Association of Thyroid Function During Pregnancy With the Risk of Pre-eclampsia and Gestational Diabetes Mellitus

ObjectiveTo estimate the association of maternal thyroid dysfunction with the risk of gestational hypertension and diabetes. Whether the association was affected by gestational age at diagnosis and thyroid autoimmunity was further explored.MethodsA cohort study of 41 647 participants was conducted. Thyroid function (ie, thyroid-stimulating hormone [TSH] and free thyroxine [FT4]) was measured by electrochemiluminescence immunoassay. Thyroid antibody positivity (eg, thyroperoxidase, thyroglobulin, and TSH receptor antibody) was indicated if the values of these antibodies exceeded the upper targets of the reference range. The relationship between maternal thyroid dysfunction and the risk of pre-eclampsia (PE) and gestational diabetes mellitus (GDM) was assessed by multivariate logistic regression.ResultsIsolated hypothyroxinemia (defined as 5th ≤ TSH ≤ 95th percentile, FT4 < 5th percentile) was associated with the risk of PE (odds ratio [OR], 1.32; 95% CI, 1.10-1.58). Overt hypothyroidism (TSH > 95th percentile; FT4 < 5th percentile) was related to the risk of severe PE (OR, 2.59; 95% CI, 1.05-6.37). Being positive for TSH receptor antibody was associated with a decreased risk of GDM (OR, 0.49; 95% CI, 0.35-0.70). A marginally significant association between overt hypothyroidism detected at the first trimester and the risk of GDM was found (OR, 1.60; 95% CI, 1.00-2.83). The association of thyroid dysfunction with the risk of PE and GDM was stronger among pregnant women who were negative for autoantibodies.ConclusionSome types of thyroid dysfunction during pregnancy were associated with the risk of PE and GDM. The associations varied by gestational age at diagnosis and by thyroid autoantibody status.     

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.     

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.     

Using a Diabetes Risk Score to Identify Patients Without Diabetes at Risk for New Hyperglycemia in the Hospital

ObjectiveTo assess the value of a validated diabetes risk test, the Cambridge Risk Score (CRS), to identify patients admitted to hospital without diabetes at risk for new hyperglycemia (NH).MethodsThis retrospective cross-sectional study included adults admitted to a hospital over a 4-year period. Patients with no diabetes diagnosis and not on antidiabetics were included. The CRS was calculated for each patient, and those with available glycated hemoglobin (HbA1C) results were investigated in a second analysis. Multivariate regression analyses were performed to assess the association among CRS, HbA1C, and the risk for NH.ResultsA total of 19,830 subjects comprised the sample, of which 38% were found to have developed NH, defined as a blood glucose level ≥140 mg/dL. After accounting for covariates, the CRS was significantly associated with NH (odds ratio [OR], 1.19 [1.16, 1.22]; P < .001). Only 17% of patients had their HbA1C values checked within 6 months of admission. Compared with patients without diabetes, patients with prediabetes based on their HbA1C level (OR, 1.59 [1.37, 1.86]; P < .001) and patients with undiagnosed diabetes (OR, 5.95 [3.50, 10.65]; P < .001) were also significantly more likely to have NH.ConclusionResults of this study show that the CRS and HbA1C levels were significantly associated with the risk of developing NH in inpatient adults without diabetes. Given that an HbA1C level was missing in most medical records of hospitalized patients without diabetes, the CRS could be a useful tool for early identification and management of NH, possibly leading to better outcomes.     

The Prevalence of Cancer and Its Relation to Disease Activity in Patients With Acromegaly: Two Centers' Experience

ObjectiveAcromegaly is characterized by increased serum concentrations of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). Although animal studies have demonstrated a relationship between these hormones and cancer risk, the results of human studies evaluating cancer prevalence in acromegaly are inconsistent. We aimed to investigate the prevalence of malignant neoplasms in patients with acromegaly.MethodsCancer risk was evaluated in a cohort of 280 patients (male/female: 120/160; mean age: 50.93 ± 12.07 years) with acromegaly. Patients were categorized into 2 groups according to the presence or absence of cancer. Standard incidence ratios were calculated as compared to the general population.ResultsFrom 280 patients, cancer was diagnosed in 19 (6.8%) patients; 9 (47%) of them had thyroid cancer, which was the most common cancer type. Standard incidence ratios of all cancers were 0.8 (95% CI, 0.5-1.1) and 1.0 (95% CI, 0.8-1.3) in men and women, respectively. Compared to patients without cancer, the current age was higher in patients with cancer (59 [49-65] to 51 [42-59], P = .027). In contrast, the age at diagnosis was similar in both groups. Not only was the time to diagnosis and disease duration similar in both groups but also the basal and current GH and IGF-1 levels. The prevalence of active disease was also similar between the groups (32% to 23%, P = .394).ConclusionOur findings were not consistent with the studies suggesting that patients with acromegaly encounter an increased cancer risk. Furthermore, there were similar basal and current GH and IGF-1 levels in patients with acromegaly, both with and without cancer.     

SARS-CoV-2 Seroprevalence in Individuals With Type 1 and Type 2 Diabetes Compared With Controls

ObjectiveData for the association between diabetes and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility are conflicting. We aimed to evaluate this association using an analytical cross-sectional study design.MethodsStudy participants were recruited from endocrine clinics of our hospital and belonged to 3 groups: group 1 (type 1 diabetes mellitus [T1DM]), group 2 (type 2 diabetes mellitus [T2DM]), and group 3 (controls). All participants submitted blood samples for SARS-CoV-2 S1/S2 immunoglobulin G antibody test (LIAISON; DiaSorin) and were interviewed for a history of documented infection.ResultsWe evaluated a total of 643 participants (T1DM, 149; T2DM, 160; control, 334; mean age, 37.9 ± 11.5 years). A total of 324 (50.4%) participants were seropositive for SARS-CoV-2. The seropositivity rate was significantly higher in the T1DM (55.7% vs 44.9%, P = .028) and T2DM (56.9% vs 44.9%, P = .013) groups than in the control group. The antibody levels in seropositive participants with T1DM and T2DM were not significantly different from those in seropositive controls. On multivariable analysis, low education status (odds ratio [OR], 1.41 [95% CI, 1.03-1.94]; P = .035), diabetes (OR, 1.68 [95% CI, 1.20-2.34]; P = .002), and overweight/obesity (OR, 1.52 [95% CI, 1.10-2.10]; P = .012) showed a significant association with SARS-CoV-2 seropositivity. The association between diabetes and SARS-CoV-2 seropositivity was found to further increase in participants with coexisting overweight/obesity (adjusted OR, 2.63 [95% CI, 1.54-4.47]; P < .001).ConclusionSARS-CoV-2 seropositivity, assessed before the onset of the national vaccination program, was significantly higher in participants with T1DM and T2DM than in controls. The antibody response did not differ between seropositive participants with and without diabetes. These findings point toward an increased SARS-CoV-2 susceptibility for patients with diabetes, in general, without any differential effect of the diabetes type.     

Predictors of Severe COVID-19 in Patients With Diabetes: A Multicenter Review

ObjectiveDiabetes is an independent risk factor for severe SARS-CoV-2 infections. This study aims to elucidate the risk factors predictive of more severe outcomes in patients with diabetes by comparing the clinical characteristics of those requiring inpatient admissions with those who remain outpatient.MethodsA retrospective review identified 832 patients—631 inpatients and 201 outpatients—with diabetes and a positive SARS-CoV-2 test result between March 1 and June 15, 2020. Comparisons between the outpatient and inpatient cohorts were conducted to identify risk factors associated with severity of disease determined by admission rate and mortality. Previous dipeptidyl peptidase 4 inhibitor use and disease outcomes were analyzed.ResultsRisk factors for increased admission included older age (odds ratio [OR], 1.04 [95% CI, 1.01-1.06]; P = .003), the presence of chronic kidney disease (OR, 2.32 [1.26-4.28]; P = .007), and a higher hemoglobin A1c at the time of admission (OR, 1.25 [1.12-1.39]; P < .001). Lower admission rates were seen in those with commercial insurance. Increased mortality was seen in individuals with older age (OR, 1.09 [1.07-1.11]; P < .001), higher body mass index number (OR, 1.04 [1.01-1.07]; P = .003), and higher hemoglobin A1c value at the time of diagnosis of COVID-19 (OR, 1.12 [1.01-1.24]; P = .028) and patients requiring hospitalization. Lower mortality was seen in those with hyperlipidemia. Dipeptidyl peptidase 4 inhibitor use prior to COVID-19 infection was not associated with a decreased hospitalization rate.ConclusionThis retrospective review offers the first analysis of outpatient predictors for admission rate and mortality of COVID-19 in patients with diabetes.     

Predictors of Hypothyroidism Following Empirical Dose Radioiodine in Toxic Thyroid Nodules: Real-Life Experience

ObjectiveWe aimed to determine the factors predicting hypothyroidism after radioactive iodine (RAI) treatment in patients with toxic adenoma and toxic multinodular goiter.MethodsWe retrospectively collected the data of 237 patients with toxic multinodular goiter or toxic adenoma who had consecutively received RAI treatment between 2014 and 2020 at 2 medical centers. Patients who received the second RAI treatment and whose medical records could not be accessed were excluded from the study. Finally, 133 patients were included in the study. RAI was administered at an empirical dose of 15 or 20 mCi.ResultsThe median age of the 133 participants was 69 years (interquartile range, 62-75 years), and 64.7% of the participants were women. A total of 42.1% of the patients had toxic adenoma, whereas 57.9% of patients had toxic multinodular goiter. The median follow-up was 24 months (interquartile range, 11-38 months). During the follow-up, 61.7% of patients became euthyroid, 30.8% developed hypothyroidism, and 7.5% remained hyperthyroid. The median month of hypothyroidism onset was 4 months (interquartile range, 2-9 months). Regression analysis revealed 2 factors that could predict hypothyroidism: thyroid-stimulating hormone (odds ratio, 2.548; 95% CI, 1.042-6.231; P = .04) and thyroid volume (odds ratio, 0.930; 95% CI, 0.885-0.978; P = .005).ConclusionOverall, 30.8% of the cases developed hypothyroidism after the RAI treatment. Approximately 78% of hypothyroidism developed within the first 10 months. The risk of hypothyroidism was higher in patients with higher thyroid-stimulating hormone and smaller thyroid volume.     

Clinical Evaluation of BRCA1/2 Mutation in Mexican Ovarian Cancer Patients

Ovarian cancer (OC) is an important cause of gynecologic cancer-related deaths. In Mexico, around 4700 new cases of OC are diagnosed per year and it represents the second cause of gynecological cancer mortality with more than 2700 deaths. Germline mutations in BRCA1/2 genes are present in 13–18% of OC cases. Few studies have evaluated the presence of mutations in BRCA genes in a population of OC Mexican patients and their relationship with clinical response and survival rates.A total of 179 OC patients were studied by molecular testing for BRCA1/2 through next-generation sequencing and multiplex ligation-dependent probe amplification. Recurrence-free survival (RFS) was estimated by the Kaplan–Meier method. BRCA mutation was detected in 33% of patients. A percentage of 66.1% were BRCA1 mutated and 33.9% were BRCA2 mutated. BRCA1 mutation carriers had a worst RFS compared with BRCA2 mutation carriers (37.6 [29–46.2] vs 72.7 [38.4–107.2]; P = 0.030). The most common mutation for BRCA1 was ex9-12del (28.2%) (Mexican founder mutation). The Mexican founder mutation had a better RFS than other BRCA1 mutations (86.1 [37.2–135.1] vs 34.5 [20.7–48.2]; P = 0.033). The presence of BRCA2 mutations in the ovarian cancer cluster region (OCCR) had a significantly better RFS than mutations in breast cancer cluster regions (BCCR) and not-related risk region (NRR) (NR vs 72.8 [39–106.6] vs 25.8 [8.3–43.2]; P = 0.013). These results demonstrate that the prevalence of BRCA1/2 positive patients in OC Mexican patients are the highest reported. Patients with mutations in BRCA2 have a better prognosis than those mutated in BRCA1. The Mexican founder mutation has an important role in clinical outcomes. These results highlight the importance to test all the HGSP (high-grade serous papillary) OC patients with or without cancer family history (CFH) in Mexican population.     

Posthemithyroidectomy Pregnancy Thyroid Function Surveillance: Frequency,Adherence, and Guideline Impact

ObjectivePosthemithyroidectomy women are at an increased risk for gestational subclinical hypothyroidism. Therefore, the American Thyroid Association (ATA) recommends increased thyroid function surveillance for this subgroup of pregnant women. The purpose of this study was to evaluate the frequency of thyroid function surveillance during pregnancy in posthemithyroidectomy women and to evaluate the adherence to the 2017 ATA guidelines and its possible impact since being published on thyroid function surveillance rates.MethodsA retrospective study of pregnant posthemithyroidectomy women operated at our institution between 1997 and 2020 was performed. The study cohort was subdivided by pregnancy dates before 2018 and 2018 onward to evaluate the impact of the 2017 ATA guidelines. Adherence to the guidelines was defined as at least 1 thyroid-stimulating hormone test in each trimester.ResultsAfter exclusions, a total of 120 pregnancies conceived by 66 women who underwent hemithyroidectomy surgeries were included in this study. Overall, serum thyroid-stimulating hormone examinations were performed during the first, second, and third pregnancy trimesters in 86.6%, 40%, and 16.6% of pregnancies, respectively (P <.005). The examination rate since 2018 was 88%, 40%, and 8% for the first, second, and third trimesters, respectively (P <.005).ConclusionAdherence to the latest ATA guidelines is low, and its publication in 2017 did not increase the thyroid function surveillance rate in posthemithyroidectomy women. Better patient education regarding the risks of gestational hypothyroidism following hemithyroidectomy and improved communications among treating surgeons, obstetricians, and endocrinologists may improve these rates.     

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.     

Correlation Between Hemoglobin Glycation Index Measured by Continuous Glucose Monitoring With Complications in Type 1 Diabetes

ObjectiveHbA1C is the “gold standard” parameter to evaluate glycemic control in diabetes; however, its correlation with mean glucose is not always perfect. The objective of this study was to correlate continuous glucose monitoring (CGM)-derived hemoglobin glycation index (HGI) with microvascular complications.MethodsWe conducted a cross-sectional study including permanent users of CGM with type 1 diabetes mellitus or latent autoimmune diabetes of the adult. HGI was estimated, and presence of microvascular complications was compared in subgroups with high or low HGI. A logistic regression analysis to assess the contribution of high HGI to chronic kidney disease (CKD) was performed.ResultsIn total, 52 participants who were aged 39.7 ± 14.7 years, with 73.1% women and 15.5 years (IQR, 7.5-29 years) since diagnosis, were included; 32.7% recorded diabetic retinopathy, 25% CKD, and 19.2% neuropathy. The median HbA1C was 7.6% (60 mmol/mol) and glucose management indicator (GMI) 7.0% (53 mmol/mol). The average HGI was 0.55% ± 0.66%. The measured HbA1C was higher in the group with high HGI (8.1% [65 mmol/mol] vs 6.9% [52 mmol/mol]; P < .001), whereas GMI (7.0% [53 mmol/mol] vs 7.0% [53 mmol/mol]; P = .495) and mean glucose were similar in both groups (153 mg/dL vs 153 mg/dL; P = .564). In the high HGI group, higher occurrence of CKD (P = .016) and neuropathy were observed (P = .025). High HGI was associated with increased risk of CKD (odds ratio [OR]: 5.05; 95% CI: 1.02-24.8; P = .04) after adjusting for time since diagnosis (OR: 1.09; 95% CI: 1.02-1.16; P = .008).ConclusionHigh HGI measured by CGM may be a useful marker for increased risk of microvascular diabetic complications.     

Predictive Role of Child-To-Adult Blood Pressure Trajectories for Incident Metabolic Syndrome: 30-Year Hanzhong Adolescent Hypertension Study

ObjectiveThe relationship between child-to-adult blood pressure (BP) trajectories and metabolic syndrome (MetS) is unknown. We aimed to determine the predictive role of BP trajectories for incident MetS and its components.MethodsThe prospective Hanzhong Adolescent Hypertension study began in 1987 and included 2692 participants free of MetS at baseline with at least 3 BP measurements available from 1987 to 2017.ResultsThe systolic BP (SBP) trajectory patterns were grouped as normal (class 1, 18.7%), high normal (class 2, 60.3%), prehypertensive (class 3, 13.1%), stage 1 hypertensive (class 4, 5.7%), and stage 2 hypertensive (class 5, 2.2%). Compared with those in the normal group, individuals in classes 2 to 5 had significantly higher risks of MetS (all Ps < .05), and those with hypertension had more than an 8-fold higher risk of MetS (both P < .05). The fully adjusted risk ratios (RRs) of central obesity increased significantly in a stepwise manner as the SBP trajectory group increased from class 1 to class 5 (P < .05). Compared with those with a normal SBP trajectory, participants in the prehypertensive group and stage 1 and stage 2 hypertensive groups had significantly higher RRs for high-risk triglycerides after full adjustment (RR = 1.89 [1.22-2.94]; RR = 3.61 [2.16-6.02]; and RR = 3.22 [1.52-6.84], respectively).ConclusionOur study suggests that BP trajectories are predictive of incident MetS outcomes. Early detection of hypertension or modest elevations in BP is crucial. The stage of hypertension based on SBP level showed a greater association with central obesity.     

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.     

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.     

Effect of Treatment of OSA With CPAP on Glycemic Control in Adults With Type 2 Diabetes: The Diabetes Sleep Treatment Trial (DSTT)

ObjectiveThe effect of obstructive sleep apnea (OSA) treatment with continuous positive airway pressure (CPAP) on glycemic measures in patients with type 2 diabetes (T2D) remains unclear. We aimed to determine whether CPAP treatment of OSA improves glycemic measures in patients with T2D.MethodsThis randomized controlled trial (N = 98) examined changes in glycemic measures following 12 weeks of active (n = 49) or sham (n = 49) CPAP and consideried participants’ adherence to CPAP therapy (percentage of days with ≥4 hours use and average hours/day of use).ResultsBaseline treatment groups were similar. Regarding the efficacy of active vs sham-CPAP over time, at 6 weeks, both groups had similar reductions in fructosamine (mean difference [MD], 95% confidence interval [CI]: CPAP ?13.10 [?25.49 to ?0.7] vs. sham ?7.26 [?20.2 to 5.69]; P = .519) but different in HbA1c (CPAP ?0.24 [?0.48 to ?0.003] vs sham 0.15 [?0.10 to 0.4]; P = .027). At 12 weeks, reductions in HbA1c values were similar by group (CPAP ?0.26 [?0.53 to 0.002] vs sham ?0.24 [?0.53 to 0.04]; P = .924). HbA1c reductions were associated with a greater percentage of cumulative days of CPAP usage ≥4 hours per day (b [SE] = 0.006 [0.002]; P = .013) and cumulative hours of CPAP use (b [SE] = 0.08 [0.08]; P = .012). CPAP use of ≥7 hours was associated with a significant reduction in HbA1c (b [SE] 0.54 [0.16]; P = .0012).ConclusionCPAP treatment of OSA did not result in sustained improved glycemic control compared to sham in the intent-to-treat analysis. CPAP adherence was associated with greater improvements in glycemic control.     

Thyroid Immune-Related Adverse Events in Patients with Cancer Treated with anti-PD1/anti-CTLA4 Immune Checkpoint Inhibitor Combination: Clinical Course and Outcomes

ObjectiveThyroid immune-related adverse events (irAEs) have been reported to have prognostic significance among patients with cancer treated with anti-programmed cell death-1 (PD1) and anti-programmed death-ligand 1 monotherapies. We evaluated the clinical course and predictors of thyroid irAEs in relation to outcomes of patients with advanced cancer treated with combination anti-PD1/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4).MethodsWe conducted a regional study and identified patients with advanced cancer who received ≥1 cycle of combination anti-PD1/anti-CTLA4 between 2015 and 2019 in Hong Kong. Thyroid function tests (TFTs) were monitored every 3 weeks. Thyroid irAE was defined by ≥2 abnormal TFTs after initiation of combination anti-PD1/anti-CTLA4 in the absence of other causes.ResultsOne hundred and three patients were included (median age: 59 years; 71.8% men). About 45% had prior anti-PD1 exposure. Upon median follow-up of 6.8 months, 17 patients (16.5%) developed thyroid irAEs, where 6 initially presented with thyrotoxicosis (overt, n = 4; subclinical, n = 2) and 11 with hypothyroidism (overt, n = 2; subclinical, n = 9). Eventually, 10 patients (58.8%) required continuous thyroxine replacement. Systemic steroid was not required in all cases. Prior anti-PD1 exposure (odds ratio, 3.67; 95% CI, 1.19–11.4; P = .024) independently predicted thyroid irAEs. Multivariable Cox regression analysis revealed that occurrence of thyroid irAEs was independently associated with better overall survival (adjusted hazard ratio, 0.34; 95% CI, 0.17–0.71; P = .004).ConclusionThyroid irAEs are common in routine clinical practice among patients with advanced cancer treated with anti-PD1/anti-CTLA4 combination and might have potential prognostic significance. Regular TFT monitoring is advised for timely treatment of thyroid irAEs to prevent potential morbidities.     

Trends in Adjuvant External Beam Radiation Therapy for Nonanaplastic Thyroid Cancer in California, 2003-2017

BackgroundExternal beam radiation therapy (EBRT) is rarely used to treat patients with differentiated or medullary thyroid cancer. Although EBRT is generally administered to patients with high-risk or unresectable diseases, neither its indications for the use nor the associated outcomes are well-defined. We used a statewide cohort to assess the trends in EBRT use and postradiation outcomes in California.MethodsA population-based study of patients within the California Cancer Registry who underwent EBRT after surgery for nonanaplastic thyroid cancer (2003-2017) was conducted. The primary outcome was the annual utilization rate of EBRT. The secondary outcomes included Kaplan-Meier analysis for cause-specific survival and identifying factors associated with improved survival after EBRT.ResultsAmong the 57 607 patients with nonanaplastic thyroid cancer from 2003 to 2017, 344 (0.6%) patients received EBRT. EBRT was utilized in 0.4% of papillary, 1.1% of follicular, and 7.7% of medullary thyroid cancers in California. Overall, 99 (28.8%) patients treated with EBRT died of thyroid cancer. The 10-year cause-specific survival of all patients with thyroid cancer after EBRT was 61.5% (95% CI: 54.8%-69.1%) and that of patients without distant disease was 80.3% (95% CI: 73.5%-87.8%). The survival outcomes varied by tumor size, histology, disease stage, patient age at diagnosis, and the presence of extrathyroidal extension (P < .05).ConclusionsThe use of adjuvant EBRT for nonanaplastic thyroid cancer remained stable and low in California from 2003 to 2017. The comparative efficacy of EBRT was not discernible in this study, but disease control appeared durable in select patients. Well-controlled observational studies and/or prospective studies are needed to better define which patients benefit from EBRT.