High Thyrotropin Levels and Risk of Mortality in the Elderly With Subclinical Hypothyroidism: A Systematic Review and Meta-analysis

ObjectiveThis study aims to determine whether elevated endogenous thyrotropin levels contribute to an increased risk of adverse outcomes, such as all-cause mortality in older adults with subclinical hypothyroidism.MethodsEight electronic databases were searched for relevant articles from inception until March 23, 2022. Cohort studies assessing the association between thyrotropin levels and the risk of mortality among older adults aged ≥60 years with subclinical hypothyroidism were eligible. The outcomes of interest were either all-cause or cardiovascular-related mortality. Two independent researchers assessed the eligibility of the studies and collected data through a previously defined data extraction form. The Newcastle-Ottawa Scale was used to evaluate the quality of evidence, and multivariate-adjusted hazard ratios (HRs) (95% Cl) were collected as the necessary risk estimate for synthesis. Random-effects models were applied for meta-analysis.ResultsOverall, 13 studies involving 44 514 participants were included in this meta-analysis. There were no significant differences in the risk of all-cause mortality (pooled HR: 1.18 [95% Cl: 0.95, 1.45], I² = 94%) and cardiovascular-related mortality (pooled HR: 1.08 [95% Cl: 0.94, 1.23], I² = 0%) between euthyroid older adults and older adults with subclinical hypothyroidism. The results remained the same when only older adults with thyrotropin ≥10 mIU/L were assessed (pooled HR for all-cause mortality and cardiovascular-related mortality, respectively: 1.53 [95% Cl: 0.81, 2.88], I² = 22%, 1.35 [95% Cl: 0.63, 2.86], I² = 43%).ConclusionHigh thyrotropin levels are not associated with increased risk for all-cause mortality as well as cardiovascular-related mortality in older adults aged ≥60 years with subclinical hypothyroidism, suggesting an unnecessity in initialing treatment.     

A Meta-analysis on Associated Risk of Mortality in Nonalcoholic Fatty Liver Disease

ObjectiveNonalcoholic fatty liver disease (NAFLD) affects much of the worldwide population and poses a significant burden to the global healthcare. The rising numbers of individuals with NAFLD and instances of mortality point toward the importance of understanding the association causes of mortality in NAFLD. This meta-analysis aimed to seek the associations of NAFLD with all-cause, cardiovascular disease (CVD)-related, liver-related, and cancer-related mortality.MethodsMEDLINE and Embase were searched for articles relating to causes of mortality between NAFLD and non-NAFLD. The DerSimonian and Laird random-effects model was used to analyze adjusted hazard ratios (HR), and a sensitivity analysis was conducted to reduce heterogeneity through a graphical display of study heterogeneity.ResultsFifteen studies involving 10 286 490 patients were included. Individuals with NAFLD exhibited an increased risk of all-cause mortality (HR, 1.32; 95% CI, 1.09-1.59; P < .01; I² = 96.00%), CVD-related mortality (HR, 1.22; 95% CI, 1.06-1.41; P < .01; I² = 81.00%), and cancer-related mortality (HR, 1.67; 95% CI, 1.15-2.41; P < .01; I² = 95.00%). However, no significant association was found between liver-related mortality and NAFLD (HR, 3.58; 95% CI, 0.69-18.46; P =.13; I² = 96.00%). The sensitivity analysis conducted with graphic display of heterogeneity and only population-based studies found similar results.ConclusionNAFLD was associated with an increased risk of all-cause, CVD-related, and cancer-related mortality but not liver-related mortality. The finding is likely because of low fibrosis prevalence in the community. However, the significant burden in other causes of mortality beyond the liver points to a need for multidisciplinary efforts to reduce the mortality risks.     

Positive Thyroid Peroxidase Antibody and Thyroglobulin Antibody are Associated With Better Clinicopathologic Features of Papillary Thyroid Cancer

ObjectiveTo compare the thyroid autoantibody status of patients with papillary thyroid cancer (PTC) and benign nodular goiter as well as possible associations between thyroid autoantibodies and clinicopathologic features of PTC.MethodsA total of 3934 participants who underwent thyroidectomy were enrolled in this retrospective study. Patients were divided into PTC and benign nodule groups according to pathological diagnosis. Based on the preoperative serum antibody results, PTC patients were divided into thyroid peroxidase antibody (TPOAb)-positive, thyroglobulin antibody (TgAb)-positive, dual TPOAb- and TgAb-positive, or antibody-negative groups.ResultsOf the 3934 enrolled patients, 2926 (74.4%) were diagnosed with PTC. Multivariate regression analyses suggested that high thyroid-stimulating hormone levels (adjusted odds ratio [OR] = 1.732, 95% CI [1.485-2.021], P < .001), positive TgAb (adjusted OR = 1.768, 95% CI [1.436-2.178], P < .001), and positive TPOAb (adjusted OR = 1.452, 95% CI [1.148-1.836], P = .002) were independent risk factors for predicting malignancy of thyroid nodules. Multinomial multiple logistic regression analyses indicated that positive TPOAb alone was an independent predictor of less central lymph node metastasis in PTC patients (adjusted OR = 0.643, 95% CI [0.448-0.923], P = .017), whereas positive TgAb alone was significantly associated with less extrathyroidal extension (adjusted OR = 0.778, 95% CI [0.622-0.974], P = .028). PTC patients with dual-positive TPOAb and TgAb displayed a decreased incidence of extrathyroidal extension (adjusted OR = 0.767, 95% CI [0.623-0.944], P = .012) and central lymph node metastasis (adjusted OR = 0.784, 95% CI [0.624-0.986], P = .037).ConclusionAlthough preoperative positive TPOAb and TgAb are independent predictive markers for PTC, they are also associated with better clinicopathologic features of PTC.     

Effects of Thyroid Dysfunction and the Thyroid-Stimulating Hormone Levels on the Risk of Atrial Fibrillation: A Systematic Review and Dose-Response Meta-Analysis from Cohort Studies

ObjectiveTo explore the relationship between thyroid dysfunction, thyroid-stimulating hormone (TSH) levels, and risks of atrial fibrillation (AF) in studies and conduct a dose-response meta-analysis on the correlation between the TSH levels and risk of AF.MethodsThirteen studies from 5 databases with 649 293 subjects (mean age, 65.1 years) were included. The dose-response meta-analysis was conducted by comparing the risk ratios (RRs) and 95% confidence intervals (CIs) for incident AF associated with different levels of TSH (vs TSH level of 0 mU/L) across studies. Data were collected until October 25, 2021.ResultsSubclinical hyperthyroidism, subclinical hypothyroidism, and clinical hyperthyroidism were associated with an increased risk of AF (RR, 1.70; 95% CI, 1.11-2.62; RR, 1.23; 95% CI, 1.05-1.44; and RR, 2.35; 95% CI, 1.07-5.16, respectively), whereas clinical hypothyroidism was not associated with the significantly increased risk of AF (RR, 1.20; 95% CI, 0.72-1.99). A nonlinear relationship was observed in 2 models (crude model, P_nonlinear < .001; adjusted model, P_nonlinear = .0391) between the TSH levels and risks of AF.ConclusionsOur study indicated that subclinical hyperthyroidism, subclinical hypothyroidism, clinical hyperthyroidism were associated with the risk of AF, and the results for the TSH levels and risk of AF were mixed, which showed a U-shaped relationship.     

Factors Predicting Long-term Estimated Glomerular Filtration Rate Decrease,a Reliable Indicator of Renal Function After Adrenalectomy in Primary Aldosteronism

ObjectiveThe long-term decrease in estimated glomerular filtration rate (eGFR) in patients with primary aldosteronism (PA) after adrenalectomy may be influenced by multiple preoperative factors. The present study aimed to provide a systematic review and meta-analysis of these factors.MethodsA systematic literature search was conducted to determine eligible observational studies on the possible association between preoperative factors and postoperative long-term eGFR decrease in patients with PA using PubMed, Web of Science, Embase, and Cochrane Library databases.ResultsA total of 8 relevant studies with 1159 patients were included. Old age (odds ratio [OR] = 1.05, 95% CI: 1.02-1.09, P = .001), high systolic blood pressure (OR = 1.05, 95% CI: 1.01-1.09, P = .01), baseline hypokalemia (OR = 0.08, 95% CI: 0.02-0.30, P < .001), and low eGFR (OR = 0.92, 95% CI: 0.87-0.97, P = .001) presented a strong association with long-term eGFR decrease after adrenalectomy.ConclusionWe provide evidence that old age, high systolic blood pressure, baseline hypokalemia, and low eGFR are associated with an increased risk of postoperative long-term eGFR decrease in patients with PA postoperatively. More attention should be given to the above factors for the timely prevention and management of renal impairment.     

Predictors of Mortality in Hypercalcemia of Advanced Chronic Liver Disease

ObjectiveHypercalcemia is sometimes observed in patients with cirrhosis, but very little is known about the epidemiology in patients with hypercalcemia of chronic liver disease (HCLD) or how its presence may modulate the overall mortality risk. We assessed the associations between the clinical and laboratory characteristics of patients with HCLD with 90-day mortality.MethodsA systematic search of the medical records at our institution over a 10-year period was performed to retrospectively identify subjects with HCLD during inpatient admission. Univariate and multivariable regression analyses were performed to detect the risk factors for all-cause 90-day mortality.ResultsThirty-eight subjects with HCLD were identified using stringent inclusion and exclusion criteria to exclude individuals with other secondary causes of hypercalcemia. A total of 35 subjects had 90-day vital status available, which revealed 40% mortality. The model for end-stage liver disease sodium score and duration of inpatient hypercalcemia were positively associated with mortality with respective odds ratios of 1.23 (95% CI, 1.06-3.23) and 1.24 (95% CI, 1.04-1.49) in a univariate regression model and 1.30 (95% CI, 1.04-1.62) and 1.33 (95% CI, 1.04-1.71) in a multivariable regression model. The admission and peak serum calcium levels were not associated with mortality. Only 6 subjects received bisphosphonates or calcitonin during their admission, limiting our ability to assess the impact of treatment on outcomes.ConclusionIn patients admitted to the hospital with HCLD, the duration of hypercalcemia was positively associated with 90-day mortality, providing a potential interventional target to reduce mortality in this high-risk population. Studies to validate the utility of treating hypercalcemia are required.     

Characteristics and Risk Factors of Pulmonary Hypertension in Patients With Hyperthyroidism

ObjectiveThis study aimed to comprehensively assess the characteristics and risk factors of hyperthyroidism with pulmonary hypertension (PH).MethodsThis was a retrospective cross-sectional analysis of 315 consecutive patients with hyperthyroidism admitted to the endocrinology department of Tongji Hospital from February 2016 to December 2017. PH was defined as a pulmonary arterial systolic pressure above 35 mm Hg measured by echocardiography.ResultsAmong the 315 patients, 208 were females, the median age was 42 (30-51) years, and the median disease duration was 12 (3-48) months. Thirty-five percent (111/315) of patients were identified with PH. Patients with hyperthyroidism and PH showed significantly higher serum concentrations of free thyroxine (FT4), free triiodothyronine, thyroid receptor antibodies, total bilirubin (TB), direct and indirect bilirubin, lower serum levels of hemoglobin and creatinine, and more severe cardiac load (P < .05 for each) compared with patients without PH. Levels of serum FT4, free triiodothyronine, thyroid receptor antibodies, and thyroid peroxidase antibody were different among groups of patients with different levels of pulmonary arterial systolic pressure (P < .05 for each). Multivariate logistic regression analysis indicated that serum FT4 (odds ratio, 1.02; 95% CI, 1.01-1.04; P = .004) and TB (OR, 1.03; 95% CI, 1.00-1.06; P = .030) were independent risk factors for PH in patients with hyperthyroidism.ConclusionElevated serum FT4 and TB levels may be independent risk factors for PH in patients with hyperthyroidism and valuable indicators for the identification and treatment of patients with PH and hyperthyroidism.     

Association of Serum Parathyroid Hormone Levels With All-Cause and Cause-Specific Mortality Among U.S. Adults

ObjectiveTo examine whether parathyroid hormone (PTH) is associated with mortality among U.S. adults.MethodsThis study included 8286 U.S. adults aged ≥20 years with a measurement of serum intact PTH from the National Health and Nutrition Examination Survey 2003-2006 linked to national mortality data through 2015. Multivariable Cox proportional hazard regression models were employed to estimate the adjusted hazard ratio (aHR) of all-cause and cause-specific (cardiovascular and cancer) mortality according to intact PTH levels (low or low-normal, <38; middle-normal, 38-56; high-normal, 57-74; high, >74 pg/mL). We also stratified the analyses by serum albumin-adjusted calcium and 25-hydroxy vitamin D (25OHD) levels.ResultsDuring a median follow-up of 10.1 years, the mean age was 49 years, and 48% were men. After adjusting for potential confounders, both the high-normal and high PTH groups showed higher risks of all-cause mortality than the low or low-normal PTH group (high-normal PTH, aHR, 1.28; 95% confidence interval [CI], 1.10-1.48; high PTH, aHR, 1.42; 95% CI, 1.19-1.69]. When stratified by calcium and 25OHD levels, the association between high PTH and mortality was also found among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL (aHR, 1.53; 95% CI, 1.17-2.01) and those with 25OHD levels of ≥20 ng/mL (aHR, 1.46, 95% CI, 1.17-1.82). We found no evidence of the increased cause-specific mortality risks in the high PTH group.ConclusionHigher PTH levels were associated with an increased risk of all-cause mortality, particularly among participants with albumin-adjusted calcium levels of ≥9.6 mg/dL or 25OHD levels of ≥20 ng/mL.     

Transverse and Longitudinal Ultrasound Location of Thyroid Nodules and Risk of Thyroid Cancer

BackgroundThe high prevalence of thyroid nodules demands accurate assessment tools to avoid unnecessary biopsies. Prior studies demonstrated a correlation between the longitudinal location of thyroid nodules and the likelihood of malignancy. No study has evaluated the predictive value of transverse location on ultrasonography with malignancy.MethodsWe retrospectively reviewed the records of thyroid nodules that underwent fine-needle aspiration over 13 years, including demographics, risk factors, nodule sonographic features, location, and surgical pathology. Univariate and multivariable logistic regression models were used to evaluate the risk of malignancy.ResultsOf the 668 thyroid nodules, 604 were analyzed with a definitive diagnosis. Thirty-seven nodules were malignant, representing a prevalence of 6.1%. In the longitudinal plane, the upper pole nodules carried the highest incidence of malignancy (14.9%). In the transverse plane, the highest incidence of malignancy occurred in nodules located laterally (12.5%) and anterior-laterally (11.8%). Compared with the upper pole, the odds of malignancy were significantly lower for lower pole (odds ratio [OR] = 0.26, 95% confidence interval [CI]: 0.09-0.70) and midlobe nodules (OR = 0.31, 95% CI: 0.12-0.83). In the transverse plane, posteriorly situated nodules carried a significantly lower risk of malignancy (OR = 0.07, 95% CI: 0.01-0.69). Multiple logistic regression confirmed these associations after adjusting for age, sex, family history, radiation exposure, nodule size, and sonographic characteristics.ConclusionBoth the transverse and longitudinal planes were independent predictors of cancer in thyroid nodules. Lateral, anterior-lateral, and upper pole nodules carried the highest risk and posterior nodules had the lowest risk of malignancy.     

Different Sodium-Glucose Cotransporter-2 Inhibitors: Can They Prevent Death?

ObjectiveSodium-glucose cotransporter-2 inhibitors (SGLT2is) in cardiovascular outcome trials (CVOTs) demonstrate cardiovascular (CV) safety and benefits. Some dedicated randomized controlled trials (RCTs) demonstrate benefit in terms of renal outcomes and hospitalization due to heart failure (HF). RCTs report differences in the secondary outcomes with respect to mortality (CV and/or all-cause). We undertook a meta-analysis of all SGLT2is for which in addition to CVOT, HF outcome/renal outcome studies are available to establish whether individual SGLT2is were able to prevent death.MethodsWe included available event-driven randomized, placebo-controlled CVOTs and dedicated RCTs of SGLT2is exploring renal outcomes and HF. We included 3 trials of empagliflozin, 3 of dapagliflozin, 2 of canagliflozin, and 2 of sotagliflozin. The efficacy outcomes included all-cause mortality and CV mortality. Hazard ratios (HRs) with 95% CIs were pooled for individual molecules.ResultsThe HR for all-cause mortality including all trials was 0.86 (0.80-0.93). The HRs for all-cause mortality in empagliflozin (N = 16 738), dapagliflozin (N = 26 208), canagliflozin (N = 14 543), and sotagliflozin (N = 11 806) were 0.86 (0.69-1.08), 0.83 (0.72-0.97), 0.86 (0.75-0.97), and 0.95 (0.81-1.11), respectively. The HR for CV mortality including all trials was 0.85 (0.78-0.92). The HRs for CV mortality in empagliflozin, dapagliflozin, sotagliflozin, and canagliflozin were 0.81 (0.63-1.03), 0.88 (0.78-1.00), 0.89 (0.74-1.07), and 0.84 (0.72-0.98), respectively.ConclusionSGLT2is as a class reduce both all-cause mortality and CV mortality. Canagliflozin possibly reduces both all-cause mortality and CV mortality, whereas dapagliflozin may reduce all-cause mortality but not CV mortality. Empagliflozin and sotagliflozin may reduce neither.     

Hyperglycemia is Associated With Increased Mortality in Critically Ill Patients With COVID-19

ObjectiveTo explore the relationship between hyperglycemia in the presence and absence of diabetes mellitus (DM) and adverse outcomes in critically ill patients with coronavirus disease 2019 (COVID-19).MethodsThe study included 133 patients with COVID-19 admitted to an intensive care unit (ICU) at an urban academic quaternary-care center between March 10 and April 8, 2020. Patients were categorized based on the presence or absence of DM and early-onset hyperglycemia (EHG), defined as a blood glucose >180 mg/dL during the first 2 days after ICU admission. The primary outcome was 14-day all-cause in-hospital mortality; also examined were 60-day all-cause in-hospital mortality and the levels of C-reactive protein, interleukin 6, procalcitonin, and lactate.ResultsCompared to non-DM patients without EHG, non-DM patients with EHG exhibited higher adjusted hazard ratios (HRs) for mortality at 14 days (HR 7.51, CI 1.70-33.24) and 60 days (HR 6.97, CI 1.86-26.13). Non-DM patients with EHG also featured higher levels of median C-reactive protein (306.3 mg/L, P = .036), procalcitonin (1.26 ng/mL, P = .028), and lactate (2.2 mmol/L, P = .023).ConclusionAmong critically ill COVID-19 patients, those without DM with EHG were at greatest risk of 14-day and 60-day in-hospital mortality. Our study was limited by its retrospective design and relatively small cohort. However, our results suggest the combination of elevated glucose and lactate may identify a specific cohort of individuals at high risk for mortality from COVID-19. Glucose testing and control are important in individuals with COVID-19, even those without preexisting diabetes.     

Long-Term Prognosis of Acute Myocardial Infarction Associated With Metabolic Health and Obesity Status

ObjectiveEmerging evidence supports the favorable cardiovascular health in nonobese subjects with healthy metabolism. However, little is known regarding the prognosis across the range of metabolic phenotypes once cardiovascular disease is established. We examined the prognosis of patients with acute myocardial infarction (AMI) stratified according to metabolic health and obesity status.MethodsThis is a retrospective study on consecutive patients with AMI admitted to a tertiary hospital between 2014 and 2021. Patients were allocated into the following 4 groups based on metabolic and obesity profile: (1) metabolically healthy obese (MHO), (2) metabolically healthy nonobese (MHNO), (3) metabolically unhealthy obese (MUO), and (4) metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Biobank Standardisation and Harmonisation for Research Excellence in the European Union Healthy Obese Project. The primary outcome was all-cause mortality. The Cox regression analysis examined the independent association between mortality and metabolic phenotypes, adjusting for age, sex, AMI type, chronic kidney disease, smoking status, and left ventricular ejection fraction.ResultsOf 9958 patients, the majority (68.5%) were MUNO, followed by MUO (25.1%), MHNO (5.6%), and MHO (0.8%). MHO had the lowest mortality (7.4%), followed by MHNO (9.7%), MUO (19.2%), and MUNO (22.6%) (P < .001). Compared with MHNO, MUO (hazard ratio [HR], 1.737; 95% confidence interval [CI], 1.282-2.355; P < .001) and MUNO (HR, 1.482; 95% CI, 1.108-1.981; P = .008) had a significantly higher mortality risk but not MHO (HR, 1.390; 95% CI, 0.594-3.251; P = .447), after adjusting for confounders. The Kaplan-Meier curves showed favorable survival in the metabolically healthy and obesity groups, with the highest overall survival in the MHO, followed by MHNO, MUO, and MUNO (P < .001).ConclusionMetabolically healthy and obese patients with AMI have favorable prognosis compared with metabolically unhealthy and nonobese patients. It is equally important to prioritize intensive metabolic risk factor management to weight reduction in the early phase after AMI.     

Association of Body Mass Index With Clinicopathological Features of Papillary Thyroid Carcinoma: A Retrospective Study

ObjectiveWe examined the effect of body mass index (BMI) on clinicopathological features of papillary thyroid carcinoma (PTC).MethodsThe clinical data of 4476 patients with PTC who underwent surgical treatment were retrospectively analyzed. According to the different BMI of patients, it can be divided into underweight (BMI < 18.5 kg/m²), normal weight (18.5 ≤ BMI < 24.0 kg/m²), overweight (24 ≤ BMI < 28 kg/m²), and obese (BMI ≥ 28 kg/m²). Spearman correlation analysis was performed to assess the relationship between the BMI and the size of PTC tumor. Multivariate binary logistic regression analysis was performed to estimate the association of overweight and obesity with clinicopathological features of PTC.ResultsThere was a positive correlation between the BMI and PTC tumor size (r = 0.087, P < .001). As compared with normal weight patients with PTC, overweight and obese patients with PTC had a greater risk of bilaterality (odds ratio [OR] = 1.295, OR = 1.669), multifocality (OR = 1.273, OR = 1.617), extrathyroidal extension (OR = 1.560, OR = 2.477), T (3 + 4) stage (OR = 1.482, OR = 2.392), and recurrence risk (intermediate-high risk) (OR = 1.215, OR = 1.718) (P < .05 for all). As compared with normal weight patients with papillary thyroid microcarcinoma (PTMC), overweight and obese patients with PTMC had a greater risk of bilaterality (OR = 1.341, OR = 1.737), multifocality (OR = 1.244, OR = 1.640), extrathyroidal extension (OR = 1.992, OR = 2.080), T (3 + 4) stage (OR = 1898, OR = 2.039), and recurrence risk (intermediate-high risk) (OR = 1.458, OR = 1.536) (P < .05 for all).ConclusionOverweight and obesity were significantly associated with aggressive clinicopathological features of PTC and PTMC. The impact of overweight and obesity should be considered when choosing treatment decisions for PTC and PTMC.     

Long-Term Follow-up of Graves Orbitopathy After Treatment With Short- or Long-Term Methimazole or Radioactive Iodine

ObjectiveThe aim of this study was to compare long-term outcomes in terms of new onset or worsening of Graves orbitopathy (GO) in patients with Graves disease treated with different therapeutic modalities for hyperthyroidism.MethodsA total of 1163 patients with Graves disease were enrolled in this study; 263 patients were treated with radioiodine and 808 patients received methimazole (MMI) therapy for a median of 18 months, of whom 178 patients continued MMI for a total of 96 months (long-term methimazole [LT-MMI]). The thyroid hormonal status and GO were evaluated regularly for a median of 159 months since enrollment.ResultsThe rates of relapse, euthyroidism, and hypothyroidism at the end of follow-up were as follows: radioiodine treatment group: 16%, 22%, and 62%, respectively; short-term MMI group: 59%, 36%, and 5%, respectively; and LT-MMI group: 18%, 80%, and 2%, respectively. During the first 18 months of therapy, worsening of GO (11.5% vs 5.7%) and de novo development of GO (12.5% vs 9.8%) were significantly more frequent after radioiodine treatment (P <.004). Overall worsening and de novo development of GO from >18 to 234 months occurred in 26 (9.9%) patients in the radioiodine group and 8 (4.5%) patients in the LT-MMI group (P <.037). No case of worsening or new onset of GO was observed in patients treated with LT-MMI from >60 to 234 months of follow-up.ConclusionProgression and development of GO were associated more with radioiodine treatment than with MMI treatment; GO may appear de novo or worsen years after radioiodine treatment but not after LT-MMI therapy.     

A Novel Scoring System for the Risk of Papillary Thyroid Cancer Metastases in Lymph Nodes Posterior to the Right of the Recurrent Laryngeal Nerve

ObjectiveSome surgeons believe that dissection posterior to the right recurrent laryngeal nerve lymph node (PRRLN-LN) is unnecessary for the low metastasis rate and high complication risk. However, persistent metastatic lymph nodes may have a higher recurrence rate, surgical risk, and complications. Thus, it is important to distinguish patients who require PRRLN-LN dissection. To identify the risk factors for lymph nodes posterior to the right recurrent laryngeal nerve metastasis (LN-prRLN) and establish a scoring system to help determine whether PRRLN-LN dissection is required in patients with papillary thyroid carcinoma.Methods821 participants were randomly allocated to the development and validation cohorts in a 2:1 ratio. A nomogram-based predictive model for LN-prRLN was established based on the risk factors identified in the development cohort.ResultsLN-prRLN was diagnosed pathologically in 124 of 821 patients (15.1%) from the entire cohort. Multivariate analysis identified age (odds ratio [OR], 0.964; 95% CI, 0.945-0.983; P < .001), tumor size (OR, 1.536; 95% CI, 1.135-2.079; P = .005), extrathyroidal extension (OR 2.271, 95% CI, 1.368-3.770; P = .002), clinically involved right central compartment lymph node metastasis (OR 1.643, 95% CI, 1.055-2.559; P = .028), and right lateral lymph node metastasis (OR 4.271, 95% CI, 2.325-7.844; P < .001) as the predictors of LN-prRLN. A risk model was established and well validated. Calibration curves to evaluate the nomogram in both the development and validation cohorts revealed a concordance index of 0.756 ± 0.058 and 0.745 ± 0.042, respectively.ConclusionOur scoring system may be useful for helping the surgeons decide which patients should undergo the dissection of PRRLN-LN.     

Risk of Breast Cancer in Females With Hypothyroidism: A Nationwide,Population-Based,Cohort Study

ObjectivesThe results of studies investigating the relationship between breast cancer and hypothyroidism vary greatly from study to study. In this study, we analyzed a large and reliable, population-based database to gain a better understanding of the correlation.MethodsThis retrospective cohort study analyzed patients with hypothyroidism between January 1, 2000 and December 31, 2012 (hypothyroidism cohort) from the Longitudinal Health Insurance Database 2000 in Taiwan. For each woman with hypothyroidism, 1 woman without a history of breast cancer was randomly selected from the Longitudinal Health Insurance Database 2000 and frequency matched (1:4) with women without hypothyroidism by age and index year of hypothyroidism. The study outcome was the diagnosis of breast cancer during a 12-year follow-up period.ResultsIn this study, 6665 women with hypothyroidism and 26 660 women without hypothyroidism were identified. The hypothyroidism cohort had a significantly higher risk of breast cancer than the nonhypothyroidism cohort (adjusted hazard ratio [aHR] 1.69 [95% CI, 1.15-2.49]; P = .01), especially in the group aged 40 to 64 years (aHR 2.07 [95% CI, 1.32-3.23]; P = .01). Women in the hypothyroidism cohort taking levothyroxine for a duration ˃588 days showed a significantly decreased risk of breast cancer (aHR 0.37 [95% CI, 0.19-0.71]; P = .003).ConclusionWomen with hypothyroidism are at a higher risk of breast cancer than those without hypothyroidism. Levothyroxine may reduce the risk of breast cancer in a woman with hypothyroidism.     

Parathyroidectomy Is Associated With Reversed Nondipping Heart Rate That Impacts Mortality in Chronic Kidney Disease Patients

ObjectiveNondipping heart rate (HR), defined as a night/day HR ratio >0.90, has been associated with increased mortality in epidemiologic studies. However, its prognostic value in stage 5 chronic kidney disease (CKD5) patients and the effects of parathyroidectomy (PTX) on nondipping HR remain unknown.MethodsThis case-control study of 162 healthy controls and 502 CKD5 patients was performed between 2011 and 2018, in which CKD5 patients were further divided into non-PTX (n = 186) and severe secondary hyperparathyroidism (SHPT) with PTX (n = 316) subgroups. Each participant underwent 24-hour Holter monitoring for HR ratio. Mortality was followed up in CKD5 patients (median time: 46.0 months).ResultsThe HR ratio in CKD5 patients was higher than in controls (0.92 ± 0.08 vs 0.81 ± 0.08, P <.001), associated with a 44% increase in mortality risk per 0.1 increment (hazard ratio, 1.44; 95% CI: 1.02-2.03; P =.04), and was positively related to serum intact parathyroid hormone levels (P <.001). PTX reversed nondipping HR in SHPT patients (n = 50, median time: 6.3 months, P <.001). Survival probabilities for PTX (n = 294) were better than non-PTX (n = 47) (hazard ratio, 0.31; 95% CI: 0.14-0.67; P <.01) in SHPT patients (serum intact parathyroid hormone >500.0 pg/mL).ConclusionCKD5 patients displayed a nondipping HR pattern, which is a prognostic marker of all-cause mortality. PTX for SHPT patients was associated with a reversal in nondipping HR ratio, which may mediate a better outcome.     

Diagnostic Accuracy of Copeptin in the Differential Diagnosis of Patients With Diabetes Insipidus: A Systematic Review and Meta-analysis

ObjectiveAccurate diagnosis of diabetes insipidus (DI) is of significant importance for correct management. We aimed to evaluate the diagnostic accuracy of copeptin level measurements in the differential diagnosis between DI and primary polydipsia (PP).MethodsA literature search of electronic databases from January 1, 2005, to July 13, 2022, was performed. Primary studies that evaluated the diagnostic accuracy of copeptin concentration in patients with DI and PP were considered eligible. Two reviewers independently screened relevant articles and extracted data. The Quality Assessment of Diagnostic Accuracy Studies 2 tool was used to assess the quality of the included studies. The hierarchical summary receiver operating characteristic model and bivariate method were used.ResultsSeven studies including 422 patients with polydipsia-polyuria syndrome were included; of the 422 patients, 189 (44.79%) presented with arginine vasopressin deficiency (AVP-D, cranial DI) and 212 (50.24%) with PP. The summary estimates of the diagnostic performance of stimulated copeptin to differentiate between PP and AVP-D were 0.93 (95% CI, 0.89-0.97) for sensitivity and 0.96 (95% CI, 0.88-1.00) for specificity. Baseline copeptin level showed high performance in identifying AVP resistance (nephrogenic DI), with a pooled sensitivity of 1.00 (95% CI, 0.82-1.00) and specificity of 1.00 (95% CI, 0.98-1.00); however, it showed little value in the differentiation between PP and AVP-D.ConclusionCopeptin level measurement is a useful tool for the differential diagnosis of patients with DI and PP. Stimulation before copeptin measurement is necessary in the diagnosis of AVP-D.     

Comparison of New Glucose-Lowering Drugs on the Risk of Pancreatitis in Type 2 Diabetes: A Network Meta-Analysis

ObjectiveTo explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus.MethodsPubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes.ResultsSeventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results.ConclusionThe most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.