Expired blood transfusion and mortality outcomes in combat trauma patients.

BACKGROUND: Expired blood can be transfused if clinically indicated but outcome data do not exist. We hypothesized that modestly outdated blood can effectively support a hemorrhaging patient until surgical control is achieved. This study assessed whether expired blood was associated with mortality in combat trauma patients. STUDY DESIGN AND METHODS: A retrospective analysis of Armed Services Blood Program and Department of Defense Trauma Registry databases evaluated combat casualty records (2001-2023). The intervention of interest was transfusion of at least one unit of whole blood (WB), red blood cells (RBC), or platelets within one week past expiration. The outcome of interest was mortality at discharge. A control cohort that only received in-date blood was matched to the treatment cohort for logistic regression analysis. RESULTS: One hundred patients received expired RBCs (86), WB (11), and platelets (3). Mortality at discharge was 11.6% for expired RBC recipients and 13.4% for the control cohort (p = .97). After adjustment for injury severity, expired RBCs were not associated with mortality (OR = 0.40 [95% CI, 0.14-1.16]; p = .09). Of 10 patients who received the most expired RBCs by volume or storage duration, two were deceased at discharge. All 14 expired WB and platelet recipients were alive at discharge, but sample sizes were underpowered for regression analysis. DISCUSSION: Transfusion of modestly outdated RBCs was not associated with mortality in combat trauma patients. Expired WB and platelet recipients did well, but sample sizes were too small to draw significant conclusions. Expired blood should be further investigated for possible use in extenuating circumstances.

Using tele-paramedicine to conduct in-home fall risk reduction after emergency department discharge: Preliminary data.

BACKGROUND: Older adults discharged from our emergency department (ED) do not receive comprehensive fall risk evaluations. We conducted a quality improvement project using an existing Community Tele-Paramedicine (CTP) program to perform in-home fall risk assessment and mitigation after ED discharge. METHODS: High falls-risk patients, as defined by STEADI score >4, were referred for a CTP home visit by community paramedics supervised virtually by emergency physicians. Home hazards assessment, Timed Up and Go test (TUG), medication reconciliation, and psychosocial evaluation were used to develop fall risk mitigation plans. Outcomes assessed at 30 days post ED-discharge included: completed CTP visits, falls, ED revisits, hospital admissions, and referrals. RESULTS: Between November 2022 and June 2023, 104 (65%) patients were discharged and referred to CTP. The mean age of enrolled patients was 80 years, 66% were female, 63% White, 79% on Medicare or Medicaid, most lived with a family member (50%) or alone (38%). Sixty-one (59%) patients received an initial CTP visit, 48 (79%) a follow-up visit, and 12 (11%) declined a visit. Abnormal TUG tests (74%), home hazards (67%), high-risk medications (36%), or need for outpatient follow-up (49%) or additional home services (41%) were frequently identified. At 30 days, only one of the CTP patients reported a fall, one patient had a fall-related ED visit, and one patient was admitted secondary to a fall. CONCLUSIONS: A quality improvement initiative using CTP to perform fall risk reduction after ED discharge identified areas of risk mitigation in the home where most falls take place. Further controlled studies are needed to assess the impact of CTP on clinical outcomes important to patients and health systems.

Variations in emergency hemorrhage panel turnaround times in 2 major medical centers using the same laboratory methods.

OBJECTIVES: Demand for rapid coagulation testing for massive transfusion events led to development of an emergency hemorrhage panel (EHP; hemoglobin, platelet count, prothrombin time/international normalized ratio, and fibrinogen), with laboratory turnaround time (TAT) of less than 20 minutes. Ten years on, we asked if current laboratory practices were meeting that TAT goal and differences were evident in TAT between the 2 major institutions in our system. METHODS: We identified EHPs ordered at our 2 largest hospitals, February 2, 2021, to July 17, 2022, comparing order to specimen draw time, specimen draw to specimen received time, laboratory analytic time, and total TAT results from emergency department and operating room. Site 1 houses a level I trauma center; site 2 includes tertiary care, transplant, and obstetrics services. RESULTS: In total, 1137 EHPs were recorded in our study period. Laboratory TAT was significantly faster at site 1 (~14 vs ~27 minutes, P < .01). Average laboratory TAT was under 20 minutes at site 1 but only for 50% of specimens at site 2. Outlier specimens were collection delays at site 1 and specimen processing delays at site 2. CONCLUSIONS: The EHP can be performed as rapidly as described. However, compromises in laboratory location, available personnel, and processing differences can degrade performance.

Genetic characterization of biohydrogen-producing purple non-sulfur bacteria Rhodobacter johrii MAY2 isolate via whole genome analysis.

Purple non-sulfur bacteria (PNSB) are a diverse group of bacteria studied for various possible applications. They are commonly surveyed in bioenergy research as they produce biohydrogen, a candidate for clean alternative energy. This study aimed to assess the biohydrogen production ability and genetically characterize a high biohydrogen-producing PNSB (MAY2) isolated from Los Baños, Laguna, Philippines via whole genome sequencing (WGS). MAY2, when grown in mixed volatile fatty acids, produced biogas with 38% hydrogen. WGS results revealed that the isolate is positively classified under the genus Rhodobacter johrii. Also, 82 genetic hallmarks for biohydrogen production were found in the isolated genome which are involved in the production of key enzymes and proteins relevant to the photofermentative and hydrogen regulation pathways. Its nitrogenase gene cluster is stringently regulated by two genes, nifA and rofN, whose function and expression are easily affected by several environmental factors.

Novel Variant and Known Mutation in 23S rRNA Gene of Mycoplasma pneumoniae, Northern Vietnam, 2023.

During a 2023 outbreak of Mycoplasma pneumoniae-associated community-acquired pneumonia among children in northern Vietnam, we analyzed M. pneumoniae isolated from nasopharyngeal samples. In almost half (6 of 13) of samples tested, we found known A2063G mutations (macrolide resistance) and a novel C2353T variant on the 23S rRNA gene.

Genome assemblies of 11 bamboo species highlight diversification induced by dynamic subgenome dominance.

Polyploidy (genome duplication) is a pivotal force in evolution. However, the interactions between parental genomes in a polyploid nucleus, frequently involving subgenome dominance, are poorly understood. Here we showcase analyses of a bamboo system (Poaceae: Bambusoideae) comprising a series of lineages from diploid (herbaceous) to tetraploid and hexaploid (woody), with 11 chromosome-level de novo genome assemblies and 476 transcriptome samples. We find that woody bamboo subgenomes exhibit stunning karyotype stability, with parallel subgenome dominance in the two tetraploid clades and a gradual shift of dominance in the hexaploid clade. Allopolyploidization and subgenome dominance have shaped the evolution of tree-like lignified culms, rapid growth and synchronous flowering characteristic of woody bamboos as large grasses. Our work provides insights into genome dominance in a remarkable polyploid system, including its dependence on genomic context and its ability to switch which subgenomes are dominant over evolutionary time.

Massive transfusion protocol reactivation as a novel marker of physician team under-triage after injury.

BACKGROUND: Large trauma centers have protocols for the assessment of injury and triaging of care with attempts to over-triage to ensure adequate care for all patients. We noted that a significant number of patients undergo a second massive transfusion protocol (MTP) activation in the first 24 h of care and conducted a retrospective cohort study of patients involved over a 3-year period. METHODS: Transfusion service records of MTP activations 2019-2021 were linked to Trauma Registry records and divided into cohorts receiving a single versus a reactivation of the MTP. Time of activation and amounts of blood products issued were linked to demographic, injury severity, and outcome data. Categorical and continuous data were compared between cohorts with chi-squared, Fisher's, and Wilcoxan tests as appropriate, and multivariable regression models were used to seek interactions (p < .05). RESULTS: MTP activation was recorded for 1884 acute trauma patients over our 3-year study period, 142 of whom (7.5%) had reactivation. Factors associated with reactivation included older age (46 vs. 40 years), higher injury severity score (ISS, 27 vs. 22), leg injuries, and presentation during morning shift change (5-7 a.m., 3.3% vs. 7.7%). Patients undergoing MTP reactivation used more RBCs (5 U vs. 2 U) and had more ICU days (3 vs. 2). CONCLUSIONS: Older patients and those presenting during shift change are at risk for failure to recognize their complex injury patterns and under-triage for trauma care. The fidelity and granularity of transfusion service records can provide unique opportunities for quality assessment and improvement in trauma care.

Role of α1-GABAA receptors in the serotonergic dorsal raphe nucleus in models of opioid reward, anxiety, and depression.

BACKGROUND: The serotonin (5-hydroxytryptamine (5-HT))-mediated system plays an important role in stress-related psychiatric disorders and substance abuse. Our previous studies showed that stress and drug exposure can modulate the dorsal raphe nucleus (DRN)-5-HT system via γ-aminobutyric acid (GABA)A receptors. Moreover, GABAA receptor-mediated inhibition of serotonergic DRN neurons is required for stress-induced reinstatement of opioid seeking. AIM/METHODS: To further test the role of GABAA receptors in the 5-HT system in stress and opioid-sensitive behaviors, our current study generated mice with conditional genetic deletions of the GABAA α1 subunit to manipulate GABAA receptors in either the DRN or the entire population of 5-HT neurons. The GABAA α1 subunit is a constituent of the most abundant GABAA subtype in the brain and the most highly expressed subunit in 5-HT DRN neurons. RESULTS: Our results showed that mice with DRN-specific knockout of α1-GABAA receptors exhibited a normal phenotype in tests of anxiety- and depression-like behaviors as well as swim stress-induced reinstatement of morphine-conditioned place preference. By contrast, mice with 5-HT neuron-specific knockout of α1-GABAA receptors exhibited an anxiolytic phenotype at baseline and increased sensitivity to post-morphine withdrawal-induced anxiety. CONCLUSIONS: Our data suggest that GABAA receptors on 5-HT neurons contribute to anxiety-like behaviors and sensitivity of those behaviors to opioid withdrawal.

The ventral hippocampus and nucleus accumbens as neural substrates for cocaine contextual memory reconsolidation.

Drug craving triggered by cues that were once associated with drug intoxication is a major contributor to continued drug-seeking behaviors. Addictive drugs engage molecular pathways of associative learning and memory. Reactivated memories are vulnerable to disruption by interference with the process of reconsolidation, hence targeting reconsolidation could be a strategy to reduce cue-induced drug craving and relapse. Here we examined the circuitry of cocaine contextual memory reconsolidation and explored neuroplasticity following memory reactivation. Mice underwent chemogenetic inhibition of either nucleus accumbens (NA) neurons or the glutamatergic projection neurons from the ventral hippocampus (vHPC) to NA using inhibitory designer receptors exclusively activated by designer drugs (iDREADD). Mice underwent cocaine conditioned place preference followed by reactivation of the cocaine contextual memory. Clozapine-N-oxide (CNO) was administered after memory reactivation to inhibit either NA neurons or the accumbens-projecting vHPC neurons during the reconsolidation period. When retested 3 days later, a significant reduction in the previously established preference for the cocaine context was found in both conditions. FosTRAP2-Ai14 mice were used to identify neurons activated by cocaine memory recall and to evaluate plasticity in NA medium spiny neurons (MSNs) and vHPC pyramidal neurons upon recall of cocaine memories. Results indicate a significant increase in dendritic spine density in NA MSNs activated by cocaine memory recall, particularly of the thin spine type. Sholl analysis indicated longer dendritic length and more branching of NA MSNs after cocaine memory recall than without memory reactivation. vHPC neurons showed increased spine density, with the most robust change in stubby spines. These results implicate a circuit involving glutamatergic projections from the vHPC onto NA neurons which is necessary for the reconsolidation of cocaine memories. Interruption of cocaine memory reconsolidation reduced drug-seeking behavior.

A maceration technique for soft plant tissue without hazardous chemicals.

Premise: Current methods for maceration of plant tissue use hazardous chemicals. The new method described here improves the safety of dissection and maceration of soft plant tissues for microscopic imaging by using the harmless enzyme pectinase. Methods and Results: Leaf material from a variety of land plants was obtained from living plants and dried herbarium specimens. Concentrations of aqueous pectinase and soaking schedules were optimized, and tissues were manually dissected while submerged in fresh solution following a soaking period. Most leaves required 2-4 h of soaking; however, delicate leaves could be macerated after 30 min while tougher leaves required 12 h to 3 days of soaking. Staining techniques can also be used with this method, and permanent or semi-permanent slides can be prepared. The epidermis, vascular tissue, and individual cells were imaged at magnifications of 10× to 400×. Only basic safety precautions were needed. Conclusions: This pectinase method is a cost-effective and safe way to obtain images of epidermal peels, separated tissues, or isolated cells from a wide range of plant taxa.

Biocompatible Ti3Au-Ag/Cu thin film coatings with enhanced mechanical and antimicrobial functionality.

BACKGROUND: Biofilm formation on medical device surfaces is a persistent problem that shelters bacteria and encourages infections and implant rejection. One promising approach to tackle this problem is to coat the medical device with an antimicrobial material. In this work, for the first time, we impart antimicrobial functionality to Ti3Au intermetallic alloy thin film coatings, while maintaining their superior mechanical hardness and biocompatibility. METHODS: A mosaic Ti sputtering target is developed to dope controlled amounts of antimicrobial elements of Ag and Cu into a Ti3Au coating matrix by precise control of individual target power levels. The resulting Ti3Au-Ag/Cu thin film coatings are then systematically characterised for their structural, chemical, morphological, mechanical, corrosion, biocompatibility-cytotoxicity and antimicrobial properties. RESULTS: X-ray diffraction patterns reveal the formation of a super hard ß-Ti3Au phase, but the thin films undergo a transition in crystal orientation from (200) to (211) with increasing Ag concentration, whereas introduction of Cu brings no observable changes in crystal orientation. Scanning and transmission electron microscopy analysis show the polyhedral shape of the Ti3Au crystal but agglomeration of Ag particles between crystal grains begins at 1.2 at% Ag and develops into large granules with increasing Ag concentration up to 4.1 at%. The smallest doping concentration of 0.2 at% Ag raises the hardness of the thin film to 14.7 GPa, a 360% improvement compared to the ∼4 GPa hardness of the standard Ti6Al4V base alloy. On the other hand, addition of Cu brings a 315-330% improvement in mechanical hardness of films throughout the entire concentration range of 0.5-7.1 at%. The thin films also show good electrochemical corrosion resistance and a > tenfold reduction in wear rate compared to Ti6Al4V alloy. All thin film samples exhibit very safe cytotoxic profiles towards L929 mouse fibroblast cells when analysed with Alamar blue assay, with ion leaching concentrations lower than 0.2 ppm for Ag and 0.08 ppm for Cu and conductivity tests reveal the positive effect of increased conductivity on myogenic differentiation. Antimicrobial tests show a drastic reduction in microbial survival over a short test period of < 20 min for Ti3Au films doped with Ag or Cu concentrations as low as 0.2-0.5 at%. CONCLUSION: Therefore, according to these results, this work presents a new antimicrobial Ti3Au-Ag/Cu coating material with excellent mechanical performance with the potential to develop wear resistant medical implant devices with resistance to biofilm formation and bacterial infection.

Sex differences in ethanol consumption and drinking despite negative consequences following adolescent social isolation stress in male and female rats.

Alcohol use disorder (AUD) is a debilitating psychiatric disorder characterized by drinking despite negative social and biological consequences. AUDs make up 71% of substance use disorders, with relapse rates as high as 80%. Current treatments stem from data conducted largely in males and fail to target the psychological distress motivating drinking in stress-vulnerable and at-risk populations. Here we employed a rat model and hypothesized that early life stress would reveal sex differences in ethanol intake and drinking despite negative consequences in adulthood. Rats were group housed or isolated postweaning to evaluate sex and stress effects on ethanol consumption in homecage drinking, self-administration (SA), and punished SA (drinking despite negative consequences) in adulthood. Stressed rats showed elevated homecage ethanol intake, an effect more pronounced in females. During SA, males were more sensitive to stress-induced elevations of drinking over time, but females drank more overall. Stressed rats, regardless of sex, responded more for ethanol than their non-stressed counterparts. Stressed females showed greater resistance to punishment-suppressed SA than stressed males, indicating a more stress-resistant drinking phenotype. Results support our hypothesis that adolescent social isolation stress enhances adult ethanol intake in a sex- and model-dependent manner with females being especially sensitive to early life stress-induced elevations in ethanol intake and punished SA in adulthood. Our findings echo the clinical literature which indicates that stress-vulnerable populations are more likely to 'self-medicate' with substances. Elucidating a potential mechanism that underlies why vulnerable populations 'self-medicate' with alcohol can lead towards developing catered pharmacotherapeutics that could reduce punishment-resistant drinking and relapse.

A Collaborative Emergency Medicine and Radiology Pulmonary Nodule Program: Identification of Associated Efficacy and Outcomes.

PURPOSE: Incidental radiologic findings are commonplace, but the episodic nature of emergency department (ED) care makes it challenging to ensure that patients obtain appropriate follow-up. Rates of follow-up range from 30% to 77%, with some studies demonstrating that more than 30% have no follow-up at all. The aim of this study is to describe and analyze the outcomes of a collaborative emergency medicine and radiology initiative to establish a formal workflow for the follow-up of pulmonary nodules identified during ED care. METHODS: A retrospective analysis was performed of patients referred to the pulmonary nodule program (PNP). Patients were divided into two categories: those with follow-up and those who do not have post-ED follow-up. The primary outcome was determining follow-up rates and outcomes, including patients referred for biopsy. The characteristics of patients who completed follow-up compared with those lost to follow-up were also examined. RESULTS: A total of 574 patients were referred to the PNP. Initial follow-up was established in 390 (69.1%); 30.8% were considered lost to follow-up, and more than half of these patients did not respond to initial contact. There were minimal differences in characteristics between patients in these two categories. Of the 259 patients who completed PNP follow-up, 26 were referred for biopsy (13%). CONCLUSIONS: The PNP provided effective transitions of care and potentially improved patient health care. Strategies to further enhance follow-up adherence will provide iterative improvement of the program. The PNP provides an implementation framework for post-ED pulmonary nodule follow-up in other health care systems and can be modified for use with other incidental diagnostic findings.

Age, admission platelet count, and mortality in severe isolated traumatic brain injury: A retrospective cohort study.

BACKGROUND: We asked whether patients >50 years of age with acute traumatic brain injury (TBI) present with lower platelet counts and whether lower platelet counts are independently associated with mortality. METHODS: We combined trauma registry and laboratory data on a retrospective cohort of all patients ≥18 years of age admitted to our Level 1 US regional trauma center 2015-2021 with severe (Head Abbreviated Injury Score [AIS] ≥3), isolated (all other AIS <3) TBI who had a first platelet count within 1 h of arrival. Age and platelet count were assessed continuously and as groups (age 18-50 vs. >50, platelet normals, and at conventional transfusion thresholds). Outcomes such as mean admission platelet counts and in-hospital mortality were assessed categorically and with logistic regression. RESULTS: Of 44,056 patients, 1298 (3%, median age: 52 [IQR 33,68], 76.1% male) met all inclusion criteria with no differences between younger and older age groups for (ISS; 18 [14,26] vs. 17 [14,26], p = .22), New ISS (NISS; 29 [19,50] vs. 28 [17,50], p = .36), or AIS-Head (4 [3,5] vs. 4 [3,5]; p = .87). Patients aged >50 had lower admission platelet counts (219,000 ± 93,000 vs. 242,000 ± 76,000/µL; p < .001) and greater in-hospital mortality (24.5% vs. 15.6%, p < .001) than those 18-50. In multivariable regression, firearms injuries (OR9.08), increasing age (OR1.004), NISS (OR1.007), and AIS-Head (OR1.05), and decreasing admission platelet counts (OR0.998) were independently associated with mortality (p < .001-.041). Platelet transfusion in the first 4 h of care was more frequent among older patients (p < .001). CONCLUSIONS: Older patients with TBI had lower admission platelet counts, which were independently associated with greater mortality.

Dual inhibition of IDO1/TDO2 enhances anti-tumor immunity in platinum-resistant non-small cell lung cancer.

BACKGROUND: The impact of non-small cell lung cancer (NSCLC) metabolism on the immune microenvironment is not well understood within platinum resistance. We have identified crucial metabolic differences between cisplatin-resistant (CR) and cisplatin-sensitive (CS) NSCLC cells with elevated indoleamine 2,3-dioxygenase-1 (IDO1) activity in CR, recognized by increased kynurenine (KYN) production. METHODS: Co-culture, syngeneic, and humanize mice models were utilized. C57BL/6 mice were inoculated with either Lewis lung carcinoma mouse cells (LLC) or their platinum-resistant counterpart (LLC-CR) cells. Humanized mice were inoculated with either A (human CS cells) or ALC (human CR cells). Mice were treated with either IDO1 inhibitor or TDO2 (tryptophan 2,3-dioxygenase-2) inhibitor at 200 mg/kg P.O. once a day for 15 days; or with a new-in-class, IDO1/TDO2 dual inhibitor AT-0174 at 170 mg/kg P.O. once a day for 15 days with and without anti-PD1 antibody (10 mg/kg, every 3 days). Immune profiles and KYN and tryptophan (TRP) production were evaluated. RESULTS: CR tumors exhibited a more highly immunosuppressive environment that debilitated robust anti-tumor immune responses. IDO1-mediated KYN production from CR cells suppressed NKG2D on immune effector natural killer (NK) and CD8+ T cells and enhanced immunosuppressive populations of regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs). Importantly, while selective IDO1 inhibition attenuated CR tumor growth, it concomitantly upregulated the TDO2 enzyme. To overcome the compensatory induction of TDO2 activity, we employed the IDO1/TDO2 dual inhibitor, AT-0174. Dual inhibition of IDO1/TDO2 in CR mice suppressed tumor growth to a greater degree than IDO1 inhibition alone. Significant enhancement in NKG2D frequency on NK and CD8+ T cells and a reduction in Tregs and MDSCs were observed following AT-1074 treatment. PD-L1 (programmed death-ligand-1) expression was increased in CR cells; therefore, we assessed dual inhibition + PD1 (programmed cell death protein-1) blocking and report profound anti-tumor growth and improved immunity in CR tumors which in turn extended overall survival in mice. CONCLUSION: Our study reports the presence of platinum-resistant lung tumors that utilize both IDO1/TDO2 enzymes for survival, and to escape immune surveillance as a consequence of KYN metabolites. We also report early in vivo data in support of the potential therapeutic efficacy of the dual IDO1/TDO2 inhibitor AT-0174 as a part of immuno-therapeutic treatment that disrupts tumor metabolism and enhances anti-tumor immunity.

Ultramassive Transfusion for Trauma in the Age of Hemostatic Resuscitation: A Retrospective Single-Center Cohort From a Large US Level-1 Trauma Center, 2011-2021.

BACKGROUND: Uncontrolled bleeding is a leading cause of death in trauma. In the last 40 years, ultramassive transfusion (UMT; ≥20 units of red blood cells [RBCs]/24 hours) for trauma has been associated with 50% to 80% mortality; the question remains as to whether the increasing number of units transfused in urgent resuscitation is a marker of futility. We asked whether the frequency and outcomes of UMT have changed in the era of hemostatic resuscitation. METHODS: We performed a retrospective cohort study of all UMTs in the first 24 hours of care over an 11-year period at a major US level-1 adult and pediatric trauma center. UMT patients were identified, and a dataset was built by linking blood bank and trauma registry data, then reviewing individual electronic health records. Success in achieving hemostatic proportions of blood products was estimated as (units of plasma + apheresis-platelets-in-plasma + cryoprecipitate-pools + whole blood]/[all units given] ≥0.5. Demographics, injury type (blunt or penetrating), severity (Injury Severity Score [ISS]), severity pattern (Abbreviated Injury Scale score for head [AIS-Head] ≥4), admitting laboratory, transfusion, selected emergency department interventions, and discharge status were assessed using χ2 tests of categorical association, the Student t-test of means, and multivariable logistic regression. P <.05 was considered significant. RESULTS: Among 66,734 trauma admissions from April 6, 2011 to December 31, 2021, we identified 6288 (9.4%) who received any blood products in the first 24 hours, 159 of whom received UMT (0.23%; 154 aged 18-90 + 5 aged 9-17), 81% in hemostatic proportions. Overall mortality was 65% (n = 103); mean ISS = 40; median time to death, 6.1 hours. In univariate analyses, death was not associated with age, sex, or more RBC units transfused beyond 20 but was associated with blunt injury, increasing injury severity, severe head injury, and failure to receive hemostatic blood product ratios. Mortality was also associated with decreased pH and evidence of coagulopathy at admission, especially hypofibrinogenemia. Multivariable logistic regression showed severe head injury, admission hypofibrinogenemia and not receiving a hemostatic resuscitation proportion of blood products as independently associated with death. CONCLUSIONS: One in 420 acute trauma patients at our center received UMT, a historically low rate. A third of these patients lived, and UMT was not itself a marker of futility. Early identification of coagulopathy was possible, and failure to give blood components in hemostatic ratios was associated with excess mortality.

Effects of pre-freeze pathogen reduction with riboflavin and UV light on red cells stored post-thaw in AS-3 additive solution.

BACKGROUND: Pathogen reduction technology (PRT) may improve the safety of RBCs for transfusion. As the Czech Republic considers PRT, we asked what effects riboflavin and UV light PRT pre-freezing has on the post-thaw recovery and properties of cryopreserved RBCs (CRBCs) after deglycerolization and liquid storage. STUDY DESIGN AND METHODS: 24 Group O whole blood (WB) units were leukoreduced and then treated with riboflavin and UV light PRT (Mirasol, Terumo BCT, USA) before cryopreservation (T-CRBC); 20 similarly-collected units were untreated controls (C-CRBC). Units were processed to RBCs and then cryopreserved with 40% glycerol (wt/vol), frozen at -80°C, stored >118 days, reconstituted as deglycerolized RBC units in AS-3, and stored at 4 ± 2°C for 21 days. One treated unit sustained massive hemolysis during the post-thaw wash process and was removed from data analysis. The remaining units were assessed pre-PRT, post-PRT, and post-thaw-wash on days 0, 7, 14, and 21 for hematocrit, volume, hemoglobin per transfusion unit, pH, % hemolysis, hemoglobin in the supernatant, potassium, phosphorus, NH3 , osmolality, ATP, and 2,3-diphosphoglycerate. RESULTS: PRT with leukoreduction caused a 5% loss of RBC followed by a 24% freeze-thaw-wash related loss for a total 28% loss but treated units contained an average of 45 g of hemoglobin, meeting European Union guidelines for CRBC. T-CRBCs displayed higher post-wash hemolysis, potassium, and ammonia concentrations, and lower ATP at the end of storage. CONCLUSIONS: Cryopreserved RBCs from Riboflavin and UV light-treated WB meet the criteria for clinical use for 7 days after thawing and provide additional protection against infectious threats.