Summary Background Gene expression microarrays are being used to develop new prognostic and predictive tests for breast cancer, and might be used at the same time to confirm oestrogen-receptor status ...and ERBB2 status. Our goal was to establish a new method to assign oestrogen receptor and ERBB2-receptor status to breast carcinoma based on mRNA expression measured using Affymetrix U133A gene-expression profiling. Methods We used gene expression data of 495 breast cancer samples to assess the correlation between oestrogen receptor ( ESR1 ) and ERBB2 mRNA and clinical status of these genes (as established by immunohistochemical IHC or fluorescence in-situ hybridisation FISH, or both). Data from 195 fine-needle aspiration (FNA) samples were used to define mRNA cutoff values that assign receptor status. We assessed the accuracy of these cutoffs in two independent datasets: 123 FNA samples and 177 tissue samples (ie, resected or core-needle biopsied tissues). Profiling was done at two institutions by use of the same platform (Affymetrix U133A GeneChip). All data were uniformly normalised with dCHIP software. Findings ESR1 and ERBB2 mRNA levels correlated closely with routine measurements for receptor status in all three datasets. Spearman's correlation coefficients ranged from 0·62 to 0·77. An ESR1 mRNA cutoff value of 500 identified oestrogen-receptor-positive status with an overall accuracy of 90% (training set), 88% (first validation set), and 96% (second validation set). An ERBB2 mRNA threshold of 1150 identified ERBB2-positive status with the overall accuracy of 93% (training set), 89% (first validation set), and 90% (second validation set). Reproducibility of mRNA measurements in 34 replicate experiments was high (correlation coefficient 0·975 for ESR1 , 0·984 for ERBB2 ). Interpretation Amounts of ESR1 and ERBB2 mRNA as measured by the Affymetrix GeneChip reliably and reproducibly establish oestrogen-receptor status and ERBB2 status, respectively.
Patients with end-stage liver disease (ESLD) who also have underlying coronary artery disease (CAD) may be at increased risk for undergoing hemodynamically challenging orthotopic liver ...transplantation. Noninvasive single-photon emission computed tomographic (SPECT) imaging is often used to determine whether a patient with ESLD has unsuspected CAD. The objective of this study was to determine the accuracy of SPECT imaging for detection of CAD in patients with ESLD. Patients with ESLD who underwent coronary angiography and SPECT imaging before orthotopic liver transplantation were analyzed retrospectively. The predictive accuracy of clinical risk factors was calculated and compared to the results of SPECT imaging. There were 473 SPECT imaging studies. Adenosine SPECT imaging had a sensitivity of 62%, specificity of 82%, positive predictive value of 30%, and negative predictive value of 95% for diagnosing severe CAD. Regadenoson SPECT imaging had a sensitivity of 35%, specificity of 88%, positive predictive value of 23%, and negative predictive value of 93% for diagnosing severe CAD. The accuracy of a standard risk factor analysis showed no statistical difference in predicting CAD compared with adenosine (sensitivity McNemar's p = 0.48, specificity McNemar's p = 1.00) or regadenoson (sensitivity McNemar's p = 0.77, specificity McNemar's p = 1.00) SPECT studies. In conclusion, the 2 pharmaceutical agents had low sensitivity but high specificity for diagnosing CAD. However, because the sensitivity of the test is low, the chances of missing patients with ESLD with CAD is high, making SPECT imaging an inaccurate screening test. A standard risk factor analysis as a predictor for CAD in patients with ESLD is less expensive, has no radiation exposure, and is as accurate as SPECT imaging.
The aim of this study was to compare ticagrelor monotherapy with dual-antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stents.
The role of abbreviated DAPT ...followed by an oral P2Y12 inhibitor after PCI remains uncertain.
Two randomized trials, including 14,628 patients undergoing PCI, comparing ticagrelor monotherapy with standard DAPT on centrally adjudicated endpoints were identified, and individual patient data were analyzed using 1-step fixed-effect models. The protocol was registered in PROSPERO (CRD42019143120). The primary outcomes were the composite of Bleeding Academic Research Consortium type 3 or 5 bleeding tested for superiority and, if met, the composite of all-cause death, myocardial infarction, or stroke at 1 year, tested for noninferiority against a margin of 1.25 on a hazard ratio (HR) scale.
Bleeding Academic Research Consortium type 3 or 5 bleeding occurred in fewer patients with ticagrelor than DAPT (0.9% vs. 1.7%, respectively; HR: 0.56; 95% confidence interval CI: 0.41 to 0.75; p < 0.001). The composite of all-cause death, myocardial infarction, or stroke occurred in 231 patients (3.2%) with ticagrelor and in 254 patients (3.5%) with DAPT (HR: 0.92; 95% CI: 0.76 to 1.10; p < 0.001 for noninferiority). Ticagrelor was associated with lower risk for all-cause (HR: 0.71; 95% CI: 0.52 to 0.96; p = 0.027) and cardiovascular (HR: 0.68; 95% CI: 0.47 to 0.99; p = 0.044) mortality. Rates of myocardial infarction (2.01% vs. 2.05%; p = 0.88), stent thrombosis (0.29% vs. 0.38%; p = 0.32), and stroke (0.47% vs. 0.36%; p = 0.30) were similar.
Ticagrelor monotherapy was associated with a lower risk for major bleeding compared with standard DAPT, without a concomitant increase in ischemic events.
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The aim of this study was to examine the association between dual-antiplatelet therapy (DAPT) cessation and cardiovascular risk after percutaneous coronary intervention in relation to age.
...Examination of outcomes by age after percutaneous coronary intervention is relevant given the aging population.
Two-year clinical outcomes, incidence, and effect of DAPT cessation on outcomes were compared by ages ≤55, 56 to 74, and ≥75 years from the PARIS (Patterns of Non-Adherence to Antiplatelet Regimens in Stented Patients) registry. DAPT cessation included physician-recommended discontinuation, interruption for surgery, and disruption (from noncompliance or bleeding). Clinical endpoints were major adverse cardiac events (MACE) (a composite of cardiac death, definite or probable stent thrombosis, spontaneous myocardial infarction, or clinically indicated target lesion revascularization), a secondary restrictive definition of MACE (MACE2) excluding target lesion revascularization, and bleeding.
A total of 1,192 patients (24%) were ≤55 years, 2,869 (57%) were 56 to 74 years, and 957 (19%) were ≥75 years of age. Patients ≥75 years of age had higher DAPT cessation rates and increased risk for MACE2, death, cardiac death, and bleeding compared with younger patients. Discontinuation and interruption were not associated with increased cardiovascular risk across age groups, whereas disruption was associated with increased risk for MACE and MACE2 in younger patients but not in patients ≥75 years of age (p for trend <0.05).
Nonadherence and outcomes vary by age, with patients ≥75 years having the highest DAPT cessation rates. We observed no association between outcomes and DAPT cessation in patients ≥75 years, whereas discontinuation was associated with lower MACE rates and disruption with increased MACE rates in patients <75 years.
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Anemia is a well-recognized risk factor for both bleeding and ischemic events after percutaneous coronary intervention (PCI). We sought to determine the impact of baseline anemia on dual antiplatelet ...therapy (DAPT) cessation patterns ≤2 years after PCI and the subsequent risk of clinical adverse events.
PARIS (Patterns of Non-Adherence to Dual Anti-Platelet Regimen in Stented Patients) was a prospective multicenter observational registry of PCI-treated patients (n=5018). Anemia was defined as baseline Hb (hemoglobin) <12 g/dL for men and <11 g/dL for women. DAPT cessation modes included physician-recommended discontinuation, temporary interruption (≤14 days), and disruption due to bleeding or noncompliance. The primary end point was 2-year major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction, or target vessel revascularization. We identified 824 (18%) anemic and 4194 (82%) nonanemic patients. Anemic patients were older and had a higher rate of diabetes mellitus, hypertension, and prior PCI. DAPT interruption and disruption were significantly more common in anemic patients throughout 2 years after PCI, whereas physician-recommended discontinuation occurred more often in anemic patients during the first year after PCI and in nonanemic patients during the second year. The 2-year adjusted risks of MACE and Bleeding Academic Research Consortium 3 or 5 bleeding events were significantly higher in anemic patients. Compared with uninterrupted DAPT, disruption, but not interruption and physician-recommended discontinuation, was associated with a higher risk of myocardial infarction in nonanemic patients and a higher risk of both myocardial infarction and MACE in anemic patients. There was no significant interaction between anemia and risk of clinical outcomes associated with each DAPT cessation mode.
Baseline anemia was associated with a significantly higher adjusted risk of MACE and major bleeding. Physicians more frequently recommend DAPT discontinuation to anemic patients during the first year, and to nonanemic patients during the second year after PCI. DAPT disruption was associated with a higher risk of MACE outcomes.
Abstract Background context Degenerative spondylolisthesis has been well described as a disorder of the lumbar spine. Few authors have suggested that a similar disorder occurs in the cervical spine. ...To our knowledge, the present study represents the largest series of patients with long-term follow-up who were managed surgically for the treatment of degenerative spondylolisthesis of the cervical spine. Purpose To describe the clinical presentation and radiographic findings associated with degenerative cervical spondylolisthesis, and to report the long-term results of surgically managed patients. Study design Analysis of 58 patients treated with anterior cervical decompression and fusion for degenerative spondylolisthesis of the cervical spine. Patient sample From 1974 to 2003, 58 patients were identified as having degenerative spondylolisthesis of the cervical spine occurring in the absence of trauma, systemic inflammatory arthropathy, or congenital abnormality. These patients were identified from a database of approximately 500 patients with degenerative cervical spine disorders treated by the senior one of us. Outcome measures Patient outcomes were evaluated with regard to neurologic improvement (Nurick grade myelopathy) and osseous fusion. Methods The records of 58 patients were reviewed. The average follow-up period was 6.9 years (range, 2–24 years). Seventy-two cervical levels demonstrated spondylolisthesis. In all cases, there was radiographic evidence of facet degeneration and subluxation. All patients were treated with anterior cervical decompression and arthrodesis with iliac crest structural graft. This most commonly involved corpectomy of the caudal vertebrae. Three patients required additional posterior facet fusion. Results Fifty-eight patients demonstrated 72 levels of involvement. The C4–C5 level was most frequently involved (43%). Two radiographically distinct types of listhesis were observed based on the amount of disc degeneration and the degree of spondylosis at adjacent levels. The average neurologic improvement was 1.5 Nurick grades. The overall fusion rate was 92%. Three patients were treated with combined anterior-posterior arthrodesis. The prevalence of myelopathy and instability pattern was greater in the listheses occurring adjacent to spondylotic levels. Conclusions Degenerative spondylolisthesis is relatively common in the cervical spine. Common to all cases is facet arthropathy and neurologic compression. Anterior cervical decompression and arthrodesis appears to yield excellent union rates and neurological improvement in those patients having cervical degenerative spondylolisthesis and significant neurological sequelae who have failed nonoperative treatments.
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