In ACS patients, serial autologous infusions of selective HDL delipidated plasma are clinically feasible and well tolerated. This therapy may offer a novel adjunct treatment for patients presenting with ACS. Further study will be needed to determine its ability to reduce clinical cardiovascular events.
Uptake of cholesterol from peripheral cells by nascent small HDL circulating in plasma is necessary to prevent atherosclerosis. This process, termed reverse cholesterol transport, produces larger cholesterol-rich HDL that transfers its cholesterol to the liver facilitating excretion. Most HDL in plasma is cholesterol-rich. We demonstrate that treating plasma with a novel selective delipidation procedure converts large to small HDL [HDL-selectively delipidated (HDL-sdl)]. HDL-sdl contains several cholesterol-depleted species resembling small a, preb-1, and other preb forms. Selective delipidation markedly increases efficacy of plasma to stimulate ABCA1-mediated cholesterol transfer from monocytic cells to HDL. Plasma from African Green monkeys underwent selective HDL delipidation. The delipidated plasma was reinfused into five monkeys. Preb-1-like HDL had a plasma residence time of 8 6 6 h and was converted entirely to large a-HDL having residence times of 13-14 h. Small a-HDL was converted entirely to large a-HDL. These findings suggest that selective HDL delipidation activates reverse cholesterol transport, in vivo and in vitro. Treatment with delipidated plasma tended to reduce diet-induced aortic atherosclerosis in monkeys measured by intravascular ultrasound. These findings link the conversion of small to large HDL, in vivo, to improvement in atherosclerosis. In 1951, it was reported that a minor component of the plasma lipoproteins was paradoxically reduced in patients who had coronary heart disease (CHD), in contrast to the bulk of plasma lipoproteins that were notably increased (1). Nine years later, the first prospective studies confirmed that a low plasma HDL cholesterol concentration is a predictor of CHD (2), as have subsequent studies of large populations (3, 4). A low plasma HDL cholesterol concentration is also a predictor of stroke (5). The relation between HDL cholesterol and CHD is strong and consistent among men and women, young and old, and in those with low or high LDL cholesterol concentrations (6); and the influence on HDL cholesterol on risk of CHD persists even during treatment with statins at typical (7) or high doses (8). These findings support the theory that HDL is a component of the lipoprotein system that not only protects against the atherogenic actions of VLDL and LDL, but also may be essential to prevent atherosclerosis even when plasma LDL cholesterol concentration is very low.HDL transports cholesterol from peripheral tissues, including arterial wall, to the liver directly or by transferring cholesterol to VLDL and LDL in plasma, which eventually deliver much of their cholesterol to the liver (9, 10). The liver can then channel the excess cholesterol for excretion into the bile. This complex process is called reverse cholesterol transport. The step that initiates cholesterol removal from macrophages, the predominant cholesterol-loaded cell type in atherosclerosis, is activation by HDL of cholesterol transporters. Although several cholesterol transporters exist in macro...
Introduction: Microbiological culture of dialysis water and fluid is a routine safety measure. In the United States (U.S.), laboratories perform these cultures on trypticase soy agar at 35-378C for 48 h (TSA-48h), not on the tryptone glucose extract agar or Reasoner's 2A agar at 17-238C for 7 days (TGEA-7d and R2A-7d, respectively) recommended by international standards. We compared culture methods to identify samples exceeding the accepted action level of 50 CFU/mL.Methods: Dialysis water and fluid samples collected from 41 U.S. dialysis programs between 2011 and 2014 were cultured at two U.S. laboratories. Each sample was cultured using (1) either TGEA-7d or R2A-7d and (2) TSA-48h. We compared proportions exceeding the action level by different methods and test characteristics of TSA-48h to those of TGEA-7d and R2A-7d. Findings:The proportion of water samples yielding colony counts 50 CFU/mL by TGEA-7d was significantly different from the proportion by TSA-48h (P 5 0.001; difference in proportion 4.3% [95%CI 1.3-7.3%]). The proportions of dialysis fluid samples 50 CFU/mL by TGEA-7d and TSA-48h were not significantly different; there were no significant differences for comparisons of R2A-7d to TSA-48h.Discussion: In dialysis fluid, TSA-48h was comparable to TGEA-7d and R2A-7d in identifying samples as having bacterial counts 50 CFU/mL. In dialysis water, TSA-48h was comparable to R2A-7d in identifying samples 50 CFU/mL, but TGEA-7d did yield significantly more results above 50 CFU/mL. Nonetheless, the negative predictive value of a TSA-48h result of <50 CFU/mL in dialysis water exceeded 95%.
Sean Loughlin What new developments are we seeing in terms of dialysis-related technology?Danilo Concepcion Companies are beginning to incorporate features such as blood volume monitoring for fluid management and biofeedback. The Centers for Medicare & Medicaid Services (CMS) is looking at fluid management as part of its quality initiative. Denny TreuWe probably are going to see more integrated systems that include water treatment, which will improve ease of use, quality, and safety. Other forthcoming technologies are going to the result in increased water purity.Joseph Pulliam We will begin to see more online monitoring for chlorine and other items, which will remove some of the potential for human errors. Sean Loughlin In terms of biomedical technicians with a focus on dialysis: Do we have enough, and are they adequately trained?Danilo Concepcion Although we have dedicated biomeds who are focused on dialysis, the level of experience and qualifications may not be adequate for the responsibility. With no mandate for certification or qualification for the technology staff aspect in dialysis, the qualifications and educational background for individuals filling the role for equipment support is left to the facility. Some facilities have taken clinical staff and have moved them to the technology support or even required from these staff dual roles of doing patient care and technology support. We have not formalized the qualifications for biomeds in the dialysis industry, compared with the formality that they have within the hospital environment.Jo-Ann Maltais I agree with Danilo. I sit on the National Nephrology Certification Organization Board of Directors, so I see information on the types of individuals who take the certification exams. To Danilo's point, many of them come from the patient care side and are unable to pass the biomedical nephrology technology exam on the first try. Furthermore, dialysis biomedical technicians do not receive adequate training. Part of that could be solved by pursuing certification, but there's not sufficient motivation it seems. Certification is not required by CMS for the biomeds, whereas it is for the patient care techs. Many of the companies and providers don't support their technicians in taking the exam, so there really isn't any motivation for the individuals to increase their technical training. Sean Loughlin Are there other thoughts on why dialysis technicians are undertrained?Danilo Concepcion From my perspective, the manufacturers of dialysis equipment have done an excellent job of simplifying maintenance and repair, so you don't always need a
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