Predictors of thirty-day readmission in nonagenarians presenting with acute heart failure with preserved ejection fraction: a nationwide analysis

BACKGROUDAcute heart failure with preserved ejection fraction (HFpEF) is a common but poorly studied cause of hospital admissions among nonagenarians. This study aimed to evaluate predictors of thirty-day readmission, in-hospital mortality, length of stay, and hospital charges in nonagenarians hospitalized with acute HFpEF.METHODSPatients hospitalized between January 2016 and December 2018 with a primary diagnosis of diastolic heart failure were identified using ICD-10 within the Nationwide Readmission Database. We excluded patients who died in index admission, and discharged in December each year to allow thirty-day follow-up. Univariate regression was performed on each variable. Variables with P-value < 0.2 were included in the multivariate regression model. RESULTSFrom a total of 45,393 index admissions, 43,646 patients (96.2%) survived to discharge. A total of 7,437 patients (15.6%) had a thirty-day readmission. Mean cost of readmission was 43,265 United States dollars (USD) per patient. Significant predictors of thirty-day readmission were chronic kidney disease stage III or higher [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.07−1.34,P = 0.002] and diabetes mellitus (aOR = 1.18, 95% CI: 1.07−1.29,P = 0.001). Meanwhile, female (aOR = 0.90, 95% CI: 0.82−0.99,P = 0.028) and palliative care encounter (aOR = 0.27, 95% CI: 0.21−0.34,P < 0.001) were associated with lower odds of readmission. Cardiac arrhythmia (aOR = 1.46, 95% CI: 1.11−1.93, P = 0.007) and aortic stenosis (aOR = 1.36, 95% CI: 1.05−1.76,P = 0.020) were amongst predictors of in-hospital mortality. CONCLUSIONSIn nonagenarians hospitalized with acute HFpEF, thirty-day readmission is common and costly. Chronic comorbidities predict poor outcomes. Further strategies need to be developed to improve the quality of care and prevent the poor outcome in nonagenarians.

By 2030, it is estimated that one every thirty-three patients will have the diagnosis of heart failure (HF). The projected cost estimates of treating HF are 160 billion United States dollars (USD) in direct costs. Because of the aging of the population, greater increase in HF prevalence will be seen in older adults. It is projected that the number of patients > 80 years with HF will grow by 66% by 2030. ^[1]HF incidence and prevalence rise dramatically with age due to structural and functional alterations in the cardiovascular system, making HF the most prevalent cardiovascular disease among elderly. HF was reported to be the second leading cause of hospitalization for patients aged 75 years and above from 2013 to 2018.^[2]Most elderly patients with HF have impaired left ventricular diastolic function without significant impairment in left ventricular systolic function, which is called heart failure with preserved ejection fraction (HFpEF).^[3–6] Increased levels of brain natriuretic peptide, older age, myocardial infarction history, and reduced diastolic function make the prognosis of HFpEF worse.^[7–9]Over the years, there have been advances in the treatment of HF, however, the mortality, hospitalization, and readmission rates are still high.In this study, we aimed to assess the predictors and causes of readmissions with acute HFpEF among nonagenarians in the United States, by using the National Readmission Database (NRD).     

Clinical implications of hepatic progenitor cell activation in non-alcoholic fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) is one of the most prominent causes of liver-related morbidity in the Western world. NAFLD is a chronic disease charac...     

A novel multimodal nanoplatform for targeting tumor necrosis

Peri-necrotic tumor regions have been found to be a source of cancer stem cells (CSC), important in tumor recurrence. Necrotic and peri-necrotic tumor zones have poor vascular supply, limiting effective exposure to systemically administered therapeutics. Therefore, there is a critical need to develop agents that can effectively target these relatively protected tumor areas. We have developed a multi-property nanoplatform with necrosis avidity, fluorescence imaging and X-ray tracking capabilities to evaluate its feasibility for therapeutic drug delivery. The developed nanoparticle consists of three elements: poly(ethylene glycol)-block-poly(ε-caprolactone) as the biodegradable carrier; hypericin as a natural compound with fluorescence and necrosis avidity; and gold nanoparticles for X-ray tracking. This reproducible nanoparticle has a hydrodynamic size of 103.9 ± 1.7 nm with a uniform spherical morphology (polydispersity index = 0.12). The nanoparticle shows safety with systemic administration and a stable 30 day profile. Intravenous nanoparticle injection into a subcutaneous tumor-bearing mouse and intra-arterial nanoparticle injection into rabbits bearing VX2 orthotopic liver tumors resulted in fluorescence and X-ray attenuation within the tumors. In addition, ex vivo and histological analysis confirmed the accumulation of hypericin and gold in areas of necrosis and peri-necrosis. This nanoplatform, therefore, has the potential to enhance putative therapeutic drug delivery to necrotic and peri-necrotic areas, and may also have an application for monitoring early response to anti-tumor therapies.

Au-Hyp-NP developed by encapsulation of gold and hypericin into PEG-PCL nanoplatform for fluorescence and X-ray tracking with tumor necrosis targeting.     

Thoracic surgery in United Arab Emirates

The United Arab Emirates (UAE) has undergone a significant change in its population and economy in the last decades and in parallel its healthcare system has evolved rapidly to provide advanced, innovative and world-leading care. At the forefront of this revolution in healthcare is the development of a multidisciplinary multimodality thoracic service provision, offered at quaternary referral hospitals amalgamating academics, training, research and innovation. Previously, thoracic service care was limited to single providers at various public and private hospitals, usually performing lower complexity cases. Most complex thoracic cases were repatriated outside the UAE. This practice was replaced with the opening of Cleveland Clinic Abu Dhabi (CCAD), in 2015, which created a multidisciplinary thoracic program. This included the start of a mini-invasive surgical and lung transplantation program. Since that time other public and private hospitals have emerged providing care in a similar model. The impact of these programs has been a decreased transfer of patients abroad for treatment. Under the umbrella of the Emirates Thoracic Society (ETS) a platform for greater collaboration aimed at improving patient care, potential research and physician education has been created. Direct links have been established with world-leading Thoracic surgery and Respiratory Medicine Centers facilitating this development and offering support and guidance. This article charts these changes in thoracic care in the recent past, present, and delineates plans for the future in the UAE.     

The HSP90 inhibitor 17-AAG synergizes with doxorubicin and U0126 in anaplastic large cell lymphoma irrespective of ALK expression

OBJECTIVE: Heat shock protein 90 (HSP90) chaperones and maintains the molecular integrity of a variety of signal transduction proteins, including the nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) oncogenic protein, a genetic abnormality that is frequently observed in anaplastic large cell lymphoma (ALCL) cells. Here we demonstrate that HSP90 is overexpressed in primary and cultured ALK-positive and ALK-negative ALCL cells, and we evaluate the potential role of the small molecule inhibitor of HSP90, 17-allylamino-17-demethoxygeldanamycin (17-AAG) in treating ALCL. METHODS: The antiproliferative effect of 17-AAG-cultured cells was determined by MTS assay. Apoptosis and cell-cycle arrest were determined by Annexin-V/propidium iodide and propidium iodide staining, respectively, and fluorescein-activated cell sorting analysis. Expression of HSP90 was evaluated by immunohistochemistry, and molecular changes were determined by Western blot. RESULTS: Treatment of cultured ALCL cells with 17-AAG induced cell-cycle arrest and apoptosis, irrespective of ALK expression. At the molecular level, 17-AAG induced degradation of ALK and Akt proteins, dephosphorylated extracellular signal-regulated kinase, and degraded the cell-cycle regulatory protein cyclin D1 and its cyclin-dependent kinases, CDK4 and CDK6, but had a differential effect on p27 and p53 proteins. Inhibition of extracellular signal-regulated kinase phosphorylation by the mitogen activated protein kinase inhibitor U0126 induced cell death in all ALCL cell lines, and sublethal concentration 17-AAG showed synergistic antiproliferative effects when combined with U0126 or doxorubicin. CONCLUSION: Our data demonstrate that targeting HSP90 function by 17-AAG may offer a novel therapeutic strategy for ALCL, either as single-agent activity or by combining 17-AAG with conventional or targeted therapeutic schemes.     

Hormone therapy and antioxidant vitamins do not improve endothelial vasodilator function in postmenopausal women with established coronary artery disease: a substudy of the Women's Angiographic Vitamin and Estrogen (WAVE) trial

We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound in 61 women who participated in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a randomized controlled trial. There were no significant differences in the baseline demographics of women receiving hormone therapy (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34 months) improved FMD (all p-values=NS). Endothelium-independent vasodilation, induced by nitroglycerin (NTG) was similar at baseline and was not affected by either therapy. In univariate and multivariate analysis, neither hormone therapy nor antioxidant vitamins were associated with FMD. Women with established coronary artery disease have impaired flow-mediated vasodilation of the brachial artery that does not improve after 3 months or up to 34 months of treatment with postmenopausal hormone therapy or antioxidant vitamins.     

Regulation of CXCR4 conformation by the small GTPase Rac1: implications for HIV infection

The chemokine receptor CXCR4 is a critical regulator of cell migration and serves as a coreceptor for HIV-1. The chemokine stromal cell derived factor-1, also known as CXCL12, binds to CXCR4 and exerts its biologic functions partly through the small guanosine triphosphate hydrolase (GTPase) Rac1 (ras-related C3 botulinum toxin substrate 1). We show in different cell types, including CD34(+) hematopoietic stem and progenitor cells, that inhibition of Rac1 causes a reversible conformational change in CXCR4, but not in the related receptors CXCR7 or CCR5. Biochemical experiments showed that Rac1 associates with CXCR4. The conformational change of CXCR4 on Rac1 inhibition blocked receptor internalization and impaired CXCL12-induced Gα(i) protein activation. Importantly, we found that the conformation adopted by CXCR4 after Rac1 inhibition prevents HIV-1 infection of both the U87-CD4-CXCR4 cell line and of primary peripheral blood mononuclear cells. In conclusion, our data show that Rac1 activity is required to maintain CXCR4 in the responsive conformation that allows receptor signaling and facilitates HIV-1 infection; this implies that Rac1 positively regulates CXCR4 function and identifies the Rac1-CXCR4 axis as a new target for preventing HIV-1 infection.     

Comparison of the postprandial release of peptide YY and proglucagon-derived peptides in the rat

Endocrine L-cells of the distal intestine synthesize both peptide YY (PYY) and proglucagon-derived peptides (PGDPs), whose release has been reported to be either parallel or selective. Here we compare the release mechanisms of PYY, glucagon-like peptide-1 (GLP-1), and oxyntomodulin-like immunoreactivity (OLI) in vivo. Anaesthetized rats were intraduodenally (ID) given either a mixed semi-liquid meal or oleic acid, or they received oleic acid or short chain fatty acids (SCFA) intracolonically (IC). The ID meal released the three peptides with a similar time-course (peak at 30 min); ID oleic acid produced a progressive release of PYY and OLI, while GLP-1 release was less. IC oleic acid or SCFA released smaller (but significant) amounts of PYY but no OLI or GLP-1. Hexamethonium inhibited most of the response to the ID meal and ID oleic acid, but did not change the PYY response to IC oleic acid. N ^G -nitro-l-arginine methyl ester (l-NAME, a nitric oxide synthase inhibitor) inhibited meal-induced PYY release and left OLI and GLP-1 unaffected. BW10 (a gastrin-releasing peptide antagonist) had no effect on the meal-induced release of either peptide. These results suggest a parallel initial release of PYY, OLI and GLP-1 after the ID meal, or oleic acid, by an indirect mechanism triggered in the proximal bowel, using nicotinic synapses, and involving nitric oxide release for PYY and an unknown mediator for PGDPs. For PYY there is a later phase of peptide release, probably induced by direct contact between nutrients and colonic L-cells. Received: 8 January 1999 / Received after revision: 25 March 1999 / Accepted: 26 April 1999