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Objectives
This study sought to build a patient?patient similarity network using multiple features of left ventricular (LV) structure and function in patients with aortic stenosis (AS). The study further validated the observations in an experimental murine model of AS.Background
The LV response in AS is variable and results in heterogeneous phenotypic presentations.Methods
The patient similarity network was developed using topological data analysis (TDA) from cross-sectional echocardiographic data collected from 246 patients with AS. Multivariate features of AS were represented on the map, and the network topology was compared with that of a murine AS model by imaging 155 animals at 3, 6, 9, or 12 months of age.Results
The topological map formed a loop in which patients with mild and severe AS were aggregated on the right and left sides, respectively (p < 0.001). These 2 regions were linked through moderate AS; with upper arm of the loop showing patients with predominantly reduced ejection fractions (EFs), and the lower arm showing patients with preserved EFs (p < 0.001). The region of severe AS showed >3 times the increased risk of balloon valvuloplasty, and transcatheter or surgical aortic valve replacement (hazard ratio: 3.88; p < 0.001) compared with the remaining patients in the map. Following aortic valve replacement, patients recovered and moved toward the zone of mild and moderate AS. Topological data analysis in mice showed a similar distribution, with 1 side of the loop corresponding to higher peak aortic velocities than the opposite side (p < 0.0001). The validity of the cross-sectional data that revealed a path of AS progression was confirmed by comparing the locations occupied by 2 groups of mice that were serially imaged. LV systolic and diastolic dysfunction were frequently identified even during moderate AS in both humans and mice.Conclusions
Multifeature assessments of patient similarity by machine-learning processes may allow precise phenotypic recognition of the pattern of LV responses during the progression of AS. 相似文献: Between April 1993 and August 1994, 12 patients with inoperable, loco-regionally advanced NSCLCA were entered in a prospective dose escalation trial and assigned to receive concurrent thoracic radiotherapy and topotecan. Patients received thoracic irradiation to a total tumor dose of 60 Gy in 30 fractions. Initial fields were to encompass the gross disease plus the mediastinum. Topotecan was delivered by bolus injection days 1 through 5, and days 22 through 26, beginning on the same day as the radiation therapy. The initial dose level was 0.5 mg/m2. Two additional dose levels of 0.75 mg/m2 and 1.0 mg/m2 were tested.
: Six patients were accessioned to the 0.5 mg/m2 dose level, three patients to the 0.75 mg/m2 dose level, and three patients to the 1.0 mg/m2 dose level. At the 0.5 mg/m2 dose level, zero of six patients had ≥Grade 4 hematologic toxicity. One of the six had Grade 3 esophagitis. At the 0.75 mg/m2 dose level, two of three patients had ≥Grade 3 nonhematologic toxicity including anorexia, fatigue, nausea, vomiting, and weakness; zero patients experienced ≥Grade 4 hematologic toxicity. At the 1.0 mg/m2 dose level one of three patients had ≥Grade 3 esophagitis, and two of three patients experienced Grade 4 neutropenia. With a follow-up of 12 to 24 months, two patients are alive and free of disease, three patients are alive with disease (two with distant metastasis, one with local disease and distant metastasis), and the remaining seven patients are dead of disease.
: The combination of topotecan and thoracic radiotherapy for nonsmall lung cancer, in the manner given by this protocol, could be safely given at a dose level of only 0.5 mg/m2 days 1 to 5 and 22 to 26 with 60 Gy of external beam radiotherapy. Higher doses of topotecan were associated with high hematologic and gastrointestinal toxicity. Distant metastasis was the primary pattern of failure. 相似文献