Neurological manifestations in liver diseases have been well-described. Parkinsonism developing in cirrhotic patients is a unique clinical, neuroradiological, and biological entity. The symptoms are often insidious in onset and occur after liver disease has made its presentation. Acute dysarthria as the presenting manifestation of cirrhosis is rare. Here we report three cases where liver disease made an unusual presentation as acute dysarthria. In all cases the abruptness of the onset prompted the treating physicians to make a diagnosis of stroke. The computed tomography (CT) scans of all these patients did not show any evidence of stroke. This was followed by magnetic resonance imaging (MRI) which showed the characteristic symmetric high-signal intensities in globus pallidus and substantia nigra in T1-weighted images, a reflection of increased tissue concentrations of manganese that helped in making a retrospective diagnosis of liver disease, confirmed later by altered serum albumin to globulin ratios and altered liver echo texture in ultra sonogram.
Introduction:Payers are implementing reimbursement restrictions for non-guideline based care. Limited information exists regarding real-world concordance with guidelines for metastatic breast cancer (MBC) treatment. Further, the impact of non-concordance on mortality is unknown. We address these gaps by using the Surveillance, Epidemiology, and End Results (SEER) Program-linked Medicare database to evaluate national concordance with NCCN guidelines and the association between concordance and mortality. Methods: From 2007 to 2013, women with de novo (n=988) or recurrent metastatic breast cancer (n=5651) were evaluated for concordance of first-line systemic therapy (hormonal therapy, chemotherapy, and Her2-targeted therapy) with NCCN guidelines. Concordance was defined as receipt of single agent or combination treatments listed on NCCN guidelines. Non-concordant treatments were grouped into 5 categories: single-agent HER2-targeted therapy (33%), adjuvant regimens used in the metastatic setting (12%), therapy mismatched with ER/HER2 status (12%), non-approved bevacizumab regimens (10%), and other miscellaneous reasons (33%). Multivariable logistic regression was used to identify predictors of non-concordance. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox regression to compare all-cause mortality associated with non-concordant vs. concordant treatment adjusted for receptor status, comorbidities, age, race, poverty level, entitlement reason, and treatment year. Results: Mean age at MBC diagnosis was 69y; 77% were white. Median follow-up was 1.2 years. The prevalence of non-concordant first-line systemic therapy was 19% for de novo MBC and 18% for recurrent MBC. Younger age, hormone-receptor negative status, and Her2-positive status were associated with non-concordant treatments for Stage IV and recurrent MBC patients (p<0.001). Higher poverty by census tract was associated with non-concordance in recurrent MBC (p<0.05). The most frequent category of non-concordant treatment in de novo MBC was use of adjuvant regimens in Stage IV MBC (43%) and use of single-agent HER2-targeted therapy (31%) in recurrent MBCs. Adjusted overall survival was similar for patients with de novo MBC receiving concordant and non-concordant treatments (HR 0.88, CI 0.72-1.65). Mortality was modestly increased for patients with recurrent MBC receiving non-concordant care (HR 1.12, CI 1.02-1.22); however, substantial differences were noted by category of non-concordance. Compared to concordant treatment, single-agent HER2-targeted therapy was associated with decreased risk of mortality (HR 0.78, CI 0.68-0.91). Increased mortality was observed for non-approved bevacizumab use (HR 1.79, CI 1.44-2.22) and other miscellaneous regimens (HR 1.42, CI 1.26-1.60). Mortality for therapy mismatched with ER/HER2 status was similar to concordant treatment (HR 1.13, CI 0.88-1.44). Conclusions: In the first-line setting, treatment inconsistent with NCCN guidelines remains common (18%). Overall mortality was not substantially higher among non-concordant patients. However, mortality risk varied (in both directions) by category of non-concordance. These findings may provide an opportunity for considering refinement of NCCN guidelines. Citation Format: Rocque GB, Williams CP, Jackson BE, Halilova KI, Pisu M, Andres F, Smita B. Concordance with National comprehensive cancer network (NCCN) metastatic breast cancer guidelines and impact on overall survival [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-07-02.
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