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Background: Afirma Genomic Sequencing Classifier (GSC) testing has been utilized for further risk stratification of thyroid nodules categorized as atypia of undetermined significance (AUS). The 2023 Bethesda system subcategorizes AUS diagnosis into AUS with nuclear atypia (AUS-N) and other atypia (AUS-O). The current study aims to determine if performance of GSC testing differs between the two AUS subcategories and between single AUS cohort and repeat AUS cohort. Methods: This retrospective study analyzed consecutive thyroid nodule fine-needle aspiration with a single or a repeat AUS diagnosis and a diagnostic GSC testing result (benign vs. suspicious). All AUS nodules were divided into AUS-N or AUS-O subcategory and followed by either surgical intervention or at least 12 months of clinical and/or ultrasound monitoring. We then assessed performance of GSC testing in each subcategory and subsequently compared the individual performance in AUS-N or AUS-O subcategory between single AUS cohort and repeat AUS cohort. Results: The study identified a total of 365 thyroid nodules subcategorized as AUS-N ( N = 106) and AUS-O ( N = 259). Both cohorts showed a significantly lower GSC benign call rate (BCR) in AUS-N nodules compared with AUS-O nodules (43% vs. 71% in single AUS, p = 0.001; 58% vs. 74% in repeat AUS, p = 0.02). The proportion of histology-proven malignancies associated with a suspicious GSC result tended to be greater in AUS-N nodules than AUS-O nodules (28% vs. 10% in single AUS, p = 0.09; 38% vs. 27% in repeat AUS, p = 0.3). Compared with AUS-N nodules, AUS-O cohorts demonstrated significantly higher specificity in the single AUS group (73% vs. 51%, p = 0.01). In both subcategories, the repeat AUS cohort yielded greater specificity, positive predictive value, and diagnostic accuracy compared with the single AUS group. However, the differences did not reach statistical significance. Conclusions: GSC BCR and diagnostic performance of GSC testing may vary in AUS-N versus AUS-O subcategories. However, there were no statistically significant differences in GSC performance between single and repeat AUS cohorts. more...

Background and Objective: Ibrutinib, an oral Bruton's tyrosine kinase inhibitor, has demonstrated efficacy as a first-line treatment for chronic lymphocytic leukemia in multiple, phase III, randomized clinical trials. This systematic literature review assessed the clinical effectiveness of ibrutinib in the first-line treatment of chronic lymphocytic leukemia in real-world clinical settings., Methods: MEDLINE, EMBASE, and relevant conference websites were searched for articles published in the USA from 1 January, 2014 to 30 June, 2020. Overall survival, progression-free survival, overall response rate, and time to next treatment were summarized., Results: This analysis included a total of 12 publications representing data from 112 to 2033 patients from community and academic centers, and the multicenter informCLL registry. Patients were predominantly male (60-99%) with a median age range from 62 to 77 years, and included those with high-risk genomic features (del[17p]: 21-33%; del[11q]: 33%; and unmutated immunoglobulin heavy chain variable gene: 59%). Real-world effectiveness with ibrutinib complemented the efficacy demonstrated in randomized clinical trials. Across various studies, the 12-month overall survival rates ranged from 95% to 96%; 18-month overall survival rates were similarly high (91%). Twelve-month progression-free survival rates ranged from 89% to 93%, and the overall response rate ranged from 71% to 90% across four studies. In the studies that reported time to next treatment, 91% and 87% of patients treated with first-line ibrutinib did not initiate new treatment at 12 months and 24 months, respectively., Conclusions: This systematic literature review confirms the benefit of ibrutinib as a first-line treatment in patients with chronic lymphocytic leukemia in real-world clinical settings and is consistent with results from randomized clinical trials, including in patients with high-risk genomic features., (© 2022. The Author(s).) more...

Background: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that presents with hypophosphatemia, bone pain, muscle weakness and fractures. We report a case series of four patients with TIO that resulted in significant muscle weakness and multiple atraumatic fractures., Case Presentation: Four patients were referred to an endocrinology clinic for the evaluation of multiple atraumatic fractures, muscle weakness, generalized muscle and joint pain. Laboratory evaluation was notable for persistent hypophosphatemia due to urinary phosphate wasting, low to low-normal 1,25-dihydroxyvitamin D, elevated alkaline phosphatase and elevated fibroblast growth factor 23 (FGF23). Tumor localization was successful, and all four patients underwent resection of phosphaturic mesenchymal tumors. Post-operatively, patients exhibited normalization of serum phosphorus, in addition to significant improvement in their ambulatory function., Conclusion: Hypophosphatemia with elevated FGF23 and low 1,25-dihydroxyvitamin D level in the setting of multiple atraumatic fractures necessitates careful evaluation for biochemical evidence of tumor-induced osteomalacia., Competing Interests: Competing interestsThe authors declared that they have no competing interests., (© The Author(s) 2020.) more...

Aim: We have previously reported an association of dihydrofolate reductase promoter polymorphisms with reduced event-free survival in childhood acute lymphoblastic leukemia (ALL) patients treated with Dana Farber Cancer Institute protocol. Here, we assessed whether these associations are applicable to other protocol, based on different methotrexate doses., Methods: Genotypes for six tag polymorphisms and resulting haplotypes were analyzed for an association with ALL outcome., Results: The association was found with the polymorphisms A-680C, A-317G and C-35T in high-risk group patients. Carriers of haplotype *1 had a remarkably higher risk of events compared with noncarriers and a lower probability of event-free survival (21.4 vs 81.3%)., Conclusion: The role of DHFR variants in predicting the outcome of childhood ALL extends beyond single-treatment protocol and can be useful biomarker in personalizing treatment. more...

Purpose: The purpose of this pilot study is to investigate the utility of, and areas of refinement for, digital photography as an educational tool for food logging in obese patients with type 2 diabetes (T2DM)., Methods: Thirty-three patients aged 18 to 70 with T2DM, body mass index at least 30 kg/m(2), and A1C 7.5% to 9% were recruited from an endocrinology clinic and randomized to a week of food logging using a digital camera (DC) or paper diary (PD), crossing over for week 2. Patients then viewed a presentation about dietary effects on blood glucose, using patient DC and blood glucose entries. Outcomes of adherence (based on number of weekly entries), changes in mean blood glucose and frequency of blood glucose checks, and patient satisfaction were compared between methods. Patient feedback on the DC intervention and presentation was also analyzed., Results: Thirty patients completed the study. Adherence was identical across methods. The mean difference in number of entries was not significant between methods. This difference increased and neared statistical significance (favoring DC) among patients who were adherent for at least 1 week (21 entries, with 2 entries per day for 5 of 7 days, n = 25). Mean blood glucose did not significantly decrease in either method. Patient satisfaction was similar between interventions. Feedback indicated concerns over photograph accuracy, forgetting to use the cameras, and embarrassment using them in public., Conclusion: Although the DC method was comparable to PD in adherence, blood glucose changes, and patient satisfaction in this pilot trial, patient feedback suggested specific areas of refinement to maximize utility of DC-based food logging as an educational tool in T2DM. more...

Obesity and starvation have opposing affects on normal physiology and are associated with adaptive changes in hormone secretion. The effects of obesity and starvation on thyroid hormone, GH, and cortisol secretion are summarized in Table 1. Although hypothyroidism is associated with some weight gain, surveys of obese individuals show that less than 10% are hypothyroid. Discrepancies have been reported in some studies, but in untreated obesity, total and free T4, total and free T3, TSH levels, and the TSH response to TRH are normal. Some reports suggest an increase in total T3 and decrease in rT3 induced by overfeeding. Treatment of obesity with hypocaloric diets causes changes in thyroid function that resemble sick euthyroid syndrome. Changes consist of a decrease in total T4 and total and free T3 with a corresponding increase in rT3. untreated obesity is also associated with low GH levels; however, levels of IGF-1 are normal. GH-binding protein levels are increased and the GH response to GHRH is decreased. These changes are reversed by drastic weight reduction. Cortisol levels are abnormal in people with abdominal obesity who exhibit an increase in urinary free cortisol but exhibit normal or decreased serum cortisol and normal ACTH levels. These changes are explained by an increase in cortisol clearance. There is also an increased response to CRH. Treatment of obesity with very low calorie diets causes a decrease in serum cortisol explained by a decrease in cortisol-binding proteins. The increase in cortisol secretion seen in patients with abdominal obesity may contribute to the metabolic syndrome (insulin resistance, glucose intolerance, dyslipidemia, and hypertension). States of chronic starvation such as seen in anorexia nervosa are also associated with changes in thyroid hormone, GH, and cortisol secretion. There is a decrease in total and free T4 and T3, and an increase in rT3 similar to findings in sick euthyroid syndrome. The TSH response to TRH is diminished and, in severe cases, thyroid-binding protein levels are decreased. In regards to GH, there is an increase in GH secretion with a decrease in IGF-1 levels. GH responses to GHRH are increased. The [table: see text] changes in cortisol secretion in patients with anorexia nervosa resemble depression. They present with increased urinary free cortisol and serum cortisol levels but without changes in ACTH levels. In contrast to the findings observed in obesity, the ACTH response to CRH is suppressed, suggesting an increased secretion of CRH. The endocrine changes observed in obesity and starvation may complicate the diagnosis of primary endocrine diseases. The increase in cortisol secretion in obesity needs to be distinguished from Cushing's syndrome, the decrease in thyroid hormone levels in anorexia nervosa needs to be distinguished from secondary hypothyroidism, and the increase in cortisol secretion observed in anorexia nervosa requires a differential diagnosis with primary depressive disorder. more...