More than 100 million units of blood are collected worldwide each year, yet the indication for red blood cell (RBC) transfusion and the optimal length of RBC storage prior to transfusion are ...uncertain.
To provide recommendations for the target hemoglobin level for RBC transfusion among hospitalized adult patients who are hemodynamically stable and the length of time RBCs should be stored prior to transfusion.
Reference librarians conducted a literature search for randomized clinical trials (RCTs) evaluating hemoglobin thresholds for RBC transfusion (1950-May 2016) and RBC storage duration (1948-May 2016) without language restrictions. The results were summarized using the Grading of Recommendations Assessment, Development and Evaluation method. For RBC transfusion thresholds, 31 RCTs included 12 587 participants and compared restrictive thresholds (transfusion not indicated until the hemoglobin level is 7-8 g/dL) with liberal thresholds (transfusion not indicated until the hemoglobin level is 9-10 g/dL). The summary estimates across trials demonstrated that restrictive RBC transfusion thresholds were not associated with higher rates of adverse clinical outcomes, including 30-day mortality, myocardial infarction, cerebrovascular accident, rebleeding, pneumonia, or thromboembolism. For RBC storage duration, 13 RCTs included 5515 participants randomly allocated to receive fresher blood or standard-issue blood. These RCTs demonstrated that fresher blood did not improve clinical outcomes.
It is good practice to consider the hemoglobin level, the overall clinical context, patient preferences, and alternative therapies when making transfusion decisions regarding an individual patient. Recommendation 1: a restrictive RBC transfusion threshold in which the transfusion is not indicated until the hemoglobin level is 7 g/dL is recommended for hospitalized adult patients who are hemodynamically stable, including critically ill patients, rather than when the hemoglobin level is 10 g/dL (strong recommendation, moderate quality evidence). A restrictive RBC transfusion threshold of 8 g/dL is recommended for patients undergoing orthopedic surgery, cardiac surgery, and those with preexisting cardiovascular disease (strong recommendation, moderate quality evidence). The restrictive transfusion threshold of 7 g/dL is likely comparable with 8 g/dL, but RCT evidence is not available for all patient categories. These recommendations do not apply to patients with acute coronary syndrome, severe thrombocytopenia (patients treated for hematological or oncological reasons who are at risk of bleeding), and chronic transfusion-dependent anemia (not recommended due to insufficient evidence). Recommendation 2: patients, including neonates, should receive RBC units selected at any point within their licensed dating period (standard issue) rather than limiting patients to transfusion of only fresh (storage length: <10 days) RBC units (strong recommendation, moderate quality evidence).
Research in RBC transfusion medicine has significantly advanced the science in recent years and provides high-quality evidence to inform guidelines. A restrictive transfusion threshold is safe in most clinical settings and the current blood banking practices of using standard-issue blood should be continued.
The AABB (formerly, the American Association of Blood Banks) developed this guideline on appropriate use of platelet transfusion in adult patients.
These guidelines are based on a systematic review ...of randomized, clinical trials and observational studies (1900 to September 2014) that reported clinical outcomes on patients receiving prophylactic or therapeutic platelet transfusions. An expert panel reviewed the data and developed recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework.
The AABB recommends that platelets should be transfused prophylactically to reduce the risk for spontaneous bleeding in hospitalized adult patients with therapy-induced hypoproliferative thrombocytopenia. The AABB recommends transfusing hospitalized adult patients with a platelet count of 10 × 109 cells/L or less to reduce the risk for spontaneous bleeding. The AABB recommends transfusing up to a single apheresis unit or equivalent. Greater doses are not more effective, and lower doses equal to one half of a standard apheresis unit are equally effective. (Grade: strong recommendation; moderate-quality evidence).
The AABB suggests prophylactic platelet transfusion for patients having elective central venous catheter placement with a platelet count less than 20 × 109 cells/L. (Grade: weak recommendation; low-quality evidence).
The AABB suggests prophylactic platelet transfusion for patients having elective diagnostic lumbar puncture with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence).
The AABB suggests prophylactic platelet transfusion for patients having major elective nonneuraxial surgery with a platelet count less than 50 × 109 cells/L. (Grade: weak recommendation; very-low-quality evidence).
The AABB recommends against routine prophylactic platelet transfusion for patients who are nonthrombocytopenic and have cardiac surgery with cardiopulmonary bypass. The AABB suggests platelet transfusion for patients having bypass who exhibit perioperative bleeding with thrombocytopenia and/or evidence of platelet dysfunction. (Grade: weak recommendation; very-low-quality evidence).
The AABB cannot recommend for or against platelet transfusion for patients receiving antiplatelet therapy who have intracranial hemorrhage (traumatic or spontaneous). (Grade: uncertain recommendation; very-low-quality evidence).
Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement ...of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP.
These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations.
The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence).
The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2.
The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence).
The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence).
The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence).
CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.
encodes a wide array of virulence factors. One novel virulence factor, an A
B
toxin known as the typhoid toxin (TT), was recently identified among a variety of
serovars. While past studies have shown ...that some serovars encode both the TT (active subunits CdtB and PltA and binding subunit PltB) and a second binding subunit (ArtB), these serovars were thought to be the exception. Here, we show that genes encoding the TT are detected in more than 100 serovars representing distinct phylogenetic lineages of
subsp.
, although clade B and section Typhi are significantly more likely to encode TT genes than serovars from other clades. Furthermore, we show that 81% of these TT-positive serovars also encode
, suggesting that the cooccurrence of both toxin binding subunits is considerably more common than previously thought. A combination of
modeling, bacterial two-hybrid system screening, and tandem affinity purification (TAP) of toxin subunits suggests that ArtB and PltB interact
, at least under some growth conditions. While different growth conditions yielded slightly higher transcript abundances of
and
, both genes had their highest relative transcript abundances when
was grown under low-Mg
conditions, suggesting that ArtB and PltB may compete for inclusion in the TT. Together, our results suggest that ArtB likely plays an important and previously underappreciated role in the biology of the TT produced by typhoidal and nontyphoidal
While previous reports had suggested that the typhoid toxin (TT) could potentially use ArtB as an alternate binding subunit, this was thought to play a minor role in the evolution and biology of the toxin. In this study, we establish that both TT genes and
are widespread among
subsp.
, suggesting that TT likely plays a broader role in
virulence that extends beyond its proposed role in typhoid fever. Furthermore, our data suggest the selective maintenance of both toxin binding subunits, which may compete for inclusion in the holotoxin. Last, our data support the importance of characterizing diverse nontyphoidal
(NTS) serovars, as the presence of classically defined typhoidal virulence factors among NTS serovars continues to challenge the typhoid-nontyphoid
paradigm.
•We used dendrochronology to reconstruct western spruce budworm outbreaks.•Our record covers three centuries in the interior Pacific Northwest.•Outbreaks were often synchronous across the ...region.•Outbreaks tended to occur during periods of transitional climate.•Increased drought frequency could lead to more outbreaks in the future.
Douglas-fir forests in the interior Pacific Northwest are subject to sporadic outbreaks of the western spruce budworm, a species widely recognized as the most destructive defoliator in western North America. Outbreaks of the western spruce budworm often occur synchronously over broad regions and lead to widespread loss of leaf area and decrease in growth rates in affected stands. In spite of the ecological and economic significance of this defoliator, the mechanisms controlling this species’ population dynamics are still not fully understood. We used dendrochronological methods to reconstruct three centuries of western spruce budworm outbreaks at thirteen sites along a transect running from central Oregon to western Montana and compared the outbreak reconstructions with regional drought history. The reconstructions reveal repeated western spruce budworm outbreaks that sometimes persisted more than a decade and were significantly synchronous among sites. Synchrony was higher in the second half of the record, possibly due to changes in forest composition and structure brought about by land use practices. Across stands and regions, there was a moderately strong relationship between initiation of synchronous outbreaks and periods of transitional climate conditions in which moisture availability was below average prior to outbreak initiation, but above average in the first few years of an outbreak. There was a weak relationship between cessation of outbreaks and one or more years of high moisture availability. Outbreaks tended to occur near the end of droughts. The association between climatic variability and outbreak dynamics observed across this transect indicates that climate is an important driver of western spruce budworm outbreaks. Other factors that we did not test, but that may influence outbreak dynamics include stand structure, forest composition, predation, and phenological synchrony between larvae and host trees. Future changes in western spruce budworm outbreak dynamics will be determined by a combination of changing climate, interactions with other disturbance agents, and changing forest composition and structure. Our results suggest that western spruce budworm outbreaks will likely intensify if drought frequency increases in the future.
Keywords: blood center operations; FFP transfusion; transfusion practices (adult) Byline: Claudia S. Cohn, Lise Estcourt, Brenda J. Grossman, Monica B. Pagano, Elizabeth S. Allen, Evan M. Bloch, ...Arturo Casadevall, Dana V. Devine, Nancy M. Dunbar, Farid Foroutan, Thomas J. Gniadek, Ruchika Goel, Jed Gorlin, Michael J. Joyner, Ryan A. Metcalf, Jay S. Raval, Todd W. Rice, Beth H. Shaz, Ralph R. Vassallo, Jeffrey L. Winters, Gregory Beaudoin, Aaron A. R. Tobian
Species with congruent geographical distributions, potentially caused by common historical and ecological spatial processes, constitute biogeographical units called chorotypes. Nevertheless, the ...degree of spatial range congruence characterizing these groups of species is rarely used as an explicit parameter. Methods conceived for the identification of patterns of shared ranges often suffer from scale bias associated with the use of grids, or the incapacity to describe the full complexity of patterns, from core areas of high spatial congruence, to long gradients of range distributions expanding from these core areas. Here, we propose a simple analytical method, Spatial Congruence Analysis (SCAN), which identifies chorotypes by mapping direct and indirect spatial relationships among species. Assessments are made under a referential value of congruence as an explicit numerical parameter. A one-layered network connects species (vertices) using pairwise spatial congruence estimates (edges). This network is then analyzed for each species, separately, by an algorithm which searches for spatial relationships to the reference species. The method was applied to two datasets: a simulated gradient of ranges and real distributions of birds. The simulated dataset showed that SCAN can describe gradients of distribution with a high level of detail. The bird dataset showed that only a small portion of range overlaps is biogeographically meaningful, and that there is a large variation in types of patterns that can be found with real distributions. Species analyzed separately may converge on similar or identical groups, may be nested in larger chorotypes, or may even generate overlapped patterns with no species in common. Chorotypes can vary from simple ones, composed by few highly congruent species, to complex, with numerous alternative component species and spatial configurations, which offer insights about possible processes driving these patterns in distinct degrees of spatial congruence. Metrics such as congruence, depth, richness, and ratio between common and total areas can be used to describe chorotypes in detail, allowing comparisons between patterns across regions and taxa.
Red blood cell transfusion is a common medical intervention with benefits and harms.
To provide recommendations for use of red blood cell transfusion in adults and children.
Standards for trustworthy ...guidelines were followed, including using Grading of Recommendations Assessment, Development and Evaluation methods, managing conflicts of interest, and making values and preferences explicit. Evidence from systematic reviews of randomized controlled trials was reviewed.
For adults, 45 randomized controlled trials with 20 599 participants compared restrictive hemoglobin-based transfusion thresholds, typically 7 to 8 g/dL, with liberal transfusion thresholds of 9 to 10 g/dL. For pediatric patients, 7 randomized controlled trials with 2730 participants compared a variety of restrictive and liberal transfusion thresholds. For most patient populations, results provided moderate quality evidence that restrictive transfusion thresholds did not adversely affect patient-important outcomes. Recommendation 1: for hospitalized adult patients who are hemodynamically stable, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). In accordance with the restrictive strategy threshold used in most trials, clinicians may choose a threshold of 7.5 g/dL for patients undergoing cardiac surgery and 8 g/dL for those undergoing orthopedic surgery or those with preexisting cardiovascular disease. Recommendation 2: for hospitalized adult patients with hematologic and oncologic disorders, the panel suggests a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (conditional recommendations, low certainty evidence). Recommendation 3: for critically ill children and those at risk of critical illness who are hemodynamically stable and without a hemoglobinopathy, cyanotic cardiac condition, or severe hypoxemia, the international panel recommends a restrictive transfusion strategy considering transfusion when the hemoglobin concentration is less than 7 g/dL (strong recommendation, moderate certainty evidence). Recommendation 4: for hemodynamically stable children with congenital heart disease, the international panel suggests a transfusion threshold that is based on the cardiac abnormality and stage of surgical repair: 7 g/dL (biventricular repair), 9 g/dL (single-ventricle palliation), or 7 to 9 g/dL (uncorrected congenital heart disease) (conditional recommendation, low certainty evidence).
It is good practice to consider overall clinical context and alternative therapies to transfusion when making transfusion decisions about an individual patient.
Fukuyama congenital muscular dystrophy (FCMD), muscle-eye-brain disease (MEB), and Walker-Warburg syndrome are congenital muscular dystrophies (CMDs) with associated developmental brain defects. ...Mutations reported in genes of FCMD and MEB patients suggest that the genes may be involved in protein glycosylation. Dystroglycan is a highly glycosylated component of the muscle dystrophin-glycoprotein complex that is also expressed in brain, where its function is unknown. Here we show that brain-selective deletion of dystroglycan in mice is sufficient to cause CMD-like brain malformations, including disarray of cerebral cortical layering, fusion of cerebral hemispheres and cerebellar folia, and aberrant migration of granule cells. Dystroglycan-null brain loses its high-affinity binding to the extracellular matrix protein laminin, and shows discontinuities in the pial surface basal lamina (glia limitans) that probably underlie the neuronal migration errors. Furthermore, mutant mice have severely blunted hippocampal long-term potentiation with electrophysiologic characterization indicating that dystroglycan might have a postsynaptic role in learning and memory. Our data strongly support the hypothesis that defects in dystroglycan are central to the pathogenesis of structural and functional brain abnormalities seen in CMD.
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