Bloodworks Northwest

In this pilot trial, we tested the feasibility of conducting a randomized controlled trial in cardiac surgery patients using extended-, 100% plasma-, cold-stored, and long-distance-shipped platelets (CSPs). We conducted a single center, controlled, double-blind pilot study in adult patients undergoing elective redo or complex cardiothoracic surgery. Patients were allocated in a week-based block randomization scheme to receive either room temperature-stored platelets (RTPs) or CSPs shipped from a Texas-based blood center and stored between 10 and 14 days. The primary outcome was defined as the feasibility of recruitment and accrual. Several other secondary endpoints were assessed. All platelet units were screened for aggregates using RTP release criteria. In a post-hoc "as treated" analysis, 15 patients received RTPs, and 9 received CSPs (including 3 who received both). We found that most CSPs (58%) were not usable for transfusion due to the presence of aggregates. This resulted in an excess of subjects receiving RTPs; consequently, the final nine transfused participants were allocated to receive CSPs without randomization. We accrued 0.7 evaluable subjects/month of active enrollment, which was below our desired primary outcome feasibility target of ≥1.2. One death within 28 days occurred in the RTP transfusion group, while none occurred in the CSPs group. In vitro testing yielded contradictory results. Due to slow recruitment and the abundance of aggregates in CSPs, this pilot trial does not support the feasibility of the study protocol.

Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.

The e antigen is the highest prevalence antigen commonly encountered in the Rh blood system, while Dib has a prevalence of nearly 100% in most populations studied. The immune response to these antigens is clinically significant with respect to hemolysis (hemolytic disease of the fetus/newborn and hemolytic transfusion reactions). A 33-year-old G6P4 pregnant woman presented for an initial prenatal visit. Anti-e was detected at the time of delivery of her 5th baby. Initial blood bank testing for her 6th pregnancy revealed strong pan-reactivity that proved to be anti-e and anti-Dib. A combined antibody titer of 16 led to pregnancy monitoring using serial fetal middle cerebral artery Doppler sonography. All results were in the normal range, indicating a low risk for severe fetal anemia. The patient donated 3 units of blood for autologous and/or neonatal transfusion. She ultimately had a vaginal delivery at ~37 weeks gestational age with minimal blood loss. Her neonate had a normal hemoglobin/hematocrit at delivery and no clinical evidence of jaundice even though he had a strongly reactive DAT, typed positive for both e and Dib, and had both antibodies eluted from his red cells. On close follow-up, he developed mild jaundice but did not require treatment. Though this pregnant patient had 2 clinically significant antibodies to high prevalence blood group antigens, they did not affect the neonate adversely. This case demonstrates that close collaboration between obstetricians, neonatologists, and transfusion medicine specialists is essential for positive patient outcomes in cases like this.

Emerging evidence suggests that RB1 inactivation may be a strong predictor of poor survival for men with prostate cancer (PC); however, large-scale validation is lacking. We analyzed whether RB1 alterations are associated with inferior survival in advanced PC and evaluated the impact of co-occurring genomic alterations on outcomes using retrospective data from the Veteran's Health Administration and Veterans Affairs Multi-Omics Analysis Platform for Prostate Cancer from 2016 to 2023. The primary outcome was overall survival (OS) from onset of metastatic castration-resistant prostate cancer (mCRPC), as well as OS from initiation of life-prolonging therapy other than androgen deprivation therapy, and time to development of mCRPC. Eighty-seven (3.5%) of the 2,512 included patients had an RB1 alteration detected. The median age at diagnosis in the RB1-altered group was 71 (IQR, 65-76) years, and 68 (IQR, 62-73) years in the RB1 wild-type group. The median overall survival from diagnosis of mCRPC was 1.31 years (95% CI, 0.89 to 1.84) in those with an RB1 alteration compared with 2.99 years (95% CI, 2.79 to 3.23). RB1 alteration alone conferred similar poor prognosis when compared with patients who had combined PTEN and TP53 alterations. A dose effect was seen with increasing numbers of tumor suppressor genes (TSGs-RB1, TP53, and PTEN) conferring poorer outcomes. The median survival of patients from diagnosis of mCRPC with zero, one, two, and three TSGs was 3.74, 2.61, 1.61, and 0.87 years, respectively. BRCA2 alterations were not associated with significantly worse outcomes unless accompanied by RB1 alteration. In this large, real-world cohort of men with mCRPC, RB1 alterations emerged as a strong indicator of poor prognosis and can be used to stratify studies alone or in conjunction with other TSG alterations.

(1)Background:Previous studies indicate that individuals who engage in regular physical activity have a higher pain threshold than those who do not exercise. However, it remains unclear how this phenomenon behaves in individuals exposed to chronic hypoxia. This study evaluates pain perception at high altitude between high-altitude natives who exercised regularly and those who did not practice physical activity.(2)Methods:Eighty-four healthy volunteers aged 20 to 30 years old with a body mass index (BMI) within the normal range (18.5–24.9) residing in the city of Puno (3825 m) were recruited. The unilateral ischemia pain provocation test was used, applying pressure with a manual sphygmomanometer to generate transient ischemia in the arm while the patient opens and closes their hand. Onset, peak, and resolution times of pain, heart rate, and oxygen saturation were recorded.(3)Results:The average time to pain onset in the right arm was 30.2 s ± 14.1 during light physical activity, whereas, during moderate physical activity, it increased to 32.5 s ± 15.4. In the left arm, the average time until pain sensation was 27.9 s ± 16.8 during light physical activity and increased to 34.6 s ± 18.5 with moderate physical activity. Regarding the progression of pain intensity, the average time to reach unbearable pain in the right arm was 54.1 s ± 16.4 during light physical activity and 53.8 s ± 19.6 during moderate physical activity; in the left arm, it was 53.0 s ± 19.6 during light physical activity, increasing to 59.3 s ± 24.5 during moderate physical activity.(4)Conclusions:A more stable and slightly higher pain tolerance in the dominant arm was observed.

ImportancePlatelet transfusion is a frequent procedure with benefits and risks.ObjectiveTo provide recommendations in adult and pediatric populations in whom platelet transfusions are commonly performed.Evidence ReviewGrading of Recommendations Assessment Development and Evaluation (GRADE) methodology was applied to findings from 21 randomized trials and 13 observational studies in contexts of limited randomized clinical trial data. Transfusion strategies using fewer (restrictive) vs greater (liberal) amounts of platelets were compared.FindingsEvidence demonstrated that restrictive transfusion strategies probably did not cause increases in mortality or bleeding relative to liberal strategies across predefined clinical populations. Exceedingly low incidence of spinal hematoma was identified in patients with thrombocytopenia undergoing lumbar puncture. Because definitions of restrictive strategies varied across trials, recommendations reflect practical guidance. The following recommendations are strong recommendations with high/moderate–certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding patients receiving chemotherapy or undergoing allogeneic stem cell transplant, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. For consumptive thrombocytopenia in neonates without major bleeding, platelet transfusion is recommended when platelet count is less than 25 × 103/μL. In patients undergoing lumbar puncture, platelet transfusion is recommended when platelet count is less than 20 × 103/μL. In patients with consumptive thrombocytopenia due to Dengue without major bleeding, platelet transfusion is not recommended. The following recommendations are conditional recommendations with low/very low–certainty evidence. For hypoproliferative thrombocytopenia in nonbleeding adults undergoing autologous stem cell transplant or with aplastic anemia, prophylactic platelet transfusion is not recommended. In adults with consumptive thrombocytopenia without major bleeding, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing central venous catheter placement in compressible anatomic sites, platelet transfusion is recommended when platelet count is less than 10 × 103/μL. In adults undergoing interventional radiology, platelet transfusion is recommended when platelet count is less than 20 × 103/μL for low-risk procedures and less than 50 × 103/μL for high-risk procedures. For adults undergoing major nonneuraxial surgery, platelet transfusion is recommended when platelet count is less than 50 × 103/μL. For patients without thrombocytopenia undergoing cardiovascular surgery in the absence of major hemorrhage, including those receiving cardiopulmonary bypass, platelet transfusion is not recommended. For nonoperative intracranial hemorrhage in adults with platelet count greater than 100 × 103/μL, including those receiving antiplatelet agents, platelet transfusion is not recommended.Conclusions And RelevanceA consistent pattern of evidence supports the implementation of restrictive platelet transfusion strategies. Restrictive strategies reduce risk of adverse reactions, mitigate platelet shortages, and reduce costs. It is good practice to consider overall clinical context and alternative therapies in the decision to perform platelet transfusion.

Oxidized low-density lipoprotein (oxLDL) promotes proatherogenic phenotypes in macrophages, accelerating the progression of atherosclerosis. Our previous studies demonstrated that oxLDL binds to its receptor CD36, stimulating mitochondrial reactive oxygen species (mtROS), which are critical in atherosclerosis development. However, the mechanisms underlying mtROS induction and their effects on macrophage cellular functions remain poorly understood. Macrophages rely on phagocytosis to clear pathogens, apoptotic cells, or other particles, a process critical for tissue homeostasis. Dysregulated or excessive particle ingestion, a key step in phagocytosis, can lead to lipid overloading and foam cell formation, a hallmark of atherosclerosis. In this study, we showed that macrophages pretreated with oxLDL exhibit increased particle ingestion, a phagocytic response significantly attenuated in Cd36-null macrophages. Further investigations revealed that oxLDL-induced phagocytosis depends on mtROS, as their suppression inhibited the process. In vivo, atherosclerosis-prone Apoe-null mice on a high-fat diet exhibited increased mtROS levels and enhanced phagocytic activity in aortic foamy macrophages compared to those from chow diet–fed mice, supporting a role of mtROS in promoting lesional macrophage phagocytosis. Mechanistically, we identified a novel signaling pathway whereby oxLDL/CD36 interaction induces the translocation of the cytosolic enzyme pyruvate kinase muscle 2 (PKM2) to mitochondria. Disruption of PKM2 mitochondrial translocation using siRNA knockdown or a specific chemical inhibitor reduced mtROS production and attenuated oxLDL-induced phagocytosis. In conclusion, our findings reveal a novel oxLDL-CD36-PKM2 signaling axis that drives mtROS production and phagocytosis in atherogenic macrophages.