Postpartum hemorrhage (PPH) is an underestimated problem in labor and delivery units and remains a leading cause of maternal morbidity and mortality worldwide. Managing PPH starts with immediate ...recognition and intervention. Goal-directed massive transfusion protocol can be achieved by properly monitoring the maternal coagulation profile during severe obstetric hemorrhage. Conventional coagulation tests (prothrombin time, activated partial thromboplastin time, international normalized ratio, fibrinogen analysis, platelet count) have long turnaround times (occasionally >60 min and provide little information about the
condition of hemostasis) compared to viscoelastic tests (VETs) (available results within 10–30 min). The outcome in actively hemorrhaging patients can be optimized by VETs, including thromboelastography (TEG), rotational thromboelastometry and Sonoclot, providing more individualized blood component therapy compared to traditional 1:1:1 ‘damage control resuscitation’ ratios of blood transfusion strategy. The main limitations of the efficacy of VETs include, but are not limited to, the lack of validation, not having well-established reference ranges for each patient group, results affected by fluid resuscitation regimes and consistent operator proficiency. Although there is limited data with the use of VETs in obstetric patients, the value of VETs is supported by guidelines with increasing evidence. This article will demonstrate two obstetric cases to evaluate the reliability of the TEG in the management of postpartum coagulopathies. The lesson we took from our two cases is presented.
BACKGROUND
Use of universally ABO‐compatible group AB plasma for trauma resuscitation can be challenging due to supply limitations. Many centers are now using group A plasma during the initial ...resuscitation of traumatically injured patients. This study was undertaken to evaluate the impact of this practice on mortality and hospital length of stay (LOS).
STUDY DESIGN AND METHODS
Seventeen trauma centers using group A plasma in trauma patients of unknown ABO group participated in this study. Eligible patients were group A, B, and AB trauma patients who received at least 1 unit of group A plasma. Data collected included patient sex, age, mechanism of injury, Trauma Injury Severity Score (TRISS) probability of survival, and number of blood products transfused. The main outcome of this study was in‐hospital mortality differences between group B and AB patients compared to group A patients. Data on early mortality (≤24 hr) and hospital LOS were also collected.
RESULTS
There were 354 B and AB patients and 809 A patients. The two study groups were comparable in terms of age, sex, TRISS probability of survival, and total number of blood products transfused. The use of group A plasma during the initial resuscitation of traumatically injured patients of unknown ABO group was not associated with increased in‐hospital mortality, early mortality, or hospital LOS for group B and AB patients compared to group A patients.
CONCLUSION
These results support the practice of issuing thawed group A plasma for the initial resuscitation of trauma patients of unknown ABO group.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
IMPORTANCE: The clinical consequences of red blood cell storage age for critically ill pediatric patients have not been examined in a large, randomized clinical trial. OBJECTIVE: To determine if the ...transfusion of fresh red blood cells (stored ≤7 days) reduced new or progressive multiple organ dysfunction syndrome compared with the use of standard-issue red blood cells in critically ill children. DESIGN, SETTING, AND PARTICIPANTS: The Age of Transfused Blood in Critically-Ill Children trial was an international, multicenter, blinded, randomized clinical trial, performed between February 2014 and November 2018 in 50 tertiary care centers. Pediatric patients between the ages of 3 days and 16 years were eligible if the first red blood cell transfusion was administered within 7 days of intensive care unit admission. A total of 15 568 patients were screened, and 13 308 were excluded. INTERVENTIONS: Patients were randomized to receive either fresh or standard-issue red blood cells. A total of 1538 patients were randomized with 768 patients in the fresh red blood cell group and 770 in the standard-issue group. MAIN OUTCOMES AND MEASURES: The primary outcome measure was new or progressive multiple organ dysfunction syndrome, measured for 28 days or to discharge or death. RESULTS: Among 1538 patients who were randomized, 1461 patients (95%) were included in the primary analysis (median age, 1.8 years; 47.3% girls), in which there were 728 patients randomized to the fresh red blood cell group and 733 to the standard-issue group. The median storage duration was 5 days (interquartile range IQR, 4-6 days) in the fresh group vs 18 days (IQR, 12-25 days) in the standard-issue group (P < .001). There were no significant differences in new or progressive multiple organ dysfunction syndrome between fresh (147 of 728 20.2%) and standard-issue red blood cell groups (133 of 732 18.2%), with an unadjusted absolute risk difference of 2.0% (95% CI, –2.0% to 6.1%; P = .33). The prevalence of sepsis was 25.8% (160 of 619) in the fresh group and 25.3% (154 of 608) in the standard-issue group. The prevalence of acute respiratory distress syndrome was 6.6% (41 of 619) in the fresh group and 4.8% (29 of 608) in the standard-issue group. Intensive care unit mortality was 4.5% (33 of 728) in the fresh group vs 3.5 % (26 of 732) in the standard-issue group (P = .34). CONCLUSIONS AND RELEVANCE: Among critically ill pediatric patients, the use of fresh red blood cells did not reduce the incidence of new or progressive multiple organ dysfunction syndrome (including mortality) compared with standard-issue red blood cells. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01977547
BACKGROUNDDelayed hemolytic transfusion reaction (DHTR) with hyperhemolysis is a potentially fatal complication resulting from alloimmunization that can cause severe hemolysis of both transfused and ...intrinsic red blood cells (RBCs). Patients with sickle cell disease often receive multiple RBC units during their lifetime and thus are likely to develop alloantibodies that increase the risk for DHTR. Treatment to decrease hemolysis includes intravenous immunoglobulin (IVIG), steroids, eculizumab, rituximab, and plasmapheresis in addition to erythropoietin (EPO), intravenous (IV) iron, vitamin B12, and folate to support erythropoiesis. RBC transfusion is preferably avoided in DHTR due to an increased risk of exacerbating the hemolysis.CASE REPORTWe report a rare case of anti‐N and anti‐Doa immunoglobulin (Ig)G alloantibody–mediated life‐threatening DHTR with hyperhemolysis in a patient with hemoglobin SS after RBC transfusion for acute chest syndrome who was successfully treated with eculizumab and HBOC‐201 (Hemopure) in addition to steroids, IVIG, EPO, IV iron, and vitamin B12. HBOC‐201 (Hemopure) was successfully used as a RBC alternative in this patient.CONCLUSIONAnti‐N and anti‐Doa IgG alloantibodies can rarely cause severe life‐threatening DHTR with hyperhemolysis. HBOC‐201 (Hemopure) can be a lifesaving alternative in this scenario. Our report also supports the use of eculizumab in DHTR; however, prospective studies are needed to determine the appropriate dose and sequence of eculizumab administration.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
BACKGROUND
Culturing residual blood components after suspected septic transfusion reactions guides management of patients and cocomponents. Current practice, accuracy of provider vital sign ...assessment, and performance of the AABB culture criteria are unknown. A multicenter international study was undertaken to investigate these issues and develop improved culture criteria.
STUDY DESIGN AND METHODS
Retrospective data for all transfusion reactions resulting in residual blood component culture in 2016 were collected from participating hospitals. The performance of the AABB culture criteria were assessed for detection of positive culture results. Modifications to the AABB criteria including 1) recommending culturing in the setting of isolated high fevers, 2) defining hypotension and tachycardia using objective parameters, and 3) incorporating antipyretic use were tested to determine if modifications improved performance. Modifications associated with improvement were incorporate into the BEST criteria. The AABB and the BEST criteria were then tested against a data set enriched for positive culture results to determine which criteria were superior.
RESULTS
Data were collected from 20 centers encompassing 779,143 transfusions, 3,187 reported transfusion reactions, and 1,104 cultured components. There was marked variation in reaction reporting and culturing rates (0.0%‐100.0%). Of 35 total positive component cultures, only one of 35 (2.9%) had concordant patient cultures; 12 of 34 (35.3%) did not have patient cultures performed. The BEST criteria had better sensitivity for detection of a positive culture result compared to the AABB criteria (74% vs. 41%), although specificity decreased (45% vs. 65%).
CONCLUSION
Compared to the AABB criteria, the BEST criteria have improved sensitivity for positive culture detection.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Clostridium septicum infections are rare but often associated with serious if not fatal outcomes. Clostridium septicum infection does not appear to be associated with a single specific defect in ...cellular or humoral immunity. It has been associated with multiple medical problems, including but not limited to leukemia, malignancy of the bowel, other solid tumors, cyclic neutropenia with enterocolitis, diabetes mellitus, and severe arteriosclerosis. Most cases of C septicum are associated with malignancy, and mortality approaches 100% if care is not rendered within 12 to 24 hours.
To evaluate outcomes of patients with C septicum bacteremia, whether treated medically or surgically or both, and to note associated conditions.
Retrospective evaluation of patients found to have C septicum bacteremia in the past 6 years.
Two teaching hospitals, Brooke Army Medical Center (250 beds) and Wilford Hall Medical Center (292 beds), were the source of our patients.
All patients found to have C septicum bacteremia during hospitalization or postmortem examination were included in the study. There were no exclusion criteria.
Mortality associated with C septicum infection.
In our case series, mortality was 33%, which is slightly lower than reported in prior studies (43%-70%).
Presumptive identification based on Gram stain, awareness of C septicum infection as a paraneoplastic syndrome, and prompt, clear communication between laboratory personnel and clinicians are necessary for early diagnosis of C septicum infection. Early institution of antibiotic therapy improves prognosis.
This document was developed through the collaborative efforts of the Society of Critical Care Medicine, the American College of Chest Physicians, and the Association of Organ Procurement ...Organizations. Under the auspices of these societies, a multidisciplinary, multi-institutional task force was convened, incorporating expertise in critical care medicine, organ donor management, and transplantation. Members of the task force were divided into 13 subcommittees, each focused on one of the following general or organ-specific areas: death determination using neurologic criteria, donation after circulatory death determination, authorization process, general contraindications to donation, hemodynamic management, endocrine dysfunction and hormone replacement therapy, pediatric donor management, cardiac donation, lung donation, liver donation, kidney donation, small bowel donation, and pancreas donation. Subcommittees were charged with generating a series of management-related questions related to their topic. For each question, subcommittees provided a summary of relevant literature and specific recommendations. The specific recommendations were approved by all members of the task force and then assembled into a complete document. Because the available literature was overwhelmingly comprised of observational studies and case series, representing low-quality evidence, a decision was made that the document would assume the form of a consensus statement rather than a formally graded guideline. The goal of this document is to provide critical care practitioners with essential information and practical recommendations related to management of the potential organ donor, based on the available literature and expert consensus.
The Community Land Model (CLM) is the land component of the Community Earth System Model (CESM) and is used in several global and regional modeling systems. In this paper, we introduce model ...developments included in CLM version 5 (CLM5), which is the default land component for CESM2. We assess an ensemble of simulations, including prescribed and prognostic vegetation state, multiple forcing data sets, and CLM4, CLM4.5, and CLM5, against a range of metrics including from the International Land Model Benchmarking (ILAMBv2) package. CLM5 includes new and updated processes and parameterizations: (1) dynamic land units, (2) updated parameterizations and structure for hydrology and snow (spatially explicit soil depth, dry surface layer, revised groundwater scheme, revised canopy interception and canopy snow processes, updated fresh snow density, simple firn model, and Model for Scale Adaptive River Transport), (3) plant hydraulics and hydraulic redistribution, (4) revised nitrogen cycling (flexible leaf stoichiometry, leaf N optimization for photosynthesis, and carbon costs for plant nitrogen uptake), (5) global crop model with six crop types and time‐evolving irrigated areas and fertilization rates, (6) updated urban building energy, (7) carbon isotopes, and (8) updated stomatal physiology. New optional features include demographically structured dynamic vegetation model (Functionally Assembled Terrestrial Ecosystem Simulator), ozone damage to plants, and fire trace gas emissions coupling to the atmosphere. Conclusive establishment of improvement or degradation of individual variables or metrics is challenged by forcing uncertainty, parametric uncertainty, and model structural complexity, but the multivariate metrics presented here suggest a general broad improvement from CLM4 to CLM5.
Plain Language Summary
The Community Land Model (CLM) is the land component of the widely used Community Earth System Model (CESM). Here, we introduce model developments included in CLM version 5 (CLM5), the default land component for CESM2 which will be used for the Coupled Model Intercomparison Project (CMIP6). CLM5 includes many new and updated processes including (1) hydrology and snow features such as spatially explicit soil depth, canopy snow processes, a simple firn model, and a more mechanistic river model, (2) plant hydraulics and hydraulic redistribution, (3) revised nitrogen cycling with flexible leaf stoichiometry, leaf N optimization for photosynthesis, and carbon costs for plant nitrogen uptake, (4) expansion to six crop types (global) and time‐evolving irrigated areas and fertilization rates, (5) improved urban building energy model, and (6) carbon isotopes. New optional features include a demographically structured dynamic vegetation model, ozone damage to plants, and fire trace gas emissions coupling to the atmosphere. Model performance is generally improved for most assessed variables and metrics, though clear establishment of improvement or degradation is challenging due to model complexity as well as observational data limitations. Nonetheless, CLM5 is increasingly suited for research into a broad range of societally relevant scientific questions related to the terrestrial system.
Key Points
Updated Community Land Model has more hydrological and ecological process fidelity and more comprehensive representation of land management.
The model is systematically evaluated using International Land Model Benchmarking system and shows marked improvement over prior versions.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Nephronophthisis-related ciliopathies (NPHP-RC) are recessive diseases characterized by renal dysplasia or degeneration. We here identify mutations of DCDC2 as causing a renal-hepatic ciliopathy. ...DCDC2 localizes to the ciliary axoneme and to mitotic spindle fibers in a cell-cycle-dependent manner. Knockdown of Dcdc2 in IMCD3 cells disrupts ciliogenesis, which is rescued by wild-type (WT) human DCDC2, but not by constructs that reflect human mutations. We show that DCDC2 interacts with DVL and DCDC2 overexpression inhibits β-catenin-dependent Wnt signaling in an effect additive to Wnt inhibitors. Mutations detected in human NPHP-RC lack these effects. A Wnt inhibitor likewise restores ciliogenesis in 3D IMCD3 cultures, emphasizing the importance of Wnt signaling for renal tubulogenesis. Knockdown of dcdc2 in zebrafish recapitulates NPHP-RC phenotypes, including renal cysts and hydrocephalus, which is rescued by a Wnt inhibitor and by WT, but not by mutant, DCDC2. We thus demonstrate a central role of Wnt signaling in the pathogenesis of NPHP-RC, suggesting an avenue for potential treatment of NPHP-RC.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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