Publications by authors named "Andrew Flagg"

4 Publications

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Additional Surgery for Occult Risk Factors After Lobectomy in Solitary Thyroid Nodules is Predicted by Cytopathology Classification and Tumor Size.

Endocr Pract 2020 Jul 24;26(7):754-760. Epub 2020 Nov 24.

Johns Hopkins University School of Medicine, Division of Endocrinology, Diabetes and Metabolism, Baltimore, Maryland. Electronic address:

Objective: Clinical practice for differentiated thyroid cancer is moving towards lobectomy rather than total thyroidectomy in patients at low risk of recurrence. However, recurrence risk assessment depends on post-operative findings, while the surgical decision is based on preoperative factors. We determined the preoperative predictors of occult higher-risk pathology and rates of completion thyroidectomy among surgical candidates with nonbenign thyroid nodules 10 to 40 mm and no evidence of extrathyroidal extension or metastasis on preoperative evaluation.

Methods: Thyroid surgery cases at a single institution from 2005-2015 were reviewed to identify those meeting American Thyroid Association (ATA) criteria for lobectomy. ATA-based risk stratification from postoperative surgical pathology was compared to preoperative cytopathology, ultrasound, and clinical findings.

Results: Of 1,995 thyroid surgeries performed for nonbenign thyroid nodules 10 to 40 mm, 349 met ATA criteria for lobectomy. Occult high-risk features such as tall cell variant, gross extrathyroidal invasion, or vascular invasion were found in 36 cases (10.7%), while intraoperative lymphadenopathy led to surgical upstaging in 13 (3.7%). Intermediate risk features such as moderate lymphadenopathy or minimal extrathyroidal extension were present in an additional 44 cases. Occult risk features were present twice as often in Bethesda class 6 cases (35%) as in lower categories (12 to 17%). In multivariable analysis, Bethesda class and nodule size, but not age, race, sex, or ultrasound features, were significant predictors of occult higher-risk pathology.

Conclusion: Most solitary thyroid nodules less than 4 cm and with cytology findings including atypia of undetermined significance through suspicious for papillary thyroid cancer would be sufficiently treated by lobectomy.

Abbreviations: ATA = American Thyroid Association; CND = central neck dissection; DTC = differentiated thyroid cancer; ETE = extrathyroidal extension; FNA = fine needle aspiration; FTC/HCC = follicular thyroid carcinoma/Hurthle cell carcinoma; NIFTP = noninvasive follicular thyroid neoplasm with papillary-like nuclear features; OR = odds ratio; PTC = papillary thyroid cancer; US = ultrasound.
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http://dx.doi.org/10.4158/EP-2019-0473DOI Listing
July 2020

Understanding Why Residents May Inaccurately Log Their Role in Operations: A Look at the 2013 In-Training Examination Survey.

Ann Thorac Surg 2016 Jan 9;101(1):323-8. Epub 2015 Oct 9.

Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Background: With increased time and quality pressures, it may be more difficult for residents in cardiothoracic surgery residency programs to get independent operative experience. That may lead residents to inaccurately report their role as "surgeon" to meet American Board of Thoracic Surgery (ABTS) case requirements.

Methods: The 2013 In-Training Examination surveyed 312 cardiothoracic surgery residents and was used to contrast residents in traditional 2-year and 3-year cardiothoracic surgery residencies (traditional, n = 216) with those in 6-year integrated or 3+4-year programs (integrated, n = 96).

Results: Traditional program residents reported a higher percentage of cases that met the ABTS criteria of surgeon than did integrated program residents (p = 0.05) but were less likely to meet requirements if all cases were logged accurately (p = 0.03). The majority of residents in each program believed that their case log accurately reflected their experience as "surgeon." Residents who tended to log cases incorrectly had lower self-reported 2012 In-Training Examination percentiles, were less likely to meet case requirements if logged properly, and felt less prepared for board examinations and eventual practice compared with residents who logged cases correctly (all p < 0.001). Residents who believed they would not meet case requirements if logged correctly cited limited surgical opportunities, poor case diversity, and a compromised training environment but not the 80-hour work week, excessive simulation, or disproportionate number of complex cases as causes.

Conclusions: Overall cardiothoracic surgery residents appear to be satisfied with their training. There were specific subsets of trainees in both traditional and Integrated programs that are misrepresenting their role on cases because they otherwise may not meet the requirements.
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http://dx.doi.org/10.1016/j.athoracsur.2015.07.047DOI Listing
January 2016

Analysis of Clostridium difficile infections after cardiac surgery: epidemiologic and economic implications from national data.

J Thorac Cardiovasc Surg 2014 Nov 13;148(5):2404-9. Epub 2014 Apr 13.

Department of Thoracic and Cardiovascular Surgery, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio. Electronic address:

Objectives: Clostridium difficile infections (CDIs) have increased during the past 2 decades, especially among cardiac surgical patients, who share many of the comorbidity risk factors for CDI. Our objectives were to use a large national database to identify the regional-, hospital-, patient-, and procedure-level risk factors for CDI; and determine mortality, resource usage, and cost of CDIs in cardiac surgery.

Methods: Using the Nationwide Inpatient Sample database, we identified 349,122 patients who had undergone coronary artery bypass, valve, or thoracic-aortic surgery from 2004 to 2008. Of these, 2581 (0.75%) had been diagnosed with CDI. Multivariable regression analysis and the propensity method were used for risk adjustment.

Results: Compared with the West, CDIs were more likely to occur in the Northeast (odds ratio [OR], 1.28; 95% confidence interval [CI], 1.12-1.47) and Midwest (OR, 1.27, 95% CI, 1.11-1.46) and less likely in the South (OR, 0.80; 95% CI, 0.70-0.90). Medium-size hospitals (OR, 0.88; 95% CI, 0.78-0.99) had a lower risk of CDI than did large hospitals. Older age (>75 years; OR, 2.59; 95% CI, 1.93-3.49), longer preoperative length of stay (OR, 1.51; 95% CI, 1.43-1.60), Medicare (OR, 1.21; 95% CI, 1.05-1.39) and Medicaid (OR, 1.60; 95% CI, 1.31-1.96) coverage, and more comorbidities were associated with CDI. Among the matched pairs, patients with CDIs had greater mortality (302 [12%] vs 187 [7.2%], P<.001), a longer median length of stay (21 vs 11 days, P<.001), and greater median hospital charges ($193,330 vs $112,245, P<.001). The cumulative incremental cost of CDIs was an estimated $212 million annually.

Conclusions: Our results have shown that CDI is associated with increased morbidity and resource usage. Additional work is needed to better understand the complex interplay among regional-, hospital-, and patient-level factors.
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http://dx.doi.org/10.1016/j.jtcvs.2014.04.017DOI Listing
November 2014

The HILDA complex coordinates a conditional switch in the 3'-untranslated region of the VEGFA mRNA.

PLoS Biol 2013 20;11(8):e1001635. Epub 2013 Aug 20.

Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.

Cell regulatory circuits integrate diverse, and sometimes conflicting, environmental cues to generate appropriate, condition-dependent responses. Here, we elucidate the components and mechanisms driving a protein-directed RNA switch in the 3'UTR of vascular endothelial growth factor (VEGF)-A. We describe a novel HILDA (hypoxia-inducible hnRNP L-DRBP76-hnRNP A2/B1) complex that coordinates a three-element RNA switch, enabling VEGFA mRNA translation during combined hypoxia and inflammation. In addition to binding the CA-rich element (CARE), heterogeneous nuclear ribonucleoprotein (hnRNP) L regulates switch assembly and function. hnRNP L undergoes two previously unrecognized, condition-dependent posttranslational modifications: IFN-γ induces prolyl hydroxylation and von Hippel-Lindau (VHL)-mediated proteasomal degradation, whereas hypoxia stimulates hnRNP L phosphorylation at Tyr(359), inducing binding to hnRNP A2/B1, which stabilizes the protein. Also, phospho-hnRNP L recruits DRBP76 (double-stranded RNA binding protein 76) to the 3'UTR, where it binds an adjacent AU-rich stem-loop (AUSL) element, "flipping" the RNA switch by disrupting the GAIT (interferon-gamma-activated inhibitor of translation) element, preventing GAIT complex binding, and driving robust VEGFA mRNA translation. The signal-dependent, HILDA complex coordinates the function of a trio of neighboring RNA elements, thereby regulating translation of VEGFA and potentially other mRNA targets. The VEGFA RNA switch might function to ensure appropriate angiogenesis and tissue oxygenation during conflicting signals from combined inflammation and hypoxia. We propose the VEGFA RNA switch as an archetype for signal-activated, protein-directed, multi-element RNA switches that regulate posttranscriptional gene expression in complex environments.
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http://dx.doi.org/10.1371/journal.pbio.1001635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3747992PMC
March 2014