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Gene expression in triple-negative breast cancer in relation to survival.
Wang S, Beeghly-Fadiel A, Cai Q, Cai H, Guo X, Shi L, Wu J, Ye F, Qiu Q, Zheng Y, Zheng W, Bao PP, Shu XO
(2018) Breast Cancer Res Treat 171: 199-207
MeSH Terms: Adult, Aged, Biomarkers, Tumor, Female, Gene Expression, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Middle Aged, Neoplasm Grading, Neoplasm Staging, Population Surveillance, Prognosis, Registries, Survival Analysis, Triple Negative Breast Neoplasms
Show Abstract · Added December 6, 2018
PURPOSE - The identification of biomarkers related to the prognosis of triple-negative breast cancer (TNBC) is critically important for improved understanding of the biology that drives TNBC progression.
METHODS - We evaluated gene expression in total RNA isolated from formalin-fixed paraffin-embedded tumor samples using the NanoString nCounter assay for 469 TNBC cases from the Shanghai Breast Cancer Survival Study. We used Cox regression to quantify Hazard Ratios (HR) and corresponding confidence intervals (CI) for overall survival (OS) and disease-free survival (DFS) in models that included adjustment for breast cancer intrinsic subtype. Of 302 genes in our discovery analysis, 22 were further evaluated in relation to OS among 134 TNBC cases from the Nashville Breast Health Study and the Southern Community Cohort Study; 16 genes were further evaluated in relation to DFS in 335 TNBC cases from four gene expression omnibus datasets. Fixed-effect meta-analysis was used to combine results across data sources.
RESULTS - Twofold higher expression of EOMES (HR 0.90, 95% CI 0.83-0.97), RASGRP1 (HR 0.89, 95% CI 0.82-0.97), and SOD2 (HR 0.80, 95% CI 0.66-0.96) was associated with better OS. Twofold higher expression of EOMES (HR 0.89, 95% CI 0.81-0.97) and RASGRP1 (HR 0.87, 95% CI 0.81-0.95) was also associated with better DFS. On the contrary, a doubling of FA2H (HR 1.14, 95% CI 1.06-1.22) and GSPT1 (HR 1.33, 95% CI 1.14-1.55) expression was associated with shorter DFS.
CONCLUSIONS - We identified five genes (EOMES, FA2H, GSPT1, RASGRP1, and SOD2) that may serve as potential prognostic biomarkers and/or therapeutic targets for TNBC.
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16 MeSH Terms
Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.
Mahmood SS, Fradley MG, Cohen JV, Nohria A, Reynolds KL, Heinzerling LM, Sullivan RJ, Damrongwatanasuk R, Chen CL, Gupta D, Kirchberger MC, Awadalla M, Hassan MZO, Moslehi JJ, Shah SP, Ganatra S, Thavendiranathan P, Lawrence DP, Groarke JD, Neilan TG
(2018) J Am Coll Cardiol 71: 1755-1764
MeSH Terms: Aged, Antineoplastic Agents, Immunological, Case-Control Studies, Female, Glucocorticoids, Humans, Male, Methylprednisolone, Middle Aged, Myocarditis, Neoplasms, Registries, Troponin T
Show Abstract · Added April 22, 2018
BACKGROUND - Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized.
OBJECTIVES - The authors sought to understand the presentation and clinical course of ICI-associated myocarditis.
METHODS - After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block.
RESULTS - The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates.
CONCLUSIONS - Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.
Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.
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13 MeSH Terms
Sleep in children with type 1 diabetes and their parents in the T1D Exchange.
Jaser SS, Foster NC, Nelson BA, Kittelsrud JM, DiMeglio LA, Quinn M, Willi SM, Simmons JH, T1D Exchange Clinic Network
(2017) Sleep Med 39: 108-115
MeSH Terms: Blood Glucose, Child, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin A, Humans, Hypoglycemia, Male, Parents, Registries, Sleep, Sleep Wake Disorders, Surveys and Questionnaires
Show Abstract · Added May 18, 2018
OBJECTIVES - Sleep has physiological and behavioral impacts on diabetes outcomes, yet little is known about the impact of sleep disturbances in children with type 1 diabetes. The current study sought to characterize sleep in children with type 1 diabetes and in their parents and to examine the associations between child sleep, glycemic control and adherence, parent sleep and well-being, parental fear of hypoglycemia, and nocturnal caregiving behavior.
METHODS - Surveys were emailed to parents of 2- to 12-year-old participants in the Type 1 Diabetes (T1D) Exchange clinic registry. Clinical data were obtained from the registry for the 515 respondents.
RESULTS - In our sample, 67% of children met criteria for poor sleep quality. Child sleep quality was related to glycemic control (HbA1c of 7.9% [63 mmol/mol] in children with poor sleep quality vs 7.6% [60 mmol/mol] in children with non-poor sleep quality; P < 0.001) but not mean frequency of blood glucose monitoring (BGM) (7.6 times/day vs 7.4 in poor/non-poor quality; P = 0.56). Associations were similar for sleep duration. Children with poor sleep quality were more likely to experience severe hypoglycemia (4% in children with poor sleep quality vs 1% in children with non-poor sleep quality; P = 0.05) and more likely to experience DKA (7% vs 4%, respectively; P < 0.001). Poorer child sleep quality was associated with poorer parental sleep quality, parental well-being, and fear of hypoglycemia (P < 0.001 for all). Child sleep was not related to the use of diabetes-related technology (CGM, insulin pump).
CONCLUSIONS - Sleep may be a modifiable factor to improve glycemic control and reduce parental distress.
Copyright © 2017 Elsevier B.V. All rights reserved.
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Health disparities among adult patients with a phenotypic diagnosis of familial hypercholesterolemia in the CASCADE-FH™ patient registry.
Amrock SM, Duell PB, Knickelbine T, Martin SS, O'Brien EC, Watson KE, Mitri J, Kindt I, Shrader P, Baum SJ, Hemphill LC, Ahmed CD, Andersen RL, Kullo IJ, McCann D, Larry JA, Murray MF, Fishberg R, Guyton JR, Wilemon K, Roe MT, Rader DJ, Ballantyne CM, Underberg JA, Thompson P, Duffy D, Linton MF, Shapiro MD, Moriarty PM, Knowles JW, Ahmad ZS
(2017) Atherosclerosis 267: 19-26
MeSH Terms: Adult, African Americans, Aged, Asian Americans, Cardiovascular Diseases, Cholesterol, HDL, Cholesterol, LDL, Ethnic Groups, Female, Health Status Disparities, Healthcare Disparities, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Hyperlipoproteinemia Type II, Male, Middle Aged, Multicenter Studies as Topic, Odds Ratio, Phenotype, Prospective Studies, Registries, Retrospective Studies, Risk Factors, Sex Factors
Show Abstract · Added April 10, 2018
BACKGROUND AND AIMS - Most familial hypercholesterolemia (FH) patients remain undertreated, and it is unclear what role health disparities may play for FH patients in the US. We sought to describe sex and racial/ethnic disparities in a national registry of US FH patients.
METHODS - We analyzed data from 3167 adults enrolled in the CAscade SCreening for Awareness and DEtection of Familial Hypercholesterolemia (CASCADE-FH) registry. Logistic regression was used to evaluate for disparities in LDL-C goals and statin use, with adjustments for covariates including age, cardiovascular risk factors, and statin intolerance.
RESULTS - In adjusted analyses, women were less likely than men to achieve treated LDL-C of <100 mg/dL (OR 0.68, 95% CI, 0.57-0.82) or ≥50% reduction from pretreatment LDL-C (OR 0.79, 95% CI, 0.65-0.96). Women were less likely than men to receive statin therapy (OR, 0.60, 95% CI, 0.50-0.73) and less likely to receive a high-intensity statin (OR, 0.60, 95% CI, 0.49-0.72). LDL-C goal achievement also varied by race/ethnicity: compared with whites, Asians and blacks were less likely to achieve LDL-C levels <100 mg/dL (Asians, OR, 0.47, 95% CI, 0.24-0.94; blacks, OR, 0.49, 95% CI, 0.32-0.74) or ≥50% reduction from pretreatment LDL-C (Asians, OR 0.56, 95% CI, 0.32-0.98; blacks, OR 0.62, 95% CI, 0.43-0.90).
CONCLUSIONS - In a contemporary US population of FH patients, we identified differences in LDL-C goal attainment and statin usage after stratifying the population by either sex or race/ethnicity. Our findings suggest that health disparities contribute to the undertreatment of US FH patients. Increased efforts are warranted to raise awareness of these disparities.
Copyright © 2017 Elsevier B.V. All rights reserved.
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24 MeSH Terms
Variation in Radiologic and Urologic Computed Tomography Interpretation of Urinary Tract Stone Burden: Results From the Registry for Stones of the Kidney and Ureter.
Tzou DT, Isaacson D, Usawachintachit M, Wang ZJ, Taguchi K, Hills NK, Hsi RS, Sherer BA, Reliford-Titus S, Duty B, Harper JD, Sorensen M, Sur RL, Stoller ML, Chi T
(2018) Urology 111: 59-64
MeSH Terms: Diagnostic Techniques, Urological, Female, Humans, Kidney Calculi, Male, Middle Aged, Prospective Studies, Radiography, Registries, Tomography, X-Ray Computed, Ureteral Calculi
Show Abstract · Added January 16, 2018
OBJECTIVE - To compare the measured stone burden recorded between urologists and radiologists, and examine how these differences could potentially impact stone management. As current urologic stone surgery guideline recommendations are based on stone size, accurate stone measurements are crucial to direct appropriate treatment. This study investigated the discrepant interpretation that often exists between urologic surgeons and radiologists' estimation of patient urinary stone burden.
MATERIALS AND METHODS - From November 2015 through August 2016, new patients prospectively enrolled into the Registry for Stones of the Kidney and Ureter (ReSKU) were included if they had computed tomography images available and an accompanying official radiologic report at the time of their urologist provider visit. Stone number and aggregate stone size were compared between the urologic interpretation and the corresponding radiologic reports.
RESULTS - Of 219 patients who met the inclusion criteria, concordance between urologic and radiologic assessment of aggregate stone size was higher for single stone sizing (63%) compared with multiple stones (32%). Statistical significance was found in comparing the mean difference in aggregate stone size for single and multiple stones (P <.01). Over 33% of stone-containing renal units had a radiologic report with an unclear size estimation or size discrepancy that could lead to non-guideline-driven surgical management.
CONCLUSION - Significant variation exists between urologic and radiologic computed tomography interpretations of stone burden. Urologists should personally review patient imaging when considering stone surgical management. A standardized method for measuring and reporting stone parameters is needed among urologists and radiologists.
Copyright © 2017 Elsevier Inc. All rights reserved.
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11 MeSH Terms
Renal Medullary Carcinoma: Establishing Standards in Practice.
Beckermann KE, Sharma D, Chaturvedi S, Msaouel P, Abboud MR, Allory Y, Bourdeaut F, Calderaro J, de Cubas AA, Derebail VK, Hong AL, Naik RP, Malouf GG, Mullen EA, Reuter VE, Roberts CWM, Walker CL, Wood CG, DeBaun MR, Van Poppel H, Tannir NM, Rathmell WK
(2017) J Oncol Pract 13: 414-421
MeSH Terms: Anemia, Sickle Cell, Carcinoma, Medullary, Humans, Kidney Neoplasms, Practice Guidelines as Topic, Registries
Show Abstract · Added July 17, 2017
Although renal medullary carcinoma (RMC) is a rare subtype of kidney cancer, it is particularly devastating in that it is nearly uniformly lethal. No established guidelines exist for the diagnosis and management of RMC. In April 2016, a panel of experts developed clinical guidelines on the basis of a literature review and consensus statements. The goal was to propose recommendations for standardized diagnostic and management approaches and to establish an international clinical registry and biorepository for RMC. Published data are limited to case reports and small retrospective reviews. The RMC Working Group prepared recommendations to inform providers and patients faced with a low level of medical evidence. The diagnosis of RMC should be considered in all patients younger than 50 years with poorly differentiated carcinoma that arises from the renal medulla. These patients should be tested for sickle cell hemoglobinopathies, and if positive, SMARCB1/INI1 loss should be confirmed by immunohistochemistry. The majority of patients with RMC are diagnosed with metastatic disease. Upfront radical nephrectomy should be considered in patients with good performance status and low metastatic burden or after response to systemic therapy. Currently, cytotoxic, platinum-based chemotherapy provides the best, albeit brief, palliative clinical benefit. Vascular endothelial growth factor-directed therapies and mammalian target of rapamycin inhibitors are ineffective in RMC as monotherapy. Therapeutic trials of novel agents are now available for RMC, and every effort should be made to enroll patients in clinical studies.
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6 MeSH Terms
Evaluation of genetic variants in association with colorectal cancer risk and survival in Asians.
Wang N, Lu Y, Khankari NK, Long J, Li HL, Gao J, Gao YT, Xiang YB, Shu XO, Zheng W
(2017) Int J Cancer 141: 1130-1139
MeSH Terms: Asian Continental Ancestry Group, Case-Control Studies, China, Colorectal Neoplasms, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Polymorphism, Single Nucleotide, Registries, Risk
Show Abstract · Added April 10, 2018
Genome-wide association studies (GWAS) have identified over 40 genetic loci associated with colorectal cancer (CRC) risk. The association of single nucleotide polymorphisms (SNPs) at these loci with CRC risk and survival has not been adequately evaluated in East Asians. GWAS-identified CRC risk variants were used to construct weighted genetic risk scores (GRSs). We evaluated these GRSs in association with CRC risk in 3,303 CRC cases and 3,553 controls using logistic regression models. Associations with overall and CRC-specific survival were assessed in 731 CRC patients using Cox regression models. The association between the GRSs (overall and Asian-specific) and CRC risk was approximately twofold (highest vs. lowest quintile), and the shape of the dose-response was linear (p  = 1.24 × 10 and 3.02 × 10 for overall GRS and Asian-specific GRS, respectively). The association of the GRS with CRC risk was stronger among those with a family history of CRC (p  = 0.007). Asian-specific GRS using previously reported survival SNPs increased risk for mortality and the shape of the dose-response was linear for CRC-specific and all-cause mortality (p  = 0.01 and 0.006, respectively). Furthermore, the minor alleles of rs6983267 and rs1957636 were associated with worse CRC-specific and overall survival. We show that GRSs constructed using GWAS-identified common variants are strongly associated with CRC risk in Asians. We confirm previous findings for the possible association between some SNPs with survival, and provide evidence for two additional CRC risk variants that may be related to CRC survival.
© 2017 UICC.
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Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry.
Humpl T, Berger RMF, Austin ED, Fasnacht Boillat MS, Bonnet D, Ivy DD, Zuk M, Beghetti M, Schulze-Neick I
(2017) Cardiol Young 27: 1123-1132
MeSH Terms: Adolescent, Antihypertensive Agents, Calcium Channel Blockers, Cardiac Catheterization, Child, Child, Preschool, Female, Humans, Hypertension, Pulmonary, Infant, Male, Phosphodiesterase 5 Inhibitors, Prognosis, Pulmonary Circulation, Pulmonary Wedge Pressure, Registries, Vasodilator Agents
Show Abstract · Added February 21, 2017
Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry. Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and <18 years of age and diagnostic cardiac catheterisation consistent with pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg). At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy. There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.
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17 MeSH Terms
Quality-of-life metrics with vagus nerve stimulation for epilepsy from provider survey data.
Englot DJ, Hassnain KH, Rolston JD, Harward SC, Sinha SR, Haglund MM
(2017) Epilepsy Behav 66: 4-9
MeSH Terms: Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Drug Resistant Epilepsy, Female, Humans, Infant, Male, Middle Aged, Outcome Assessment (Health Care), Quality of Life, Registries, Vagus Nerve Stimulation, Young Adult
Show Abstract · Added June 23, 2017
OBJECTIVE - Drug-resistant epilepsy is a devastating disorder associated with diminished quality of life (QOL). Surgical resection leads to seizure freedom and improved QOL in many epilepsy patients, but not all individuals are candidates for resection. In these cases, neuromodulation-based therapies such as vagus nerve stimulation (VNS) are often used, but most VNS studies focus exclusively on reduction of seizure frequency. QOL changes and predictors with VNS remain poorly understood.
METHOD - Using the VNS Therapy Patient Outcome Registry, we examined 7 metrics related to QOL after VNS for epilepsy in over 5000 patients (including over 3000 with ≥12months follow-up), as subjectively assessed by treating physicians. Trends and predictors of QOL changes were examined and related to post-operative seizure outcome and likelihood of VNS generator replacement.
RESULTS - After VNS therapy, physicians reported patient improvement in alertness (58-63%, range over follow-up period), post-ictal state (55-62%), cluster seizures (48-56%), mood change (43-49%), verbal communication (38-45%), school/professional achievements (29-39%), and memory (29-38%). Predictors of net QOL improvement included shorter time to implant (odds ratio [OR], 1.3; 95% confidence interval [CI], 1.1-1.6), generalized seizure type (OR, 1.2; 95% CI, 1.0-1.4), female gender (OR, 1.2; 95% CI, 1.0-1.4), and Caucasian ethnicity (OR, 1.3; 95% CI, 1.0-1.5). No significant trends were observed over time. Patients with net QOL improvement were more likely to have favorable seizure outcomes (chi square [χ]=148.1, p<0.001) and more likely to undergo VNS generator replacement (χ=68.9, p<0.001) than those with worsened/unchanged QOL.
SIGNIFICANCE - VNS for drug-resistant epilepsy is associated with improvement on various QOL metrics subjectively rated by physicians. QOL improvement is associated with favorable seizure outcome and a higher likelihood of generator replacement, suggesting satisfaction with therapy. It is important to consider QOL metrics in neuromodulation for epilepsy, given the deleterious effects of seizures on patient QOL.
Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.
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Plasma hepatocyte growth factor is a novel marker of AL cardiac amyloidosis.
Swiger KJ, Friedman EA, Brittain EL, Tomasek KA, Huang S, Su YR, Sawyer DB, Lenihan DJ
(2016) Amyloid 23: 242-248
MeSH Terms: Aged, Amyloidosis, Biomarkers, Cardiomyopathies, Cohort Studies, Diagnosis, Differential, Female, Galectin 3, Heart Failure, Systolic, Hepatocyte Growth Factor, Humans, Hypertrophy, Left Ventricular, Immunoglobulin Light Chains, Interleukin-6, Male, Middle Aged, Prealbumin, Registries, Survival Analysis, Vascular Endothelial Growth Factor A
Show Abstract · Added June 7, 2018
BACKGROUND - Cardiac amyloidosis is an infiltrative cardiomyopathy that is challenging to diagnose. We hypothesized that the novel biomarkers hepatocyte growth factor (HGF), galectin-3 (GAL-3), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) would be elevated in cardiac amyloidosis and may be able to discriminate from non-cardiac systemic amyloidosis or other cardiomyopathies with similar clinical or morphologic characteristics.
METHODS - Patients were selected from the Vanderbilt Main Heart Registry according to the following groups: (1) amyloid light-chain (AL) cardiac amyloidosis (n = 26); (2) transthyretin (ATTR) cardiac amyloidosis (n = 7); (3) left ventricular hypertrophy (LVH) (n = 45); (4) systolic heart failure (n = 42); and (5) non-cardiac systemic amyloidosis (n = 7). Biomarkers were measured in stored plasma samples. Biomarkers' discrimination performance in predicting AL cardiac amyloidosis (i.e., Concordance index) was reported. A survival analysis was used to explore the relationship between HGF levels and mortality among AL cardiac amyloidosis patients.
RESULTS - HGF levels were markedly elevated in patients with AL cardiac amyloidosis (median = 622, interquartile range (IQR): 299-1228 pg/mL) compared with the other groups, including those with non-cardiac systemic amyloidosis (median = 134, IQR: 94-163 pg/mL, p < 0.001). HGF was not a specific marker for ATTR amyloidosis. Gal-3 was elevated in all groups with amyloidosis but could not differentiate between those with and without cardiac involvement. There was no difference in IL-6 or VEGF between those with AL cardiac amyloidosis compared to other groups (p = 0.13 and 0.057, respectively).
CONCLUSIONS - HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.
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