Optimal hyperglycemia thresholds in patients undergoing chemotherapy: a cross sectional study of oncologists' practices.

PURPOSE: Neither the United States nor the European oncology guidelines include details for appropriate management of hyperglycemia in cancer patients. The aim was to identify fasting and random blood glucose thresholds, and hemoglobin A1c (HbA1c) targets used by oncologists in clinical practice when managing hyperglycemia in patients with cancer undergoing chemotherapy. METHODS: This national, cross sectional study utilized a questionnaire to collect oncologists' perceptions about optimal blood glucose thresholds and HbA1c targets in patients with cancer undergoing chemotherapy. Descriptive statistics were calculated to summarize glucose thresholds, HbA1c targets, and sample characteristics. Responses to an open-ended question about oncologists' approach to hyperglycemia management were analyzed via thematic analysis using an inductive approach. RESULTS: Respondents (n = 229) were on average 52.1 years of age, 67.7% men, and 91.3% White. For patients without diabetes but experiencing hyperglycemia, oncologists targeted lower and upper fasting blood glucose levels between 75-121 mg/dL and 105-135 mg/dL, respectively. For patients with diabetes, the targets for lower and upper fasting blood glucose levels ranged between 100-130 mg/dL and 128-150 mg/dL, respectively. Fasting blood glucose (95.6%) and HbA1c (78.6%) were the most commonly used clinical indicators to consider chemotherapy dose reduction, delay, or discontinuation due to hyperglycemia in patients receiving chemotherapy with curative intent. Among those receiving palliative intent chemotherapy, the preferred clinical parameters were random blood glucose (90.0%), patient-reported blood glucose readings (70.7%), continuous glucose monitoring readings (65.1%), and patient-reported symptoms of hyperglycemia (65.1%). Three main themes emerged about oncologists' approach to hyperglycemia management: 1) identification of high-risk patients; 2) need for early identification, screening, and diagnosis of hyperglycemia; and 3) multiple hyperglycemia management strategies. CONCLUSION: Oncologists reported a wide variation of target blood glucose ranges considered appropriate in patients undergoing chemotherapy. Lack of clear guidance for hyperglycemia management during chemotherapy in the United States may be contributing to a lack of consistency in clinical practice.

Oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients with cancer undergoing chemotherapy: a cross sectional study.

PURPOSE: To assess oncologists' responsibility, comfort, and knowledge managing hyperglycemia in patients undergoing chemotherapy. METHODS: In this cross-sectional study, a questionnaire collected oncologists' perceptions about professionals responsible for managing hyperglycemia during chemotherapy; comfort (score range 12-120); and knowledge (score range 0-16). Descriptive statistics were calculated including Student t-tests and one-way ANOVA for mean score differences. Multivariable linear regression identified predictors of comfort and knowledge scores. RESULTS: Respondents (N = 229) were 67.7% men, 91.3% White and mean age 52.1 years. Oncologists perceived endocrinologists/diabetologists and primary care physicians as those responsible for managing hyperglycemia during chemotherapy, and most frequently referred to these clinicians. Reasons for referral included lack of time to manage hyperglycemia (62.4%), belief that patients would benefit from referral to an alternative provider clinician (54.1%), and not perceiving hyperglycemia management in their scope of practice (52.4%). The top-3 barriers to patient referral were long wait times for primary care (69.9%) and endocrinology (68.1%) visits, and patient's provider outside of the oncologist's institution (52.8%). The top-3 barriers to treating hyperglycemia were lack of knowledge about when to start insulin, how to adjust insulin, and what insulin type works best. Women (ß = 1.67, 95% CI: 0.16, 3.18) and oncologists in suburban areas (ß = 6.98, 95% CI: 2.53, 11.44) had higher comfort scores than their respective counterparts; oncologists working in practices with > 10 oncologists had lower comfort scores (ß = -2.75, 95% CI: -4.96, -0.53) than those in practices with ≤ 10. No significant predictors were identified for knowledge. CONCLUSION: Oncologists expected endocrinology or primary care clinicians to manage hyperglycemia during chemotherapy, but long wait times were among the top barriers cited when referring patients. New models that provide prompt and coordinated care are needed.

Salvage Cryoablation for Local Recurrences of Thyroid Cancer Inseparable from the Trachea and Neurovascular Structures.

PURPOSE: To demonstrate safety, feasibility, and effectiveness of cryoablation of recurrent papillary thyroid cancer ineligible for reoperation because of scarring, eligible for focal ablation as defined within 2015 American Thyroid Association guideline sections C16 and C17. MATERIALS AND METHODS: With multidisciplinary consensus, cryoablation was performed with curative intent for 15 tumors in 10 patients between January 2019 and July 2021. Demographics, procedural details, and serial postprocedural imaging findings were analyzed. RESULTS: The mean age was 72.5 years (range, 57-88 years), and 80% of the patients were women. The tumors (mean size, 16 mm ± 6; range, 9-29 mm) received 1 session of cryoablation with 100% technical success. The mean and median postcryoablation tumor volumetric involution rates were 88% and 99%, respectively, with 9 (60%) of 15 tumors involuting completely or down to the scar and 6 (40%) involuting partially at the end of the study period. Tumor size did not increase after cryoablation (0% local progression rate). All tumors abutted the trachea, skin, and/or vascular structures, and hydrodissection failed in all cases because of scarring. The major adverse event rate was 20% (3/15), with 2 cases of voice change and 1 case of Horner syndrome; all resolved at 6 months with no permanent sequelae. No vascular, tracheal, dermal, or infectious adverse events occurred during a mean follow-up of 242 days (range, 114-627 days). One patient died at 386 days after cryoablation because of unrelated cholangiocarcinoma. CONCLUSIONS: Cryoablation of local recurrences of papillary thyroid cancer abutting the trachea and/or neurovascular structures in the setting of hydrodissection failure because of scarring yielded a mean volumetric involution of 88%, primary efficacy of 60%, and objective response rate of 100% with no local recurrences or permanent complications during a mean follow-up of 242 days. The secondary efficacy and longer-term outcomes remain forthcoming.

Towards De-Implementation of low-value thyroid care in older adults.

PURPOSE OF REVIEW: This review discusses the current literature regarding low-value thyroid care in older adults, summarizing recent findings pertaining to screening for thyroid dysfunction and management of hypothyroidism, thyroid nodules and low-risk differentiated thyroid cancer. RECENT FINDINGS: Despite a shift to a "less is more" paradigm for clinical thyroid care in older adults in recent years, current studies demonstrate that low-value care practices are still prevalent. Ineffective and potentially harmful services, such as routine treatment of subclinical hypothyroidism which can lead to overtreatment with thyroid hormone, inappropriate use of thyroid ultrasound, blanket fine needle aspiration biopsies of thyroid nodules, and more aggressive approaches to low-risk differentiated thyroid cancers, have been shown to contribute to adverse effects, particularly in comorbid older adults. SUMMARY: Low-value thyroid care is common in older adults and can trigger a cascade of overdiagnosis and overtreatment leading to patient harm and increased healthcare costs, highlighting the urgent need for de-implementation efforts.

Postoperative Surveillance in Older Adults With T1N0M0 Low-risk Papillary Thyroid Cancer.

BACKGROUND: The frequency and cost of postoperative surveillance for older adults (>65 y) with T1N0M0 low-risk papillary thyroid cancer (PTC) have not been well studied. METHODS: Using the SEER-Medicare (2006-2013) database, frequency and cost of surveillance concordant with American Thyroid Association (ATA) guidelines (defined as an office visit, ≥1 thyroglobulin measurement, and ultrasound 6- to 24-month postoperatively) were analyzed for the overall cohort of single-surgery T1N0M0 low-risk PTC, stratified by lobectomy versus total thyroidectomy. RESULTS: Majority of 2097 patients in the study were white (86.7%) and female (77.5%). Median age and tumor size were 72 y (interquartile range 68-76) and 0.6 cm (interquartile range 0.3-1.1 cm), respectively; 72.9% of patients underwent total thyroidectomy. Approximately 77.5% of patients had a postoperative surveillance visit; however, only 15.9% of patients received ATA-concordant surveillance. Patients who underwent total thyroidectomy as compared with lobectomy were more likely to undergo surveillance testing, thyroglobulin (61.7% versus 24.8%) and ultrasound (37.5% versus 29.2%) (all P < 0.01), and receive ATA-concordant surveillance (18.5% versus 9.0%, P < 0.001). Total surveillance cost during the study period was $621,099. Diagnostic radioactive iodine, ablation, and advanced imaging (such as positron emission tomography scans) accounted for 55.5% of costs ($344,692), whereas ATA-concordant care accounted for 44.5% of costs. After multivariate adjustment, patients who underwent total thyroidectomy as compared with lobectomy were twice as likely to receive ATA-concordant surveillance (adjusted odds ratio 2.0, 95% confidence interval: 1.5-2.8, P < 0.001). CONCLUSIONS: Majority of older adults with T1N0M0 low-risk PTC do not receive ATA-concordant surveillance; discordant care was costly. Total thyroidectomy was the strongest predictor of receiving ATA-concordant care.

Best Practices in Transgender Health: A Clinician's Guide.

Providing culturally competent and medically knowledgeable care to the transgender community is increasingly falling within the realms of practice for primary care providers. The purpose of this article is to provide an overview of best practices as they relate to transgender care. This article is by no means a comprehensive guide, but rather a starting point for clinicians as they provide high-quality care to their transgender patients.

A practical method of I-131 thyroid cancer therapy dose optimization using estimated effective renal clearance.

In thyroid cancer patients with renal impairment or other complicating factors, it is important to maximize I-131 therapy efficacy while minimizing bone marrow and lung damage. We developed a web-based calculator based on a modified Benua and Leeper method to calculate the maximum I-131 dose to reduce the risk of these toxicities, based on the effective renal clearance of I-123 as measured from two whole-body I-123 scans, performed at 0 and 24 h post-administration.

The Impact of Pathologically Positive Lymph Nodes in the Clinically Negative Neck: An Analysis of 39,301 Patients with Papillary Thyroid Cancer.

PURPOSE: Management of patients with low-risk papillary thyroid cancer (PTC) with clinically uninvolved lymph nodes (cN0 LNs), but who harbor metastatic central LNs (pN1a), remains unclear. The number of central LNs examined, radioactive iodine (RAI) utilization, and survival were compared across cN0 patients based on pN stage: pN0 (negative) versus pNx (unknown) versus pN1a (pathologically positive). METHODS: Adults with a PTC ≥1 cm who were cN0 preoperatively were compared based on surgical pathology using the National Cancer Data Base (NCDB; 2003-2011), after univariate and multivariate adjustment. Overall survival (OS) was examined using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards modeling. RESULTS: Overall, 39,301 patients were included; median tumor size was 1.9 cm. More LNs were examined for pN1a versus pN0 diagnosis (pN1a median = 5 LNs vs. pN0 median = 2 LNs; p < 0.0001), with a median of two central LNs found to be positive on surgical resection. Compared with pN0, pN1a patients were 78% more likely to receive RAI (odds ratio 1.78, 95% confidence interval [CI] 1.65-1.91; p < 0.0001). After adjusting for receipt of RAI, no difference in OS was observed for pN1a versus pN0 or pNx patients (p = 0.72). Treatment with RAI was associated with improved OS (hazard ratio 0.78, 95% CI 0.62-0.98, p = 0.03), but the effect of RAI did not differ based on pN stage (interaction p = 0.67). CONCLUSION: More LNs were examined for positive versus negative pN diagnosis in patients with cN0 PTC. Unsuspected central neck nodal metastases in cN0 PTC patients are associated with increased RAI utilization, but no survival difference.

Comparative effects of acute hypoglycemia and hyperglycemia on pro-atherothrombotic biomarkers and endothelial function in non-diabetic humans.

BACKGROUND: The comparative effects of acute moderate hyperglycemia and hypoglycemia on in vivo endothelial function together with pro-inflammatory and pro-atherothrombotic responses in healthy individuals have not been determined. METHODS: To investigate this question, 45 healthy subjects were compared during glucose clamp studies consisting of euinsulinemic hyperglycemia and hyperinsulinemic hyperglycemia (plasma glucose 11.1mmol/L, both with pancreatic clamps) and hyperinsulinemic euglycemia and hyperinsulinemic hypoglycemia (plasma glucose 5.1 and 2.9mmol/L, respectively). Two-dimensional Doppler ultrasound was used to determine brachial artery endothelial function. RESULTS: Insulin levels during euinsulinemia hyperglycemia were 194±23 and (850±49-988±114) pmol/L during all hyperinsulinemic protocols. Responses of VCAM-1, ICAM-1, E-selectin, P-selectin, PAI-1, and IL-6 were increased (p<0.05-0.0001) during euinsulinemic hyperglycemia or hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia. PAI-1 was increased (p<0.04) during hypoglycemia as compared to euinsulinemic hyperglycemia, and TNF-α responses were also increased during hypoglycemia as compared to hyperinsulinemic euglycemia or hyperinsulinemic hyperglycemia (p<0.05). In vivo endothelial function was similarly blunted by acute moderate hyperglycemia or hypoglycemia. CONCLUSION: In summary, acute moderate hypoglycemia and euinsulinemic hyperglycemia can result in similar endothelial dysfunction and pro-atherothrombotic responses. Fibrinolytic balance was reduced by a greater extent by hypoglycemia as compared to moderate hyperglycemia. Acutely, hyperinsulinemia can prevent the acute pro-atherothrombotic and pro-inflammatory effects of moderate hyperglycemia but not hypoglycemia.

Knowledge of pathologically versus clinically negative lymph nodes is associated with reduced use of radioactive iodine post-thyroidectomy for low-risk papillary thyroid cancer.

Cervical lymph node metastases are common in papillary thyroid cancer (PTC). Clinically negative lymph nodes confer uncertainty about true lymph node status, potentially prompting empiric postoperative radioactive iodine (RAI) administration even in low-risk patients. We examined the association of clinically (cN0) versus pathologically negative (pN0) lymph nodes with utilization of RAI for low-risk PTC. Using the National Cancer Database 1998-2011, adults with PTC who underwent total thyroidectomy for Stage I/II tumors 1-4 cm were evaluated for receipt of RAI based on cN0 versus pN0 status. Cut-point analysis was conducted to determine the number of pN0 nodes associated with the greatest decrease in the odds of receipt of RAI. Survival models and multivariate analyses predicting RAI use were conducted separately for all patients and patients <45 years. 64,980 patients met study criteria; 39,778 (61.2 %) were cN0 versus 25,202 (38.8 %) pN0. Patients with pN0 nodes were more likely to have negative surgical margins and multifocal disease (all p < 0.001). The mean negative nodes reported in surgical pathology specimens was 4; ≥5 pathologically negative lymph nodes provided the best cut-point associated with reduced RAI administration (OR 0.91, CI 0.85-0.97). After multivariable adjustment, pN0 patients with ≥5 nodes examined were less likely to receive RAI compared to cN0 patients across all ages (OR 0.89, p < 0.001) and for patients aged <45 years (0R 0.86, p = 0.001). Patients with <5 pN0 nodes did not differ in RAI use compared to cN0 controls. Unadjusted survival was improved for pN0 versus cN0 patients across all ages (p < 0.001), but not for patients <45 years (p = 0.11); adjusted survival for all ages did not differ (p = 0.13). Pathological confirmation of negative lymph nodes in patients with PTC appears to influence the decision to administer postoperative RAI if ≥5 negative lymph nodes are removed. It is possible that fewer excised lymph nodes may be viewed by clinicians as incidentally resected and thus may suboptimally represent the true nodal status of the central neck. Further research is warranted to determine if there is an optimal number of lymph nodes that should be resected to standardize pathological diagnosis.

Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans.

We investigated the separate and combined effects of hyperglycemia and hyperinsulinemia on markers of endothelial function, proinflammatory and proatherothrombotic responses in overweight/obese nondiabetic humans. Twenty-two individuals (13 F/9 M, BMI 30.1 ± 4.1 kg/m(2)) were studied during four randomized, single-blind protocols. The pancreatic clamp technique was combined with 4-h glucose clamps consisting of either 1) euinsulinemia-euglycemia, 2) euinsulinemia-hyperglycemia, 3) hyperinsulinemia-hyperglycemia, or 4) hyperinsulinemia-euglycemia. Insulin levels were higher (998 ± 66 vs. 194 ± 22 pmol/l) during hyperinsulinemia compared with euinsulinemia. Glucose levels were 11.1 mmol/l during hyperinsulinemia compared with 5.1 ± 0.1 mmol/l during euglycemia. VCAM, ICAM, P-selectin, E-selectin, IL-6, adiponectin, and PAI-1 responses were all increased (P < 0.01-0.0001), and endothelial function was decreased (P < 0.0005) during euinsulinemia-hyperglycemia compared with other protocols. Hyperinsulinemia in the presence of hyperglycemia prevented the increase in proinflammatory and proatherothrombotic markers while also normalizing vascular endothelial function. We conclude that 4 h of moderate hyperglycemia can result in increases of proinflammatory markers (ICAM, VCAM, IL-6, E-selectin), platelet activation (P-selectin), reduced fibrinolytic balance (increased PAI-1), and disordered endothelial function in a group of obese and overweight individuals. Hyperinsulinemia prevents the actions of moderate hyperglycemia to reduce endothelial function and increase proinflammatory and proatherothrombotic markers.

Adjuvant radioactive iodine therapy is associated with improved survival for patients with intermediate-risk papillary thyroid cancer.

CONTEXT: Papillary thyroid cancer (PTC) is the most common endocrine malignancy. The long-term prognosis is generally excellent. Due to a paucity of data, debate exists regarding the benefit of adjuvant radioactive iodine therapy (RAI) for intermediate-risk patients. OBJECTIVE: The objective of the study was to examine the impact of RAI on overall survival in intermediate-risk PTC patients. DESIGN/SETTING: Adult patients with intermediate-risk PTC who underwent total thyroidectomy with/without RAI in the National Cancer Database, 1998-2006, participated in the study. PATIENTS: Intermediate-risk patients, as defined by American Thyroid Association risk and American Joint Commission on Cancer disease stage T3, N0, M0 or Mx, and T1-3, N1, M0, or Mx were included in the study. Patients with aggressive variants and multiple primaries were excluded. MAIN OUTCOME MEASURES: Overall survival (OS) for patients treated with and without RAI using univariate and multivariate regression analyses was measured. RESULTS: A total of 21 870 patients were included; 15 418 (70.5%) received RAI and 6452 (29.5%) did not. Mean follow-up was 6 years, with the longest follow-up of 14 years. In an unadjusted analysis, RAI was associated with improved OS in all patients (P < .001) as well as in a subgroup analysis among patients younger than 45 years (n = 12 612, P = .002) and 65 years old and older (median OS 140 vs 128 mo, n = 2122, P = .008). After a multivariate adjustment for demographic and clinical factors, RAI was associated with a 29% reduction in the risk of death, with a hazard risk 0.71 (95% confidence interval 0.62-0.82, P < .001). For age younger than 45 years, RAI was associated with a 36% reduction in risk of death, with a hazard risk 0.64 (95% confidence interval 0.45- 0.92, P = .016). CONCLUSION: This is the first nationally representative study of intermediate-risk PTC patients and RAI therapy demonstrating an association of RAI with improved overall survival. We recommend that this patient group should be considered for RAI therapy.

Appropriate dosing of adjuvant radioactive iodine for differentiated thyroid cancer.

PURPOSE OF REVIEW: The incidence of well differentiated thyroid cancer (WDTC) is increasing in the US population and is now a major public health concern. Although surgery is the mainstay of treatment, radioactive iodine (RAI) is routinely used for adjuvant therapy, remnant ablation, and for the treatment of metastatic disease. Despite excellent prognosis and stable mortality rates, the use of RAI is increasing in many low and intermediate risk WDTC patients without clear indication that it changes the outcome. As a result, the current treatment paradigm has shifted towards a risk-stratified approach. RECENT FINDINGS: Although there is widespread acceptance that RAI improves overall and recurrence-free survival in patients with metastatic disease, controversy remains regarding radioactive remnant ablation use in low and intermediate risk patients. Additional studies have shown that reduced doses of RAI can provide similar rates of remnant ablation and adjuvant therapy in low and intermediate risk patients without adversely affecting the recurrence rates and mortality. SUMMARY: Recent studies suggest potential new paradigms in radioactive remnant ablation dosing and indications for use. Risk stratification is important in determining the proper use and dosing of RAI.

The renin-angiotensin-aldosterone system: a pivotal role in insulin sensitivity and glycemic control.

PURPOSE OF REVIEW: Diabetes mellitus is an exploding epidemic costing billions of dollars yearly. Type 2 diabetes mellitus is characterized by insulin resistance and is closely associated with arterial hypertension. Emerging literature has demonstrated that modulation of the renin-angiotensin-aldosterone system by use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers leads to improved insulin sensitivity, glycemic control and possibly prevention of type 2 diabetes mellitus. RECENT FINDINGS: Several major studies investigating angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use in either hypertensive or heart failure patients have found lower incidence of type 2 diabetes mellitus when compared with placebo, beta-blocker, calcium-channel blocker or diuretic. None of these trials, however, studied prevention of diabetes as a primary endpoint. The Dream Trial and upcoming NAVIGATOR, ONTARGET/TRANSCEND trials specifically look at the prevention of diabetes as a primary endpoint. Several studies have evaluated possible mechanisms of how the renin-angiotensin-aldosterone system can alter insulin sensitivity and glycemic control. SUMMARY: This review will focus on the recent literature that demonstrates renin-angiotensin-aldosterone system modulation and its effects on diabetes prevention, glycemic control and insulin sensitivity, as well as possible mechanisms for achieving this goal.

Endocannabinoid system overactivity and the metabolic syndrome: prospects for treatment.

The endocannabinoid system (ECS) plays a physiologic role in modulating energy balance, feeding behavior, lipoprotein metabolism, insulin sensitivity, and glucose homeostasis, which when dysregulated can all contribute to cardiometabolic risk. Evidence has suggested that the ECS is overactive in human obesity and in animal models of genetic and diet-induced obesity. ECS stimulation centrally and peripherally drives metabolic processes that mimic the metabolic syndrome. These findings have led to the development of potential novel therapeutic targets, including the drug rimonabant, a selective CB1 receptor antagonist, which has been shown to promote weight loss, reduce inflammation, improve dyslipidemia, and improve glucose homeostasis.

Role of the endocannabinoid system in management of patients with type 2 diabetes mellitus and cardiovascular risk factors.

OBJECTIVE: To review the role of the endogenous cannabinoid system (ECS) in the peripheral and central regulation of food intake, appetite, and energy storage and discuss the potential for the ECS to be an important target for lowering cardiovascular risk. METHODS: Materials used for this article were identified through a MEDLINE search of the pertinent literature (1975 to present), including English-language randomized controlled, prospective, cohort, review, and observational studies. We summarize the available experimental and clinical data. RESULTS: The ECS is composed of two 7-transmembrane G protein-coupled cannabinoid receptor subtypes, CB1 and CB2, endogenous cannabinoid ligands (anandamide and 2-arachidonoylglycerol), and the enzymes that synthesize and break down the ligands. Understanding the role of the ECS in central and peripheral metabolic processes related to the regulation of food intake and energy balance as well as the endocrine role of excess adipose tissue, particularly visceral adipose tissue, and its promotion of global cardiometabolic risk has led to the development of pharmacologic agents with potential for blockade of CB1 receptors. In several studies, rimonabant (20 mg daily) demonstrated a favorable effect on various risk factors for cardiovascular disease, including dyslipidemia, abdominal obesity, insulin resistance, blood pressure, and measures of inflammation. CONCLUSION: The ECS has been shown to have a key role in the regulation of energy balance, and modulation of this system may affect multiple cardiometabolic risk factors. Clinical studies involving pharmacologic blockade of CB1 receptors in overweight patients with and without type 2 diabetes have demonstrated effective weight loss and improvements in several risk factors for cardiovascular disease.