Stored platelet hemostatic phenotype and function is not altered when donors are on testosterone replacement therapy.

BACKGROUND: Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. STUDY DESIGN AND METHODS: Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. RESULTS: TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. DISCUSSION: Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.

Testosterone supplementation increases red blood cell susceptibility to oxidative stress, decreases membrane deformability, and decreases survival after cold storage and transfusion.

BACKGROUND: Blood collection from donors on testosterone therapy (TT) is restricted to red blood cell (RBC) concentrates to avoid patient exposure to supraphysiological testosterone (T). The objective of this study was to identify TT-related changes in RBC characteristics relevant to transfusion effectiveness in patients. STUDY DESIGN: This was a two-part study with cohorts of patients and blood donors on TT. In part 1, we conducted longitudinal evaluation of RBCs collected before and at three time points after initiation of T. RBC assays included storage and oxidative hemolysis, membrane deformability (elongation index), and oximetry. In part 2, we evaluated the fate of transfused RBCs from TT donors in immunodeficient mice and by retrospective analyses of NIH's vein-to-vein databases. RESULTS: TT increased oxidative hemolysis (1.45-fold change) and decreased RBC membrane deformability. Plasma free testosterone was positively correlated with oxidative hemolysis (r = .552) and negatively correlated with the elongation index (r = -.472). Stored and gamma-irradiated RBCs from TT donors had lower posttransfusion recovery in mice compared to controls (41.6 ± 12 vs. 55.3 ± 20.5%). Recipients of RBCs from male donors taking T had 25% lower hemoglobin increments compared to recipients of RBCs from non-TT male donors, and had increased incidence (OR, 1.80) of requiring additional RBC transfusions within 48 h of the index transfusion event. CONCLUSIONS: TT is associated with altered RBC characteristics and transfusion effectiveness. These results suggest that clinical utilization of TT RBCs may be less effective in recipients who benefit from longer RBC survival, such as chronically transfused patients.

Comparison of platelet quality and function across apheresis collection platforms.

BACKGROUND: Platelet concentrates (PLT) can be manufactured using a combination of apheresis collection devices and suspension media (plasma or platelet additive solution (PAS)). It is unclear how platelet quality and hemostatic function differ across the current in-use manufacturing methods in the United States. The objective of this study was therefore to compare baseline function of PLT collected using different apheresis collection platforms and storage media. STUDY DESIGN AND METHODS: PLT were collected at two sites with identical protocols (N = 5 per site, N = 10 total per group) on the MCS® + 9000 (Haemonetics; "MCS"), the Trima Accel® 7 (Terumo; "Trima"), and the Amicus Cell Separator (Fresenius Kabi, "Amicus"). MCS PLT were collected into plasma while Trima and Amicus PLT were collected into plasma or PAS (Trima into Isoplate and Amicus into InterSol; yielding groups "TP", "TI" and "AP", "AI", respectively). PLT units were sampled 1 h after collection and assayed to compare cellular counts, biochemistry, and hemostatic function. RESULTS: Differences in biochemistry were most evident between plasma and PAS groups, as anticipated. MCS and TP had the highest clot strength as assessed by viscoelastometry. AI had the lowest thrombin generation capacity. Both TP and TI had the highest responses on platelet aggregometry. AI had the greatest number of microparticles. DISCUSSION: Platelet quality and function differ among collection platforms at baseline. MCS and Trima platelets overall appear to trend toward higher hemostatic function. Future investigations will assess how these differences change throughout storage, and if these in vitro measures are clinically relevant.

Parental sensitivity modifies the associations between maternal prenatal stress exposure, autonomic nervous system functioning and infant temperament in a diverse, low-income sample.

Evidence suggests that adversity experienced during fetal development may shape infant physiologic functioning and temperament. Parental sensitivity is associated with child stress regulation and may act as a buffer against risk for intergenerational health effects of pre- or postnatal adversity. Building upon prior evidence in a racially and ethnically diverse sample of infants (M infant age = 6.5 months) and women of low socioeconomic status, this study examined whether coded parenting sensitivity moderated the association between an objective measure of prenatal stress exposures (Stressful Life Events (SLE)) and infant parasympathetic (respiratory sinus arrhythmia; RSA) or sympathetic (pre-ejection period; PEP) nervous system functioning assessed during administration of the Still-Face-Paradigm (SFP) (n = 66), as well as maternal report of temperament (n = 154). Results showed that parental sensitivity moderated the associations between prenatal stress exposures and infant RSA reactivity, RSA recovery, PEP recovery, and temperamental negativity. Findings indicate that greater parental sensitivity is associated with lower infant autonomic nervous system reactivity and greater recovery from challenge. Results support the hypothesis that parental sensitivity buffers infants from the risk of prenatal stress exposure associations with offspring cross-system physiologic reactivity and regulation, potentially shaping trajectories of health and development and promoting resilience.

Cold-stored platelet function is not significantly altered by agitation or manual mixing.

BACKGROUND: Cold storage of platelets (CS-PLT), results in better maintained hemostatic function compared to room-temperature stored platelets (RT-PLT), leading to increased interest and use of CS-PLT for actively bleeding patients. However, questions remain on best storage practices for CS-PLT, as agitation of CS-PLT is optional per the United States Food and Drug Administration. CS-PLT storage and handling protocols needed to be determined prior to upcoming clinical trials, and blood banking standard operating procedures need to be updated accordingly for the release of units due to potentially modified aggregate morphology without agitation. STUDY DESIGN AND METHODS: We visually assessed aggregate formation, then measured surface receptor expression (GPVI, CD42b (GPIbα), CD49 (GPIa/ITGA2), CD41/61 (ITGA2B/ITGB3; GPIIB/GPIIIA; PACI), CD62P, CD63, HLAI), thrombin generation, aggregation (collagen, adenosine diphosphate [ADP], and epinephrine activation), and viscoelastic function (ExTEM, FibTEM) in CS-PLT (Trima collection, 100% plasma) stored for 21 days either with or without agitation (Phase 1, n = 10 donor-paired units) and then without agitation with or without daily manual mixing to minimize aggregate formation and reduce potential effects of sedimentation (Phase 2, n = 10 donor-paired units). RESULTS: Agitation resulted in macroaggregate formation, whereas no agitation caused film-like sediment. We found no substantial differences in CS-PLT function between storage conditions, as surface receptor expression, thrombin generation, aggregation, and clot formation were relatively similar between intra-Phase storage conditions. DISCUSSION: Storage duration and not condition impacted phenotype and function. CS-PLT can be stored with or without agitation, and with or without daily mixing and standard metrics of hemostatic function will not be significantly altered.

The risk of thromboembolic events with early intravenous 2- and 4-g bolus dosing of tranexamic acid compared to placebo in patients with severe traumatic bleeding: A secondary analysis of a randomized, double-blind, placebo-controlled, single-center trial.

BACKGROUND: Screening for the risk of thromboembolism (TE) due to tranexamic acid (TXA) in patients with severe traumatic injury has not been performed in randomized clinical trials. Our objective was to determine if TXA dose was independently-associated with thromboembolism. STUDY DESIGN AND METHODS: This is a secondary analysis of a single-center, double-blinded, randomized controlled trial comparing placebo to a 2-g or 4-g intravenous TXA bolus dose in trauma patients with severe injury. We used multivariable discrete-time Cox regression models to identify associations with risk for thromboembolic events within 30 days post-enrollment. Event curves were created using discrete-time Cox regression. RESULTS: There were 50 patients in the placebo group, 49 in the 2-g, and 50 in the 4-g TXA group. In adjusted analyses for thromboembolism, a 2-g dose of TXA had an hazard ratio (HR, 95% confidence interval [CI]) of 3.20 (1.12-9.11) (p = .029), and a 4-g dose of TXA had an HR (95% CI) of 5.33 (1.94-14.63) (p = .001). Event curves demonstrated a higher probability of thromboembolism for both doses of TXA compared to placebo. Other parameters independently associated with thromboembolism include time from injury to TXA administration, body mass index, and total blood products transfused. DISCUSSION: In patients with severe traumatic injury, there was a dose-dependent increase in the risk of at least one thromboembolic event with TXA. TXA should not be withheld, but thromboembolism screening should be considered for patients receiving a dose of at least 2-g TXA intravenously for traumatic hemorrhage.

Mutant three-repeat tau expression initiates retinal ganglion cell death through Caspase-2.

The microtubule-associated protein tau is implicated in multiple degenerative diseases including retinal diseases such as glaucoma; however, the way tau initiates retinopathy is unclear. Previous retinal assessments in mouse models of tauopathy suggest that mutations in four-repeat (4R) tau are associated with disease-induced retinal dysfunction, while shifting tau isoform ratio to favor three-repeat (3R) tau production enhanced photoreceptor function. To further understand how alterations in tau expression impact the retina, we analyzed the retinas of transgenic mice overexpressing mutant 3R tau (m3R tau-Tg), a model known to exhibit Pick's Disease pathology in the brain. Analysis of retinal cross-sections from young (3 month) and adult (9 month) mice detected asymmetric 3R tau immunoreactivity in m3R tau-Tg retina, concentrated in the retinal ganglion and amacrine cells of the dorsal retinal periphery. Accumulation of hyperphosphorylated tau was detected specifically in the detergent insoluble fraction of the adult m3R tau-Tg retina. RNA-seq analysis highlighted biological pathways associated with tauopathy that were uniquely altered in m3R tau-Tg retina. The upregulation of transcript encoding apoptotic protease caspase-2 coincided with increased immunostaining in predominantly 3R tau positive retinal regions. In adult m3R tau-Tg, the dorsal peripheral retina of the adult m3R tau-Tg exhibited decreased cell density in the ganglion cell layer (GCL) and reduced thickness of the inner plexiform layer (IPL) compared to the ventral peripheral retina. Together, these data indicate that mutant 3R tau may mediate toxicity in retinal ganglion cells (RGC) by promoting caspase-2 expression which results in RGC degeneration. The m3R tau-Tg line has the potential to be used to assess tau-mediated RGC degeneration and test novel therapeutics for degenerative diseases such as glaucoma.

Efficacy of Early Prophylaxis Against Catheter-Associated Thrombosis in Critically Ill Children: A Bayesian Phase 2b Randomized Clinical Trial.

OBJECTIVES: We obtained preliminary evidence on the efficacy of early prophylaxis on the risk of central venous catheter-associated deep venous thrombosis and its effect on thrombin generation in critically ill children. DESIGN: Bayesian phase 2b randomized clinical trial. SETTING: Seven PICUs. PATIENTS: Children less than 18 years old with a newly inserted central venous catheter and at low risk of bleeding. INTERVENTION: Enoxaparin adjusted to anti-Xa level of 0.2-0.5 international units/mL started at less than 24 hours after insertion of central venous catheter (enoxaparin arm) versus usual care without placebo (usual care arm). MEASUREMENTS AND MAIN RESULTS: At the interim analysis, the proportion of central venous catheter-associated deep venous thrombosis on ultrasonography in the usual care arm, which was 54.2% of 24 children, was significantly higher than that previously reported. This resulted in misspecification of the preapproved Bayesian analysis, reversal of direction of treatment effect, and early termination of the randomized clinical trial. Nevertheless, with 30.4% of 23 children with central venous catheter-associated deep venous thrombosis on ultrasonography in the enoxaparin arm, risk ratio of central venous catheter-associated deep venous thrombosis was 0.55 (95% credible interval, 0.24-1.11). Including children without ultrasonography, clinically relevant central venous catheter-associated deep venous thrombosis developed in one of 27 children (3.7%) in the enoxaparin arm and seven of 24 (29.2%) in the usual care arm (p = 0.02). Clinically relevant bleeding developed in one child randomized to the enoxaparin arm. Response profile of endogenous thrombin potential, a measure of thrombin generation, was not statistically different between trial arms. CONCLUSIONS: These findings suggest the efficacy and safety of early prophylaxis that should be validated in a pivotal randomized clinical trial.

Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro.

BACKGROUND: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf-stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction. STUDY DESIGN AND METHODS: Hemostatic adjunct study products were psoralen-treated PR-cryoprecipitated fibrinogen complex (PR-Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR-Cryo FC and Cryo were stored for 10 days at 20-24°C. Adjuncts were added to coagulopathies (dilutional, 3:7 whole blood [WB]:normal saline; or lytic, WB + 75 ng/ml tissue plasminogen activator), and hemostatic function was assessed by rotational thromboelastometry and thrombin generation. RESULTS: PR of cryoprecipitate did not reduce levels of FVIII, FXIII, or VWF. PR-Cryo FC rescued dilutional coagulopathy similarly to Cryo, while generating significantly more thrombin than FibCon, which also rescued dilutional coagulopathy. Storage out to 10 days at 20-24°C did not diminish the hemostatic function of PR-Cryo FC. DISCUSSION: PR-Cryo FC provides similar and/or improved hemostatic rescue compared to FibCon in dilutional coagulopathies, and this rescue ability is stable over 10 days of storage. In hemorrhaging patients, where every minute delay is associated with a 5% increase in mortality, the immediate availability of PR-Cryo FC has the potential to improve outcomes.

Reducing Venous Thromboembolism Risk Through a Collaborative Team Approach.

PURPOSE: Venous thromboembolism (VTE) is a preventable cause of death following surgical procedures and is associated with increased cost and patient complications. The purpose of this article is to outline a collaborative team approach to reducing VTE rates within an organization in an effort to increase the quality and safety of care provided. DESIGN: An interdisciplinary team collaborated on an approach to reduce VTE rates within the organization following a literature review of best practices related to risk assessment, nurse driven protocols, interdisciplinary collaboration, and autonomy. METHODS: Through an interdisciplinary collaborative effort, improvements were made toward decreasing rates of the patient safety indicator-12: perioperative pulmonary embolism/deep vein thrombosis. FINDINGS: Following implementation of several initiatives, the VTE rate within the organization steadily decreased and has remained below benchmark for over 18 months. CONCLUSION: The successful improvements led by the interdisciplinary VTE Committee demonstrate the impact of best practices implemented through shared decision-making and autonomy.

Metabolic phenotypes of standard and cold-stored platelets.

BACKGROUND: Conventional platelet (PLT) storage at room temperature under continuous agitation results in a limited shelf life (5 days) and an increased risk of bacterial contamination. However, both of these aspects can be ameliorated by cold storage. Preliminary work has suggested that PLTs can be cold stored for up to 3 weeks, while preserving their metabolic activity longer than in PLTs stored at room temperature. As such, in the present study, we hypothesized that the metabolic phenotypes of PLTs stored at 4°C for 3 weeks could be comparable to that of room temperature-stored PLTs at 22°C for 5 days. STUDY DESIGN AND METHODS: Metabolomics analyses were performed on nine apheresis PLT concentrates stored either at room temperature (22°C) for 5 days or refrigerated conditions (4°C) for up to 3 weeks. RESULTS: Refrigeration did not impact the rate of decline in glutamine or the intracellular levels of Krebs cycle metabolites upstream to fumarate and malate. It did, however, decrease oxidant stress (to glutathione and purines) and slowed down the activation of the pentose phosphate pathway, glycolysis, and fatty acid metabolism (acyl-carnitines). CONCLUSION: The overall metabolic phenotypes of 4°C PLTs at Storage Day 10 are comparable to PLTs stored at 22°C at the end of their 5-day shelf life, while additional changes in glycolysis, purine, and fatty acid metabolism are noted by Day 21.

The use of low-titer group O whole blood is independently associated with improved survival compared to component therapy in adults with severe traumatic hemorrhage.

BACKGROUND: There is a resurgence in the use of low-titer group O whole blood (LTOWB) for hemorrhagic shock. We hypothesized the use of LTOWB compared to component therapy (CT) would be independently associated with improved 24-hour mortality. STUDY DESIGN AND METHODS: In this prospective observational study, trauma patients 18 years of age or older with massive transfusion protocol activations were included from August 17, 2018, to May 14, 2019. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour blood product totals, multiple organ dysfunction scores (MODS), and 28-day mortality. Multivariable logistic regression (MVLR) and Cox regression were performed to determine independent associations. RESULTS: There were no clinically meaningful differences in measures of injury severity between study groups (CT, n = 42; LTOWB, n = 44). There was no difference in MODS between study groups. The unadjusted mortality was not statistically different between the study groups (9/42 [21%] for CT vs. 7/44 [16%] for LTOWB; p = 0.518). In the MVLR model, LTOWB increased the odds of 24-hour survival by 23% (odds ratio 0.81, 95% confidence interval 0.69-0.96; p = 0.017). Adjusted survival curve analysis indicated improved survival at both 24 hours and 28 days for LTOWB patients (p < 0.001). Further stratification showed an association between LTOWB use and survival when maximum clot firmness (MCF) was 60 mm or less (p = 0.009). CONCLUSIONS: The use of LTOWB is independently associated with improved 24-hour and 28-day survival, and does not increase organ dysfunction at 72 hours. Use of LTOWB most impacted survival of patients with reduced clot firmness (MCF ≤60 mm). Collectively, these data support the clinical use and continued study of LTOWB for hemostatic resuscitation.

Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial.

PURPOSE: We conducted a randomized, double-blind, vehicle-controlled clinical trial to investigate the use of a new proprietary hyaluronan (HA) formulation for the prevention of acute skin toxicity in breast cancer patients undergoing radiotherapy (RT). METHODS: Thirty women with breast cancer undergoing whole breast RT were enrolled. Each patient was randomly assigned to HA formulation (study cream, S) on the medial or lateral half of the irradiated breast and the control cream (placebo, P) on the other half. The primary endpoint was physician's evaluation of skin symptoms at week 5 during RT and week 2 post-RT. We also collected patients' independent assessment of skin after RT, patient's product preference, and an independent physician panel assessment of skin reactions based on photographs. RESULTS: Twenty-eight patients were evaluable. On physician's evaluation, there was no significant difference in radiation dermatitis between S and P and no overall preference to either cream at week 5 during or week 2 post-RT. More patients preferred S in evaluating skin appearance and skin reactions, but this did not reach statistical significance. Univariate analysis showed that physicians had an overall preference to the S cream at week 2 post-RT in patients with larger breasts. On the independent panel assessment, 3 reviewers saw no significant difference in radiation toxicity, whereas one reviewer reported better skin outcome with S cream at week 5. CONCLUSIONS: We found a nonstatistically significant patient preference but overall no significant radioprotective effects for this HA formulation compared with placebo except in patients with larger breasts. TRIAL REGISTRATION: The study was registered at www.clinicaltrials.gov (NCT02165605).

Effect of leukoreduction and pathogen reduction on the hemostatic function of whole blood.

BACKGROUND: There is renewed interest in the use of whole blood (WB) for resuscitation of patients in hemorrhagic shock. Leukoreduction with platelet-sparing filters and pathogen reduction may be used to improve the safety profile of WB, yet the effects of leukoreduction and pathogen reduction on WB hemostatic function are not well characterized. STUDY DESIGN AND METHODS: Blood from 32 healthy group O donors was divided into treatment groups (n = 8 for each group): untreated, pathogen reduced (PR+ ), leukoreduced using an in-line filter (LR+ ), or PR+ LR+ . Units were stored without agitation for 21 days between 1° and 6°C, with sampling on days 0 (pre- and post-treatments), 1, 3, 5, 10, 15, and 21 for hemostatic function as assessed by thromboelastometry, thrombin generation, platelet activation factors, and platelet impedance aggregometry. RESULTS: From day 3 (D3) to D15 of storage, platelet count was reduced in PR+ /LR+ units compared to PR- /LR- units. From D10 to D21 of storage, maximum clot firmness (MCF) was reduced in PR+ /LR+ units compared to PR- /LR- units. From D3 to D21 of storage, platelet aggregation was reduced in PR+ /LR+ units compared to PR- /LR- units. Total thrombin generation was similar in all groups from D0 to D21. CONCLUSIONS: The combination of LR with a platelet-sparing filter and PR significantly reduces hemostatic function compared to either treatment alone or untreated WB. The clinical consequences of LR and PR of WB in patients with severe bleeding should be examined in trials before both are used in combination in patients.

Effect of plasma processing and storage on microparticle abundance, nitric oxide scavenging, and vasoactivity.

BACKGROUND: We set out to define the impact of collection, processing, and storage on plasma product microparticle (MP) abundance, potential for nitric oxide (NO) scavenging, and vasoactivity. STUDY DESIGN AND METHODS: Three currently US licensed products were tested: liquid plasma (LP), fresh frozen plasma (FFP), and solvent detergent plasma (SDP), along with a product under development, spray-dried solvent detergent plasma (SD-SDP) with/without beads. Vasoactivity was assessed in vitro using rabbit aortic vascular rings; MP abundance was determined by flow cytometry; and NO scavenging capacity/rate was determined using a biochemical NO consumption assay. All samples were analyzed unprocessed and following centrifugation at two speeds (2,500× g to remove platelets, and 25,000× g to remove microparticles). RESULTS: Significant differences in vasoactivity were observed, with SD-SDP minus beads demonstrating the greatest constriction and FFP the lowest constriction response. All products exhibited the same total NO scavenging capacity; however, significant differences were observed in the maximal rate of scavenging, with SD-SDP minus beads and FFP reacting fastest and SDP the slowest. Across all products, platelet and microparticle depletion had no effect on vasoactivity or NO scavenging (total or rate). Microparticles (RBC derived) were found only in FFP and LP, with relative abundance (LP > FFP). Additionally, storage had no effect on total or RBC-derived MP abundance, NO scavenging, or vasoactivity. CONCLUSION: Although vasoactivity differed between plasma products, we did not find similar differences in either total or RBC-derived MP abundance or NO scavenging capacity/rate.

Donor-specific HLA antibody-mediated complement activation is a significant indicator of antibody-mediated rejection and poor long-term graft outcome during lung transplantation: a single center cohort study.

Complement-mediated allograft injury, elicited by donor-specific HLA antibodies (DSA), is a defining pathophysiological characteristic of allograft damage. We aimed to study DSA-induced complement activation as a diagnostic marker of antibody-mediated rejection (AMR) and a risk stratification tool for graft loss in the context of lung transplantation (LT). We identified 38 DSA-positive patients whose serum samples were submitted for C3d deposition testing via the C3d assay. Among these 38 patients, 15 had AMR (DSAPos AMRPos ). Results were reported for each patient as the C3d ratio for each DSA, the immunodominant DSA, and the C3d ratio for all DSA present in a sample (C3d ratioSUM ). DSAPos AMRPos patients had higher C3d ratioSUM values (58.66 (-1.32 to 118.6) vs. 1.52 (0.30 to 2.74), P = 0.0016) and increased immunodominant C3d ratios (41.87 (1.72 to 82.02) vs. 0.69 (0.21 to 1.19), P = 0.001) when compared with DSAPos AMRNeg patients. Specificity and calculated positive predictive value of the immunodominant C3d ratio and BCMsum tests for AMR diagnosis were both 100% (CI = 17.4-100) in this cohort. Worst graft survival was associated with both immunodominant C3d ratio ≥4 or C3d ratioSUM ≥10 or BCMsum >7000, suggesting that the antibody composition and/or strength are the principal determinants of an HLA DSA's capacity to activate complement.

Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Surveillance Data Published Between April 1, 2016 and January 31, 2017 - United States.

The Summary of Notifiable Noninfectious Conditions and Disease Outbreaks: Surveillance Data Published Between April 1, 2016 and January 31, 2017 - United States, herein referred to as the Summary (Noninfectious), contains official statistics for nationally notifiable noninfectious conditions and disease outbreaks. This Summary (Noninfectious) is being published in the same volume of MMWR as the annual Summary of Notifiable Infectious Diseases and Conditions (1). Data on notifiable noninfectious conditions and disease outbreaks from prior years have been published previously (2,3).

Summary of Notifiable Infectious Diseases and Conditions - United States, 2015.

The Summary of Notifiable Infectious Diseases and Conditions - United States, 2015 (hereafter referred to as the summary) contains the official statistics, in tabular and graphical form, for the reported occurrence of nationally notifiable infectious diseases and conditions in the United States for 2015. Unless otherwise noted, data are final totals for 2015 reported as of June 30, 2016. These statistics are collected and compiled from reports sent by U.S. state and territories, New York City, and District of Columbia health departments to the National Notifiable Diseases Surveillance System (NNDSS), which is operated by CDC in collaboration with the Council of State and Territorial Epidemiologists (CSTE). This summary is available at https://www.cdc.gov/MMWR/MMWR_nd/index.html. This site also includes summary publications from previous years.

Introduction to the Summary of Notifiable Noninfectious Conditions and Disease Outbreaks - United States.

With this 2016 Summary of Notifiable Noninfectious Conditions and Disease Outbreaks - United States, CDC is publishing official statistics for the occurrence of nationally notifiable noninfectious conditions and disease outbreaks for the second time in the same volume of MMWR as the annual Summary of Notifiable Infectious Diseases and Conditions (1). As was the case for the 2015 Summary of Notifiable Noninfectious Conditions and Disease Outbreaks (2), this joint publication is the result of a request by the Council of State and Territorial Epidemiologists (CSTE) to provide readers with information on all nationally notifiable conditions and disease outbreaks in a single publication.