Effects of newer anti-hyperglycemic agents on cardiovascular outcomes in older adults: Systematic review and meta-analysis.

AIM: To demonstrate cardiovascular safety of dipeptidyl peptidase-4 inhibitors (DPP-4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and sodium/glucose cotransporter 2 inhibitors (SGLT-2i) across age-groups. METHODS: PubMed, Embase and Cochrane were searched for cardiovascular outcome trials (CVOTs) testing newer agents until August 31, 2022 (PROSPERO ID CRD42021260167). Studies with ≥1000 T2D participants enrolled for ≥12 months were included. Random effect models were used to report relative-risk (RR) for three-point major adverse cardiovascular events (3P-MACE) and its components by age subgroups (65 years; 75 years). RESULTS: For SGLT-2is, five CVOTs (46,969 patients, 45-50 % ≥65 years) were included. SGLT-2is reduced risk of MACE (RR; 0.91 [CI, 0.85-0.98]); cardiovascular death (CV-death) (RR; 0.84 [CI, 0.73-0.96]); and all-cause mortality (ACM) (RR; 0.86 [CI, 0.79-0.93]) with no difference in subgroups <65 or ≥65 years. For GLP-1RAs, nine CVOTs (n = 64,236, 34-75 % ≥65 years) were included. GLP-1RAs reduced risk of MACE (RR; 0.89 [CI, 0.83-0.95]), stroke (RR; 0.86 [CI, 0.76-0.97]) and ACM (RR; 0.90 [CI, 0.83-0.97]) with no significant difference in subgroups <65 or ≥65 years. Additionally, GLP-1RAs reduced risk of MACE (10 %), ACM (12 %) and CV-death (12 %) with no significant difference in subgroups <75 or ≥75 years. Four CVOTs (n = 33,063; 35-58 % ≥65 years) with DPP-4is were included. There were no significant differences in risk for CV outcomes with DPP-4is compared to placebo in any of the age subgroups. CONCLUSION: The overall cardiovascular safety profile of newer anti-hyperglycemic agents is consistent in older and younger individuals.

Predictors of racial differences in weight loss: the PROPEL trial.

OBJECTIVE: Studies have consistently shown that African American individuals lose less weight in response to behavioral interventions, but the mechanisms leading to this result have been understudied. METHODS: Data were derived from the PROmoting Successful Weight Loss in Primary CarE in Louisiana (PROPEL) study, which was a cluster-randomized, two-arm trial conducted in primary care clinics. In the PROPEL trial, African American individuals lost less weight compared with patients who belonged to other racial groups after 24 months. In the current study, counterfactual mediation analyses among 445 patients in the intervention arm of PROPEL were used to determine which variables mediated the relationship between race and weight loss. The mediators included treatment engagement, psychosocial, and lifestyle factors. RESULTS: At 6 months, daily weighing mediated 33% (p = 0.008) of the racial differences in weight loss. At 24 months, session attendance and daily weighing mediated 35% (p = 0.027) and 66% (p = 0.005) of the racial differences in weight loss, respectively. None of the psychosocial or lifestyle variables mediated the race-weight loss association. CONCLUSIONS: Strategies specifically targeting engagement, such as improving session attendance and self-weighing behaviors, among African American individuals are needed to support more equitable weight losses over extended time periods.

Vasoactive mediators of hypertension in obesity.

Obesity is associated with hypertension. However, the mechanisms involved are not fully understood. Therefore, we investigated the relationship between obesity and vasoactive mediators. In this cross-sectional study, blood pressure (BP) and vasoactive mediators of hypertension are compared among 135 adults in the nonobese, obese, and morbidly obese body mass index (BMI) ranges (BMI ≤27, 30-40, and >40 kg/m2, respectively). Angiotensinogen, angiotensin II, renin, aldosterone, endothelin-1 (ET-1), neprilysin, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), cyclic guanosine monophosphate (cGMP), and cyclic adenosine monophosphate (cAMP) levels were measured and their relationship to BP, BMI, race, and gender were investigated. Systolic and diastolic BP (SBP and DSP) were significantly higher in subjects with obesity and morbid obesity compared with nonobese. Angiotensin II, ET-1, and neprilysin were significantly higher in subjects with morbid obesity while BNP was lower. Levels of angiotensinogen, renin, aldosterone, ANP, cGMP, and cAMP did not differ between the groups. BMI was positively related to SBP, DBP, angiotensin II, ET-1, and neprilysin, and inversely related to cGMP and BNP. Age, male gender, and African-American race were associated with higher SBP. SBP was positively related to angiotensin II and ET-1 and inversely related to aldosterone, renin, and cGMP. On multivariate analyses, age, BMI, gender, and race were the main determinants of SBP, and excluding these variables, angiotensin II, aldosterone, renin, and ET-1 accounted for 21.1% ability to predict SBP. Obesity, especially morbid obesity, is associated with higher BP, higher angiotensin II and ET-1 (vasoconstrictors), and lower levels BNP and cGMP (vasodilators). SBP variability can be partly explained by angiotensin II, aldosterone, renin, and ET-1.NEW & NOTEWORTHY Our data show that obesity, especially morbid obesity, is associated with higher blood pressure levels and increases angiotensin II and endotherlin-1 (ET-1) (vasoconstrictors) and lower levels BNP and cGMP (vasodilators) and that systolic blood pressure variability can be partly explained by levels of angiotensin II, aldosterone, renin, and ET-1. The effect of these mediators on blood pressure is in addition to the effects of other known factors related to age, male gender, and AA race.

Initial weight loss and early intervention adherence predict long-term weight loss during the Promoting Successful Weight Loss in Primary Care in Louisiana lifestyle intervention.

OBJECTIVE: This study tested whether initial weight change (WC), self-weighing, and adherence to the expected WC trajectory predict longer-term WC in an underserved primary-care population with obesity. METHODS: Data from the intervention group (n = 452; 88% women; 74% Black; BMI 37.3 kg/m2 [SD: 4.6]) of the Promoting Successful Weight Loss in Primary Care in Louisiana trial were analyzed. Initial (2-, 4-, and 8-week) percentage WC was calculated from baseline clinic weights and daily at-home weights. Weights were considered adherent if they were on the expected WC trajectory (10% at 6 months with lower [7.5%] and upper [12.5%] bounds). Linear mixed-effects models tested whether initial WC and the number of daily and adherent weights predicted WC at 6, 12, and 24 months. RESULTS: Percentage WC during the initial 2, 4, and 8 weeks predicted percentage WC at 6 (R2 = 0.15, R2 = 0.28, and R2 = 0.50), 12 (R2 = 0.11, R2 = 0.19, and R2 = 0.32), and 24 (R2 = 0.09, R2 = 0.11, and R2 = 0.16) months (all p < 0.01). Initial daily and adherent weights were significantly associated with WC as individual predictors, but they only marginally improved predictions beyond initial weight loss alone in multivariable models. CONCLUSIONS: These results highlight the importance of initial WC for predicting long-term WC and show that self-weighing and adherence to the expected WC trajectory can improve WC prediction.

Cardiovascular Outcomes Trials of Incretin-Based Therapies.

The cardiovascular (CV) safety of glucagon-like peptide 1 (GLP-1) receptor agonists has been established in robust cardiovascular outcomes trials (CVOTs) in patients with type 2 diabetes at high CV risk. The GLP-1 receptor agonists liraglutide, dulaglutide, and injectable semaglutide demonstrated a significant CV benefit in these trials and now have indications to reduce the risk of major adverse CV events, including CV death, myocardial infarction, and stroke in adult patients with type 2 diabetes and established cardiovascular disease or high CV risk (dulaglutide). The dipeptidyl peptidase 4 inhibitors have also demonstrated CV safety in dedicated CVOTs but have not been associated with any CV benefit. Guidelines for the treatment of type 2 diabetes have evolved from a glucocentric focus to one that now focuses on reducing overall CV risk by personalizing therapy and using drugs such as GLP-1 receptor agonists with proven CV benefits.

Cardiovascular Outcome Trials with Glucose-Lowering Drugs.

PURPOSE OF REVIEW: This review summarizes recent cardiovascular outcome trials (CVOTs) with glucose-lowering drugs. RECENT FINDINGS: The majority of recent CVOTs with glucose-lowering drugs have tested dipeptidyl peptidase-4 inhibitors (DPP4-i), glucagon-like peptide-1 receptors agonists (GLP1-RA), and sodium-glucose cotransporter 2 inhibitors (SGLT2i), but studies have also been performed with other agents including thiazolidinediones and insulin. All CVOTs with DPP4-I, GLP1-RA, and SGLT2-i have demonstrated the cardiovascular (CV) safety of these agents compared to usual care. However, certain GLP1-RAs (liraglutide, subcutaneous semaglutide, albiglutide, dulaglutide) and SGLT2-i (empagliflozin, canagliflozin) have demonstrated a CV benefit, showing significant reductions in composite cardiovascular outcomes. Furthermore, all SGLT2-i also significantly decreased the risk for hospitalization for heart failure. Results from these studies have altered clinical guidelines worldwide and have resulted in new indications for some glucose-lowering drugs. In patients with T2D and high risk for CVD, GLP-1RA or SGLT2-i with proven cardiovascular benefit are recommended, irrespective of glycemic control.

Sex differences in soluble prorenin receptor in patients with type 2 diabetes.

BACKGROUND: The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. METHODS: Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. RESULTS: Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. CONCLUSIONS: In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

Weight Loss in Underserved Patients - A Cluster-Randomized Trial.

BACKGROUND: Evidence of the effectiveness of treatment for obesity delivered in primary care settings in underserved populations is lacking. METHODS: We conducted a cluster-randomized trial to test the effectiveness of a high-intensity, lifestyle-based program for obesity treatment delivered in primary care clinics in which a high percentage of the patients were from low-income populations. We randomly assigned 18 clinics to provide patients with either an intensive lifestyle intervention, which focused on reduced caloric intake and increased physical activity, or usual care. Patients in the intensive-lifestyle group participated in a high-intensity program delivered by health coaches embedded in the clinics. The program consisted of weekly sessions for the first 6 months, followed by monthly sessions for the remaining 18 months. Patients in the usual-care group received standard care from their primary care team. The primary outcome was the percent change from baseline in body weight at 24 months. RESULTS: All 18 clinics (9 assigned to the intensive program and 9 assigned to usual care) completed 24 months of participation; a median of 40.5 patients were enrolled at each clinic. A total of 803 adults with obesity were enrolled: 452 were assigned to the intensive-lifestyle group, and 351 were assigned to the usual-care group; 67.2% of the patients were Black, and 65.5% had an annual household income of less than $40,000. Of the enrolled patients, 83.4% completed the 24-month trial. The percent weight loss at 24 months was significantly greater in the intensive-lifestyle group (change in body weight, -4.99%; 95% confidence interval [CI], -6.02 to -3.96) than in the usual-care group (-0.48%; 95% CI, -1.57 to 0.61), with a mean between-group difference of -4.51 percentage points (95% CI, -5.93 to -3.10) (P<0.001). There were no significant between-group differences in serious adverse events. CONCLUSIONS: A high-intensity, lifestyle-based treatment program for obesity delivered in an underserved primary care population resulted in clinically significant weight loss at 24 months. (Funded by the Patient-Centered Outcomes Research Institute and others; PROPEL ClinicalTrials.gov number, NCT02561221.).

Racial and sex differences in the polymorphisms of the endocannabinoid receptor genes in obesity.

BACKGROUND: Obesity is a global epidemic and prevalence of obesity is higher in African Americans (AAs) compared to Caucasians. The endocannabinoid system (EC) and polymorphism in the endocannabinoid receptor type 1 (CNR1) gene 3813A/G and 4895A/G and in the fatty acid amide hydrolase (FAAH) are associated with obesity. The objective was to explore racial and sex differences in these polymorphisms and the biochemical abnormalities seen in obesity. METHODS: A cross-sectional study of 667 subjects (53.67% female; 49.18% AA; 69.72% were obese (body mass index [BMI] ≥30)) were screened for CNR1 3813, 4895 and FAAH 385 polymorphisms using a real-time polymerase chain reaction (PCR) system. RESULTS: Subjects with FAAH 385 polymorphisms were more likely to be obese (75.14% vs. 67.81, P = 0.046). There were no significant sex differences for CNR1 3813 and CNR1 4895; or between obese and control group. AAs had higher prevalence of CNR1 3813 (OR, 2.80, 95% CI, 1.95-4.04) and FAAH 385 (OR, 2.48, 95% CI, 1.82-3.38). Association between African American race and the three genotypes persisted after adjustment of all the variables (P < 0.001). CONCLUSION: FAAH 385 polymorphism is more likely seen in obese and in older subjects. AAs had higher prevalence of CNR1 3813 and FAAH 385 polymorphisms; and lower prevalence of CNR1 4895 polymorphism. These findings may explain some of the racial differences, but not the sex differences in the clinical expression of obesity.

Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are recommended for glycaemic management in patients with type 2 diabetes (T2D). Oral semaglutide, the first oral GLP-1RA, has recently been approved for clinical use, based on the results of the randomized, Phase 3a Peptide InnOvatioN for Early diabEtes tReatment (PIONEER) clinical trials. The PIONEER programme tested oral semaglutide in patients with T2D of duration ranging from 3.5 to 15 years, from monotherapy through to insulin add-on, in global populations and two trials dedicated to Japanese patients. Outcomes (glycated haemoglobin [HbA1c] and body weight reduction, plus other relevant efficacy and safety endpoints) were tested against both placebo and active standard-of-care medications. A separate trial evaluated the cardiovascular safety of oral semaglutide in patients with T2D at high cardiovascular risk. Over periods of treatment up to 78 weeks, oral semaglutide 7 and 14 mg once daily reduced HbA1c and body weight across the spectrum of T2D, and improved other diabetes-related endpoints, such as fasting plasma glucose. Oral semaglutide provided significantly better efficacy than placebo and commonly used glucose-lowering medications from the dipeptidyl peptidase-4 inhibitor (sitagliptin) and sodium-glucose co-transporter-2 inhibitor (empagliflozin) classes, as well as the subcutaneous GLP-1RAs liraglutide and dulaglutide. Oral semaglutide was well tolerated in line with the known safety profile of GLP-1RAs, with transient gastrointestinal events being the most common side effects reported. Cardiovascular safety was demonstrated for oral semaglutide in patients with cardiovascular disease or high cardiovascular risk. The results of the PIONEER programme suggest that oral semaglutide is efficacious and well tolerated for glycaemic control of T2D. The availability of oral semaglutide may help to broaden treatment choice and facilitate adoption of earlier GLP-1RA treatment in the paradigm of T2D management.

Effect of metformin on neurodegenerative disease among elderly adult US veterans with type 2 diabetes mellitus.

OBJECTIVE: This study aimed to evaluate the association between metformin treatment and the risk of neurodegenerative disease (ND) among elderly adults with type 2 diabetes mellitus (T2DM). DESIGN/SETTING/PARTICIPANTS: This retrospective longitudinal cohort study examined the effects of the length of metformin exposure on ND among elderly US veterans with T2DM and insulin treatment using the Veterans Affairs electronic medical record database. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary clinical outcome was defined as diagnosis of ND including dementia, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and mild cognitive impairment during the follow-up period. The secondary clinical outcomes were separately measured by AD, PD, HD, dementia and mild cognitive impairment. RESULT: Adjusted by propensity score weight, a total of 5528 patients (mean age, 63.2±10.9 years; male, 98%; white, 60%) with a median follow-up of 5.2 years were selected. Those with ND or other mental disorders at baseline or who were on insulin for less than two-thirds of the study period were excluded. The incidence rate of ND was 11.48 per 1000 person-years among patients with metformin treatment, compared with 25.45 per 1000 person-years for those without metformin. Compared with no metformin use, 2-4 years and >4 years of metformin exposure were significantly associated with lower risk of ND (adjusted HR (aHR)=0.62, 95% CI 0.45 to 0.85; aHR=0.19, 95% CI 0.12 to 0.31, respectively), while metformin exposure in the first 2 years showed no significant influence. CONCLUSION: We conclude that long-term metformin therapy (>2 years) was associated with lower incidence of ND among elderly veterans with T2DM. We need to conduct a study with more representative population and more robust method for causal inferences. Further investigation into the mechanism involved is needed along with randomised trials to confirm a potential neuroprotective effect of metformin.

Challenging the conventional wisdom on diabetic nephropathy: Is microalbuminuria the earliest event?

Microalbuminuria, urine albumin-to-creatinine ratio >30 and less than <300 mg/g has widely been accepted as biomarker of early diabetic kidney disease (DKD). Based on absence of beta-2 microglobulinuria in earlier studies on microalbuminuria, its possible tubular origin has been dismissed. Microalbuminuria has been assumed as a marker of endothelial injury. Low-molecular-weight (LMW) proteins are smaller than albumin and less restricted by the glomerular filtration barrier. Normal individuals excrete no >10 to 20 mg/day low-molecular-weight proteins in urine, as they are absorbed in the proximal tubules. Thus, LMW proteinuria, or non-albumin proteinuria (NAP) is a reliable marker of tubular dysfunction in patients without glomerular involvement. In some cohorts of patients with diabetes (DM), tubular proteinuria preceded microalbuminuria, and similar to the findings reported by Han et al. in this issue of the journal, the tubular origin of these proteins was confirmed through correlations with the increased urinary concentrations of N­Acetyl­ß­d­Glucosaminidase (NAG), a marker of tubular-lysosomal injury. Observations show significant NAP in the urine of DM patients without microalbuminuria; and that NAP correlates with NAG. In many studies it appears that NAP often precedes microalbuminuria, and is likely not the earliest biomarker of diabetic kidney disease. The conclusion that microalbuminuria is a biomarker of glomerular endothelial injury and that it is the earliest finding in DKD requires a re-appraisal. Data increasingly suggest that in early stages of DKD, NAP precedes microalbuminuria, and that microalbuminuria itself may be a consequence of impaired tubular reabsorption.

Promoting Successful Weight Loss in Primary Care in Louisiana (PROPEL): Rationale, design and baseline characteristics.

Underserved and minority populations suffer from a disproportionately high prevalence of obesity and related comorbidities. Effective obesity treatment programs delivered in primary care that produce significant weight loss are currently lacking. The purpose of this trial is to test the effectiveness of a pragmatic, high intensity lifestyle-based obesity treatment program delivered within primary care among an underserved population. We hypothesize that, relative to patients who receive usual care, patients who receive a high-intensity, health literacy- and culturally-appropriate lifestyle intervention will have greater percent reductions in body weight over 24 months. Eighteen clinics (N = 803 patients) serving low income populations with a high proportion of African Americans in Louisiana were randomized to the intervention or usual car. Patients in the intervention participate in a high-intensity lifestyle program delivered by health coaches employed by an academic health center and embedded in the primary care clinics. The program consists of weekly (16 in-person/6 telephone) sessions in the first six months, followed by sessions held at least monthly for the remaining 18 months. Primary care practitioners in usual care receive information on weight management and the current Centers for Medicare and Medicaid Services reimbursement for obesity treatment. The primary outcome is percent weight loss at 24 months. Secondary outcomes include absolute 24-month changes in body weight, waist circumference, blood pressure, fasting glucose and lipids, health-related quality of life, and weight-related quality of life. The results will provide evidence on the effectiveness of implementing high-intensity lifestyle and obesity counseling in primary care settings among underserved populations. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02561221.

Patient-centered assessment on disease burden, quality of life, and treatment satisfaction associated with acromegaly.

The study aimed to assess the economic burden, health-related quality of life (HRQoL), and acromegaly treatment satisfaction in the USA. A web-based, cross-sectional survey was distributed to members of Acromegaly Community. Data related to comorbidities, treatment patterns, and treatment satisfaction were collected. The costs over the past 3 months included out-of-pocket cost, sick leave, leave of absence, direct loss of job due to acromegaly, unemployment, assistance to perform household chores, and family member loss of income. The HRQoL was assessed by Acromegaly Quality of Life (AcroQoL) and EQ-5D-3L questionnaires. Among 106 patients who completed the survey (mean age: 46 years, female: 76.4%), 44.3% presented with ≥5 comorbidities, and 90.6% reporting acromegaly-related symptoms. Compared with the low-symptom group 0-3 (n=41), the 4+ symptoms group (n=65) was more likely to have depression (OR=2.3, 95% CI 1.1 to 5.2) and cardiovascular disease (OR=5.8, 95% CI 2.0 to 16.7), and experienced higher costs (loss of job: $8874 vs $1717, P=0.02; unemployment disability: $17,102 vs $429, P=0.003; household chores: $2160 vs $932, P=0.0003; family members' income loss: $692 vs $122, P=0.03). The high-symptom group had lower HRQoL scores, compared with the low-symptom group (EQ-5D-3L: 0.53 vs 0.75, P<0.0001; AcroQoL: 27 vs 56, P<0.0001). Only 55.7% among patients requiring injections for acromegaly were satisfied. Patients with acromegaly who presented with multiple acromegaly-related symptoms were evidenced to have experienced higher economic burden and poorer quality of life than patients with the same diagnosis but fewer symptoms. The low rate of treatment satisfaction warrants need for further studies.

Association of Malignancy Prevalence With Test Properties and Performance of the Gene Expression Classifier in Indeterminate Thyroid Nodules.

Importance: It is crucial for clinicians to know the malignancy prevalence within each indeterminate cytologic category to estimate the performance of the gene expression classifier (GEC). Objective: To examine the variability in the performance of the GEC. Design, Setting, and Participants: This retrospective cohort study of patients with Bethesda category III and IV thyroid nodules used single-institution data from January 1, 2013, through February 29, 2016. Expected negative predictive value (NPV) was calculated by adopting published sensitivity and specificity. Observed NPV was calculated based on the true-negative rate. Outcomes were compared with pooled data from 11 studies published January 1, 2010, to January 31, 2016. Results: A total of 145 patients with 154 thyroid nodules were included in the study (mean [SD] age, 56.0 [16.2] years; 106 females [73.1%]). Malignancy prevalence was 45%. On the basis of this prevalence, the expected NPV is 85% and the observed NPV is 69%. If the prevalence is assumed to be 25%, the expected NPV would be 94%, whereas the observed NPV would be 85%. Pooled data analysis of 11 studies comprising 1303 participants revealed a malignancy prevalence of 31% (95% CI, 29%-34%) and a pooled NPV of 92% (95% CI, 87%-96%). Conclusions and Relevance: In this study, variability in the performance of the GEC was not solely a function of malignancy prevalence and may have been attributable to intrinsic variability of the test sensitivity and specificity. The utility of the GEC in practice is elusive because of this variability. A better definition of the GEC's intrinsic properties is needed.

Optimal timing for a repeat fine-needle aspiration biopsy of thyroid nodule following an initial nondiagnostic fine-needle aspiration.

BACKGROUND: In the case of a nondiagnostic thyroid fine-needle aspiration (FNA) biopsy result, recent guidelines from the Bethesda system recommend repeat thyroid FNA after 3 months to prevent false-positive results. We aimed to examine our institutional data to determine whether the 3-month period affects the diagnostic yield of repeat biopsies. METHODS: A retrospective review of patient records over a 5-year period at our institution was performed. Patients who required repeat FNA due to nondiagnostic results were included. The time between the FNA biopsies, adequacy of the FNA specimens, as well as the surgical pathology diagnosis were analyzed. RESULTS: We identified 317 patients who required a repeat FNA. Of these, 96 (30.3%) patients had repeat FNAs less than 3 months after initial biopsy, while 221 (69.7%) patients had repeat FNAs in greater than 3 months. One hundred five patients were referred to our clinic with an initial nondiagnostic biopsy from an outside institution. Repeat FNA was nondiagnostic in 35 patients (11.04%) in the total study population. There was no difference in satisfactory diagnostic yield between repeat FNAs performed greater than 3 months (201 patients, 90.95%) or less than 3 months (81 patients, 84.38%) after the initial biopsy (P = .117). Of the 35 patients with repeat nondiagnostic biopsy, 17 patients underwent diagnostic lobectomy and 3 (17.6%) patients were found to have malignant disease. CONCLUSIONS: Early (<3 months) repeat FNA does not affect diagnostic yield of the subsequent sample. Patients with suspicious thyroid nodules could therefore receive a repeat FNA as soon as needed, rather than waiting 3 months. The shortened biopsy interval would alleviate stress on patients with benign nodules and expedite surgical intervention in patients with malignancy.

The significance of enlarged cervical lymph nodes in diagnosing thyroid cancer.

INTRODUCTION: We aim to investigate the significance of enlarged cervical lymph nodes (ECLN) identified by initial surgeon-performed ultrasound (US) as a tool for determining the risk of malignancy in the patients presenting with suspicious thyroid nodules. METHODS: Radiological and surgical reports were retrospectively reviewed for the patients with suspicious thyroid nodules who underwent thyroidectomy and preoperative comprehensive neck US. Ultrasonographic features of the identified cervical lymph nodes were correlated with the final pathology report. Patients with malignancy other than papillary thyroid cancer (PTC) were excluded. RESULTS: The study consisted of 440 patients. On final pathology, PTC was found in 142 patients (32.3%), the remaining 298 (67.7%) exhibited benign findings. ECLN (>1 cm) were found in 66 (46.5%) patient with PTC compared to only 53 (17.8%) patients with benign nodules (P < 0.001). Of the 119 patients with ECLN, 54.6% had benign appearing ECLN with no suspicious features, 26.1% had one suspicious feature, and 19.3% had more than one suspicious features. Benign appearing ECLN had a positive predictive value (PPV) of 41.54%, negative predictive value (NPV) of 59.02%, sensitivity of 51.92%, and specificity of 48.65% in predicting malignancy as opposed to the absence of ECLN. While as opposed to benign looking ECLN, ECLN with only one suspicious feature had a PPV of 70.97%, NPV of 50.00%, sensitivity of 33.33%, and specificity of 83.02%, and ECLN with two or more suspicious feature had a PPV of 73.91%, NPV of 48.96%, sensitivity of 25.76%, and specificity of 88.68%. CONCLUSION: ECLN are associated with an increased likelihood of thyroid malignancy in the patients undergoing evaluation of a suspicious nodule. The risk of malignancy in thyroid nodules increases with the presence of suspicious ultrasonographic features on cervical lymph nodes.

Impact of thyroidectomy on cardiac manifestations of Graves' disease.

OBJECTIVES/HYPOTHESIS: Graves' disease (GD) has multiple adverse effects on the cardiovascular system. We aimed to examine the outcome of thyroidectomy in patients with cardiac manifestations of GD and evaluate their associated postoperative complications. STUDY DESIGN: Retrospective analysis using a prospectively collected database. METHODS: A retrospective analysis of our prospectively collected thyroid surgery database was performed. Forty patients with hyperthyroidism due to GD were identified, and each was appropriately age matched to a euthyroid patient with multinodular goiter (MNG). All patients underwent total thyroidectomy. Data relating to cardiac comorbidities were collected from preoperative and postoperative clinic notes, hospital admissions, electrocardiograms, echocardiograms, and blood work. Perioperative biochemical, cardiovascular, and postoperative outcomes were analyzed. RESULTS: Twenty-four (60%) GD patients and 14 (35.0%) MNG patients had cardiac manifestations (P = .001). Hypertension resolved in 41.7% of GD patients and 7.7% of MNG patients (P = .00002). Two of the three GD patients with congestive heart failure (CHF) had resolution of CHF with significant improvement in ejection fraction, whereas the one MNG patient with CHF saw no change. Additionally, the majority of GD patients saw a resolution of their tachycardia (68.8%) and atrial fibrillation (100%). Four postoperative complications occurred in both the GD and MNG groups (4/40, 10%). CONCLUSIONS: Surgical treatment of GD in patients with cardiac manifestations offers rapid clinical improvement of hypertension, impaired left ventricular systolic function, and arrhythmias. When performed by a high-volume surgeon, the complication rate is similar to thyroidectomy for other benign disease. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1256-1259, 2016.

Evaluation of a Remote Monitoring System for Diabetes Control.

PURPOSE: The use of technology to implement cost-effective health care management on a large scale may be an alternative for diabetes management but needs to be evaluated in controlled trials. This study assessed the utility and cost-effectiveness of an automated Diabetes Remote Monitoring and Management System (DRMS) in glycemic control versus usual care. METHODS: In this randomized, controlled study, patients with uncontrolled diabetes on insulin were randomized to use of the DRMS or usual care. Participants in both groups were followed up for 6 months and had 3 clinic visits at 0, 3, and 6 months. The DRMS used text messages or phone calls to remind patients to test their blood glucose and to report results via an automated system, with no human interaction unless a patient had severely high or low blood glucose. The DRMS made adjustments to insulin dose(s) based on validated algorithms. Participants reported medication adherence through the Morisky Medication Adherence Scale-8, and diabetes-specific quality of life through the diabetes Daily Quality of Life questionnaire. A cost-effectiveness analysis was conducted based on the estimated overall costs of DRMS and usual care. FINDINGS: A total of 98 patients were enrolled (59 [60%] female; mean age, 59 years); 87 participants (89%) completed follow-up. HbA1c was similar between the DRMS and control groups at 3 months (7.60% vs 8.10%) and at 6 months (8.10% vs 7.90%). Changes from baseline to 6 months were not statistically significant for self-reported medication adherence and diabetes-specific quality of life, with the exception of the Daily Quality of Life-Social/Vocational Concerns subscale score (P = 0.04). IMPLICATIONS: An automated system like the DRMS may improve glycemic control to the same degree as usual clinic care and may significantly improve the social/vocational aspects of quality of life. Cost-effectiveness analysis found DRMS to be cost-effective when compared to usual care and suggests DRMS has a good scale of economy for program scale up. Further research is needed to determine how to sustain the benefits seen with the automated system over longer periods.

Examining the Bethesda criteria risk stratification of thyroid nodules.

BACKGROUND: The Bethesda criteria are proposed for appropriate stratification of malignancy risk in thyroid nodules, but controversy exists regarding their accuracy and reliability in decision making. Additionally, previous studies have suggested higher rates of both malignancy and false negative fine needle aspiration biopsy (FNA) associated with increasing nodule size. This study aims to determine the accuracy of ultrasound (US)-guided FNA using the current Bethesda criteria in surgical practice. We also aimed to investigate the relationship between nodule size and malignancy. METHODS: A retrospective analysis of US-guided FNAs by a single surgeon during a 4.5 year period. FNA results using Bethesda criteria were compared to final surgical pathology. RESULTS: 611 patients with thyroid nodules underwent US-guided FNA. FNA results in 375 subsequently excised thyroid nodules were recorded according to the Bethesda criteria: 192 (51%) benign, 65 (17%) atypia of unknown significance/follicular lesion of undetermined significance (AUS/FLUS), 42 (11%), suspicious for follicular neoplasm (SFN), 17 (5%) suspicious for malignancy (SM), 28 (8%) malignancy, and 31 (8%) non-diagnostic. Malignancy was confirmed by surgical pathology in 15%, 34%, 50%, 88%, 100%, and 39% of the above groups respectively. Sensitivity, specificity, and false-negative rate were 61%, 99%, and 15% respectively. No correlation existed between the size of nodules with indeterminate FNA results and malignancy rate (p=0.89), or size of nodules with non-diagnostic FNA and malignancy rate (p=0.50). CONCLUSION: The current Bethesda risk stratification system underestimated malignancy rates in benign, indeterminate and non-diagnostic cytopathologic categories in our experience. There was no positive linear correlation between nodule size and malignancy rate in these cytopathologic categories.