Expression of Resistin, Chemerin, and Chemerin's Receptor in the Unstable Carotid Atherosclerotic Plaque.

Background and Purpose: Unstable carotid plaques are a common cause of ischemic strokes. Identifying markers that reflect/contribute to plaque instability has become a prominent focus in cardiovascular research. The adipokines, resistin and chemerin, and ChemR23 (chemerin receptor), may play a role in carotid atherosclerosis, making them potential candidates to assess plaque instability. However, the expression and interrelationship of resistin and chemerin (and ChemR23) protein and mRNA within the carotid atherosclerotic plaque remains elusive. Thus, we investigated herein, the association between plaque mRNA and protein expression of resistin and chemerin (and ChemR23) and carotid plaque instability in humans, and whether sex differences exist in the relationship between these adipokines and plaque instability. Methods: Human carotid plaques were processed for immunohistochemical/mRNA analysis of resistin, chemerin, and ChemR23. Plaque instability was assessed by gold-standard histological classifications. A semi-quantitative scoring system was used to determine the intensity of adipokine expression on macrophages/foam cells, as well as the percentage of inflammatory cells stained positive. Plaque adipokine protein expression was also digitally quantified and mRNA expression was assessed by qRT-PCR. Results: Resistin and chemerin mRNA expression was 80% and 32% lower, respectively, in unstable versus stable plaques (P<0.05), while no difference in ChemR23 mRNA expression was observed. In contrast, greater resistin staining intensity and percentage of cells stained positive were detected in unstable versus stable plaques (P<0.01). Similarly, chemerin and ChemR23 staining intensity and percentage of cells stained were positively associated with plaque instability (P<0.05). No strong sex-specific relationship was observed between adipokines and plaque instability. Conclusions: This study examined the relationship between resistin, chemerin, and ChemR23, and carotid plaque instability, with a specific analysis at the plaque level. We reported a positive association between plaque instability and protein levels of resistin, chemerin, and ChemR23 but a negative association with resistin and chemerin mRNA expression. This suggests these adipokines exert proinflammatory roles in the process of carotid atherosclerosis and may be regulated via a negative feedback regulatory mechanism.

Carotid Endarterectomy Outcomes in the Elderly: A Canadian Institutional Experience.

BACKGROUND: Carotid endarterectomy (CEA) is a well-established surgical intervention for stroke prevention in patients with carotid stenosis of all ages. However, the decision to proceed to operate in the elderly involves a more complicated risk-benefit assessment due in part to increased comorbidities and reduced life expectancy. Some studies suggest that CEA is more risky in the elderly with worse outcomes, whereas others have found no difference. Our objective was to evaluate and compare outcomes of CEA between elderly and younger patients at our institution. METHODS: All hospital charts were reviewed for consecutive patients undergoing CEA from the Jewish General Hospital and the Royal Victoria Hospital from October 2009 to December 2015. Primary outcomes were ipsilateral stroke, death, and restenosis at 30 days and 1 year. Secondary outcomes were cranial nerve injury, myocardial infarction (MI), hematoma, wound infection, cerebral hyperperfusion, and transient ischemic attacks within 30 days. Primary and secondary outcomes were compared between patients aged ≥80 years and <80 years. RESULTS: A total of 361 patients were included in this study with a mean age of 70.2 ± 9.5 years (n = 247 [68.4%] male and n = 272 [75.8%] symptomatic). Elderly patients were more often symptomatic (93.8% vs. 71.6%, P < 0.0001) and had an increased length of stay (2.8 ± 5.3 vs. 1.6 ± 1.8, P = 0.001). There was no statistically significant difference in primary outcomes between patients aged <80 years and ≥80 years, including 30-day stroke (1.7% vs. 0%), death (no deaths in either group), restenosis (8.8% vs. 12.3%), 1-year stroke (1.7% vs. 0%), death (0.7% vs. 0%), or restenosis (14.9% vs. 13.8%). However, elderly patients had significantly increased MI risk postoperatively (4.6% vs. 0.7%, P = 0.01). Other complications, including cranial nerve injury (3.7% in <80 years vs. 4.6% in the elderly group), were similar between the groups. CONCLUSIONS: We found that CEA in the elderly does not have an increased risk of stroke or death up to one year postoperatively. However, the postoperative length of stay is increased and complicated by significantly more MIs, which should weigh into the decision of whether to perform CEA on an elderly patient.

A Rare Case When Acromegaly Meets Cushing Syndrome.

Acromegaly is very uncommon, as is non-iatrogenic Cushing syndrome; we discuss a patient who was found to have both a pituitary adenoma causing acromegaly and a cortisol-producing adrenal adenoma causing Cushing syndrome within 1 year. She was a healthy, 44-year-old woman who presented with visual changes and was found to have bitemporal hemianopsia and a 3.3-cm pituitary mass along with central hypogonadism, central hypothyroidism, and suppressed adrenocorticotropin and discrepant cortisol. After transsphenoidal resection she had declining, but persistently elevated, insulin-like growth factor 1 (IGF-1), raising concern for persistent acromegaly. She also was experiencing several cushingoid symptoms and was found to have elevated salivary and urinary cortisol. An abdominal computed tomography scan showed a 3.1-cm adrenal adenoma, and she subsequently underwent adrenalectomy. Following adrenalectomy, her cortisol levels normalized, and her IGF-1, growth hormone, and oral glucose tolerance test showed substantial improvement consistent with previous reports linking hypercortisolism and elevated IGF-1 levels. Combinations of pituitary and adrenal disease are seen in a handful of genetic syndromes; however, her clinical presentation and genetics do not fit with known syndromes. This case describes two rare endocrine tumors in one patient and associated limitations of routine laboratory testing.

Navigating the Debate on Managing Large (≥4 cm) Thyroid Nodules.

Purpose: Discordant practice guidelines for managing large thyroid nodules may result in unnecessary surgeries and costs. Recent data suggest similar false-negative rates in fine needle aspiration (FNA) biopsies between small (<4 cm) and large (≥4 cm) nodules, indicating that monitoring rather than surgery may be appropriate for large biopsy-negative nodules. We investigated the management of thyroid nodules ≥4 cm to determine the proportion of surgeries not necessary for diagnostic purposes and examined for potential predictors. Methods: This was a retrospective cohort study of patients who received a FNA of nodule(s) ≥4 cm between 11/1/2014 and 10/31/2019 at the University of Vermont Medical Center. A surgery was considered unnecessary if the FNA result was benign in the absence of any of the following: compressive symptoms, family history of thyroid cancer in a first degree relative, history of neck irradiation, toxic nodule or toxic multinodular goiter, or substernal extension. Data were analyzed with Wilcoxon rank sum tests, chi square, or Fisher's exact tests. Results: 177 patients had a ≥4 cm nodule during the timeframe and half (54.2%) had surgery. Patients who underwent surgery were significantly younger (51.5 years vs. 62 years; P < 0.001), more likely to report obstructive symptoms (34.4% vs. 12.1%; P < 0.001) and had a larger nodule size (5.0 cm vs. 4.7 cm; P=0.26). Forty-one patients with benign (Bethesda II) FNA results had surgery, all with negative surgical pathology. Thirteen percentage (23/177) of surgeries were potentially not necessary for diagnostic purposes. Conclusion: Approximately half of our patients with ≥4 cm nodules had surgery, with 13% having surgery not necessary for diagnostic purposes revealing opportunities for improving care and costs.

A Case of Diabetic Ketoacidosis in a Patient on an SGLT2 Inhibitor and a Ketogenic Diet: A Critical Trio Not to Be Missed.

Results from major clinical trials have shown significant cardiorenal-protective benefits of SGLT2 inhibitors in patients with type 2 diabetes (T2DM), leading to increased popularity. A rare but serious side effect of SGLT2 inhibitors is euglycemic diabetic ketoacidosis (EDKA), which presents more covertly but has been described. Identification and report of modifiable risk factors would be an important step in helping clinicians appropriately counsel patients. In this case report, we present DKA in a patient on an SGLT2 inhibitor and ketogenic diet (KD). A 47-year-old male with a history of poorly controlled T2DM on metformin and empagliflozin presented to the emergency department (ED) with several days of pharyngitis, dyspnea, emesis, abdominal pain, and anorexia. Of note, one month prior to this event, he presented to the ED with malaise and was found to have an anion gap of 21, a bicarbonate level of 13 mmol/L, a pH level of 7.22, 3+ ketonuria, and a glucose level of 7 mmol/L (127 mg/dl). Additional workup was negative, and findings were attributed to his KD. His use of empagliflozin was not identified on his medication list. At second presentation, the patient was tachypneic and tachycardic and had mild abdominal tenderness. Labs revealed anion gap 28, bicarbonate 5 mmol/l, pH 6.94, 3+ ketonuria, glucose 14.9 mmol/L (269 mg/dl), and beta-hydroxybutyrate 8.9 mmol/L. The patient was diagnosed with DKA and was treated accordingly. With closure of anion gap, the patient was transitioned to insulin and metformin, and his empagliflozin was discontinued indefinitely. Before prescribing this medication class, physicians should inquire about low-carbohydrate diets given the higher risk for DKA, though knowledge of this risk is still not widespread.