Mass Transport in High-Flux Hemodialysis: Application of Engineering Principles to Clinical Prescription.

An understanding of the processes underlying mass transfer is paramount for the attainment of adequate solute removal in the dialytic treatment of patients with kidney failure. In this review, engineering principles are applied to characterize the physical mechanisms behind the two major modes of mass transfer during hemodialysis, namely diffusion and convection. The manner in which flow rate, dialyzer geometry, and membrane microstructure affect these processes is discussed, with concepts such as boundary layers, effective membrane diffusivity, and sieving coefficients highlighted as critical considerations.

A real-time assay for cell-penetrating peptide-mediated delivery of molecular cargos.

Cell-penetrating peptides (CPPs) are capable of transporting molecules to which they are tethered across cellular membranes. Unsurprisingly, CPPs have attracted attention for their potential drug delivery applications, but several technical hurdles remain to be overcome. Chief among them is the so-called 'endosomal escape problem,' i.

Continuous renal replacement therapy principles.

Continuous renal replacement therapy (CRRT) is an extracorporeal blood purification therapy that aims to support kidney function over an extended period of time. One of the main objectives of CRRT is the removal of excess fluid and solutes retained as a consequence of acute kidney injury. Because prescription of CRRT requires goals to be set with regard to the rate and extent of solute and fluid removal, a comprehensive understanding of the mechanism by which solute and fluid removal occurs during CRRT is essential.

Extracorporeal Blood Purification and Organ Support in the Critically Ill Patient during COVID-19 Pandemic: Expert Review and Recommendation.

Critically ill COVID-19 patients are generally admitted to the ICU for respiratory insufficiency which can evolve into a multiple-organ dysfunction syndrome requiring extracorporeal organ support. Ongoing advances in technology and science and progress in information technology support the development of integrated multi-organ support platforms for personalized treatment according to the changing needs of the patient. Based on pathophysiological derangements observed in COVID-19 patients, a rationale emerges for sequential extracorporeal therapies designed to remove inflammatory mediators and support different organ systems.

Uremic Toxins and their Relation to Dialysis Efficacy.

Toxin retention is felt to be a major contributor to the development of uremia in patients with advanced chronic kidney disease and end-stage renal disease (ESRD). Uremic retention compounds are classically divided into 3 categories: small solutes, middle molecules, and protein-bound toxins. Compounds comprising the first category, for which the upper molecular weight limit is generally considered to be 500 Da, possess a high degree of water solubility and minimal or absent protein binding.

Haemodialysis membranes.

Haemodialysis is an extracorporeal process in which the blood is cleansed via removal of uraemic retention products by a semipermeable membrane. Traditionally, dialysis membranes have been broadly classified on the basis of their composition (cellulosic or noncellulosic) and water permeability (low flux or high flux). However, advances in materials technology and polymer chemistry have led to the development of membranes with specific characteristics and refined properties that mandate a reconsideration of traditional membrane classification systems.

Advances in Machine Technology.

Continuous renal replacement therapy (CRRT) machines have evolved into devices specifically designed for critically ill over the past 40 years. In this chapter, a brief history of this evolution is first provided, with emphasis on the manner in which changes have been made to address the specific needs of the critically ill patient with acute kidney injury. Subsequently, specific examples of technology developments for CRRT machines are discussed, including the user interface, pumps, pressure monitoring, safety features, and anticoagulation capabilities.

Membranes and Sorbents.

For continuous renal replacement therapy (CRRT), the extracorporeal filter provides solute depuration, fluid removal, and control of electrolyte and acid-base balance in critically ill patients with acute kidney injury (AKI). The membranes comprising CRRT filters are almost exclusively based on hollow fiber designs and, while adapted from the chronic hemodialysis field, have features that are specific to the requirements of CRRT nevertheless. In addition, these devices have evolved through the 40 years of CRRT in response to changes in clinical practice and the desire to extend the solute removal spectrum.

Renal replacement therapy for AKI: When? How much? When to stop?

Severe acute kidney injury (AKI) requiring renal replacement therapy (RRT) is a serious clinical disorder in the intensive care unit (ICU), occurring in a significant proportion of critically ill patients. However, many questions remain about the optimal administration of RRT with regard to several important considerations, including treatment dose, timing of treatment initiation and cessation, therapy mode, type of anticoagulation, and management of fluid overload. While Level 1 evidence exists for RRT dosing in AKI, all the studies contributing to this evidence base employed fixed-dose regimens throughout a patient's continuous RRT (CRRT) course, without regard for the possibility of individualizing treatment dose according to the clinical status of a given patient at a specific time.

Modeling of Internal Filtration in Theranova Hemodialyzers.

High retention onset (HRO) is the designation for a new class of hemodialysis membranes. A unique characteristic of this class is the highly selective and controlled porosity resulting in sieving properties that provide a clinically desirable balance between middle/large molecular weight solute removal and albumin loss. Another defining feature of this membrane class is the relatively small fiber diameter, which produces high convective volumes in the form of internal filtration.

Multidimensional Classification of Dialysis Membranes.

Hemodialysis is a process of mass separation by a semipermeable membrane, utilized to cleanse blood from waste products retained in case of kidney failure. Traditionally, dialysis membranes have been classified based on composition and hydraulic conductance, creating the net differentiation between cellulosic versus non-cellulosic on one hand and low-flux versus high-flux on the other. With the evolution of biomaterials and improved spinning technology, new membranes have been introduced in the market with specific characteristics and refined individual properties.

Solute Transport in Hemodialysis: Advances and Limitations of Current Membrane Technology.

Extracorporeal therapy for end-stage renal disease is now provided to more than three million patients globally. Nearly all treatments are performed with filters containing hollow fiber membranes, removing solutes and water by diffusion, convection, and ultrafiltration. In this review, we will provide a detailed quantitative analysis of the transport processes involved in different hemodialysis (HD) therapies.

Renal replacement therapy practices for patients with acute kidney injury in China.

Recent data indicate AKI is very common among hospitalized Chinese patients and continuous renal replacement therapy (CRRT) is increasingly offered for treatment. However, only anecdotal information regarding CRRT's use in relation to other modalities and the specific manner in which it is prescribed exists currently. This report summarizes the results of a comprehensive physician survey designed to characterize contemporary dialytic management of AKI patients in China, especially with respect to the utilization of CRRT.

Quantification and Dosing of Renal Replacement Therapy in Acute Kidney Injury: A Reappraisal.

Background/aims: Delivered dialysis therapy is routinely measured in the management of patients with end-stage renal disease; yet, the quantification of renal replacement prescription and delivery in acute kidney injury (AKI) is less established. While continuous renal replacement therapy (CRRT) is widely understood to have greater solute clearance capabilities relative to intermittent therapies, neither urea nor any other solute is specifically employed for CRRT dose assessments in clinical practice at present. Instead, the normalized effluent rate is the gold standard for CRRT dosing, although this parameter does not provide an accurate estimation of actual solute clearance for different modalities.

Extracorporeal Sorbent Technologies: Basic Concepts and Clinical Application.

Limitations imposed by the characteristics of some solutes and the structure of dialysis membranes have spurred new interest in the use of mechanisms beyond diffusion and convection for extracorporeal solute removal. Sorbents have been utilized for more than 50 years in extracorporeal blood treatments for specific purposes, and better understanding of their basic aspects may further expand the potential for their clinical application. In this chapter, the basic principles applying to sorbents are discussed, including composition and structure, along with the fundamental mechanisms of solute removal.

The future of critical care: renal support in 2027.

Since its inception four decades ago, both the clinical and technologic aspects of continuous renal replacement therapy (CRRT) have evolved substantially. Devices now specifically designed for critically ill patients with acute kidney injury are widely available and the clinical challenges associated with treating this complex patient population continue to be addressed. However, several important questions remain unanswered, leaving doubts in the minds of many clinicians about therapy prescription/delivery and patient management.

Data analytics for continuous renal replacement therapy: historical limitations and recent technology advances.

Purpose: Dialysis is a highly quantitative therapy involving large volumes of both clinical and technical data. While automated data collection has been implemented for chronic dialysis, this has not been done for acute kidney injury patients treated with continuous renal replacement therapy (CRRT).

Methods: After a brief review of the fundamental aspects of electronic medical records (EMRs), a new tool designed to provide clinicians with individualized CRRT treatment data is analyzed, with emphasis on its quality assurance capabilities.

Nomenclature for renal replacement therapy in acute kidney injury: basic principles.

This article reports the conclusions of a consensus expert conference on the basic principles and nomenclature of renal replacement therapy (RRT) currently utilized to manage acute kidney injury (AKI). This multidisciplinary consensus conference discusses common definitions, components, techniques, and operations of the machines and platforms used to deliver extracorporeal therapies, utilizing a "machine-centric" rather than a "patient-centric" approach. We provide a detailed description of the performance characteristics of membranes, filters, transmembrane transport of solutes and fluid, flows, and methods of measurement of delivered treatment, focusing on continuous renal replacement therapies (CRRT) which are utilized in the management of critically ill patients with AKI.

InAlAs/InGaAs avalanche photodiode arrays for free space optical communication.

In free space optical communication, photodetectors serve not only as communications receivers but also as position sensitive detectors (PSDs) for pointing, tracking, and stabilization. Typically, two separate detectors are utilized to perform these tasks, but recent advances in the fabrication and development of large-area, low-noise avalanche photodiode (APD) arrays have enabled these devices to be used both as PSDs and as communications receivers. This combined functionality allows for more flexibility and simplicity in optical system design without sacrificing the sensitivity and bandwidth performance of smaller, single-element data receivers.

Phase 1/2 study of orteronel (TAK-700), an investigational 17,20-lyase inhibitor, with docetaxel-prednisone in metastatic castration-resistant prostate cancer.

Background: Docetaxel-prednisone (DP) is an approved therapy for metastatic castration-resistant prostate cancer (mCRPC). Orteronel (TAK-700) is an investigational, selective, non-steroidal inhibitor of 17,20-lyase, a key enzyme in androgenic hormone production. This phase 1/2 study evaluated orteronel plus DP in mCRPC patients.

Pleistocene and ecological effects on continental-scale genetic differentiation in the bobcat (Lynx rufus).

The potential for widespread, mobile species to exhibit genetic structure without clear geographic barriers is a topic of growing interest. Yet the patterns and mechanisms of structure--particularly over broad spatial scales--remain largely unexplored for these species. Bobcats occur across North America and possess many characteristics expected to promote gene flow.

Hemodynamic effects of once-daily tadalafil in men with signs and symptoms of benign prostatic hyperplasia on concomitant α1-adrenergic antagonist therapy: results of a multicenter randomized, double-blind, placebo-controlled trial.

Objective: To investigate the safety of daily coadministration of α-blockers with tadalafil 5 mg in men with lower urinary tract symptoms secondary to benign prostatic hyperplasia. The standard-of-care medical therapy for moderate to severe symptoms of benign prostatic hyperplasia is α(1)-adrenergic antagonist (α-blocker) therapy.

Methods: Men aged ≥ 45 years receiving stable α-blocker therapy were evaluated for eligibility before a 2-week single-blind, placebo lead-in period.

Stochastic population dynamics in populations of western terrestrial garter snakes with divergent life histories.

Comparative evaluations of population dynamics in species with temporal and spatial variation in life-history traits are rare because they require long-term demographic time series from multiple populations. We present such an analysis using demographic data collected during the interval 1978-1996 for six populations of western terrestrial garter snakes (Thamnophis elegans) from two evolutionarily divergent ecotypes. Three replicate populations from a slow-living ecotype, found in mountain meadows of northeastern California, were characterized by individuals that develop slowly, mature late, reproduce infrequently with small reproductive effort, and live longer than individuals of three populations of a fast-living ecotype found at lakeshore locales.

Blood-membrane interactions during dialysis.

In extracorporeal renal replacement therapies, the dialyzer is not only the site at which solute removal occurs but also the extracorporeal circuit component having the largest surface area exposed to blood. Therefore, it is not surprising that interactions between blood components and the dialyzer membrane influence the dialysis procedure in several ways. Based on engineering principles, fluid flow along a surface such as membrane results in the development of a boundary layer which can influence solute removal.

Emergency medical services education and licensure--a road map for the future.

Fragmentation exists nationwide in regards to Emergency Medical Services (EMS). This fragmentation is evident throughout the EMS system in the way we educate, train, certify, and recertify the pre-hospital professional. In Louisiana EMS, there are two facets of our education system: the training/education institution and the instructors who facilitate the education.