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Introduction: In 2018, platelet (PLT) additive solution‐E (PAS‐E) was introduced. The implementation of PAS‐E was expected to diminish the number of allergic reactions in recipients following a PLT transfusion. Here, we evaluated the efficacy and safety of transfusions with PLTs stored in PAS‐E. Study Design and Methods: After implementation of PAS‐E, data were collected from 2 cohorts of patients with hematological disorders as well as oncology patients, receiving PLTs in PAS‐E. A similar patient group in a recent RCT, receiving PLTs in plasma, was used as a historical control group for both cohorts. Endpoints were corrected count increments (CCIs), bleeding scores (only reported in cohort 1), and the incidence of adverse reactions. Results: In cohort 1, the mean 1‐h CCI was 14.3 ± 6.9, and the 24‐h CCI was 8.7 ± 5.6. In cohort 2, the 1‐h CCI was 11.6 ± 7.8 and the 24‐h CCI was 7.0 ± 6.1. In the control group, the 1‐h CCI was 15.4 ± 5.5 and 24‐h CCI 8.7 ± 4.8. Bleeding complications of WHO grade ≥2 occurred in 40% of patients in cohort 1 compared to 44% in plasma PCs. The incidence of adverse reactions was 1.2% in the two PAS‐E cohorts, compared to 3.0% in plasma PCs. National hemovigilance data showed a significant reduction in allergic reactions with PAS‐E PC transfusions as compared to plasma PCs with an odds ratio of 0.46 (CI 95% 0.37–0.58). Conclusion: The CCIs of PLTs in PAS‐E were decreased compared to plasma PCs, but clinically acceptable. Allergic transfusion reactions were decreased in PAS‐E PCs compared to plasma PCs. [ABSTRACT FROM AUTHOR]

Introduction: A major contributor to coronavirus disease 2019 (COVID‐19) progression and severity is a dysregulated innate and adaptive immune response. Interleukin‐38 (IL−38) is an IL‐1 family member with broad anti‐inflammatory properties, but thus far little is known about its role in viral infections. Recent studies have shown inconsistent results, as one study finding an increase in circulating IL‐38 in COVID‐19 patients in comparison to healthy controls, whereas two other studies report no differences in IL‐38 concentrations. Methods: Here, we present an exploratory, retrospective cohort study of circulating IL‐38 concentrations in hospitalized COVID‐19 patients admitted to two Dutch hospitals (discovery n = 148 and validation n = 184) and age‐ and sex‐matched healthy subjects. Plasma IL‐38 concentrations were measured by enzyme‐linked immunosorbent assay, disease‐related proteins by proximity extension assay, and clinical data were retrieved from hospital records. Results: IL‐38 concentrations were stable during hospitalization and similar to those of healthy control subjects. IL‐38 was not associated with rates of intensive care unit admission or mortality. Only in men in the discovery cohort, IL‐38 concentrations were positively correlated with hospitalization duration. A positive correlation between IL‐38 and the inflammatory biomarker d‐dimer was observed in men of the validation cohort. In women of the validation cohort, IL‐38 concentrations correlated negatively with thrombocyte numbers. Furthermore, plasma IL‐38 concentrations in the validation cohort correlated positively with TNF, TNFRSF9, IL‐10Ra, neurotrophil 3, polymeric immunoglobulin receptor, CHL1, CD244, superoxide dismutase 2, and fatty acid binding protein 2, and negatively with SERPINA12 and cartilage oligomeric matrix protein. Conclusions: These data indicate that IL‐38 is not associated with disease outcomes in hospitalized COVID‐19 patients. However, moderate correlations between IL‐38 concentrations and biomarkers of disease were identified in one of two cohorts. While we demonstrate that IL‐38 concentrations are not indicative of COVID‐19 severity, its anti‐inflammatory effects may reduce COVID‐19 severity and should be experimentally investigated. [ABSTRACT FROM AUTHOR]

The secondary shifts of a photosynthetic membrane protein with a high density of chromophores and very tight packing was used to analyze the light-harvesting 2 (LH2) complex of Rhodopseudomonas acidophila. A relation found between secondary shift anomalies and protein-protein or pigment-protein tertiary and quaternary contacts suggested that higher-order interactions in the tightly packed complex could induce localized perturbations of the backbone conformation and electronic structure, related to functional pigment-protein or protein-protein interactions.

The CHHC/C[P.sup.3] experiment was used to detect through-space long-range intermolecular correlations between the two [alpha]-helical membrane spanning segments. The CHHC/C[P.sup.3] experiment was found to be useful to discriminate between intra-helical and inter-helical constraints.

The electronic ground states of the bacteriochlorophyll a type B800 and type B850 in the light-harvesting 2 complex of Rhodopseudomonas acidophila strain 10050 is characterized by magic angle spinning (MAS) dipolar (super 13)C-(super 13)C, correlation NMR spectroscopy. The electronic coupling between the B850 cofactors due to macrocycle overlap is the predominant mechanism behind the additional red shift in the B850.

Background: The Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) is a unique national database in the Netherlands that was launched in 2007. Transfusion laboratories register the presence of irregular RBC alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing, unknown in their own laboratory information system.Study Design and Methods: Data from the TRIX database 10 years after implementation have been analyzed to demonstrate the added value of TRIX for transfusion practice. TRIX antibody registration, antibody disappearance likelihood, and differences between men and women have been analyzed and evaluated.Results: In the 10-year period 2007 to 2016, a total of 80,164 alloantibodies have been identified and registered in 62,110 individuals. Of the antibodies, 81% were reported in women and 19% in men (female:male, 4.3:1). Rh (DCcEe and Cw ), K, Fya , and Jka antibodies account for 65.6% of all antibody registrations. M and Lewis antibodies account for 18.6% of all antibodies. Antibody disappearance likelihood is relatively high for the clinically relevant antibodies directed against Jkb , s, Fyb , and e. Antibodies directed against D, Fya , and K have a relatively low antibody disappearance likelihood.Conclusion: TRIX is a unique and useful tool for transfusion laboratories for timely and up-to-date information on the presence of erythrocyte antibodies, which improves pretransfusion testing and compatible blood selection. TRIX also provides macro data on the prevalence of individual antibodies and antibody disappearance likelihoods that can be used for developing blood type matching strategies for patient groups at risk. © 2019 AABB. [ABSTRACT FROM AUTHOR]

Background: Both one‐stage (OSA) and chromogenic substrate assays (CSA) are used to measure factor VIII (FVIII) activity. Factors explaining analytical variation in FVIII activity levels are still to be completely elucidated. Aim: The aim of this study was to investigate and quantify the analytical variation in OSA and CSA. Methods: Factors determining analytical variation were studied in sixteen lyophilized plasma samples (FVIII activity <0.01‐1.94 IU/mL) and distributed by the ECAT surveys. To elucidate the causes of OSA variation, we exchanged deficient plasma between three company set‐ups. Results: On average, 206 (range 164‐230) laboratories used the OSA to measure FVIII activity and 30 (range 12‐51) used CSA. The coefficient of variation of OSA and CSA increased with lower FVIII levels (FVIII <0.05 IU/mL). This resulted in misclassification of a severe haemophilia A sample into a moderate or mild haemophilia A sample in 4/30 (13.3%) of CSA measurements, while this was 37/139 (26.6%) for OSA. OSA measurements performed with reagents and equipment from Werfen showed slightly lower FVIII activity (0.93, IQR 0.88‐0.98 IU/mL) compared to measurements with Stago (1.07, IQR 1.02‐1.14 IU/mL) and Siemens (1.03, IQR 0.97‐1.07 IU/mL). Part of this difference is explained by the value of the calibrator. For CSA, the measured FVIII levels were similar using the different kits. Conclusions: In the lower range (<0.05 IU/mL), analytical variation of FVIII measurements is high in both OSA and CSA measurements. The variation in FVIII activity levels was partly explained by specific manufacturers. Further standardization of FVIII measurements and understanding of analytical variation is required. [ABSTRACT FROM AUTHOR]

The article presents a study on probing secondary, tertiary and quaternary structure along with protein-cofactor interactions for a Helical Transmembrane Protein Complex through ¹H Spin Diffusion with magic angle spinning NMR Spectroscopy. Membrane proteins are generally comprised of helical segments with narrow shift dispersion and the inter-helical distances between the segments. The helical transmembrane protein complex will be demonstrated to get the access to four classes.

The electronic ground states of the bacteriochlorophyll a type 6800 and type B850 in the light- harvesting 2 complex of Rhodopseudomonas acidophila strain 10050 have been characterized by magic angle spinning (MAS) dipolar 13C-13C correlation NMR spectroscopy. Uniformly [13C,15N] enriched light- harvesting 2 (LH2) complexes were prepared biosynthetically, while [13C,15N]-B800 LH2 complexes were obtained after reconstitution of apoprotein with uniformly (13C,15N)-enriched bacteriochlorophyll cofactors. Extensive sets of isotropic 13C NMFI chemical shifts were obtained for each bacteriochlorin ring species in the LH2 protein. 13C isotropic shifts in the protein have been compared to the corresponding shifts of monomeric BChI a dissolved in acetone-d6. Density functional theory calculations were performed to estimate ring current effects induced by adjacent cofactors. By correction for the ring current shifts, the 13C shift effects due to the interactions with the protein matrix were resolved. The chemical shift changes provide a clear evidence for a global electronic effect on the B800 and B850 macrocycles, which is attributed to the dielectrics of the protein environment, in contrast with local effects due to interaction with specific amino acid residues. Considerable shifts of -6.2 < δσ < +5.8 ppm are detected for 13C nuclei in both the 6800 and the 8850 bacteriochlorin rings. Because the shift effects for the 6800 and B850 are similar, the polarization of the electronic ground states induced by the protein environment is comparable for both cofactors and corresponds with a red shift of &tild;30 nm relative to the monomeric BChl dissolved in acetone-d6. The electronic coupling between the 6850 cofactors due to macrocycle overlap is the predominant mechanism behind the additional red shift in the 8850. [ABSTRACT FROM AUTHOR]

This I RHAG i allele (gnomAD allele frequency in Caucasians: 0-00062) has previously been associated with the Rh-null regulatory phenotype.1 The Rh-null phenotype of the regulatory type is very rare and this is, to our knowledge, the first reported Dutch individual with this phenotype. Genetic analysis of maternal genomic DNA revealed the presence of normal I RHD i and I RHCE i genes and no variants explaining the Rh-null phenotype. An acidified glycerol lysis test of the proband showed increased erythrocyte lysis of the individuals carrying the variant compared to a wild-type reference, demonstrating markedly increased osmotic fragility of the subject's erythrocytes (right). [Extracted from the article]

The potential protective or pathogenic role of the adaptive immune response to SARS-CoV-2 infection has been vigorously debated. While COVID-19 patients consistently generate a T lymphocyte response to SARS-CoV-2 antigens, evidence of significant immune dysregulation in these patients continues to accumulate. In this study, next generation sequencing of the T cell receptor beta chain (TRB) repertoire was conducted in hospitalized COVID-19 patients to determine if immunogenetic differences of the TRB repertoire contribute to disease course severity. Clustering of highly similar TRB CDR3 amino acid sequences across COVID-19 patients yielded 781 shared TRB sequences. The TRB sequences were then filtered for known associations with common diseases such as EBV and CMV. The remaining sequences were cross-referenced to a publicly accessible dataset that mapped COVID-19 specific TCRs to the SARS-CoV-2 genome. We identified 158 SARS-CoV-2 specific TRB sequences belonging to 134 clusters in our COVID-19 patients. Next, we investigated 113 SARS-CoV-2 specific clusters binding only one peptide target in relation to disease course. Distinct skewing of SARS-CoV-2 specific TRB sequences toward the nonstructural proteins (NSPs) encoded within ORF1a/b of the SARS-CoV-2 genome was observed in clusters associated with critical disease course when compared to COVID-19 clusters associated with a severe disease course. These data imply that T-lymphocyte reactivity towards peptides from NSPs of SARS-CoV-2 may not constitute an effective adaptive immune response and thus may negatively affect disease severity., (©2021 Society for Leukocyte Biology.)

Background: The Transfusion Register of Irregular Antibodies and Cross-match Problems (TRIX) is a unique national database in the Netherlands that was launched in 2007. Transfusion laboratories register the presence of irregular RBC alloantibodies for their patients and can consult the database for information that is relevant for pretransfusion testing, unknown in their own laboratory information system., Study Design and Methods: Data from the TRIX database 10 years after implementation have been analyzed to demonstrate the added value of TRIX for transfusion practice. TRIX antibody registration, antibody disappearance likelihood, and differences between men and women have been analyzed and evaluated., Results: In the 10-year period 2007 to 2016, a total of 80,164 alloantibodies have been identified and registered in 62,110 individuals. Of the antibodies, 81% were reported in women and 19% in men (female:male, 4.3:1). Rh (DCcEe and C w ), K, Fy a , and Jk a antibodies account for 65.6% of all antibody registrations. M and Lewis antibodies account for 18.6% of all antibodies. Antibody disappearance likelihood is relatively high for the clinically relevant antibodies directed against Jk b , s, Fy b , and e. Antibodies directed against D, Fy a , and K have a relatively low antibody disappearance likelihood., Conclusion: TRIX is a unique and useful tool for transfusion laboratories for timely and up-to-date information on the presence of erythrocyte antibodies, which improves pretransfusion testing and compatible blood selection. TRIX also provides macro data on the prevalence of individual antibodies and antibody disappearance likelihoods that can be used for developing blood type matching strategies for patient groups at risk. © 2019 AABB., (© 2019 AABB.)

Background: An increase in urine calcium compared to the consensus value was observed in some urine samples of the Dutch External Quality Assessment Scheme (EQAS). It appeared that the increase was due to the addition of oxalate by the EQAS organizers and preanalytical acidification of the samples by some of the participants. Because of this observation, the effect of urine acidification on urine calcium level in EQAS and patient samples with added oxalate was investigated., Methods: Twenty-four EQAS urine samples and 20 patient urine samples were subject to recovery measurements of urine calcium before and after addition of sodium oxalate and acidification., Results: Differences in urine calcium between acidified and non-acidified samples up to 30.9% have been observed in EQAS samples with added oxalate. Patient samples show differences up to 80%. Differences between acidified and non-acidified samples are minimal for low calcium oxalate levels but increase with higher levels. Samples without added oxalate show equal urine calcium results between acidified and non-acidified samples., Conclusions: Urine calcium results are decreased in non-acidified samples with an excess of oxalate. In case of hyperoxaluria, acidification of patient urine collections and EQAS samples is recommended for correct urine calcium values.