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Objective: To test the hypothesis that the spondyloepiphyseal dysplasia congenita (sedc) heterozygous (sedc/+) mouse, a COL2A1 mutant, is a model for the study of osteoarthritis (OA) in the absence of dwarfism and to investigate the presence of HtrA1, Ddr2, and Mmp-13 and their possible involvement in a universal mechanism leading to OA.Design: Whole mount skeletons of adult animals were analyzed to determine whether sedc/+ mice exhibit dwarfism. To characterize progression of osteoarthritic degeneration over time, knee and temporomandibular joints from sedc/+ and wild-type mice were analyzed histologically, and severity of articular cartilage degradation was graded using the Osteoarthritis Research Society International (OARSI) scoring system. Immunohistochemistry was used to detect changes in expression of HtrA1, Ddr2, and Mmp-13 in articular cartilage of knees.Results: As previously reported, the sedc/+ skeleton morphology was indistinguishable from wild type, and skeletal measurements revealed no significant differences. The sedc/+ mouse did, however, show significantly higher OARSI scores in knee (9, 12 and 18 months) and temporomandibular joints at all ages examined. Histological staining showed regions of proteoglycan degradation as early as 2 months in both temporomandibular and knee joints of the mutant. Cartilage fissuring and erosion were observed to begin between 2 and 6 months in temporomandibular joints and 9 months in knee joints from sedc/+ mice. Immunohistochemistry of mutant knee articular cartilage showed increased expression of HtrA1, Ddr2, and Mmp-13 compared to wild type, which upregulation preceded fibrillation and fissuring of the articular surfaces.Conclusions: With regard to skeletal morphology, the sedc/+ mouse appears phenotypically normal but develops premature OA as hypothesized. We conclude that the sedc/+ mouse is a useful model for the study of OA in individuals with overtly normal skeletal structure and a predisposition for articular cartilage degeneration. [ABSTRACT FROM AUTHOR]

Background: The objective of this systematic evaluation was to identify the sentinel standards necessary to obtain a core level of communication required of a clinical perfusionist during cardiopulmonary bypass (CPB). Once these sentinel standards were identified and a core level of communication was established (via four simulated case scenarios), a team of cardiac healthcare professionals was assembled to interpret both the accuracy of response and the speed of response encountered in each case scenario.Methods: Four simulated case scenarios were utilized in order to replicate the typical patterns of verbal exchange that occur during surgeries using extracorporeal technology. The simulated case scenarios included CPB interactions associated with preparation, initiation, maintenance, termination and post CPB. For all CPB interactions, two variables were measured: accuracy of the perfusionist’s response and speed of the perfusionist’s response. The cases took place in a controlled setting within an empty operating room at The Children’s Hospital of Philadelphia. Four clinical perfusionists each represented the role of the “perfusionist” in all simulated case scenarios.Results: When analyzing the accuracy and speed of the responses, each clinical perfusionist recorded an average score of 96.3% or higher with all case scenarios. Since the clinical perfusionists who participated in the scenarios were primarily pediatric perfusionists, the scores were best during the pediatric case scenario, 99.3% (Case Scenario #4). The lowest scores were captured during Case Scenario #3 (96.3%) which involved a more intense adult patient scenario.Conclusion: The systematic evaluation of both response accuracy and response time (presented in various adult and pediatric patient case scenarios) can be beneficial within the realm of perfusion education. Students will be introduced to core communication concepts within the clinical realm. This study supports the idea that simulation and evaluation may ease the transition for students from the didactic to clinical realm in terms of communication. Further studies need to be developed in order to define “standard” CPB communication guidelines for perfusion students. [ABSTRACT FROM PUBLISHER]

Intravenous (IV) Δ9-tetrahydrocannabinol (THC) induces transient psychotic symptoms in healthy subjects and in schizophrenic patients, but the psychotomimetic mechanism is unknown. One possibility is that THC stimulates dopamine (DA) release in the striatum. In this study we tested whether IV THC led to an increase in striatal DA release compared to placebo. We also investigated whether DA release and positive psychotic symptoms were related. Eleven healthy male volunteers completed two 123I-iodobenzamide ([123I]IBZM) single photon emission tomography (SPET) sessions and received IV THC (2.5 mg) or placebo in a randomized counterbalanced order, under double-blind conditions. Analysable data were obtained from nine participants. The Positive and Negative Syndrome Scale (PANSS) was used to rate psychotomimetic effects. Striatal binding index values were calculated using the occipital cortex as a reference region. Both the PANSS positive and general symptoms increased significantly at 30 min following IV THC. There were no significant differences in binding index in the caudate or putamen under THC compared to placebo conditions. Positive psychotic symptoms and DA release were unrelated. THC did not lead to a significant increase in DA release even though the dose was sufficient for participants to have psychotic symptoms. These findings do not support a central role for striatal DA in THC-elicited psychosis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Recent work suggests that heavy use of cannabis is associated with an increased risk of schizophrenia-like psychosis. However, there is a dearth of experimental studies of the effects of the constituents of cannabis, such as Delta9-tetrahydrocannabinol (THC). In a study of intravenous (i.v.) synthetic THC in healthy humans, we aimed to study the relationship of the psychotic symptoms induced by THC to the consequent anxiety and neuropsychological impairment. METHOD: Twenty-two healthy adult males aged 28+/-6 years (mean+/-s.d.) participated in experimental sessions in which i.v. THC (2.5 mg) was administered under double-blind, placebo-controlled conditions. Self-rated and investigator-rated measurements of mood and psychosis [the University of Wales Institute of Science and Technology Mood Adjective Checklist (UMACL), the Positive and Negative Syndrome Scale (PANSS) and the Community Assessment of Psychic Experiences (CAPE)] were made at baseline and at 30, 80 and 120 min post-injection. Participants also completed a series of neuropsychological tests [the Rey Auditory Verbal Learning Task (RAVLT), Digit Span, Verbal Fluency and the Baddeley Reasoning Task] within 45 min of injection. RESULTS: THC-induced positive psychotic symptoms, and participant- and investigator-rated measurements of these were highly correlated. Participants showed an increase in anxiety ratings but there was no relationship between either self- or investigator-rated positive psychotic symptoms and anxiety. THC also impaired neuropsychological performance but once again there was no relationship between THC-induced positive psychotic symptoms and deficits in working memory/executive function. CONCLUSIONS: These findings confirm that THC can induce a transient, acute psychotic reaction in psychiatrically well individuals. The extent of the psychotic reaction was not related to the degree of anxiety or cognitive impairment. [ABSTRACT FROM AUTHOR]

The influence of haematocrit on blood cyclosporin measurements has been studied in 276 paired blood and plasma samples from 21 renal transplant patients. A highly significant correlation was found between blood and plasma cyclosporin concentrations, r = 0.8744, but the correlation between blood or plasma cyclosporin and haematocrit was not significant. The ratio of blood/plasma cyclosporin did not significantly increase with increasing haematocrit. It was concluded that in vivo the influence of haematocrit on the measurement of blood cyclosporin concentrations was negligible. [ABSTRACT FROM AUTHOR]

In 14 patients receiving chronic amiodarone therapy the appearance of multilamellar inclusion bodies in peripheral blood neutrophils was related to both plasma concentrations of amiodarone and its desethyl metabolite and unwanted effects of the drug. Seven of the patients had well defined inclusion bodies. In this group mean amiodarone and desethylamiodarone concentrations were significantly higher than in the remaining seven patients and all but one had unwanted effects of the drug. Of the seven patients without inclusion bodies only one, with high plasma amiodarone and desethylamiodarone concentrations, had unwanted effects of the drug. It is concluded that the appearance of multilamellar bodies in the blood neutrophils of amiodarone-treated patients may help to distinguish those patients at risk of long-term amiodarone toxicity. [ABSTRACT FROM AUTHOR]

Twelve healthy volunteers received four separate doses of cyclosporin (5 mg kg-1). On three occasions the neat oil suspension (Sandimmun) was given dispersed in a different liquid vehicle and on one occasion the suspension was taken directly. Measurement of whole blood cyclosporin concentrations by radioimmunoassay showed no significant difference in the pharmacokinetic parameters of absorption between the neat preparation and the three dispersants used (milk, milk + chocolate flavouring and orange juice). [ABSTRACT FROM AUTHOR]

Technology in healthcare has become increasingly prevalent and user friendly. In the last decade, advances in hands-free methods of data input have become more viable in a variety of medical professions. The aim of this study was to assess the advantages or disadvantages of hands-free charting through a voice-to-text app designed for perfusionists. Twelve clinical perfusion students using two different simulated bypass cases were recorded and assessed for the number of events noticed and charted, as well as the speed at which they accomplished these steps. Paper charts were compared with a custom app with voice-to-text charting capability. Data was analyzed using linear mixed models to detect differences in length of time until a chartable event was noticed, and how long after noticing an event it took to record the event. Timeliness of recording an event was made by assessing log-transformed time data. There was significantly more information recorded when charting on paper, while charting with voice-to-text resulted in significantly faster mean time from noticing an event to the recording of it. There was no significant difference between how many events were noticed and recorded. When using paper charting, a higher percentage of events that were missed were drug administration events, while voice charting had a higher percentage of missed events that were associated with cardioplegia delivery or bypass timing. With a decreased time interval between noticing an event and charting the event, speech-to-text for perfusion could be of benefit in situations where many events occur at once, such as emergency situations or highly active portions of bypass such as initiation and termination. While efforts were made to make the app as intuitive as possible, there is room for improvement., (© Copyright 2021 AMSECT.)

The aim of this study was to develop and validate a UHPLC-MS/MS assay to quantify cyclosporin (CYC), tacrolimus (TAC), sirolimus (SIR) and everolimus (EVE) in human whole blood for therapeutic drug monitoring. Analytes were extracted from 50 μL human whole blood by protein precipitation. The separation of the drugs was performed on an Acquity UPLC BEH C18 column. Analytes were eluted with a mobile phase consisting of 2 mM ammonium acetate with 0.1% formic acid (v/v) in deionised water and 2 mM ammonium acetate with 0.1% formic acid (v/v) in methanol at a flow rate of 300 μL/min in gradient elution. The method performance was evaluated by analysing patient blood samples and/or external quality control samples [proficiency testing (PT) scheme]. The method was linear from 23.75 to 1094.0, 1.3 to 42.4, 1.3 to 47.0 and 1.2-41.6 μg/mL for CYC, TAC, SIR and EVE, respectively. The within- and between-assay reproducibility results were ˂ 11%. Results from PT and patient sample quantification were comparable to those obtained previously by an in-house validated method using protein precipitation and liquid-liquid extraction. This method showed good analytical performance for quantifying CYC, TAC, SIR and EVE in whole blood over their respective calibration ranges., (© 2021 John Wiley & Sons, Ltd.)

Continuous cerebral tissue saturation monitoring with near infrared spectroscopy may help clinicians identify cerebral desaturation early; however, patients have reported discomfort from near infrared spectroscopy monitoring pads on the forehead. This study aims to compare upper extremity near infrared spectroscopy monitoring to cerebral near infrared spectroscopy monitoring to assess its viability as a surrogate for cerebral saturation. A retrospective analysis of 10 femorally cannulated veno-arterial extracorporeal membrane oxygenation patients was performed comparing left (L) and right (R) upper extremity (deltoid) near infrared spectroscopy monitoring to cerebral near infrared spectroscopy monitoring (n = 20 data sets, 10 left and 10 right) and right radial blood gasses. Deltoid and cerebral near infrared spectroscopy values were recorded every 15 minutes for at least 24 hours when possible, were plotted on scatter grams, and were analyzed using Pearson product-moment coefficient (r). Based on the concept of covariance, a moderate-good relationship r = 0.50-0.75 was noted in 10% (n = 2) of the study group. A fair relationship r = 0.25-0.50 was noted in 50% (n = 10), and little or no relationship was noted in 40% (n = 8). None of the study group displayed a good to excellent relationship (r = 0.75 or above). In addition, coefficient of multiple determination for multiple regression R 2 was calculated and strong fit of the regression line was not noted. Although cerebral near infrared spectroscopy monitoring has been extremely helpful in identifying low cerebral tissue saturation on veno-arterial extracorporeal membrane oxygenation patients, the use of upper extremity (peripheral deltoid) tissue monitoring does not provide adequate correlation and should not be used as a surrogate to cerebral monitoring.

This study presents, for the first time, the development and validation of a liquid chromatography and time-of-flight mass-spectrometry (LC-TOF-MS) based assay to quantify mycophenolic acid (MPA) in patient samples as part of a routine therapeutic drug monitoring service. MPA was extracted from 50 μl human plasma by protein precipitation, using sulindac as internal standard (IS). Separation was obtained on a Luna™ Omega polar C 18 column kept at 40°C. The mobile phase consisted of a mixture of acetonitrile-deionized water (50:50, v/v) with 0.1% formic acid at a flow rate of 350 μl/min. Analyte and IS were monitored on a TOF-MS using a Jet-Stream™ (electrospray) interface running in positive mode. Assay performance was evaluated by analysing patient plasma (N = 69) and external quality assessment (N = 6) samples. The retention times were 2.66 and 2.18 min for MPA and IS, respectively. The lower limit of quantification of MPA was 0.1 μg/ml. The within- and between-assay reproducibility results ranged from 1.81 to 10.72%. Patient and external quality assessment sample results were comparable with those obtained previously by an in-house validated LC-MS/MS method. This method showed satisfactory analytical performance for the determination of MPA in plasma over the calibration range of 0.1-15.0 μg/ml., (© 2020 John Wiley & Sons, Ltd.)

Perfusionists are leaving the workforce in higher rates as baby-boomers retire, yet the volume of cases involving perfusion continues to increase. This change has resulted in a high-demand market with organizations competing for the same candidates. The purpose of this study was to use a choice-based conjoint (CBC) analysis to determine what attributes of employment opportunities are most important to perfusionists so hiring organizations are better equipped to produce employment offers specific to each candidate. The Sawtooth Software Discover program was used to create a CBC survey that was distributed to perfusionists. After a series of demographic questions, respondents chose between three employment offers that comprised eight attributes, each with three varying options. Completed surveys were analyzed using the Discover software, producing importance scores. Two hundred forty surveys were completed, 154 (64%) male and 86 (36%) female. Extracorporeal membrane oxygenation (ECMO) impact to the perfusionist and hours worked per week ranked most important, at 19.4% and 17.5%, respectively. A significant difference exists between ECMO impact to perfusionists and all other attributes. The least important attributes were annual continuing education funds and sign-on bonus/relocation, at 6.8% and 4.7%, respectively. Respondents in their 20s and 30s find the importance of ECMO impact to be significantly less important than those in their 50s. Perfusionists with a master's degree believe salary to be significantly more important than perfusionists with other types of perfusion education. Based on the respondents who completed this survey, the impact ECMO has on the perfusionist was the most significant job attribute. Offering large sign-on bonuses and relocation packages to entice new employees is not indicated as a viable way to satisfy perfusionists. Appropriate management of hours worked, days on call, and how ECMO impacts the perfusionists will be most impactful in recruitment of new employees., (© Copyright 2020 AMSECT.)

Background: Vacuum-assisted venous drainage has gained widespread use within the pediatric perfusion community for use during cardiopulmonary bypass. It is questioned whether its efficiency may be compromised with application of excessive cardiotomy suction to the infant hard-shell venous reservoir. An in vitro simulation circuit was used to research this phenomenon. A comparison of three different infant hard-shell venous reservoirs also took place to determine if one reservoir type was more advantageous when handling cardiotomy suction. The reservoirs tested were the Maquet VHK 11000, Medtronic Affinity Pixie, and Terumo Capiox FX05., Methods: The in vitro simulation circuit consisted of a 1 L reservoir bag that was cannulated at one access point with an Edwards Lifesciences 10Fr aortic cannula and the other access area with an Edwards Lifesciences 10Fr right angle venous cannula and 12Fr right angle venous cannula that were joined together. Key points of measurement and response variables were the pressures on the connection of the venous cannulas, inlet of the venous reservoir, and flow through the venous line. Vacuum was applied and manipulated with a Maquet VAVD Controller to settings of -20 mmHg, -30 mmHg, -40 mmHg, -50 mmHg, and -60 mmHg. Cardiotomy suction was added at settings of 1 LPM, 2 LPM, 3 LPM, and 4 LPM. Values from each response variable were monitored and recorded. These data were utilized to compare the reservoirs with a random coefficient model for each response variable., Conclusions: There is an adverse effect of excessive cardiotomy suction on the efficacy of vacuum-assisted venous drainage in infant hard-shell venous reservoirs. There is no significant difference between the VHK 11000, Pixie, and FX05 regarding their ability to handle this occurrence. An important discovery was that the FX05 showed a greater transfer of vacuum to the venous cannulas and reservoir inlet.

Heater-cooler units (HCUs) play a vital role in temperature management during cardiopulmonary bypass. In recent years, HCUs have been shown to play a significant role in the propagation of bacteria causing patient infection and significant harm. As a result, various institutions across the world have begun moving the HCU either far away or outside of the operative theater entirely. The purpose of this study was to examine the effect that the increased length of HCU water lines have on the ability of the device to heat and cool. We hypothesized that the increase in water line distance leads to a decrease in HCU efficiency and that insulating the water lines would blunt the effect of this increase in distance. Five water line conditions were compared under two cooling and two warming ranges. Short water lines, long water lines, and long water lines with foam, rubber, or tape insulation were compared. Cooling from an arterial line temperature of 26.7-19.7°C showed no difference between conditions with the exception that every long line condition takes significantly longer to cool than short water lines. Cooling from 35.6 to 28.6°C revealed that all insulations reduce the cooling time compared with long water lines without insulation, but only foam insulation reduces to the level of the short water lines. During warming conditions, all insulations reduced the warming time compared with long uninsulated water lines, but none were comparable with short water lines. Increased water line length leads to a decrease in HCU efficiency. Insulation is effective at increasing efficiency of long water lines, but only at warmer temperatures and not to the level of short water lines. Only foam-insulated long water lines were able to match the efficiency of short water lines, but only across a single temperature range.

The use of extracorporeal membrane oxygenation (ECMO) has greatly increased over the years; however, the survival rate is only above 56%. There has been a drastic increase in ECMO centers and cases. ECMO has become a popular therapy route for patients with respiratory and cardiac complications; however, patient safety is a major concern. Perfusion and non-perfusion students from the University of Nebraska Medical Center were recruited to participate in three simulation trials. The trials consisted of five different tasks that are required for managing or preventing catastrophic events on ECMO. Students were evaluated for the time it took to complete each task, number of errors made, and protocol referencing. The data indicated that there was a decrease in time for the 1st vs. 2nd trial ( p = .02) for perfusion students and a decrease from the 1st to 3rd trial ( p = .001) for the circuit set-up simulation. There was a decrease in priming time from the 1st to 3rd trial ( p = .02) and for the pump change ( p = .0098) for the perfusion students as well. The non-perfusion students had a significant decrease in time for the circuit set-up in the 1st vs. 2nd ( p = .004) and 1st vs. 3rd trial ( p = .002). There was a decrease in time for priming (.004), pump change ( p = .002), tubing change ( p = .0098), and errors during the tubing change ( p = .02) in the non-perfusion students. Both groups felt more confident after the simulations and the non-perfusion students specifically felt like they were more familiar with the purpose of ECMO after the simulation. ECMO simulations and protocols may improve patient safety by strengthening the skills needed for rapid management, fewer errors, and higher levels of confidence during the management of ECMO and catastrophic events.

Safety devices such as bubble detectors and level detectors have been in use for more than 40 years and initially reduced the risks associated with gaseous emboli during cardiopulmonary bypass; however, the risks have not been eliminated. This research explored a new safety device designed to further reduce these risks: Flow Awareness Technology. This device visually alerts the perfusionist when the ratio of venous return does not equal the amount of arterial flow. To determine the efficacy of this device, 33 participants with no perfusion background were randomly assigned to Group A (flow awareness only), Group B (level detector only), or Group C (control). These participants were instructed to turn off the arterial pump when they noticed that the fluid in the venous reservoir had begun to drop or if their assigned safety device was triggered. The venous line was fully occluded at times unknown to the participants. These times coincided with before, during, or after times that the participants were expected to paper-chart known values. Each participant's amount of fluid lost (in milliliters) from the reservoir and reaction time (in seconds) to shut off the arterial roller pump were measured. Group A lost an average of 80.8 mL, Group B lost an average of 173.6 mL, and Group C lost an average of 140.3 mL. Average measured time for each group is as follows: Group A took 2.16 seconds, Group B took 4.31 seconds, and Group C took 4.09 seconds to shut off the arterial pump. Statistics support the hypothesis that Flow Awareness Technology significantly reduces the reaction time to an adverse event such as a sudden occlusion of the venous line, thus reducing the amount of fluid lost during such an event.

Hemodilution is a common perioperative practice. The deleterious effects of excessive hemodilution and subsequent edema formation have been well documented by numerous authors. Colloid oncotic pressure (COP) is a reliable clinical indicator of hemodilution in cardiac surgery. The intent of this study is to determine if a correlation exists between COP and various patient outcome variables. It would also be helpful to know if there is a particular COP value to avoid preventing or limiting patient morbidity. Blood samples from 61 adult patients (mean age = 70 years old) undergoing cardiopulmonary bypass surgery were collected for COP calculation and comparison. Sample collection was performed before heparinization, during cardiopulmonary bypass, at the conclusion of cardiopulmonary bypass, and in the intensive care unit. The resultant values obtained were used to generate a calculated COP. The lowest sustained COP was then compared with various patient outcome variables such as fluid balance, post-operative weight gain, post-operative blood loss, extubation time, length of stay, and blood products administered. A statistically significant difference ( p < .05) was found between the COP and each of the monitored continuous variables. The data also suggest that maintaining a patient's COP at or above 15 mmHg could be desirable. Frequent monitoring of a patient's COP can provide a potential benefit to clinical decision making.