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Extracellular vesicles (EVs) accumulate during packed red blood cell (PRBC) storage. To date, the involvement of EVs in transfusion-related immunomodulation (TRIM) has not been prospectively evaluated in intensive care unit (ICU) patients. This was a prospective subanalysis of a recent observational feasibility study in postoperative ICU patients after: (1) open aortic surgery (Aorta), (2) bilateral lung transplantation (LuTx), and (3) other types of surgery (Comparison). Patient plasma was collected three times each before and after leukoreduced PRBC transfusion at 30-min intervals. The total number of EVs and EVs derived from erythrocytes (EryEVs), total platelets (total PEVs), activated platelets, granulocytes (GEVs), monocytes, and myeloid cells in PRBC samples and patient plasma were analyzed by flow cytometry. Statistical analysis was performed by Spearman's correlation test, linear mixed models and pairwise comparisons by Wilcoxon matched-pairs test. Twenty-three patients (Aorta n = 5, LuTx n = 9, Comparison n = 9) were included in the final analysis. All EV subgroups analyzed were detectable in all PRBCs samples (n = 23), but concentrations did not correlate with storage time. Moreover, all EVs analyzed were detectable in all plasma samples (n = 138), and EV counts were consistent before transfusion. Concentrations of total EVs, EryEVs, total PEVs, and GEVs increased after transfusion compared with baseline in the entire cohort but not in specific study groups. Furthermore, the change in plasma EV counts (total EVs and EryEVs) after transfusion correlated with PRBC storage time in the entire cohort. Extracellular vesicles were detectable in all PRBC and plasma samples. Individual EV subtypes increased after transfusion in the entire cohort, and in part correlated with storage duration. Future clinical studies to investigate the role of EVs in TRIM are warranted and should anticipate a larger sample size.Trial registration: Clinicaltrials.gov: NCT03782623.
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Transfusión de Eritrocitos , Vesículas Extracelulares , Humanos , Transfusión de Eritrocitos/efectos adversos , Estudios Prospectivos , Aorta , Cuidados CríticosRESUMEN
OBJECTIVE: The aim of this retrospective study was to assess the prevalence of anaemia in a cohort of patients undergoing elective general surgery at a university hospital. Furthermore, the authors investigated the influence of anaemia on short-term and long-term postoperative outcome. BACKGROUND: Awareness of the negative impact of preoperative anaemia on perioperative morbidity and mortality is rising. Anaemia is a potentially modifiable factor, and its therapy might improve patient outcome in elective surgery. Nevertheless, patients with preoperative anaemia frequently undergo elective surgery without receiving adequate preoperative treatment. METHODS: In this single-centre cohort study, the authors analyzed 6908 adult patients who underwent elective general surgery. Patients undergoing day-clinic surgery were excluded. In all patients, preoperative haemoglobin concentration and haematocrit was available. RESULTS: Of all patients analyzed, 32.9% were anaemic (21.0% mild, 11.8% moderate, 1.1% severe). Median time to last follow-up was 5.2 years. During the whole study period, 27.1% of patients died (1.2% died during the hospital stay); median time to death was 1.3 years. Patients with preoperative anaemia had significantly higher mortality rates ( P <0.001) and a higher probability of postoperative complications ( P <0.001). Likewise, receiving blood transfusions was associated with a higher risk of death ( P <0.001). CONCLUSION: This retrospective single-centre analysis confirmed that preoperative anaemia is common, and is a significant risk factor for unfavourable postoperative outcome. As anaemia is a modifiable risk factor, the implementation of a patient blood management concept is crucial to reduce detrimental postoperative events associated with anaemia.
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Anemia , Adulto , Humanos , Estudios Retrospectivos , Prevalencia , Estudios de Cohortes , Anemia/epidemiología , HospitalesRESUMEN
Background: The COVID-19 pandemic has changed worldwide hygiene practices. In particular, the use of filtering face piece (FFP) masks markedly increased. Concerns have been raised regarding possible negative respiratory effects of wearing FFP masks. The aim of this study was to investigate gas exchange and subjective breathing effort in hospital personnel wearing FFP2 or FFP3 masks. Methods: In this prospective, single-centre, crossover study, 200 hospital workers were assigned to alternately wear FFP2 or FFP3 masks for 1â h during routine activities. Capillary blood gas analysis was performed to evaluate gas exchange while wearing the FFP masks. The primary end-point was the change in capillary partial pressure of carbon dioxide (PcCO2). In addition, capillary partial pressure of oxygen (PcO2), respiratory rate and subjective breathing effort were assessed at the end of each hour. Changes between time points and study groups were estimated using univariate and multivariate models. Results: PcCO2 increased from 36.8±3.5 to 37.2±3.3â mmHg (p=0.047) and 37.4±3.2â mmHg (p=0.003) in individuals wearing FFP2 or FFP3 masks, respectively. Age (p=0.021) and male sex (p<0.001) were significantly associated with increased PcCO2. Similarly, the PcO2 increased from 70.7±8.4 to 73.4±8.8â mmHg (p<0.001) and 72.8±8.5â mmHg (p=0.004) in individuals wearing FFP2 or FFP3 masks, respectively. Respiratory rate and subjective breathing effort increased significantly while wearing FFP2 and FFP3 masks (p<0.001 for all analyses). The order of wearing FFP2 or FFP3 masks did not significantly affect the results. Conclusions: An hour of wearing FFP2 or FFP3 masks increased PcCO2 values, respiratory rate and subjective breathing effort in healthcare personnel performing routine activities.
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This retrospective study evaluated temporal and regional trends of patient admissions to hospitals, intensive care units (ICU), and intermediate care units (IMCU) as well as outcomes during the COVID-19 pandemic in Austria. We analysed anonymous data from patients admitted to Austrian hospitals with COVID-19 between January 1st, 2020 and December 31st, 2021. We performed descriptive analyses and logistic regression analyses for in-hospital mortality, IMCU or ICU admission, and in-hospital mortality following ICU admission. 68,193 patients were included, 8304 (12.3%) were primarily admitted to ICU, 3592 (5.3%) to IMCU. Hospital mortality was 17.3%; risk factors were male sex (OR 1.67, 95% CI 1.60-1.75, p < 0.001) and high age (OR 7.86, 95% CI 7.07-8.74, p < 0.001 for 90+ vs. 60-64 years). Mortality was higher in the first half of 2020 (OR 1.15, 95% CI 1.04-1.27, p = 0.01) and the second half of 2021 (OR 1.11, 95% CI 1.05-1.17, p < 0.001) compared to the second half of 2020 and differed regionally. ICU or IMCU admission was most likely between 55 and 74 years, and less likely in younger and older age groups. We find mortality in Austrian COVID-19-patients to be almost linearly associated with age, ICU admission to be less likely in older individuals, and outcomes to differ between regions and over time.
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COVID-19 , Humanos , Masculino , Anciano , Femenino , COVID-19/epidemiología , Austria/epidemiología , Estudios Retrospectivos , Pandemias , SARS-CoV-2 , Unidades de Cuidados Intensivos , Hospitales , Mortalidad HospitalariaRESUMEN
Introduction: Eicosanoids are bioactive lipids present in packed red blood cells (PRBCs), and might play a role in transfusion-related immunomodulation (TRIM). We tested the feasibility of analyzing eicosanoid profiles in PRBC supernatant and in plasma samples of postoperative intensive care unit (ICU) patients transfused with one unit of PRBCs. Methods: We conducted a prospective, observational feasibility study enrolling postoperative ICU patients: 1) patients treated with acetylsalicylic acid following abdominal aortic surgery (Aorta); 2) patients on immunosuppressants after bilateral lung transplantation (LuTx); and 3) patients undergoing other types of major surgery (Comparison). Abundances of arachidonic acid (AA) and seven pre-defined eicosanoids were assessed by liquid chromatography and tandem mass spectrometry. PRBC supernatant was sampled directly from the unit immediately prior to transfusion. Spearman's correlations between eicosanoid abundance in PRBCs and storage duration were assessed. Patient plasma was collected at 30-min intervals: Three times each before and after transfusion. To investigate temporal changes in eicosanoid abundances, we fitted linear mixed models. Results: Of 128 patients screened, 21 were included in the final analysis (Aorta n = 4, LuTx n = 8, Comparison n = 9). In total, 21 PRBC and 125 plasma samples were analyzed. Except for 20-hydroxyeicosatetraenoic acid (HETE), all analyzed eicosanoids were detectable in PRBCs, and their abundance positively correlated with storage duration of PRBCs. While 5-HETE, 12-HETE/8-HETE, 15-HETE, 20-HETE, and AA were detectable in virtually all plasma samples, 9-HETE and 11-HETE were detectable in only 57% and 23% of plasma samples, respectively. Conclusions: Recruitment of ICU patients into this transfusion study was challenging but feasible. Eicosanoid abundances increased in PRBC supernatants during storage. In plasma of ICU patients, eicosanoid abundances were ubiquitously detectable and showed limited fluctuations over time prior to transfusion. Taken together, larger clinical studies seem warranted and feasible to further investigate the role of PRBC-derived eicosanoids in TRIM.
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Storage of packed red blood cells is associated with changes in erythrocytes that over time increasingly impair cellular function and potentially contribute to adverse effects associated with blood transfusion. Exposure of phosphatidylserine at the outer membrane leaflet of erythrocytes and shedding of microvesicles (MVs) during packed red blood cell storage are alterations assumed to increase the risk of prothrombotic events in recipients. Here, we used rotational thromboelastometry to study the coagulation process in blood samples with erythrocytes from stored PRBCs reconstituted with freshly prepared platelet-rich plasma. We explored the influence of following effects on the coagulation process: 1) PRBC storage duration, 2) differences between erythrocytes from stored PRBCs compared to freshly drawn erythrocytes, and 3) the contribution of added MVs. Interestingly, despite of a higher fraction of PS-positive cells, erythrocytes from PRBCs stored for 6 weeks revealed longer clotting times than samples with erythrocytes stored for 2 or 4 weeks. Further, clotting times and clot formation times were considerably increased in samples reconstituted with erythrocytes from stored PRBCs as compared to fresh erythrocytes. Moreover, MVs added to reconstituted samples elicited only comparably small and ambiguous effects on coagulation. Thus, this study provides no evidence for an amplified clotting process from prolonged storage of PRBCs but on the contrary implicates a loss of function, which may be of clinical significance in massive transfusion. Our observations add to the increasing body of evidence viewing erythrocytes as active players in the clotting process.
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Pantothenate kinase-associated neurodegeneration (PKAN) is a progressive neurodegenerative disease caused by mutations in the pantothenate kinase 2 (PANK2) gene and associated with iron deposition in basal ganglia. Pantothenate kinase isoforms catalyze the first step in coenzyme A (CoA) biosynthesis. Since PANK2 is the only isoform in erythrocytes, these cells are an excellent ex vivo model to study the effect of PANK2 point mutations on expression/stability and activity of the protein as well as on the downstream molecular consequences. PKAN erythrocytes containing the T528M PANK2 mutant had residual enzyme activities but variable PANK2 abundances indicating an impaired regulation of the protein. Patients with G521R/G521R, G521R/G262R, and R264N/L275fs PANK2 mutants had no residual enzyme activity and strongly reduced PANK2 abundance. G521R inactivates the catalytic activity of the enzyme, whereas G262R and the R264N point mutations impair the switch from the inactive to the active conformation of the PANK2 dimer. Metabolites in cytosolic extracts were analyzed by gas chromatography-mass spectrometry and multivariate analytic methods revealing changes in the carboxylate metabolism of erythrocytes from PKAN patients as compared to that of the carrier and healthy control. Assuming low/absent CoA levels in PKAN erythrocytes, changes are consistent with a model of altered citrate channeling where citrate is preferentially converted to α-ketoglutarate and α-hydroxyglutarate instead of being used for de novo acetyl-CoA generation. This finding hints at the importance of carboxylate metabolism in PKAN pathology with potential links to reduced cytoplasmic acetyl-CoA levels in neurons and to aberrant brain iron regulation.
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Enfermedades Neurodegenerativas , Neurodegeneración Asociada a Pantotenato Quinasa , Acetilcoenzima A , Citratos , Ácido Cítrico , Eritrocitos/metabolismo , Humanos , Hierro/metabolismo , Mutación , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Neurodegeneración Asociada a Pantotenato Quinasa/patología , Fosfotransferasas (Aceptor de Grupo Alcohol) , Isoformas de Proteínas/genéticaRESUMEN
Ascorbic acid (AA; or vitamin C) is an important physiological antioxidant and radical scavenger. Some mammalian species, including homo sapiens, have lost the ability to synthetize AA and depend on its nutritional uptake. Erythrocytes from AA-auxotroph mammals express high amounts of the glucose transporter GLUT1. This isoform enables rapid uptake of glucose as well as dehydroascorbate (DHA), the fully oxidized form of AA. Here, we explored the effects of DHA uptake on the redox metabolism of human erythrocytes. DHA uptake enhanced plasma membrane electron transport (PMET) activity. This process is mediated by DCytb, a membrane bound cytochrome catalyzing extracellular reduction of Fe3+ and ascorbate free radical (AFR), the first oxidized form of AA. DHA uptake also decreased cellular radical oxygen species (ROS) levels. Both effects were massively enhanced in the presence of physiological glucose concentrations. Reduction of DHA to AA largely depleted intracellular glutathione (GSH) and induced the efflux of its oxidized form, GSSG. GSSG efflux could be inhibited by MK-571 (IC 50 = 5 µM), indicating involvement of multidrug resistance associated protein (MRP1/4). DHA-dependent GSH depletion and GSSG efflux were completely rescued in the presence of 5 mM glucose and, partially, by 2-deoxy-glucose (2-DG), respectively. These findings indicate that human erythrocytes are physiologically adapted to recycle AA both intracellularly via GLUT1-mediated DHA uptake and reduction and extracellularly via DCytb-mediated AFR reduction. We discuss the possibility that this improved erythrocyte-mediated AA recycling was a prerequisite for the emergence of AA auxotrophy which independently occurred at least twice during mammalian evolution.
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Numerous observations indicate that red blood cells (RBCs) affect T-cell activation and proliferation. We have studied effects of packed RBCs (PRBCs) on T-cell receptor (TCR) signaling and the molecular mechanisms whereby (P)RBCs modulate T-cell activation. In line with previous reports, PRBCs attenuated the expression of T-cell activation markers CD25 and CD69 upon costimulation via CD3/CD28. In addition, T-cell proliferation and cytokine expression were markedly reduced when T-cells were stimulated in the presence of PRBCs. Inhibitory activity of PRBCs required direct cell-cell contact and intact PRBCs. The production of activation-induced cellular reactive oxygen species, which act as second messengers in T-cells, was completely abrogated to levels of unstimulated T-cells in the presence of PRBCs. Phosphorylation of the TCR-related zeta chain and thus proximal TCR signal transduction was unaffected by PRBCs, ruling out mechanisms based on secreted factors and steric interaction restrictions. In large part, downstream signaling events requiring reactive oxygen species for full functionality were affected, as confirmed by an untargeted MS-based phosphoproteomics approach. PRBCs inhibited T-cell activation more efficiently than treatment with 1 mM of the antioxidant N-acetyl cysteine. Taken together, our data imply that inflammation-related radical reactions are modulated by PRBCs. These immunomodulating effects may be responsible for clinical observations associated with transfusion of PRBCs.
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Antígenos CD/inmunología , Antígenos de Diferenciación de Linfocitos T/inmunología , Eritrocitos/inmunología , Subunidad alfa del Receptor de Interleucina-2/inmunología , Lectinas Tipo C/inmunología , Especies Reactivas de Oxígeno/metabolismo , Linfocitos T/inmunología , Antígenos CD/metabolismo , Antígenos de Diferenciación de Linfocitos T/metabolismo , Proliferación Celular/fisiología , Células Cultivadas , Eritrocitos/metabolismo , Humanos , Inmunomodulación , Subunidad alfa del Receptor de Interleucina-2/metabolismo , Lectinas Tipo C/metabolismo , Leucocitos Mononucleares , Activación de Linfocitos , Fosforilación , Transducción de Señal , Linfocitos T/metabolismoAsunto(s)
Anemia/tratamiento farmacológico , Hierro/administración & dosificación , Readmisión del Paciente , Complicaciones Posoperatorias/prevención & control , Cuidados Preoperatorios/métodos , Administración Intravenosa , Anemia/diagnóstico , Humanos , Estudios Multicéntricos como Asunto/métodos , Readmisión del Paciente/tendencias , Complicaciones Posoperatorias/diagnóstico , Cuidados Preoperatorios/tendencias , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Medición de Riesgo , Resultado del TratamientoRESUMEN
BACKGROUND: Anemia is a risk factor for adverse outcomes, which can be aggravated by unnecessary phlebotomies. In blood culture testing, up to 30 ml of blood can be withdrawn per sample, even though most manufacturers recommend blood volumes of 10 ml or less. After assessing the filling volume of blood culture bottles at our institution, we investigated whether an educational intervention could optimize filling volume of blood culture bottles without negatively affecting microbiology testing. METHODS: We weighed 10,147 blood cultures before and 11,806 blood cultures after a six-month educational intervention, during which employees were trained regarding correct filling volume via lectures, handouts, emails, and posters placed at strategic places. RESULTS: Before the educational intervention, only 31% of aerobic and 34% of anaerobic blood cultures were filled correctly with 5-10 ml of blood. The educational intervention increased the percentage of correctly filled bottles to 43% (P < 0.001) for both aerobic and anaerobic samples without negatively affecting results of microbiologic testing. In addition, sample volume was reduced from 11.0 ± 6.5 to 9.4 ± 5.1 ml (P < 0.001) in aerobic bottles and from 10.1 ± 5.6 to 8.8 ± 4.8 ml (P < 0.001) in anaerobic bottles. CONCLUSION: Education of medical personnel is a simple and effective way to reduce iatrogenic blood loss and possibly moderate the extent of phlebotomy-induced anemia.
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Cultivo de Sangre , Flebotomía , Técnicas Bacteriológicas , HumanosRESUMEN
OBJECTIVE: Pantothenate kinase 2-associated neurodegeneration (PKAN) is a rare neurodegenerative disease caused by mutations in the pantothenate kinase 2 (PANK2) gene. PKAN is associated with iron deposition in the basal ganglia and, occasionally, with the occurrence of misshaped erythrocytes (acanthocytes). The aim of this study was to assess residual activity of PANK2 in erythrocytes of PKAN patients and to correlate these data with the type of PANK2 mutations and the progression of neurodegeneration. METHODS: Residual PANK2 activities in erythrocytes of 14 PKAN patients and 14 related carriers were assessed by a radiometric assay. Clinical data on neurodegeneration included the Barry-Albright Dystonia Scale (BAD-Scale) besides further general patient features. A molecular visualization and analysis program was used to rationalize the influence of the PKAN causing mutations on a molecular level. RESULTS: Erythrocytes of PKAN patients had markedly reduced or no PANK2 activity. However, patients with at least one allele of the c.1583C > T (T528M) or the c.833G > T (R278L) variant exhibited 12-56% of residual PANK2 activity. In line, molecular modeling indicated only minor effects on enzyme structure for these point mutations. On average, these patients with c.1583C > T or c.833G > T variant had lower BAD scores corresponding to lower symptom severity than patients with other PANK2 point mutations. INTERPRETATION: Residual erythrocyte PANK2 activity could be a predictor for the progression of neurodegeneration in PKAN patients. Erythrocytes are an interesting patient-derived cell system with still underestimated diagnostic potential.
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Progresión de la Enfermedad , Eritrocitos/metabolismo , Neurodegeneración Asociada a Pantotenato Quinasa/sangre , Neurodegeneración Asociada a Pantotenato Quinasa/diagnóstico , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Sistema de Registros , Adolescente , Adulto , Bancos de Muestras Biológicas , Femenino , Humanos , Masculino , Neurodegeneración Asociada a Pantotenato Quinasa/genética , Neurodegeneración Asociada a Pantotenato Quinasa/patología , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Pronóstico , Adulto JovenRESUMEN
Recent studies indicate that erythrocytes actively modulate blood clotting and thrombus formation. The lipid mediator lysophosphatidic acid (LPA) is produced by activated platelets, and triggers a signaling process in erythrocytes. This results in cellular calcium uptake and exposure of phosphatidylserine (PS) at the cell surface, thereby generating activated membrane binding sites for factors of the clotting cascade. Moreover, erythrocytes of patients with a bleeding disorder and mutations in the scramblase TMEM16F show impaired PS exposure and microvesiculation upon treatment with calcium ionophore. We report that TMEM16F inhibitors tannic acid (TA) and epigallocatechin-3-gallate (EGCG) inhibit LPA-induced PS exposure and calcium uptake at low micromolar concentrations; fluoxetine, an antidepressant and a known activator of TMEM16F, enhances these processes. These effectors likewise modulate erythrocyte PS exposure and microvesicle shedding induced by calcium ionophore treatment. Further, LPA-treated erythrocytes triggered thrombin generation in platelet-free plasma which was partially impaired in the presence of TA and EGCG. Thus, this study suggests that LPA activates the scramblase TMEM16F in erythrocytes, thereby possibly mediating a pro-thrombotic function in these cells. EGCG as well as fluoxetine, substances with potentially high plasma concentrations due to alimentation or medical treatment, should be considered as potential effectors of systemic hemostatic regulation.
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Anoctaminas/metabolismo , Micropartículas Derivadas de Células/metabolismo , Eritrocitos/metabolismo , Lisofosfolípidos/metabolismo , Fosfatidilserinas/metabolismo , Proteínas de Transferencia de Fosfolípidos/metabolismo , Trombosis/metabolismo , Eritrocitos/citología , Hemostasis , Humanos , Trombina/metabolismoRESUMEN
PURPOSE OF REVIEW: Over the last decades, clinical studies have suggested that transfusion of red blood cells (RBCs) might negatively impact patient outcomes. Even though large randomized clinical trials did not show differences in mortality when transfusing fresh versus standard-issue RBC units, data imply that RBCs at the very end of storage could elicit negative effects. RECENT FINDINGS: Certain alterations of RBCs during cold storage -- such as an increase of potassium and lactate in the storage solution -- have been discovered a century ago. In recent years, proteomic and metabolomic studies have shed more light into pathophysiological changes of RBCs during storage and have helped to specify the definition of old blood. These advancements are now utilized to increase the quality of stored RBCs and devise therapeutic strategies (e.g. nitric oxide, haptoglobin, or reduction of the iron load) when transfusing old blood. SUMMARY: Further research to improve the quality of RBC units and to study populations potentially at risk is warranted. Until the question whether transfusion of old blood is detrimental for specific patient populations has been answered, a deliberate use of RBC transfusion should be implemented.
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Conservación de la Sangre/estadística & datos numéricos , Transfusión de Eritrocitos/efectos adversos , Eritrocitos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
BACKGROUND: Destruction of the endothelial glycocalyx has been observed within lung and kidney grafts during ischemic organ preservation. We aimed to quantify glycocalyx damage within human liver grafts after organ preservation and correlate the results with graft injury and postoperative graft function in patients undergoing orthotopic liver transplantation (OLT). METHODS: Syndecan-1 (Sdc-1) was measured as indicator of glycocalyx degradation in effluents of 38 liver grafts and serum of patients undergoing OLT. Effluent Sdc-1 concentrations were correlated with hepatic injury markers from the effluent. Furthermore, we assessed the association of Sdc-1 with early allograft dysfunction (EAD), 1-year graft survival, and 1-year patient survival. RESULTS: Effluent Sdc-1 concentrations correlated with effluent concentrations of hepatocellular injury markers, including alkaline phosphatase (R = 0.543, P = 0.003), aspartate aminotransferase (R = 0.420, P = 0.029), and lactate (R = 0.574, P = 0.002). Sdc-1 effluent concentrations were greater in patients who developed EAD compared with those without EAD (4720 [4374-5133] vs 3838 [3202-4240] ng/mL, P = 0.015). Furthermore, receiver operating characteristics analyses revealed that effluent Sdc-1 concentrations (AUC = 0.82, P = 0.017) and serum Sdc-1 concentrations (AUC = 0.84, P = 0.006) were associated with the development of EAD. These results were confirmed by regression analyses. No association was found between Sdc-1 and 1-year graft survival or 1-year patient survival. CONCLUSIONS: Our data suggest that the glycocalyx is damaged within human liver grafts during preservation and the extent of glycocalyx damage correlates with the severity of hepatocellular injury. Recipients of livers grafts with greater glycocalyx damage might be at higher risk for development of EAD after OLT.
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Enfermedad Hepática en Estado Terminal/cirugía , Glicocálix/patología , Trasplante de Hígado/efectos adversos , Hígado/patología , Preservación de Órganos/efectos adversos , Anciano , Enfermedad Hepática en Estado Terminal/sangre , Enfermedad Hepática en Estado Terminal/mortalidad , Células Endoteliales/citología , Células Endoteliales/patología , Femenino , Glicocálix/metabolismo , Supervivencia de Injerto , Humanos , Hígado/citología , Masculino , Persona de Mediana Edad , Proyectos Piloto , Periodo Posoperatorio , Estudios Prospectivos , Factores de Riesgo , Sindecano-1/sangre , Sindecano-1/metabolismoRESUMEN
BACKGROUND: The product of the concentrations of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor binding protein-7 (urinary [TIMP-2] × [IGFBP-7]) has been suggested as biomarker for early detection of acute kidney injury (AKI) in various clinical settings. However, the performance of urinary [TIMP-2] × [IGFBP-7] to predict AKI has never been assessed in patients undergoing orthotopic liver transplantation (OLT). Thus, the aim of this study was to assess the early predictive value of urinary [TIMP-2] × [IGFBP-7] for the development of AKI after OLT. METHODS: In this observational study, urinary [TIMP-2] × [IGFBP-7] was measured in samples from adult OLT patients. AKI was diagnosed and classified according to KDIGO criteria. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of urinary [TIMP-2] × [IGFBP-7] for the development of AKI. RESULTS: Forty patients (mean age 55 ± 8 years) were included. Twenty-eight patients (70%) developed AKI stage 1, 2, or 3 within 48 h after OLT. Urinary [TIMP-2] × [IGFBP-7] was not predictive for AKI at the end of OLT (AUC: 0.54, CI [0.32-0.75], P = 0.72), at day 1 (AUC: 0.60, CI [0.41-0.79], P = 0.31), or day 2 after OLT (AUC: 0.63, CI [0.46-0.8], P = 0.18). CONCLUSION: Based on our results, routine clinical use of urinary [TIMP-2] × [IGFBP-7] cannot be recommended for risk assessment of AKI in patients undergoing OLT.
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Lesión Renal Aguda/orina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/orina , Fallo Renal Crónico/cirugía , Trasplante de Hígado , Complicaciones Posoperatorias/orina , Inhibidor Tisular de Metaloproteinasa-2/orina , Biomarcadores/orina , Femenino , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las PruebasRESUMEN
BACKGROUND: Experimental and volunteer studies have reported pulmonary vasoconstriction during transfusion of packed red blood cells (PRBCs) stored for prolonged periods. The primary aim of this study was to evaluate whether transfusion of PRBCs stored over 21 days (standard-issue, siPRBCs) increases pulmonary artery pressure (PAP) to a greater extent than transfusion of PRBCs stored for less then 14 days (fresh, fPRBCs) in critically ill patients following cardiac surgery. The key secondary aim was to assess whether the pulmonary vascular resistance index (PVRI) increases after transfusion of siPRBCs to a greater extent than after transfusion of fPRBCs. METHODS: The study was performed as a single-center, double-blinded, parallel-group, randomized clinical trial. Leukoreduced PRBCs were transfused while continuously measuring hemodynamic parameters. Systemic concentrations of syndecan-1 were measured to assess glycocalyx injury. After randomizing 19 patients between January 2014 and June 2016, the study was stopped due to protracted patient recruitment. RESULTS: Of 19 randomized patients, 11 patients were transfused and included in statistical analyses. Eight patients were excluded prior to transfusion, 6 patients received fPRBCs (10±3 storage days), whereas 5 patients received siPRBCs (33±4 storage days). The increase in PAP (7±3 vs. 2±2 mmHg, P = 0.012) was greater during transfusion of siPRBCs than during transfusion of fPRBCs. In addition, the change in PVRI (150±89 vs. -4±37 dyn·s·cm-5·m2, P = 0.018) was greater after transfusion of siPRBCs than after transfusion of fPRBCs. The increase in PAP correlated with the change of systemic syndecan-1 concentrations at the end of transfusion (R = 0.64,P = 0.034). CONCLUSION: Although this study is underpowered and results require verification in larger clinical trials, our findings suggest that transfusion of siPRBCs increases PAP and PVRI to a greater extent than transfusion of fPRBCs in critically ill patients following cardiac surgery. Glycocalyx injury might contribute to pulmonary vasoconstriction associated with transfusion of stored blood.
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Procedimientos Quirúrgicos Cardíacos/efectos adversos , Transfusión de Eritrocitos/efectos adversos , Hemorragia Posoperatoria/terapia , Arteria Pulmonar/fisiopatología , Vasoconstricción , Anciano , Enfermedad Crítica/terapia , Método Doble Ciego , Almacenaje de Medicamentos , Células Endoteliales/citología , Células Endoteliales/patología , Femenino , Glicocálix/patología , Humanos , Masculino , Persona de Mediana Edad , Hemorragia Posoperatoria/etiología , Arteria Pulmonar/patología , Factores de Tiempo , Resistencia VascularRESUMEN
BACKGROUND: Few and inconsistent data exist describing the effect of storage duration on glycated hemoglobin (HbA1c) concentrations of red blood cells (RBCs), impeding interpretation of HbA1c values in transfused diabetic patients. Hence the aim of this study was to evaluate to what extent HbA1c concentrations of RBCs change during the maximum allowed storage period of 42 days. STUDY DESIGN AND METHODS: Blood was drawn from 16 volunteers, leukofiltered, and stored under standard blood banking conditions. HbA1c concentrations of RBCs were measured on Days 1 and 42 of storage using three different validated devices (ion-exchange high-performance liquid chromatography Method A1 and A2, turbidimetric immunoassay Method B). RESULTS: Mean HbA1c concentrations of RBCs on Day 1 were 5.3 ± 0.3% (Method A1), 5.4 ± 0.4% (Method A2), and 5.1 ± 0.4% (Method B). HbA1c concentrations increased to 5.6 ± 0.3% (A1, p < 0.0001), 5.7 ± 0.3% (A2, p = 0.004), and 5.5 ± 0.4% (B, p < 0.0001) on Day 42, respectively, corresponding to a 1.06-fold increase across all methods. Glucose concentrations in the storage solution of RBCs decreased from 495 ± 27 to 225 ± 55 mg/dL (p < 0.0001), confirming that stored RBCs were metabolically active. CONCLUSION: These results suggest a significant, albeit minor, and most likely clinically insignificant increase in HbA1c concentrations during storage of RBCs for 42 days.
Asunto(s)
Bancos de Sangre , Conservación de la Sangre , Eritrocitos/metabolismo , Hemoglobina Glucada/metabolismo , Adulto , Eritrocitos/citología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
BACKGROUND: Elevated concentrations of D-dopachrome tautomerase (D-DT) were associated with adverse outcome in various clinical settings. However, no study assessed D-DT concentrations in patients requiring orthotopic liver transplantation (OLT). The aim of this observational study was to measure serum D-DT concentrations in patients undergoing OLT and associate D-DT with survival and acute kidney injury (AKI). METHODS: Forty-seven adults with end-stage liver disease undergoing OLT were included. Areas under the receiver operating curves (AUC) were calculated to assess predictive values of D-DT for outcome and AKI after OLT. Survival was analyzed by Kaplan-Meier curves. RESULTS: Serum D-DT concentrations were greater in non-survivors than in survivors prior to OLT (86 [50-117] vs. 53 [31-71] ng/ml, P = 0.008), and on day 1 (357 [238-724] vs. 189 [135-309] ng/ml, P = 0.001) and day 2 (210 [142-471] vs. 159 [120-204] ng/ml, P = 0.004) following OLT. Serum D-DT concentrations predicted lethal outcome when measured preoperatively (AUC = 0.75, P = 0.017) and on postoperative day 1 (AUC = 0.75, P = 0.015). One-year survival of patients with preoperative D-DT concentrations >85 ng/ml was 50%, whereas that of patients with preoperative D-DT concentrations <85 ng/ml was 83% (Chi2 = 5.83, P = 0.016). In contrast, D-DT was not associated with AKI after OLT. CONCLUSION: In patients undergoing OLT, serum D-DT might predict outcome after OLT.