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Item Empiric tranexamic acid use provides no benefit in urgent orthopedic surgery following injury(BMJ, 2023-03-10) Carr, Bryan; Li, Shi-Wen; Hill, Jamel G.; Feizpour, Cyrus; Zarzaur, Ben L.; Savage, Stephanie; Surgery, School of MedicineBackground: Orthopedic literature has demonstrated a significant decrease in postoperative transfusion requirements when tranexamic acid (TXA) was given during elective joint arthroplasty. The purpose of this study was to evaluate the empiric use of TXA in semi-urgent orthopedic procedures following injury. We hypothesized that TXA would be associated with increased rates of venous thromboembolic events (VTE) and have no effect on transfusion requirements. Methods: Patients who empirically received TXA during a semi-urgent orthopedic surgery following injury (TXA+) were matched using propensity scoring to historical controls (CONTROL) who did not receive TXA. Outcomes included VTE within 6 months of injury and packed red blood cell utilization. Multivariable logistic regression and generalized linear modeling were used to determine odds of VTE and transfusion. Results: 200 patients were included in each group. There was no difference in mortality between groups. TXA+ patients did not have an increase in VTE events (OR 0.680, 95% CI 0.206 to 2.248). TXA+ patients had a significantly higher odds of being transfused during their hospital stay (OR 2.175, 95% CI 1.246 to 3.797) and during the index surgery (increased 0.95 units (SD 0.16), p<0.0001). Overall transfusion was also significantly higher in the TXA+ group (p=0.0021). Conclusion: Empiric use of TXA in semi-urgent orthopedic surgeries did not increase the odds of VTE. Despite the elective literature, TXA administration did not associate with less transfusion requirements. A properly powered, prospective, randomized trial should be designed to elucidate the risks and benefits associated with TXA use in this setting.Item High rate of inappropriate blood transfusions in the management of children with severe anemia in Ugandan hospitals(BMC, 2018-07-18) Opoka, Robert O.; Ssemata, Andrew S.; Oyang, William; Nambuya, Harriet; John, Chandy C.; Tumwine, James K.; Karamagi, Charles; Pediatrics, School of MedicineBACKGROUND: Severe anaemia (SA) is a common reason for hospitalisation of children in sub-Saharan Africa but the extent to which blood transfusion is used appropriately in the management of severe anemia has hitherto remained unknown. We report on the use of blood transfusion in the management of anemic children in two hospitals in Uganda. METHODS: Inpatient records of children 0-5 years of age admitted to Lira and Jinja regional referral hospitals in Uganda were reviewed for children admitted on selected days between June 2016 and May 2017. Data was extracted on the results, if any, of pre-transfusion hemoglobin (Hb) level, whether or not a blood transfusion was given and inpatient outcome for all children with a diagnosis of 'severe anemia'. Qualitative data was also collected from health workers to explain the reasons for the clinical practices at the two hospitals. RESULTS: Overall, 574/2275 (25.2%) of the children admitted in the two hospitals were assigned a diagnosis of SA. However 551 (95.9%) of children assigned a diagnosis of SA received a blood transfusion, accounting for 551/560 (98.4%) of the blood transfusions in the pediatric wards. Of the blood transfusions in SA children, only 245 (44.5%) was given appropriately per criteria (Pre-transfusion Hb ≤ 6 g/dL), while 306 (55.5%) was given inappropriately; (pre-transfusion Hb not done, n = 216, or when a transfusion is not indicated [Hb > 6.0 g/dl], n = 90). SA children transfused appropriately per Hb criteria had lower inpatient mortality compared to those transfused inappropriately, (7 (2.9%) vs. 22 (7.2%), [OR 0.4, 95% CI 0.16, 0.90]). Major issues identified by health workers as affecting use of blood transfusion included late presentation of SA children to hospital and unreliable availability of equipment for measurement of Hb. CONCLUSION: More than half the blood transfusions given in the management of anemic children admitted to Lira and Jinja hospitals was given inappropriately either without pre-transfusion Hb testing or when not indicated. Verification of Hb level by laboratory testing and training of health workers to adhere to transfusion guidelines could result in a substantial decrease in inappropriate blood transfusion in Ugandan hospitals.Item Iron overload in thalassemia: different organs at different rates(American Society of Hematology, 2017-12-08) Taher, Ali T.; Saliba, Antoine N.; Medicine, School of MedicineThalassemic disorders lie on a phenotypic spectrum of clinical severity that depends on the severity of the globin gene mutation and coinheritance of other genetic determinants. Iron overload is associated with increased morbidity in both patients with transfusion-dependent thalassemia (TDT) and non-transfusion-dependent thalassemia (NTDT). The predominant mechanisms driving the process of iron loading include increased iron burden secondary to transfusion therapy in TDT and enhanced intestinal absorption secondary to ineffective erythropoiesis and hepcidin suppression in NTDT. Different organs are affected differently by iron overload in TDT and NTDT owing to the underlying iron loading mechanism and rate of iron accumulation. Serum ferritin measurement and noninvasive imaging techniques are available to diagnose iron overload, quantify its extent in different organs, and monitor clinical response to therapy. This chapter discusses the general approach to iron chelation therapy based on organ involvement using the available iron chelators: deferoxamine, deferiprone, and deferasirox. Other novel experimental options for treatment and prevention of complications associated with iron overload in thalassemia are briefly discussed.Item Life-Threatening Bleeding in Children: A Prospective Observational Study(Wolters Kluwer, 2021) Leonard, Julie C.; Josephson, Cassandra D.; Luther, James F.; Wisniewski, Stephen R.; Allen, Christine; Chiusolo, Fabrizio; Davis, Adrienne L.; Finkelstein, Robert A.; Fitzgerald, Julie C.; Gaines, Barbara A.; Goobie, Susan M.; Hanson, Sheila J.; Hewes, Hilary A.; Johnson, Laurie H.; McCollum, Mark O.; Muszynski, Jennifer A.; Nair, Alison B.; Rosenberg, Robert B.; Rouse, Thomas M.; Sikavitsas, Athina; Singleton, Marcy N.; Steiner, Marie E.; Upperman, Jeffrey S.; Vogel, Adam M.; Wills, Hale; Winkler, Margaret K.; Spinella, Philip C.; Surgery, School of MedicineObjectives: The purpose of our study was to describe children with life-threatening bleeding. Design: We conducted a prospective observational study of children with life-threatening bleeding events. Setting: Twenty-four childrens hospitals in the United States, Canada, and Italy participated. Subjects: Children 0-17 years old who received greater than 40 mL/kg total blood products over 6 hours or were transfused under massive transfusion protocol were included. Interventions: Children were compared according bleeding etiology: trauma, operative, or medical. Measurements and main results: Patient characteristics, therapies administered, and clinical outcomes were analyzed. Among 449 enrolled children, 55.0% were male, and the median age was 7.3 years. Bleeding etiology was 46.1% trauma, 34.1% operative, and 19.8% medical. Prior to the life-threatening bleeding event, most had age-adjusted hypotension (61.2%), and 25% were hypothermic. Children with medical bleeding had higher median Pediatric Risk of Mortality scores (18) compared with children with trauma (11) and operative bleeding (12). Median Glasgow Coma Scale scores were lower for children with trauma (3) compared with operative (14) or medical bleeding (10.5). Median time from bleeding onset to first transfusion was 8 minutes for RBCs, 34 minutes for plasma, and 42 minutes for platelets. Postevent acute respiratory distress syndrome (20.3%) and acute kidney injury (18.5%) were common. Twenty-eight-day mortality was 37.5% and higher among children with medical bleeding (65.2%) compared with trauma (36.1%) and operative (23.8%). There were 82 hemorrhage deaths; 65.8% occurred by 6 hours and 86.5% by 24 hours. Conclusions: Patient characteristics and outcomes among children with life-threatening bleeding varied by cause of bleeding. Mortality was high, and death from hemorrhage in this population occurred rapidly.Item Multifocal Myeloid Sarcomas: A Rare Presentation of AML(BMJ Publishing Group, 2017-10-04) Angsubhakorn, Natthapon; Suvannasankha, Attaya; Medicine, School of MedicineItem Multiple ‘doughnut’ granulomas in a liver transplant patient with CMV reactivation(BMJ, 2018-12-22) Dejhansathit, Siroj; Miller, Adam Michael; Suvannasankha, Attaya; Medicine, School of MedicineItem Sarcopenia is associated with blood transfusions in head and neck cancer free flap surgery(Wiley, 2021-04) Jones, Alexander Joseph; Campiti, Vincent J.; Alwani, Mohamedkazim; Novinger, Leah J.; Tucker, Brady Jay; Bonetto, Andrea; Yesensky, Jessica A.; Sim, Michael W.; Moore, Michael G.; Mantravadi, Avinash V.; Otolaryngology -- Head and Neck Surgery, School of MedicineObjective: To determine if sarcopenia is a predictor of blood transfusion requirements in head and neck cancer free flap reconstruction (HNCFFR). Methods: A single-institution, retrospective review was performed of HNCFFR patients with preoperative abdominal imaging from 2014 to 2019. Demographics, comorbidities (modified Charlson Comorbidity Index [mCCI]), skeletal muscle index (cm2/m2), oncologic history, intraoperative data, and 30-day postoperative complications (Clavien-Dindo score [CD]) were collected. Binary logistic regression was performed to determine predictors of transfusion. Results: Eighty (33.5%), 66 (27.6%), and 110 (46.0%) of n = 239 total patients received an intraoperative, postoperative, or any perioperative blood transfusion, respectively. Sixty-two (25.9%) patients had sarcopenia. Patients receiving intraoperative transfusions had older age (P = .035), more frequent alcoholism (P = .028) and sarcopenia (P < .001), greater mCCI (P < .001), lower preoperative hemoglobin (P < .001), reconstruction with flaps other than forearm (P = .003), and greater operative times (P = .001), intravenous fluids (P < .001), and estimated blood loss (EBL, P < .001). Postoperative transfusions were associated with major complications (CD ≥ 3; P < .001). Multivariate regression determined sarcopenia (P = .023), mCCI (P = .013), preoperative hemoglobin (P = .002), operative time (P = .036), and EBL (P < .001) as independent predictors of intraoperative transfusion requirements. Postoperative transfusions were predicted by preoperative hemoglobin (P = .007), osseous flap (P = .036), and CD ≥ 3 (P < .001). A perioperative transfusion was predicted by sarcopenia (P = .021), preoperative hemoglobin (P < .001), operative time (P = .008), and CD ≥ 3 (P = .018). Conclusion: Sarcopenia is associated with increased blood transfusions in HNCFFR. Patients should be counseled preoperatively on the associated risks, and the increased blood product requirement should be accounted in resource-limited scenarios.Item Serial “death diamond” TEGs are a bedside indicator of futile resuscitation during massive transfusion(Wolters Kluwer, 2023) Moore, Ernest E.; Moore, Hunter B.; Thomas, Scott G.; Farrell, Michael S.; Sixta, Sherry; Coleman, Julia R.; Miller, Joseph B.; Bunch, Connor M.; Waxman, Dan; Walsh, Mark M.; Emergency Medicine, School of MedicineSerial DDs could serve as rapid check points to gauge the likelihood of success of continued resuscitation. Loudon et al.’s work combined with the use of serial DDs may serve as building blocks toward a trial using VETs to predict continued futile resuscitation.Item Tissue Oxygenation Changes After Transfusion and Outcomes in Preterm Infants: A Secondary Near-Infrared Spectroscopy Study of the Transfusion of Prematures Randomized Clinical Trial (TOP NIRS)(American Medical Association, 2023-09-05) Chock, Valerie Y.; Kirpalani, Haresh; Bell, Edward F.; Tan, Sylvia; Hintz, Susan R.; Ball, M. Bethany; Smith, Emily; Das, Abhik; Loggins, Yvonne C.; Sood, Beena G.; Chalak, Lina F.; Wyckoff, Myra H.; Kicklighter, Stephen D.; Kennedy, Kathleen A.; Patel, Ravi M.; Carlo, Waldemar A.; Johnson, Karen J.; Watterberg, Kristi L.; Sánchez, Pablo J.; Laptook, Abbot R.; Seabrook, Ruth B.; Cotten, C. Michael; Mancini, Toni; Sokol, Gregory M.; Ohls, Robin K.; Hibbs, Anna Maria; Poindexter, Brenda B.; Reynolds, Anne Marie; DeMauro, Sara B.; Chawla, Sanjay; Baserga, Mariana; Walsh, Michele C.; Higgins, Rosemary D.; Van Meurs, Krisa P.; Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network; Pediatrics, School of MedicineImportance: Preterm infants with varying degrees of anemia have different tissue oxygen saturation responses to red blood cell (RBC) transfusion, and low cerebral saturation may be associated with adverse outcomes. Objective: To determine whether RBC transfusion in preterm infants is associated with increases in cerebral and mesenteric tissue saturation (Csat and Msat, respectively) or decreases in cerebral and mesenteric fractional tissue oxygen extraction (cFTOE and mFTOE, respectively) and whether associations vary based on degree of anemia, and to investigate the association of Csat with death or neurodevelopmental impairment (NDI) at 22 to 26 months corrected age. Design, setting, and participants: This was a prospective observational secondary study conducted among a subset of infants between August 2015 and April 2017 in the Transfusion of Prematures (TOP) multicenter randomized clinical trial at 16 neonatal intensive care units of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Preterm neonates with gestational age 22 to 28 weeks and birth weight 1000 g or less were randomized to higher or lower hemoglobin thresholds for transfusion. Data were analyzed between October 2020 and May 2022. Interventions: Near-infrared spectroscopy monitoring of Csat and Msat. Main outcomes and measures: Primary outcomes were changes in Csat, Msat, cFTOE, and mFTOE after transfusion between hemoglobin threshold groups, adjusting for age at transfusion, gestational age, birth weight stratum, and center. Secondary outcome at 22 to 26 months was death or NDI defined as cognitive delay (Bayley Scales of Infant and Toddler Development-III score <85), cerebral palsy with Gross Motor Function Classification System level II or greater, or severe vision or hearing impairment. Results: A total of 179 infants (45 [44.6%] male) with mean (SD) gestational age 25.9 (1.5) weeks were enrolled, and valid data were captured from 101 infants during 237 transfusion events. Transfusion was associated with a significant increase in mean Csat of 4.8% (95% CI, 2.7%-6.9%) in the lower-hemoglobin threshold group compared to 2.7% (95% CI, 1.2%-4.2%) in the higher-hemoglobin threshold group, while mean Msat increased 6.7% (95% CI, 2.4%-11.0%) vs 5.6% (95% CI, 2.7%-8.5%). Mean cFTOE and mFTOE decreased in both groups to a similar extent. There was no significant change in peripheral oxygen saturation (SpO2) in either group (0.2% vs -0.2%). NDI or death occurred in 36 infants (37%). Number of transfusions with mean pretransfusion Csat less than 50% was associated with NDI or death (odds ratio, 2.41; 95% CI, 1.08-5.41; P = .03). Conclusions and relevance: In this secondary study of the TOP randomized clinical trial, Csat and Msat were increased after transfusion despite no change in SpO2. Lower pretransfusion Csat may be associated with adverse outcomes, supporting further investigation of targeted tissue saturation monitoring in preterm infants with anemia.Item Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review(MDPI, 2021-01-17) Walsh, Mark; Moore, Ernest E.; Moore, Hunter B.; Thomas, Scott; Kwaan, Hau C.; Speybroeck, Jacob; Marsee, Mathew; Bunch, Connor M.; Stillson, John; Thomas, Anthony V.; Grisoli, Annie; Aversa, John; Fulkerson, Daniel; Vande Lune, Stefani; Sjeklocha, Lucas; Tran, Quincy K.; Medicine, School of MedicineThis narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed.