CytoSorb on the Septic Shock

Background: Septic shock, defined as organ dysfunction caused by a dysregulated host response to infection, is a condition associated with high morbidity and mortality. One of the hallmarks of sepsis is the excessive release of cytokines and other inflammatory mediators that cause septic shock and multi-organ failure (MOF). New adsorbents are now available as adjuvant therapy aimed at modulating the cytokine "storm" in sepsis. They are thought to be useful if adopted early (within 8-24 hours of the diagnosis of septic shock) in patients who are unresponsive to standard therapy. Here we report our experience with CytoSorb. Method(s): From January 2021 to May 2022, 46 patients with septic shock were treated with continuous renal replacement therapy (CRRT) associated with hemoadsorption with CytoSorb. All cases presented organ failure including AKI. Surgical patients (n = 13) were treated with surgery, COVID patients (n = 15) and medical patients (n = 16) with medical therapy;all surgery cases were operated on before starting the haemadsorption and in some cases reoperation with the need to suspend the adsorption. The mean age was 69 +/- 17 years (SD). On admission the mean SAPSII score was 50 +/- 11 (SD). CRRT as hemodiafiltration (CVVHDF) was performed. All patients received at least one CytoSorb treatment and additional treatments (up to 21 filters in a Covid patient) according to our indication. The CytoSorb cartridge was installed in series to the high cut-off filter;blood flow rates were maintained between 120 and 150 mL/min while dialysis doses from 18 to 45 mL/kg/hour. CytoSorb was renewed every 24 hours. We evaluated the impact of CytoSorb on 30-day survival, haemodynamics and relevant outcomes. Result(s): The 30-day survival was 30%. During treatment with CytoSorb, patients had a hemodynamic stabilization with a significant improvement in MAP, a reduction in amines and a decrease in PCR and PCT (Figure 1). Mortality at 30 days among medical patients was almost comparable to that of COVID patients and higher than that of surgical patients (70%, 69% and 61%, respectively). It should be noted that almost half of the deceased patients arrived late in the hospital, thus leading to a late start of treatment. Conclusion(s): We confirm the efficacy and usefulness of the CytoSorb if adopted early in patients who do not respond to standard therapy. CytoSorb treatment was safe and well tolerated with no device-related adverse events during or after treatment sessions.

Stability and WBE biomarkers possibility of 17 antiviral drugs in sewage and gravity sewers.

Wastewater-based epidemiology (WBE) is a promising technique for monitoring the rapidly increasing use of antiviral drugs during the COVID-19 pandemic. It is essential to evaluate the in-sewer stability of antiviral drugs in order to determine appropriate biomarkers. This study developed an analytical method for quantification of 17 typical antiviral drugs, and investigated the stability of target compounds in sewer through 4 laboratory-scale gravity sewer reactors. Nine antiviral drugs (lamivudine, acyclovir, amantadine, favipiravir, nevirapine, oseltamivir, ganciclovir, emtricitabine and telbivudine) were observed to be stable and recommended as appropriate biomarkers for WBE. As for the other 8 unstable drugs (abacavir, arbidol, ribavirin, zidovudine, ritonavir, lopinavir, remdesivir and efavirenz), their attenuation was driven by adsorption, biodegradation and diffusion. Moreover, reaction kinetics revealed that the effects of sediments and biofilms were regarded to be independent in gravity sewers, and the rate constants of removal by biofilms was directly proportional to the ratio of surface area against wastewater volume. The study highlighted the potential importance of flow velocity for compound stability, since an increased flow velocity significantly accelerated the removal of unstable biomarkers. In addition, a framework for graded evaluation of biomarker stability was proposed to provide reference for researchers to select suitable WBE biomarkers. Compared with current classification method, this framework considered the influences of residence time and different removal mechanisms, which additionally screened four antiviral drugs as viable WBE biomarkers. This is the first study to report the stability of antiviral drugs in gravity sewers.

Conceptual Design of a UVC-LED Air Purifier to Reduce Airborne Pathogen Transmission—A Feasibility Study

Existing indoor closed ultraviolet-C (UVC) air purifiers (UVC in a box) have faced technological challenges during the COVID-19 breakout, owing to demands of low energy consumption, high flow rates, and high kill rates at the same time. A new conceptual design of a novel UVC-LED (light-emitting diode) air purifier for a low-cost solution to mitigate airborne diseases is proposed. The concept focuses on performance and robustness. It contains a dust-filter assembly, an innovative UVC chamber, and a fan. The low-cost dust filter aims to suppress dust accumulation in the UVC chamber to ensure durability and is conceptually shown to be easily replaced while mitigating any possible contamination. The chamber includes novel turbulence-generating grids and a novel LED arrangement. The turbulent generator promotes air mixing, while the LEDs inactivate the pathogens at a high flow rate and sufficient kill rate. The conceptual design is portable and can fit into ventilation ducts. Computational fluid dynamics and UVC ray methods were used for analysis. The design produces a kill rate above 97% for COVID and tuberculosis and above 92% for influenza A at a flow rate of 100 L/s and power consumption of less than 300 W. An analysis of the dust-filter performance yields the irradiation and flow fields.

Assessment of Mobile Air Cleaners to Reduce the Concentration of Infectious Aerosol Particles Indoors

Airborne transmission via aerosol particles without close human contact is a possible source of infection with airborne viruses such as SARS-CoV-2 or influenza. Reducing this indirect infection risk, which is mostly present indoors, requires wearing adequate respiratory masks, the inactivation of the viruses with radiation or electric charges, filtering of the room air, or supplying ambient air by means of ventilation systems or open windows. For rooms without heating, ventilation, and air conditioning (HVAC) systems, mobile air cleaners are a possibility for filtering out aerosol particles and therefore lowering the probability of indirect infections. The main questions are as follows: (1) How effectively do mobile air cleaners filter the air in a room? (2) What are the parameters that influence this efficiency? (3) Are there room situations that completely prevent the air cleaner from filtering the air? (4) Does the air cleaner flow make the stay in the room uncomfortable? To answer these questions, particle imaging methods were employed. Particle image velocimetry (PIV) was used to determine the flow field in the proximity of the air cleaner inlet and outlet to assess regions of unpleasant air movements. The filtering efficiency was quantified by means of particle image counting as a measure for the particle concentration at multiple locations in the room simultaneously. Moreover, different room occupancies and room geometries were investigated. Our results confirm that mobile air cleaners are suitable devices for reducing the viral load indoors. Elongated room geometries, e.g., hallways, lead to a reduced filtering efficiency, which needs to be compensated by increasing the volume flow rate of the device or by deploying multiple smaller devices. As compared to an empty room, a room occupied with desks, desk separation walls, and people does not change the filtering efficiency significantly, i.e., the change was less than 10%. Finally, the flow induced by the investigated mobile air cleaner does not reach uncomfortable levels, as by defined room comfort standards under these conditions, while at the same time reaching air exchange rates above 6, a value which is recommended for potentially infectious environments.

Numerical Study on the Impact of Large Air Purifiers, Physical Distancing, and Mask Wearing in Classrooms

The risk of COVID-19 infection from virulent aerosols is particularly high indoors. This is especially true for classrooms, which often do not have pre-installed ventilation and are occupied by a large number of students at the same time. It has been found that precautionary measures, such as the use of air purifiers (AP), physical distancing, and the wearing of masks, can reduce the risk of infection. To quantify the actual effect of precautions, it is not possible in experimental studies to expose subjects to virulent aerosols. Therefore, in this study, we develop a computational fluid dynamics (CFD) model to evaluate the impact of applying the aforementioned precautions in classrooms on reducing aerosol concentration and potential exposure in the presence of index or infected patients. A CFD-coupled Wells–Riley model is used to quantify the infection probability (IP) in the presence of index patients. Different cases are simulated by varying the occupancy of the room (half/full), the volumetric flow rate of the AP, two different locations of the AP, and the effect of wearing masks. The results suggest that using an AP reduces the spread of virulent aerosols and thereby reduces the risk of infection. However, the risk of the person sitting adjacent to the index patient is only marginally reduced and can be avoided with the half capacity of the class (physical distancing method) or by wearing face masks of high efficiencies.

Managing Building Water Disruptions in a Post-COVID World: Water Quality and Safety Risk Assessment Tool for Academic Institutions and School Settings

Fluctuating building occupancy during the COVID-19 pandemic contributed to poor water quality and safety conditions in building water distribution systems (BWDSs). Natural disasters, man-made events, or academic institutional calendars (i.e., semesters or holiday breaks) can disrupt building occupant water usage, which typically increases water age within a BWDS. High water age, in turn, is known to propagate poor water quality and safety conditions, which potentially exposes building occupants to waterborne pathogens (e.g., Legionella) associated with respiratory disease or hazardous chemicals (e.g., lead). Other influencing factors are green building design and municipal water supply changes. Regardless of the cause, an increasing number of water management policies require building owners to improve building water management practices. The present study developed a Water Quality and Safety Risk Assessment (WQSRA) tool to address gaps in building water management for academic institutions and school settings. The tool is intended to assist with future implementation of water management programs as the result of pending policies for the built environment. The WQSRA was modeled after water management practices created for controlling water contaminants in healthcare facilities. Yet, a novel WQSRA tool was adapted specifically for educational settings to allow building owners to evaluate risk from water hazards to determine an appropriate level of risk mitigation measures for implementation. An exemplar WQSRA tool is presented for safety, facility, industrial hygiene, and allied professionals to address current gaps in building water management programs. Academic institutions and school settings should examine the WQSRA tool and formulate an organization-specific policy to determine implementation before, during, and after building water-disruptive events associated with natural or man-made disasters.

Effect of Transportation Operation on Air Quality in China Based on MODIS AOD during the Epidemic

With the rapid growth of automobile numbers and the increased traffic congestion, traffic has increasingly significant effects on regional air quality and regional sustainable development in China. This study tried to quantify the effect of transportation operation on regional air quality based on MODIS AOD. This paper analyzed the space-time characteristics of air quality and traffic during the epidemic by series analysis and kernel density analysis, and quantified the relationship between air quality and traffic through a Geographically Weighted Regression (GWR) model. The main research conclusions are as follows: The epidemic has a great impact on traffic and regional air quality. PM2.5 and NO2 had the same trend with traffic congestion delay index (CDI), but they were not as obvious as CDI. Both cities with traffic congestion and cities with the worst air quality showed strong spatial dependence. The concentration areas of high AOD value in the east areas of the Hu line were consistent with the two gathering centers formed by cities with traffic congestion in space, and also consistent with the gathering center of cities with poor air quality. The concentration area of AOD decline was consistent with the gathering center formed by cities with the worst air quality. AOD had a strong positive correlation with road network density, and its GWR correlation coefficient was 0.68, then These provinces suitable for GWR or not suitable were divided. This study has a great significance for the transportation planning, regional planning, air quality control strategies and regional sustainable development, etc.

Large-eddy simulations to define building-specific similarity relationships for natural ventilation flow rates

Natural ventilation can play an important role towards preventing the spread of airborne infections in indoor environments. However, quantifying natural ventilation flow rates is a challenging task due to significant variability in the boundary conditions that drive the flow. In the current study, we propose and validate an efficient strategy for using computational fluid dynamics to assess natural ventilation flow rates under variable conditions, considering the test case of a single-room home in a dense urban slum. The method characterizes the dimensionless ventilation rate as a function of the dimensionless ventilation Richardson number and the wind direction. First, the high-fidelity large-eddy simulation (LES) predictions are validated against full-scale ventilation rate measurements. Next, simulations with identical Richardson numbers, but varying dimensional wind speeds and temperatures, are compared to verify the proposed similarity relationship. Last, the functional form of the similarity relationship is determined based on 32 LES. Validation of the surrogate model against full-scale measurements demonstrates that the proposed strategy can efficiently inform accurate building-specific similarity relationships for natural ventilation flow rates in complex urban environments.

Risk of failure in dental implant osseointegration among people with the post-covid syndrome

Dental implants are a standard of care in contemporary dental practice and are widely employed for the restoration of missing teeth. The long-term utility of an implant is largely dependent on the successful implant osseointegration and maintenance of the same over time. Bone metabolism and inflammatory mechanism are interrelated phenomena and are usually collectively termed osteoimmunology, which may affect the predictability and success of implant osseointegration. Many biochemical mediators of inflammation, especially Interleukin (IL)1, IL-6, and Tumour necrosis factor (TNF)alpha, have been documented to increase the activity of bone-resorbing cells through the Receptor Activator of Nuclear Factor Kappa-B (RANK) and Receptor Activator of Nuclear Factor Kappa-B Ligand (RANKL)systems. Some of the earlier studies with very limited data suggest that SARS-CoV2 infection may also directly affect bone resorption. Thus, it is imperative to understand the pathophysiology of osseointegration in COVID-19 patients, to enhance successful implant osseointegration and prevent peri-implant bone loss in these patients. Here, we present a summary of the connection between inflammatory pathways and bone metabolism on a molecular basis which may assume a significant bearing in situations of exaggerated host immune response as seen in COVID-19 infection.Copyright © 2022 Wolters Kluwer Medknow Publications. All rights reserved.

Teaching Analytical Instrumentation Through Remote Access – A Gas Chromatography Perspective

An approach to online laboratory exercises for analytical chemistry students with demonstrated practical exercises through the use of remote-controlled gas chromatography (GC) instrumentation is discussed. The approach allows for a practical-based learning activity to be carried out by students who are unable to attend in-person laboratory exercises and was conducted during the COVID-19 pandemic. Learning activities focused on the operation of GC instrumentation were completed prior to a research-based analysis activity being conducted by students. At the end of this experiment, the students are expected to understand, independently operate, and learn how to achieve better separation through the manipulation of GC settings, such as split/splitless injections, carrier gas flow rate, and oven temperature, and apply principles of GC to a practical application. Additional flexibility from this approach could also be beneficial during postpandemic and/or in the circumstance where students cannot physically attend the class.

Predicting Dust Pollution in the Passenger Compartment

Fine dust particles, which are present in the air in large quantities, are dangerous to human health. They enter the body through the lungs, but move to almost all organs, causing a number of respiratory diseases, pneumonia and are carriers of the coronavirus. This research proposes a method for numerically calculating the process of dust pollution of the passenger compartment when fine dust enters the cabin through the ventilation system. To calculate the concentration field of dust in the cabin, the equation of convective-diffusion dust dispersion is used, which takes into account the intensity of dust entering the passenger compartment, the unevenness of the air flow velocity field in the passenger compartment, diffusion, and additional dust emission from the floor surface. To calculate the velocity field of the air flow in the car interior, a potential flow model is used, the modeling equation is the Laplace equation for the velocity potential. For the numerical integration of the convective-diffusion dispersion equation of fine dust in the cabin, implicit finite-difference splitting schemes are used. For the numerical solution of the equation for the aerodynamic velocity potential, the alternating-triangular method of A. Samarsky is used. The computer code has been developed that implements the method of numerical calculation. The results of computational experiments to assess the level of dust pollution in the passenger compartment are presented. © 2022 Kaunas University of Technology. All rights reserved.

Effect of Dialysate Flow Rate (DFR) Reduction on Adequacy in a Chronic Hemodialysis Unit

Background: The Covid-19 pandemic has introduced a number of challenges in managing populations with both acute kidney failure and those dependent on chronic dialysis. Due to a shortage of outpatient dialysis supplies, on February 14, 2022, the Dpt. of Veteran's Affairs issued a memorandum to dialysis units requiring a contingency standard of care. This required a universal reduction of dialysate flow rate to 500 cc/min. Prior to this change, the standard prescription at the Lexington, KY VA unit was 750 cc/min. We evaluated the effect of this change on the adequacy of our dialysis population. Method(s): Data was collected for sp Kt/V urea and urea reduction ratio for 17 chronic hemodialysis patients for the two months prior and three months following the reduction of dialysate flow rate to 500 cc/min from the previous standard of 750 cc/min. There was no change of blood flow rate or dialysis time during this 5 month period for all the patients included. Result(s): A trend towards lower clearance values as measured by single-pool Kt/V and urea reduction ratio was noted between January and April of 2022. Table 1 shows the average spKt/V and URR for each month. The majority of patients maintained adequate spKt/V of >1.2 and urea reduction ratio of >65%. However, 4 patients (23.5% of the population) failed to reach Kt/V and URR goal in April 2022. Conclusion(s): Though this represents only 17 patients from one dialysis unit, the data suggests a significant decline in adequacy due to this reduction in dialysis flow rate to 500 cc/min. Until the current dialysis supply shortage has been addressed, adaptive measures such as utilizing higher efficiency dialyzers or increasing blood flow rates may be necessary.

Hemodynamic Parameters After Prone Positioning of COVID-19 Patients

Aim of the study. To examine the effect of prone positioning on hemodynamics in patients with COVID-19. Materials and methods. The study enrolled 84 patients of both sexes with community-acquired multiseg-mental viral and bacterial pneumonia associated with COVID-19, who were divided into groups according to the type of respiratory support. The tests were performed using the integrated hardware and software system for noninvasive central hemodynamic assessment by volumetric compression oscillometry. Results. We found that the pulse blood pressure velocity decreased from 281 [242.0;314.0] to 252 [209;304] mm Hg/s in patients with severe COVID-19 on oxygen support (p=0.005);volume ejection rate decreased from 251 [200;294] to 226 [186;260] ml/s (P=0.03);actual/estimated normalized vascular resistance ratio dropped from 0.549 [0.400;0.700] to 0.450 [0.300;0.600] (P=0.002), while the arterial wall compliance increased from 1.37 [1.28;1.67] to 1.45[1.10;1.60] ml/mm Hg (P=0.009). Prone positioning of patients on noninvasive lung ventilation associated with a reduction of linear blood flow rate from 40.0 [34.0;42.0] to 42.5 [42.5;47.25] cm/s (P=0.04) and arterial wall compliance from 1.4 [1.24;1.50] to 1.32 [1.14;1.49] ml/mm Hg (P=0.03). Prone positioning of patients on invasive lung ventilation did not result in significant hemodynamic changes. Conclusion. The greatest hemodynamic changes during prone positioning were found in patients on oxygen respiratory support, whereas the least significant alterations were seen in patients on invasive ventilatory support. Copyright © 2021, V.A. Negovsky Research Institute of General Reanimatology. All rights reserved.

A Retrospective Data Analysis in a General Icu Population: Acute Dialysis Catheter Type and Dialysis Efficiency

Introduction: Acute kidney injury in intensive care units (ICUs) is often treated with Continuous Renal Replacement Therapy (CRRT). Longer and uninterrupted CRRT sessions benefit patients, providers, and institutions. The impact of acute dialysis catheters on CRRT efficiency has only been evaluated in limited, single-centered Australian studies. This multicenter retrospective analysis examines associations between catheter type and multiple CRRT efficiency-related outcomes in a general ICU population. Method(s): CRRT session data from April 2018-July 2020 in two US ICUs were analyzed. Both units replaced three different acute dialysis catheters with a single new catheter in May 2019. Study intervals were divided into pre-/postchange periods, excluding a transition period (April-June 2019). To evaluate the pandemic's effects, the post-change period was further divided into pre-COVID/COVID periods. Outcome measures included treatment stoppage type (elective/non-elective), circuit life, blood flow rate, and frequency of all/vascular access (VA)-related alarm interruptions. Result(s): In total, 1,1037 CRRT sessions were analyzed. Compared to pre-change sessions (n=530), post-change period (n=507) had a reduced proportion of unintended stoppages (adjusted OR=0.42, 95% CI 0.28-0.62, p<0.001), longer circuit life (adjusted OR=1.31, 95% CI 1.14-1.49, p<0.001), increased blood flow rate (adjusted OR=1.03, 95% CI 1.01-1.05, p<0.01), and fewer VA-related interruptions (adjusted OR=0.80, 95% CI 0.66-0.96, p=0.014) and all interruptions (adjusted OR=0.95, 95% CI 0.87-1.05, p=0.31). Sessions during (n=340) and before (n=167) the pandemic were statistically similar except for a decreased proportion of unintended stoppages (adjusted OR=0.39, 95% CI 0.22-0.70, p<0.01). Discussion and conclusion: Adopting a different dialysis catheter was associated with longer CRRT sessions with fewer interruptions in the critically ill. Although the efficiency metrics were largely similar before and during the COVID19 pandemic, a notable increase in session volume was observed during the pandemic months. Future studies are warranted to evaluate the clinical impacts of CRRT efficiency and different catheter designs on patients and providers.

Effects of Brush-Type Ionizer Materials on Virus Inactivation.

Many studies have found that bioaerosols are harmful to humans. In particular, infectious viruses, such as the virus that causes COVID-19, are increasing. Therefore, the research on methods for reducing bioaerosols is becoming progressively more important. The purpose of this study was to improve the existing electrostatic precipitator, which generates high concentrations of ozone, by reducing bioaerosols effectively without significant ozone production. A brush-type ionizer was studied as a replacement for the existing electrostatic precipitator. The study, which was conducted at the laboratory scale, determined the amounts of ions generated with different ionizer materials (carbon, copper, and stainless steel) and voltages (-1, -2, and -3 kV), as well as it compared the virus inactivation efficiency under the various conditions. As a result, about two million ions were produced when a voltage of -3 kV was applied to all of the materials, and 99.9 ± 0.2% and 98.8 ± 0.6% virus inactivation efficiencies were confirmed in the cases of carbon and copper, respectively. In addition, an assessment of the effect of flow velocity confirmed that the inactivation efficiency decreased as the flow velocity increased. However, the results for the flow velocities of 0.2 and 0.4 m/s had similar trends. Therefore, this system can be used with flow velocities up to 0.4 m/s.

Minimal recovery of drug from extracorporeal treatment in a case of phenytoin toxicity associated with coma and hypothermia

Background: The Extracorporeal Treatments in Poisoning (EXTRIP) workgroup provides a weak conditional recommendation in support of hemodialysis (HD) for select patients with severe phenytoin poisoning. Despite this recommendation, the HD clearance of phenytoin is poorly studied. We present a patient who developed phenytoin toxicity that was treated with hemodialysis and report on the efficacy of phenytoin removal during HD. Case report: An 87-year-old man with epilepsy who was maintained on a stable dose of 300mg phenytoin extended-release daily was admitted to the hospital for treatment of Coronavirus Disease 2019 and congestive heart failure. On hospital day 14, the patient had a gradual onset of depressed mental status with hypothermia (nadir 35 degrees Celsius). At this time, he had a rising total blood phenytoin concentration (peak 49.3 mcg/mL [therapeutic 10-20mcg/mL] with an albumin of 3.8 g/dL [normal 3.4-5.4 g/dL]). The patient's other medications included furosemide, aspirin, atorvastatin, digoxin, doxycycline, metoprolol tartrate, and warfarin;he was also receiving albumin and crystalloid for hypovolemia (albumin nadir on hospital day 14: 2.5 g/dL). Free phenytoin concentrations were not available. Alternate etiologies of hypothermia (endocrine, infectious) were excluded. The Poison Control Center was consulted and recommended HD because of the concern for prolonged coma, as per EXTRIP guidelines. The patient received three sessions of HD over a period of 6 days at 2.5-3 h per session using an F160 Optiflux membrane filter (Fresenius Medical Care, Waltham, MA, USA), with a blood flow rate of 350mL/min and a dialysate flow rate of 700mL/min. After the first session of HD (2.5 h) on hospital day 21, his hypothermia resolved and his phenytoin concentration fell from 39.2mcg/mL to 34.2 mcg/mL with only mild improvement in his mental status. After 6 days (hospital day 27), his phenytoin concentration decreased to 19.5 mcg/mL and his mental status normalized. Effluent from the first HD session had phenytoin concentrations below the limit of detection (0.50mcg/mL). Thus, no greater than 52mg of phenytoin was removed during a 2.5-h session of hemodialysis. Discussion(s): The reason for the sudden increase in blood phenytoin concentrations in this patient is unclear in the absence of drug-drug interactions or dosing changes to the phenytoin. Although uncommonly reported, patients with phenytoin toxicity can experience hypothermia. In this case, the patient's hypothermia resolved during HD, although it is unclear if this was related to changes in phenytoin concentration or (more likely) direct extracorporeal warming via the HD machine. If the patient's phenytoin clearance from the first session were extrapolated to subsequent sessions an estimated maximum of 166.4mg of phenytoin would be removed in 8 total hours of HD, which is far less than previously reported phenytoin clearances on the order of grams. This difference may be related to the use of high cutoff dialysis membranes in prior studies, which are not routinely used. Conclusion(s): Although HD rapidly resolved this patient's hypothermia, a minimal amount of phenytoin was recovered in the patient's dialysate. Prior studies suggesting consequential clearance and efficacy of phenytoin removal by extracorporeal treatment may not apply to routine HD methods. Further studies on the utility of extracorporeal treatment for phenytoin toxicity are needed.

Oral Presentation: Performance of an Artificial Intelligence System Tool for the Detection of ADRs from Patients' Reports During the Covid-19 Vaccination Campaign: An International Journal of Medical Toxicology and Drug Experience

Introduction: During the recent covid-19 vaccination campaign, the number of ICSRs reported by patients and professionals has dramatically increased, reaching up to almost 1 M declarations only in Europe (EMA numbers). To deal with such growing amount of data, Synapse Medicine®, in collaboration with The French National Agency for Medicines and Health Products Safety (ANSM), have developed an artificial intelligence (AI) tool, the Medication Shield, which, based on a natural language processing algorithm, is able to detect ADRs from patients' reports and to code them into an appropriate MedDRA preferred term (PT). Before the covid-19 pandemic, this system was successful in detecting ADRs from the patient reports declared through the French web national reporting system (1, 2). However, how it behaves in conditions of higher reporting flow rate is unknown at present. Objective: To evaluate the performance of the Medication Shield in detecting vaccine-related ADRs from patients' ICSRs declared across the covid-19 vaccination campaign. Methods: A machine learning (ML) pipeline composed by a light Gradient Boosting Machine ensemble model was employed to detect and code covid-19 vaccine-related ADRs from patients' ICSRs declared through the web reporting system during the vaccination campaign (Jan 2021-Apr 2022). The encoding of regional pharmacovigilance centers was employed as the reference ground truth to train the algorithm in a supervised manner. Moreover, a panel of three pharmacologists, with significant experience in ADRs encoding, was set-up to perform a case-by-case analysis of 200 hundreds reports for which the algorithm provided improper encoding. Results: Overall, 65.191 ICSRs were extracted and used to train our ML algorithm. Of this, 54.987 were employed to validate the system. Importantly, almost 86% of the ICSRs were related to covid vaccines. Because the percentage of newly reported ADRs increased over time and was higher for vaccine than not-vaccine related reports, we split the training and validation sets in batches with similar ADRs distribution. Performance evaluation is currently under process. Initial feedbacks from the analysis performed by the experts are showing an uneven distribution of false positive and false negative across samples. Results from the other experts are needed to confirm this finding. Conclusion: The core findings of this study will be gathered in the forthcoming weeks and be ready for the ISoP meeting in September. This work will provide new insights about the effectiveness of deploying AI as a support to treat real world data in a context of sanitary crisis.

ASAIO 2022 Annual Meeting Abstracts

The proceedings contain 226 papers. The topics discussed include: identification of biomarkers sensitive to pulsatile and continuous flow for identification of promising continuous flow VAD modulation protocols to mitigate non-surgical bleeding events;comprehensive machine learning analysis of pre-implantation risk factors for right heart failure after LVAD implantation;combining VA-ECMO And Impella (EC-Pella) before reperfusion mitigates left ventricular loading and injury due to VA-ECMO in acute myocardial infarction;platelet function at the intersection of the COVID-19 'cytokine storm' and mechanical circulatory support;a dialysate free portable artificial kidney device;durable right heart mechanical support system: a multi-day proof-of-concept study in pulmonary hypertension sheep;a dual-action nitric oxide-releasing slippery surface coating for extracorporeal organ support: first evaluation at clinically relevant blood flow rate for partial lung support;cannula add-on for pressure and flow measurement in VADs;and comparison of interlaboratory CFD simulations of the FDA benchmark blood pump model.

Impact of Dialysis Clinical Operating Conditions on Human Serum Protein-Mediated Inflammatory Biomarkers Released in Patients Using Polyarylethersulfone Membranes

Hemodialysis (HD) is a life-sustaining treatment of crucial importance in managing end-stage renal disease (ESRD). However, this membrane-based therapy is associated with acute side-effects due to bioincompatibility issues and limitations on the removal of uremic toxins. The present study assessed the influence of hydrodynamic conditions applied during HD treatment on protein-mediated inflammatory and thrombotic responses. The membrane modules considered are commonly used in Canadian hospitals and are comprised of a polymer blend of polyarylether sulfone-polyvinylpyrrolidone (PAES). The membranes morphology and hydrophilicity were assessed using SEM, AFM, BET, and zeta potential. An in vitro study evaluated the adsorptive behavior of fibrinogen (FB) to the membrane under different flow conditions. Lower rates of 200 mL/min promoted slower and significant FB adsorption, leading to more severe inflammatory and thrombotic responses. Hydrodynamic conditions also affected the concentration of all inflammatory biomarkers. Lower flow rates triggered more complement activation as well as coagulation, clotting, and inflammatory responses compared to higher flow rates. At the end of the dialysis session, patients treated with a Qb of 200 mL/min presented a significant increase in the concentration of C5a (232%), properdin (114%), serpin (545%), IL-1α (50%), IL-6 (450%), and vWF (212%). IL-1β and TNF-α concentrations declined by 12.5 and 35.5%, respectively. Male patients experienced more severe inflammatory responses than female patients at the operating conditions considered. Comparing the pre- and post-dialysis levels of female and male patients, female patients experienced significantly higher levels of IL-6 and properdin, while male patients presented higher levels of C5a, IL-1α, and IL-6. The results of this study will help clinical doctors evaluate the impact of HD operating conditions on blood activations before prescribing treatment and inform expectations for outcomes in female and male patients.

Penetration Efficiency and Concentration Distribution of Nanoparticles in a Hollow Tapered Cylinder

Knowing particle penetration efficiencies and concentration distributions in an inlet channel of a sampling device is beneficial for the robust assessment, attribution and quantification of nanoparticles produced by various activities. The aim of this research is to evaluate the effect of the presence or absence of a conical column inside a hollow tapered cylinder on the nanoparticle penetration efficiency and its outlet concentration profile for different flow rates. The particle penetration characteristics of various sizes from 3 nm to 20 nm were numerically investigated by using the flow field and convection diffusion equations within the hollow tapered cylinder. Firstly, the proposed model of the nanoparticle penetration efficiency for the hollow tapered cylinder with the conical column is validated with the experimental data in the literature. Then, the results indicate that the concentration at the outlet of the hollow tapered cylinder with the conical column exhibits annular profiles for 3 nm and 5 nm nanoparticles at a flow rate of 2.0 L/min, which is found to avoid centralizing the particles in the exit area. In addition, the penetration efficiency of nanoparticles can be improved by increasing flow rates or removing the conical column inside the hollow tapered cylinder. Finally, the ring-shaped concentration profile of the 10 nm nanoparticles at the outlet of the hollow conical cylinder with the conical column becomes more obvious as the flow rate decreases. This study interprets and quantitatively decides the nanoparticle penetration efficiency and its exit concentration profile for the hollow tapered cylinder with or without the conical column. Therefore, the results can provide some useful design references for the transport of nanoparticles in the hollow tapered cylinder.