Évaluation des technologies de réduction des agents pathogènes InterceptMC et MirasolMC pour le traitement des produits sanguins labiles au Québec / Assessment of InterceptTM and MirasolTM Pathogen Reduction Technologies for the Treatment of Labile Blood Products in Quebec

MANDAT: L'Institut national d'excellence en santé et en services sociaux (INESSS) a reçu le mandat de la Direction de la biovigilance et de la biologie médicale (DBBM) du ministère de la Santé et des Services sociaux (MSSS) de réévaluer la pertinence de l'introduction des technologies de réduction des agents pathogènes (TRP) InterceptMC et MirasolMC pour le traitement des produits sanguins labiles au Québec. Il s'agit de la deuxième évaluation de ces technologies par l'INESSS à la suite de la recommandation en 2017 de ne pas introduire le procédé InterceptMC dans la chaîne de production des produits sanguins labiles au Québec. DESCRIPTION: Les TRP InterceptMC et MirasolMC sont des processus qui visent à inactiver certains virus, parasites et bactéries par l'utilisation d'agents chimiques ou physiques. Contrairement aux produits sanguins stables, les produits sanguins labiles (culots globulaires, plasma et plaquettes) offerts au Québec ne sont actuellement pas soumis à un tel processus. Advenant leur introduction, ces technologies pourraient s'ajouter aux

MANDATE: The Institut national d'excellence en santé et en services sociaux (INESSS) was mandated by the Direction de la biovigilance et de la biologie médicale (DBBM) of the Ministère de la Santé et des Services sociaux (MSSS) to reassess the relevance of introducing InterceptTM and MirasolTM pathogen reduction technologies (PRTs) for the treatment of labile blood products in Quebec. This is the second assessment of these technologies by INESSS following the recommendation in 2017 not to introduce the InterceptTM Blood System in the labile blood products' production chain in Quebec. DESCRIPTION: Intercept™ and Mirasol™ are PRTs that aim to inactivate certain viruses, parasites, and bacteria through the use of chemical or physical agents. Unlike stable blood products, labile blood products (packed red blood cells, plasma, and platelets) offered in Quebec are not currently subjected to such a process. If introduced, these technologies could be added to the various preventive measures that are already being used to reduce the risks of contamination. ASSESSMENT PROCESS: The assessment used an approach based on the overall value appraisal that the Institute advocates in its Statement of Principles and ethical fondations. A rapid review of the literature was carried out in order to mobilize evidence and reassess the relevance of introducing PRTs in the labile blood products' production chain in Québec. PRT manufacturers were invited to transmit relevant information. Contextual and experiential data was collected from stakeholders through a meeting with Héma-Québec, an expert advisory committee, a focus group with representatives of patient organizations, and a citizen panel. A budget impact analysis (BIA) aiming to quantify the expected financial impact following the introduction of a PRT for the treatment of plasma and platelets was also conducted. The comprehensive scientific, contextual, and experiential data was interpreted using a multidimensional framework to guide certain consultation processes as well as the deliberation process for the development of recommendations by the "Comité délibératif permanent - Remboursement et accès". Socio-CULTURAL DIMENSION: Héma-Québec deploys the preventive measures it deems necessary to ensure the safety of labile blood products distributed in Quebec. Similarly, the Canadian Blood Services (CBS) is implementing preventive measures for the other Canadian provinces and has gradually been rolling out PRTs since January 2022 for the treatment of platelet units in selected hospitals. Some countries that are socially and economically comparable to Canada have taken divergent positions on PRTs, with some being favourable, such as France and Switzerland, and others being unfavourable, such as England. Considering a partial or complete introduction in other countries and Canadian provinces and based on the precautionary principle, the Comité de biovigilance decided that it would be important to consider a strategic introduction of PRTs in order to prepare for the emergence of various pathogens in Quebec. However, the committee has specified that this technology should not replace current preventive measures and should apply only to a small percentage of labile blood products. Although Héma-Québec deems the infectious risks associated with labile blood products to be minimal, it considers the risks associated with the emergence of known pathogen agents (KPAs) and unknown pathogen agents (UPAs) to be legitimate and it regards PRTs as an insurance policy against these intangible and unpredictable risks. Moreover, following the Coronavirus Disease 2019 (COVID-19) pandemic, the potential risk of an emerging pathogen has become more apparent according to the representatives of patient associations that we consulted. Despite the transfusion safety measures in place for labile blood products, this awareness may, for some, have influenced their risk perception. POPULATION DIMENSION: Transfusion safety is a shared responsibility between Héma-Québec, which ensures the safety of blood products, and transfusion hospitals, which are responsible for the quality of the transfusion procedure for patients. Héma-Québec receives nearly 800 orders of labile blood products daily and delivers more than 295,000 of these products annually to hospital centres. Only plasma and platelet units, which represent 22% of the labile blood products distributed, could potentially be treated by PRTs. In order to meet transfusion safety needs, the blood system in Quebec could benefit from better communication on transfusion complications, more preventive measures for noninfectious complications, alternative treatments to transfusions, and increased selfsufficiency in labile blood products. Since the risk of infectious complications associated with transfusions is currently considered low and acceptable by all stakeholders consulted, the main benefit of a PRT occurs during the hypothetical emergence of an UPA. CLINICAL DIMENSION: Intercept™ and Mirasol™ technologies have been shown to be effective on a wide range of viruses, bacteria, and protozoa in laboratory tests. However, the effectiveness of these two PRTs is limited against certain spores, biofilms, residual endotoxins, prions, multidrug-resistant Gram-negative bacteria, and non-enveloped viruses. In addition, there are concerns about the lack of efficacy of Mirasol™ technology against blood-borne viruses such as hepatitis B and cytomegalovirus (CMV). The effects of Intercept™ and Mirasol™ technologies on the biological properties of platelets or plasma are considered acceptable. Both technologies have no effect on bleeding or haemostatic function. However, treatment with both PRTs is accompanied by a statistically significant decrease in post-transfusion platelet recovery, a decrease in the time interval between transfusions, and a statistically significant increase in the number of transfusions per patient. Finally, some studies report a statistically significant increase in the number of transfusion-refractory patients and an increase in alloimmunization rates for platelets treated with Intercept™ compared to conventional platelets. Long-term toxicity or oncogenicity associated with residual amotosalen is also a concern for the Intercept™ technology, especially in pediatrics. ORGANIZATIONAL DIMENSION: Héma-Québec is facing supply chain challenges due to an increase in demand, a constrained pool of donors and a limited shelf life for labile products. PRTs have the potential to reduce the time it takes to make certain labile blood products available if they are accompanied by the withdrawal of bacterial testing. However, compared to untreated products, PRTs lead to an increase in the frequency and number of transfusions per patient, which can thus affect blood product stocks. However, uncertainty remains as to the actual impact of PRTs on plasma or platelet stocks. Moreover, the introduction of these technologies would require changes in the production chain, such as the rapid treatment of collected blood products. According to HémaQuébec, the scale of these changes as well as the resources mobilized would be limited. CBS has made the decision to remove bacterial screening and irradiation from the production chain of products treated with Intercept™ in other Canadian provinces. However, in Quebec, the withdrawal of certain preventive measures that have shown their effectiveness in ensuring the safety of labile products is not unanimous and is not planned by Héma-Québec in the short term. ECONOMIC DIMENSION: A scientific literature update on economic efficiency identified one recently published study specifically assessing Intercept™. According to this analysis, the use of a PRT would have an incremental cost-utility ratio (ICUR) of $9.3 million per QALY gained compared to current preventive measures. This ICUR could see a downturn in the event of the emergence of an UPA, decreasing to $8.6M or approximately $331K per QALY earned, depending on scenario analyses based on rates of infectious transmission of previous pathogens. The conclusions established in the 2017 assessment by INESSS remain unchanged. Uncertainty remains as to the system's willingness to pay for a health intervention such as a PRT according to an insurance principle. Regarding the budgetary impact estimated by INESSS, the uncertainty surrounding certain BIA parameters, in particular the introduction strategy, supported a scenariobased approach. INESSS estimates that the introduction of a PRT to treat only 10% of platelet units, in a partial introduction scenario, would generate a net budget impact of $11.6 million over 10 years. The net budgetary impact is estimated at $157.4 million over 10 years when it is assumed that PRT would treat 100% of platelets and plasma. INESSS Recommendation: Based on the information available to date and given the importance of the uncertainties raised about the added value of PRTs in the production chain of labile blood products in Quebec, INESSS considers that it would not be fair and equitable to implement such a technology. INESSS may reassess the available PRTs, at the request of the Ministère de la Santé et des Services sociaux (MSSS), when new information likely to influence the recommendation becomes available

Research Note: Age-related effects of feeder space availability on welfare of broilers reared to 56 days of age Part 2: Blood physiological variables.

Consumption of poultry meat has increased dramatically due to the relative price-competitiveness as compared to other meat products. The rapid growth and increased production efficiency of modern genetic strains is perceived to negatively impact the welfare of the animal. Hematological analyses such as acid-base balance provide a thorough evaluation of the welfare in both animals and humans. This study investigated the effects of feeder space availability on welfare of broilers grown to heavy weights using blood physiological variables. The study was a randomized complete block design. In each of the 2 trials, a total of 1,440 one-d-old Ross × Ross 708 chicks (straight-run) were obtained from a commercial hatchery. Chicks were equally and randomly allocated to 32 pens based on feeder space treatment. Treatments were 4 different feeder space allocations: 2.3 (Single feeder), 2.30, 4.60, and 6.90 cm/bird. To maintain uniform bird:feeder floor space, 3 feeders were installed in each pen, except for the single feeder pen. Blood samples (3 mL) were collected from the brachial wing vein of 3 birds per pen on d 27 and 55, which were then analyzed immediately for whole blood physiological variables. The remaining blood samples were centrifuged to collect plasma that was used for corticosterone and thyroid hormones analysis. Results show there was no effect of feeder space on most of the selected physiological variables, but age had significant effects on most of the examined variables. However, all observed changes were within physiological ranges. Plasma corticosterone and blood glucose were not affected by feeder space and age, indicating absence of physiological stress. The results are in broad agreement with those reported in the literature and on homeostatic variation of broilers grown to heavy weights. In conclusion, expanding feeder allowance does not enhance the welfare of broilers grown to heavy weights.

How blood met plastics, plant and animal extracts: Material encounters between medicine and industry in the twentieth century.

Twentieth-century medicine saw the remarkable rise of complex machines and infrastructures to process blood for medical purposes, such as transfusion, dialysis, and cardiac surgery. Instead of attributing these developments to technological ingenuity, this article argues for the primacy of material encounters as a promising focal point of medical historiography. In fact, blood's special properties consistently clashed with most materials used in medical practice, provoking a series of material exchanges. Drawing on a combination of epistemological and network approaches, three exemplary cases are presented to examine blood's encounters with plastics, plant and animal extracts: William M. Bayliss's (1860-1926) injections of dissolved gum acacia to expand diminished blood volume; Charles H. Best's (1899-1978) production of the anticoagulant heparin from animal organs; and the preservation of fragile blood cells by silicone coatings inside of John H. Gibbon Jr.'s (1903-1973) heart-lung machine. The case studies demonstrate how the complementarity of blood and these materials produced hybridizations between medicine and a range of industrial branches, from colonial forestry and meatpacking to commercial chemistry. In this light, the paper concludes by discussing the dependencies of today's healthcare environments on globally distributed, capitalistically appropriated resources in the face of crises like the COVID-19 pandemic.

The incidence rate and influence factors of hemolysis, lipemia, icterus in fasting serum biochemistry specimens.

OBJECTIVE: Hemolysis, icterus, and lipemia (HIL) of blood samples have been a concern in hospitals because they reflect pre-analytical processes' quality control. However, very few studies investigate the influence of patients' gender, age, and department, as well as sample-related turnaround time, on the incidence rate of HIL in fasting serum biochemistry specimens. METHODS: A retrospective, descriptive study was conducted to investigate the incidence rate of HIL based on the HIL index in 501,612 fasting serum biochemistry specimens from January 2017 to May 2018 in a tertiary university hospital with 4,200 beds in Sichuan, southwest China. A subgroup analysis was conducted to evaluate the differences in the HIL incidence rate by gender, age and department of patients, and turnaround time of specimens. RESULTS: The incidence rate of hemolysis, lipemia and icterus was 384, 53, and 612 per 10,000 specimens. The male patients had a significantly elevated incidence of hemolysis (4.13% vs. 3.54%), lipemia (0.67% vs. 0.38%), and icterus (6.95% vs. 5.43%) than female patients. Hemolysis, lipemia, and icterus incidence rate were significantly associated with the male sex with an odds ratio (OR) of 1.174 [95% confidence interval (CI), 1.140-1.208], 1.757 (95%CI: 1.623-1.903), and 1.303 (95%CI: 1.273-1.333), respectively, (P<0.05). The hospitalized patients had a higher incidence of hemolysis (4.03% vs. 3.54%), lipemia (0.63% vs. 0.36%), and icterus (7.10% vs. 4.75%) than outpatients (P<0.001). Specimens with relatively longer transfer time and/or detection time had a higher HIL incidence (P<0.001). The Pediatrics had the highest incidence of hemolysis (16.2%) with an adjusted OR (AOR) of 4.93 (95%CI, 4.59-5.29, P<0.001). The Neonatology department had the highest icterus incidence (30.1%) with an AOR of 4.93 (95%CI: 4.59-5.29, P<0.001). The Neonatology department (2.32%) and Gastrointestinal Surgery (2.05%) had the highest lipemia incidence, with an AOR of 1.17 (95%CI: 0.91-1.51) and 4.76 (95%CI: 4.70-5.53), both P-value <0.001. There was an increasing tendency of hemolysis and icterus incidence for children under one year or adults aged more than 40. CONCLUSION: Evaluation of HIL incidence rate and HIL-related influence factors in fasting serum biochemistry specimens are impartment to interpret the results more accurately and provide better clinical services to patients.

Hematological Adaptations to Post-Exercise Sauna Bathing With No Fluid Intake: A Randomized Cross-Over Study.

Purpose: Sauna bathing is recommended to improve the sports training process, yet empirical evidence confirming its effectiveness is still inconclusive. We examined the effects of post-exercise sauna bathing on hematological adaptations and exercise capacity in healthy men. Methods: Thirteen physical education students participated in randomized cross-over study: two, 4-week interventions, with 10-week washout. The interventions involved 3 times per week 60-min stationary cycling either with 30-min of post-exercise sauna bathing (89 ± 3°C, 10 ± 2% RH) or without; no fluid was ingested during both exercise and sauna sessions. Before and after both interventions, participants were tested for total hemoglobin mass (tHb-mass), intravascular volumes, erythropoietin, ferritin, red blood cell parameters with reticulocyte fractions, along with maximal/peak and submaximal variables in a graded exercise test (GXT). Results: Regardless of intervention type, tHb-mass increased (p = .014) whereas ferritin concentration decreased (p = .027); however, changes in tHb-mass were within the range of typical error (<1.8%). Absolute and relative values of maximal power and power at gas exchange threshold, as well as peak oxygen uptake (all p < .010), also increased irrespective of intervention type. Conclusions: The use of post-exercise sauna bathing with fluid intake restrictions does not provide any additional benefits in tested variables over endurance training alone. Thus, further evidence is required before recommendations to utilize this post-exercise conditioning strategy are deemed valid.

Mechanism of Blood-Heart-Barrier Leakage: Implications for COVID-19 Induced Cardiovascular Injury.

Although blood-heart-barrier (BHB) leakage is the hallmark of congestive (cardio-pulmonary) heart failure (CHF), the primary cause of death in elderly, and during viral myocarditis resulting from the novel coronavirus variants such as the severe acute respiratory syndrome novel corona virus 2 (SARS-CoV-2) known as COVID-19, the mechanism is unclear. The goal of this project is to determine the mechanism of the BHB in CHF. Endocardial endothelium (EE) is the BHB against leakage of blood from endocardium to the interstitium; however, this BHB is broken during CHF. Previous studies from our laboratory, and others have shown a robust activation of matrix metalloproteinase-9 (MMP-9) during CHF. MMP-9 degrades the connexins leading to EE dysfunction. We demonstrated juxtacrine coupling of EE with myocyte and mitochondria (Mito) but how it works still remains at large. To test whether activation of MMP-9 causes EE barrier dysfunction, we hypothesized that if that were the case then treatment with hydroxychloroquine (HCQ) could, in fact, inhibit MMP-9, and thus preserve the EE barrier/juxtacrine signaling, and synchronous endothelial-myocyte coupling. To determine this, CHF was created by aorta-vena cava fistula (AVF) employing the mouse as a model system. The sham, and AVF mice were treated with HCQ. Cardiac hypertrophy, tissue remodeling-induced mitochondrial-myocyte, and endothelial-myocyte contractions were measured. Microvascular leakage was measured using FITC-albumin conjugate. The cardiac function was measured by echocardiography (Echo). Results suggest that MMP-9 activation, endocardial endothelial leakage, endothelial-myocyte (E-M) uncoupling, dyssynchronous mitochondrial fusion-fission (Mfn2/Drp1 ratio), and mito-myocyte uncoupling in the AVF heart failure were found to be rampant; however, treatment with HCQ successfully mitigated some of the deleterious cardiac alterations during CHF. The findings have direct relevance to the gamut of cardiac manifestations, and the resultant phenotypes arising from the ongoing complications of COVID-19 in human subjects.

Non-equilibrium phase transition at a critical point of human blood.

Blood is the basic medium in the existence, evolution and physiological balance of animals and represents the biochemical "Internet" of the body; at least human blood exhibit the presence of an emergent phase that is highly unusual. Homeostasis, the state of the optimal functioning of the body, is maintained in living organisms by many chemical and physical conditions, particularly temperature. However, no regulatory mechanism has been identified that has led to a predetermined (molecularly encoded) optimal, individually variable, very specific temperature of around 36 °C. Additionally, the homeostatic temperature range, which is kept within predetermined limits, is merely an empirical fact. In the following, I will show that the reference temperature that is necessary to achieve homeostasis can be established, and a preset homeostatic range can be determined, using an original experimental method and refined tools of mathematical physics related to the nonlinear measures of the complexity of human blood. Moreover, signatures of a macroscopic coherent state in a non-equilibrium system at a critical temperature are obtained.

Synonymous mutations reveal genome-wide levels of positive selection in healthy tissues.

Genetic alterations under positive selection in healthy tissues have implications for cancer risk. However, total levels of positive selection across the genome remain unknown. Passenger mutations are influenced by all driver mutations, regardless of type or location in the genome. Therefore, the total number of passengers can be used to estimate the total number of drivers-including unidentified drivers outside of cancer genes that are traditionally missed. Here we analyze the variant allele frequency spectrum of synonymous mutations from healthy blood and esophagus to quantify levels of missing positive selection. In blood, we find that only 30% of passengers can be explained by single-nucleotide variants in driver genes, suggesting high levels of positive selection for mutations elsewhere in the genome. In contrast, more than half of all passengers in the esophagus can be explained by just the two driver genes NOTCH1 and TP53, suggesting little positive selection elsewhere.

Whole Blood Transcriptome Analysis Reveals the Correlation between Specific Immune Cells and Septicemic Melioidosis.

Melioidosis is a serious infectious disease caused by the environmental Gram-negative bacillus Burkholderia pseudomallei. It has been shown that the host immune system, mainly comprising various types of immune cells, fights against the disease. The present study was to specify correlation between septicemic melioidosis and the levels of multiple immune cells. First, the genes with differential expression patterns between patients with septicemic melioidosis (B. pseudomallei) and health donors (control/healthy) were identified. These genes being related to cytokine binding, cell adhesion molecule binding, and MHC relevant proteins may influence immune response. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed 23 enriched immune response pathways. We further leveraged the microarray data to investigate the relationship between immune response and septicemic melioidosis, using the CIBERSORT analysis. Comparison of the percentages of 22 immune cell types in B. pseudomallei vs. control/healthy revealed that those of CD4 memory resting cells, CD8+ T cells, B memory cells, and CD4 memory activated cells were low, whereas those of M0 macrophages, neutrophils, and gamma delta T cells were high. The multivariate logistic regression analysis further revealed that CD8+ T cells, M0 macrophages, neutrophils, and naive CD4+ cells were strongly associated with the onset of septicemic melioidosis, and M2 macrophages and neutrophils were associated with the survival in septicemic melioidosis. Taken together, these data point to a complex role of immune cells on the development and progression of melioidosis.

Autofluorescence of blood and its application in biomedical and clinical research.

Autofluorescence of blood has been explored as a label free approach for detection of cell types, as well as for diagnosis and detection of infection, cancer, and other diseases. Although blood autofluorescence is used to indicate the presence of several physiological abnormalities with high sensitivity, it often lacks disease specificity due to use of a limited number of fluorophores in the detection of several abnormal conditions. In addition, the measurement of autofluorescence is sensitive to the type of sample, sample preparation, and spectroscopy method used for the measurement. Therefore, while current blood autofluorescence detection approaches may not be suitable for primary clinical diagnosis, it certainly has tremendous potential in developing methods for large scale screening that can identify high risk groups for further diagnosis using highly specific diagnostic tests. This review discusses the source of blood autofluorescence, the role of spectroscopy methods, and various applications that have used autofluorescence of blood, to explore the potential of blood autofluorescence in biomedical research and clinical applications.

Lower blood pH as a strong prognostic factor for fatal outcomes in critically ill COVID-19 patients at an intensive care unit: A multivariable analysis.

BACKGROUND: Data of critically ill COVID-19 patients are being evaluated worldwide, not only to understand the various aspects of the disease and to refine treatment strategies but also to improve clinical decision-making. For clinical decision-making in particular, prognostic factors of a lethal course of the disease would be highly relevant. METHODS: In this retrospective cohort study, we analyzed the first 59 adult critically ill Covid-19 patients treated in one of the intensive care units of the University Medical Center Regensburg, Germany. Using uni- and multivariable regression models, we extracted a set of parameters that allowed for prognosing in-hospital mortality. RESULTS: Within the cohort, 19 patients died (mortality 32.2%). Blood pH value, mean arterial pressure, base excess, troponin, and procalcitonin were identified as highly significant prognostic factors of in-hospital mortality. However, no significant differences were found for other parameters expected to be relevant prognostic factors, like low arterial partial pressure of oxygen or high lactate levels. In the multivariable logistic regression analysis, the pH value and the mean arterial pressure turned out to be the most influential prognostic factors for a lethal course.

Biochemical and hormonal parameters of goats kept in a controlled environment consuming water with different levels of salinity / [Parâmetros bioquímicos e hormonais de caprinos consumindo água com diferentes níveis de salinidade mantidos em ambiente controlado]

The objective of this work was to evaluate the biochemical and hormonal variables of Moxotó and Canindé goats submitted to two temperatures - 26.0±0.6 (thermoneutral) and 32.0±1.2°C (above thermal comfort zone) - and consuming water with three levels of salinity (1.0, 6.0 and 12.0 dSm-1). Thirty-six animals (18 of each breed) were used, with an average age of 5.0±0.6months and an average weight of 20.0±2.3kg, housed in metabolic cages inside a climate chamber. The animals were distributed in a completely randomized design with a 2 × 2 × 3 factorial scheme (2 breeds, 2 temperatures and 3 levels of salinity) and three replications. The glucose and urea had a significant effect (P>0.05) according to water salinity. Glucose, cholesterol, protein, albumin, globulin, aspartate aminotransferase and hormones (T4, T3 and cortisol) varied according to temperature (P<0.05). There was a significant effect of time on hormonal variables (P<0.05). Biochemical and hormonal variables changed according to temperature and day shift, so that metabolism was reduced in the animals under thermal stress and accelerated when animals were in the thermal comfort zone.(AU)

O objetivo do trabalho foi avaliar as variáveis bioquímicas e hormonais de caprinos das raças Moxotó e Canindé, submetidos a duas temperaturas (26,0±0,6ºC e 32,0±1,2ºC), termoneutra e acima da zona de conforto térmico, respectivamente), consumindo água com três níveis de salinidade (1,0, 6,0 e 12,0dSm-1), utilizando-se 36 animais (18 de cada raça), com idade média de 5,0±0,6 meses e peso médio de 20,0±2,3kg, alojados em gaiolas metabólicas no interior de uma câmara climática. Os animais foram distribuídos em um delineamento inteiramente ao acaso, com esquema fatorial de 2 x 2 x 3 (2 raças, 2 temperaturas e 3 níveis de salinidade) e três repetições. A glicose e a ureia apresentaram efeito significativo (P<0,05) em função da salinidade da água. Glicose, colesterol, proteína, albumina, globulina, AST e hormônios (T4, T3 e cortisol) variaram conforme as temperaturas (P<0,05). Observou-se efeito significativo do horário sobre as variáveis hormonais (P<0,05). As variáveis bioquímicas e hormonais sofrem alterações em função da temperatura e do turno do dia, de modo que o metabolismo é reduzido em animais sob estresse térmico e acelerado quando os animais encontram-se na zona de conforto térmico.(AU)

Early Outcomes of Bivalirudin Therapy for Thrombotic Thrombocytopenia and Cerebral Venous Sinus Thrombosis After Ad26.COV2.S Vaccination.

Vaccine-induced thrombotic thrombocytopenia is a newly described disease process in the setting of expanding access to COVID-19 vaccination. The United States Centers for Disease Control and Prevention recommends treatment with an alternative to heparin in patients suspected of having vaccine-induced thrombotic thrombocytopenia. At this time there have been no reported outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. We describe the early outcomes from the treatment of vaccine-induced thrombotic thrombocytopenia with bivalirudin as a heparin alternative. A 40-year-old Caucasian woman was found to have thrombocytopenia, cerebral venous sinus thrombosis, and pulmonary embolism following vaccination for COVID-19 with Ad26.COV2.S. She exhibited a steady rise in platelet count: 20×109/L at hospital day 0, 115×109/L at discharge on hospital day 6, and 182×109/L on outpatient follow-up on day 9. While the patient exhibited a transient drop in hemoglobin, there was no clinical evidence of bleeding. This patient did not demonstrate any clinical sequelae of thrombosis, and she reported resolution of her headache. Vaccination with Ad26.COV2.S appears to be associated with a small but significant risk for thrombotic thrombocytopenia within 13 days of receipt. The Centers for Disease Control and Prevention guidance to consider an alternative to heparin was not accompanied by specifically recommended alternatives. A single patient treated with bivalirudin for suspected vaccine-induced thrombotic thrombocytopenia subsequently experienced symptom improvement and a rise in platelet count and did not demonstrate any immediate negative outcomes. A provider may consider bivalirudin as an alternative to heparin in patients with suspected vaccine-induced thrombotic thrombocytopenia following Ad26.COV2.S vaccination, pending more definitive research.

Pattern formation in drying blood drops.

Patterns in dried droplets are commonly observed as rings left after spills of dirty water or coffee have evaporated. Patterns are also seen in dried blood droplets and the patterns have been shown to differ from patients afflicted with different medical conditions. This has been proposed as the basis for a new generation of low-cost blood diagnostics. Before these diagnostics can be widely used, the underlying mechanisms leading to pattern formation in these systems must be understood. We analyse the height profile and appearance of dispersions prepared with red blood cells (RBCs) from healthy donors. The red cell concentrations and diluent were varied and compared with simple polystyrene particle systems to identify the dominant mechanistic variables. Typically, a high concentration of non-volatile components suppresses ring formation. However, RBC suspensions display a greater volume of edge deposition when the red cell concentration is higher. This discrepancy is caused by the consolidation front halting during drying for most blood suspensions. This prevents the standard horizontal drying mechanism and leads to two clearly defined regions in final crack patterns and height profile. This article is part of a discussion meeting issue 'A cracking approach to inventing new tough materials: fracture stranger than friction'.

Switching from Intravenous to Oral Tacrolimus Reduces its Blood Concentration in Paediatric Cancer Patients.

BACKGROUND/AIM: Tacrolimus is an essential immunosuppressant for successful allogeneic haematopoietic stem cell transplantation (Allo-HSCT). This study aimed to examine the change in the blood concentration of tacrolimus during switching from intravenous to oral administration in allo-HSCT for paediatric cancer to predict the optimal dosage. PATIENTS AND METHODS: We retrospectively examined the medical records of 63 patients who received allo-HSCT and were administered tacrolimus. To compare bioavailability among different dose ranges, the blood concentration was divided by the dose (C/D). RESULTS: Thirty-nine patients (age range=children 1-15 years, adults 17-67 years) were switched to oral administration of tacrolimus. The C/D after switching was significantly lower in children than in adults (p=0.039). There was a strong positive correlation between age and C/D in children, whereas no correlation was observed in adults. CONCLUSION: In paediatric cancer patients, switching tacrolimus administration route may result in reduced blood concentrations. This tendency is more prominent in younger children.

Dynamic entropy of human blood.

Temperature control is a process that is used by biological systems to maintain a stable internal state for survival. People have an individually variable physiological temperature of about 36.6 °C, which can be modified by many undesirable factors. Based on an analysis of a time series of extracellular ionic fluxes that were obtained using the non-invasive solute-semiconductor interface technique, I show that this extremely specific (critical) temperature is encoded by a local minimum in the dynamic entropy of an isolated drop of human blood. Moreover, a dynamic zeroth-order normal fluid/"superfluid" nonequilibrium phase transition, which was reflected by a spontaneous symmetry breaking that occurred in the phase space, was revealed. The critical scaling of the dynamic measures for the covariates such as the spectral signature and Lyapunov exponent was also determined.

Effects of Different Chromium Compounds on Hematology and Inflammatory Cytokines in Rats Fed High-Fat Diet.

The aim of the study was to determine how a high-fat diet supplemented with various forms of chromium affects hematological and immune parameters of the blood of rats. The rats received a standard diet or a high-fat diet supplemented with chromium at 0.3 mg/kg body weight (BW) in the form of chromium(III) picolinate, chromium(III)-methionine or nano-sized chromium. Selected hematological parameters were determined in the blood of the rats, including total white blood cell (WBC) count, leukogram, red blood cell (RBC) count, hemoglobin level (HGB), hematocrit (HCT), platelet count (PLT) and platelet percentage (PCT), as well as immune parameters: levels of immunoglobulins A and E (IgA and IgE), interleukin-6 (IL-6), interleukin-2 (IL-2), and tumor necrosis factor α (TNF-α); activity of ceruloplasmin (Cp); and levels of caspase 3 and 8 (Casp3 and Casp8). Feeding rats a high-fat diet increased blood markers of induction of inflammation, ie pro-inflammatory cytokines IL-6 and TNF-α, and also significantly increased IgE. The diet had no effect on the blood count, except for an increase in the number of neutrophils. The chromium compounds tested, particularly Cr-Met and Cr-NPs, stimulated the immune system of the rats, as indicated by increased concentrations of IgA, IgE, IL-2, IL-6, TNF-α, and Cp. Given the increase in inflammatory mediators induced by chromium, it should not be used to mitigate the effects of a high-fat diet. Moreover, chromium picolinate and chromium nanoparticles were shown to increase the content of caspase 3 and 8 in the blood of rats, which indicates a pro-apoptotic effect. The effects of the use of chromium nanoparticles include reductions in the WBC count and in the thrombocyte count (leuko- and thrombopenia). Taking account these data the use of chromium as dietary supplement should be reconsidered.