Molecular Testing for Bethesda III Thyroid Nodules: Trends in Implementation, Cytopathology Call Rates, Surgery Rates, and Malignancy Yield at a Single Institution.

Background: Molecular testing (MT) has become standard practice to more accurately rule out malignancy in indeterminate Bethesda III (BIII) thyroid lesions. We sought to assess the adoption of this technology and its impact on cytology reporting, malignancy yield, and rates of surgery across community and academic sites affiliated with a tertiary medical center. Methods: We performed a retrospective cross-sectional study including all fine-needle aspirations (FNAs) analyzed at our institution from 2017 to 2021. We analyzed trends in MT utilization by platform and by community or academic site. We compared BIII call rates, MT utilization rates, rates of subsequent surgery, and malignancy yield on final pathology before and after MT became readily available using chi-square analysis and linear regression. Results: A total of 8960 FNAs were analyzed at our institution from 2017 to 2021. There was broad adoption of MT across both community and academic sites. There was a significant increase in both the BIII rate and the utilization of MT between the pre- and post-MT periods (p < 0.001 and p < 0.001). There was no significant change in the the malignancy yield on final pathology (57.1% vs. 50.0%, p = 0.347), while the positive predictive value of MT decreased from 85% to 50% (p = 0.008 [confidence interval 9.5-52.5% decrease]). Conclusions: The use of MT increased across the institution over the study period, with the largest increase seen after a dedicated pass for MT was routinely collected. This increased availability of MT may have led to an unintended increase in the rates of BIII lesions, MT utilization, and surgery for benign nodules. Physicians who use MT should be aware of potential consequences of its adoption to appropriately counsel patients.

The impact of social determinants of health on thyroid cancer mortality and time to treatment.

BACKGROUND: Whereas racial disparities in thyroid cancer care are well established, the role of social determinants of health is less clear. We aimed to assess the individual and cumulative impact of social determinants of health on mortality and time to treatment among patients with thyroid cancer. METHODS: We collected social determinants of health data from thyroid cancer patients registered in the National Cancer Database from 2004 to 2017. We created a count variable for patients in the lowest quartile of each social determinant of health (ie, low income, low education, and no insurance). We assessed the association of social determinants of health with mortality and time to treatment and the association between cumulative social determinants of health count and time to treatment using Cox regression. RESULTS: Of the 142,024 patients we identified, patients with longer time to treatment had greater mortality compared to patients treated within 90 days (90-180 days, adjusted hazard ratio 1.21 (95% confidence interval 1.13-1.29, P < .001); >180 days, adjusted hazard ratio 1.57 (95% confidence interval 1.41-1.76, (P < .001). Compared to patients with no adverse social determinants of health, patients with 1, 2, or 3 adverse social determinants of health had a 10%, 12%, and 34%, respectively, higher likelihood of longer time to treatment (1 social determinant of health, hazard ratio 0.90, 95% confidence interval 0.89-0.92, P < .001; 2 social determinants of health, hazard ratio 0.88, 95% confidence interval 0.87-0.90, P < .001; 3 social determinants of health, hazard ratio 0.66, 95% confidence interval 0.62-0.71, P < .001 for all). On subgroup analysis by race, each adverse social determinant of health was associated with an increased likelihood of a longer time to treatment for Black and Hispanic patients (P < .05). CONCLUSION: A greater number of adverse social determinants of health leads to a higher likelihood of a longer time to treatment for patients with thyroid cancer, which, in turn, is associated with an increased risk for mortality.

Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19.

BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans. METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon. RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ2 = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66). CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.

Optimal surgeon-volume threshold for neck dissections in the setting of primary thyroid malignancies.

BACKGROUND: Although the surgeon-volume relationship is well documented for thyroidectomy, less is known about central neck and lateral neck dissections. The aim of this study was to evaluate and determine the surgeon-volume threshold for central neck and lateral neck dissections for thyroid cancer. METHODS: A retrospective analysis of patients with thyroid malignancies who received a central or lateral neck dissection in the New York Statewide Planning and Research Cooperative System was performed (2007-2017). Demographic variables included age, sex, race, and a Charlson Comorbidity Score. Thirty-day complications were identified using International Classification of Diseases (ICD) codes for central neck, lateral neck, and other surgical complications. Optimal surgeon-volume threshold was estimated using a change-point logistic regression. Using the identified threshold, surgeons were then classified to low versus high volume surgeons. Logistic regression analysis was conducted to examine the effect of high-volume status on outcomes. RESULTS: In total, 3,808 patients who underwent neck dissections (3,485 central neck dissections and 977 lateral neck dissections) were analyzed. Surgeon-volume threshold to distinguish high volume surgeons for central neck dissections and lateral neck dissections was 7.0 (95% bootstrap confidence interval 1.3-7.5) and 3.3 (1.2-4.8) neck dissections/year, respectively. For central neck dissection, high volume surgeons were associated with a lower rate of vocal cord paralysis (odds ratio 0.45 [0.24-0.82]), hypocalcemia (0.31 [0.14-0.65]), and all-cause complications (0.42 [0.29-0.59]). For lateral neck dissection, high volume surgeons were associated with a lower odds all-cause complications (0.42 [0.23-0.74]) but not lateral neck specific complications (0.18 [0.01-1.07]). CONCLUSION: A threshold of 7.0 central neck dissections and 3.3 lateral neck dissections for thyroid cancer per year improves outcomes. Guidelines for training and centralization of care can be guided by these results to reduce complications.

Open repair of a plantar artery pseudoaneurysm after Morton's neurectomy.

A 65-year-old woman presented to our institution with 4 months of severe pain on the plantar aspect of her foot. She had chronic foot pain secondary to Morton's neuroma and had recently undergone neurectomy. She was found to have a large pseudoaneurysm on the plantar aspect of her foot. She was taken to the operating room for an open repair from a plantar approach. We obtained the patient's consent to publish this case.

Transient Surface CCR5 Expression by Naive CD8+ T Cells within Inflamed Lymph Nodes Is Dependent on High Endothelial Venule Interaction and Augments Th Cell-Dependent Memory Response.

In inflamed lymph nodes, Ag-specific CD4(+) and CD8(+) T cells encounter Ag-bearing dendritic cells and, together, this complex enhances the release of CCL3 and CCL4, which facilitate additional interaction with naive CD8(+) T cells. Although blocking CCL3 and CCL4 has no effect on primary CD8(+) T cell responses, it dramatically impairs the development of memory CD8(+) T cells upon Ag rechallenge. Despite the absence of detectable surface CCR5 expression on circulating native CD8(+) T cells, these data imply that naive CD8(+) T cells are capable of expressing surface CCR5 prior to cognate Ag-induced TCR signaling in inflamed lymph nodes; however, the molecular mechanisms have not been characterized to date. In this study, we show that CCR5, the receptor for CCL3 and CCL4, can be transiently upregulated on a subset of naive CD8(+) T cells and that this upregulation is dependent on direct contact with the high endothelial venule in inflamed lymph node. Binding of CD62L and CD11a on T cells to their ligands CD34 and CD54 on the high endothelial venule can be enhanced during inflammation. This enhanced binding and subsequent signaling promote the translocation of CCR5 molecules from intracellular vesicles to the surface of the CD8(+) T cell. The upregulation of CCR5 on the surface of the CD8(+) T cells increases the number of contacts with Ag-bearing dendritic cells, which ultimately results in increased CD8(+) T cell response to Ag rechallenge.

Administration of reconstituted polyphenol oil bodies efficiently suppresses dendritic cell inflammatory pathways and acute intestinal inflammation.

Polyphenols are natural compounds capable of interfering with the inflammatory pathways of several in vitro model systems. In this study, we developed a stable and effective strategy to administer polyphenols to treat in vivo models of acute intestinal inflammation. The in vitro suppressive properties of several polyphenols were first tested and compared for dendritic cells (DCs) production of inflammatory cytokines. A combination of the polyphenols, quercetin and piperine, were then encapsulated into reconstituted oil bodies (OBs) in order to increase their stability. Our results showed that administration of low dose reconstituted polyphenol OBs inhibited LPS-mediated inflammatory cytokine secretion, including IL-6, IL-23, and IL-12, while increasing IL-10 and IL-1Rα production. Mice treated with the polyphenol-containing reconstituted OBs (ROBs) were partially protected from dextran sodium sulfate (DSS)-induced colitis and associated weight loss, while mortality and inflammatory scores revealed an overall anti-inflammatory effect that was likely mediated by impaired DC immune responses. Our study indicates that the administration of reconstituted quercetin and piperine-containing OBs may represent an effective and potent anti-inflammatory strategy to treat acute intestinal inflammation.

Quantification of lymph node transit times reveals differences in antigen surveillance strategies of naive CD4+ and CD8+ T cells.

Naïve T cells continually recirculate between blood and secondary lymphoid organs, scanning dendritic cells (DC) for foreign antigen. Despite its importance for understanding how adaptive immune responses are efficiently initiated from rare precursors, a detailed quantitative analysis of this fundamental process has not been reported. Here we measure lymph node (LN) entry, transit, and exit rates for naïve CD4(+) and CD8(+) T cells, then use intravital imaging and mathematical modeling to relate cell-cell interaction dynamics to population behavior. Our studies reveal marked differences between CD4(+) vs. CD8(+) T cells. CD4(+) T cells recirculate more rapidly, homing to LNs more efficiently, traversing LNs twice as quickly, and spending ∼1/3 of their transit time interacting with MHCII on DC. In contrast, adoptively transferred CD8(+) T cells enter and leave the LN more slowly, with a transit time unaffected by the absence of MHCI molecules on host cells. Together, these data reveal an unexpectedly asymmetric role for MHC interactions in controlling CD4(+) vs. CD8(+) T lymphocyte recirculation, as well as distinct contributions of T cell receptor (TCR)-independent factors to the LN transit time, exposing the divergent surveillance strategies used by the two lymphocyte populations in scanning for foreign antigen.