolved mechanisms to control the bacteria colonizing their mucosal barriers to prevent invasion. While the breach of barriers by bacteria typically leads to overt infection, increasing evidence supports a role for translocation of commensal bacteria across an impaired gut barrier to extraintestinal sites in the pathogenesis of autoimmune and other chronic, non-infectious diseases. Whether gut commensal translocation is a cause or consequence of the disease is incompletely defined. Here we discuss factors that lead to translocation of live bacteria across the gut barrier. We expand upon our recently published demonstration that translocation of the gut pathobiont Enterococcus gallinarum can induce autoimmunity in susceptible hosts and postulate on the role of Enterococcus species as instigators of chronic, non-infectious diseases.

A Diet-Sensitive Commensal Lactobacillus Strain Mediates TLR7-Dependent Systemic Autoimmunity.

Western lifestyle is linked to autoimmune and metabolic diseases, driven by changes in diet and gut microbiota composition. Using Toll-like receptor 7 (TLR7)-dependent mouse models of systemic lupus erythematosus (SLE), we dissect dietary effects on the gut microbiota and find that Lactobacillus reuteri can drive autoimmunity but is ameliorated by dietary resistant starch (RS). Culture of internal organs and 16S rDNA sequencing revealed TLR7-dependent translocation of L. reuteri in mice and fecal enrichment of Lactobacillus in a subset of SLE patients. L. reuteri colonization worsened autoimmune manifestations under specific-pathogen-free and gnotobiotic conditions, notably increasing plasmacytoid dendritic cells (pDCs) and interferon signaling. However, RS suppressed the abundance and translocation of L. reuteri via short-chain fatty acids, which inhibited its growth. Additionally, RS decreased pDCs, interferon pathways, organ involvement, and mortality. Thus, RS exerts beneficial effects in lupus-prone hosts through suppressing a pathobiont that promotes interferon pathways implicated in the pathogenesis of human autoimmunity.

The impact of nanoparticle ligand density on dendritic-cell targeted vaccines.

Dendritic-cell (DC) targeted antigen delivery systems hold promise for enhancing vaccine efficacy and delivery of therapeutics. However, it is not known how the number and density of targeting ligands on such systems may affect DC function and subsequent T cell response. We modified the surface of biodegradable nanoparticles loaded with antigen with different densities of the mAb to the DC lectin DEC-205 receptor and assessed changes in the cytokine response of DCs and T cells. DEC-205 targeted nanoparticles unexpectedly induced a differential cytokine response that depended on the density of ligands on the surface. Strikingly, nanoparticle surface density of DEC-205 mAb increased the amount of anti-inflammatory, IL-10, produced by DCs and T cells. Boosting mice with DEC-205 targeted OVA-nanoparticles after immunization with an antigen in CFA induced a similar pattern of IL-10 response. The correlation between DC production of IL-10 as a function of the density of anti-DEC-205 is shown to be due to cross-linking of the DEC-205 receptor. Cross-linking also increased DC expression of the scavenger receptor CD36, and blockade of CD36 largely abrogated the IL-10 response. Our studies highlight the importance of target ligand density in the design of vaccine delivery systems.