Introduction and Objective: Diabetes affects approximately one in 10 Americans and costs the nation an estimated $413 billion annually. While Certified Diabetes Care and Education Specialist (CDCES) services improve health outcomes, utilization remains low due to various barriers. To address this, the University of Pittsburgh Medical Center (UPMC) Division of Endocrinology partnered with the UPMC Health Plan to launch a proactive CDCES program. This study aims to analyze the cost and clinical outcomes for program participants compared to a control group. Methods: The intervention group consisted of individuals with type 2 diabetes who engaged with the proactive CDCES group between January and December 2023. In contrast, the comparison group included individuals with type 2 diabetes who had access to CDCES services via standard referral pathways. For the analysis, 2,082 individuals in the proactive CDCES intervention were matched with 6,246 controls using an optimal 1:3 propensity score matching ratio based on clinical and demographic criteria. T-tests and Chi-square tests of proportions were used to evaluate 12-month changes in HbA1c levels, health care costs per member per month (PMPM), and utilization. Results: After matching, average HbA1c was 8.7±2.1 in both CDCES and control groups. Within 12 months, the intervention group demonstrated a significantly greater reduction in HbA1c compared to the control group (-7.6% vs. 5.9%, p=0.0002). Total cost PMPM was 38% lower in the intervention group (p<0.0001). The intervention group also experienced significantly lower hospital inpatient and observation utilization, alongside significantly higher Continuous Glucose Monitor (CGM) utilization (all p<0.0001). Conclusion: The proactive CDCES program led to bigger decreases in HbA1c levels, lower unplanned healthcare utilization, and higher CGM prescriptions while significantly reducing total cost of care. To improve clinical and cost outcomes, healthcare systems should implement strategies that increase CDCES utilization. Disclosure E. Karslioglu French: None. M.E. Knueven: None. J. Kanter: None. T. Grumski: None. H. McClain: None. E. Beckjord: Advisory Panel; Current; Omada Health, Inc.

Objective: Continuous glucose monitoring (CGM) is an effective tool for individuals with type 2 diabetes (T2D) on insulin. This study evaluated the effect of using CGM to reduce hyperglycemia, by focusing on food and lifestyle choices, in people with T2D not taking insulin. Methods: A 6-month randomized, prospective four-center study was conducted. The primary end point was a within-group reduction in time above range >180 mg/dL (TAR180) at 3 months. Participants were asked not to make diabetes medication changes in the first 3 months. Seventy-two adults not on insulin or sulfonylurea therapy, with glycated hemoglobin (HbA1c) 7.5%-12%, were randomized to use CGM alone (n = 31) or CGM plus a food logging app (n = 41) to aid diabetes management. Participants attended guided education visits. Differences in CGM metrics, HbA1c, and body weight were compared. Results: The CGM alone group decreased TAR180 from 55% at baseline to 27% at 3 months (P < 0.001) and 21% at 6 months (P < 0.001); the CGM plus food logging app group decreased TAR180 from 53% at baseline to 30% at both 3 and 6 months (P < 0.001 for both). For all participants, time in range (70-180 mg/dL) increased from 46% at baseline to 71% at 3 months (P < 0.001) and to 72% at 6 months (P < 0.001). HbA1c and weight were reduced by 1.3% (P < 0.001) and 7 pounds (lbs.) (P < 0.001) for all participants at 6 months. Conclusion: People with T2D not taking insulin showed large, clinically significant improvements in CGM metrics and HbA1c when using either CGM alone or with a food logging app. This occurred with a near absence of medication changes in the first 3 months and were therefore likely due to changes in food and/or lifestyle choices.

Background: TERT promoter mutations in thyroid cancer are associated with aggressive disease, including recurrence, distant metastasis, and disease-related mortality. We aim to assess histological and disease-related outcomes when TERT mutation is detected alone or with other alterations during preoperative testing. Methods: A retrospective, single-institution study was performed, including all adult patients undergoing initial diagnostic thyroid nodule evaluation with TERT promoter mutation (C228T/C250T) detected in preoperative thyroid fine needle aspiration samples using TSv3 testing. Results: Of 70 thyroid nodules, 18 (26%) were isolated (iTERT), and 52 (74%) were associated with ≥1 concurrently detected mutation (TERT+). The most common additional abnormalities were BRAFV600E (23, 44%), RAS (19, 37%), and copy number alterations (CNA; 15, 29%). Patients with iTERT were older than those with TERT+ nodules (p = 0.007). While nodule size was similar between the two groups (mean size 3.2 cm, p = 0.18), Bethesda III/IV cytology was more likely with iTERT (94% vs. Bethesda V/VI 56%, p = 0.007). Histology was available for 9 (50%) iTERT and 51 (98%) TERT+ nodules and malignancy was higher with preoperative detection of TERT+ compared with iTERT (96% vs. 67%, p = 0.02). Poorly differentiated or anaplastic cancers were diagnosed in 33% of the malignancies at an equivalent rate in both cohorts. At median follow-up of 13.1 months (interquartile range 26.2, 7.2-33.4), distant metastasis occurred in 32.7% of patients including 17% (1/6) with iTERT versus 33% of patients with TERT+ (p = 0.65). None of the iTERT patients had locoregional recurrence as compared with 25% of TERT+ patients (p = 0.31). Conclusions: When preoperatively detected, TERT promoter mutations are more often seen in association with additional driver mutations or other genetic alterations such as CNA, but when present, carries a very high risk of malignancy (93%). Up to 1/3 are poorly differentiated or anaplastic thyroid cancer, and this likelihood is equivalent when TERT is present in isolation or in combination with other mutation. Thus, surgery should be strongly considered in iTERT nodules, and total thyroidectomy should be favored when TERT+ is identified.

Background: CGM is established as an effective tool for those with T2D on insulin. This study evaluated the effect of using CGM to reduce hyperglycemia in people not taking insulin, by focusing on food and lifestyle choices. Methods: A randomized, prospective, four-center study was conducted. The primary endpoint was reduction in % time with glucose >180 mg/dL (TAR) at 3 months. Seventy-two adults not on insulin or sulfonylurea therapy, with glycated hemoglobin (HbA1c) 7.5-12%, were randomized to use CGM alone (n=31) or CGM with a connected food logging app (n=41) to aid diabetes management. There were 3 to 4 education and CGM data-review visits over 90 days. Within and between arm differences in CGM metrics, HbA1c, and body weight were compared. Results: Study groups improved TAR by 28% (CGM) and 23% (CGM + app) and % time with glucose 70-180 mg/dL (TIR) by 27% (CGM) and 23% (CGM + app) while keeping % time <70 mg/dL (TBR) below 1% (Table). No differences were observed between groups. Additionally, both groups had reductions in HbA1c of at least 1.0% and weight of at least 4lbs. Participants using the food app logged an average of 15 meals per week over 90 days. Conclusion: People with T2D not using insulin showed large, clinically significant improvements in CGM metrics and HbA1c when using either CGM alone or CGM plus a food logging application. Disclosure T.W. Martens: Research Support; Abbott. Other Relationship; Abbott. Advisory Panel; Dexcom, Inc. Research Support; Dexcom, Inc., Insulet Corporation, Lilly Diabetes. Other Relationship; Lilly Diabetes. Advisory Panel; Lilly Diabetes. Research Support; Medtronic, Novo Nordisk. Other Relationship; Novo Nordisk. Research Support; Sanofi. Advisory Panel; Sanofi. Other Relationship; Sanofi. Research Support; Tandem Diabetes Care, Inc. H.J. Willis: Research Support; Abbott. Other Relationship; Abbott. Research Support; Academy of Nutrition and Dietetics, Dexcom, Inc. D.F. Kruger: Advisory Panel; Abbott. Research Support; Beta Bionics, Inc., Carmot Therapeutics, Inc. Speaker's Bureau; Dexcom, Inc. Advisory Panel; Dexcom, Inc., Lilly Diabetes. Speaker's Bureau; Lilly Diabetes. Advisory Panel; Insulet Corporation. Research Support; Insulet Corporation. Advisory Panel; MannKind Corporation, Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Advisory Panel; Provention Bio, Inc. Speaker's Bureau; Sanofi, Xeris Pharmaceuticals, Inc. Advisory Panel; Pendulum Therapeutics. Research Support; Tandem Diabetes Care, Inc. Advisory Panel; Cequr. Speaker's Bureau; Cequr. Advisory Panel; Medtronic, embecta, Ascensia Diabetes Care. Research Support; Abbott. Advisory Panel; Sanofi. E. Karslioglu-French: Research Support; Abbott, Pfizer Inc. D.W. Steenkamp: Consultant; Abbott. Research Support; Novo Nordisk A/S, MannKind Corporation, Tandem Diabetes Care, Inc. Funding Abbott Diabetes Care

Introduction: Most people with Type 2 DM receive care directed by their PCP and do not access endocrinologists. TACos are proactive e-consults that provide therapeutic treatment recommendations. Diabetes TACos have been implemented at University of Pittsburgh Medical Center (UPMC) PCP practices by a collaborative team of the Division of Endocrinology, Clinical Analytics, UPMC PCPs, and UPMC Health Plan. Our previous analysis showed significant HbA1c reduction 6 months following TACos. A 12-month evaluation of a larger patient population demonstrates even more positive outcomes. Methods: The analysis included 574 individuals who received a TACos (intervention) matched to 1722 controls based on clinical and demographic criteria. The intervention and control groups were matched using 3:1 optimal propensity score matching. Twelve-month changes in HbA1c and health care costs per member per month (PMPM) were evaluated using an observational matched design and intention-to-treat (ITT) analysis. Results: Sixty-five percent of the TACos recommendations were implemented by PCPs. Percent change in HbA1c in 12 months after TACos was significantly higher in the intervention group (-13.9%, p=0.0003) vs the control group (-10%). Median total cost PMPM in 12 months after TACos was significantly lower in the intervention group (-24%, p<0.001) vs the control group. Inpatient hospital and observation utilization were significantly lower and SGLT2/GLP1 utilization was significantly higher in the intervention group. Conclusion: Members who received TACos had higher percent reduction in HbA1c; lower total cost; lower inpatient admission and 30-day readmissions; and higher SGLT2/GLP1 utilization compared to comparison group. TACos can improve diabetes control and decrease medical costs for people with Type 2 DM whose care is managed by their PCP. Disclosure E. Karslioglu-French: Research Support; Abbott, Pfizer Inc. J. Kanter: None. M.E. Winger: None. K.R. Williams: None. T. Grumski: None. J. Schuster: None. E. Beckjord: None.

INTRODUCTION:Thyroid cytopathology cases with suspicious for malignancy (SFM) diagnosis often result in resection. However, molecular testing offers details that may provide additional insights. In this study, the molecular profiles of SFM cases from two institutions that routinely used ThyroSeq v3 (TSV3) were examined. MATERIALS AND METHODS:Following institutional review board approval, SFM thyroid cytopathology cases with TSV3 results were retrieved from the databases of two institutions. Molecular information including molecular-derived risk of malignancy (MDROM), cytologic-histologic correlation data, and other related parameters were calculated. Statistical comparisons were made with a p <.05 considered significant. RESULTS:The core data set comprised 114 SFM cases that passed TSV3 quality assurance. All TSV3 results were reported as positive or negative for genomic alterations and all except five cases provided a probability of malignancy estimate. The overall combined baseline MDROM of 75.7% (95% CI, 70.0-81.4) was comparable to the risk of malignancy (74%) published in the Bethesda System. There was a statistically significant difference between the combined MDROMs of resected and unresected cohorts (79.0% vs 58.6%; p = .0153). Interestingly, the MDROMs of the resected cohorts from the two institutions were statistically different (75.0% vs 85.3%; p = .020). Cytologic-histologic correlation revealed malignant outcome in 88.5% of resected cases. CONCLUSIONS:Molecular analyses of SFM cases demonstrated higher risk genomic alterations that were associated with histologically overt neoplasms, resulting in increased malignancy outcome compared to baseline. MDROM analysis revealed differences in the cytopathologic practice patterns regarding follicular-patterned neoplasms at the two institutions.

A prediction model to assess the risk of hospital readmission can be valuable to identify patients who may benefit from extra care. Developing hospital-specific readmission risk prediction models using local data is not feasible for many institutions. Models developed on data from one hospital may not generalize well to another hospital. There is a lack of an end-to-end adaptable readmission model that can generalize to unseen test domains. We propose an early readmission risk domain generalization network, ERR-DGN, for cross-domain knowledge transfer. ERR-DGN internalizes the shared patterns and characteristics that are consistent across source domains, enabling it to adapt to a new domain. It transforms source datasets to a common embedding space while capturing relevant temporal long-term dependencies of sequential data. Domain generalization is then applied on domain-specific fully connected linear layers. The model is optimized by a loss function that integrates distribution discrepancy loss to match the mean embeddings of multiple source distributions with the task-specific loss.A model was developed using electronic health record (EHR) data of 201,688 patients with diabetes across urban, suburban, rural, and mixed hospital systems to enhance 30-day readmission predictions among patients with diabetes on 67,066 unseen patients at a rural hospital. We also explored how model performance varied by the number of sites and over time. The proposed method outperformed the baseline models, yielding a 6 % increase in F1-score (0.79 ± 0.006 vs. 0.73 ± 0.007). Model performance peaked with the inclusion of three sites. Performance of the model was relatively stable for 3 years then declined at 4 years. ERR-DGN may be a proficient tool for learning data from multiple sites and subsequently applying a hospitalization readmission prediction model to a new site. Including a relatively small number of varied sites may be sufficient to achieve peak performance. Periodic retraining at least every 3 years may mitigate model degradation over time.

BRAFK601E is an uncommon mutation typically found in encapsulated follicular-patterned thyroid tumors. Previous studies on BRAFK601E-positive thyroid tumors were conducted before the implementation of the non-invasive follicular neoplasm with papillary-like nuclear features (NIFTP) diagnosis. This study aimed to characterize BRAFK601E-positive tumors and evaluate changes in the diagnosis and management of these patients after the introduction of NIFTP. We evaluated 25 thyroid tumors that were positive for BRAFK601E and diagnosed considering the NIFTP criteria. Clinicopathologic characteristics and recurrence rates of these tumors were compared to 29 BRAFK601E-positive tumors diagnosed prior to the acceptance of the NIFTP diagnosis. RNA-seq analysis was performed on 10 BRAFK601E-positive tumors. In the current study, 72% of BRAFK601E-positive tumors were diagnosed as non-invasive tumors on resection, with NIFTP (48% of all tumors) being the most common diagnosis. BRAFK601E-positive tumors exhibited a RAS-like gene expression profile with a BRAF-RAS score (BRS) and thyroid differentiation score (TDS) distinct from BRAFV600E-positive tumors (P < 0.001). Since 2016, patients with BRAFK601E-positive tumors less frequently underwent total thyroidectomy (41% vs 100%, P < 0.001) and received radioiodine (7% vs 75%, P < 0.001). None of the tumors positive for an isolated BRAFK601E mutation from the current or 2016 studies showed recurrences on follow-up. Our study demonstrates that most BRAFK601E-positive tumors are low-risk, RAS-like tumors, which were diagnosed as NIFTP in half of all study cases. Since 2016, patients with BRAFK601E-positive nodules have received less aggressive treatment. The risk of recurrence of BRAFK601E-positive tumors without other high-risk features appears to be low, and lobectomy without radioiodine is likely a sufficient treatment for these patients.

Background: Molecular testing (MT) is emerging as a potential prognostic factor that can be available before treatment of differentiated thyroid carcinoma begins. Among patients eligible for either lobectomy or total thyroidectomy as their initial therapy, our study aims were to assess (1) if conventionally available preoperative factors are associated with incomplete response to initial therapy, and (2) if MT results can be a surrogate for the ATA Risk Stratification System (RSS) to estimate risk of recurrence.Methods: The data of consecutive thyroid cancer patients without preoperative lateral neck disease or distant metastasis who underwent index thyroidectomy between November 1, 2017 and October 31, 2021 were reviewed. Logistic regression models including preoperative variables such as MT and/or the postoperatively available RSS were constructed to predict disease recurrence, either structural or biochemical. Model discrimination using the c-statistic and goodness-of-fit test were compared.Results: Among 945 patients studied, 50 (5.2%) recurred with 18-month median follow-up. Recurrences were detected in 17 (2.9%), 20 (6.7%), and 13 (22.8%) patients with RSS-low, -intermediate, and -high cancers, respectively (p < 0.001). In multivariable analysis, only tumor size was associated with recurrence (odds ratio [OR] 1.3, 95% confidence interval [CI] 1.1-1.5). In a different model analyzing 440 (46.6%) patients with available MT results, recurrence was associated with both larger tumor size (OR 1.4 [95% CI 1.1-1.8]) and MT results (p < 0.001). Including MT improved the c-statistic by 27%, which was statistically no different than the model incorporating only the RSS (p = 0.15).Conclusions: Disease recurrence was observed across all ATA RSS categories in short-term follow-up, and tumor size was the only conventional preoperative factor associated with recurrence. When MT results were incorporated, they not only improved predictive ability beyond tumor size alone, but also yielded similar ability as the gold standard ATA RSS. Thus, MT results might aid the development of novel preoperative risk stratification algorithms.

BACKGROUND Indeterminate thyroid cytopathology diagnoses represent differing degrees of risk that are corroborated by follow-up studies. However, traditional cytologic-histologic correlation may overestimate the risk of malignancy (ROM) because only a subset of cases undergo resection. Alternatively, some molecular tests provide probability of malignancy data to calculate the molecular-derived risk of malignancy (MDROM) and the positive call rate (PCR). The authors investigated MDROMs and PCRs of indeterminate diagnoses for individual cytopathologists as quality metrics. METHODS This study was approved by the Department of Pathology Quality Improvement Program. Thyroid cytopathology diagnoses and ThyroSeq v3 results were retrieved for each cytopathologist for a 2-year period with at least 3 years of follow-up for the atypia of undetermined significance (AUS), follicular neoplasia (FN), and follicular neoplasia, oncocytic-type (ONC) cytopathologic diagnoses. MDROMs and PCRs were compared with reference ROMs and cytologic-histologic correlation outcomes. RESULTS The overall MDROMs (and ranges for cytopathologists) for the AUS, FN, and ONC categories were 13.4% (range, 5.8%-20.8%), 28.1% (range, 22.1%-36.7%), and 27.0% (range, 19.5%-41.5%), respectively, and most individual cytopathologists' MDROMs were within reference ROM ranges. However, PCRs more effectively parsed the differences in cytopathologists' ROM performance. Although the overall PCRs were not significantly different across cytopathologists (p = .06), the AUS PCRs were quite different (p = .002). By cytologic-histologic correlation, six of 55 resected cases (10.9%) were falsely negative, and there were no false-positive cases. CONCLUSIONS MDROMs and PCRs evaluate concordance with reference ROMs and with one another and provide individual feedback, which potentially facilitates quality improvement.

In the United States, many individuals with diabetes mellitus (DM) do not achieve treatment goals despite the availability of effective interventions. Provider clinical inertia is one cause of these unfavorable outcomes. Targeted automatic eConsults (TACos) are an emerging technology-based intervention with potential to address clinical inertia in primary care (PC). TACos prospectively identify at-risk patients and use unsolicited specialist recommendations to prompt treatment intensification. Through a payer-provider collaboration, a TACos intervention was piloted for adults with uncontrolled DM (HbA1c >8%) to understand impact on DM clinical inertia and outcomes. Clinical inertia was assessed by measuring whether a PC provider implemented recommended therapeutic changes. Six-month changes in HbA1c and health care costs per member per month were evaluated using an observational matched design and intention-to-treat (ITT) analysis. The analysis included 196 individuals who received a TACos between February 2021 and August 2021 (ITT group) matched to 392 controls based on clinical and demographic criteria. TACos recommendations were implemented 65% of the time. Median percent change in HbA1c was significantly greater for the ITT group versus controls (-10.9% vs. -10.2%; P = 0.0359). Median total costs were 7.9% lower in the ITT group (P = 0.0900). A per protocol analysis was done to examine effects between ITT group individuals with an implemented TACos recommendation (n = 126) and controls. Median percent change in HbA1c was significantly greater (-19.5% vs. -10.2%; P < 0.0001), but there was no difference in total costs (-7.9%; P = 0.1753). TACos may feasibly address clinical inertia in PC and improve HbA1c for uncontrolled DM.

Background: More than 10% of the US population has diabetes. However, a national shortage of endocrinologists limits access to diabetes specialty care, creating a delay of several weeks to months for a new patient appointment in endocrine clinic. Econsults, which are asynchronous provider-to-provider communications embedded in the electronic medical record, are a relatively new pathway to seek consultation from specialists. The most common reason for endocrine econsult is uncontrolled diabetes. However, there is little evidence on effectiveness of econsults in improving diabetes control. Methods: We completed a retrospective chart review of all endocrine econsults that were completed for adults with diabetes within a large integrated health system in 2022. We compared HbA1c values before and 3, 6, 12 months after econsult to assess glycemic change. We also analyzed how many econsults were followed by an endocrinology office visit. Results: Of 212 diabetes econsults completed in 2022, 8% (16/212) were for type 1 DM, and 92% (196/212) were for type 2 DM management. Follow-up HbA1c values were available in 189 patients. Eighty-eight percent (166/189) of patients had improvement in HbA1c 12 months following econsult. Only 15% (32/212) of all econsults were followed by a video or in-person visit with an endocrinologist, while 85% (180/212) did not require a follow-up endocrine appointment. Of the patients who only received econsult, mean HbA1c improved from 9.9% at baseline to 7.4% at 12 months (p<0.05). Of the 31 patients with type 2 DM who required a follow-up appointment with endocrinologist, mean HbA1c improved from 10.4% at baseline to 7.1% post-visit (p<0.05). Of note, 6 patients were diagnosed with new-onset type 1 DM during econsult process and were triaged to an immediate video visit to start appropriate insulin treatment and prevent DKA. Conclusion: Econsult is an efficient and effective model which can expand access to diabetes specialty care for patients with uncontrolled diabetes. Disclosure E. Karslioglu-French: Research Support; Abbott. M. Zupa: None. J. Quaytman: None. Funding Pittsburgh Foundation Grant (MR2022-128717)

Diabetic ketoacidosis (DKA) has traditionally been treated with a continuous intravenous insulin infusion, often requiring management in an intensive care unit (ICU) or step-down unit. There has been growing evidence supporting the use of subcutaneous rapid-acting insulin analogs to treat mild-to-moderate DKA (alert patient able to tolerate oral fluid intake, pH >7.0, bicarbonate ≥10), helping to decrease costs and ICU-bed utilization. We sought to establish the efficacy and safety of a subcutaneous insulin lispro protocol developed at UPMC for the treatment of mild-to-moderate DKA. A retrospective chart review was performed on patients across 15 institutions in the UPMC network from February-October 2022 who had the adult DKA PowerPlan subcutaneous insulin lispro subphase ordered. Of 111 cases analyzed, 47 cases were included that properly used the PowerPlan to treat mild-to-moderate DKA. DKA resolution using the PowerPlan was reached in 45/47 (95.7%) cases. The two unsuccessful cases involved delayed recognition of DKA in the emergency department and premature transition to a prandial insulin regimen before DKA resolution. Hypoglycemia (defined as glucose <70) occurred in 9/47 (19.1%) encounters. Only 1/47 (2.1%) encounters involved hypoglycemia directly attributable to the subcutaneous insulin lispro PowerPlan. The remaining cases of hypoglycemia were attributed to not reducing insulin doses when glucoses were <250, giving insulin doses sooner than 2 hours before the prior dose, not starting dextrose-containing fluids when glucoses were <250, and higher co-administered basal insulin doses (>0.3 units/kg). Overall, these results suggest that a subcutaneous insulin analog can be safely and effectively used to treat mild-to-moderate DKA in non-ICU settings. Disclosure J.Quaytman: None. E.Karslioglu-french: Research Support; Abbott. A.Donihi: None.

Introduction Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. Research design and methods Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%–12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. Results Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD). Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites. The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. Conclusions In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

BACKGROUND Noninvasive encapsulated follicular variant papillary thyroid carcinoma (EFVPTC) was reclassified as "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) in 2016. Most existing studies that examined outcomes included patients managed as EFVPTC and only retrospectively reclassified as NIFTP. This is the first study to evaluate the clinicopathological, molecular and surveillance characteristics of patients diagnosed with NIFTP at the time of surgery and managed based on this diagnosis. METHODS We performed a retrospective cohort study of consecutive cases diagnosed as NIFTP from June 2016 to October 2021 identified from electronic medical records at a large tertiary care institution. Patients with co-existing low risk thyroid cancers ≥1.0 cm in size or any size aggressive histology were excluded, and review of demographic, clinical, imaging, cytologic, and molecular genetic data was performed. Initial care was delivered according to existing clinical guidelines, with a consensus institutional plan for 5-year follow-up after surgery. RESULTS Among 79 patients with 84 nodules diagnosed as NIFTP after surgery, 83.5% (66/79) were females and the mean age was 51 years (range 21-84). Mean NIFTP size was 2.4 cm (range 0.15-8.0). On ultrasound, the majority of nodules were categorized as TI-RADS 3 (55.3%, 42/76) and TI-RADS 4 (36.8%, 28/76). On cytology, they were typically diagnosed as Bethesda III (69.1%, 47/68) or Bethesda IV (23.5%, 16/68). Molecular testing was performed on 62 nodules, and molecular alterations were found in 93.5% (58/62). The most common alterations identified in NIFTP were RAS mutation (75.4%, 43/57), THADA fusion (12.3%, 7/57) and BRAF K601E mutation (7.0%, 4/57). Fifty-two (65.8%) patients underwent lobectomy and 27 (34.2%) total thyroidectomy, and no patient received completion thyroidectomy. Twenty-one patients (26.5%) had co-existing papillary or follicular microcarcinoma. None of the patients received radioiodine ablation. On a mean follow-up of 28.5 months (range 6-69 months), no structural or biochemical recurrences were observed. CONCLUSIONS In this large cohort of patients with NIFTP diagnosed at the time of surgery and managed typically by lobectomy with no radioiodine ablation, no evidence of tumor recurrence was identified on a limited follow-up. This finding supports indolent clinical course of NIFTP.

Introduction Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. Research design and methods Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for >= 1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for >= 90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. Results Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%+/- 1.3%, from 9.4%+/- 1.0% at baseline to 8.0%+/- 1.2% after device use, p<0.0001 (mean +/- SD). Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%+/- 0.14% (mean +/- SE), from baseline 9.2%+/- 1.0% to 8.1%+/- 1.1%, p <= 0.0001, with moderate to high heterogeneity between sites (Q=43.9, I-2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites. The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. Conclusions In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

EIF1AX gene mutations are reported in both benign and malignant thyroid tumors, with unclear outcomes when detected preoperatively. The aim of this study was to determine the features and outcomes of thyroid nodules with various types of mutation identified in cytologic (fine-needle aspiration) samples on preoperative ThyroSeq testing and with surgical outcomes. In this single-institution retrospective study of 31 consecutive patients, 77% were female and nodule size ranged from 1.5 to 9.4 cm with widely varying cytologic and TI-RADS ultrasound categorizations. Among two main mutational hotspots, 55% were located in exon 2 and 45% at the intron 5/exon 6 splice site. On histology, 45% of -positive nodules were cancer/noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) including 19% encapsulated follicular variant papillary thyroid carcinoma, 10% follicular carcinoma, 10% anaplastic carcinoma (ATC), and 7% NIFTP. Almost half (48%) of patients had one or more coexisting mutations, most frequently RAS. The prevalence of cancer/NIFTP was 80% for mutation with coexisting molecular alteration vs 13% with an isolated mutation (P = 0.0002). Cancer probability was associated with mutation type and was 64% for splice-site mutation and 29% for non-splice mutation (P = 0.075). All 3 nodules with EIF1AX+RAS+TERT+TP53 mutations were ATC. In summary, in this study, all nodules with an isolated non-splice mutation were benign, one-third of those with an isolated splice mutation were cancer, and most nodules with coexisting with RAS or other alterations were malignant. These findings suggest that clinical management decisions for patients with EIF1AX-mutant nodules should consider both the type of mutation and its co-occurrence with other genetic alterations.

INTRODUCTION:Indeterminate thyroid cytology diagnoses are associated with intermediate risks of malignancy. Application of molecular testing (MT) to indeterminate specimens provides additional diagnostic and prognostic information. While a positive or suspicious MT result may prompt surgery, a negative MT result is associated with a low probability of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features and approximates that of a benign cytology diagnosis. Furthermore, ThyroSeq v3 MT has a "currently negative" result for findings with the probability of cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear feature that is slightly greater than that for the negative ThyroSeq v3 MT result but less than 10%, suggesting active surveillance. In this report, we discuss a case of a patient for whom clinical, cytologic, and molecular surveillance led to timely surgery and management. CLINICAL DETAILS:A 53-year-old man with a thyroid isthmus nodule had a fine-needle aspiration cytology diagnosis of atypia of undetermined significance and a subsequent ThyroSeq v3 MT, which revealed an EIF1AX mutation and a "currently negative" MT result. Surveillance with additional fine-needle aspiration samples demonstrated concerning genomic alterations (fluctuating EIF1AX allelic frequency and a non-V600E BRAF mutation), culminating in the conversion to a positive MT result 3 years later. Resection revealed an encapsulated noninvasive, oncocytic solid subtype of papillary thyroid carcinoma with increased mitotic activity. CONCLUSION:The case is notable for clinical, cytologic, and molecular surveillance demonstrating sequential pathologic alterations in an indeterminate thyroid nodule with EIF1AX mutation, leading to timely resection of the neoplasm before invasion manifested.

BACKGROUND:Molecular testing improves the diagnostic accuracy of thyroid cancer. Whether specific molecular testing results are associated with tumor phenotype or provide prognostic information needs further delineation. METHODS:Consecutive thyroid cancer patients after index thyroidectomy with ThyroSeq version 3 (Rye Brook, NY) molecular testing obtained on preoperative fine-needle aspiration or thyroidectomy specimens from patients with thyroid cancer were categorized into 3 molecular risk groups based on detected mutations, fusions, copy number alterations, and/or gene expression alterations and correlated with histopathology and recurrence, defined as biochemical or structural. RESULTS:Of 578 patients, 49.9%, 37.5%, and 12.6% had molecular risk group-low, molecular risk group-intermediate, and molecular risk group-high cancers, respectively. With a median 19-month follow-up, 9.1% patients recurred. Compared with molecular risk group-low, molecular risk group-intermediate cancers were diagnosed in younger patients and more often had microscopic extrathyroidal extension, involved margins, and nodal disease. Compared with molecular risk group-intermediate, molecular risk group-high cancers were diagnosed in older patients and more often had gross extrathyroidal extension and vascular invasion. In multivariable analysis, recurrence was more likely in molecular risk group-high cancers than in molecular risk group-intermediate (hazard ratio = 4.0; 95% confidence interval, 1.9-8.6; P < .001) and more likely in molecular risk group-intermediate than in molecular risk group-low (hazard ratio = 5.0; 95% confidence interval, 2.0-12.5; P < .001). CONCLUSION:Using modern comprehensive genotyping, the genetic profile of thyroid cancers can be categorized into 3 novel molecular risk groups that were associated with histopathologic phenotype and recurrence in short-term follow-up.