Directional coronary atherectomy: experience in 310 patients

This article describes the acute and long-term clinical outcomes of 310 consecutive patients who underwent directional coronary atherectomy (DCA) for treatment of coronary artery disease. An overall procedural success rate of 95% was noted with a total major complication rate of 5%. Analyses of minimal luminal diameter (MLD) were performed pre- and post-procedure for 160 patients. Clinical follow-up including treadmill testing and/or clinical symptoms was obtained on 293 patients. Results of angiographic analyses corresponded with the Kuntz model suggesting that larger MLDs are associated with lower restenosis rates. The overall target vessel revascularization rate was 27.6%, with a mean post-procedure percent diameter stenosis of 16%. These results indicate that DCA is associated with acceptable clinical restenosis rates, complications and long-term outcome.     

Fisetin for COVID-19 in skilled nursing facilities: Senolytic trials in the COVID era

The burden of senescent cells (SnCs), which do not divide but are metabolically active and resistant to death by apoptosis, is increased in older adults and those with chronic diseases. These individuals are also at the greatest risk for morbidity and mortality from SARS-CoV-2 infection. SARS-CoV-2 complications include cytokine storm and multiorgan failure mediated by the same factors as often produced by SnCs through their senescence-associated secretory phenotype (SASP). The SASP can be amplified by infection-related pathogen-associated molecular profile factors. Senolytic agents, such as Fisetin, selectively eliminate SnCs and delay, prevent, or alleviate multiple disorders in aged experimental animals and animal models of human chronic diseases, including obesity, diabetes, and respiratory diseases. Senolytics are now in clinical trials for multiple conditions linked to SnCs, including frailty; obesity/diabetes; osteoporosis; and cardiovascular, kidney, and lung diseases, which are also risk factors for SARS-CoV-2 morbidity and mortality. A clinical trial is underway to test if senolytics decrease SARS-CoV-2 progression and morbidity in hospitalized older adults. We describe here a National Institutes of Health-funded, multicenter, placebo-controlled clinical trial of Fisetin for older adult skilled nursing facility (SNF) residents who have been, or become, SARS-CoV-2 rtPCR-positive, including the rationale for targeting fundamental aging mechanisms in such patients. We consider logistic challenges of conducting trials in long-term care settings in the SARS-CoV-2 era, including restricted access, consent procedures, methods for obtaining biospecimens and clinical data, staffing, investigational product administration issues, and potential solutions for these challenges. We propose developing a national network of SNFs engaged in interventional clinical trials.     

Physical Frailty Phenotype and the Development of Geriatric Syndromes in Older Adults with Coronary Heart Disease

BackgroundFrailty, a clinical state of vulnerability, is associated with subsequent adverse geriatric syndromes in the general population. We examined the long-term impact of frailty on geriatric outcomes among older patients with coronary heart disease.MethodsWe used the National Health and Aging Trends Study, a prospective cohort study linked to a Medicare sample. Coronary heart disease was identified by self-report or International Classification of Diseases (ICD) codes 1-year prior to the baseline visit. Frailty was measured using the Fried physical frailty phenotype. Geriatric outcomes were assessed annually during a 6-year follow-up.ResultsOf the 4656 participants, 1213 (26%) had a history of coronary heart disease 1-year prior to their baseline visit. Compared to those without frailty, subjects with frailty were older (ages ≥75: 80.9% vs 68.9%, P < 0.001), more likely to be female, and belong to an ethnic minority. The prevalence of hypertension, stroke, falls, disability, anxiety/depression, and multimorbidity were much higher in the frail, than nonfrail, participants. In a discrete time survival model, the incidence of geriatric syndromes during 6-year follow-up including 1) dementia, 2) loss of independence, 3) activities of daily living disability, 4) instrumental activities of daily living disability, and 5) mobility disability were significantly higher in the frail than in the nonfrail older patients with coronary heart disease.ConclusionIn patients with coronary heart disease, frailty is a risk factor for the accelerated development of geriatric outcomes. Efforts to identify frailty in the context of coronary heart disease are needed, as well as interventions to limit or reverse frailty status for older patients with coronary heart disease.     

Spatial distribution of orofacial cleft defect births in Harris County, Texas, 1990 to 1994, and historical evidence for the presence of low-level radioactivity in tap water

BACKGROUND: While both ionizing and nonionizing radiation are known to impair human reproductive capacity, the role of low-level domestic radiation continues to be an unsettled issue. OBJECTIVES: We examined the geostatistical distribution (residential longitude and latitude) of orofacial cleft birth cases adjusted for the underlying population distribution. Furthermore, we examined the cleft birth rates enumerated by zip codes for possible associations with levels of radium and radon in drinking water. METHODS: Cleft births and unaffected live births in Harris County, Texas, from 1990 to 1994, were geocoded by residential addresses and tested for spatial clusters using the space-time clustering program SaTScan. Historical sample data on local variations in water quality facilitated the assessment of the association of orofacial cleft defect births with low-level radiation exposure. RESULTS: A cluster of significantly greater than expected numbers of cleft defect births was identified in northwest Harris County, (relative risk = 3.0, P = 0.043), where the presence of elevated levels of radium (> 3 pCi/L) and radon (> 300 pCi/L) in the tap water has been known since the 1980s. CONCLUSIONS: Despite the ecological design of the study, lacking individual exposure measurements for cleft birth residences, there was strong suggestive evidence of an association between elevated radiation levels in tap water and elevated cleft birth prevalence rates by zip codes. Attention of physicians is invited to environmental causes as potential risk factors for orofacial cleft. This would aid in genetic counseling and the development of future preventive measures.     

Antibodies to Nipah-like virus in bats (Pteropus lylei), Cambodia

Serum specimens from fruit bats were obtained at restaurants in Cambodia. We detected antibodies cross-reactive to Nipah virus by enzyme immunoassay in 11 (11.5%) of 96 Lyle's flying foxes (Pteropus lylei). Our study suggests that viruses closely related to Nipah or Hendra viruses are more widespread in Southeast Asia than previously documented.     

Serum interleukin-6 and hemoglobin as physiological correlates in the geriatric syndrome of frailty: a pilot study

OBJECTIVES: To determine specific physiological correlates of the geriatric syndrome of frailty that warrant further investigation. DESIGN: Population-based case-control study. SETTING: General Clinical Research Center at Johns Hopkins Bayview Medical Center. PARTICIPANTS: Community-dwelling adults aged 74 and older from Baltimore, Maryland. MEASUREMENTS: Frailty status was determined using a recently validated screening tool that consists of weight loss, fatigue, low levels of physical activity, and measurements of grip strength and walking speed. Serum interleukin-6 (IL-6) was measured using enzyme-linked immunosorbent assay, and standard complete blood count was performed using a Coulter counter. RESULTS: Eleven frail and 19 nonfrail subjects with mean age +/- standard deviation of 84.9 +/- 6.7 vs 81.3 +/- 4.1 years, respectively, completed the study. The frail subjects had significantly higher serum IL-6 levels and significantly lower hemoglobin and hematocrit than the nonfrail subjects (4.4 +/-2.9 vs 2.8 +/- 1.6 pg/mL, 12.1 +/- 1.1 vs 13.9 +/- 1.0 g/dL, and 35.8% +/- 3.1% vs 40.6% +/- 2.8%, respectively). No significant difference was observed in mean corpuscular volume, red blood cell distribution width, or white blood cell and platelet counts between the frail and nonfrail groups. Furthermore, there was an inverse correlation between serum IL-6 level and hemoglobin (Pearson's correlation coefficient: -0.46) and hematocrit (-0.48) in the frail group but not in the nonfrail group. CONCLUSION: These results suggest that frail subjects have evidence of inflammation and lower hemoglobin and hematocrit levels. This subclinical anemia is normocytic and is hence unlikely due to myelosuppression or iron deficiency and is potentially related to the increased chronic inflammatory state marked by serum IL-6 elevation. Further studies are indicated to better characterize the immune and hematological changes that underlie frailty.     

Frailty and the older man.

Frailty is a wasting syndrome of advanced age that leaves a person vulnerable to falls, functional decline, morbidity, and mortality. The cause of this syndrome is complex but likely has a biologic basis. Studies by the authors' research group have validated a phenotype of frailty [table: see text] and have established a gender difference in prevalence with women twice as likely to develop the syndrome as men. Using a biologic model that includes sarcopenia, neuroendocrine decline, and immune dysfunction as potential causes, several physiologic gender differences may explain these differing levels of frailty. First, higher baseline levels of muscle mass may protect men from reaching a threshold of weakness and muscle mass loss that may put them into a category of frailty. Specific neuroendocrine and hormonal factors that may make men less likely to develop frailty than women include testosterone and GH, which may provide advantages in muscle mass maintenance, and cortisol, which is likely less dysregulated in older men as compared to older women. There is also evidence of immune system dimorphism that is, in part, responsive to sex steroids, perhaps making men more vulnerable to sepsis and infection and women more vulnerable to chronic inflammatory conditions and muscle mass loss. The net effect of the hormonal dysregulation and immune system dysfunction is an accelerated loss of muscle mass. There is also evidence that lower levels of activity and lower caloric intake in women as compared to men may also influence the phenotype of frailty and make women more vulnerable then men to the syndrome.     

ELISA and multiplex technologies for cytokine measurement in inflammation and aging research

Over the last decade there has been an enormous expansion of research focused on defining the role of inflammation in aging, age-related diseases, disability, and frailty. The availability of methods to measure cytokines and other inflammatory mediators or markers with high sensitivity and specificity is critically important. Enzyme-linked immunosorbent assay (ELISA), the most widely used and best validated method, is limited by its ability to measure only a single protein in each sample. Recent developments in serum cytokine quantification technology include multiplex arrays, which offer the potential of better evaluating the complexity and dynamic nature of inflammatory responses and offer substantial cost and sample savings over traditional ELISA measurements. Despite potential advantages of this new technology, experience with these techniques is limited, and it has not emerged to date as the gold standard in inflammatory mediator measurement. This article reviews ELISA and the emerging multiplex technologies, compares the cost and effectiveness of recently developed multiplex arrays with traditional ELISA technology, and provides specific recommendations for investigators interested in measuring serum inflammatory mediators in older adults.