Evaluation of the hepatotoxicity of Psoralea corylifolia L. based on a zebrafish model.

Objective: Psoralea corylifolia L. (FP) has received increasing attention due to its potential hepatotoxicity. Methods: In this study, zebrafish were treated with different concentrations of an aqueous extract of FP (AEFP; 40, 50, or 60 µg/mL), and the hepatotoxic effects of tonicity were determined by the mortality rate, liver morphology, fluorescence area and intensity of the liver, biochemical indices, and pathological tissue staining. The mRNA expression of target genes in the bile acid metabolic signaling pathway and lipid metabolic pathway was detected by qPCR, and the mechanism of toxicity was initially investigated. AEFP (50 µg/mL) was administered in combination with FXR or a peroxisome proliferator-activated receptor α (PPARα) agonist/inhibitor to further define the target of toxicity. Results: Experiments on toxic effects showed that, compared with no treatment, AEFP administration resulted in liver atrophy, a smaller fluorescence area in the liver, and a lower fluorescence intensity (p < 0.05); alanine transaminase (ALT), aspartate transaminase (AST), and γ-GT levels were significantly elevated in zebrafish (p < 0.01), and TBA, TBIL, total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were elevated to different degrees (p < 0.05); and increased lipid droplets in the liver appeared as fatty deposits. Molecular biological validation revealed that AEFP inhibited the expression of the FXR gene, causing an increase in the expression of the downstream genes SHP, CYP7A1, CYP8B1, BSEP, MRP2, NTCP, peroxisome proliferator-activated receptor γ (PPARγ), ME-1, SCD-1, lipoprotein lipase (LPL), CPT-1, and CPT-2 and a decrease in the expression of PPARα (p < 0.05). Conclusion: This study demonstrated that tonic acid extracts are hepatotoxic to zebrafish through the inhibition of FXR and PPARα expression, thereby causing bile acid and lipid metabolism disorders.

The enhanced hepatotoxicity of isobavachalcone in depigmented zebrafish due to calcium signaling dysregulation and lipid metabolism disorder.

Isobavachalcone (IBC) is a flavonoid component derived from Psoraleae Fructus that can increase skin pigmentation and treat vitiligo. However, IBC has been reported to be hepatotoxic. Current studies on IBC hepatotoxicity are mostly on normal organisms but lack studies on hepatotoxicity in patients. This study established the depigmented zebrafish model by using phenylthiourea (PTU) and investigated the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC and the underlying mechanism. Morphological, histological, and ultrastructural examination and RT-qPCR verification were used to evaluate the effects of IBC on the livers of zebrafish larvae. IBC significantly decreased liver volume, altered lipid metabolism, and induced pathological and ultrastructural changes in the livers of zebrafish with depigmentation compared with normal zebrafish. The RNA-sequencing and RT-qPCR results showed that the difference in hepatotoxicity between normal and depigmented zebrafish caused by IBC was closely related to the calcium signaling pathway, lipid decomposition and metabolism, and oxidative stress. This work delved into the mechanism of the enhanced IBC-induced hepatotoxicity in depigmented zebrafish and provided a new insight into the hepatotoxicity of IBC.

Using routine health-care data to search for unknown transfusion-transmitted disease: a nationwide, agnostic retrospective cohort study.

BACKGROUND: Identification and prevention of transfusion-transmitted disease is essential for blood transfusion safety. However, current surveillance systems are largely driven by reports of sentinel events, which is an approach that might be inadequate for identifying transmission of pathogens not known to be transmissible or pathogens with long incubation periods. Using a combination of health-data registers and blood-bank databases, we aimed to perform an agnostic search for potential transfusion-transmitted diseases and to identify unknown threats to the blood supply. METHODS: In this nationwide, agnostic retrospective cohort study, we developed a systematic algorithm for performing a phenome-wide search for transfusion-transmitted disease without consideration of any a-priori suspicion of blood-borne transmissibility. We applied this algorithm to a nationwide Swedish transfusion database (SCANDAT-3S) to test for possible transmission of 1155 disease entities based on all relevant diagnostic coding systems in use during the period. We ascertained health outcomes of blood donors and transfusion recipients from the Swedish National Inpatient Register, Swedish Cause of Death Register, and Swedish Cancer Register. Analyses were two-pronged, studying both disease diagnosis concordance between donors and recipients and a possible shared increased disease risk among all recipients of a given donor. For both approaches, we used Cox proportional hazards regression models with time-dependent covariates. Adjustment for multiple comparisons was done using a false discovery rate method. FINDINGS: The analyses included data on 1·72 million patients who had received 18·97 million transfusions (red blood cell, plasma, platelet, or whole blood units) between Jan 1, 1968, and Dec 31, 2017, from 1·04 million blood donors. The median follow-up was 4·5 (IQR 0·9-11·4) years for recipients and 18·5 (8·3-26·2) years for donors. We found evidence of transfusion-transmission for 15 diseases, of which 13 were validated using a second conceptually different approach. We identified transmission of viral hepatitis and its complications (eg, oesophageal varices) but also transmission of other conditions (eg, pneumonia of unknown origin). The diseases that could not be validated in this second approach, HIV and abnormal findings in specimens from male genital organs, were not statistically significant after adjustment for multiple testing. The effect sizes were small (close to 1) for other conditions. INTERPRETATION: We find no strong evidence of unexpected, widespread transfusion-transmitted disease. This novel approach serves as a proof-of-concept for agnostic, data-driven surveillance for transfusion-transmitted disease using routinely collected blood-bank and health-care data. FUNDING: Department of Health and Human Services, US National Heart, Lung, and Blood Institute, US National Institutes of Health, Swedish Research Council and Region Stockholm.

Intracerebral Hemorrhage Among Blood Donors and Their Transfusion Recipients.

Importance: Recent reports have suggested that cerebral amyloid angiopathy, a common cause of multiple spontaneous intracerebral hemorrhages (ICHs), may be transmissible through parenteral injection of contaminated cadaveric pituitary hormone in humans. Objective: To determine whether spontaneous ICH in blood donors after blood donation is associated with development of spontaneous ICH in transfusion recipients. Design, Setting, and Participants: Exploratory retrospective cohort study using nationwide blood bank and health register data from Sweden (main cohort) and Denmark (validation cohort) and including all 1 089 370 patients aged 5 to 80 years recorded to have received a red blood cell transfusion from January 1, 1970 (Sweden), or January 1, 1980 (Denmark), until December 31, 2017. Exposures: Receipt of red blood cell transfusions from blood donors who subsequently developed (1) a single spontaneous ICH, (2) multiple spontaneous ICHs, or (3) no spontaneous ICH. Main Outcomes and Measures: Spontaneous ICH in transfusion recipients; ischemic stroke was a negative control outcome. Results: A total of 759 858 patients from Sweden (median age, 65 [IQR, 48-73] years; 59% female) and 329 512 from Denmark (median age, 64 [IQR, 50-73] years; 58% female) were included, with a median follow-up of 5.8 (IQR, 1.4-12.5) years and 6.1 (IQR, 1.5-11.6) years, respectively. Patients who underwent transfusion with red blood cell units from donors who developed multiple spontaneous ICHs had a significantly higher risk of a single spontaneous ICH themselves, compared with patients receiving transfusions from donors who did not develop spontaneous ICH, in both the Swedish cohort (unadjusted incidence rate [IR], 3.16 vs 1.12 per 1000 person-years; adjusted hazard ratio [HR], 2.73; 95% CI, 1.72-4.35; P < .001) and the Danish cohort (unadjusted IR, 2.82 vs 1.09 per 1000 person-years; adjusted HR, 2.32; 95% CI, 1.04-5.19; P = .04). No significant difference was found for patients receiving transfusions from donors who developed a single spontaneous ICH in the Swedish cohort (unadjusted IR, 1.35 vs 1.12 per 1000 person-years; adjusted HR, 1.06; 95% CI, 0.84-1.36; P = .62) nor the Danish cohort (unadjusted IR, 1.36 vs 1.09 per 1000 person-years; adjusted HR, 1.06; 95% CI, 0.70-1.60; P = .73), nor for ischemic stroke as a negative control outcome. Conclusions and Relevance: In an exploratory analysis of patients who received red blood cell transfusions, patients who underwent transfusion with red blood cells from donors who later developed multiple spontaneous ICHs were at significantly increased risk of spontaneous ICH themselves. This may suggest a transfusion-transmissible agent associated with some types of spontaneous ICH, although the findings may be susceptible to selection bias and residual confounding, and further research is needed to investigate if transfusion transmission of cerebral amyloid angiopathy might explain this association.

Mortality Among Patients Undergoing Blood Transfusion in Relation to Donor Sex and Parity: A Natural Experiment.

Importance: Prior evidence suggests that plasma and platelet transfusions from female and parous donors are associated with adverse clinical outcomes, which has led to the predominant use of male donors for plasma and platelets in many countries. However, studies on red blood cell transfusions have been conflicting. Objective: To determine whether blood donor sex and parity affect mortality of patients undergoing transfusion with red blood cells. Design, Setting, and Participants: This cohort study used nationwide blood bank and health register data in Sweden and involved a natural experiment created by donor sex and parity being concealed and randomly allocated. Patients were included if they were 18 to 90 years old, did not have a history of blood transfusion, and received a transfusion between January 1, 2010, and December 31, 2017. Patients were followed up from their first red blood cell transfusion until death, emigration, or end of study (June 30, 2018). Data analysis was performed between June 15 and December 15, 2021. Exposures: (1) Female vs male donors and (2) parous or nonparous female vs male donors. Main Outcomes and Measures: Overall survival up to 2 years estimated using inverse probability-weighted Kaplan-Meier estimates and relative risk for additional transfusions within 24 hours. Results: Among the 368 778 included patients (mean [SD] age, 66.3 [17.7] years; 57.3% female), 2-year survival differences comparing red blood cell transfusions from female and parous donors to male donors were -0.1% (95% CI, -1.3% to 1.1%) and 0.3% (95% CI, -0.6% to 1.2%), respectively. No statistically significant survival differences were observed regardless of patient sex or age. Median (IQR) hemoglobin counts for female donors (13.5 [13.0-14.0] g/dL) were lower than for male donors (14.9 [14.4-15.5] g/dL). Red blood cell transfusions from female donors were associated with a relative risk of 1.12 (95% CI, 1.08-1.17) for additional transfusions within 24 hours but not after adjusting for donor hemoglobin counts (relative risk, 1.03; 95% CI, 0.98-1.08). Pretransfusion patient characteristics were naturally distributed as-if randomized. Conclusions and Relevance: In this nationwide cohort study involving a natural experiment, after accounting for the lower hemoglobin values in blood from female donors, patients undergoing transfusion with blood from female or parous donors did not have higher 2-year mortality compared with recipients of blood from male donors.

Patterns and determinants of blood transfusion in intensive care in Sweden between 2010 and 2018: A nationwide, retrospective cohort study.

BACKGROUND: Intensive care unit (ICU) patients are transfused with blood products for a number of reasons, from massive ongoing hemorrhage, to mild anemia following blood sampling, combined with bone marrow depression due to critical illness. There's a paucity of data on transfusions in ICUs and most studies are based on audits or surveys. The aim of this study was to provide a complete picture of ICU-related transfusions in Sweden. METHODS: We conducted a register based retrospective cohort study with data on all adult patient admissions from 82 of 84 Swedish ICUs between 2010 and 2018, as recorded in the Swedish Intensive Care Register. Transfusions were obtained from the SCANDAT-3 database. Descriptive statistics were computed, characterizing transfused and nontransfused patients. The distribution of blood use comparing different ICUs was investigated by computing the observed proportion of ICU stays with a transfusion, as well as the expected proportion. RESULTS: In 330,938 ICU episodes analyzed, at least one transfusion was administered for 106,062 (32%). For both red-cell units and plasma, the fraction of patients who were transfused decreased during the study period from 31.3% in 2010 to 24.6% in 2018 for red-cells, and from 16.6% in 2010 to 9.4% in 2018 for plasma. After adjusting for a range of factors, substantial variation in transfusion frequency remained, especially for plasma units. CONCLUSION: Despite continuous decreases in utilization, transfusions remain common among Swedish ICU patients. There is considerable unexplained variation in transfusion rates. More research is needed to establish stronger critiera for when to transfuse ICU patients.

Joint Optimization of Control Strategy and Energy Consumption for Energy Harvesting WSAN.

With the rapid development of wireless sensor technology, recent progress in wireless sensor and actuator networks (WSANs) with energy harvesting provide the possibility for various real-time applications. Meanwhile, extensive research activities are carried out in the fields of efficient energy allocation and control strategy design. However, the joint design considering physical plant control, energy harvesting, and consumption is rarely concerned in existing works. In this paper, in order to enhance system control stability and promote quality of service for the WSAN energy efficiency, a novel three-step joint optimization algorithm is proposed through control strategy and energy management analysis. First, the optimal sampling interval can be obtained based on energy harvesting, consumption, and remaining conditions. Then, the control gain for each sampling interval is derived by using a backward iteration. Finally, the optimal control strategy is determined as a linear function of the current plant states and previous control strategies. The application of UAV formation flight system demonstrates that better system performance and control stability can be achieved by the proposed joint optimization design for all poor, sufficient, and general energy harvesting scenarios.

Adverse outcomes in chronic myeloid leukemia patients treated with tyrosine kinase inhibitors: Follow-up of patients diagnosed 2002-2017 in a complete coverage and nationwide agnostic register study.

Tyrosine kinase inhibitors (TKIs) have profoundly improved the clinical outcome for patients with chronic myeloid leukemia (CML), but their overall survival is still subnormal and the treatment is associated with adverse events. In a large cohort-study, we assessed the morbidity in 1328 Swedish CML chronic phase patients diagnosed 2002-2017 and treated with TKIs, as compared to that in carefully matched control individuals. Several Swedish patient registers with near-complete nationwide coverage were utilized for data acquisition. Median follow-up was 6 (IQR, 3-10) years with a total follow-up of 8510 person-years for the full cohort. Among 670 analyzed disease categories, the patient cohort showed a significantly increased risk in 142 while, strikingly, no category was more common in controls. Increased incidence rate ratios/IRR (95% CI) for more severe events among patients included acute myocardial infarction (AMI) 2.0 (1.5-2.6), heart failure 2.6 (2.2-3.2), pneumonia 2.8 (2.3-3.5), and unspecified sepsis 3.5 (2.6-4.7). When comparing patients on 2nd generation TKIs vs. imatinib in a within-cohort analysis, nilotinib generated elevated IRRs for AMI (2.9; 1.5-5.6) and chronic ischemic heart disease (2.2; 1.2-3.9), dasatinib for pleural effusion (11.6; 7.6-17.7) and infectious complications, for example, acute upper respiratory infections (3.0; 1.4-6.0). Our extensive real-world data reveal significant risk increases of severe morbidity in TKI-treated CML patients, as compared to matched controls, particularly for 2nd generation TKIs. Whether this increased morbidity may also translate into increased mortality, thus preventing CML patients to achieve a normalized overall survival, needs to be further explored.

The frequency of misattributed paternity in Sweden is low and decreasing: A nationwide cohort study.

BACKGROUND: The occurrence of misattributed paternity has consequences throughout society with implications ranging from inheritance and royal succession to transplantation. However, its frequency in Sweden is unknown. OBJECTIVE: To estimate the contemporary frequency of misattributed paternity in Sweden. METHODS: The study was based on nationwide ABO blood group data and a nationwide register of familial relationships in Sweden. These data were analysed using both a frequentist Poisson model and the Bayesian Gibbs model. The conduct of the study was approved by the regional ethics committee in Stockholm, Sweden (reference numbers 2018/167-31 and 2019-04656). RESULTS: Nearly two million mother-father-offspring family units were included. Overall, the frequency of misattributed paternity was estimated at 1.7% in both models. Misattributed paternity was more common among parents with low educational levels, and has decreased over time to a current 1%. CONCLUSIONS: The misattributed paternity rate is similar to the rates in other West European populations. Apart from widespread societal implications, studies on heritability may consider misattributed paternity as a minor source of error.

Visible-blind ultraviolet narrowband photomultiplication-type organic photodetector with an ultrahigh external quantum efficiency of over 1 000 000.

A visible-blind ultraviolet (UV) photodetector can detect UV signals and is not interfered with by visible light or infrared light in the environment. In order to realize high-performance visible-blind UV organic photodetectors (OPDs), we design photomultiplication-type (PM-type) OPDs by using a novel strategy. Firstly, wide bandgap organic semiconductor materials, which do not absorb visible light, are selected as donors to absorb UV light. Secondly, a very small amount of C60 is used as an acceptor to trap photogenerated electrons. These accumulating electrons near the Al electrode form a potential, which leads to band bending and narrowing of the interface barrier, thereby assisting hole-tunneling injection to form a multiplication. The fabricated visible-blind UV PM-type OPDs with donor/acceptor doping ratio of 50 : 1 exhibit a narrowband response with full-width at half-maximum (FWHM) of approximately 36 nm, an ultrahigh external quantum efficiency of 1.08 × 106% and a remarkable specific detectivity of 1.28 × 1014 jones at 335 nm wavelength under -14 V bias. The UV-to-visible rejection ratio exceeds 103 by adjusting the donor/acceptor mixing ratios. The devices made with other wide bandgap organic materials also showed similar performance, indicating that this device structure provides an effective method for the preparation of high-performance visible-blind UV PM-type OPDs. In addition, we prepared a flexible visible-blind UV PM-type OPD based on a PET substrate and integrated it with a flexible OLED to fabricate a wearable UV monitor, which can visually detect the intensity of UV light.

Short-term health outcomes following whole blood donation: A nationwide, retrospective cohort study.

BACKGROUND: Blood donation is associated with a number of adverse events. Most of these are both uncommon and nonsevere, leading to mild discomfort for the donor at worst. However, adverse events occurring outside of the donation facility have largely not been studied. In this study, we aim to further the understanding by performing the first large-scale analysis of short-term risks following whole blood donation. METHODS: We set up a nationwide cohort of donors who donated whole blood between 1987 and 2018. Analyses were conducted using conditional logistic regression in a self-comparison design, where each donor was compared only to themselves, considering the 30-day risk of 16 outcomes following whole blood donation. Outcomes included cardiac/vascular diseases such as myocardial infarction, unspecified conditions such as fainting, accidents or external causes of injury, and death. RESULTS: A total of 963,311 donors were included; of whom, 19,670 experienced at least one of the outcomes within 30 days of a blood donation. For fainting and hypotonia, we observed transient 2- to 5-fold risk increases on the day of donation and the subsequent 2-3 days. Importantly, the risk increase for the most pronounced effect corresponded to less than one additional events of fainting per 200,000 blood donations. Risks of all other outcomes were either unaffected or lower than expected right after blood donation. DISCUSSION: To conclude, we found no evidence of new or unexpected short-term health effects after blood donation and confirmed that risks of hypotension-related events requiring hospital care are present but small.

An agnostic study of associations between ABO and RhD blood group and phenome-wide disease risk.

Background: There are multiple known associations between the ABO and RhD blood groups and disease. No systematic population-based studies elucidating associations between a large number of disease categories and blood group have been conducted. Methods: Using SCANDAT3-S, a comprehensive nationwide blood donation-transfusion database, we modeled outcomes for 1217 disease categories including 70 million person-years of follow-up, accruing from 5.1 million individuals. Results: We discovered 49 and 1 associations between a disease and ABO and RhD blood groups, respectively, after adjustment for multiple testing. We identified new associations such as a decreased risk of kidney stones and blood group B as compared to blood group O. We also expanded previous knowledge on other associations such as pregnancy-induced hypertension and blood groups A and AB as compared to blood group O and RhD positive as compared to negative. Conclusions: Our findings generate strong further support for previously known associations, but also indicate new interesting relations. Funding: Swedish Research Council.

The blood types that many people are familiar with, such as O-negative or AB-positive, are determined by two systems of antigens or proteins on the surface of the red blood cells: the ABO system and the RhD system. The ABO system types people's blood as A, B or AB if they have A and/or B antigens, or as type O if they have neither; while the RhD system provides the positive or negative label depending on whether or not the RhD antigen is present. Previous studies have found that some ABO blood groups are linked to increased risk and severity of a variety of conditions, including blood clots in veins, bleeding disorders and gastric ulcers. Despite the known influence that blood groups can have on disease, the connection has not been fully studied in many conditions, particularly for RhD status. Knowing the differences in risk and disease severity between different populations could help clinicians identify individuals that they need to monitor more closely and include blood group information in prediction models. To fill this gap in information, Dahlén et al. systematically looked for relationships between diseases and blood groups using records from 5.1 million people on a Swedish national blood donation-transfusion database. Examining 1,217 disease categories revealed that the vast majority did not appear to have a connection to either the ABO or RhD systems of classifying blood. However, the analysis identified 49 diseases with links to ABO blood types and one linked to RhD status. One notable finding was that people with blood group B have an decreased risk of kidney stones. The distribution of blood groups varies significantly around the world, so this relationship between disease and blood group may in part explain regional differences in disease occurrence. In the future, identifying relationships with blood groups may help to better understand the underlying biological mechanisms of diseases and lead to new avenues of research.

Patterns of red-cell transfusion use in obstetric practice in sweden 2003-2017: A nationwide study.

BACKGROUND: There is a paucity of data on patterns of red-cell transfusions in obstetrical care, but some studies have suggested an increase in transfusion rates during the last decade. The purpose of this study was to investigate maternal characteristics, temporal trends and hospital variations in red-cell use in a large contemporary obstetric cohort in Sweden. STUDY DESIGN AND METHODS: Nationwide observational cohort study of maternal red-cell transfusions for all deliveries in Sweden between 2003 and 2017. RESULTS: The proportion of deliveries that received red-cell transfusions was stable during the study period, although the number of red-cell units administered per delivery declined. Among transfused women, most received a low-volume transfusion of 1 or 2 units. Red-cell transfusion was more common among the nulliparous, for instrumental and caesarean deliveries, and with increased maternal age. We saw large variations in transfusion rates between hospitals in Sweden, despite adjusting for age and parity. CONCLUSIONS: In comparison to other high-resource countries we see a high proportion of deliveries with maternal red-cell transfusions. However, we do not see an increase in red-cell use over time.

Costs associated with transfusion therapy in patients with myelodysplastic syndromes in Sweden: a nationwide retrospective cohort study.

BACKGROUND AND OBJECTIVES: Blood transfusion is a cornerstone therapy for many patients with myelodysplastic syndromes (MDS), but ranges from few to no transfusions to intensive transfusion therapy. To date, no large studies have described transfusion use or costs for patients with MDS, accounting for the range of disease severity. MATERIALS AND METHODS: A nationwide cohort study was conducted with all patients diagnosed with MDS in Sweden between 2008 and 2017, based on the Swedish MDS register and the Swedish part of the Scandinavian Donations and Transfusions Database 3 (SCANDAT3-S). Patients were followed from diagnosis until death, emigration, allogeneic hematopoietic stem cell transplantation or end of follow-up. Average cumulative transfusion count and costs over time were calculated, stratified by the revised international prognostic scoring system (IPSS-R) and age at diagnosis. Costs calculations used data on incident transfusions and laboratory testing and were divided into: direct material costs, direct labour costs and laboratory costs. RESULTS: In total, 2311 patients were included in the cohort. In the first four years after diagnosis, patients in the very low IPSS-R category received on average 25 red cell (95% confidence interval, 20-32) and 4 (3-7) platelet transfusions. Conversely, patients in the very high-risk category received on average 171 (135-200) red cell and 66 (51-78) platelet transfusions. Correspondingly, transfusion costs ranged from $8805 ($6482-$11 625) to $80 106 ($61 460-$95 792). CONCLUSION: Transfusion count and costs for patients with MDS increased markedly with IPSS-R risk category, but were similar across age groups. Transfusion costs were considerable for the highest IPSS-R risk categories.

Frequent platelet donation is associated with lymphopenia and risk of infections: A nationwide cohort study.

BACKGROUND: Recently, plateletpheresis donations using a widely used leukoreduction system (LRS) chamber have been associated with T-cell lymphopenia. However, clinical health consequences of plateletpheresis-associated lymphopenia are still unknown. STUDY DESIGN AND METHODS: A nationwide cohort study using the SCANDAT3-S database was conducted with all platelet- and plasmapheresis donors in Sweden between 1996 and 2017. A Cox proportional hazards model, using donations as time-dependent exposures, was used to assess the risk of infections associated with plateletpheresis donations using an LRS chamber. RESULTS: A total of 74 408 apheresis donors were included. Among donors with the same donation frequency, plateletpheresis donors using an LRS chamber were at an increased risk of immunosuppression-related infections and common bacterial infections in a dose-dependent manner. While very frequent donors and infections were rare in absolute terms resulting in wide confidence intervals (CIs), the increased risk was significant starting at one-third or less of the allowed donation frequency in a 10-year exposure window, with hazard ratios reaching 10 or more. No plateletpheresis donors that used an LRS chamber experienced a Pneumocystis jirovecii, aspergillus, disseminated mycobacterial, or cryptococcal infection. In a subcohort (n = 42), donations with LRS were associated with low CD4+ T-cell counts (Pearson's R = -0.41; 95% CI, - 0.63 to -0.12). CONCLUSION: Frequent plateletpheresis donation using an LRS chamber was associated with CD4+ T-cell lymphopenia and an increased risk of infections. These findings suggest a need to monitor T-lymphocyte counts in frequent platelet donors and to conduct future investigations of long-term donor health and for regulators to consider steps to mitigate lymphodepletion in donors.

Patterns of blood use in Sweden from 2008 to 2017: A nationwide cohort study.

BACKGROUND: Transfusion patterns in Sweden have not been characterized on a nationwide level. STUDY DESIGN AND METHODS: We conducted a nationwide descriptive cohort study in Sweden from 2008 to 2017. Data on blood donors, donations, component manufacture, transfusions, and transfused patients were extracted from Swedish portion of the Scandinavian Donations and Transfusions (SCANDAT3-S) database. RESULTS: A total of 708 436 patients received 5 587 684 red cell, plasma, or platelet transfusions during the study period. The age-standardized transfusion rate decreased markedly during the study period for red cell units (from 53 to 39 units/1000 persons) and plasma units (from 11 to 4.9 units/1000 persons), but remained relatively constant for platelet concentrates. The transfusion rate was 30%-40% higher in males than in females in the first year of life, and higher in males over 45 years than in females. Between age 20 and 45, the majority of red cells were transfused to female patients with obstetric indications, whereas trauma was the predominant indication for male contemporaries. In females over 80 years, the largest proportion of red cells were administered due to trauma. Overall, hematological patients received 36% of all platelet units. There were large regional differences in transfusion rates for red cell units, ranging from less than 30 to greater than 60/1000 persons. CONCLUSION: Transfusion rates in Sweden remain high but have decreased strikingly during the study period - with the exception of platelet transfusions. Based on the available data, it is difficult to draw firm conclusions about whether transfusion rates can be further reduced.

The Swedish Scandinavian donations and transfusions database (SCANDAT3-S) - 50 years of donor and recipient follow-up.

BACKGROUND: The two previous versions of the Scandinavian donations and transfusions (SCANDAT) databases, encompassing data on blood donors, blood components, transfusions, and transfused patients linked to national health registers in Sweden and Denmark up until 2012, have been used to study donor health, disease transmission, the role of donor characteristics, and more. STUDY DESIGN AND METHODS: Here we describe the creation of the Swedish portion of the third iteration of SCANDAT - SCANDAT3-S - with follow-up from 1968 to the end of 2017, resulting in up to 50 years of uninterrupted follow-up for donors and recipients. The database now also includes non-transfused non-donors with a blood typing result, increased temporal resolution for transfusions, and linkages to laboratory and drug prescription data. RESULTS: After data cleaning, the database contained 23 579 863 donation records, 21 383 317 transfusion records, and 8 071 066 unique persons with valid identification. In total, the database offers 28 638 436 person-years of follow-up for donors, 13 582 350 person-years of follow-up for transfusion recipients, and 65 613 639 person-years of follow-up for non-recipient non-donors, with possibility for future extension. Additionally, the database includes 167 820 412 dispense records for prescribed drugs and 316,338,442 laboratory test results. Since the latest update in 2012, >99.9% of all donations were traceable to a donor with valid identification, and >97% of all transfusions to a recipient with valid identification. CONCLUSION: With extended follow-up and more clinical detail, the Swedish portion of the third and latest iteration of the SCANDAT database should allow for more comprehensive analysis of donation and transfusion-related research questions.

Risk of hematological malignancy in blood donors: A nationwide cohort study.

BACKGROUND: There has been a concern that blood donations can increase the risk of hematological malignancies. We investigated if blood donations increase the risk of developing hematological malignancies, specifically acute lymphoblastic leukemia, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), chronic myeloid leukemia, Hodgkin lymphoma, and myeloma, as well other non-Hodgkin lymphoma. STUDY DESIGN AND METHODS: In total, the study included 1,021,433 Swedish blood donors, with 19.5 million person-years of follow-up. Two sets of analysis were performed. In the first cohort analysis, standardized incidence ratios (SIRs) were calculated, comparing the incidence of the different types of hematological cancers in blood donors to that of the general population. In the second analysis, a nested case-control study was conducted, investigating the association between number of donations and the risk of each type of malignancy. RESULTS: Apart from a modestly elevated risk of CLL (SIR, 1.07; 95% confidence interval [CI], 1.01-1.15) and a modestly decreased risk of AML (SIR, 0.85; 95% CI, 0.77-0.83), the risk of hematological malignancies did not differ between blood donors and the general population. In the nested case-control study there were no convincing associations between number of prior whole blood donations and site-specific malignancy risk. CONCLUSIONS: There was no convincing evidence of an increased risk in any hematological malignancy when interpreting the results from both series of analyses.

Blood use in hematologic malignancies: a nationwide overview in Sweden between 2000 and 2010.

BACKGROUND: Patients with hematologic malignancies receive large numbers of blood transfusions, and transfusion practices for this patient group are increasingly being scrutinized by randomized controlled trials. However, no studies so far have presented current transfusion statistics on a population level for this patient group. STUDY DESIGN AND METHODS: A retrospective descriptive study was conducted that was based on the Scandinavian Donations and Transfusions Database (SCANDAT2), which includes data on all blood donations and transfusions in Sweden and Denmark since the 1960s. Incident cases of hematologic malignancies were identified in the Swedish Cancer Register between 2000 and 2010. Cases were divided into nine patient groups based on diagnosis. RESULTS: A total of 28,693 patients were included in the cohort. Overall, the transfusion pattern varied depending on diagnosis and age. Patients with aggressive and acute diagnoses generally received more transfusions with immediate decline in transfusion incidence after diagnosis, whereas chronic diagnoses generally maintained more stable, but lower, transfusion incidence. In general, patients with leukemia received more transfusions than patients with lymphoma, and patients with acute leukemia as well as patients that had undergone allogeneic stem cell transplantations received the most transfusions. Within 2 years after diagnosis, patients with acute myeloid leukemia diagnosed at ages 0 to 65 years received on average between 30 to 40 red blood cell transfusions and platelet transfusions, respectively, corresponding to direct material costs close to 200,000 SEK (23,809 USD). CONCLUSION: Results from this population-based overview of blood use in hematologic malignancies showed high variability depending on diagnosis and age.