bluuebunny/crossref_metadata_2025_split huggingface dataset:
Managing Thyroid Nodules in Qatar During the COVID19 Pandemic
Authors: Alamer Zaina , Karuppasamy Gowri , Alsaud Arwa , Jaber Tania , Farghaly Hanan , Rohani Zaina Seros , Zirie Mahmoud A , Naem Emad 
Published: May 2021

Abstract
Background: The Coronavirus disease 2019 (COVID-19) pandemic impacted health care systems in all countries, including Qatar. Hamad Medical Corporation (HMC); In compliance with recommendations, suspended all non-urgent procedures, including thyroid fine needle aspiration biopsies (FNAB). Thyroid nodules are second most common cause of referral to HMC endocrine clinic. FNABs are gold standard to differentiate benign from malignant nodules.1- 2
Methods: Our approach includes a teleconsultation to obtain patient’s history and risk factors. Reviewing neck ultrasound (US), obtaining a calcitonin level if indicated, considering comorbidities associated with a high risk of COVID-19 morbidity and mortality.3
Results: We developed a pathway triaging thyroid (FNAB) to:1-Urgent: patients at higher risk of aggressive thyroid malignancy. Benefits of early detection and treatment outweigh the risk of COVID-19 exposure.4 FNAB should not be delayed.2-Semi-urgent: patients at low risk for COVID-19 and high suspicion thyroid nodules, but no evidence that early detection improves survival2, FNAB may be delayed up to 12 months.3-Non-urgent: patients with asymptomatic nodules that have low or intermediate suspicion US pattern.2 Also, includes nodules with ATA high suspicion US pattern in pregnant women and patients at high risk for COVID-19. The risks outweigh the benefits. FNAB should be delayed until outbreak is controlled.4 When urgent FNAB is indicated, safety of patients and medical staff needs to be addressed.5 We recommend testing patient for COVID-19 before FNAB, utilizing US guidance with rapid on-site adequacy evaluation in all cases. Cervical lymph node FNAB with TG washout should be done if indicated. The patient should wear a mask. All medical staff involved should wear personal protective equipment (PPE). The operator should wear N95 mask and face shield. The patient should be informed about cytopathology results via telemedicine.
Conclusion: Triaging thyroid (FNAB) during the COVID-19 pandemic should be based on nodule characteristics and risk of COVID-19 morbidity and mortality. Our group recommends deferring FNAB for asymptomatic patients.4FNAB should not be delayed in selected patients who benefit from early detection and intervention.
Table1: Triage of Thyroid fine needle aspiration biopsies (FNAB). ATA: American thyroid association. US: ultrasound.
Telehealth for Endocrinology: Effect on Utilization in Non-Pandemic Care
Authors: Williams Alexander , Walsh Colin , Griffith Michelle 
Published: May 2021

Abstract
Telehealth (TH) usage increased exponentially with the COVID-19 pandemic, aided by more permissive policies. Prior to the pandemic, policy makers and payers expressed concern that telehealth might lead to over-utilization of services. This contributed to a limited reimbursement environment. To assess evidence for this concern, we studied real-world TH at an academic medical center and hypothesized that TH would not increase utilization. We compared pre-pandemic utilization in a retrospective cohort of adult endocrinology patients with either TH (synchronous audio-visual visits) or conventional visits (CV) between 11/1/2017 - 3/16/2020. We focused on a pre-pandemic cohort to reflect usual practice. TH patients (i.e., 1+ TH visit with endocrinology in the study period) were identified using billing modifiers in EHR-derived data. CV patients were matched for provider and primary diagnosis, then selected from EHR-derived data in a 1:3 ratio. A minority of providers were performing TH visits pre-pandemic. Matching was performed to eliminate confounding from individual practice variation and to assure ability to compare patients with similar diagnoses. The majority of TH encounters in our practice during the study were clinic-to-clinic, with patients at a TH-enabled remote clinic. 75 TH and 225 CV patients were identified. 77% (55) of TH and 72% (163) of CV patients were female. The mean age was 45.2 (SD 12.4) and 49.6 (SD 16.7) years, respectively. Among TH patients, 68% (51) were white and 12% (9) were black with no statistically significant demographic differences between groups. The most common TH primary diagnoses were DM (33 patients) and thyroid disease (33 patients). Other TH diagnoses included pituitary/adrenal conditions, hyperparathyroidism, PCOS, and hypogonadism. TH patients had median follow-up of 21 months (IQR 13-25) and CV patients 18 months (IQR 11-25), p=0.613. TH patients had a range of 1 to 9 TH encounters during this time (median 2, IQR 1-3). Median TH visits per month were 0.20 (IQR 0.11-0.3). Looking at all endocrine encounters, TH patients had a median of 0.24 (IQR 0.015-0.36) encounters per month. CV patients had median of 0.20 encounters per month (IQR 0.11-0.37). Total encounters per month did not vary significantly between groups (p=0.0512, Wilcoxon rank-sum test). Patients with primary thyroid diagnoses had similar frequencies of TSH testing with TH median 4 tests (IQR 2-7); CV median 3 tests (IQR 1-5), p=0.057. A1c testing frequency was similar in patients with primary diagnosis of DM. TH patients had median 2 tests (IQR 1-3.5); CV median 3 (IQR 1-5), p=0.8012. In conclusion, TH was not associated with higher utilization of visits or lab testing in a small study of a pre-pandemic telehealth program. Coupled with larger scale and replicative studies, these findings might inform policy making and support continuation of telehealth in the post-pandemic environment.
Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome
Authors: Subbu Karthik , Tariq Zunera , Erickson Dana Z , Bancos Irina , Donegan Diane 
Published: May 2021

Abstract
Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE.
Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE.
Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred &gt;3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P &lt; 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS.
Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.
Monitoring Thyroid Function Tests in Patients With Type 1 Diabetes Mellitus: Adherence to Recommended Guidelines and Comparison of Practice Patterns in a Health Care System
Authors: Cui Ling , Walsh Madeleine , Potluri Sai Deepika , Suleman Nawar , Schroeder Pamela 
Published: May 2021

Abstract
Approximately 1.7 million people in the U.S. have type 1 diabetes mellitus. Autoimmune thyroid disease occurs in 17 to 30% of patients with type 1 diabetes. The American Diabetes Association recommends that thyroid function be assessed at diagnosis of type 1 diabetes and repeated every 1 to 2 years thereafter or sooner if clinically indicated. With Centricity, our former electronic medical records (EMR) system, an EMR aid automatically imported key diabetes metrics including the TSH test. Our new EMR system, MedConnect, does not have an EMR aid that imports these metrics. We hypothesized that the screening rate for thyroid dysfunction in type 1 diabetic patients would be higher with the previous EMR system than with the new EMR system. We also hypothesized that the screening rate in patients followed by an endocrinologist would be higher than in those followed by a primary care physician.
Methods: We compared practice patterns with Centricity (from June 1, 2013, to May 30, 2016) versus MedConnect (from January 1, 2017, to December 31, 2019) in both primary care and endocrinology clinics. A total of 502 patients (271 Centricity, 231 MedConnect) were identified by chart review with age ≥18 years and ICD 9/10 codes for type 1 diabetes mellitus in outpatient clinics in our multicenter system.
Results: Baseline TSH was done in 253 of 271 (93.4%) Centricity patients and in 181 of 231 (78.4%) MedConnect patients. The odds of baseline TSH with Centricity was 3.88 times higher compared to MedConnect (OR = 3.88, 95% CI=2.19,6.88). Of the 214 patients with normal baseline TSH, 135 (63.1%) had repeat TSH done in 1-2 years; and of the 136 MedConnect patients with normal baseline TSH, 86 (63.2%) had repeat TSH done in 1-2 years. Of 434 patients with baseline TSH, 81 (18.6%) had abnormal TSH. Of these patients, 67 (82.7%) had hypothyroidism, 1 (1.2%) had hyperthyroidism, 8 (9.8%) had subclinical hypothyroidism, and 5 (6.1%) had subclinical hyperthyroidism. Of the total 502 patients, 380 (75.7%) were followed by an endocrinologist and 122 (24.3%) were followed by a primary care provider. Among patients followed by an endocrinologist, 348 (91.6%) had a baseline TSH result. Only 86 of 122 (70.5 %) patients followed by a primary care physician had a baseline TSH. Endocrinologists had 4.6 times higher odds of TSH screening at baseline compared with primary care physicians (p &lt;0.0001).
Conclusion: Thyroid function was not assessed at baseline in all patients with type 1 diabetes mellitus and was not followed at the recommended intervals per the guidelines. Higher screening rates were seen with an EMR aid. Endocrinologists screened significantly more patients than primary care physicians. Education of providers regarding the guidelines is needed, and addition of an EMR aid may help to improve detecting thyroid dysfunction in patients with type 1 diabetes mellitus.
Aggressive Thyroid Cancer is Associated With Suppressor Circulating Immunophenotype
Authors: Kotwal Anupam , Bornschlegl Svetlana , Gustafson Michael , Dietz Allan , Delivanis Danae Anastasia , Ryder Mabel M 
Published: May 2021

Abstract
Introduction: The influence of the immune system on follicular cell-derived thyroid cancer behavior has been suggested by various studies but this information has not been comprehensively translated into a prediction for thyroid cancer prognosis. We aimed to identify circulating immune cell profiles associated with thyroid cancer prognosis. This information would be a significant advance in the field of thyroid cancer management. Methods: We performed a single-center prospective cohort study of 32 follicular-cell derived thyroid cancer patients enrolled at the time of initial or subsequent surgery. We performed peripheral blood multi-parameter flow cytometry and collected relevant clinicopathologic, biochemical and radiologic data. We classified patients based on the AJCC TNM cancer stage, American Thyroid Association (ATA) initial risk of recurrence, and status of disease during follow-up. Results: On initial immunophenotyping, patients with aggressive/advanced thyroid cancer (ATA high risk vs. intermediate/low risk; AJCC stage 3/4 vs. 1/2; recurrence or distant metastases vs. no evidence of disease during follow-up) demonstrated increased circulating monocytes and granulocytes but decreased all lymphocytes, T cells (specifically CD4+ and gamma delta) and natural killer (NK) T-like cells. Further immunophenotyping revealed that aggressive/advanced thyroid cancer had increased circulating CD4+CD45+RO effector memory but decreased CD4+CD45+RA central memory T cells and increased regulatory T cells. Stage 3/4 thyroid cancer patients additionally had increased circulating CD33+HLADR- myeloid-derived suppressor cells (MDSCs) as compared to stage1/2. Conclusions: Aggressive thyroid cancer at presentation (AJCC stage, ATA risk category) or during follow-up (distant metastases) is characterized by a circulating immunophenotype comprising of increased immune suppressor cells (regulatory T cells, MDSCs, effector memory T cells) but decreased immune activator cells (CD4+ T cells, gamma delta T cells, NK T-like cells, central memory T cells) as compared to less aggressive thyroid cancer. This circulating immunophenotype may serve as a biomarker for cancer prognosis and guide the selection and development of novel immunotherapies for advanced thyroid cancer.
Low Protein Expression of ATRX and ZNRF3 as a Novel Prognostic Marker of Adult Adrenocortical Carcinoma
Authors: Brondani Vânia Balderrama , Lacombe Amanda Meneses Ferreira , Mariani Beatriz Marinho , Montenegro Luciana Ribeiro , Cauduro Ibere Soares , Neto João Evangelista Bezerra , Mendonca Berenice Bilharinho , Almeida Madson Q , Zerbini Maria Claudia Nogueira , Villares Fragoso Maria Candida Barisson 
Published: May 2021

Abstract
Adrenocortical carcinoma (ACC) is a rare malignant neoplasia that is usually associated with a dismal prognosis. ACC overall survival (OS) depends on the particular biology of the tumor. Pan-genomic studies have demonstrated the involvement of ATRX and ZNRF3 genes in adrenocortical tumorigenesis. Aim: To evaluate ATRX and ZNRF3 protein expression in a large cohort of adults with ACC followed at a single tertiary referral center to establish the prognostic value of these genes. Methods: Two pathologists analyzed immunohistochemically-stained slides for ATRX and ZNRF3 (blinded assessment) proteins using tissue microarrays comprising tissue samples from 82 ACC (kappa 0.854; P&lt;0.001). Cohort: female 76.8%; median age 38.2 (15.3–85.4) years; 67.5% of patients presented with hypercortisolism; ENSAT stage 1, 11.12%; 2, 44.44%; 3 and 4: (44.44%). The median follow-up time was 39.58 (1.4–406.8) months; 39 patients died during this period. Low protein expression was defined as follows: ATRX, when &lt; 25% of tumor cells were immunoreacted; ZNRF3, when a score &lt; 3 (extension + intensity) was established. Results: Low ATRX protein expression was positively associated with the age at diagnosis (P&lt; 0.001), and it was negatively correlated with tumor size (P=0.020) and with Weiss score (P=0.033). Low ZNRF3 protein expression correlated negatively with tumor weight (P=0.026), with tumor size (P= 0.005), and with Weiss score (P=0.002). Regarding OS, the low protein expression of ATRX and ZNRF3 was associated with a decrease of OS (P=0.045 and P=0.012, respectively). The Cox model for ATRX protein expression showed a HR of 0.521 (95% CI 0.273–0.997; P=0.049); for ZNRF3 expression, HR = 0.441 (95% CI 0.229–0.852; P=0.015). The combined protein expression of both genes was also associated with a decrease in OS in this cohort (P=0.02). The high ATRX and ZNRF3 protein expressions were positively associated with optimistic recurrence-free survival (P=0.027, P=0.005, respectively). Conclusion: The knowledge of tumor biology is an important step to deliver personalized medicine, affording the opportunity to design better clinical approaches and targeted therapies. This study brought pan-genomic studies closer to clinical practice with an easily accessible tool for stratifying patients with ACC. We demonstrated that low levels of protein expression of ATRX and ZNRF3 are negative prognostic markers of ACC.
Circulating Tumour Cells and MicroRNA in Thyroid Cancer - a Systematic Review
Authors: Bappayya Shaneel , Clydesdale Hamish , Tsao Simon 
Published: May 2021

Abstract
Background: Thyroid cancer (TC) is the most common endocrine malignancy worldwide. Currently available circulating biomarkers such as thyroglobulin and calcitonin present severe limitations to the diagnosis and management of often difficult-to-diagnose lesions. There is increasing interest in the utility of circulating tumour cells (CTCs) and microRNAs to diagnose and optimise the management of patients with TC.
Methods: In this study, we undertake a systematic review to gain a better understanding of the utility of CTCs and microRNAs in the diagnosis and management of patients with TC. A systematic review of the literature was performed by searching electronic bibliographic databases MEDLINE, EMBASE, SCOPUS and Web of Science. Studies which measured CTCs or microRNA levels in peripheral blood from TC patients were included. Review articles, conference abstracts, and foreign language papers were excluded.
Results: There were 238 records screened for inclusion. Full texts of 47 articles were reviewed and included for qualitative analysis.
CTCs demonstrated value in disease monitoring by distinguishing between disease recurrence and remission in patients with papillary thyroid cancer (PTC) and differentiated thyroid cancer (DTC). Higher CTC counts were associated with poorer progression free survival. This is consistent with CTC studies in other cancers such as breast and colorectal.
A total of 31 microRNA biomarker candidates were investigated in studies reviewed. Circulating miR-222, miR-221 and miR-146b were most commonly increased in patients with PTC compared to benign nodules and healthy controls, and were associated with poorer prognostic factors including extrathyroidal invasion and metastatic lymph nodes. Circulating miR-222-3p and miR-17-5p demonstrated discriminatory power between medullary thyroid cancer (MTC) and benign nodules and healthy controls.
Conclusion: CTCs demonstrate a promising avenue for disease monitoring and detection of local and distant recurrence in patients with DTC. Several microRNA candidates demonstrate value in diagnosis of PTC and MTC. There is a large degree of heterogeneity in studies assessing the
utility of microRNA biomarker candidates. Further studies are warranted to ascertain the value of circulating microRNA in disease monitoring and prognosis.
Comparison of Diagnostic Performance in Thyroid Nodules on US: Deep Convolutional Neural Network Models vs Endocrinologists With Various Experiences
Authors: Kang Sunyoung , Lee Eunjung , Kim Yoo Hyung , Kwon Seul Ki , Jung Kyong Yeun , Park Young Joo , Park Do Joon , Cho Sun Wook , Kwak Jin Young 
Published: May 2021

Abstract
Objectives: To diagnose thyroid cancer, ultrasonography is a primary tool, but diagnostic accuracy varies according to the proficiency of clinicians. The aim of this study was to compare diagnostic performance between deep convolutional neural network (CNN) models and endocrinologist with various experiences. Methods: Patients who underwent fine needle aspiration at endocrinology department in Seoul National University Hospital, between April 2014 and June 2019, were reviewed. Among them, thyroid nodules which were pathologically confirmed by surgery and maximal diameter greater than 1cm were included. Ultrasonography images of thyroid nodules were reviewed by 13 endocrinologists with various experiences: 0 month (E0, n=8), 1 year (E1, n=2), and &gt;5 years (E5, n=3). Results: Of total 451 thyroid nodules, 66.5% was diagnosed as cancer and 83.7% was papillary thyroid cancer (PTC). Sensitivity and specificity of CNN were 85.3% and 63.6%, respectively, and its area under the curve (AUC) was 0.855. Compared to CNN, mean accuracy of E0 group was significantly lower (Accuracy 68.7% vs 78.0%, P &lt;0.001), and after CNN-assistance, that of E0 was significantly improved (68.7% [before] vs 73.93% [after], P = 0.008). E1 and E5 groups showed similar diagnostic performance to CNN, and CNN-assistance did not change it. Next, subgroup analysis was performed according to the histologic subtypes. AUC of CNN in PTC (0.925) was much higher than that of other cancers including FTC (0.529). Interestingly, CNN-assistance significantly improved diagnostic performance for PTC not only in beginners (E0), but also a subset of experienced endocrinologist (E1 and E5). Conclusions: CNN has good diagnostic performance in the diagnosis of PTC. Endocrinologist with lower experience in ultrasonography, CNN-assistance is beneficial for improving diagnostic performance especially in PTC.
Evaluation of Thrombotic Risk in Thyroid Cancer
Authors: Akamnonu Chukwuka , Cohen David A 
Published: May 2021

Abstract
Introduction: Current guidelines from the International Society of Thrombosis and Hemostasis recommend limited screenings for deep vein thrombosis (DVT) or pulmonary embolism (PE) with no identifiable precipitating factor (termed unprovoked). There is paucity of data with regards to thyroid cancer screening in the setting of an unprovoked VTE. Studies from Europe have shown an association between VTE and thyroid cancer; however, these studies do not account for differences in iodine availability, thus the need for studies in the United States. Understanding the risk of thyroid cancer as a provocative factor in developing a deep venous thrombosis (DVT) or pulmonary embolism (PE) may be able to facilitate case detection of disease and prevent future morbidity and mortality from thyroid cancer and/or VTE. Objectives: The primary objective of this study is to understand the risk of developing VTE in the setting of thyroid cancer. Methods: In this retrospective chart review study, we reviewed electronic medical records of patients with a history of DVT or PE between ages 18-99, presenting to all outpatient clinics at a single academic medical center in New Jersey between October 1, 2015, and Dec 31, 2018. We screened for coexistent cancer history among this group, and from this sample we further isolated cases of thyroid cancer. Results: 345 patients were found to have a history of VTE. 187 were female (54%) and 113 (29%) had a history of malignancy. The most common cancers were breast (19%), colorectal (9%), leukemia (9%), prostate (8%), and lymphoma (8%). Thyroid cancer accounted for 2% of all discovered cases. Conclusion: In this retrospective analysis, 2% of all patients with VTE and cancer carried a diagnosis of thyroid cancer. Although this suggests a relatively low risk, given the medical burden of a venous thromboembolism and the comparable proportion of thyroid cancer in all new cancer cases, thyroid cancer should be considered a provoking factor in unprovoked VTE.