Malignancy risk of hyperfunctioning thyroid nodules compared with non-toxic nodules: systematic review and a meta-analysis

Abstract Background Hyperfunctioning or hot nodules are thought to be rarely malignant. As such, current guidelines recommend that hot nodules be excluded from further malignancy risk stratification. The objective of this systematic review and meta-analysis is to compare the malignancy risk in hot nodules and non-toxic nodules in observational studies. Methods Ovid MEDLINE Daily and Ovid MEDLINE, EMBASE, Scopus, and Web of Science databases were searched. Observational studies which met all of the following were included: (1) use thyroid scintigraphy for nodule assessment, (2) inclusion of both hyperfunctioning and non-functioning nodules based on scintigraphy, (3) available postoperative histopathologic nodule results, (4) published up to November 12, 2020 in either English or French. The following data was extracted: malignancy outcomes include malignancy rate, mapping of the carcinoma within the hot nodule, inclusion of microcarcinomas, and presence of gene mutations. Results Among the seven included studies, overall incidence of malignancy in all hot thyroid nodules ranged from 5 to 100% in comparison with non-toxic nodules, 3.8–46%. Odds of malignancy were also compared between hot and non-toxic thyroid nodules, separated into solitary nodules, multiple nodules and combination of the two. Pooled odds ratio (OR) of solitary thyroid nodules revealed a single hot nodule OR of 0.38 (95% confidence interval (CI) 0.25, 0.59), toxic multinodular goiter OR of 0.51 (95% CI 0.34, 0.75), and a combined hot nodule OR of 0.45 (95% CI 0.31, 0.65). The odds of malignancy are reduced by 55% in hot nodules; however, the incidence was not zero. Conclusions Odds of malignancy of hot nodules is reduced compared with non-toxic nodules; however, the incidence of malignancy reported in hot nodules was higher than expected. These findings highlight the need for further studies into the malignancy risk of hot nodules

The impact of depression and antidepressant usage on primary biliary cholangitis clinical outcomes.

Depression is prevalent in primary biliary cholangitis (PBC) patients. Our aims were to examine the effects of depression and antidepressants on hepatic outcomes of PBC patients.We used the UK Health Improvement Network database to identify PBC patients between 1974 and 2007. Our primary outcome was one of three clinical events: decompensated cirrhosis, liver transplantation and death. We assessed depression and each class of antidepressant medication in adjusted multivariate Cox proportional hazards models to identify independent predictors of outcomes. In a sensitivity analysis, the study population was restricted to PBC patients using ursodeoxycholic acid (UDCA).We identified 1,177 PBC patients during our study period. In our cohort, 86 patients (7.3%) had a depression diagnosis prior to PBC diagnosis, while 79 patients (6.7%) had a depression diagnosis after PBC diagnosis. Ten-year incidence of mortality, decompensated cirrhosis, and liver transplantation were 13.4%, 6.6%, and 2.0%, respectively. In our adjusted models, depression status was not a predictor of poor outcomes. After studying all classes of antidepressants, using the atypical antidepressant mirtazapine after PBC diagnosis was significantly protective (Adjusted HR 0.23: 95% CI 0.07-0.72) against poor liver outcomes (decompensation, liver transplant, mortality), which remained statistically significant in patients using UCDA (HR 0.21: 95% CI 0.05-0.83).In our study, depression was not associated with poor clinical outcomes. However, using the antidepressant mirtazapine was associated with decreased mortality, decompensated cirrhosis and liver transplantation in PBC patients. These findings support further assessment of mirtazapine as a potential treatment for PBC patients

Flow diagram of identified PBC patients in The Health Improvement Network between April 1974 and May 2007.

<p>Flow diagram of identified PBC patients in The Health Improvement Network between April 1974 and May 2007.</p

Kaplan-meier curves indicating 10-year decompensation, liver transplant and mortality free survival among PBC patients according to mirtazapine usage.

<p>Kaplan-meier curves indicating 10-year decompensation, liver transplant and mortality free survival among PBC patients according to mirtazapine usage.</p

Patients characteristics according to depression status.

<p>Patients characteristics according to depression status.</p

The Association of Smoking and Surgery in Inflammatory Bowel Disease is Modified by Age at Diagnosis

OBJECTIVES: We assessed the association of smoking at diagnosis of inflammatory bowel disease (IBD) on the need for an intestinal resection. METHODS: The Health Improvement Network was used to identify an inception cohort of Crohn's disease (n=1519) and ulcerative colitis (n=3600) patients from 1999–2009. Poisson regression explored temporal trends for the proportion of newly diagnosed IBD patients who never smoked before their diagnosis and the risk of surgery within 3 years of diagnosis. Cox proportional hazard models assessed the association between smoking and surgery, and effect modification was explored for age at diagnosis. RESULTS: The rate of never smokers increased by 3% per year for newly diagnosed Crohn's disease patients (incidence rate ratio (IRR) 1.03; 95% confidence interval (CI): 1.02–1.05), but not for ulcerative colitis. The rate of surgery decreased among Crohn's disease patients aged 17–40 years (IRR 0.96; 95% CI: 0.93–0.98), but not for ulcerative colitis. Smoking at diagnosis increased the risk of surgery for Crohn's disease patients diagnosed after the age of 40 (hazard ratio (HR) 2.99; 95% CI: 1.52–5.92), but not for those diagnosed before age 40. Ulcerative colitis patients diagnosed between the ages of 17 and 40 years and who quit smoking before their diagnosis were more likely to undergo a colectomy (ex-smoker vs. never smoker: HR 1.66; 95% CI: 1.04–2.66). The age-specific findings were consistent across sensitivity analyses for Crohn's disease, but not ulcerative colitis. CONCLUSIONS: In this study, the association of smoking and surgical resection was dependent on the age at diagnosis of IBD