The impact of patient-reported frailty on cardiovascular outcomes in elderly patients after non-ST-acute coronary syndrome.

BACKGROUND: As life expectancy increases, the population of older individuals with coronary artery disease and frailty is growing. We aimed to assess the impact of patient-reported frailty on the treatment and prognosis of elderly early survivors of non-ST-elevation acute coronary syndrome (NSTE-ACS). METHODS: Frailty data were obtained from two prospective trials, POPular Age and the POPular Age Registry, which both assessed elderly NSTE-ACS patients. Frailty was assessed one month after admission with the Groningen Frailty Indicator (GFI) and was defined as a GFI-score of 4 or higher. In these early survivors of NSTE-ACS, we assessed differences in treatment and 1-year outcomes between frail and non-frail patients, considering major adverse cardiovascular events (MACE, including cardiovascular mortality, myocardial infarction, and stroke) and major bleeding. RESULTS: The total study population consisted of 2192 NSTE-ACS patients, aged ≥70 years. The GFI-score was available in 1320 patients (79 ± 5 years, 37% women), of whom 712 (54%) were considered frail. Frail patients were at higher risk for MACE than non-frail patients (9.7% vs. 5.1%, adjusted hazard ratio [HR] 1.57, 95% confidence interval [CI] 1.01-2.43, p = 0.04), but not for major bleeding (3.7% vs. 2.8%, adjusted HR 1.23, 95% CI 0.65-2.32, p = 0.53). Cubic spline analysis showed a gradual increase of the risk for clinical outcomes with higher GFI-scores. CONCLUSIONS: In elderly NSTE-ACS patients who survived 1-month follow-up, patient-reported frailty was independently associated with a higher risk for 1-year MACE, but not with major bleeding. These findings emphasize the importance of frailty screening for risk stratification in elderly NSTE-ACS patients.

Safety considerations with the use of platelet inhibitors for elderly patients with non-ST- elevation acute coronary syndrome.

Introduction: Dual antiplatelet therapy (DAPT) is standard treatment for patients with acute coronary syndrome (ACS). This includes lifelong aspirin combined with a P2Y12 inhibitor for 1 year. The indication for one of the P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor) is dependent on the treatment strategy; whether patients undergo coronary angiography or are treated medically only. Tailoring antiplatelet therapy to the risk profile of the individual patient is of specific importance to the older patient.Areas covered: In this review, we discuss dual antiplatelet therapy in elderly patients with ACS. We present the options to tailor antiplatelet therapy based on platelet function testing, CYP2C19 genotyping and patients' thrombotic and bleeding risk. Finally, we discuss alternatives for dual antiplatelet therapy.Expert opinion: DAPT in elderly patients with ACS should consist of aspirin with clopidogrel or ticagrelor. Weighing patients' thrombotic and bleeding risk, based on clinical judgment or with use of specific risk scores, is probably the most convenient method to individualize antiplatelet therapy; however, CYP2C19 genotyping can also be used. In elderly patients with an increased bleeding risk, clopidogrel is a safe and effective alternative to ticagrelor. An alternative to 12 months DAPT could be ticagrelor monotherapy after a short period of DAPT.

Long-term follow-up after bypass surgery or coronary stenting in elderly with multivessel disease.

BACKGROUND: We sought to compare long-term follow-up of coronary artery bypass grafting (CABG) with percutaneous coronary intervention (PCI) in elderly patients with left main or multivessel disease, hypothesising that completeness of revascularisation and severity of coronary artery disease are predictors of adverse outcomes. METHODS: Patients aged ≥75 years with multivessel disease or left main disease who underwent PCI or CABG between 2012-2016 were included in this retrospective cohort study. Baseline characteristics from the index procedure were collected. Severity of coronary artery disease and completeness of revascularisation were assessed. Primary outcome was all-cause mortality, in addition we captured major adverse cardiac and cerebral events, bleedings, recurrent angina and new onset atrial fibrillation. RESULTS: A total of 597 patients were included. Median follow-up was 4 years (interquartile range 2.8-5.3 years). At baseline, patients in the PCI group more often had a previous medical history of CABG and more frequently underwent an urgent procedure compared with patients in the CABG group. Mortality at 5­year follow-up was significantly higher in patients who underwent PCI compared with CABG (39.9% vs 25.4%, p < 0.001). Furthermore, acute coronary syndrome (ACS), repeat revascularisation and recurrent angina occurred more frequently after PCI, while occurrence of bleedings and new onset atrial fibrillation were more frequent after CABG. Neither completeness of revascularisation nor severity of coronary artery disease was a predictor for any of the outcomes. CONCLUSION: Long-term mortality was higher in elderly patients with multivessel disease undergoing PCI compared with CABG. In addition, patients undergoing PCI had a higher risk of ACS, repeat revascularisation and recurrent angina.

A practical guide on how to handle patients with bleeding events while on oral antithrombotic treatment.

Bleeding is a feared complication in patients who are treated with antithrombotic therapy (oral anticoagulation or antiplatelet therapy). Management of antithrombotic therapy after bleeding poses a dilemma where restarting the crucial medication could lead to recurrent bleeding, while interrupting or even discontinuing treatment could increase the thrombotic risk. In this review, we provide recommendations regarding the treatment of patients with a bleeding event while on oral antithrombotic therapy, based on the literature and expert opinion.

Management of elderly patients with a non-ST-segment-elevation acute coronary syndrome.

Elderly patients with an acute coronary syndrome are underrepresented in randomised controlled trials. Neither the European Society of Cardiology nor the American Heart Association/American College of Cardiology acute coronary syndrome guidelines provide specific recommendations for elderly patients. However, elderly patients are at higher thrombotic and bleeding risk compared with younger patients leading to difficulties in choosing the optimal treatment. In this review, we discuss the uncertainties we encounter in treating elderly patients with non-ST-elevation acute coronary syndrome and suggest treatment options based on the existing literature.

Automated, multiplex assay for high-frequency microsatellite instability in colorectal cancer.

PURPOSE: In a series of hereditary nonpolyposis colorectal cancer (HNPCC) patients, we evaluated the sensitivities of the individual microsatellites recommended by the National Cancer Institute (NCI) consensus workshop for detection of high-frequency microsatellite instability (MSI-H). On the basis of this evaluation, we developed a three-marker assay that assigns microsatellite instability (MSI) in a multiplex polymerase chain reaction. METHODS: Individual marker sensitivity was assessed in 18 HNPCC tumors. Multiplex and NCI assays were then assessed in a series of 120 patients with early-onset colon cancer. RESULTS: The sensitivity of microsatellite markers BAT25, BAT26, D2S123, D5S346, and D17S250 for ASI in HNPCC cancers was 100%, 94%, 72%, 50%, and 50%, respectively. The three most accurate markers were combined and optimized in a multiplex assay that assigned MSI-H whenever at least two of three markers revealed ASI. In early-onset colon cancers, the prevalence of MSI-H determined by the multiplex assay and by the NCI assay was 16% and 23%, respectively. The additional MSI-H tumors and patients with MSI-H identified by the NCI assay lacked the traits characteristic of MSI-H seen in tumors and patients identified by the multiplex assay: retention of heterozygosity (NCI additional 22% v multiplex 84%; P =.003), characteristic tumor morphology (0% v 64%; P =.006), and 5-year cancer survival rate (44% v 100%; P =.0003). CONCLUSION: The multiplex assay identifies colon cancers with MSI-H by assessing three highly accurate microsatellite markers. This assay identifies a smaller MSI-H cohort with more homogeneous clinical features and is superior as a marker of favorable prognosis. It merits prospective evaluation as a marker of prognosis and as a screening test for HNPCC.

A novel approach to reducing postoperative intraperitoneal adhesions through the inhibition of insulinlike growth factor I activity.

HYPOTHESIS: Interference with insulinlike growth factor I (IGF-I) activity, both systemically and intraperitoneally, reduces postoperative intraperitoneal adhesion severity. SETTING: Experimental animal model. DESIGN, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Adult female rats were subjected to hypophysectomy, sham hypophysectomy (control), IGF binding protein 4 (IGFBP-4) treatment, or albumin treatment (control). All rats underwent laparotomy and uterine horn abrasion with adjacent parietal peritoneal trauma for the purpose of creating postoperative intraperitoneal adhesions. Glucocorticoids and thyroid hormone were replaced in the hypophysectomy group. On postoperative day 10, rats were weighed, subjected to phlebotomy, and killed. Postmortem laparotomies were performed and blinded observers scored uterine-peritoneal adhesions on a 0 to 3 scoring system. Plasma IGFBP-4 levels and organ weights were measured in the IGFBP-4 and albumin treatment groups. Blood samples in all rats were analyzed for IGF-I levels. RESULTS: Rats with low IGF-I levels (hypophysectomy) and inhibited IGF-I activity (IGFBP-4 treatment) formed significantly less severe adhesions than their control counterparts. As expected, rats in the hypophysectomy group displayed greater weight loss and lower plasma IGF-I levels than sham-treated rats. Rats treated with IGFBP-4 and those treated with albumin demonstrated no differences in body weight, organ weights, IGF-I levels, and IGFBP-4 levels. CONCLUSIONS: Both the reduction of systemic IGF-I levels via hypophysectomy and the inhibition of local intraperitoneal IGF-I activity via IGFBP-4 treatment resulted in diminished postoperative adhesion severity. Treatment with IGFBP-4 may play a role in postoperative adhesion prophylaxis in the future.

The effect of combining aromatase inhibitors with antiestrogens on tumor growth in a nude mouse model for breast cancer.

We have previously established a model for postmenopausal, hormone-dependent breast cancer in nude mice which is responsive to both antiestrogens and aromatase inhibitors. In this model, MCF-7 human breast carcinoma cells transfected with the aromatase gene (MCF-7CA) synthesize sufficient estrogen to form tumors in ovariectomized nude mice. In the present study we used this intratumoral aromatase model to investigate the effects on tumor growth of the new nonsteroidal aromatase inhibitors letrozole (CGS 20,267) and anastrozole (ZD 1033) and the antiestrogens tamoxifen (ICI 47,474) and faslodex (ICI 182,780). Furthermore, we determined whether the inhibition of estrogen synthesis together with inhibition of estrogen action would be more effective in controlling breast tumor growth. The results of our studies indicate that the aromatase inhibitors anastrozole and letrozole, as well as the new pure antiestrogen faslodex, have potent antitumor effects in the mouse model. In the treatment of mice with mammary tumors, letrozole was more effective in suppressing tumor growth than anastrozole. This was consistent with the Ki values of these inhibitors against placental aromatase and the IC50 values in cell culture (MCF-7CA), which indicated the greater potency of letrozole as an aromatase inhibitor. Letrozole also had greater antitumor effects than tamoxifen and faslodex. The antitumor effect of letrozole was substantial, making it difficult to detect any additional effect on the tumors when letrozole was combined with the antiestrogens. However, the combined treatment of anastrozole + tamoxifen and anastrozole + faslodex also did not increase efficacy compared to the aromatase inhibitor alone. In addition, combining the two antiestrogens did not suppress tumor growth more effectively than faslodex alone. Our results show that treatment with the combinations of aromatase inhibitors with either tamoxifen or faslodex are not more effective in blocking estrogen stimulation of tumor growth than the aromatase inhibitors alone.

Brain tissue oxygenation during hemorrhagic shock, resuscitation, and alterations in ventilation.

OBJECTIVES: Recently developed polarographic microelectrodes permit continuous, reliable monitoring of oxygen tension in brain tissue (PbrO2). The aim of this study was to investigate the feasibility and utility of directly monitoring PbrO2 in cerebral tissue during changes in oxygenation or ventilation and during hemorrhagic shock and resuscitation. We also sought to develop a model in which treatment protocols could be evaluated using PbrO2 as an end point. METHODS: Licox Clark-type polarographic probes were inserted in the brain tissue of 16 swine to monitor PbrO2. In eight swine, changes in PbrO2 were observed over a range of fractional concentrations of inspired O2 (FiO2) as well as during periods of hyperventilation and hypoventilation. In eight other swine, PbrO2 was monitored during a graded hemorrhage of up to 70% estimated blood volume and during the resuscitation period. RESULTS: When FiO2 was elevated to 100%, PbrO2 increased from a baseline of 15+/-2 mm Hg to 36+/-11 mm Hg. Hyperventilation while breathing 100% oxygen resulted in a 40% decrease in PbrO2 (p < 0.05), whereas hypoventilation increased PbrO2 to 88 mm Hg (p < 0.01). A graded hemorrhage to 50% estimated blood volume significantly reduced PbrO2, mean arterial pressure, and intracranial pressure (p < 0.01). Continued hemorrhage to 70% estimated blood volume resulted in a PbrO2 of 2.9+/-1.5 mm Hg. After resuscitation, PbrO2 was significantly elevated, reaching 65+/-13 mm Hg (p < 0.01), whereas mean arterial pressure and cerebral perfusion pressure simply returned to baseline. CONCLUSION: Directly measured PbrO2 was highly responsive to changes in FiO2, ventilatory rate, and blood volume in this experimental model. In particular, hypoventilation significantly increased PbrO2, whereas hyperventilation had the opposite effect. The postresuscitation increase in PbrO2 may reflect changes in both O2 delivery and O2 metabolism. These experiments set the stage for future investigations of a variety of resuscitation protocols in both normal and injured brain.

Yoga, meditation, and imagery: clinical applications.

Hatha yoga and meditation as adjunctive therapies for promoting and maintaining wellness offer an excellent example of the mind-body connection at work. Hatha yoga creates balance, physically and emotionally, by using postures, or asanas, combined with breathing techniques, or pranayama. Meditation and guided imagery not only support the physical and emotional work being done by the postures and breathing, they open the door to self-actualization to create the perfect union of the mind, body, and spirit. This report discusses the definitions of hatha yoga, meditation, and imagery and their clinical applications. Three case studies from private practice are presented.

Radiofrequency catheter ablation of an intraatrial reentrant tachycardia: evidence of an area of slow conduction.

Radiofrequency catheter ablation for intraatrial reentrant tachycardia has not been previously reported. This article describes a patient with a demonstrable area of slowed conduction in the lateral right atrium that responded to radiofrequency catheter ablation in the area of the fractionated electrogram with elimination of the tachycardia. This patient also had the common form of atrioventricular nodal reentrant tachycardia, which was also successfully ablated.