27 research outputs found

    Concordance of Cross-Sectional Imaging and Adrenal Venous Sampling Results for Patients with Surgically Treated Primary Hyperaldosteronism​

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    Background Adrenal venous sampling (AVS) is used to distinguish unilateral from bilateral aldosterone hypersecretion as a cause of primary hyperaldosteronism (PHA). This distinction is critical because unilateral disease is treated, and often cured, by adrenalectomy, whereas bilateral hypersecretion should be managed medically. Methods We performed a retrospective cohort review of adult patients undergoing index adrenalectomy for PHA at the University of Nebraska Medical Center from July of 2013 to June of 2022. Clinical and pathologic variables were assessed including patient age at surgery, sex, race or ethnicity, body mass index, systolic and diastolic blood pressure, number and type of antihypertensive medications pre- and post-operatively, potassium level and supplementation, PAC, PRA, ARR, imaging findings, adrenal venous sampling results and concordance of imaging findings with AVS and surgical outcomes. Statistical analysis was performed with Mann Whitney U and chi-squared Fisher’s exact using STATA version 17. Results In our cohort, 21 patients were identified who underwent adrenalectomy for primary hyperaldosteronism. Of these, 2 patients did not have any imaging findings and 19 were image localized. For patients with image localization AVS was concordant in 9, discordant in 4, and nondiagnostic in 6. For both patients without image localization the AVS was lateralizing. The overall discordance between imaging results and AVS was 40%. The only significant difference between patients with concordant and discordant results was the aldosterone level with concordant patients having a mean of 58ng/dL compared with discordant patients 23ng/dL (p = 0.0022). There was a significant reduction in antihypertensive medications in the entire cohort from a mean of 3.2 medications to 1.2 medications (p \u3c 0.001). Conclusions and Future Directions In this cohort, 40% of patients with selective AVS had discordant imaging and AVS results. Preoperative plasma aldosterone concentration was positively associated with concordance, with higher PAC more likely to have imaging and AVS concordance. Overall, hypertension was significantly improved following adrenalectomy for PHA with a median decrease of 2 antihypertensives. Our results support the recommendation to perform AVS on all candidates for adrenalectomy for PHA. Further study is warranted to identify factors associated with discordance.https://digitalcommons.unmc.edu/surp2022/1008/thumbnail.jp

    Relaxin and the Immune Landscape of Benign and Malignant Thyroid Disease

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    Thyroid cancer is the most common endocrine cancer, and its incidence has significantly increased over the last 40 years. Recent studies have suggested relaxin—a peptide hormone secreted by the ovaries during pregnancy with anti-fibrotic actions in chronic inflammation—as a potential marker of thyroid cancer occurrence and progression. However, it is unknown how relaxin behaves in benign versus malignant thyroid tissue. We hypothesized that relaxin levels would be decreased in benign and normal cancer-adjacent thyroid tissue relative to malignant tissue and increased in patients with lymphocytic thyroiditis, an autoimmune disorder involving chronic inflammation of the thyroid. Using the Integrated Cancer Repository for Cancer Research, benign, malignant, and normal cancer-adjacent thyroid tissue and accompanying clinical information were obtained. Tissue microarrays of each group were created, and immunofluorescence was performed to evaluate levels of relaxin. Our results indicated that relaxin is increased in malignant tissue relative to both normal cancer-adjacent and benign thyroid tissue, but there is no significant difference between benign and normal cancer-adjacent thyroid tissue. There is also an association between increased relaxin levels and lymphocytic thyroiditis. However, there is no association between significant differences in relaxin and other clinical factors like hypothyroidism and hyperthyroidism.https://digitalcommons.unmc.edu/surp2022/1016/thumbnail.jp

    Circulating immunophenotypes are potentially prognostic in follicular cell-derived thyroid cancer

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    BackgroundExploring the immune interface of follicular cell-derived thyroid cancer has prognostic and therapeutic potential. The available literature is lacking for comprehensive immunophenotyping in relation to clinical outcomes. In this study, we identify circulating immunophenotypes associated with thyroid cancer prognosis.MethodsWe conducted a pilot observational study of adults with follicular cell-derived thyroid cancer who underwent surgery at our tertiary care referral center and had consented for flow cytometry on peripheral blood collected at the time of thyroidectomy.ResultsOf the 32 included subjects, 20 (62%) had well differentiated, 5 (16%) had poorly differentiated, and 7 (22%) had anaplastic thyroid cancer. The most frequent AJCC stage was 4 (59%) and the ATA risk of recurrence category was high (56%). Patients with AJCC stage 3/4 demonstrated fewer circulating mononuclear cells (CD45+), more monocytes (CD14+), fewer total lymphocytes (CD14-), fewer T cells (CD3+), fewer CD4+ T cells, fewer gamma-delta T cells, fewer natural killer (NK) T-like cells, more myeloid-derived suppressor cells (MDSCs; Lin-CD33+HLADR-), and more effector memory T cells but similar CD8+ T cells compared to stage1/2. Immunophenotype comparisons by ATA risk stratification and course of thyroid cancer were comparable to those observed for stage, except for significant differences in memory T cell subtypes. The median follow-up was 58 months.ConclusionsAggressive follicular cell-derived thyroid cancer either at presentation or during follow-up is associated with down-regulation of the T cell populations specifically CD4+ T cells, gamma-delta T cells, and NK T-like cells but up-regulation of MDSCs and altered memory T cells. These immunophenotypes are potential prognostic biomarkers supporting future investigation for developing targeted immunotherapies against advanced thyroid cancer

    Should BRAFV600E be Incorporated into Treatment Recommendations for Thyroid Cancer?

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    Around 90% of all well-differentiated thyroid cancers are papillary thyroid carcinomas (PTC). PTCs have a recurrence rate of around 20% and a low mortality rate of around 5%. Within PTCs, around 60% of them have the BRAFV600E mutation. Currently, there is a debate on whether BRAFV600E is an independent predictor of tumor aggressiveness and recurrence. This study looks at whether BRAFV600E is an independent predictor of recurrence and outcomes in PTC. Tissue microarrays (TMA) were made from well-differentiated thyroid tumors and stained for the BRAFV600E mutation. BRAFV600E expression was calculated using an H-score: the staining intensity (0-3) multiplied by the amount of tumor that stained positive. A univariate analysis showed that BRAFV600E was significantly associated with age (p=0.0259), gender (p=0.019), extrathyroidal extension (p=0.049), positive margins (p=0.033), lymph node ratio (p=0.0106), N stage (p=0.015), AJCC 8 stage (p=0.0042), ATA risk category (p=0.018), and time to recurrence (p=0.0487). A multivariable analysis found that only extrathyroidal extension was an independent predictor of recurrence. Overall, BRAFV600E was not an independent predictor of recurrence in this cohort. Current treatment plans based on risk of recurrence appear to be appropriate, and it is not recommended that BRAFV600E be included as an independent variable.https://digitalcommons.unmc.edu/surp2021/1058/thumbnail.jp

    Comparative Immunohistochemical Analysis of EHD1 Expression in Adjacent, Metastatic, and Normal Thyroid Tissue

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    The discovery of prognostic biomarkers plays a crucial role in enhancing the treatment and care of individuals with differentiated thyroid cancer (DTC) who are at risk of disease progression. A significant breakthrough came with earlier research, which revealed higher levels of the EHD1 protein in papillary DTC when compared to the surrounding healthy tissue. This exciting finding served as the driving force behind the initiation of a more extensive investigation aimed at validating EHD1 as a potential biomarker and exploring its connection with clinical outcomes. By unraveling the potential implications of EHD1 in DTC cases, this study holds the promise of advancing our understanding and approach to managing this type of cancer effectively.https://digitalcommons.unmc.edu/surp2023/1001/thumbnail.jp

    Investigating Immune Profiles in Differentiated Thyroid Cancer by Multiplex Immunofluorescence

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    BACKGROUND: As the most common endocrine malignancy in the United States (U.S.), differentiated thyroid cancer (DTC) accounts for 3.8% of all cancers in the U.S., with roughly 10% of cases progressing to distant metastatic DTC, which is associated with a poor five year survival outcome despite conventional management, including surgery and radioactive iodine ablation. Recently, novel immunotherapies have garnered attention as a viable therapeutic resource for patients with advanced DTC. However, the response to therapy has been variable and unpredictable, which may be associated with an immune suppressive circulating phenotype. Nonetheless, the intra-tumoral immune infiltrate remains to be elucidated, demonstrating a critical need to address the gap in understanding in order to better prognosticate the disease. OBJECTIVE: To identify and compare tumor-infiltrating immune markers with those present in the adjacent normal thyroid tissue, and collate these immune infiltrates with tumor characteristics. METHODS: Twenty-nine adult tissue samples containing tumor and stromal regions were collected from patients with DTC. The samples were analyzed using multiplex immunofluorescence (MxIF) with antibodies against cell-surface molecules CD56, PD-1, PD-L1, FOXP3, CD3, CD8, CD4, CD45, CD68, CD163, INOS, HLA-DR, CD33, and CD19. 17 of the specimens were analyzed using HALO and a positive threshold was assigned based on review by a trained researcher. RESULTS: In evaluating the immune profiles, important differences in the immune infiltrates between different stages of the cancer were observed. Generally, PD-1 and PD-L1 were highly expressed within the tumor, despite variability in lymphocyte infiltration, indicating the importance of PD-1 and PD-L1 as potential predictive biomarkers for the aggressiveness of thyroid cancer. Tumor from patients with distant metastases demonstrated higher T cell infiltration, T regulatory cells, macrophages and PD-L1 positive cells as compared to localized tumor. CONCLUSION: Immune profiling demonstrated significant differences between tumor and adjacent healthy regions, particularly in terms of PD-1 and PD-L1 expression and lymphocyte infiltration, indicating that higher intratumor infiltration of T regulatory cells, macrophages and PD-1/PD-L1 positive cells may be associated with advanced thyroid cancer. Therefore, the data demonstrates the efficacy of MxIF in gathering valuable information regarding the tumor microenvironment, which will have major implications in guiding the selection of patients for immunotherapy.https://digitalcommons.unmc.edu/surp2021/1042/thumbnail.jp

    Search for electroweak production of single top quarks in ppˉp\bar{p} collisions.

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    We present a search for electroweak production of single top quarks in the electron+jets and muon+jets decay channels. The measurements use ~90 pb^-1 of data from Run 1 of the Fermilab Tevatron collider, collected at 1.8 TeV with the DZero detector between 1992 and 1995. We use events that include a tagging muon, implying the presence of a b jet, to set an upper limit at the 95% confidence level on the cross section for the s-channel process ppbar->tb+X of 39 pb. The upper limit for the t-channel process ppbar->tqb+X is 58 pb. (arXiv

    Search for first-generation scalar and vector leptoquarks

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    We describe a search for the pair production of first-generation scalar and vector leptoquarks in the eejj and enujj channels by the D0 Collaboration. The data are from the 1992--1996 ppbar run at sqrt{s} = 1.8 TeV at the Fermilab Tevatron collider. We find no evidence for leptoquark production; in addition, no kinematically interesting events are observed using relaxed selection criteria. The results from the eejj and enujj channels are combined with those from a previous D0 analysis of the nunujj channel to obtain 95% confidence level (C.L.) upper limits on the leptoquark pair-production cross section as a function of mass and of beta, the branching fraction to a charged lepton. These limits are compared to next-to-leading-order theory to set 95% C.L. lower limits on the mass of a first-generation scalar leptoquark of 225, 204, and 79 GeV/c^2 for beta=1, 1/2, and 0, respectively. For vector leptoquarks with gauge (Yang-Mills) couplings, 95% C.L. lower limits of 345, 337, and 206 GeV/c^2 are set on the mass for beta=1, 1/2, and 0, respectively. Mass limits for vector leptoquarks are also set for anomalous vector couplings

    Frequency and Predictors of Self-Reported Hypoglycemia in Insulin-Treated Diabetes

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    AIMS: Hypoglycemia is a limiting factor for achieving stringent glycemic control in diabetes. This study analyzes the frequency and predictors of hypoglycemia in insulin-treated diabetes in an ambulatory setting. METHODS: A retrospective chart review was performed to study self-monitored blood glucose (SMBG) data for 3 months prior to a patient\u27s HbA1c test. RESULTS: Hypoglycemia occurred more frequently in type 1 than in type 2 diabetes; however, 19% of type 2 diabetes patients did experience at least one episode of severe hypoglycemia. For type 1 diabetes, hypoglycemia had a positive association with glycemic variability and duration of diabetes and a negative association with HbA1c and lowest blood glucose (BG). For type 2 diabetes, a positive association was noted with glycemic variability and a negative association with age and lowest BG. CONCLUSIONS: Delineating factors predisposing to hypoglycemia in type 2 diabetes is difficult. Lower HbA1c is a potential predictor of hypoglycemia in type 1 but not in type 2 diabetes. Longer duration of diabetes for type 1 and younger age for type 2 are associated with more hypoglycemia. Glycemic variability portends increased risk for hypoglycemia and should be a focus of further research

    Identification of Immune Biomarkers in Thyroid Cancer

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    Thyroid cancer is the most common endocrine malignancy, estimated to be the second most common cancer in women by 2030. The frequency of differentiated thyroid cancer (DTC), the most common subtype of thyroid cancer, is higher in patients with autoimmune thyroid disease but the influence of the immune milieu on thyroid carcinogenesis remains unclear. To address this gap in knowledge, we performed clinical and translational experiments to identify immune biomarkers for the occurrence and prognosis of DTC. Multiparameter flow cytometry of peripheral blood from 32 adults found advanced thyroid cancer either at presentation or during the disease-course to be associated with circulating suppressor immune phenotypes characterized by less CD4+ T cells, gamma-delta T cells and NK T-like cells but more myeloid-derived suppressor cells (MDSCs); and altered memory T cells. Building on these results, our investigation of the tumor immune microenvironment in 17 paired samples of DTC via multiplex immunofluorescence revealed more immune checkpoint programmed death ligand 1 (PD-L1) and a trend for more CD163 (M2 macrophage marker) intratumorally compared to adjacent thyroid tissue. Exploratory analysis found a trend for more PD-L1, CD68 (macrophage marker), and FOXP3 (T regulatory cell marker) in distant metastatic DTC cases suggesting their potential role as prognostic biomarkers. The key findings of immune alteration in circulation and tumor microenvironment of DTC served as the basis for our investigation of proteins relaxin (RLN2), which plays a role in M2 macrophage polarization and extracellular matrix remodeling, and EPS15 homology domain 1 (EHD1), which plays role in T-cell signaling. We identified these in surgical thyroid tissue from 181 adults with non-metastatic DTC compared to thyroid tissue from 185 adults with benign thyroid disease. The expression of these proteins, along with CD68 (macrophage marker) and CD163 (M2 macrophage marker), was significantly higher in cancerous compared to benign thyroid tissue, demonstrating their role as biomarkers in the occurrence and potentially prognosis of DTC. To conclude, the findings in this thesis demonstrate the role of the immune milieu in thyroid carcinogenesis. These findings are expected to be a significant contribution to the field of carcinogenesis by improving prognostication and identifying targets for novel therapies, thus heralding a new era in personalized patient care
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