A review of air pollution as a driver of cardiovascular disease risk across the diabetes spectrum.

The prevalence of diabetes is estimated to reach almost 630 million cases worldwide by the year 2045; of current and projected cases, over 90% are type 2 diabetes. Air pollution exposure has been implicated in the onset and progression of diabetes. Increased exposure to fine particulate matter air pollution (PM2.5) is associated with increases in blood glucose and glycated hemoglobin (HbA1c) across the glycemic spectrum, including normoglycemia, prediabetes, and all forms of diabetes. Air pollution exposure is a driver of cardiovascular disease onset and exacerbation and can increase cardiovascular risk among those with diabetes. In this review, we summarize the literature describing the relationships between air pollution exposure, diabetes and cardiovascular disease, highlighting how airborne pollutants can disrupt glucose homeostasis. We discuss how air pollution and diabetes, via shared mechanisms leading to endothelial dysfunction, drive increased cardiovascular disease risk. We identify portable air cleaners as potentially useful tools to prevent adverse cardiovascular outcomes due to air pollution exposure across the diabetes spectrum, while emphasizing the need for further study in this particular population. Given the enormity of the health and financial impacts of air pollution exposure on patients with diabetes, a greater understanding of the interventions to reduce cardiovascular risk in this population is needed.

Indolent behavior of malignant Bethesda III nodules compared to Bethesda V/VI nodules.

BACKGROUND: The Bethesda System classifies all fine needle aspiration specimens into one of six categories. We speculated that cancers within each Bethesda category would have distinct clinical behavior. METHODS: This is a retrospective analysis of patients from a single academic medical center with a histologic diagnosis of thyroid cancer who had an initial diagnosis of Bethesda III, IV, V, or VI cytology. RESULTS: A total of 556 cases were included, with 87 cases of Bethesda III, 109 cases of IV, 120 cases of V, and 240 cases of VI. Bethesda III showed similarities with V/VI compared to IV with predominance of papillary thyroid cancer. The interval from diagnosis to surgery was longer in Bethesda III compared to Bethesda V/VI (median 78 vs. 41 days, p<0.001) (Figure 1). Yet, patients with Bethesda III had a higher probability of achieving remission (62 vs.46 %, p<0.03), a lower possibility of recurrence (8 vs. 24%, p<0.001) and a shorter interval to achieve remission (median 1218 vs.1682 days p = 0.02) compared to Bethesda V/VI which did not change after adjusting for age, gender, radioactive iodine therapy, mode of surgery and tumor size. More than 70% of Bethesda III that later presented with recurrence had T3/T4 disease or distant metastasis. CONCLUSIONS: Cancers with Bethesda III cytology had a less aggressive clinical phenotype with better prognosis compared to V/VI despite histological similarities. The time to remission was shorter in Bethesda III despite a longer interval between diagnosis and surgery. The initial cytological diagnosis may guide management.

Reviewing the cardiovascular and other health effects of olive oil: Limitations and future directions of current supplement formulations.

AIMS: We reviewed the literature to date for high-level evidence on the cardiovascular and other health effects of olive oil with a focus on the amount, frequency of use and type of olive oil consumed in prior studies. A total of twelve prospective cohort studies with sample sizes of at least 4000 individuals and one meta-analysis were identified. DATA SYNTHESIS: The majority of cohorts followed individuals aged ≥55 years old, free of cardiovascular disease (CVD) at baseline but at high risk, over periods of 4-10 years and with daily consumption amounts of 10-35 g/day. With the exception of the PREDIMED cohort that employed extra virgin olive oil, most remaining studies did not differentiate between different types of olive oil. Taken together, the data suggests an association between greater olive oil consumption and a lower CVD incidence/mortality and stroke risk. We use this information to evaluate the use of commercially available, capsule-based olive oil dietary supplements and suggest future directions. Notably, achieving minimum total daily doses described in the aforementioned studies would be challenging with current market formulations of olive oil supplements dosed at 1-1.25 g/capsule. CONCLUSIONS: Outside of mechanistic studies, little progress has been made in determining the olive oil component(s) underlying the observed health effects given the lack of compositional reporting and consistency across large scale human studies. We propose the use of supplements of varying composition, such as varying total phenolic content, in pragmatic trial designs focused on low-cost methodologies to address this question.

The Current Status of Preclinical Endocrine Education in U.S. Medical Schools.

OBJECTIVE: To characterize the current landscape of preclinical medical endocrine education in U.S. allopathic medical schools. METHODS: U.S. endocrine curriculum directors were asked to voluntarily complete a 16-question email survey surveying the status of endocrine preclinical education at their medical school. RESULTS: Sixty-nine of 155 (45%) endocrine block director respondents completed the online survey between July 2021 and September 2021. A larger incoming class, a longer duration of the endocrine curriculum, and the offering of a separate endocrine curriculum (ie apart from the teaching of other organ systems) were each independently associated with an increased number of faculty teaching the course. Schools that used a gland-/organ-based curriculum only and those that used a combination of gland-/organ-based curriculum with topic-based curriculum differed significantly in their use of large lectures, small groups, and several curriculum components, including point of care glucose testing, continuous glucose monitoring, and insulin pumps. CONCLUSION: This survey study reports the current landscape of preclinical endocrine education in the United States and describes opportunities to improve interest in pursuing endocrinology as a career.

Driving Factors to Pursue Endocrinology Training Fellowship: Empirical Survey Data and Future Strategies.

OBJECTIVE: There is a current and anticipated labor shortage of endocrinologists in the United States. Over the past decade, the number of applications to endocrinology fellowship programs has plateaued despite increased available positions, and interest in endocrinology has declined relative to other internal medicine subspecialty fields. The examination of driving factors for pursuit of endocrinology as a subspecialty career is needed. METHODS: A 12-question online survey was developed to identify the primary reasons for current endocrinology fellows/trainees to pursue the field. This survey was sent to 152 U.S. endocrinology fellowship program directors for completion by their fellows between July and August 2021. RESULTS: A total of 176 of 629 fellows (28.0%) completed the survey. The majority (57.4%) had decided to pursue endocrinology as a career during residency, while 27.3% had decided during medical school. The endocrinology rotation during residency was ranked by 79 fellows (44.9%) as the most influential factor, followed by having positive experiences with a clinical mentor (27.3%). Endocrinology exposure during medical school was sparse, with only 2.8% noting the availability of an endocrinology student interest group, while 59.7% reported inadequate endocrinology exposure during their medical school curriculum. CONCLUSION: The majority of current endocrinology fellows/trainees report that exposure to the field during medical school was limited, and that their endocrinology elective and mentorship experiences during residency were the most influential factors for pursuing endocrinology as a subspecialty. Improved integration of endocrinology experiences between medical school and residency may enhance career interest in endocrinology.

Prevalence of cancer and the benign call rate of afirma gene classifier in 18 F-Fluorodeoxyglucose positron emission tomography positive cytologically indeterminate thyroid nodules.

BACKGROUND: 18 F-Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) positive (PET+) cytologically indeterminate thyroid nodules (ITNs) have variable cancer risk in the literature. The benign call rate (BCR) of Afirma Gene Classifier (Gene Expression Classifier, GEC, or Genome Sequence Classifier, GSC) in (PET +) ITNs is unknown. METHODS: This is a retrospective study at our institution of all patients with (PET+) ITNs (Bethesda III/IV) from 1 January 2010 to 21 May 2019 who underwent Afirma testing and/or surgery or repeat FNA with benign cytology. RESULTS: Forty-five (PET+) ITNs were identified: 31 Afirma-tested (GEC = 20, GSC = 11) and 14 either underwent surgery (n = 13) or repeat FNA (Benign cytology) (n = 1) without Afirma. The prevalence of cancer and noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including only resected nodules and ITN with repeat benign FNA (n = 33) was 36.4% (12/33). Excluding all Afirma "suspicious" non-resected ITNs and assuming all Afirma "benign" ITNs were truly benign, that prevalence was 28.6% (12/42). The BCR with GSC was 64% compared to 25% with GEC (p = 0.056). Combining GSC/GEC-tested ITNs, the BCR was higher in ITNs demonstrating low/very low-risk sonographic pattern by the American Thyroid Association (ATA) classification and ITNs scoring <4 by the American College of Radiology Thyroid Imaging, Reporting and Data System (ACR-TI-RADS) than ITNs with higher sonographic pattern/score (p = 0.025). CONCLUSIONS: The prevalence of cancer/NIFTP in (PET+) ITNs was 28.6-36.4% depending on the method of calculation. The BCR of Afirma GSC was 64%. Combining Afirma GEC/GSC-tested ITNs, BCR was higher in ITNs with a lower risk sonographic pattern.

Features of Cytologically Indeterminate Molecularly Benign Nodules Treated With Surgery.

BACKGROUND: Most cytologically indeterminate thyroid nodules (ITNs) with benign molecular testing are not surgically removed. The data on clinical outcomes of these nodules are limited. METHODS: We retrospectively analyzed all ITNs where molecular testing was performed either with the Afirma gene expression classifier or Afirma gene sequencing classifier between 2011 and 2018 at a single institution. RESULTS: Thirty-eight out of 289 molecularly benign ITNs were ultimately resected. The most common reason for surgery was compressive symptoms (39%). In multivariable modeling, patients aged <40 years, nodules ≥3 cm, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with higher surgery rates with hazard ratios for surgery of 3.5 (P < 0.001), 3.2 (P < 0.001), 16.8 (P < 0.001), and 7.31 (P < 0.001), respectively. Of resected nodules, 5 were malignant. False-negative rate (FNR) was 1.7%, presuming all unresected nodules were truly benign and 13.2% restricting analysis to resected cases. The FNR was significantly higher in nodules with a high-risk sonographic appearance for cancer (American Thyroid Association high-risk classification and American College of Radiology Thyroid Imaging Reporting and Data Systems score of 5) compared with nodules with all other sonographic categories (11.8% vs 1.1%; P = 0.03 and 11.1% vs 1.1%; P = 0.02, respectively). CONCLUSIONS: Younger age, larger nodule size, presence of an Afirma suspicious nodule other than the index nodule, and compressive symptoms were associated with a higher rate of surgery. The FNR of benign Afirma was significantly higher in nodules with high-risk sonographic features.

Hypoglycemia awareness and burden among hospitalized patients at high risk for hypoglycemia.

BACKGROUND: Hypoglycemia, a common complication of insulin therapy in patients with diabetes, is associated with increased hospital morbidity and mortality. Hypoglycemia may be underrecognized in hospitalized patients due to impaired counter regulation or reduced recognition. Beta blocker (BB) use may also affect hypoglycemia recognition. AIM: To characterize hypoglycemia unawareness and patient perceived hypoglycemia burden in hospitalized patients. MATERIALS AND METHODS: Over a 2-month period, we prospectively identified non-critically ill cognitively intact hospitalized insulin-requiring patients who were undergoing bedside glucose monitoring. Participants were included if they reported any episode of hypoglycemia in the 30 days prior to admission and either had no BB use or were on stable BB for 90 days. Hypoglycemia unawareness was assessed using the Clarke score and burden of hypoglycemia was assessed with the (TRIM-HYPO) score. RESULTS: Of the 46 participants, 20 were not taking a BB and 26 were taking a BB. Predictors of hypoglycemia during admission included glucose coefficient of variation and hospital length of stay. Nine participants (20%) had hypoglycemia unawareness (Clarke score ≥4). Participants with a history of coronary artery disease were less likely to have impaired awareness. Burden of hypoglycemia was associated with more hypoglycemia and longer hospital length of stay. There were no differences in measures of hypoglycemia unawareness or burden according to BB use. CONCLUSIONS: BB use was not related to hypoglycemia unawareness, or burden in hospitalized high risk patients. Hypoglycemia burden may identify patients at higher risk of hypoglycemia during admission.

Effect of beta blocker use and type on hypoglycemia risk among hospitalized insulin requiring patients.

BACKGROUND: Although beta blockers could increase the risk of hypoglycemia, the difference between subtypes on hypoglycemia and mortality have not been studied. This study sought to determine the relationship between type of beta blocker and incidence of hypoglycemia and mortality in hospitalized patients. METHODS: We retrospectively identified non-critically ill hospitalized insulin requiring patients who were undergoing bedside glucose monitoring and received either carvedilol or a selective beta blocker (metoprolol or atenolol). Patients receiving other beta blockers were excluded. Hypoglycemia was defined as any glucose < 3.9 mmol/L within 24 h of admission (Hypo1day) or throughout hospitalization (HypoT) and any glucose < 2.2 mmol/L throughout hospitalization (Hyposevere). RESULTS: There were 1020 patients on carvedilol, 886 on selective beta blockers, and 10,216 on no beta blocker at admission. After controlling for other variables, the odds of Hypo1day, HypoT and Hyposevere were higher for carvedilol and selective beta blocker recipients than non-recipients, but only in basal insulin nonusers. The odds of Hypo1day (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.28, 3.09, p = 0.0002) and HypoT (OR 1.38, 95% CI 1.02, 1.86, p = 0.03) but not Hyposevere (OR 1.90, 95% CI 0.90, 4.02, p = 0.09) were greater for selective beta blocker vs. carvedilol recipients in basal insulin nonusers. Hypo1day, HypoT, and Hyposevere were all associated with increased mortality in adjusted models among non-beta blocker and selective beta blocker recipients, but not among carvedilol recipients. CONCLUSIONS: Beta blocker use is associated with increased odds of hypoglycemia among hospitalized patients not requiring basal insulin, and odds are greater for selective beta blockers than for carvedilol. The odds of hypoglycemia-associated mortality are increased with selective beta blocker use or nonusers but not in carvedilol users, warranting further study.