Real-World Performance of the Afirma Genomic Sequencing Classifier (GSC)-A Meta-analysis.

CONTEXT: The Afirma® GSC aids in risk stratifying indeterminate thyroid nodule cytology (ITN). The 2018 GSC validation study (VS) reported a sensitivity (SN) of 91%, specificity (SP) of 68%, positive predictive value (PPV) of 47%, and negative predictive value (NPV) of 96%. Since then, 13 independent real-world (RW) postvalidation studies have been published. OBJECTIVE: This study's objective is to compare the RW GSC performance to the VS metrics. METHODS: Rules and assumptions applying to this analysis include: (1) At least 1 patient with molecular benign results must have surgery for that study to be included in SN, SP, and NPV analyses. (2) Molecular benign results without surgical histology are considered true negatives (TN) (as are molecular benign results with benign surgical histology). (3) Unoperated patients with suspicious results are either excluded from analysis (observed PPV [oPPV] and observed SP [oSP]) or assumed histology negatives (false positives; conservative PPV [cPPV] and conservative SP [cSP]) 4. Noninvasive follicular thyroid neoplasm with papillary-like nuclear features is considered malignant. RESULTS: In RW studies, the GSC demonstrates a SN, oSP, oPPV, and NPV of 97%, 88%, 65%, 99% respectively, and conservative RW performance showed cSP of 80% and cPPV of 49%, all significantly higher than the VS except for SN and cPPV. There was also a higher benign call rate (BCR) of 67% in RW studies compared to 54% in the VS (P < 0.05). CONCLUSION: RW data for the Afirma GSC demonstrates significantly better oSP and oPPV performance than the VS, indicating an increased yield of cancers for resected GSC suspicious nodules. The higher BCR likely increases the overall rate of clinical observation in lieu of surgery.

Vitamin D Toxicity Managed with Peritoneal Dialysis.

Vitamin D deficiency is a global health issue that afflicts more than one billion children and adults worldwide. Vitamin D supplementation has increased over the years, whether through medical prescriptions, over-the-counter, or online purchasing. This is driven by a more recognized association between vitamin D sufficiency status and lower risk of cancer. In addition, more recently, it is used as a potential prophylactic and treatment for COVID-19 infection. This can lead to toxicity from overingestion. While rare, it has been reported in the literature. In this case report, we present a 75-year-old man with severe hypercalcemia secondary to vitamin D toxicity managed with peritoneal dialysis. He presented with biochemical evidence of hypercalcemia, acute kidney injury, and pancreatitis. Workup for his hypercalcemia led to the diagnosis of vitamin D toxicity as shown by a level greater than 200 ng/dL (Ref: 20-50 ng/mL) was confirmed by liquid chromatography-mass spectroscopy. Cornerstone medical management of hypercalcemia was provided which included aggressive intravenous fluid hydration, intravenous diuretics, calcitonin, bisphosphonate, and corticosteroid therapy. At every interruption of therapy, calcium levels trended upward. A thorough literature review yielded the finding of a sole case report from 1966 presented at the Third International Congress of Nephrology, in which peritoneal dialysis was used in the management of vitamin D toxicity and hypercalcemia. This modality is established to cause vitamin D deficiency. In collaboration with the nephrology team, 10 sessions of peritoneal dialysis were undertaken with resolution of hypercalcemia and downtrend in 25-hydroxyvitamin D levels as measured by dilution.

Single Institution Experience with Afirma and Thyroseq Testing in Indeterminate Thyroid Nodules.

Background: Thyroid nodules are a very common often incidental finding on physical examination or imaging. Of those who undergo fine needle aspiration, cytology is indeterminate in up to 15%. Molecular testing is increasingly being used to help identify which nodules may be high risk for malignancy and guide management with regard to clinical follow-up or surgical intervention. Recently there has been an increase in publication of independent studies assessing the performance of these molecular tests and comparing "real-world" data with the validation studies. Methods: This retrospective study identified all thyroid nodules at our institution that had Afirma gene expression classifier (GEC), genomic sequencing classifier (GSC), or Thyroseq v3 molecular testing from January 2014 to January 2020 and compared measurements of test performance between them at our institution, and then with the original validation studies and other published institutional data. Results: Overall, the benign call rate was highest in the Afirma GSC group (78%) compared with the GEC group (60%) and Thyroseq group (66%). Surgical histopathology revealed malignancy in 6 of 31of biopsied nodules in the GEC group, 8 of 13 in the GSC group, and 3 of 16 in the Thyroseq v3 group. Based on our data, the GSC specificity (73.7%) and positive predictive value (PPV) (61.5%) were higher than the GEC specificity (60.4%) and PPV (22.2%) as well as Thyroseq v3 specificity (55.2%) and PPV (18.8%). Conclusions: From our short-term institutional experience, we found that the GSC classified more cytologically indeterminate nodules as benign compared with the Afirma GEC, and had improved specificity and PPV, which is similar to the validation study and other institutions' reported experiences. We also found that the Thyroseq v3 was similar to the Afirma GEC in terms of specificity and PPV, both of which are much lower than the validation studies.