Research Spotlight

Posted November 15th 2018

Outcomes of Operative Treatment for Adult Cervical Deformity: A Prospective Multicenter Assessment With 1-Year Follow-up.

Richard Hostin M.D.

Richard Hostin M.D.

Ailon, T., J. S. Smith, C. I. Shaffrey, H. J. Kim, G. Mundis, M. Gupta, E. Klineberg, F. Schwab, V. Lafage, R. Lafage, P. Passias, T. Protopsaltis, B. Neuman, A. Daniels, J. K. Scheer, A. Soroceanu, R. Hart, R. Hostin, D. Burton, V. Deviren, T. J. Albert, K. D. Riew, S. Bess and C. P. Ames (2018). “Outcomes of Operative Treatment for Adult Cervical Deformity: A Prospective Multicenter Assessment With 1-Year Follow-up.” Neurosurgery 83(5): 1031-1039.

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BACKGROUND: Despite the potential for profound impact of adult cervical deformity (ACD) on function and health-related quality of life (HRQOL), there are few high-quality studies that assess outcomes of surgical treatment for these patients. OBJECTIVE: To determine the impact of surgical treatment for ACD on HRQOL. METHODS: We conducted a prospective cohort study of surgically treated ACD patients eligible for 1-yr follow-up. Baseline deformity characteristics, surgical parameters, and 1-yr HRQOL outcomes were assessed. RESULTS: Of 77 ACD patients, 55 (71%) had 1-yr follow-up (64% women, mean age of 62 yr, mean Charlson Comorbidity Index of 0.6, previous cervical surgery in 47%). Diagnoses included cervical sagittal imbalance (56%), cervical kyphosis (55%), proximal junctional kyphosis (7%) and coronal deformity (9%). Posterior fusion was performed in 85% (mean levels = 10), and anterior fusion was performed in 53% (mean levels = 5). Three-column osteotomy was performed in 24% of patients. One year following surgery, ACD patients had significant improvement in Neck Disability Index (50.5 to 38.0, P < .001), neck pain numeric rating scale score (6.9 to 4.3, P < .001), EuroQol 5 dimension (EQ-5D) index (0.51 to 0.66, P < .001), and EQ-5D subscores: mobility (1.9 to 1.7, P = .019), usual activities (2.2 to 1.9, P = .007), pain/discomfort (2.4 to 2.1, P < .001), anxiety/depression (1.8 to 1.5, P = .014). CONCLUSION: Based on a prospective multicenter series of ACD patients, surgical treatment provided significant improvement in multiple measures of pain and function, including Neck Disability Index, neck pain numeric rating scale score, and EQ-5D. Further follow-up will be necessary to assess the long-term durability of these improved outcomes.


Posted November 15th 2018

Treatment Patterns by EGFR Mutation Status in Non-Small Cell Lung Cancer Patients in the USA: A Retrospective Database Analysis.

Eric Nadler M.D.

Eric Nadler M.D.

Aguilar, K. M., K. B. Winfree, C. E. Muehlenbein, Y. E. Zhu, T. Wilson, S. Wetmore and E. S. Nadler (2018). “Treatment Patterns by EGFR Mutation Status in Non-Small Cell Lung Cancer Patients in the USA: A Retrospective Database Analysis.” Adv Ther 35(11): 1905-1919.

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INTRODUCTION: Targeted therapies, including tyrosine kinase inhibitors (TKIs) that target the sensitizing epidermal growth factor receptor (EGFR) gene are recommended for patients with non-small cell lung cancer (NSCLC). Most patients with NSCLC who test positive for the EGFR mutation and receive TKIs develop resistance to these drugs. Questions remain regarding which treatment sequence is optimal for patients with EGFR-mutant NSCLC, and few studies have evaluated patterns of TKI treatment use in NSCLC, irrespective of EGFR mutation status, in a real-world setting. This population-based study aimed to evaluate treatment patterns at a national level in the USA. METHODS: This retrospective observational study used data from the US Oncology Network’s iKnowMed database. Patients with advanced NSCLC who initiated first-line therapy with erlotinib and/or intravenous chemotherapy between January 1, 2012 and June 30, 2015 and met all other study criteria were included. Descriptive analyses assessed demographic and clinical characteristics and treatment patterns among the overall study cohort, as well as for specific erlotinib treatment subgroups, stratified by EGFR status. RESULTS: Among the 3108 patients identified, 18.5% were EGFR positive, 49.8% were EGFR negative, and 31.7% were EGFR documented unknown. For the overall cohort, 18.4% received first-line erlotinib monotherapy, fewer than 1% received first-line combination therapy (erlotinib plus chemotherapy), 4.7% received second-line erlotinib monotherapy, and 3.3% received second-line combination therapy. First-line erlotinib monotherapy was used in 77.8% of all EGFR positive patients. Almost two-thirds of the overall cohort were not observed to have advanced to second-line therapy. CONCLUSIONS: As treatment options evolve, this study provides real-world treatment patterns that suggest concordance with NCCN guidelines and confirm the remaining need to understand sequencing of therapies and related outcomes. FUNDING: Eli Lilly and Company.


Posted October 15th 2018

The Name of the Dog.

Taimur Safdur M.D.

Taimur Safdur M.D.

Safder, T. (2018). “The Name of the Dog.” N Engl J Med 379(14): 1299-1301.

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It was July 1, my first day of residency, and a queasy feeling lodged in my stomach as I donned my new white coat. It was different from the previous ones I’d worn — not just longer, but heavier. I was carrying in my pockets everything I thought I needed as a freshly minted doctor: my three favorite pens, a glossy Littmann Cardiology III stethoscope, copies of studies related to my patient with cirrhosis, and of course my trusty purple Sabatine’s Pocket Medicine. Before the day was over, my bodily-fluid–covered white coat would have made a fitting prop for a CSI episode, my attending physician wasn’t nearly as impressed as I’d hoped with the studies I waved in front of her, and worst of all, I had lost all three of my pens. But with the aid of my pockets, I’d gotten through. I’d played my part reasonably well most of the day, but the moment when my attending had brought me up short with a question kept replaying in my mind. During morning rounds, I had presented a patient who was admitted for chest pain after walking his dog. My attending had asked, “What was the name of his dog?” (Excerpt from text of this commentary, p. 1299-1300; no abstract available.)


Posted October 15th 2018

Transcatheter Mitral-Valve Repair in Patients with Heart Failure.

Michael J. Mack M.D.

Michael J. Mack M.D.

Stone, G. W., J. Lindenfeld, W. T. Abraham, S. Kar, D. S. Lim, J. M. Mishell, B. Whisenant, P. A. Grayburn, M. Rinaldi, S. R. Kapadia, V. Rajagopal, I. J. Sarembock, A. Brieke, S. O. Marx, D. J. Cohen, N. J. Weissman and M. J. Mack (2018). “Transcatheter Mitral-Valve Repair in Patients with Heart Failure.” N Engl J Med Sep 23. [Epub ahead of print].

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BACKGROUND: Among patients with heart failure who have mitral regurgitation due to left ventricular dysfunction, the prognosis is poor. Transcatheter mitral-valve repair may improve their clinical outcomes. METHODS: At 78 sites in the United States and Canada, we enrolled patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy. Patients were randomly assigned to transcatheter mitral-valve repair plus medical therapy (device group) or medical therapy alone (control group). The primary effectiveness end point was all hospitalizations for heart failure within 24 months of follow-up. The primary safety end point was freedom from device-related complications at 12 months; the rate for this end point was compared with a prespecified objective performance goal of 88.0%. RESULTS: Of the 614 patients who were enrolled in the trial, 302 were assigned to the device group and 312 to the control group. The annualized rate of all hospitalizations for heart failure within 24 months was 35.8% per patient-year in the device group as compared with 67.9% per patient-year in the control group (hazard ratio, 0.53; 95% confidence interval [CI], 0.40 to 0.70; P<0.001). The rate of freedom from device-related complications at 12 months was 96.6% (lower 95% confidence limit, 94.8%; P<0.001 for comparison with the performance goal). Death from any cause within 24 months occurred in 29.1% of the patients in the device group as compared with 46.1% in the control group (hazard ratio, 0.62; 95% CI, 0.46 to 0.82; P<0.001). CONCLUSIONS: Among patients with heart failure and moderate-to-severe or severe secondary mitral regurgitation who remained symptomatic despite the use of maximal doses of guideline-directed medical therapy, transcatheter mitral-valve repair resulted in a lower rate of hospitalization for heart failure and lower all-cause mortality within 24 months of follow-up than medical therapy alone. The rate of freedom from device-related complications exceeded a prespecified safety threshold. (Funded by Abbott; COAPT ClinicalTrials.gov number, NCT01626079.)


Posted October 15th 2018

Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.

James W. Choi M.D.

James W. Choi M.D.

Stone, G. W., S. G. Ellis, T. Gori, D. C. Metzger, B. Stein, M. Erickson, J. Torzewski, J. Williams, Jr., W. Lawson, T. M. Broderick, A. Kabour, G. Piegari, J. Cavendish, B. Bertolet, J. W. Choi, S. O. Marx, P. Genereux and D. J. Kereiakes (2018). “Blinded outcomes and angina assessment of coronary bioresorbable scaffolds: 30-day and 1-year results from the ABSORB IV randomised trial.” Lancet Sep 24. [Epub ahead of print].

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BACKGROUND: Previous studies showed more adverse events with coronary bioresorbable vascular scaffolds (BVS) than with metallic drug-eluting stents (DES), although in one randomised trial angina was reduced with BVS. However, these early studies were unmasked, lesions smaller than intended for the scaffold were frequently enrolled, implantation technique was suboptimal, and patients with myocardial infarction, in whom BVS might be well suited, were excluded. METHODS: In the active-controlled, blinded, multicentre, randomised ABSORB IV trial, patients with stable coronary artery disease or acute coronary syndromes aged 18 years or older were recruited from 147 hospitals in five countries (the USA, Germany, Australia, Singapore, and Canada). Enrolled patients were randomly assigned (1:1) to receive polymeric everolimus-eluting BVS (Absorb; Abbott Vascular, Santa Clara, CA, USA) with optimised implantation technique or cobalt-chromium everolimus-eluting stents (EES; Xience; Abbott Vascular, Santa Clara, CA, USA). Randomisation was stratified by diabetic status, whether patients would have been eligible for enrolment in the previous ABSORB III trial, and site. Patients and clinical assessors were masked to randomisation. The primary endpoint was target lesion failure (cardiac death, target vessel myocardial infarction, or ischaemia-driven target lesion revascularisation) at 30 days, tested for non-inferiority with a 2.9% margin for the risk difference. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02173379, and is closed to accrual. FINDINGS: Between Aug 15, 2014, and March 31, 2017, we screened 18 722 patients for eligibility, 2604 of whom were enrolled. 1296 patients were assigned to BVS, and 1308 patients were assigned to EES. Follow-up data at 30 days and 1 year, respectively, were available for 1288 and 1254 patients with BVS and for 1303 and 1272 patients with EES. Biomarker-positive acute coronary syndromes were present in 622 (24%) of 2602 patients, and, by angiographic core laboratory analysis, 78 (3%) of 2893 of lesions were in very small vessels. Target lesion failure at 30 days occurred in 64 (5.0%) patients assigned to BVS and 48 (3.7%) patients assigned to EES (difference 1.3%, upper 97.5% confidence limit 2.89; one-sided pnon-inferiority=0.0244). Target lesion failure at 1 year occurred in 98 (7.8%) patients assigned to BVS and 82 (6.4%) patients assigned to EES (difference 1.4%, upper 97.5% confidence limit 3.4; one-sided pnon-inferiority=0.0006). Angina, adjudicated by a central events committee at 1 year, occurred in 270 (20.3%) patients assigned to BVS and 274 (20.5%) patients assigned to EES (difference -0.3%, 95% CI -3.4% to 2.9%; one-sided pnon-inferiority=0.0008; two-sided psuperiority=0.8603). Device thrombosis within 1 year occurred in nine (0.7%) patients assigned to BVS and four (0.3%) patients assigned to EES (p=0.1586). INTERPRETATION: Polymeric BVS implanted with optimised technique in an expanded patient population resulted in non-inferior 30-day and 1-year rates of target lesion failure and angina compared with metallic DES. FUNDING: Abbott Vascular.