Assessing Adequacy: A Meta-Analysis of Rapid Onsite Evaluation of Thyroid Nodules.

INTRODUCTION: Fine-needle aspiration (FNA) is the standard form of preoperative evaluation of thyroid nodule cytological status. A significant number FNAs are classified as inadequate for interpretation, requiring a repeat FNA which is potentially avoidable, costly, and delays treatment. To address these concerns and maximize first-time FNA adequacy, rapid onsite evaluation (ROSE) of FNA specimens was introduced. Our study aims to determine the impact of ROSE on FNA adequacy. METHODS: PubMed, Embase, and Web of Science were searched for primary articles assessing the adequacy of ROSE in thyroid nodules. RESULTS: A total of 17 studies were included for a total of 24,649 thyroid nodes. Thirteen thousand two hundred fifteen (53.6%) thyroid nodules were assessed utilizing ROSE and 11,434 (46.4%) were not. Pooled adequacy increased significantly from 76% without ROSE to 92% with rose (P = 0.001). Use of ROSE increased the odds of adequate FNA by 22% (risk ratio (RR) = 1.22, 95% confidence interval (CI) = 1.12-1.32). At institutions with less than 85% effective diagnostic adequacy without ROSE, the risk for diagnostic adequacy increased by 28% with ROSE implementation (RR = 1.28, 95% CI = 1.20-1.37). In contrast, in studies reported from institutions with an effective diagnostic rate greater than 85% without the use of ROSE, the diagnostic adequacy only increased by 5% with ROSE implementation (RR = 1.05, 95% CI = 1.03-1.06). CONCLUSIONS: The use of ROSE during first-time FNA of thyroid nodules can significantly improve adequacy, especially at institutions with baseline high inadequacy rates. Implementation of ROSE can reduce repeat FNAs and its associated consequences.

Survival Outcomes of Medullary Thyroid Cancer With and Without Amyloid Deposition.

OBJECTIVE: Amyloid deposition within tumor stroma is a distinctive histologic feature of medullary thyroid cancer (MTC). However, its prognostic significance remains uncertain. We aimed to elucidate the impact of amyloid status on survival outcomes in a large cohort. METHODS: The Surveillance, Epidemiology, and End Results registry was queried to identify patients diagnosed with MTC from 2000 to 2019. Patients with amyloid-positive (International Classification of Diseases for Oncology, third edition code 8345/3) and amyloid negative (International Classification of Diseases for Oncology, third edition code 8510/3) tumors were analyzed. Overall and disease-specific survival were compared between matched cohorts using Kaplan-Meier and Cox proportional hazards analyses. RESULTS: Of the 2526 MTC patients, 511 of which were amyloid-positive and 2015 that were amyloid negative. Amyloid-positive patients displayed lower T stage (T3/4: 28% vs 85%, P < .001) and less extrathyroidal extension (11.3% vs 81.6%, P < .001). No difference in distant metastasis rate was observed between groups (14.5% vs 14.4%, P = .98). However, amyloid-positive patients showed a tendency for distal lymph node metastasis (1.2% vs 0.3%, P = .020). On univariate analysis, amyloid-positive status showed comparable overall survival times (mean 172.2 vs 177.8 months, P = .17), but a trend toward worse cancer-specific survival (hazard ratios [HR] = 1.31, 95% CI = 0.99-1.71, P = .051). After adjusting for covariates, amyloid deposition did not independently predict overall (HR = 1.15, 95% CI = 0.91-1.47, P = .25) or cancer-specific survival (HR = 1.30, 95% CI = 0.96-1.77, P = .09). Initiating therapy later than 1 month following diagnosis was associated with worse overall survival (HR = 1.25, 95% CI = 1.02-1.54, P = .029). CONCLUSIONS: The presence of amyloid in MTC paradoxically associates with lower T stage yet exhibits a trend toward worse cancer-specific mortality. Amyloid deposition alone does not independently influence prognosis. Delayed treatment adversely impacted overall survival.

Cardiovascular Health by Graves' Disease Management Modality - Surgery Versus Radioactive Iodine Versus Antithyroid Medications: A Network Meta-Analysis.

INTRODUCTION: Graves' disease is an autoimmune disorder of the thyroid gland associated with the overproduction of thyroid hormones. Excess secretion of thyroid hormones leads to cardiovascular consequences. Treatment options include antithyroid medications (ATM), radioactive iodine (RAI) ablation, and total thyroidectomy. We examined the cardiovascular outcomes following Graves' disease management modality. METHODS: A systematic search was performed up to September 22nd, 2021, using PubMed, EMBASE, and Web of Science databases. We conducted a network meta-analysis analyzing cardiovascular outcomes of interest, including congestive heart failure (CHF), arrhythmia, atrial fibrillation (AF), and hypertension. RESULTS: Three studies were included in this analysis totaling 6700 patients with Graves' disease, of which 74% were female. The mean age was 44.34 y. When compared to pretreatment, management options lowered the risk of maintaining arrhythmia 81% with surgery (relative risk [RR] = 0.19; 95% confidence interval [CI] = 0.12 to 0.31), 67% with ATM (RR = 0.33; 95% CI = 0.23 to 0.49), and 50% with RAI (RR = 0.50; 95% CI = 0.13 to 1.95). Risk of maintaining CHF was reduced 80% with surgery (RR = 0.20; 95% CI = 0.08 to 0.49), 41% with ATM (RR = 0.59; 95%CI = 0.52 to 0.67), and only 7% with RAI (RR = 0.93; 95%CI = 0.68 to 1.26). Treatment-ranking analysis found all parameters, including CHF, arrhythmia, AF, and hypertension, to be in favor of surgical treatment over medical treatment and RAI ablation. CONCLUSIONS: This is the first network meta-analysis analyzing the cardiovascular outcomes in Graves' disease patients by treatment option. Our study demonstrated that surgery is superior to RAI and medical treatment.

Recommend with caution: A meta-analysis investigating papillary thyroid carcinoma tumor progression under active surveillance.

BACKGROUND: Papillary thyroid carcinoma (PTC) is an indolent disease with favorable outcomes. The non-surgical treatment approach known as active surveillance (AS) has been introduced as an alternative treatment instead of the traditional thyroidectomy. However, 10-15 % of PTC tend to progress. We sought to determine factors predicting the progression of PTC under AS. METHODS: A systematic search was performed in January 2022 using PubMed, Embase, Google Scholar, Web of Science, and ScienceDirect. PRISMA guidelines were used by multiple reviewers to extract study characteristics (author name, publication date, journal name, country, institution, and study design), as well as main outcomes and measures. A combination of utilization of thyroid replacement therapy, baseline tumor size and volume, follow-up tumor size and volume, and the presence of lymph node metastasis and its distribution, as well as surveillance duration, were the main measures of this study. RESULTS: Nine studies with 4166 patients were included, of which 354 showed tumor progression during AS (15 %; 95%CI = 7 % - 23 %). The average follow-up period was 41.58 months. The mean tumor maximum diameter was 8.54 mm (95%CI = 7.04-10.03). Tumor progression was most commonly secondary to an increase in volume by ≥50 % (75 %; 95%CI = 68 % - 80 %), then increase in diameter by ≥3 mm (41 %; 95%CI = 13 % - 76 %), and finally the development of lymph node metastasis (13 %; 95%CI = 9 % - 19 %). Approximately only 2 % of all patients thus developed new lymph node metastasis. Patient age, sex, and tumor size were not associated with higher risks of tumor progression. 12 % of AS patients eventually underwent surgery, though only 40 % (95%CI = 27 % - 53 %) of these patients displayed tumor progression. CONCLUSIONS: Our meta-analysis determined a tumor progression rate of 15 % in patients who underwent AS management, 13 % of which (2 % of all patients) developed lymph node metastasis. We found no protective or risk factors for tumor progression, and that almost half of all patients who underwent delayed surgery did so for reasons other than tumor progression. While not biopsying small (<1 cm) or very low suspicious nodules is already recommended, AS may be an appropriate treatment option in patients appropriately counseled, considering the low risk of advanced tumor progression but also the considerable patient population who fail to adhere to treatment. Alternatively, in aim of preventing overtreatment in patients who would rather take proactive measures against their low-risk carcinoma, minimally-invasive ablation techniques may be an attractive option.

A Predictive Model of Adaptive Resistance to BRAF/MEK Inhibitors in Melanoma.

The adaptive acquisition of resistance to BRAF and MEK inhibitor-based therapy is a common feature of melanoma cells and contributes to poor patient treatment outcomes. Leveraging insights from a proteomic study and publicly available transcriptomic data, we evaluated the predictive capacity of a gene panel corresponding to proteins differentially abundant between treatment-sensitive and treatment-resistant cell lines, deciphering predictors of treatment resistance and potential resistance mechanisms to BRAF/MEK inhibitor therapy in patient biopsy samples. From our analysis, a 13-gene signature panel, in both test and validation datasets, could identify treatment-resistant or progressed melanoma cases with an accuracy and sensitivity of over 70%. The dysregulation of HMOX1, ICAM, MMP2, and SPARC defined a BRAF/MEK treatment-resistant landscape, with resistant cases showing a >2-fold risk of expression of these genes. Furthermore, we utilized a combination of functional enrichment- and gene expression-derived scores to model and identify pathways, such as HMOX1-mediated mitochondrial stress response, as potential key drivers of the emergence of a BRAF/MEK inhibitor-resistant state in melanoma cells. Overall, our results highlight the utility of these genes in predicting treatment outcomes and the underlying mechanisms that can be targeted to reduce the development of resistance to BRAF/MEK targeted therapy.

Efficacy and Safety of Radiofrequency Ablation of Thyroid Nodules: A Multi-institutional Prospective Cohort Study.

BACKGROUND: Radiofrequency ablation (RFA) has been recently adopted into the practice of thyroidology in the United States, although its use as an alternative to traditional thyroid surgery in Asia and Europe came near the turn of the 21st century. In the United States, only a few studies with small sample sizes have been published to date. We examined outcomes of benign thyroid nodules treated with RFA from 2 North American institutions. METHODS: We performed a prospective, multi-institutional cohort study of thyroid nodules treated with RFA between July 2019 and January 2022. Demographics, sonographic characteristics of thyroid nodules, thyroid function profiles, procedural details, complications, and nodule volume measurements at 1, 3, 6, and 12 months follow-up were evaluated. Adjusted multivariate logistic regression analysis was performed to identify sonographic features associated with treatment failure. RESULTS: A total of 233 nodules were included. The median and interquartile range of volume reduction rate (VRR) at 1, 3, 6, and 12 months were 54% [interquartile range (IQR): 36%-73%], 58% (IQR: 37%-80%), 73% (IQR: 51%-90%), and 76% (IQR: 52%-90%), respectively ( P <0.001). Four patients presented with toxic adenomas. All patients were confirmed euthyroid at 3-month postprocedure follow-up. Two patients developed temporary hoarseness of voice, but no hematoma or nodular rupture occurred postprocedure. Elastography was significantly associated with VRR. Compared with soft nodules, stiff nodules were more likely to have a lower VRR (odds ratio: 11.64, 95% confidence interval: 3.81-35.53, P <0.05), and mixed elasticity was also more likely to have a lower VRR (odds ratio: 4.9; 95% confidence interval: 1.62-14.85, P <0.05). CONCLUSIONS: This is the largest multi-institutional North American study examining thyroid nodule treatment response to RFA. RFA is a safe and effective treatment option that allows preservation of thyroid function with minimal risk of procedural complications.

Accuracy of the 'CUT' Score for Assessing Malignancy in Bethesda 3 and 4 Thyroid Nodules in North American Population: A Retrospective Study.

BACKGROUND: The CUT score is a thyroid nodule malignancy risk assessment scoring system intended to guide surgeons in treating Bethesda 3 and 4 thyroid nodules. It is based on clinical (C) and ultrasonographic (U) features and a five-tiered (T) representing cytology. PURPOSE: Our study aimed to assess the utility of the CUT score in predicting thyroid malignancy in the North American population. The main reason for creating this score is to reduce unnecessary surgeries on these challenging thyroid nodules. MATERIALS AND METHODS: A retrospective record review study applied the CUT score to 219 Bethesda 3 and 4 thyroid nodules. A total of 203 Bethesda 3 and 16 Bethesda 4 nodules from patients treated between January 2015 and December 2019 at a single institution were assessed. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the CUT diagnostic test. Binary logistic regression analysis was performed. Iteration of analysis was performed after stratification according to body mass index to assess CUT score accuracy in obese and non-obese patients. RESULTS: Of 219 nodules analyzed, 148 were characterized as benign and 71 as malignant. Prevalence rates of malignancy were 29.6% (n = 60) and 68.8% (n = 11) in Bethesda 3 and 4 nodules, respectively. The mean CU (clinical, ultrasonography) score was 5.35 ± 1.38 in benign nodules versus 4.96 ± 1.5 in malignant nodules (p = 0.08). The area under the curve (AUC = 0.433) for the association of CUT scores with nodule malignancy was not significant (p = 0.13). The CUT score was insignificant as a diagnostic test for nodule malignancy in obese (AUC = 0.45; p = 0.72) and non-obese patients (AUC = 0.39; p = 0.08). CONCLUSION: The CUT score did not correlate with preoperative malignancy risk estimates in Bethesda 3 thyroid nodules and, therefore, may have limited utility as a predictor of malignancy in these thyroid nodules.

What happens to patients undergoing cancer surgery with psychiatric comorbidities?: A nationwide retrospective cohort study.

OBJECTIVE: We aimed to describe the surgical outcomes and readmissions rates in patients with psychological comorbidities who underwent surgical intervention for cancer. BACKGROUND: The Hospital Readmission Reduction Program, a campaign by the Affordable Care Act, penalizes hospitals for greater readmission rates. One prevalent patient risk factor associated with hospital readmission is a comorbid psychiatric condition. Currently, no studies exist identifying psychiatric comorbidities and their effects on patients with cancer undergoing surgical intervention. METHODS: A cross-sectional analysis was performed using the Nationwide Readmissions Database for 2010-2014 and included adult patients undergoing cancer resection operations. Multivariable logistic regression analyses were utilized to assess determinants of surgical outcomes and readmissions. RESULTS: Of 1 016 636 eligible patients, 11.6% had psychiatric comorbidities. Patients with psychiatric disorders had greater risks of mortality (odds ratio [OR] = 1.21, 95% confidence interval [CI] = 1.18-1.25), complications (OR = 1.51, 95%CI = 1.50-1.52), extended length of stay (OR = 1.21, 95%CI = 1.20-1.22), and incurred healthcare expenditure at primary admission (OR = 1.16, 95% CI = 1.15-1.18). Psychiatric comorbidities were associated with an increased likelihood of readmission (OR = 1.13, 95%CI = 1.11-1.15). CONCLUSIONS: Concomitant psychiatric conditions were attributed to poor surgical outcomes and a higher risk of readmissions. Multidisciplinary care within the perioperative setting should be encouraged for patients with psychiatric disorders.

Deciphering excess healthcare burden in head and neck cancer patients with cardiovascular comorbidity.

BACKGROUND: This study aimed to determine the perioperative surgical outcomes for head and neck cancer patients with cardiovascular diseases (CVDs). METHODS: A cross-sectional analysis was performed using data from the Nationwide Readmissions Database between 2010 and 2014. Logistic regression analysis by enter and backward stepwise methods were used. RESULTS: A total of 8346 patients met the inclusion criteria. Patients with concomitant CVD had a higher frequency of complications (57.6%) compared with those without (47.4%) (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.23-1.48, p < 0.001). Patients with CVD comorbidities were prone to experience in-patient mortality at both admission (OR = 2.4, 95% CI = 1.42-4.05) and readmission (OR = 2.55, 95% CI = 1.10-5.87). CVD patients have prolonged hospital admission (OR = 1.14, 95% CI = 1.02-1.27, p = 0.020) and higher cost (OR = 1.28, 95% CI = 1.15-1.43, p < 0.001). Patients with congestive heart failure were prone to 30 days readmission (OR = 1.67, 95% CI = 1.10-2.53, p = 0.019) and 90 days (OR = 1.65, 95% CI = 1.14-2.39, p = 0.010). CONCLUSION: This is the first study identifying factors predicting higher risk of perioperative complications of surgical management of head and neck cancer. Those with CVD had higher risk of adverse events.

Asthma and COVID-19; different entities, same outcome: a meta-analysis of 107,983 patients.

OBJECTIVE: There are varying reports of the prevalence and effect of comorbid asthma in coronavirus disease-2019 (COVID-19) patients. We sought to conduct a meta-analysis comparing asthmatic and non-asthmatic patients to determine the clinical significance of preexisting asthma in COVID-19 patients. DATA SOURCES: Online databases PubMed, ScienceDirect, Web of Science, and Scopus, were searched up to July 15, 2020, for papers comparing asthma versus non-asthma COVID-19 patients. STUDY SELECTION: According to prespecified inclusion criteria, this analysis included eleven retrospective studies with 107,983 COVID-19 patients. Subgroup analysis was performed based on age groups. RESULTS: The mean age of the patients was 59.9 years (95%CI = 51.9-67.9). Across studies, the prevalence of asthma was 11.2% (95%CI: 9.1%-13.3%) among COVID-19 patients who attended the hospitals. Asthma patients were more likely to be younger (SMD = -0.36, 95%CI = -0.61 to -0.10, p = 0.005), and obese (OR = 1.98, 95%CI = 1.54-2.55, p < 0.001), there was no differential risk of hospitalization rate, ICU admission, or development of acute respiratory distress syndrome (ARDS) between asthmatic and non-asthmatic cohorts. However, asthmatic patients had increased risk of endotracheal intubation (RR = 1.27, 95%CI = 1.02-1.58, p = 0.030) especially patients aged <50 years (RR = 6.68, 95%CI = 1.76-11.13, p = 0.009). Despite this result, asthmatic patients had better recovery with a higher liability of being discharged and were less likely to die (RR = 0.80, 95%CI = 0.65-0.97, p = 0.026). CONCLUSION: To our knowledge, our meta-analysis is the largest to shed light on preexisting asthma as a predictor of intubation in COVID-19, especially in young and obese patients. Identifying high-risk groups is crucial for designing more effective intervention plans and optimization of efficient resource allocation.

Excess of cesarean births in pregnant women with COVID-19: A meta-analysis.

BACKGROUND: Studies have suggested that cesarean birth in pregnant women with COVID-19 may decrease maternal adverse events and perinatal transmission. This systematic review aimed to evaluate variations in clinical presentation, laboratory findings, and maternal/neonatal outcomes in COVID-19 patients who delivered vaginally versus via cesarean. METHODS: A comprehensive search following PRISMA guidelines was performed for studies published up to May 23, 2020, using PubMed, Web of Science, Scopus, Embase, Cochrane, Science Direct, and clinicaltrials.gov. Original retrospective and prospective studies, case reports, or case series with sufficient data for estimating the association of COVID-19 with different pregnancy outcomes with no language restriction and published in peer-reviewed journals were included. Pooled mean and arcsine transformation proportions were applied. Next, a two-arm meta-analysis was performed comparing the perinatal outcomes between the study groups. RESULTS: Forty-two studies with a total of 602 pregnant women with COVID-19 were included. The mean age was 31.8 years. Subgroup analysis showed that Americans had the lowest gestational age (mean = 32.7, 95%CI = 27.0-38.4, P < 0.001) and the highest incidence of maternal ICU admission (95%CI = 0.45%-2.20, P < 0.001) of all nationalities in the study. There was no significant difference in perinatal complications, premature rupture of membrane, placenta previa/accreta, or gestational hypertension/pre-eclampsia between women who delivered vaginally versus by cesarean. Importantly, there were also no significant differences in maternal or neonatal outcomes. CONCLUSION: Vaginal delivery was not associated with worse maternal or neonatal outcomes when compared with cesarean. The decision to pursue a cesarean birth should be based on standard indications, not COVID-19 status.

Thyroidectomy practice in pediatric population: a national perspective.

PURPOSE: To examine presentations and outcomes of pediatric patients underoing thyroidectomy. MATERIALS AND METHODS: A retrospective cross-sectional analysis of the Nationwide Readmissions Database, 2010-2014, was performed. Study population included pediatric (<18 years) inpatients undergoing thyroidectomy. RESULTS: A total of 361 patients were included. Mean age was 13.5 ± 0.2 years, and 79.8% were female. Thyroid diseases included: (i) 19.0% thyroid cancer, (ii) 5.4% Multiple Endocrine Neoplasia type II, (iii) 33.6% toxic nodular disease, and (iv) 42.0% non-toxic benign disease. Total thyroidectomy was performed in 67.7% of the patients, and 3.2% of the patients who had initial lobectomy were readmitted within 3 months for completion thyroidectomy. Postoperative complications were reported in 14.2% of the sample, and hypocalcemia was the most common complication (98.2%). Risk of hypocalcemia was significantly higher in patients who had thyroid cancer (risk = 20.9%, p = 0.011) or toxic thyroid diseases (risk = 19.8%, p = 0.033). Of the study population, 25.6% were managed exclusively in children's hospitals. Management in children's hospitals was not associated with improved outcomes or shorter hospital stay; however, it was associated with a significantly higher cost of health services [US $19,4575.0 ± 195.49 vs. US $13,788.00 ± 238.51, p < 0.001]. CONCLUSIONS: This study reports a national perspective on thyroidectomy in the pediatric population. Most thyroid surgeries performed in the pediatric population are performed for benign conditions. Most pediatric thyroidectomies are performed at low-volume centers. Surgeries performed in children's hospitals are significantly higher in cost without any associated improvement in outcomes or length of hospital stay.

Trampoline Injuries in Children and Adolescents: A Jumping Threat.

OBJECTIVE: As trampoline use grows more popular in the United States, the frequency of injuries continues to climb. We hypothesized that toddlers would be at the highest risk for trampoline injuries requiring hospitalization. METHODS: The National Electronic Injury Surveillance System database was examined for trampoline injuries from 2009 to 2018. Patients were categorized into 3 main age groups: toddlers (<2 years), children (2-12 years), and adolescents (13-18 years). Regression models were used to identify patients at high risk for injury or hospitalization. RESULTS: There was a total of 800,969 meeting inclusion criteria, with 433,827 (54.2%) occurring at their own homes and 86,372 (18.1%) at the sporting venue. Of the total, 36,789 (4.6%) were admitted to a hospital. Fractures (N = 270,884, 34%), strain/sprain injuries (N = 264,990, 33%), followed by skin contusions/abrasions (N = 115,708, 14%) were the most common diagnoses. The most frequent injury sites were lower and upper extremities accounting for 329,219 (41.1%) and 244,032 (30.5%), whereas 175,645 (21.9%) had head and neck injuries. Musculoskeletal injuries (74%) and concussions (2.6%) were more frequent in adolescents than children (67.6% and 1.6%) and toddlers (56.3% and 1.3%). Internal organ and soft tissue injuries were frequent in toddlers. There were no fatalities reported in the injured patients. Multivariate analysis showed adolescents, female sex, extremity injuries, and musculoskeletal injuries were associated with hospitalization. Injury at a sporting venue was not associated with hospitalization. CONCLUSIONS: Adolescents and girls are at increased risk of trampoline injury, warranting hospitalization. Safety standards may help prevent extremity and musculoskeletal injuries in the pediatric population. Finally, use of trampolines at sporting venues does not appear to be particularly dangerous.

The Diagnostic Performance of Ultrasonography in the Evaluation of Extrathyroidal Extension in Papillary Thyroid Carcinoma: A Systematic Review and Meta-Analysis.

Extrathyroidal extension (ETE) in patients with papillary thyroid carcinoma (PTC) is an indication of disease progression and can influence treatment aggressiveness. This meta-analysis assesses the diagnostic accuracy of ultrasonography (US) in detecting ETE. A systematic review and meta-analysis were performed by searching PubMed, Embase, and Cochrane for studies published up to April 2022. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated. The areas under the curve (AUC) for summary receiver operating curves were compared. A total of 11 studies analyzed ETE in 3795 patients with PTC. The sensitivity of ETE detection was 76% (95%CI = 74-78%). The specificity of ETE detection was 51% (95%CI = 49-54%). The DOR of detecting ETE by US was 5.32 (95%CI = 2.54-11.14). The AUC of ETE detection was determined to be 0.6874 ± 0.0841. We report an up-to-date analysis elucidating the diagnostic accuracy of ETE detection by US. Our work suggests the diagnostic accuracy of US in detecting ETE is adequate. Considering the importance of ETE detection on preoperative assessment, ancillary studies such as adjunct imaging studies and genetic testing should be considered.

Radiofrequency Ablation of Indeterminate Thyroid Nodules: The First North American Comparative Analysis.

Thyroid nodules can be classified as benign, malignant, or indeterminate, the latter of which make up 10-30% of nodules. Radiofrequency ablation (RFA) has become an attractive and promising therapy for the treatment of benign thyroid nodules. However, few studies have investigated the safety and efficacy of RFA for the management of indeterminate thyroid nodules. In this study, 178 patients with thyroid nodules diagnosed as benign (Bethesda II) or indeterminate (Bethesda III/IV) by preoperative cytopathological analysis were included. Patients in the benign and indeterminate cohorts had similar thyroid nodule volume reduction rates at 65.60% and 64.20%, respectively (p = 0.68). The two groups had similar nodular regrowth rates, at 11.2% for benign nodules and 9.40% for indeterminate nodules (p = 0.72). A total of three cases of transient dysphonia were reported. RFA of indeterminate thyroid nodules was comparable to that of benign thyroid nodules in all parameters of interest, including volume reduction rate. To our best knowledge, our work is the first North American analysis comparing benign and indeterminate thyroid nodules and suggests RFA to be a promising modality for the management of indeterminate thyroid nodules.

Association of BRAFV600E Mutation with the Aggressive Behavior of Papillary Thyroid Microcarcinoma: A Meta-Analysis of 33 Studies.

An association between the BRAFV600E mutation and the clinicopathological progression of papillary thyroid microcarcinoma (PTMC) has been suggested. We aimed to summarize the relevant literature and determine the predictive value of BRAFV600E mutation in predicting clinical outcomes and risk stratification in patients with PTMC. A systematic search using PubMed, Cochrane, and Embase up to February 2020 was performed. A total of 33 studies met the inclusion criteria, resulting in a pool of 8838 patients, of whom 5043 (57.1%) patients were positive for BRAFV600E mutation. Tumors with positive BRAFV600E mutation had a higher tendency for multifocality (RR = 1.09, 95%CI = 1.03-1.16), extrathyroidal extension (RR = 1.79, 95%CI = 1.37-2.32), and lymph node metastasis (RR = 1.43, 95%CI = 1.19-1.71). Patients with BRAFV600E mutation were at increased risk of disease recurrence (RR = 1.90, 95%CI = 1.43-2.53). PTMC in patients positive for the BRAFV600E mutation is more aggressive than wild-type BRAF PTMC. Since BRAF-mutated PTMC is generally more resistant to radioiodine treatment, patients with BRAFV600E-mutated PTMC may require earlier management, such as a minimally invasive ablative intervention. Conservative management by active surveillance may be suitable for patients with wild-type BRAFV600E PTMC.

Time-varying Reproductive Rates for SARS-CoV-2 and its Implications as a Means of Disease Surveillance on Lockdown Restrictions.

OBJECTIVE: To quantify the time-varying reproductive rates for SARS-CoV-2 and its implication in Louisiana. SUMMARY OF BACKGROUND DATA: Basic reproductive number (R0) and effective reproductive number (Re or Rt) are 2 measures of the ability of an infectious agent to spread in the environment. They differ in that R0 assumes zero immunity in the population, while Re or Rt accounts for change over time. Reproductive number modeling is influenced by several factors, including serial interval, the time between the onset of symptoms in an infector, and a secondary case. Quantification of the ability of a pathogen to spread is essential in guiding policy. METHODS: Here, we construct epidemic curves and calculate daily Rt values for the state of Louisiana and each of its 9 regions. RESULTS: Our results demonstrated variation over both time and geography in calculated R0 and Rt values. Generally, as time has progressed, predicted R0 and Rt values have decreased. In Louisiana, mean Rt was calculated at 3.07 in March and 0.82 by May. A reproductive number less than one is important as it indicates infectious spread will decline with time. The most recent finding of mean Rt = 0.82 is important. It stands in stark contrast to the situation in April when New Orleans, Louisiana, had the highest per capita coronavirus mortality rate in the United States - twice that of New York City and 4 times the rate in Seattle. CONCLUSION: As locations around the world begin to lift restrictions, monitoring of infectious spread will be essential.

Meta-analysis on Serial Intervals and Reproductive Rates for SARS-CoV-2.

OBJECTIVE: The aim of this study was to systematically review and meta-analyze all literature reporting the basic reproductive number (R0), effective reproductive number (Re or Rt), and the serial interval (SI) values of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection. SUMMARY BACKGROUND DATA: To assess the rate at which an infectious disease can spread in a population, the 2 measures, R0 and Re or Rt, are widely used. One of the parameters which influence the calculations is the SI, the period between symptom onset in an infector and an infectee. METHODS: Web of Science, PubMed, Scopus, and Science Direct searching up to May 10, 2020, was performed. A continuous random-effect model was applied using the DerSimonian-Laird (inverse variance) method. Heterogeneity and publication bias were assessed. RESULTS: A total of 39 articles met the eligibility criteria. Our results demonstrated the mean SI was 5.45 days, with the 95% confidence interval (CI) of 4.23 to 6.66. Pooled estimates for reproduction rates was 3.14 (95% CI: 2.69-3.59) for R0 and 3.18 (95% CI: 2.89-3.47) for Rt. Subgroup analysis by geographical region and date of publication revealed variations over both time and geography in calculated R0 and Rt values. As time has progressed, predicted R0 and Rt values had decreased globally. CONCLUSIONS: The study findings indicate that one SARS-CoV-2-infected person is likely to infect 3 persons, supporting that COVID-19 is a highly contagious disease. As an essential objective metrics implied in risk assessment for this emerging pandemic, monitoring R0 and Re is necessary to indicate the effectiveness or failures of mitigation efforts.

Outcomes of Subtotal Parathyroidectomy Versus Total Parathyroidectomy With Autotransplantation for Tertiary Hyperparathyroidism: Multi-institutional Study.

OBJECTIVES: Due to the paucity of data and controversy regarding the preferred surgical approach for managing tertiary HPT, we sought to investigate the outcomes of different surgical approaches in managing this challenging disease. METHODS: We performed a multi-center retrospective study to include patients with tertiary HPT who underwent STPX or total parathyroidectomy with autotransplantation (TPX-A). RESULTS: One hundred five patients had kidney transplant, and 43 were on dialysis. In the kidney transplant group, 61 patients underwent STPX, and 44 for TPX-A. Patients' demographics were not significantly different (48.61 ±â€Š9.31 vs 47.95 ±â€Š12.73 years, P = 0.759. The postoperative follow-up showed that the TPX-A cohort had a higher rate of hypoparathyroidism (N = 20, 45.45%) versus (N = 14, 22.95%) with the STPX cohort (P = 0.013). The cure among the TPX-A cohorts (84.09%) over the STPX cohort (73.77%) (P = 0.153). The long-term follow-up showed that the rate of developing temporary (N = 16, 41.03%) or permanent (N = 8, 20.51%) hypoparathyroidism was significantly higher among patients who underwent TPX-A over the patients who underwent STPX (N = 7, 17.95%), and (N = 4, 10.26%), respectively (P = 0.012). There was no statistical difference between the persistence (N = 3, 7.69%) or the recurrence (N = 2, 5.13%) of the HPT in the TPX-A cohort and the STPX cohort (N = 2, 5.13%). (N = 4, 10.26%), respectively, P = 0.644. CONCLUSIONS: To our knowledge, this is the largest multi-center study that compared different approaches for managing tertiary HPT. Showing that STPX is the better modality in patients diagnosed with tertiary HPT and had kidney transplants avoiding the risk of hypoparathyroidism.

Hidden in plain sight: The effects of BCG vaccination in the COVID-19 pandemic.

To investigate the relationship between Bacille Calmette-Guérin (BCG) vaccination and SARS-CoV-2 by a bioinformatics approach, two datasets for the SARS-CoV-2 infection group and BCG-vaccinated group were downloaded. Differentially Expressed Genes were identified. Gene ontology and pathways were functionally enriched, and networking was constructed in NetworkAnalyst. Lastly, the correlation between post-BCG vaccination and COVID-19 transcriptome signatures was established. A total of 161 DEGs (113 upregulated DEGs and 48 downregulated genes) were identified in the SARS-CoV-2 group. In the pathway enrichment analysis, a cross-reference of upregulated Kyoto Encyclopedia of Genes and Genomes pathways in SARS-CoV-2 with downregulated counterparts in the BCG-vaccinated group, resulted in the intersection of 45 common pathways, accounting for 86.5% of SARS-CoV-2 upregulated pathways. Of these intersecting pathways, a vast majority were immune and inflammatory pathways with top significance in interleukin-17, tumor necrosis factor, NOD-like receptors, and nuclear factor-κB signaling pathways. Given the inverse relationship of the specific differentially expressed gene pathways highlighted in our results, the BCG-vaccine may play a protective role against COVID-19 by mounting a nonspecific immunological response and further investigation of this relationship is warranted.