Citations

Abstract Interventional pulmonology (IP) fellowship training has undergone increased popularity and growth. The Accreditation Council of Graduate Medical Education recently recognized IP medicine as a new subspecialty, which leads to new challenges and opportunities for a young subspecialty. Although the specialty-specific requirements are in progress, IP fellowship programs must plan ahead for the known common program requirements and anticipated accreditation process. The educational leadership in IP must identify and execute solutions to sustain continued excellence. This includes transitioning to a new regulatory environment with issues of funding new fellowships, keeping up to date with training/assessment of new procedures, and shaping the future through recruitment of talent to lead the young subspecialty.

Abstract Organs that face external environments, such as skin and gut, are lined by epithelia, which have two functions – to provide a semi-permeable barrier and to sense stimuli. The intestinal lumen is filled with diverse chemical and physical stimuli. Intestinal epithelial cells sense these stimuli and signal to enteric neurons which coordinate a range of physiologic processes required for normal digestive tract function. Yet, the neuro-epithelial connections between intestinal epithelial cells and enteric neurons remain poorly resolved, which leaves us with limited mechanistic understanding of their function. We describe the development of a two-compartment microfluidic device for modeling neuro-epithelial interactions, and apply it to form the gut’s neuro-epithelial connections. The device contains epithelial and neuronal compartments connected by microgrooves. The epithelial compartment was designed for cell seeding via injection and confinement of intestinal epithelial cells derived from human intestinal organoids. We demonstrated that organoids planarized effectively and retained epithelial phenotype for over a week. In the second chamber we dissociated and cultured intestinal myenteric neurons including intrinsic primary afferent neurons (IPANs) from transgenic mice that expressed the fluorescent protein tdTomato. IPANs extended projections into microgrooves, surrounded and frequently made contacts with epithelial cells. The density and directionality of neuronal projections were enhanced by the presence of epithelial cells in the adjacent compartment. Our microfluidic device represents a platform for dissecting structure and function of neuro-epithelial connections in the gut and other organs (skin, lung, bladder, and others) in health and disease.

ObjectiveAnalyze age‐related changes in histologic features and biochemical properties of human auricular cartilage and two subsites of nasal cartilages (quadrangular cartilage and dorsal septal articulation with upper lateral cartilages).Study DesignProspective cross‐sectional study of nasal and auricular cartilages from seventy‐three (73) live donors.MethodsAuricular cartilage (AC), quadrangular cartilage (QC), and dorsal septal cartilage articulation (DSA) with the upper lateral cartilage (ULCs) were collected intraoperatively. Histochemical staining was used: Safranin O for glycosaminoglycans (GAGs), Verhoeff's for elastin, and Masson's trichrome for collagen. ImageJ2 software was used to calculate cell count and percent stained for each cartilage type. R studio “ggplot” package was used to visualize age versus cell count or percent stained.ResultsParticipant ages ranged from 20 to 77 years, average 46.5 years. There was a significant decline in GAGs with age for the DSA subsite, (n = 64, p < 0.001). Significant increase in collagen content with age was observed for DSA subsite (n = 66, p < 0.001) and the QC subsite (n = 64, p < 0.05). There was a statistically insignificant decline in elastin with age (n = 41, p = 0.309) for AC. Cell count declined with age at all cartilage subsites.ConclusionOur findings confirm that there were age‐related decreases in cartilage glycosaminoglycan content, and chondrocyte cell count in both auricular and nasal cartilages. We have also confirmed that collagen content increases with age for both auricular and nasal cartilage. The histologic findings while not statistically significant in all comparisons, provides additional evidence that there is some loss of structural integrity and flexibility in nasal and auricular cartilage with aging.Level of EvidenceNA Laryngoscope, 134:1220–1226, 2024

Importance Colorectal cancers (CRCs) with deficient DNA mismatch repair (dMMR) account for 15% of all CRCs. Deficient MMR is a predictive biomarker associated with responsiveness to immune checkpoint inhibitors (ICIs) in solid tumors, including CRC. The remarkable effectiveness of ICIs in metastatic CRC has led to their evaluation in the neoadjuvant and adjuvant treatment of localized disease. Observations Multiple prospective phase 2 studies in limited numbers of patients with localized dMMR CRC demonstrate high complete clinical and pathological response rates (60%-100%) to neoadjuvant ICIs, with low rates of grade 3 or higher ICI-related toxic effects. Given the median follow-up of 12 to 25 months in these studies, longer-term monitoring is needed to determine the durability of response and to ensure that oncologic outcomes are not compromised in patients undergoing nonoperative management. Neoadjuvant ICI therapy is especially attractive for patients with rectal cancer given the significant morbidity that accompanies pelvic irradiation and total mesorectal excision. Ongoing and planned prospective phase 2 trials will provide further data on important issues, including optimal neoadjuvant treatment duration, ICI monotherapy vs combination, and the need for adjuvant ICI therapy. Conclusions and Relevance While this review found that early results of neoadjuvant immunotherapy for localized dMMR CRC show high rates of major and complete pathological response, longer-term follow-up data are needed to ensure that oncologic outcomes are not compromised and are ideally improved. Neoadjuvant ICI therapy in localized dMMR CRC represents a potential paradigm shift with implications for organ preservation.