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OBJECTIVES: To describe the mid-term clinical and functional cardiac contractility modulation therapy (CCM) recipients in an urban population with heart failure. BACKGROUND: CCM is a non-excitatory electrical therapy for patients with systolic heart failure with NYHA class III symptoms and ejection fraction (EF) 25-45%. How CCM affects a broad range of clinical measures, including diastolic dysfunction (DD) and weight change, is unexplored. METHODS: We reviewed 31 consecutive patients at our center who underwent CCM implant. NYHA class, hospitalizations, ejection fraction (EF), diastolic function, and weight were compared pre- and post-CCM implant. RESULTS: Mean age and follow-up time was 63 ± 10 years and 1.4 ± 0.8 years, respectively. Mean NYHA class improved by 0.97 functional classes (p < 0.001), and improvement occurred in 68% of patients. Mean annualized hospitalizations improved (0.8 ± 0.8 vs. 0.4 ± 1.0 hospitalizations/year, p = 0.048), and after exclusion of a single outlier, change in annualized days hospitalized also improved (total cohort 3.8 ± 4.7 vs. 3.7 ± 14.8 days/year; p = 0.96; after exclusion, 3.8 ± 4.7 vs. 1.1 ± 1.9 days/year, p < 0.001). Mean EF improved by 8% (p = 0.002), and among those with DD pre-CCM, mean DD improvement was 0.8 "grades" (p < 0.001). Mean weight change was 8.5 pounds lost, amounting to 4% of body weight (p = 0.002, p = 0.002, respectively), with 77% of patients having lost weight after CCM. Five patients (16%) experienced procedural complications; incidence skewed toward early implants. CONCLUSION: In an observational cohort, CCM therapy resulted in improvement in NYHA class, hospitalizations, systolic and diastolic function, and weight.
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Cardiovascular disease (CVD) and cancer are leading causes of death globally, particularly among the rapidly growing population of older adults (OAs). CVD is a leading cause of mortality among cancer survivors, often accelerated by cancer treatments associated with short- or long-term cardiotoxicity. Moreover, there is a dynamic relationship among CVD, cancer, and aging, characterized by shared risk factors and biological hallmarks, that plays an important role in caring for OAs, optimizing treatment approaches, and developing preventive strategies. Assessment of geriatric domains (eg, functional status, comorbidities, cognition, polypharmacy, nutritional status, social support, psychological well-being) is critical to individualizing treatment of OAs with cancer. The authors discuss considerations in caring for an aging population with cancer, including methods for the assessment of OAs with CVD and/or cardiovascular risk factors planned for cancer therapy. Multidisciplinary care is critical in optimizing patient outcomes and maintaining quality of life in this growing vulnerable population.
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The equity of a drug target is principally evaluated by its genetic vulnerability with tools ranging from antisense- and microRNA-driven knockdowns to induced expression of the target protein. In order to upgrade the process of antibacterial target identification and discern its most effective type of inhibition, an in silico toolbox that evaluates its genetic and chemical vulnerability leading either to stasis or cidal outcome was constructed and validated. By precise simulation and careful experimentation using enolpyruvyl shikimate-3-phosphate synthase and its specific inhibitor glyphosate, it was shown that genetic knockdown is distinct from chemical knockdown. It was also observed that depending on the particular mechanism of inhibition, viz competitive, uncompetitive, and noncompetitive, the antimicrobial potency of an inhibitor could be orders of magnitude different. Susceptibility of Escherichia coli to glyphosate and the lack of it in Mycobacterium tuberculosis could be predicted by the in silico platform. Finally, as predicted and simulated in the in silico platform, the translation of growth inhibition to a cidal effect was able to be demonstrated experimentally by altering the carbon source from sorbitol to glucose.