Novel method for determining when a field-collected donor unit is sufficiently full.

BACKGROUND: Whole blood (WB) collections can occur downrange for immediate administration. An important aspect of these collections is determining when the unit is sufficiently full. This project tested a novel method for determining when a field collection is complete. METHODS: The amount of empty space at the top of WB units, destined to become LTOWB or separated into components, that were collected at blood centers or hospitals was measured by holding a WB unit off the ground and placing the top of a piece of string where the donor tubing entered the bag. The string was marked where it intersected the top of the column of blood in the bag and measured from the top. The WB units were also weighed. RESULTS: A total of 15 different bags, two of which were measured in two different filling volumes, from 15 hospitals or blood centers were measured and weighed. The most commonly used blood bag, Terumo Imuflex SP, had a median string length of 9 mm (range: 2-24 mm) and weighed a median of 565.1 g (range: 524.8-636.7 g). CONCLUSION: Pieces of string can be precut to the appropriate length depending on the type of bag before a mission where field WB collections might be required and a mark placed on the bag before the collection commences to indicate when the unit is full.

Rate of D-alloimmunization in trauma does not depend on the number of RhD-positive units transfused: The BEST collaborative study.

BACKGROUND: Evidence indicates the life-saving benefits of early blood product transfusion in severe trauma resuscitation. Many of these products will be RhD-positive, so understanding the D-alloimmunization rate is important. METHODS: This was a multicenter, retrospective study whereby injured RhD-negative patients between 18-50 years of age who received at least one unit of RhD-positive red blood cells (RBC) or low titer group O whole blood (LTOWB) during their resuscitation between 1 January, 2010 through 31 December, 2019 were identified. If an antibody detection test was performed ≥14 days after the index RhD-positive transfusion then basic demographic information was collected, including whether the patient became D-alloimmunized. The overall D-alloimmunization rate, and the rate stratified by the number of units transfused, were calculated. RESULTS: Data were collected from nine institutions. Five institutions reported fewer than 10 eligible patients each and were excluded. From the remaining four institutions, all from the USA, there were 235 eligible patients; 77 (random effects estimate: 32.7%; 95% CI: 19.1-50.1%) became D-alloimmunized. Three of the institutions reported D-alloimmunization rates ≥38.6%, while the remaining institution's rate was 12.2%. In both random and fixed-effects models, the rate of D-alloimmunization was not significantly different between those who received one RhD-positive unit and those who received multiple RhD-positive units. CONCLUSION: In this large, multicenter study of injured patients, the overall rate of D-alloimmunization fell within the range previously reported. The rate of D-alloimmunization did not increase as the number of transfused RhD-positive units increased. These data can help to inform RhD type selection decisions.

Single Plasma Unit Transfusions in Adults Are Either Unnecessary or Underdosed.

OBJECTIVES: Previous studies of blood product use have shown higher inappropriate use of plasma compared with other products. Given typical weight-based dosing of plasma, we hypothesized that single plasma transfusions in adults would either be a nontherapeutic dose or outside clinical guidelines. METHODS: A single-center, retrospective review of nonoperative, nonapheresis plasma use was conducted from January 2020 to April 2020. Plasma transfusions were reviewed for compliance with clinical guidelines formulated at our institution as well as national and society guidelines. RESULTS: During the study period, 313 units of plasma were transfused. Of these, 152 (48.6%) were given against institutional or national guidelines, 126 plasma units (40.3%) were transfused as single units, and 187 (59.7%) were given as part of multiple-unit transfusions. All single-unit plasma transfusions during the study period were either underdosed or outside clinical guidelines. Units transfused with an indication of "Other" were significantly more likely to be outside clinical guidelines. CONCLUSIONS: Nonoperative, nonapheresis plasma use is often outside clinical guidelines. Single-unit plasma transfusions in adults are a potential target for patient blood management programs seeking to minimize unnecessary plasma use.

THOR-AABB Working Party Recommendations for a Prehospital Blood Product Transfusion Program.

The evidence for the lifesaving benefits of prehospital transfusions is increasing. As such, emergency medical services (EMS) might increasingly become interested in providing this important intervention. While a few EMS and air medical agencies have been providing exclusively red blood cell (RBC) transfusions to their patients for many years, transfusing plasma in addition to the RBCs, or simply using low titer group O whole blood (LTOWB) in place of two separate components, will be a novel experience for many services. The recommendations presented in this document were created by the Trauma, Hemostasis and Oxygenation Research (THOR)-AABB (formerly known as the American Association of Blood Banks) Working Party, and they are intended to provide a framework for implementing prehospital blood transfusion programs in line with the best available evidence. These recommendations cover all aspects of such a program including storing, transporting, and transfusing blood products in the prehospital phase of hemorrhagic resuscitation.

Tick-borne encephalitis among US travellers, 2010-20.

BACKGROUND: Tick-borne encephalitis (TBE) is an arboviral disease that is focally endemic in parts of Europe and Asia. TBE cases among US travellers are rare, with previous reports of only six cases among civilian travellers through 2009 and nine military-related cases through 2020. A TBE vaccine was licenced in the USA in August 2021. Understanding TBE epidemiology and risks among US travellers can help with the counselling of travellers going to TBE-endemic areas. METHODS: Diagnostic testing for TBE in the USA is typically performed at the Centers for Disease Control and Prevention (CDC) because no commercial testing is available. Diagnostic testing for TBE at CDC since 2010 was reviewed. For individuals with evidence of TBE virus infection, information was gathered on demographics, clinical presentations and risk factors for infection. RESULTS: From 2010-20, six patients with TBE were identified. Cases occurred among both paediatric and adult travellers and all were male. Patients were diagnosed with meningitis (n = 2) or encephalitis (n = 4); none died. Cases had travelled to various countries in Europe or Russia. Three cases reported visiting friends or relatives. Activities reported included hiking, camping, trail running, or working outdoors, and two cases had a recognized tick bite. CONCLUSIONS: TBE cases among US travellers are uncommon, with these six cases being the only known TBE cases among civilian travellers during this 11-year period. Nonetheless, given potential disease severity, pre-travel counselling for travellers to TBE-endemic areas should include information on measures to reduce the risk for TBE and other tick-borne diseases, including possible TBE vaccine use if a traveller's itinerary puts them at higher risk for infection. Clinicians should consider the diagnosis of TBE in a patient with a neurologic or febrile illness recently returned from a TBE-endemic country, particularly if a tick bite or possible tick exposure is reported.

A viral genome packaging motor transitions between cyclic and helical symmetry to translocate dsDNA.

Molecular segregation and biopolymer manipulation require the action of molecular motors to do work by applying directional forces to macromolecules. The additional strand conserved E (ASCE) ring motors are an ancient family of molecular motors responsible for diverse biological polymer manipulation tasks. Viruses use ASCE segregation motors to package their genomes into their protein capsids and provide accessible experimental systems due to their relative simplicity. We show by cryo-EM-focused image reconstruction that ASCE ATPases in viral double-stranded DNA (dsDNA) packaging motors adopt helical symmetry complementary to their dsDNA substrates. Together with previous data, our results suggest that these motors cycle between helical and planar configurations, providing a possible mechanism for directional translocation of DNA. Similar changes in quaternary structure have been observed for proteasome and helicase motors, suggesting an ancient and common mechanism of force generation that has been adapted for specific tasks over the course of evolution.

Prehospital Plasma Transfusion: What Does the Literature Show?

BACKGROUND: Early initiation of blood products transfusion after injury has been associated with improved patient outcomes following traumatic injury. The ability to transfuse patients' plasma in the prehospital setting provides a prime opportunity to begin resuscitation with blood products earlier and with a more balanced plasma: RBC ratio than what has traditionally been done. Published studies on the use of prehospital plasma show a complex relationship between its use and improved survival. SUMMARY: Examination of the literature shows that there may be a mortality benefit from the use of prehospital plasma, but that it may be limited to certain subgroups of trauma patients. The likelihood of realizing these survival benefits appears to be predicted by several factors including the type of injury, length of transport time, presence of traumatic brain injury, and total number of blood products transfused, whether the patient required only a few products or a massive transfusion. When taken as a whole the evidence appears to show that prehospital plasma may have a mortality benefit that is most clearly demonstrated in patients with blunt injuries, moderate transfusion requirements, traumatic brain injury, and/or transport time greater than 20 min, as well as those who demonstrate a certain cytokine expression profile. KEY MESSAGES: The evidence suggests that a targeted use of prehospital plasma will most likely maximize the benefits from the use of this limited resource. It is also possible that prehospital plasma may best be provided through whole blood as survival benefits were greatest in patients who received both prehospital plasma and RBCs.

Seasonal Activity of Haemaphysalis longicornis (Acari: Ixodidae) in Southern New York State.

The Asian longhorned tick, Haemaphysalis longicornis Neumann, is a species native to eastern Asia that has recently been discovered in the United States. In its native range, H. longicornis transmits pathogens that cause disease in humans and livestock. It is currently unknown whether H. longicornis will act as a vector in the United States. Understanding its seasonal activity patterns will be important in identifying which times of the year represent greatest potential risk to humans and livestock should this species become a threat to animal or public health. A study site was established in Yonkers, NY near the residence associated with the first reported human bite from H. longicornis in the United States. Ticks were collected once each week from July 2018 to November 2019. Haemaphysalis longicornis larvae were most active from August to November, nymphs from April to July, and adult females from June to September. This pattern of activity suggests that H. longicornis is capable of completing a generation within a single year and matches the patterns observed in its other ranges in the northern hemisphere. The data presented here contribute to a growing database for H. longicornis phenology in the northeastern United States. Potential implications of the short life cycle for the tick's vectorial capacity are discussed.

NMR structure of a vestigial nuclease provides insight into the evolution of functional transitions in viral dsDNA packaging motors.

Double-stranded DNA viruses use ATP-powered molecular motors to package their genomic DNA. To ensure efficient genome encapsidation, these motors regulate functional transitions between initiation, translocation, and termination modes. Here, we report structural and biophysical analyses of the C-terminal domain of the bacteriophage phi29 ATPase (CTD) that suggest a structural basis for these functional transitions. Sedimentation experiments show that the inter-domain linker in the full-length protein promotes oligomerization and thus may play a role in assembly of the functional motor. The NMR solution structure of the CTD indicates it is a vestigial nuclease domain that likely evolved from conserved nuclease domains in phage terminases. Despite the loss of nuclease activity, fluorescence binding assays confirm the CTD retains its DNA binding capabilities and fitting the CTD into cryoEM density of the phi29 motor shows that the CTD directly binds DNA. However, the interacting residues differ from those identified by NMR titration in solution, suggesting that packaging motors undergo conformational changes to transition between initiation, translocation, and termination. Taken together, these results provide insight into the evolution of functional transitions in viral dsDNA packaging motors.

COVID-19 Testing, Epidemic Features, Hospital Outcomes, and Household Prevalence, New York State-March 2020.

BACKGROUND: The US' coronavirus disease 2019 (COVID-19) epidemic has grown extensively since February 2020, with substantial associated hospitalizations and mortality; New York State has emerged as the national epicenter. We report on the extent of testing and test results during the month of March in New York State, along with risk factors, outcomes, and household prevalence among initial cases subject to in-depth investigations. METHODS: Specimen collection for COVID-19 testing was conducted in healthcare settings, community-based collection sites, and by home testing teams. Information on demographics, risk factors, and hospital outcomes of cases was obtained through epidemiological investigations and an electronic medical records match, and summarized descriptively. Active testing of initial case's households enabled estimation of household prevalence. RESULTS: During March in New York State, outside of New York City, a total of 47 326 persons tested positive for severe acute respiratory syndrome coronavirus 2, out of 141 495 tests (33% test-positive), with the highest number of cases located in the metropolitan region counties. Among 229 initial cases diagnosed through 12 March, by 30 March 13% were hospitalized and 2% died. Testing conducted among 498 members of these case's households found prevalent infection among 57%, excluding first-reported cases 38%. In these homes, we found a significant age gradient in prevalence, from 23% among those < 5 years to 68% among those ≥ 65 years (P < .0001). CONCLUSIONS: New York State faced a substantial and increasing COVID-19 outbreak during March 2020. The earliest cases had high levels of infection in their households and by the end of the month, the risks of hospitalization and death were high.

Multistate Infestation with the Exotic Disease-Vector Tick Haemaphysalis longicornis - United States, August 2017-September 2018.

Haemaphysalis longicornis is a tick indigenous to eastern Asia and an important vector of human and animal disease agents, resulting in such outcomes as human hemorrhagic fever and reduction of production in dairy cattle by 25%. H. longicornis was discovered on a sheep in New Jersey in August 2017 (1). This was the first detection in the United States outside of quarantine. In the spring of 2018, the tick was again detected at the index site, and later, in other counties in New Jersey, in seven other states in the eastern United States, and in Arkansas. The hosts included six species of domestic animals, six species of wildlife, and humans. To forestall adverse consequences in humans, pets, livestock, and wildlife, several critical actions are indicated, including expanded surveillance to determine the evolving distribution of H. longicornis, detection of pathogens that H. longicornis currently harbors, determination of the capacity of H. longicornis to serve as a vector for a range of potential pathogens, and evaluation of effective agents and methods for the control of H. longicornis.

Potential role of deer tick virus in Powassan encephalitis cases in Lyme disease-endemic areas of New York, U.S.A.

Powassan virus, a member of the tick-borne encephalitis group of flaviviruses, encompasses 2 lineages with separate enzootic cycles. The prototype lineage of Powassan virus (POWV) is principally maintained between Ixodes cookei ticks and the groundhog (Marmota momax) or striped skunk (Mephitis mephitis), whereas the deer tick virus (DTV) lineage is believed to be maintained between Ixodes scapularis ticks and the white-footed mouse (Peromyscus leucopus). We report 14 cases of Powassan encephalitis from New York during 2004-2012. Ten (72%) of the patients were residents of the Lower Hudson Valley, a Lyme disease-endemic area in which I. scapularis ticks account for most human tick bites. This finding suggests that many of these cases were caused by DTV rather than POWV. In 2 patients, DTV infection was confirmed by genetic sequencing. As molecular testing becomes increasingly available, more cases of Powassan encephalitis may be determined to be attributable to the DTV lineage.

The antitumor activity of the human FOLR1-specific monoclonal antibody, farletuzumab, in an ovarian cancer mouse model is mediated by antibody-dependent cellular cytotoxicity.

Because of its high mortality rate, ovarian cancer is a leading cause of death among women and a highly unmet medical need. New therapeutic agents that are effective and well tolerated are needed and cancer antigen-specific monoclonal antibodies that have direct pharmacologic effects or can stimulate immunological responses represent a promising class of agents for the treatment of this disease. The human folate receptor α (FOLR1), which is overexpressed in ovarian cancer but largely absent in normal tissues, appears to play a role in the transformed phenotype in ovarian cancer, cisplatin sensitivity, and growth in depleted folate conditions and therefore has potential as a target for passive immunotherapy. The anti-FOLR1 monoclonal antibody MORAb-003 (farletuzumab) was previously shown to elicit antibody dependent cellular cytotoxicity (ADCC) and inhibit tumor growth of human tumor xenografts in nude mice. Because of its promising preclinical profile, farletuzumab has been evaluated in clinical trials as a potential therapeutic agent for ovarian cancer. In this report, we demonstrated that farletuzumab's antitumor effect against an experimental model of ovarian cancer is mediated by its ADCC activity.

Predicted effects of proposed tightened acceptance criterion for Pb proficiency testing (PT) on PT sample pass rates for Pb point-of-care testing.

BACKGROUND: There is current advocacy for change in Pb proficiency testing (PT) acceptance criterion from ± 4 µg/dl ([Pb] <40 µg/dl; criterion a) to ± 2 µg/dl ([Pb] <20 µg/dl, criterion b). We examined the effect of this proposed change on PT sample pass rates for point-of-care testing (POCT) as predicted by imprecision of POCT PT sample results. METHODS: Inter-site standard deviations (s) of POCT PT results were tabulated as a function of [Pb] and characterized as a linear function of [Pb] (r(2)>0.8). Given s, predicted minimum, random-error-only PT failure rates (Fp) as a function of [Pb] were computed as the fraction of a normal distribution of results ([Pb]± s) that would fall outside of boundaries of acceptance criterion a or b. RESULTS: For [Pb]=2-20 µg/dl, current observed PT sample failure rates using criterion a range from 3 to 6%, which are greater than the predicted minimum failure rates based on s alone (Fp(a)=0-6%). In contrast, predicted minimum failure rates based on s using criterion b are greatly increased (Fp(b)=5-35%). CONCLUSIONS: Given the degree of inter-site imprecision among POCT Pb PT results, adoption of criterion b for PT acceptance will dramatically increase Pb PT sample failure rates for POCT due to random-error alone.

Echocardiography in patients with symptomatic intracranial stenosis.

BACKGROUND: Echocardiography is often performed in patients with stroke, even when alternative stroke causes are identified. We evaluated the use of echocardiography in patients with transient ischemic attack (TIA) or stroke caused by stenosis of a major intracranial artery. METHODS: The Warfarin Versus Aspirin for Symptomatic Intracranial Disease (WASID) trial was a National Institutes of Health-funded, randomized, double-blind, multicenter clinical trial in which 569 patients with TIA or ischemic stroke attributed to angiographically proven 50% to 99% stenosis of a major intracranial artery were randomly assigned to warfarin or aspirin. Patients with unequivocal cardiac sources of embolism were excluded. The risk of ischemic stroke, myocardial infarction, and vascular death was compared among patients who had or did not have echocardiography performed before enrollment, and Cox proportional hazards models were used to determine whether echocardiographic abnormalities present in greater than 5% of patients were associated with these outcomes. RESULTS: In all, 264 of 569 patients in WASID had echocardiograms; 37% were transesophageal. Of these 264 patients, 69 had subsequent ischemic stroke, myocardial infarction, or vascular death. Patients who underwent echocardiography had similar event rates to those who did not (P = .18). Common abnormalities identified on echocardiography were not associated with subsequent risk in this population. CONCLUSIONS: Among patients with TIA or stroke caused by intracranial arterial stenosis, echocardiography appears to offer limited diagnostic and prognostic value.

A clinicopathological study of nodal marginal zone B-cell lymphoma. A report on 21 cases.

AIMS: To report the clinicopathological findings of 21 cases of primary nodal marginal zone B-cell lymphoma (NMZL). NMZL is a recently characterized lymphoma and few series have been published. METHODS AND RESULTS: The clinical data were characteristic of a disseminated disease at presentation: presence of peripheral and abdominal lymph nodes, bone marrow involvement (62%), disease stage III and IV (76%), elevated lactate dehydrogenase (LDH) (48%). Other features included peripheral blood involvement (23%), anaemia (24%), thrombocytopenia (10%) and presence of serum M component (33%), while the previously reported association with hepatitis C virus and cryoglobulinaemia was not found. Relapses were frequent but the majority of patients receiving chemotherapy had a good initial response. Morphological features were heterogeneous and there were some differences compared with other marginal zone B-cell lymphomas (MZL). Pure monocytoid B-cell lymphomas were rare (10%) but a minor component of monocytoid B cell was observed more frequently (23%). Plasmacytoid or plasmacytic differentiation was a very common feature (61%). Large cells and a high mitotic count were also frequent (57%). CONCLUSION: NMZL can be distinguished from splenic MZL and extranodal MZL by its aggressive morphology and disseminated disease at presentation.

Bcl-2, cell cycle regulatory proteins and corticosensitivity in childhood acute lymphoblastic leukaemia.

The results of treatment in childhood acute lymphoblastic leukemia (ALL) remain incompletely satisfactory because of relapses observed even with high dose chemotherapy. The aim of this study was to evaluate the role of bcl-2 or cell cycle regulatory protein expression in peripheral blood cells before and during the first 48 hours of corticotherapy, and corticosensitivity criteria for predicting relapse and prognosis. Fifty two children presenting with ALL were studied at diagnosis and during the first 48 hours of treatment for the level of cell proliferation by measurement of DNA content, and for expression of several cell proliferation regulatory proteins by Western blot. Two criteria for corticosensitivity were used: 1--the number of blast cells present after seven days of treatment with a threshold at 1 G/L (usual criterion), 2--the D8/D1 blast cell ratio, which is independent of the initial leucocytosis. Relapse in the total patient population or in B-cell ALL could only be predicted by the level of leucocytosis before treatment or by p27kip1 expression during the first 48 hours of treatment. Disease free survival was significantly longer when the D8/D1 blast cell ratio was under the 0.75 quartile in the entire patient population (p = 0.03). Among the proteins analyzed, bcl-2 expression before treatment and p27kip1 expression analyzed after 48 hours of corticotherapy were the sole variables associated with significant differences in disease free survival duration in the entire patient population (p < 0.01 and p = 0.04 respectively) or in the B-cell ALL subgroup (p < 0.01). Comparable results were obtained for the overall survival data. The significance of these results is discussed but such a study on blood blast cells needs to be validated in a larger series.