Citations

Background Until 2015, standard of care for low-risk papillary thyroid cancer (PTC) >1 cm was a total or near-total thyroidectomy. Despite changes in guidelines and surgical management of low-risk PTC since 2015, little data are available regarding the effect on the need for additional surgery or risk for development of lymph node metastases. Our aim was to determine outcomes in patients who underwent initial thyroid lobectomy for low-risk PTC at a high-volume tertiary care institution. Methods Retrospective review of patients ≥18 years old with biopsy proven low-risk PTC 1-4 cm who underwent partial thyroidectomy (eg, lobectomy/isthmusectomy) at Mayo Clinic, Rochester, MN, between March 2016 and June 30, 2019. Results From 1481 thyroidectomies performed during study period, 940 contained PTC on final pathology. Of these, 87 (of 123) patients who had an initial thyroid lobectomy met inclusion criteria. Five (6%) of these patients proceeded to completion thyroidectomy (CT), with 3 requiring CT and radioactive iodine in the first postoperative year and 2 undergoing only CT in the second postoperative year. No postoperative complications were reported. No patient in this cohort required additional surgery or treatment for newly discovered lymph node metastases during the follow-up period. 43 (of 72, 60%) patients not on thyroxine therapy preoperatively were started on thyroxine therapy postoperatively. Conclusions Early outcomes for those undergoing thyroid lobectomy for low-risk PTC at our institution have been favorable. These results support the 2015 American Thyroid Association guidelines to offer lobectomy for those with low-risk PTC 1-4 cm.

Background Using computed tomography angiography to differentiate between components of carotid atherosclerotic lesions remains largely elusive. This study sought to validate a semi-automated software for computed tomography angiography plaque analysis using histologic comparisons. Materials and Methods A retrospective review was performed of consecutive patients that underwent a carotid endarterectomy, with pre-procedural computed tomography angiography imaging of the cervical arterial vasculature available for review. Images were evaluated using a commercially-available software package, which produced segmented analyses of intraplaque components (e.g. intraplaque hemorrhage, lipid-rich necrotic core, and calcifications). On imaging, each component was assessed in terms of its (1) presence or absence, and (2) both volume and proportion of the total plaque volume (if present). On histological evaluation of carotid endarterectomy specimens, each component was evaluated as an estimated proportion of total plaque volume. Results Of 80 included patients, 30 (37.5%) were female. The average age was 69.7 years (SD = 9.1). Based on imaging, intraplaque hemorrhage was the smallest contributor to plaque composition (1.2% of volumes on average). Statistically significant linear associations were noted between the proportion of intraplaque hemorrhage, lipid-rich necrotic core, and calcifications on histology and the volume of each component on imaging ( p values ranged from 0.0008 to 0.01). Area under curve were poor for intraplaque hemorrhage and lipid-rich necrotic core (0.59 and 0.61, respectively) and acceptable for calcifications (0.73). Conclusion Semi-automated analyses of computed tomography angiography have limited diagnostic accuracy in the detection of intraplaque hemorrhage and lipid-rich necrotic core in carotid artery plaques. However, volumetric imaging measurements of different components corresponded with histologic analysis.

There is currently limited and mixed evidence for the cognitive benefits of Computerized Cognitive Training (CCT) and yoga in persons with Mild Cognitive Impairment (pwMCI). The objective of this study was to investigate the benefit of computerized cognitive training (CCT) vs. physical (yoga) intervention on cognitive abilities. Participants in this study were part of the larger Mayo Clinic’s Healthy Action to Benefit Independence and Thinking (HABIT) program comparative effectiveness trial. The HABIT program is designed for pwMCI and their care partner and consists of five behavioral interventions: CCT, Memory Support System-Calendar (MSS-Calendar), wellness education, support groups, and yoga. The subtractive study design randomly withheld one of the interventions for a total of five study arms. Longitudinal mixed-effects regression models were used to investigate the hypothesis that CCT and yoga has a greater positive impact on psychomotor and basic attention abilities at 12 months post-intervention as compared to the other HABIT interventions. Findings showed CCT had a positive impact compared to yoga on the Cogstate psychomotor/attention composite at 12 months post-intervention (ES = 0.54; unadjusted p value = 0.007, adjusted p value = 0.021). The impact of yoga or combining CCT with yoga did not show statistically significant improvement. Continued CCT practice at home showed further benefit on psychomotor/attention at 12 months post-intervention. There was no significant benefit of CCT or yoga on Cogstate learning/working memory composite.

The mammalian liver's regenerative ability has led researchers to engineer animals as incubators for expansion of human hepatocytes. The expansion properties of human hepatocytes in immunodeficient mice are well known. However, little has been reported about larger animals that are more scalable and practical for clinical purposes. Therefore, we engineered immunodeficient swine to support expansion of human hepatocytes and identify barriers to their clinical application. Immunodeficient swine were engineered by knockout of the recombinase-activating gene 2 ( RAG2 ) and fumarylacetoacetate hydrolase (FAH). Immature human hepatocytes (ihHCs) were injected into fetal swine by intrauterine cell transplantation (IUCT) at day 40 of gestation. Human albumin was measured as a marker of engraftment. Cytotoxicity against ihHCs was measured in transplanted piglets and control swine. We initially detected higher levels of human albumin in cord blood of newborn FAH/ RAG2 -deficient (FR) pigs compared with immunocompetent controls (196.26 ng/dL vs. 39.29 ng/dL, p = 0.008), indicating successful engraftment of ihHCs after IUCT and adaptive immunity in the fetus. Although rare hepatocytes staining positive for human albumin were observed, levels of human albumin did not rise after birth, but declined, suggesting rejection of xenografted ihHCs. Cytotoxicity against ihHCs increased after birth by 3.8% (95% CI: [2.1%–5.4%], p < 0.001) and inversely correlated with declining levels of human albumin ( p = 2.1 × 10 −5 , R 2 = 0.17). Circulating numbers of T cells and B cells were negligible in FR pigs. However, circulating natural killer (NK) cells exerted cytotoxicity against ihHCs. NK cell activity was lower in immunodeficient piglets after IUCT than in naive controls (30.4% vs. 40.1%, p = 0.011, 95% CI for difference [2.7%–16.7%]). In conclusion, ihHCs were successfully engrafted in FR swine after IUCT. NK cells were a significant barrier to expansion of hepatocytes. New approaches are needed to overcome this hurdle and allow large-scale expansion of human hepatocytes in immunodeficient swine. Impact statement There is currently a need for robust expansion of human hepatocytes. We describe an immunodeficient swine model into which we engrafted immature human hepatocytes (ihHCs). We identified the mechanism of the eventual graft rejection by the intact NK cell population, which has not been previously shown to have a significant role in xenograft rejection. By both improving engraftment and reducing NK cell-mediated cytotoxicity toward the graft through intrauterine cell transfer, we confirmed the presence of residual adaptive immunity in this model of immunodeficiency and the ability to induce hyposensitization in the NK cell population by taking advantage of the fetal microenvironment.

Neurotropic viruses target the brain and contribute to neurologic diseases. Caspase recruitment domain containing family member 9 (CARD9) controls protective immunity in a variety of infectious disorders. To investigate the effect of CARD9 in neurotropic virus infection, CARD9−/− and corresponding C57BL/6 wild-type control mice were infected with Theiler’s murine encephalomyelitis virus (TMEV). Brain tissue was analyzed by histology, immunohistochemistry and molecular analyses, and spleens by flow cytometry. To determine the impact of CARD9 deficiency on T cell responses in vitro, antigen presentation assays were utilized. Genetic ablation of CARD9 enhanced early pro-inflammatory cytokine responses and accelerated infiltration of T and B cells in the brain, together with a transient increase in TMEV-infected cells in the hippocampus. CARD9−/− mice showed an increased loss of neuronal nuclear protein+ mature neurons and doublecortin+ neuronal precursor cells and an increase in β-amyloid precursor protein+ damaged axons in the hippocampus. No effect of CARD9 deficiency was found on the initiation of CD8+ T cell responses by flow cytometry and co-culture experiments using virus-exposed dendritic cells or microglia-enriched glial cell mixtures, respectively. The present study indicates that CARD9 is dispensable for the initiation of early antiviral responses and TMEV elimination but may contribute to the modulation of neuroinflammation, thereby reducing hippocampal injury following neurotropic virus infection.

Autonomous cortisol secretion (ACS) affects up to 50% of patients with adrenal adenomas. Despite the limited evidence, clinical guidelines recommend measurement of serum concentrations of dehydroepiandrosterone-sulfate (DHEA-S) and corticotropin (ACTH) to aid in the diagnosis of ACS. Our objective was to determine the accuracy of serum concentrations of DHEA-S and ACTH in diagnosing ACS. We conducted a retrospective single center study of adults with adrenal adenoma evaluated between 2000−2020. Main outcome measure was diagnostic accuracy of DHEA-S and ACTH. ACS was defined as post-dexamethasone cortisol >1.8 mcg/dL. Of 468 patients, ACS was diagnosed in 256 (55%) patients with a median post-DST cortisol of 3.45 mcg/dL (range, 1.9–32.7). Patients with ACS demonstrated lower serum concentrations of DHEA-S (35 vs. 87.3 mcg/dL, p < 0.0001) and ACTH (8.3 vs. 16 pg/mL, p < 0.0001) compared to patients with non-functioning adrenal tumors (NFAT). Serum DHEA-S concentration <40 mcg/dL diagnosed ACS with 84% specificity and 81% PPV, while serum ACTH concentration <10 pg/mL diagnosed ACS with 75% specificity and 78% PPV. The combination of serum concentrations of DHEA-S <40 mcg/dL and ACTH <10 pg/mL diagnosed ACS with the highest accuracy with 92% specificity and 87% PPV. Serum concentrations of DHEA-S and ACTH provide additional value in diagnosing ACS.

Mono‐and polyunsaturated fats in nuts, such as pistachios (PI), may improve lipoprotein and glycemic status. Overweight persons trend for dyslipidemia and high diabetes risk. The lower limits of PI consumption required for health benefits are unknown. This study determined if PI at bedtime promotes beneficial changes in metabolic status in overweight persons. Overweight subjects (n=22; 55 ± 2 yrs; 90 ± 3.6 kg; BMI 31 ± 1) were randomized to 35.4 g PI self‐administered at bedtime or control (CO; no PI) for 6 weeks. There was no difference in physical activity level between subjects receiving PI and CO. Body weight was not different in PI and CO at wk 0, 1, 2, 4, and 6. HDL cholesterol at wk 0 and 6 in PI was 49.2 ± 3.5 to 50.3 ± 3.0, and CO was 60.8 ± 3.8 and 58.0 ± 2.7 mg/dL, at wk 6 PI had improved slightly relative to CO (P= 0.12). Plasma glucose at wk 0 and 6 in PI was 104.6 ± 2.8 and 99.6 ± 2.6 mg/dL, and CO was 102.0 ± 2.8 and 101.1 ± 2.6 mg/dL, at wk 6 PI had improved slightly relative to CO (P= 0.16). Plasma insulin at wk 0 and 6 in PI was 8.5 ± 1.0 and 8.4 ± 0.9, and CO was 7.2 ± 0.7 to 8.8 ± 0.7 μU/mL, at wk 6 PI had improved slightly relative to CO (P = 0.21). Beneficial changes in HDL, glucose, and insulin probably requires slightly more than 35.4 g/d PI for 6 wks. To increase the probability of metabolic health benefits, nutritionists may wish to encourage levels of daily PI consumption higher than those administered in this study.