Research Spotlight

Posted February 15th 2020

Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction in Patients With Nonalcoholic Fatty Liver Disease.

Milton Packer M.D.E
Milton Packer M.D.

Packer, M. (2020). “Atrial Fibrillation and Heart Failure With Preserved Ejection Fraction in Patients With Nonalcoholic Fatty Liver Disease.” Am J Med 133(2): 170-177.

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The most common causes of chronic liver disease in the developed world-nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH)-are the hepatic manifestations of an insulin-resistant state that is linked to visceral adiposity and systemic inflammation. NAFLD and NASH lead to an expansion of epicardial adipose tissue and the release of proinflammatory adipocytokines that cause microcirculatory dysfunction and fibrosis of the adjoining myocardium, resulting in atrial fibrillation as well as heart failure with a preserved ejection fraction (HFpEF). Inflammatory changes in the left atrium lead to electroanatomical remodeling; thus, NAFLD and NASH markedly increase the risk of atrial fibrillation. Simultaneously, patients with NAFLD or NASH commonly show diastolic dysfunction or latent HFpEF. Interventions include 1) weight loss by caloric restriction, bariatric surgery, or intensive exercise, and 2) drugs that ameliorate fat-mediated inflammation in both the liver and heart (eg, statins, metformin, sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide-1 receptor agonists, and pioglitazone). Patients with NAFLD or NASH commonly have an inflammation-related atrial and ventricular myopathy, which may contribute to symptoms and long-term outcomes.


Posted February 15th 2020

A meta-analysis of the accuracy of a neuroendocrine tumor mRNA genomic biomarker (NETest) in blood.

Andrew S. Paulson M.D.
Andrew S. Paulson M.D.

Oberg, K., A. Califano, J. R. Strosberg, S. Ma, U. Pape, L. Bodei, G. Kaltsas, C. Toumpanakis, J. R. Goldenring, A. Frilling and S. Paulson (2020). “A meta-analysis of the accuracy of a neuroendocrine tumor mRNA genomic biomarker (NETest) in blood.” Ann Oncol 31(2): 202-212.

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BACKGROUND: The lack of an accurate blood biomarker in neuroendocrine tumor (NET) disease has hindered management. The advance of genomic medicine and the development of molecular biomarkers has provided a strategy-liquid biopsy-to facilitate real-time management. We reviewed the role of a blood mRNA-based NET biomarker, the NETest, as an in vitro diagnostic (IVD). PATIENTS AND METHODS: A systematic review of the literature using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was undertaken. The methodological quality was evaluated using the QUADAS-2 tool. We identified ten original scientific papers that met the inclusion criteria. These were assessed by qualitative analysis and thereafter meta-analysis. Data were pooled and a median [95% confidence interval (CI)] diagnostic odds ratio (DOR), positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated. For the meta-analysis, a generic inverse variance method was undertaken using the accuracy and area under the curve (AUC) data. RESULTS: The ten studies exhibited moderate to high methodological quality. They evaluated NETest usage both as a diagnostic and as a monitoring tool. The meta-analysis identified the diagnostic accuracy of the NETest to be 95%-96% with a mean DOR of 5 853, +LR of 195, and -LR of 0.06. The NETest was 84.5%-85.5% accurate in differentiating stable disease from progressive disease. As a marker of natural history, the accuracy was 91.5%-97.8%. As an interventional/response biomarker, the accuracy was 93.7%-97.4%. The pooled AUC for the NETest was 0.954 +/- 0.005, with a z-statistic of 175.06 (P < 0.001). CONCLUSIONS: The NETest is an accurate biomarker suitable for clinical use in NET disease management. The meta-analysis supports the utility of the NETest as an IVD to establish a diagnosis and monitor therapeutic efficacy. The use of this as a biomarker provides information relevant to NET management consistent with observations regarding utility of liquid biopsies in other oncological disciplines.E


Posted February 15th 2020

Comparative Effectiveness of Sleep Apnea Screening Instruments During Inpatient Rehabilitation Following Moderate to Severe TBI.

Marie Dahdah, Ph.D.
Marie Dahdah, Ph.D.

Nakase-Richardson, R., D. J. Schwartz, L. Drasher-Phillips, J. M. Ketchum, K. Calero, M. N. Dahdah, K. R. Monden, K. Bell, U. Magalang, J. M. Hoffman, J. Whyte, J. Bogner and J. M. Zeitzer (2020). “Comparative Effectiveness of Sleep Apnea Screening Instruments During Inpatient Rehabilitation Following Moderate to Severe TBI.” Arch Phys Med Rehabil 101(2): 283-296.

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OBJECTIVE: To determine the diagnostic sensitivity and specificity and comparative effectiveness of traditional sleep apnea screening tools in traumatic brain injury (TBI) neurorehabilitation admissions. DESIGN: Prospective diagnostic comparative effectiveness trial of sleep apnea screening tools relative to the criterion standard, attended level 1 polysomnography including encephalography. SETTING: Six TBI Model System Inpatient Rehabilitation Centers. PARTICIPANTS: Between May 2017 and February 2019, 449 of 896 screened were eligible for the trial with 345 consented (77% consented). Additional screening left 263 eligible for and completing polysomnography with final analyses completed on 248. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Area under the curve (AUC) of screening tools relative to total apnea hypopnea index>/=15 (AHI, moderate to severe apnea) measured at a median of 47 days post-TBI (interquartile range, 29-47). RESULTS: The Berlin high-risk score (receiving operating curve [ROC] AUC=0.634) was inferior to the Multivariable Apnea Prediction Index (MAPI) (ROC AUC=0.780) (P=.0211; CI, 0.018-0.223) and Snoring, Tired, Observed, Blood Pressure, Body Mass Index, Age, Neck Circumference, and Gender (STOPBANG) score (ROC AUC=0.785) (P=.001; CI, 0.063-0.230), both of which had comparable AUC (P=.7245; CI, -0.047 to 0.068). Findings were similar for AHI>/=30 (severe apnea); however, no differences across scales was observed at AHI>/=5. The pattern was similar across TBI severity subgroups except for posttraumatic amnesia (PTA) status wherein the MAPI outperformed the Berlin. Youden’s index to determine risk yielded lower sensitivities but higher specificities relative to non-TBI samples. CONCLUSION: This study is the first to provide clinicians with data to support a choice for which sleep apnea screening tools are more effective during inpatient rehabilitation for TBI (STOPBANG, MAPI vs Berlin) to help reduce comorbidity and possibly improve neurologic outcome.


Posted February 15th 2020

Observational Study of Treatment Patterns in Patients with Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Non-Small Cell Lung Cancer After First-Line EGFR-Tyrosine Kinase Inhibitors.

Eric Nadler M.D.
Eric Nadler M.D.

Nadler, E., M. Pavilack, J. L. Espirito, J. Clark and A. Fernandes (2020). “Observational Study of Treatment Patterns in Patients with Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Non-Small Cell Lung Cancer After First-Line EGFR-Tyrosine Kinase Inhibitors.” Adv Ther 37(2): 946-954.

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INTRODUCTION: Epidermal growth factor receptor (EGFR) mutations are observed in approximately 15% of patients with non-small cell lung cancer (NSCLC) in the USA. Little is known about treatment patterns in EGFR mutation-positive NSCLC following progression on or after first-line (1L) treatment with first- or second-generation EGFR tyrosine kinase inhibitors (EGFR-TKIs). Osimertinib, a third-generation EGFR-TKI, is a treatment option for patients with EGFR T790M-positive NSCLC following progression on 1L EGFR-TKIs. This study analyzed real-world treatment sequencing of EGFR-TKIs, EGFR T790M testing rates, and disposition of patients with EGFR mutations after 1L EGFR-TKI post-FDA approval of osimertinib in patients with EGFR mutation-positive NSCLC. METHODS: Adult patients with stage IV NSCLC and documented EGFR mutation-positive status were identified between December 1, 2015 and May 31, 2017 from the US Oncology Network iKnowMed electronic health record (EHR). Data were abstracted from the EHR database and supplemented by chart review. RESULTS: Of 308 patients, 302 (98%) received an EGFR-TKI overall, and 246 patients (80%) received a 1L EGFR-TKI. The most common 1L EGFR-TKI was erlotinib (66%); the remaining 1L regimens were predominantly combination chemotherapies with or without an EGFR-TKI. Only 80 patients (26%) received any 2L therapy. The most common EGFR-TKIs used as 2L monotherapy in patients who received 1L EGFR-TKI were afatinib and osimertinib (n = 7 for both). Among all patients treated with 1L EGFR-TKI (n = 246), 47 (19%) were tested for EGFR T790M [16 patients (34%) were positive], 48 (20%) remained on 1L EGFR-TKI, 29 (12%) received subsequent therapy, 38 (15%) had died on or after their 1L EGFR-TKI therapy, and 131 (53%) stopped their EGFR-TKI with no recorded evidence of having received subsequent therapy at follow-up end. CONCLUSION: Following 1L EGFR-TKI treatment, 19% of patients were tested for EGFR T790M, and most (69%) had no record of receiving any subsequent therapy.


Posted February 15th 2020

Society of Interventional Radiology Position Statement on the Role of Percutaneous Ablation in Renal Cell Carcinoma: Endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology.

Marco Cura M.D.
Marco Cura M.D.

Morris, C. S., M. O. Baerlocher, S. R. Dariushnia, E. D. McLoney, N. Abi-Jaoudeh, K. Nelson, M. Cura, A. K. Abdel Aal, J. W. Mitchell, S. Madassery, S. Partovi, T. D. McClure, A. L. Tam and S. Patel (2020). “Society of Interventional Radiology Position Statement on the Role of Percutaneous Ablation in Renal Cell Carcinoma: Endorsed by the Canadian Association for Interventional Radiology and the Society of Interventional Oncology.” J Vasc Interv Radiol 31(2): 189-194.e183.

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In accordance with multidisciplinary and society guidelines, Society of Interventional Radiology (SIR) considers thermal PA to be an acceptable treatment option for stage T1a renal cell carcinoma (RCC) neoplasms (≤4 cm in diameter) in carefully selected patients and can be offered over active surveillance. Perccutaneous ablation (PA) may also have a potential beneficial role to play in the treatment of T1b tumors as well as oligometastatic RCC. However, future research in this area is warranted before strong recommendations can be made. SIR also recommends further investigation directly comparing ablation modalities, as well as comparing PA to surgical therapies with RCTs or other prospective study designs with adherence to standardized reporting of trials. RECOMMENDATIONS: 1. In patients with small renal tumors (stage T1a), percutaneous thermal ablation is a safe and effective treatment with fewer complications than nephrectomy and acceptable long-term oncological and survival outcomes. (Level of Evidence: C; Strength of Recommendation: Moderate). 2. In selected patients with suspected T1a RCC, percutaneous thermal ablation should be offered over active surveillance. (Level of Evidence: C; Strength of Recommendation: Moderate). 3. Percutaneous biopsy of small renal masses is recommended before or during PA, whenever possible. (Level of Evidence C; Strength of Recommendation: Moderate). 4. In high-risk patients with T1b RCC who are not surgical candidates, percutaneous thermal ablation may be an appropriate treatment option; however, further research in this area is required. (Level of Evidence D; Strength of Recommendation: Weak). 5. PA of oligometastatic RCC may be appropriate in patients with surgically resectable primary RCC who are not candidates for metastasectomy. (Level of Evidence D; Strength of Recommendation: Weak). 6. Radiofrequency ablation, cryoablation, and MW ablation are all appropriate modalities for thermal ablation, and method of ablation should be left to the discretion of the operating physician. (Level of Evidence: D; Strength of Recommendation: Weak). (Excerpt from text, p. 192-193; no abstract available.)