HemoCleanse (United States)

Abstract RATIONALE: Hypoxemia is a common and life-threatening complication of emergency tracheal intubation. Preoxygenation with supplemental oxygen prior to induction of anesthesia decreases the risk of hypoxemia during intubation. An oxygen mask is the most common method of preoxygenation used in current clinical care. While preoxygenation using noninvasive ventilation has been shown to reduce hypoxemia during intubation compared to preoxygenation with an oxygen mask, noninvasive ventilation may not be suitable for all patients or settings. When an oxygen mask is used, whether the type of mask affects the incidence of hypoxemia is not known.METHODS: We conducted a secondary analysis of the Pragmatic Trial Examining Oxygenation Prior to Intubation (PREOXI) and Direct vs Video Laryngoscope (DEVICE) randomized controlled trials. We compared the incidence of hypoxemia, defined as a peripheral oxygen saturation <85% between induction and 2 minutes after tracheal intubation, between participants preoxygenated with facemask oxygen (either a nonrebreather or facemask without oxygen reservoir) versus a bag-mask device without manual ventilation. The primary analysis was a propensity weighted multivariate logistic regression adjusting for body mass index (BMI), APACHE II score, intubation location (ICU vs ED) and hypoxemic respiratory failure prior to intubation as covariates.RESULTS: Of the 2440 participants enrolled in the PREOXI and DEVICE trials, 1077 were preoxygenated using facemask oxygen and 148 were preoxygenated using a bag-mask device without manual ventilation. The median highest Fraction of Inspired Oxygen (FiO2) prior to intubation was 0.3 (interquartile range [IQR] 0.21 to 0.66) in both the facemask oxygen and bag-mask device groups. A total of 168/1077 (16%) of participants in the facemask oxygen group and 28/148 (19%) of participants in the bag-mask device groups received heated high flow nasal cannula oxygen in the hour prior to intubation. Hypoxemia occurred in 156/1034 (15.1%) participants in the facemask oxygen group and 20/139 (14.4%) participants in the bag-mask device group. In the multivariate analysis, participants preoxygenated with facemask oxygen had similar odds of hypoxemia to those preoxygenated with a bag-mask device (aOR:1.21, 95%CI:[0.70,2.09]). The median lowest oxygen saturation between induction and 2 minutes after tracheal intubation was 97 (IQR 91 to 100) in the facemask oxygen group and 98 (IQR 93 to 100), P=0.33 in the bag-mask device group.CONCLUSIONS: In this secondary analysis of two trials which enrolled critically ill adults undergoing emergency tracheal intubation, preoxygenation with facemask oxygen was not associated with decreased incidence of hypoxemia compared to preoxygenation with a bag-mask device.

An oral sorbent to remove NH4+ within the small intestine of end-stage kidney disease (ESKD) patients could reduce blood urea levels and diminish their dialysis treatment burden. But current sorbent materials like amorphous zirconium phosphate particles Zr(HPO4)2·H2O (ZrP) lack the selectivity to remove NH4+ in water solution with other competing ions. Our previous work found that a gas-permeable, hydrophobic polydimethylsiloxane (PDMS) coating on ZrP improved the material's selectivity for NH4+. However, a competing ion Ca2+ was still removed by PDMS-coated ZrP sorbent, and the permeability of the PDMS coating to Ca2+ was increased after low-pH stomach-like condition exposure. An alternative hydrophobic and gas permeable coating has been investigated─perfluorooctyltriethoxysilane (FOTS). The coating was attached in place of PDMS to a tetraethyl orthosilicate-coated ZrP surface. Surface atomic composition analysis and scanning electron microscopy observation verified the successful application of the FOTS coating. Water contact angle analysis validated the FOTS coating was hydrophobic (145.0 ± 3.2°). In vitro competing ion studies indicated the FOTS coating attached to ZrP increased NH4+ removal by 53% versus uncoated ZrP. FOTS offers complete selectivity for NH4+ over Ca2+ with similar NH4+ capacity as the previous PDMS coating. Moreover, FOTS-coated ZrP maintained NH4+ removal capacity and selectivity after the acid exposure study, indicating excellent acid resistance while NH4+ selectivity of ZrP-PDMS decreased by 72%. The results suggested that FOTS-coated ZrP is promising as an oral sorbent for ESKD patients.

In course of developing an anticoagulant and antibacterial catheter lock solution, we demonstrated that the components and alcohol formed an effective skin antiseptic. Ash Access formed a sister company to focus on development and clinical trials of this skin preparation and exchanged intellectual property for part ownership. Zurex Pharma now has Food and Drug Administration (FDA) approval on the new pre-operative skin preparation, ZuraGard™, and has made successful steps toward production and marketing of the product. The steps toward FDA approval, the size of the market, and user needs are clearer for a second product in the field than for the first.

When sodium citrate is used as an anticoagulant catheter lock the best concentration is 7%, since this provides a density approximately the same as blood. Our laboratory found that the addition of methylene blue and parabens greatly augmented antibacterial properties. Ash Access sponsored a randomized clinical trial in 400 dialysis patients with tunneled CVC, and this showed a significant decrease in incidence of catheter-related bloodstream infection (CRBSI) defined by stringent criteria. The FDA decided that the study missed its primary endpoint, and that the product was mis-classified, so they did not give approval to market. The licensee decided not to appeal to the decision to the physician panel and ended support of the project. Rights to market the catheter lock eventually returned to Ash Access.

A sorbent with a high enough capacity for NH4+ could serve as an oral binder to lower urea levels in end-stage kidney disease (ESKD) patients. A hydrogen-loaded cation exchanger such as zirconium phosphate Zr(HPO4)2·H2O (ZrP) is a promising candidate for this application. However, the NH4+ binding selectivity versus other ions must be improved. Here, we have developed a gas-permeable and hydrophobic surface coating on an amorphous form of ZrP using tetraethyl orthosilicate and methoxy-terminated polydimethylsiloxane. The hydrophobic coating serves as a barrier to ions in water solution from reaching the ion-exchanger's surface. Meanwhile, its gas-permeable nature allows for gaseous ammonia transfer to the cation exchanger. In vitro studies were designed to replicate the small intestine's expected ion concentrations and exposure time to the sorbent. The effectiveness of the coating was measured with NH4+ and Ca2+ solutions and uncoated ZrP as the negative control. X-ray photoelectron spectroscopy and scanning electron microscopy measurements show that the coating successfully modifies the surface of the cation exchanger─ZrP. Water contact angle studies indicate that coated ZrP is hydrophobic with an angle of (149.8 ± 2.5°). Simulated small intestine solution studies show that the coated ZrP will bind 94% (±11%) more NH4+ than uncoated ZrP in the presence of Ca2+. Meanwhile, Ca2+ binding decreases by 64% (±6%). The nearly fourfold increase in NH4+ selectivity can be attributed to the gas-permeable and hydrophobic coating applied on the ZrP surface. This work suggests a novel pathway to develop a selective cation exchanger for treating ESKD patients.

Dual-lumen "acute" central venous catheters (CVC) for dialysis were developed in the 1970s and tunneled "chronic" CVC in the 1980s. Fibrous sheathing of these catheters diminished the patency after weeks to months of use. Double catheters like Canaud/Tesio worked better and longer than single body catheters but were tedious to place. I decided that the optimal CVC design would be a single body that split into two tips within the vena cava. The "Ash Split Cath(TM) " was developed in cooperation with a company focused on dialysis access catheters, and quickly became widely used around the world. However, the patent did not prevent other companies from marketing split-tip catheters. A disagreement on the terms of a royalty agreement further weakened the relationship between the marketing company and our R&D company.

Abstract A personalized approach based on a patient’s or pathogen’s unique genomic sequence is the foundation of precision medicine. Genomic findings must be robust and reproducible, and experimental data capture should adhere to FAIR guiding principles. Moreover, effective precision medicine requires standardized reporting that extends beyond wet lab procedures to computational methods. The BioCompute framework (https://osf.io/zm97b/) enables standardized reporting of genomic sequence data provenance, including provenance domain, usability domain, execution domain, verification kit, and error domain. This framework facilitates communication and promotes interoperability. Bioinformatics computation instances that employ the BioCompute framework are easily relayed, repeated if needed and compared by scientists, regulators, test developers, and clinicians. Easing the burden of performing the aforementioned tasks greatly extends the range of practical application. Large clinical trials, precision medicine, and regulatory submissions require a set of agreed upon standards that ensures efficient communication and documentation of genomic analyses. The BioCompute paradigm and the resulting BioCompute Objects (BCO) offer that standard, and are freely accessible as a GitHub organization (https://github.com/biocompute-objects) following the “Open-Stand.org principles for collaborative open standards development”. By communication of high-throughput sequencing studies using a BCO, regulatory agencies (e.g., FDA), diagnostic test developers, researchers, and clinicians can expand collaboration to drive innovation in precision medicine, potentially decreasing the time and cost associated with next generation sequencing workflow exchange, reporting, and regulatory reviews.

The selective chemical binding of sorbents is well suited to treatment of hepatic failure and drug overdose. The Sorbent Suspension Reactor (SSR) is a dialysate regenerating device in which a suspension of powdered activated carbon is enclosed by a cylindrical sheet membrane. A rotating paddle and shunts create a high shear rate at the membrane surface on the reactor wall without excessive particle density polarization. A standard hemodialysis machine operates the extracorporeal blood circuit, including a hollow fiber dialyzer; the SSR system replaces the single-pass dialysate system with a dialysate-regenerating reactor. At dialysate flow rate = 450 mL/min, SSR should remove most toxins, resulting in water-soluble toxin clearance by SSR/hemodialysis system equal to the BioLogic-DT™. The DT was FDA-approved and clinically used to treat hepatic encephalopathy and drug overdose. A prototype SSR has chemical performance similar to the DT. Creatinine binding of activated carbon in the SSR generally exceeds theoretical equilibrium binding of a well-mixed suspension. A full-scale reactor has been constructed and has demonstrated capability to regenerate dialysate at flow = 450 mL/min. Tests are now beginning to confirm clearance rates for various small molecular weight toxins. Tests have also shown that SSR can also treat dialysate containing 5% albumin at flow rates in excess of 100 mL/min. When further developed, SSR will allow extracorporeal detoxification by powdered sorbents with the same efficacy as the DT but with greater simplicity, biocompatibility, and flexibility.