Protective anti-chlamydial vaccine regimen-induced CD4+ T cell response mediates early inhibition of pathogenic CD8+ T cell response following genital challenge.

We have demonstrated previously that TNF-α-producing CD8+ T cells mediate chlamydial pathogenesis, likely in an antigen (Ag)-specific fashion. Here we hypothesize that inhibition of Ag-specific CD8+ T cell response after immunization and/or challenge would correlate with protection against oviduct pathology induced by a protective vaccine regimen. Intranasal (i.n.) live chlamydial elementary body (EB), intramuscular (i.m.) live EB, or i.n. irrelevant antigen, bovine serum albumin (BSA), immunized animals induced near-total protection, 50% protection, or no protection, respectively against oviduct pathology following i.vag. C. muridarum challenge. In these models, we evaluated Ag-specific CD8+ T cell cytokine response at various time-periods after immunization or challenge. The results show protective efficacy of vaccine regimens correlated with reduction of Ag-specific CD8+ T cell TNF-α responses following i.vag. chlamydial challenge, not after immunization. Depletion of CD4+ T cells abrogated, whereas adoptive transfer of Ag-specific CD4+ T cells induced the significant reduction of Ag-specific CD8+ T cell TNF-α response after chlamydial challenge. In conclusion, protective anti-chlamydial vaccine regimens induce Ag-specific CD4+ T cell response that mediate early inhibition of pathogenic CD8+ T cell response following challenge and may serve as a predictive biomarker of protection against Chlamydia -induced chronic pathologies.

Reimagining the Rheumatology Fellowship Interview: Using Participatory Design-Thinking Process to Create a More Applicant-Centered Experience.

OBJECTIVE: Design thinking is a creative problem-solving process used to better understand users' needs and experiences so that a product or service can be improved. Its emphasis on empathy, iterative prototyping, and participatory collaboration make it an ideal methodology for innovation in medical education. We apply this framework to the virtual rheumatology fellowship interview process so that interviews can become more applicant centered. METHODS: This educational quality improvement project uses a design-thinking framework to identify opportunities and challenges for rheumatology fellowship applicants. The investigators use the 5-step process (Empathize, Define, Ideate, Prototype, Test) and incorporate rapid qualitative analysis of semistructured interviews to innovate the interview experience. The iterative and collaborative nature of this process has empowered participants to codesign an applicant-centered interview experience. RESULTS: Interviews with fellowship applicants (n = 9), fellow physicians (n = 4), and faculty members (n = 3) identified three major dynamics of the interview process: (1) Is it a safe environment to ask questions? (2) How do I exchange information effectively? and (3) How do I fit all these data into the bigger picture? Creative brainstorming techniques at a series of three workshops yielded four prototypes emphasizing customization, hybridization, facilitation, and preparation. A finalized applicant-centered interview template was devised in preparation for the 2023-2024 application season. CONCLUSION: Design thinking has yielded insights into three important dynamics that drive applicant experiences. These insights allow for a redesign of processes so that virtual interviews can be more applicant centered. This framework allows for further iterations and modifications as the needs of applicants and programs evolve over time.

A case of TAFRO syndrome with DIC and neurologic and cardiac involvement.

We highlight a novel case of TAFRO syndrome with disseminated intravascular coagulation, neurologic changes, and non-ischemic cardiomyopathy. Through this clinical vignette, we hope to raise awareness of TAFRO syndrome and encourage providers to maintain a high level of suspicion for it when evaluating patients who meet the diagnostic criteria.

Pulmonary AL amyloidosis: A review and update on treatment options.

Amyloidosis is a rare disease that involves the extracellular deposition of abnormally folded proteins, precipitating organ dysfunction. Pulmonary amyloidosis is frequently characterized by the AL amyloid subtype and can be localized or associated with systemic involvement, presenting in a nodular, diffuse alveolar-septal, or tracheobronchial pattern. Presentation of disease can vary from clinically silent to severe. Pulmonary amyloidosis is typically first suspected on CT scan of the chest. Diagnostic workup requires tissue biopsy and identification by immunohistochemical staining. Systemic treatment has evolved over recent years to include the combination of daratumumab, bortezomib, cyclophosphamide, and dexamethasone (dara-VCD) as first-line therapy, with the goal of quickly attaining complete hematologic response. Through clinical vignettes, we review pulmonary AL amyloidosis and discuss current treatment options.