Anaplastic Transformation of Differentiated Thyroid Carcinoma.

OBJECTIVES: Anaplastic thyroid carcinoma (ATC) is a rare but highly aggressive form of thyroid cancer. Increasingly, patients with ATC present with concurrent foci of well-differentiated thyroid carcinoma (WDTC); however, the significance of these pathologic findings remains unclear. The objective of this study is to determine whether the presence of WDTC within anaplastic tumors is a prognosticator of survival. METHODS: A retrospective cohort study of all cases of biopsy-proven ATC managed at a tertiary care academic medical center from 2002 to 2020 was performed. Mean age at diagnosis, median survival time, and locations of distant metastases were assessed. The impact of clinical markers such as presence of differentiation, demographic variables, and oncologic information on overall survival was also determined via univariate and multivariate analysis. RESULTS: Forty-five patients were included in this study. The mean age at diagnosis was 69.1 years. Median survival time was 6.1 months after diagnosis. The most common location of distant metastases was the lung (40%). The presence of limited areas of WDTC in patients with predominantly anaplastic thyroid tumors was not significantly associated with improved outcomes (p = 0.509). Smaller tumor size and use of chemotherapy in ATC patients were significantly associated with prolonged survival (p = 0.026 and 0.010, respectively). CONCLUSIONS: Clinical outcomes for ATC remain poor. The presence of foci of differentiation within anaplastic thyroid tumors does not appear to improve overall survival-the anaplastic component evidently drives outcomes. Further studies into novel therapies are needed to improve survival in ATC. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:437-442, 2023.

Hearing outcomes in children with Congenital Cytomegalovirus: A multi-center, single-enterprise experience.

BACKGROUND: Cytomegalovirus (CMV) is the most common cause of non-genetic sensorineural hearing loss (SNHL) in the United States; yet screening for congenital CMV (cCMV) remains controversial. CMV related SNHL can be present at birth, or develop in a delayed manner, and it is a consistent feature in children with either symptomatic or asymptomatic disease. A retrospective chart review was performed to determine the characteristics of patients diagnosed with cCMV and SNHL. METHODS: The electronic database warehouse of the Nemours Children's Health System (NCHS) was queried from 01/01/2004 to 10/05/2019. ICD 9 (771.1) and ICD 10 (B25.9, P35.1) diagnostic codes were used to identify patients throughout the system with a diagnosis of cCMV infection. Patient demographics including gender, race/ethnicity, age of diagnosis, results of newborn hearing screening (NBHS), detection and progression of hearing loss, presence of antiviral therapy, and frequency of monitoring were collected, and descriptive statistics performed. RESULTS: Of the 170 patients confirmed to have cCMV, 153 (90%) were symptomatic and 17 (10%) were asymptomatic. CNS involvement (63.5%), radiographic evidence of disease present (69.4%), and SNHL (50.6%) were the most common manifestations of the disease. Of these 170 patients, 83 (48.8%) were determined to have SNHL eligible for evaluation. For these patients with SNHL, the average time of hearing monitoring was 50.6 months. At the time of initial reported detection 63 of 83 (76%) had bilateral hearing loss and 20 (24%) had unilateral loss. Over the study period 3 (15%) progressed from unilateral to bilateral involvement, and 32 (47%) had a deterioration in hearing, with severe to profound SNHL in at least one ear identified at the last visit in 53 (64%) patients. Newborn hearing testing results were available for 69 (83%) of those with hearing loss and 26 patients passed initial testing. However, of the 26 patients who passed, 22 (85%) eventually developed SNHL by their last visit. Within our cohort, females with cCMV were significantly more likely to have SNHL than males with cCMV (62.3% versus 37.6%; p < 0.01). CONCLUSION: In the absence of targeted or universal cCMV screening, the majority of children identified with this condition present symptomatically. Approximately one half of children with symptomatic cCMV failed NBHS at birth while at least 25% develop SNHL later in life. Children with cCMV are at high risk of delayed onset loss and such children, particularly females, should be monitored closely.

The Regulation of Inflammation by Innate and Adaptive Lymphocytes.

Inflammation plays an essential role in the control of pathogens and in shaping the ensuing adaptive immune responses. Traditionally, innate immunity has been described as a rapid response triggered through generic and nonspecific means that by definition lacks the ability to remember. Recently, it has become clear that some innate immune cells are epigenetically reprogrammed or "imprinted" by past experiences. These "trained" innate immune cells display altered inflammatory responses upon subsequent pathogen encounter. Remembrance of past pathogen encounters has classically been attributed to cohorts of antigen-specific memory T and B cells following the resolution of infection. During recall responses, memory T and B cells quickly respond by proliferating, producing effector cytokines, and performing various effector functions. An often-overlooked effector function of memory CD4 and CD8 T cells is the promotion of an inflammatory milieu at the initial site of infection that mirrors the primary encounter. This memory-conditioned inflammatory response, in conjunction with other secondary effector T cell functions, results in better control and more rapid resolution of both infection and the associated tissue pathology. Recent advancements in our understanding of inflammatory triggers, imprinting of the innate immune responses, and the role of T cell memory in regulating inflammation are discussed.