Publications by authors named "V L Young"

1,509 Publications

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Localized laryngeal amyloidosis: A systematic review.

Am J Otolaryngol 2022 Jul 28;43(5):103550. Epub 2022 Jul 28.

UCSF Voice and Swallowing Center, Department of Otolaryngology-Head and Neck Surgery, University of California San Francisco, San Francisco, CA, USA. Electronic address:

Objective: The larynx is the most common site of localized head and neck amyloidosis. Our study aimed to review the clinical features, treatments, and outcomes associated with localized laryngeal amyloidosis (LA). We also compared these features between two different time periods to evaluate the evolution of LA management.

Methods: A literature search using PubMed, CINAHL, Embase, and Cochrane Library identified cases of LA published between 1891 and 2021. Biopsy-proven cases of localized LA were included. Non-English studies, animal studies, and reviews were excluded.

Results: 282 patients (1891-1999: 142 patients, 2000-2021: 140 patients) from 129 studies were included. Results are reported as 1891-2000 vs. 2000-2021: Mean age was 48.5 years (range, 8-90 years) vs. 46.0 years (range, 9-84 years). The most common presenting symptoms were dysphonia (n = 30, 95 % vs. n = 127, 96 %) and difficulty breathing (n = 37, 27 % vs. n = 35, 27 %). A total of 62 (44 %) vs. 46 (33 %) lesions were found in the true vocal folds and 35 (25 %) vs. 59 (42 %) were found in the false vocal folds. 133 (94 %) vs. 137 (98 %) patients underwent surgical interventions to investigate and/or treat LA. Recurrent LA was reported in 27 (19 %) vs. 33 (24 %) patients with a mean time to recurrence of 25.4 months (range, 0.3-132 months) vs. 34.5 months (range, 0.8-144 months). Of cases reporting survival rate, 104 (97 %) vs. 107 (99 %) were alive at source study endpoints.

Conclusion: LA typically exhibits an indolent course; therefore, early intervention may address longstanding symptoms. Recurrent disease poses a clinical challenge in patients with LA.
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http://dx.doi.org/10.1016/j.amjoto.2022.103550DOI Listing
July 2022

Intestinal Inflammation Reversibly Alters the Microbiota to Drive Susceptibility to Clostridioides difficile Colonization in a Mouse Model of Colitis.

mBio 2022 Jul 28:e0190422. Epub 2022 Jul 28.

Department of Microbiology & Immunology, University of Michigan Medical Schoolgrid.471406.0, Ann Arbor, Michigan, USA.

Susceptibility to Clostridioides difficile infection (CDI) typically follows the administration of antibiotics. Patients with inflammatory bowel disease (IBD) have increased incidence of CDI, even in the absence of antibiotic treatment. However, the mechanisms underlying this susceptibility are not well understood. To explore the intersection between CDI and IBD, we recently described a mouse model where colitis triggered by the murine gut bacterium, Helicobacter hepaticus, in IL-10 mice led to susceptibility to C. difficile colonization without antibiotic administration. The current work disentangles the relative contributions of inflammation and gut microbiota in colonization resistance to C. difficile in this model. We show that inflammation drives changes in microbiota composition, which leads to CDI susceptibility. Decreasing inflammation with an anti-p40 monoclonal antibody promotes a shift of the microbiota back toward a colonization-resistant state. Transferring microbiota from susceptible and resistant mice to germfree animals transfers the susceptibility phenotype, supporting the primacy of the microbiota in colonization resistance. These findings shine light on the complex interactions between the host, microbiota, and C. difficile in the context of intestinal inflammation, and may form a basis for the development of strategies to prevent or treat CDI in IBD patients. Patients with inflammatory bowel disease (IBD) have an increased risk of developing C. difficile infection (CDI), even in the absence of antibiotic treatment. Yet, mechanisms regulating C. difficile colonization in IBD patients remain unclear. Here, we use an antibiotic-independent mouse model to demonstrate that intestinal inflammation alters microbiota composition to permit C. difficile colonization in mice with colitis. Notably, treating inflammation with an anti-p40 monoclonal antibody, a clinically relevant IBD therapeutic, restores microbiota-mediated colonization resistance to the pathogen. Through microbiota transfer experiments in germfree mice, we confirm that the microbiota shaped in the setting of IBD is the primary driver of susceptibility to colonization. Collectively, our findings provide insight into CDI pathogenesis in the context of intestinal inflammation, which may inform methods to manage infection in IBD patients. More broadly, this work advances our understanding of mechanisms by which the host-microbiota interface modulates colonization resistance to C. difficile.
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http://dx.doi.org/10.1128/mbio.01904-22DOI Listing
July 2022

The Gut Bacterial Community Potentiates Clostridioides difficile Infection Severity.

mBio 2022 Jul 20:e0118322. Epub 2022 Jul 20.

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, USA.

The severity of Clostridioides difficile infections (CDI) has increased over the last few decades. Patient age, white blood cell count, and creatinine levels as well as C. difficile ribotype and toxin genes have been associated with disease severity. However, it is unclear whether specific members of the gut microbiota are associated with variations in disease severity. The gut microbiota is known to interact with C. difficile during infection. Perturbations to the gut microbiota are necessary for C. difficile to colonize the gut. The gut microbiota can inhibit C. difficile colonization through bile acid metabolism, nutrient consumption, and bacteriocin production. Here, we sought to demonstrate that members of the gut bacterial communities can also contribute to disease severity. We derived diverse gut communities by colonizing germfree mice with different human fecal communities. The mice were then infected with a single C. difficile ribotype 027 clinical isolate, which resulted in moribundity and histopathologic differences. The variation in severity was associated with the human fecal community that the mice received. Generally, bacterial populations with pathogenic potential, such as , , and Klebsiella, were associated with more-severe outcomes. Bacterial groups associated with fiber degradation and bile acid metabolism, such as , , , and , were associated with less-severe outcomes. These data indicate that, in addition to the host and C. difficile subtype, populations of gut bacteria can influence CDI disease severity. Clostridioides difficile colonization can be asymptomatic or develop into an infection ranging in severity from mild diarrhea to toxic megacolon, sepsis, and death. Models that predict severity and guide treatment decisions are based on clinical factors and C. difficile characteristics. Although the gut microbiome plays a role in protecting against CDI, its effect on CDI disease severity is unclear and has not been incorporated into disease severity models. We demonstrated that variation in the microbiome of mice colonized with human feces yielded a range of disease outcomes. These results revealed groups of bacteria associated with both severe and mild C. difficile infection outcomes. Gut bacterial community data from patients with CDI could improve our ability to identify patients at risk of developing more severe disease and improve interventions that target C. difficile and the gut bacteria to reduce host damage.
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http://dx.doi.org/10.1128/mbio.01183-22DOI Listing
July 2022

Impact of Curricula and Electives on Primary Care Specialty Choice: A Narrative Synthesis.

Fam Med 2022 Jul;54(7):572-577

Department of Family and Community Medicine, Medical College of Wisconsin - Central Wisconsin, Wausau, WI.

Background And Objectives: Educational components and electives that may influence medical student choice of primary care careers have been studied individually, but not reviewed or synthesized. Examining educational components and electives in a comprehensive manner may inform evidence-based approaches to raise the number of primary care physicians in the United States and help optimize use of finite resources. We sought to determine evidence-based educational components and electives associated with increased medical student choice of primary care careers.

Methods: We searched PubMed, Scopus, and CINAHL for undergraduate medical education articles in English describing an educational component or elective and outcome relevant to primary care specialty choice. We assessed titles, then abstracts, and finally full texts for inclusion in a narrative synthesis.

Results: The searches returned 11,211 articles and we found 42 that met the inclusion criteria. The most described components were outpatient clinical rotations, preclinical courses, and preceptorships. The most common electives were international health, summer preceptorships, and rural medicine. While most articles described curricula that appeared to have a positive correlation with primary care specialty choice, six articles found limited benefit. In sum, results were mixed.

Conclusions: The current literature is limited, and many contemporary electives have not been studied with respect to primary care choice. Increased attention and funding to studying the impact of electives and other educational components on primary care specialty choice is warranted.
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http://dx.doi.org/10.22454/FamMed.2022.638811DOI Listing
July 2022

Medical School Characteristics, Policies, and Practices That Support Primary Care Specialty Choice: A Scoping Review of 5 Decades of Research.

Fam Med 2022 Jul;54(7):542-554

Departments of Public Health & Preventive Medicine and Family Medicine, SUNY Upstate Medical University, Syracuse, NY.

Background And Objectives: The United States, like many other nations, faces a chronic shortage of primary care physicians. The purpose of this scoping review was to synthesize literature describing evidence-based institutional practices and interventions that support medical students' choices of primary care specialties, published in the United States, Canada, Australia, and New Zealand.

Methods: We surveyed peer-reviewed, published research. An experienced medical librarian conducted searches of multiple databases. Articles were selected for inclusion based on explicit criteria. We charted articles by topic, methodology, year of publication, journal, country of origin, and presence or absence of funding. We then scored included articles for quality. Finally, we defined and described six common stages of development of institutional interventions.

Results: We reviewed 8,083 articles and identified 199 articles meeting inclusion criteria and 41 related articles. As a group, studies were of low quality, but improved over time. Most were quantitative studies conducted in the United States. Many studies utilized one of four common methodologic approaches: retrospective surveys, studies of programs or curricula, large-scale multi-institution comparisons, and single-institution exemplars. Most studies developed groundwork or examined effectiveness or impact, with few studies of planning or piloting. Few studies examined state or regional workforce outcomes.

Conclusions: Research examining medical school interventions and institutional practices to support primary care specialty choice would benefit from stronger theoretical grounding, greater investment in planning and piloting, consistent use of language, more qualitative methods, and innovative approaches. Robust funding mechanisms are needed to advance these goals.
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http://dx.doi.org/10.22454/FamMed.2022.440132DOI Listing
July 2022
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