Improved Constraints on Primordial Gravitational Waves using Planck, WMAP, and BICEP/Keck Observations through the 2018 Observing Season.

We present results from an analysis of all data taken by the BICEP2, Keck Array, and BICEP3 CMB polarization experiments up to and including the 2018 observing season. We add additional Keck Array observations at 220 GHz and BICEP3 observations at 95 GHz to the previous 95/150/220 GHz dataset. The Q/U maps now reach depths of 2.8, 2.8, and 8.8 µK_{CMB} arcmin at 95, 150, and 220 GHz, respectively, over an effective area of ≈600 square degrees at 95 GHz and ≈400 square degrees at 150 and 220 GHz. The 220 GHz maps now achieve a signal-to-noise ratio on polarized dust emission exceeding that of Planck at 353 GHz. We take auto- and cross-spectra between these maps and publicly available WMAP and Planck maps at frequencies from 23 to 353 GHz and evaluate the joint likelihood of the spectra versus a multicomponent model of lensed ΛCDM+r+dust+synchrotron+noise. The foreground model has seven parameters, and no longer requires a prior on the frequency spectral index of the dust emission taken from measurements on other regions of the sky. This model is an adequate description of the data at the current noise levels. The likelihood analysis yields the constraint r_{0.05}<0.036 at 95% confidence. Running maximum likelihood search on simulations we obtain unbiased results and find that σ(r)=0.009. These are the strongest constraints to date on primordial gravitational waves.

Survey of current practice for prevention of transfusion-transmitted cytomegalovirus in the United States: leucoreduction vs. cytomegalovirus-seronegative.

BACKGROUND AND OBJECTIVES: Cytomegalovirus (CMV) is a significant pathogen transmissible through blood transfusion that can have devastating effects on immunocompromised patients. Current transfusion practice provides two choices for transfusion of cellular blood components that reduce the risk of transfusion-transmitted CMV (TT-CMV): blood components collected from CMV seronegative donors and leucocyte-reduced (LR) blood components. MATERIALS AND METHODS: A web-based survey was designed and administered to AABB physician members in April 2007 to collect information regarding current blood banking and clinical practices for prevention of TT-CMV in the United States. RESULTS: Individuals representing 183 different institutions completed the entire survey (an institutional response rate of 32.5%). Sixty-five percent of respondents indicated that their institution considered that CMV-seronegative and LR products are equally effective in preventing TT-CMV. When analyzed by institutional type, academic institutions and community hospitals were more likely to subscribe to the premise that LR blood components are equally effective at preventing TT-CMV, than were community blood centres and government institutions. However, reported practices for specific patient populations did not match this view of equivalence between CMV-seronegative and LR products with many patient populations preferentially receiving CMV-seronegative components. Fetal and neonatal populations were more likely than other patient populations to receive CMV-seronegative products to reduce the risk of TT-CMV. CONCLUSION: There is wide variability in transfusion practices to reduce the risk of TT-CMV. Lack of a consensus approach may reflect the conflicting data that exist in the literature as well as adherence to longstanding practice.

Lymphadenopathy associated virus infection of a blood donor--recipient pair with acquired immunodeficiency syndrome.

A retrovirus isolated from three patients with the acquired immunodeficiency syndrome (AIDS) in the United States was morphologically and antigenically identical to lymphadenopathy associated virus isolated in France. Two of these isolates were from a blood donor-recipient pair, each of whom developed AIDS. Lymphadenopathy associated virus was isolated from the blood donor's lymphocytes 12 months after his onset of AIDS symptoms and from the blood recipient's lymphocytes 1 month after her onset of AIDS symptoms. Two isolates from the blood donor-recipient pair and an isolate from an epidemiologically unrelated homosexual man were examined by competitive radioimmunoassay to determine their antigenic relatedness to each other and to other human retroviruses. The major core proteins (p25) of the isolates were antigenically identical and all three isolates were identical to prototype lymphadenopathy associated virus isolated in France.

Treatment of severe platelet dysfunction and hemorrhage after cardiopulmonary bypass: reduction in blood product usage with desmopressin.

Impairment of platelet function commonly occurs after cardiopulmonary bypass, and may result in substantial bleeding. Because desmopressin acetate (a synthetic analogue of vasopressin) shortens bleeding time in a variety of platelet disorders, a controlled clinical trial of intravenous desmopressin was performed in 39 patients with excessive mediastinal bleeding (greater than 100 ml/h) and a prolonged template bleeding time (greater than 10 minutes) more than 2 hours after termination of cardiopulmonary bypass. Twenty-three desmopressin recipients and 16 control patients (no desmopressin) were similar in surgical procedure, pump time, platelet count, template bleeding time and amount of bleeding before therapy (p = NS). Compared with the control group, the patients receiving desmopressin (20 micrograms; mean 0.3 micrograms/kg) utilized fewer blood products (29 +/- 19 versus 15 +/- 13 units/patient; p less than 0.05), especially platelets (12 +/- 9 versus 4 +/- 7 units/patient; p = 0.004), while achieving a similarly effective reduction in mediastinal bleeding (4.8- and 4.3-fold, p = 0.001 for both). Severe platelet dysfunction was partially corrected within 1 hour after desmopressin infusion, during which interval no blood products were administered: the template bleeding time shortened (from 17 to 12.5 minutes, p less than 0.05), whereas the platelet count remained unchanged (at 96 +/- 35 and 105 +/- 31 X 10(3)/mm3, p = NS). The plasma levels of two factor VIII components increased: procoagulant activity (VIII:C) from 0.97 +/- 0.43 to 1.52 +/- 0.74 units/ml (p less than 0.05) and von Willebrand factor (VIII:vWF) from 1.28 to 1.78 units/ml (p less than 0.05); these increases correlated with the shortening of the bleeding time (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic trial of cryofiltration in patients with rheumatoid arthritis.

Cryofiltration, a new technique for on-line plasma separation and its treatment by cold filtration, enables the selective removal of immune complexes and eliminates the need for replacement proteins. Fifteen patients with rheumatoid arthritis were treated for nine to 10 consecutive sessions over a three- to five-week period. Circulating immune complexes decreased by an average of 78 percent and rheumatoid factor by 32 percent. This was accompanied by significant clinical improvement in morning stiffness, articular index, 50-foot walking time, grip strength, and target joint circumference. Cryofiltration might thus be beneficial for a subgroup of rheumatoid arthritis patients in whom conventional therapy has failed.

Unrecognized human immunodeficiency virus type 1 infection in a cohort of transfused neonates: a retrospective investigation.

OBJECTIVE: To retrospectively identify unrecognized human immunodeficiency virus type 1 (HIV-1) infection among a cohort of children transfused as neonates before donated blood was routinely screened for HIV-1 antibody. METHODS: Records at a large, private, metropolitan hospital were reviewed to identify children who were transfused as neonates between January 1980 and March 1985 and discharged alive from the hospital. Multiple data sources were used to locate these children. Parents or guardians were contacted, and their children were offered HIV-1 antibody testing and physical examination. RESULTS: Of the 775 children identified as having received transfusions during the project period, 644 (83%) were located, and 443 (69%) were evaluated for HIV-1 infection. Among those evaluated, 33 (7%) had antibody to HIV-1, including 14 whose infections had not been previously diagnosed. At the time of enrollment, 13 children infected with HIV-1 were asymptomatic an average of 63 months after transfusion. CONCLUSION: HIV-1 antibody testing should be considered for all children, regardless of clinical status, who were transfused before routine blood donor screening was implemented in March 1985, particularly in areas with a high incidence of acquired immunodeficiency syndrome during those years.

Advances in the use of therapeutic pheresis for the management of rheumatic diseases.

Twenty-two patients with rheumatoid arthritis, 3 with seronegative juvenile rheumatoid arthritis, 4 with systemic lupus erythematosus, and 4 with psoriatic arthritis have undergone therapeutic pheresis at our institution over the last 3 yr. Lymphoplasmapheresis appears to be the most effective form of pheresis in treating rheumatoid arthritis. After achieving a remission with 20 treatments performed in 11 wk, a flare may be preventable by pheresing patients 3 times a week every 6 wk provided the patient is on a concomitant, long-acting agent. Therapeutic pheresis has been disappointing in seronegative juvenile rheumatoid arthritis. Life-threatening complications of systemic lupus erythematosus may respond dramatically to pheresis. In treating less severe disease on a long-term basis, pheresis has demonstrated excellent steroid sparing properties. Nonspondylytic psoriatic arthritis responds slowly to pheresis, but arthritic remissions may be prolonged, even though skin response is variable. Experience in the use of pheresis for treating these diseases has allowed for the development of criteria for deciding whether to institute such therapy as an adjunct to more standard modes of treatment for individual patients. Also, a variety of "technical" factors can influence the outcome of therapy, and these must be managed appropriately. Therapeutic pheresis is a promising tool for investigating and treating rheumatic diseases.

Confirmation of the safety of autologous blood donation by patients awaiting heart or lung transplantation. A controlled study using hemodynamic monitoring.

BACKGROUND: Though earlier investigations have demonstrated the efficacy of autologous blood transfusion in reducing allogeneic blood exposure in patients undergoing heart or lung transplantation, questions remain regarding the safety of blood donation by patients with severe heart or lung disease. METHODS: Response to autologous blood donation by candidates for heart and lung transplantation and a group of age- and gender-matched control subjects was studied. Heart rate, blood pressure, oxygen saturation, and cardiac rhythm were examined before and after phlebotomy, and response to orthostatic challenge was evaluated. Patients were also questioned regarding impressions of changes in subjective sense of well being. Differences between patients and control subjects were evaluated by the paired t test and Fisher's exact test. An alpha of 0.05 was used in all testing to determine statistical significance. RESULTS: Eighteen candidates for heart transplantation, 16 candidates for lung transplantation, and their matched control subjects were studied. Though patients and control subjects differed with respect to baseline hemodynamic measurements, significant differences between the groups' responses to phlebotomy were not observed. After whole blood donation, orthostatic challenge resulted in a mean change in mean arterial pressure of -2.1 mm Hg in candidates for heart transplantation compared with a mean of +3.6 mm Hg in their control subjects (p = 0.062). In candidates for lung transplantation there was a mean change of +2.2 mm Hg after orthostatic challenge versus a mean change of +8.5 mm Hg in their control subjects (p = 0.052). Furthermore, no changes in cardiac rhythm or arterial oxygen saturation were detected. CONCLUSIONS: The hemodynamic effects of autologous blood donation in a group of patients with significant cardiac or pulmonary disease were not different from those observed in patients considered acceptable candidates for autologous blood collection. On the basis of these objective findings, we believe that patients with less severe degrees of heart or lung disease should not be excluded from participation in autologous blood donation programs.

Leukocyte-reduced blood components in transfusion medicine. Current indications and prospects for the future.

Transfusion medicine is a rapidly evolving specialty, and efforts are ongoing to improve the safety and quality of blood component therapy. Leukocytes are known to be the cause of numerous adverse effects of transfusion therapy, and their removal from red cells and platelet components may be desirable in a variety of clinical settings. The various complications of transfusion that can be attributed to contaminating leukocytes and the benefits of leukocyte depletion are addressed in this article. Laboratory as well as clinical data are summarized.

Performance of an automated solid-phase red cell adherence system compared with that of a manual gel microcolumn assay for the identification of antibodies eluted from red blood cells.

IgG antibodies coating red blood cells (RBCs) can be removed by elution procedures and their specificity determined by antibody identification studies. Although such testing is traditionally performed using the tube agglutination assay, prior studies have shown that the gel microcolumn (GMC) assay may also be used with comparable results. The purpose of this study was to compare an automated solid-phase red cell adherence (SPRCA) system with a GMC assay for the detection of antibodies eluted from RBCs. Acid eluates from 51 peripheral blood (PB) and 7 cord blood (CB) samples were evaluated by both an automated SPRCA instrument and a manual GMC assay. The concordance rate between the two systems for peripheral RBC samples was 88.2 percent (45 of 51), including cases with alloantibodies (n = 8), warm autoantibodies (n = 12), antibodies with no identifiable specificity (n = 2), and negative results (n = 23). There were six discordant cases, of which four had alloantibodies (including anti-Jka, -E, and -e) demonstrable by the SPRCA system only. In the remaining 2 cases, anti-Fya and antibodies with no identifiable specificity were demonstrable by the GMC assay only. All seven CB specimens produced concordant results, showing anti-A (n = 3), -B (n = 1), maternal anti-Jka (n = 2), or a negative result (n = 1). Automated SPRCA technology has a performance that is comparable with that of a manual GMC assay for identifying antibodies eluted from PB and CB RBCs.

Acute hemolytic transfusion reactions--a fresh look at pathogenesis and considerations regarding therapy.

A review of our knowledge of acute hemolytic transfusion reactions indicates that we have learned much in recent years about the pathogenetic mechanisms involved. An approach to effective therapy for patients suffering such reactions should be based on our latest understanding of the pathophysiology of this syndrome. However, changes in our therapeutic approach have not kept abreast of our increased awareness of the etiologic factors, and the patient, therefore, is not getting the benefit of our increased knowledge in this area. The primary pathogenetic mechanisms involved in these reactions appear to be disseminated intravascular coagulation and a series of hemodynamic alterations leading to ischemic necrosis of tissues. Therapy would best be aimed at interfering with these primary pathophysiologic pathways.

Plasmapheresis in the treatment of acute relapsing inflammatory demyelinating polyradiculoneuropathy associated with human immunodeficiency virus infection: a case report.

Neurologic complications, including both the acute and chronic forms of inflammatory demyelinating polyradiculoneuropathy (IDP) are becoming more prevalent among patients with the acquired immunodeficiency syndrome (AIDS) and AIDS-related-complex (ARC). Although the etiology of the above radiculoneuropathies is not known, an autoimmune process has been postulated. Plasmapheresis has been reported to be of benefit in both the acute and chronic forms of these neuropathies. In this report we describe the use of plasmapheresis in the treatment of a patient with ARC and the acute relapsing form of IDP. The treatment consisted of an intensive course of plasmapheresis following his initial presentation and after an acute relapse which occurred several weeks after his initial presentation. Both the initial presentation and relapse involved respiratory compromise necessitating intubation and mechanical ventilation. In both instances marked clinical improvement was achieved after initiation of plasmapheresis. Thus, plasmapheresis may have a role in the management of acute relapsing IDP associated with human immunodeficiency virus infection.

Prevention of adverse reactions to blood transfusion by the administration of saline-washed red blood cells.

We prospectively compared the incidence of complications following saline-washed versus packed red blood cell transfusions, to determine whether routine use of washed red blood cells could reduce significantly the incidence of transfusion reactions. Clinical reports of reactions were evaluated carefully to confirm whether the reaction was caused by transfusion. In 3,799 washed red blood cell transfusions, there were eight confirmed reactions (0.21%). Of 6,359 packed red blood cell transfusions, 31 reactions occurred (0.49%). The difference in incidence of confirmed complications was statistically significant (p less than 0.03). Administration of washed red blood cells to all patients requiring transfusions can thus be seen to reduce significantly the incidence of adverse reactions. This is likely the result of the removal of leukocytes and plasma achieved by the washing process. The increased safety of washed red blood cells must be weighed against their extra expense to determine their cost-effectiveness in transfusion therapy.

Treatment of renal allograft rejection by exchange plasma-lymphocytapheresis.

Therapy for acute renal allograft rejection generally consists of administration of high doses of corticosteroids along with cytotoxic drugs. Failure of this treatment usually dictates removal of the graft. We describe a patient who was rejecting a renal transplant from his HLA-identical, mixed lymphocyte culture-compatible brother. This acute rejection episode was unresponsive to three days of therapy with high doses of steroids, azathioprine and coumadin. The patient rapidly improved following intensive exchange plasmapheresis and lymphocytapheresis. This therapy produced depletion of immunoglobulins, complement components, coagulation factors and circulating lymphocytes, and resulted in dramatic improvement in renal function and reversal of the rejection crisis. We suggest that intensive pheresis may represent an important adjunct to currently available therapy for the treatment of acute renal allograft rejection.

Cisplatin-induced nonimmunologic adsorption of immunoglobulin by red cells.

Antibodies to cisplatin, an extensively used anticancer chemotherapeutic agent, have been implicated previously as a cause of immune hemolytic anemia. Investigation of a suspected case of cisplatin-induced hemolytic anemia in a 40-year-old man demonstrated that IgG could be adsorbed nonimmunologically by reagent red cells in vitro. This phenomenon was found to be a source of possible error in the interpretation of studies identifying specific cisplatin antibodies. Furthermore, cisplatin was found to be capable of producing a positive direct antiglobulin test (DAT), owing to the nonspecific adsorption of immunoglobulin and complement in vivo. Although this finding did not result in acute hemolysis, it may cause confusion in the investigation of DAT-positive hemolytic anemias. We question whether previous reports of cisplatin-induced hemolytic anemia are accurate in their assessment that such hemolysis was mediated immunologically. Future studies of suspected cases of hemolysis induced by this drug should include serologic investigation adequate to demonstrate the presence of specific cisplatin antibodies. A positive DAT in such patients should not be considered proof of drug-induced immune hemolytic anemia.

Use of autologous pregnancy plasma to treat a flare of juvenile rheumatoid arthritis: case report and literature review.

A patient with juvenile rheumatoid arthritis whose disease was in remission during pregnancy underwent third-trimester plasmaphereses. The stored plasma was returned to her 1 year postpartum, when the disease flared, without beneficial results. The literature on the use of blood products in rheumatoid arthritis and pregnancy is reviewed.