[The Immune System of the Critically Ill Patient]. / Das Immunsystem des kritisch Kranken.

Critically ill patients often experience a dysregulated immune response, leading to immune dysfunction. Sepsis, trauma, severe infections, and certain medical conditions can trigger a state of systemic inflammation, known as the cytokine storm. This hyperactive immune response can cause collateral damage to healthy tissues and organs, exacerbating the patient's condition. On the other hand, some critically ill patients may suffer from immune paralysis which can increase the risk of nosocomial infections.Fever is an evolutionary adaptation that evolved as an effective defense mechanism to fight invading pathogens. By raising body temperature, fever enhances the immune response, inhibits pathogen growth, promotes recovery, and aids in the formation of immune memory. Understanding the role of fever in the context of immune defense is crucial for optimizing medical interventions and supporting the body's natural ability to combat infections.Future Directions: Advancements in immunology research and technology hold promise for better understanding the immune system's complexities in critically ill patients. Personalized medicine approaches may be developed to tailor therapies to individual patients based on their immune profile, optimizing treatment outcomes. Based on recent studies prognostic parameters such as lymphocyte count, IL-10 concentration and mHLA-DR expression can be used to stratify the immunological response pattern in septic patients.Conclusion: The immune system's response in critically ill patients is a multifaceted process, involving intricate interactions between various immune cells, cytokines, and organs. Striking the delicate balance between immune activation and suppression remains a significant challenge in clinical practice. Continued research and therapeutic innovations are vital to improve patient outcomes and reduce the burden of critical illness on healthcare systems.

Microcirculatory tissue oxygenation correlates with kidney function after transcatheter aortic valve implantation-Results from a prospective observational study.

Introduction: Kidney dysfunction is common in patients with aortic stenosis (AS) and correction of the aortic valve by transcatheter aortic valve implantation (TAVI) often affects kidney function. This may be due to microcirculatory changes. Methods: We evaluated skin microcirculation with a hyperspectral imaging (HSI) system, and compared tissue oxygenation (StO2), near-infrared perfusion index (NIR), tissue hemoglobin index (THI) and tissue water index (TWI) in 40 patients undergoing TAVI versus 20 control patients. HSI parameters were measured before TAVI (t1), directly after TAVI (t2), and on postinterventional day 3 (t3). The primary outcome was the correlation of tissue oxygenation (StO2) to the creatinine level after TAVI. Results: We performed 116 HSI image recordings in patients undergoing TAVI for the treatment of severe aortic stenosis and 20 HSI image recordings in control patients. Patients with AS had a lower THI at the palm (p = 0.034) and a higher TWI at the fingertips (p = 0.003) in comparison to control patients. TAVI led to an increase of TWI, but had no uniform enduring effect on StO2 and THI. Tissue oxygenation StO2 at both measurement sites correlated negatively with creatinine levels after TAVI at t2 (palm: ρ = -0.415; p = 0.009; fingertip: ρ = -0.519; p < 0.001) and t3 (palm: ρ = -0.427; p = 0.008; fingertip: ρ = -0.398; p = 0.013). Patients with higher THI at t3 reported higher physical capacity and general health scores 120 days after TAVI. Conclusion: HSI is a promising technique for periinterventional monitoring of tissue oxygenation and microcirculatory perfusion quality, which are related to kidney function, physical capacity, and clinical outcomes after TAVI. Clinical trial registration: https://drks.de/search/de/trial, identifier DRKS00024765.

Interpreting Iron Homeostasis in Congenital and Acquired Disorders.

Mammalian cells require iron to satisfy their metabolic needs and to accomplish specialized functions, such as hematopoiesis, mitochondrial biogenesis, energy metabolism, or oxygen transport. Iron homeostasis is balanced by the interplay of proteins responsible for iron import, storage, and export. A misbalance of iron homeostasis may cause either iron deficiencies or iron overload diseases. The clinical work-up of iron dysregulation is highly important, as severe symptoms and pathologies may arise. Treating iron overload or iron deficiency is important to avoid cellular damage and severe symptoms and improve patient outcomes. The impressive progress made in the past years in understanding mechanisms that maintain iron homeostasis has already changed clinical practice for treating iron-related diseases and is expected to improve patient management even further in the future.

Prospective clinical study testing the efficacy and safety of a new formula to increase the precision of oxygen therapy in the initiation phase of cardiopulmonary bypass.

INTRODUCTION: During cardiopulmonary bypass (CPB), supranormal concentrations of oxygen are routinely administered with the intention to prevent cellular hypoxia. However, hyperoxemia may have adverse effects on patient outcome. Oxygen settings are based on the perfusionist's individual work experience rather than profound recommendations and studies analyzing the effect of oxygen levels are in need of methodological improvement. We aimed to advance perfusion technique by developing and clinically applying a formula for tailored oxygen therapy in CPB. METHODS: A formula to precalculate the oxygenator setting before CPB was developed. The newly-derived formula was then evaluated in a prospective, single-center pilot study to test whether a predefined arterial partial oxygen pressure (PaO2) of 150-250 mmHg could be reached. 80 patients were enrolled in the study between April and September 2021. RESULTS: The mean oxygen fraction calculated for the setting of the gas blender was 52% ±0,12. The mean PaO2 after initiation of the CPB was 193 ± 99 mmHg (min-max: 61-484, median 163 mmHg). 38.75% of the values were in the desired PaO2 corridor of 150 to 250 mmHg. 8.75% of all PaO2 values were below <79.9 mmHg, 31.25% between 80 and 149.9 mmHg, 38.75% between 150 and 249.9 mmHg and 21.25%>250 mmHg. CONCLUSIONS: Conceptually, perfusion technique should be goal-directed, guided by objective parameters and formulas. Although the optimal CPB oxygenation target remains unknown, it is nevertheless important to develop strategies to tailor oxygen therapy to aid in creating evidence as to what level of oxygen is best for patients during CPB. The formula we derived needs further adjustments to increase results in the target range.

Increased prevalence of clonal hematopoiesis of indeterminate potential in hospitalized patients with COVID-19.

Clonal hematopoiesis of indeterminate potential (CHIP) leads to higher mortality, carries a cardiovascular risk and alters inflammation. All three aspects harbor overlaps with the clinical manifestation of COVID-19. This study aimed to identify the impact of CHIP on COVID-19 pathophysiology. 90 hospitalized patients were analyzed for CHIP. In addition, their disease course and outcome were evaluated. With a prevalence of 37.8%, the frequency of a CHIP-driver mutation was significantly higher than the prevalence expected based on median age (17%). CHIP increases the risk of hospitalization in the course of the disease but has no age-independent impact on the outcome within the group of hospitalized patients. Especially in younger patients (45 - 65 years), CHIP was associated with persistent lymphopenia. In older patients (> 65 years), on the other hand, CHIP-positive patients developed neutrophilia in the long run. To what extent increased values of cardiac biomarkers are caused by CHIP independent of age could not be elaborated solely based on this study. In conclusion, our results indicate an increased susceptibility to a severe course of COVID-19 requiring hospitalization associated with CHIP. Secondly, they link it to a differentially regulated cellular immune response under the pressure of SARS-CoV-2 infection. Hence, a patient's CHIP-status bears the potential to serve as biomarker for risk stratification and to early guide treatment of COVID-19 patients.

Plasma Transfusion in Septic Shock-A Secondary Analysis of a Retrospective Single-Center Cohort.

In sepsis, both beneficial and detrimental effects of fresh frozen plasma (FFP) transfusion have been reported. The aim of this study was to analyze the indication for and effect of FFP transfusion in patients with septic shock. We performed a secondary analysis of a retrospective single-center cohort of all patients treated for septic shock at the interdisciplinary surgical intensive care unit (ICU) of the Heidelberg University Hospital. Septic shock was defined according to sepsis-3 criteria. To assess the effects of FFP administration in the early phase of septic shock, we compared patients with and without FFP transfusion during the first 48 h of septic shock. Patients who died during the first 48 h of septic shock were excluded from the analysis. Primary endpoints were 30- and 90-day mortality. A total of 261 patients were identified, of which 100 (38.3%) received FFP transfusion within the first 48 h after septic shock onset. The unmatched analysis showed a trend toward higher 30- and 90-d mortality in the FFP group (30 d: +7% p = 0.261; 90 d: +11.9% p = 0.061). In the propensity-matched analysis, 30- and 90-day mortality were similar between groups. Plasma administration did not influence fluid or vasopressor need, lactate levels, ICU stay, or days on a ventilator. We found no significant harm or associated benefit of FFP use in the early phase of septic shock. Finally, plasma should only be used in patients with a strong indication according to current recommendations, as a conclusive evaluation of the risk-benefit ratio for plasma transfusion in septic shock cannot be made based on the current data.

Red Blood Cell-Derived Microparticles Exert No Cancer Promoting Effects on Colorectal Cancer Cells In Vitro.

The biomedical consequences of allogeneic blood transfusions and the possible pathomechanisms of transfusion-related morbidity and mortality are still not entirely understood. In retrospective studies, allogeneic transfusion was associated with increased rates of cancer recurrence, metastasis and death in patients with colorectal cancer. However, correlation does not imply causation. The purpose of this study was to elucidate this empirical observation further in order to address insecurity among patients and clinicians. We focused on the in vitro effect of microparticles derived from red blood cell units (RMPs). We incubated different colon carcinoma cells with RMPs and analyzed their effects on growth, invasion, migration and tumor marker expression. Furthermore, effects on Wnt, Akt and ERK signaling were explored. Our results show RMPs do not seem to affect functional and phenotypic characteristics of different colon carcinoma cells and did not induce or inhibit Wnt, Akt or ERK signaling, albeit in cell culture models lacking tumor microenvironment. Allogeneic blood transfusions are associated with poor prognosis, but RMPs do not seem to convey tumor-enhancing effects. Most likely, the circumstances that necessitate the transfusion, such as preoperative anemia, tumor stage, perioperative blood loss and extension of surgery, take center stage.

Safety of Intraoperative Cell Salvage in Cancer Surgery: An Updated Meta-Analysis of the Current Literature.

Background: Allogeneic blood transfusions in oncologic surgery are associated with increased recurrence and mortality. Adverse effects on outcome could be reduced or avoided by using intraoperative autologous blood cell salvage (IOCS). However, there are concerns regarding the safety of the autologous IOCS blood. Previous meta-analyses from 2012 and 2020 did not identify increased risk of cancer recurrence after using autologous IOCS blood. The objective of this review was to reassess a greater number of IOCS-treated patients to present an updated and more robust analysis of the current literature. Methods: This systematic review includes full-text articles listed in PubMed, Cochrane, Cochrane Reviews, and Web of Science. We analyzed publications that discussed cell salvage or autotransfusion combined with the following outcomes: cancer recurrence, mortality, survival, allogeneic transfusion rate and requirements, length of hospital stay (LOS). To rate the strength of evidence, a Grading of Recommendations Assessment, Development and Evaluation (GRADE) of the underlying evidence was applied. Results: In the updated meta-analysis, 7 further observational studies were added to the original 27 observational studies included in the former 2020 analysis. Studies compared either unfiltered (n = 2,311) or filtered (n = 850) IOCS (total n = 3,161) versus non-IOCS use (n = 5,342). Control patients were either treated with autologous predonated blood (n = 484), with allogeneic transfusion (n = 4,113), or did not receive a blood transfusion (n = 745). However, the current literature still contains only observational studies on these topics, and the strength of evidence remains low. The risk of cancer recurrence was reduced in recipients of autologous salvaged blood with or without LDF (odds ratio [OR] 0.76, 95% confidence interval [CI]: 0.64-0.90) compared to nontransfused patients or patients with allogeneic transfusion. There was no difference in mortality (OR 0.95, 95% CI: 0.71-1.27) and LOS (mean difference -0.07 days, 95% CI: -0.63 to 0.48) between patients treated with IOCS blood or those in whom IOCS was not used. Due to high heterogeneity, transfusion rates or volumes could not be analyzed. Conclusion: Randomized controlled trials comparing mortality and cancer recurrence rate of IOCS with or without LDF filtration versus allogeneic blood transfusion were not found. Outcome was similar or better in patients receiving IOCS during cancer surgery compared to patients with allogeneic blood transfusion or nontransfused patients.

Coagulopathies in Intensive Care Medicine: Balancing Act between Thrombosis and Bleeding.

Patient Blood Management advocates an individualized treatment approach, tailored to each patient's needs, in order to reduce unnecessary exposure to allogeneic blood products. The optimization of hemostasis and minimization of blood loss is of high importance when it comes to critical care patients, as coagulopathies are a common phenomenon among them and may significantly impact morbidity and mortality. Treating coagulopathies is complex as thrombotic and hemorrhagic conditions may coexist and the medications at hand to modulate hemostasis can be powerful. The cornerstones of coagulation management are an appropriate patient evaluation, including the individual risk of bleeding weighed against the risk of thrombosis, a proper diagnostic work-up of the coagulopathy's etiology, treatment with targeted therapies, and transfusion of blood product components when clinically indicated in a goal-directed manner. In this article, we will outline various reasons for coagulopathy in critical care patients to highlight the aspects that need special consideration. The treatment options outlined in this article include anticoagulation, anticoagulant reversal, clotting factor concentrates, antifibrinolytic agents, desmopressin, fresh frozen plasma, and platelets. This article outlines concepts with the aim of the minimization of complications associated with coagulopathies in critically ill patients. Hereditary coagulopathies will be omitted in this review.

The effect of the interruption of agitation, temporary cooling, and pneumatic tube transportation on platelet quality during storage for transfusion.

BACKGROUND: Conditions during blood product storage and transportation should maintain quality. The aim of this in vitro study was to investigate the effect of interruption of agitation, temporary cooling (TC), and pneumatic tube system transportation (PTST) on the aggregation ability (AA) and mitochondrial function (MF) of platelet concentrates (PC). STUDY DESIGN AND METHODS: A PC was divided equally into four subunits and then allocated to four test groups. The control group (I) was stored as recommended (continuous agitation, 22 ± 2°C) for 4 days. The test groups were stored without agitation (II), stored as recommended, albeit 4°C for 60 minutes on day (d)2 (III) and PTST (IV). Aggregometry was measured using Multiplate (RocheAG; ADPtest, ASPItest, TRAPtest, COLtest) and MF using Oxygraph-2k (Oroboros Instruments). The basal and maximum mitochondrial respiratory rate (MMRR) were determined. AA and MF were measured daily in I and II and AA in III and IV on d2 after TC/PTST. Statistical analysis was performed using tests for matched observations. RESULTS: Eleven PCs were used. TRAP-6 induced AA was significantly lower in II when compared to I on d4 (P = 0.015*). In III the ASPItest was significantly lower (P = 0.032*). IV showed no significant differences. The basal and MMRR were significantly reduced over 4 days in I and II (for both rates in both groups: P = <0.0001*). No significant differences occurred on d4 (P = 0.495). CONCLUSION: Our results indicate that ex vivo AA and MF of PCs are unaffected, even in no-ideal storage and transport circumstances with respect to agitation, temperature, and force.

Plasma Transfusion Practice in Adult Surgical Patients: Systematic Review of the Literature.

BACKGROUND: Plasma transfusions are most commonly used therapeutically for bleeding or prophylactically in non-bleeding patients prior to invasive procedures or surgery. Although plasma transfusions generally seem to decline, plasma usage for indications that lack evidence of efficacy prevail. SUMMARY: There is wide international, interinstitutional, and interindividual variance regarding the compliance with guidelines based on published references, supported by appropriate testing. There is furthermore a profound lack of evidence from randomized controlled trials comparing the effect of plasma transfusion with that of other therapeutic interventions for most indications, including massive bleeding. The expected benefit of a plasma transfusion needs to be balanced carefully against the associated risk of adverse events. In light of the heterogeneous nature of bleeding conditions and their rapid evolvement over time, fibrinogen and factor concentrate therapy, directed at specific phases of coagulation identified by alternative laboratory assays, may offer advantages over conventional blood product ratio-driven resuscitation. However, their outcome benefit has not been demonstrated in well-powered prospective trials. This systematic review will detail the current evidence base for plasma transfusion in adult surgical patients.

Granisetron reduces the need for uterotonics but not sympathomimetics during cesarean delivery.

OBJECTIVE: To assess the effect of a 5-hydroxytryptamine-3 receptor antagonist (granisetron) on the use of sympathomimetic (cafedrine/theodrenaline) and uterotonic (oxytocin) agents after spinal anesthesia during cesarean delivery. METHODS: A retrospective observational analysis was conducted using intraoperative records (n=240) created at a single hospital in Germany between November 1, 2016, and July 31, 2017. The granisetron group (n=120) had received 3 mg of granisetron immediately before induction of spinal anesthesia. The control group (n=120) had not received granisetron. The primary endpoints were the intraoperative requirements for sympathomimetic and uterotonic agents. The secondary endpoints were parameters of intraprocedural maternal hemodynamic and clinical states. RESULTS: More patients in the granisetron group than in the control group received intraoperative cafedrine/theodrenaline (P=0.045), with the cumulative intraoperative dosage also increased in the granisetron group (P=0.016). By contrast, the cumulative intraoperative dose of oxytocin was lower in the granisetron group than in the control group (P<0.001). Decreases in heart rate and mean arterial blood pressure were lower in the granisetron group versus the control group (P=0.015 and P=0.002, respectively). CONCLUSION: Treatment with granisetron immediately before cesarean delivery did not reduce the perioperative requirement for sympathomimetics but did reduce the need for uterotonics. REGISTERED AT CLINICALTRIALS.GOV (NCT03318536).

Systemic LPS induces toll-like receptor 3 (TLR3) expression and apoptosis in testicular mouse tissue.

It is well known that sepsis and inflammation reduce male fertility. Within the testis, toll-like receptor 3 (TLR3) is constitutively expressed and recognizes double-stranded RNA (dsRNA) from viruses, degraded bacteria, damaged tissues and necrotic cells. To characterize the potential role of TLR3 in response to testicular infections, its expression and downstream signaling were investigated upon challenge with lipopolysaccharides (LPS) in two mouse strains that differ in their immuno-competence regarding T cell-regulated immunity. Thereto, Balb/c and Foxn1nu mice were randomized into six interventional groups treated with either i.v. application of saline or LPS followed by 20 min, 5 h 30 min and 18 h of observation and two sham-treated control groups. LPS administration induced a significant stress response; the amplification was manifested for TLR3 and interleukin 6 (IL6) mRNA in the impaired testis 5 h 30 min after LPS injection. TLR3 immunostaining revealed that TLR3 was primarily localized in spermatocytes. The TLR3 expression displayed different temporal dynamics between both mouse strains. However, immunofluorescence staining indicated only punctual interferon regulatory factor 3 (IRF3) expression upon LPS treatment along with minor alterations in interferon ß (IFNß) mRNA expression. Induction of acute inflammation was closely followed by a significant shift of the Bax/Bcl2 ratio to pro-apoptotic signaling accompanied by augmented TUNEL-positive cells 18 h after LPS injection with again differing patterns in both mouse strains. In conclusion, this study shows the involvement of TLR3 in response to LPS-induced testicular inflammation in immuno-competent and -incompetent mice, yet lacking transmission into its signaling pathway.

Red blood cell transfusion and its alternatives in oncologic surgery-A critical evaluation.

Although blood transfusions have been used for more than 100 years and their potential to save lives is indisputable, there is still limited data on medium- and long-term outcomes after hemotherapy. Until recently, red blood cell transfusions represented the most commonly employed treatment for cancer anemia. As transfusions have been related to worse patient outcome in oncologic surgery, preventive strategies and alternative treatment approaches in the perioperative setting are warranted. This review aims to evaluate the evidence concerning the impact of transfusion on the course of malignant diseases with a focus on oncologic surgery and to provide a bundle of measures to improve patient care. The perioperative period is pivotal in determining long-term cancer outcome. An increasingly recognized area for improvement during this highly sensitive period is the treatment of anemia for three main reasons: Firstly, anemia has been recognized as an independent predictor of poor prognosis in cancer patients. Secondly, anemia is largely undertreated. Thirdly and probably most importantly, anemia therapy relied and often still relies heavily on red blood cell (RBC) transfusions, which may be an often suboptimal stopgap treatment. Perioperative RBC transfusions should be kept to a minimum due to growing concerns regarding the associated risks, which this review tries to clarify by providing an update of recent literature. This review furthermore discusses treatments for anemia and provides best-practice approaches to improve perioperative management of oncology patients undergoing surgery.

Preoperative anemia and extensive transfusion during stay-in-hospital are critical for patient`s mortality: A retrospective multicenter cohort study of oncological patients undergoing radical cystectomy.

BACKGROUND: Preoperative anemia and allogeneic blood transfusions (ABTs) may affect outcomes in cancer surgery. The prevalence of anemia, the use of ABTs, the risks of transfusions, lengths of stay and mortality of oncological patients undergoing radical cystectomy were investigated in three University Hospitals in Germany. PATIENTS AND METHODS: Hospital records of 220 consecutive patients undergoing radical cystectomy from 2010 to 2012 were retrospectively analyzed for independent risk factors of ABT and unfavorable outcomes (readmission, increased length of stay (LOS) or death) using multivariate regression analysis. RESULTS: Preoperative anemia was present in 40%. 70% of patients received blood transfusions. Low preoperative and intraoperative nadir hemoglobin levels were associated with receipt of ABT (OR 1.33, P = 0.04 and OR 2.94, P < 0.001 respectively). Transfusion of ten or more red blood cell units (RBCs) during the entire hospital stay was a predictor of an increased LOS (P < 0.001) and death (OR 52, 95%CI [5.9, 461.3], P < 0.001), compared to non-transfused patients. Preoperative ABT and ASA scores were associated with ≥10RBCs. CONCLUSION: Anemic patients undergoing radical cystectomy had a high risk to receive ABTs. Preoperative transfusions and transfusion of ≥10RBCs during the entire hospital stay may increase patient`s mortality. Prospective, randomized controlled studies have to follow this study.

The Fibrin Cleavage Product Bß15-42 Channels Endothelial and Tubular Regeneration in the Post-acute Course During Murine Renal Ischemia Reperfusion Injury.

Early and adequate restoration of endothelial and tubular renal function is a substantial step during regeneration after ischemia reperfusion (IR) injury, occurring, e.g., in kidney transplantation, renal surgery, and sepsis. While tubular epithelial cell injury has long been of central importance, recent perception includes the renal vascular endothelium. In this regard, the fibrin cleavage product fibrinopeptide Bß15-42 mitigate IR injury by stabilizing interendothelial junctions through its affinity to VE-cadherin. Therefore, this study focused on the effect of Bß15-42 on post-acute physiological renal regeneration. For this, adult male C57BL/6 mice were exposed to a 30 min bilateral renal ischemia and reperfusion for 24 h or 48 h. Animals were randomized in a non-operative control group, two operative groups each treated with i.v. administration of either saline or Bß15-42 (2.4 mg/kg) immediately prior to reperfusion. Endothelial activation and inflammatory response was attenuated in renal tissue homogenates by single application of Bß15-42. Meanwhile, Bß15-42 did not affect acute kidney injury markers. Regarding the angiogenetic players VEGF-A, Angiopoietin-1, Angiopoietin-2, however, we observed significant higher expressions at mRNA and trend to higher protein level in Bß15-42 treated mice, compared to saline treated mice after 48 h of IR, thus pointing toward an increased angiogenetic activity. Similar dynamics were observed for the intermediate filament vimentin, the cytoprotective protein klotho, stathmin and the proliferation cellular nuclear antigen, which were significantly up-regulated at the same points in time. These results suggest a beneficial effect of anatomical contiguously located endothelial cells on tubular regeneration through stabilization of endothelial integrity. Therefore, it seems that Bß15-42 represents a novel pharmacological approach in the targeted therapy of acute renal failure in everyday clinical practice.

Microparticles from stored red blood cells enhance procoagulant and proinflammatory activity.

BACKGROUND: The pathomechanisms of morbidity due to blood transfusions are not yet entirely understood. Elevated levels of red blood cell-derived microparticles (RMPs) are found in coagulation-related pathologies and also in stored blood. Previous research has shown that RMPs mediate transfusion-related complications by the intrinsic pathway. We hypothesized that RMPs might play a role in post-transfusion thrombotic complications by enhancing procoagulant activity also through the extrinsic pathway of coagulation. STUDY DESIGN AND METHODS: In this laboratory study, blood from 18 healthy volunteers was stimulated with microparticles from expired stored red blood cells. Various clotting parameters were recorded. Flow cytometry, enzyme-linked immunosorbent assays, and real-time polymerase chain reaction were used to investigate possible mediating mechanisms. RESULTS: The addition of RMPs shortened the clotting time from 194 to 161 seconds (p < 0.001). After incubation with RMPs, there was increased expression of tissue factor (TF) on monocytes and in plasma. TF messenger RNA expression increased in a time-dependent and concentration-dependent manner. There was a significant induction of interleukin-1ß and interleukin-6. After stimulation with RMPs, there was a significant increase in the number of activated platelets, an increased percentage of PAC-1/CD62P (procaspase activating compound-1/platelet surface P-selectin) double-positive platelets, and an increased number of platelet-neutrophil duplets and platelet-monocyte duplets, indicating enhanced interaction of platelets with neutrophils and monocytes. Levels of CXCL-8 (C-X-C motif chemokine ligand 1) and interleukin-6 were significantly higher after treatment with RMPs. CONCLUSION: Our results suggest that RMPs trigger coagulation through TF signaling, induce the secretion of proinflammatory cytokines, and induce cell-cell interaction between platelets and neutrophils. Thus, under certain conditions, RMPs could play a role in post-transfusion complications through these mechanisms.

Patient Blood Management is Associated With a Substantial Reduction of Red Blood Cell Utilization and Safe for Patient's Outcome: A Prospective, Multicenter Cohort Study With a Noninferiority Design.

OBJECTIVE: To determine whether the implementation of patient blood management (PBM) is effective to decrease the use of red blood cell without impairment of patient's safety. BACKGROUND: The World Health Organization encouraged all member states to implement PBM programs employing multiple combined strategies to increase and preserve autologous erythrocyte volume to minimize red blood cell transfusions. Data regarding safety issues are not sufficiently available. METHODS: In this prospective, multicenter study, surgical inpatients from four German University Hospitals were analyzed before (pre-PBM) and after the implementation of PBM. PBM program included multiple measures (ie, preoperative optimization of hemoglobin levels, blood-sparing techniques, and standardization of transfusion practice). Primary aim was to show noninferiority of the PBM cohort with a margin of 0.5%. Secondary endpoints included red blood cell utilization. RESULTS: A total of 129,719 patients discharged between July 2012 and June 2015 with different inclusion periods for pre-PBM (54,513 patients) and PBM (75,206 patients) were analyzed. The primary endpoint was 6.53% in the pre-PBM versus 6.34% in the PBM cohort. The noninferiority aim was achieved (P < 0.001). Incidence of acute renal failure decreased in the PBM cohort (2.39% vs 1.67%; P < 0.001, regression model). The mean number of red blood cell transfused per patient was reduced from 1.21 ±â€Š0.05 to 1.00 ±â€Š0.05 (relative change by 17%, P < 0.001). CONCLUSIONS: The data presented show that implementation of PBM with a more conscious handling of transfusion practice can be achieved even in large hospitals without impairment of patient's safety. Further studies should elucidate which PBM measures are most clinically and cost effective. TRIAL REGISTRATION: PBM-Study ClinicalTrials.gov, NCT01820949.

Novel method to leukoreduce murine blood for transfusion: how to reduce animal usage.

BACKGROUND: Basic research on the pathomechanisms of transfusion-related adverse events depends on murine transfusion models, in which leukoreduction (LR) is a prevalent standard. The commonly used neonatal LR filter (LRF) is associated with considerable animal numbers. A more efficient method would help support the guiding principles of "replacement, reduction, refinement" (3Rs). STUDY DESIGN AND METHODS: Blood from C57BL/6 and C57BL/6-Tg(UBC-GFP)30Scha/J mice was leukoreduced using (1) a neonatal LRF, (2) a syringe LRF, or (3) CD45 microbeads. Product quality was assessed according to US Food and Drug Administration (FDA) standards. White blood cell numbers were analyzed by flow cytometry; hemoglobin concentrations and hematocrit were measured and in vivo posttransfusion recoveries were determined after 2 weeks of storage. RESULTS: Using the neonatal filter, a LR of 99.56% was achieved with wastage of 12.4 mL in comparison to 99.68% and 1-mL hold-up volume with the syringe filter and 99.11 ± 0.24% LR and 0.1-mL wastage using microbeads. All techniques achieved FDA quality standards, apart from posttransfusion recovery rate, which was only reached by the microbeads-based technique. CONCLUSION: LR with CD45 microbeads not only reduces animal usage but also provides a more efficacious method regarding posttransfusion red blood cell recovery and, hence, provides a promising alternative to commonly used methods.