Transient Improvement in Erythropoiesis Is Achieved Via the Chaperone AHSP With Early Administration of Propranolol in Burn Patients.

Burn patients experience erythropoietin resistant anemia in which early commitment and late maturation of erythroblasts are defective. The authors previously showed that propranolol (Prop) treatment restores erythroid committed progenitors, but terminal maturation remains impaired. Hemoglobinization and maturation occur during terminal erythropoiesis and these processes are aided by an erythroblast intrinsic functional protein called alpha-hemoglobin stabilizing protein (AHSP). The authors evaluated the role of AHSP in PBMC- (peripheral blood mono nuclear cell) derived erythroblasts and the implications of Prop in burn patients. Blood samples were collected at three time points from 17 patients receiving standard burn care (SBC) or Prop. Five healthy volunteers provided control plasma (CP). PBMCs were placed in biphasic cultures with 5% autologous plasma (BP) or CP. Erythroblasts were harvested during mid and late maturation stages; the percentage of AHSP+ erythroblasts, AHSP expression, and relative distribution of reticulocytes and polychromatophilic erythroblasts (PolyE) were determined by cytometry. During the second time point (7-10 days postburn), Prop cohort required 35% less transfusions. At mid maturation, PBMCs from Prop-treated patients cultured in BP had 33% more AHSP+ erythroblasts and 40% more AHSP expression compared with SBC. Furthermore, at late maturation, Prop had 50% more reticulocytes and 30% less PolyEs in CP vs BP compared with SBC (11% and 6%, respectively). AHSP is positively associated with late-stage maturation of PBMC-derived erythroblasts in the presence of CP. Albeit transiently, this is more pronounced in Prop than SBC. Early administration of propranolol in burn patients supports erythropoiesis via the chaperone AHSP.

A Shift in Myeloid Cell Phenotype via Down Regulation of Siglec-1 in Island Macrophages of Bone Marrow Is Associated With Decreased Late Erythroblasts Seen in Anemia of Critical Illness.

Burn injury has been shown to significantly dampen erythropoiesis in both burn patients and in murine models. Our previous findings elucidated the erythropoietin independent defects in red cell development stages involving erythroid progenitor production and late stage erythroblast enucleation processes. We hypothesized that macrophages (MØ) in erythroblast islands (EBI) could be yet another roadblock impeding erythropoiesis following burn injury. Here we highlight that the methodology to study EBI can be achieved with single cell suspensions using a simple technique such as flow cytometry, as obtaining the central erythroblast island macrophages (EBIMØs) of interest is a delicate process. We elucidated the requisite of EBIMØ from the erythroblast as well as the MØ perspective. In addition to the primary erythropoiesis organ, the bone marrow (BM), spleens were also examined for extra-medullary erythropoiesis. Femurs and spleens were harvested from adult mice (B6D2F1) subjected to 15% total body surface area (TBSA) scald burn (B) or sham burn (S). Total bone marrow cells (TBM) and splenocytes were probed for total erythrons, early and late erythroblasts and EBIMØ by flow cytometry. There was only a marginal increase in the number of EBIMØ after burn, but, between the signatures of EBIMØ, Siglec-1 expression (MFI) was reduced by 40% in B with and a parallel 44% decrease in TBM erythrons in the BM. There were more (2.5-fold) EEBs and less LEBs (2.4-fold) per million TBM cells in B; with a corresponding decrease in Siglec-1 and Ly6G expressions in EBIMØ associated with EEB. Conversely, extra-medullary erythropoiesis was robust in spleens from B. Not only were the numbers of EBIMØs increased in B (p < 0.002), both EEBs and LEBs associated with EBIMØ were higher by 30 and 75%, respectively. Importantly, an increase in Siglec-1 and Vcam1 expressing F480+ splenic macrophages was observed after burn injury. Therefore, stagnant EEBs in the BM after burn injury could be due to low Siglec1 expressing EBIMØ, which perhaps impede their maturation into LEBs and reticulocytes. Repercussion of myeloid cell phenotype specific to BM after burn injury could plausibly account for a defective late stage RBC maturation resulting in anemia of critical illness. Summary Sentence: Characterization of erythroblast island macrophages (EBIMØ) in the bone marrow and spleen at different stages of erythropoiesis after burn injury.

How Does SCORTEN Score?

The Toxic Epidermal Necrolysis-specific severity of illness score (SCORTEN) was developed to predict mortality in patients with Stevens Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). Several studies have attempted to assess the accuracy of SCORTEN with mixed results. The objective of this study is to compare the predicted and actual mortality for patients with SJS/TEN admitted to a single high-volume burn center.This retrospective study included adult and pediatric patients admitted to our burn center with biopsy-confirmed SJS/TEN between February 2008 and February 2016. SCORTEN scores were calculated for each patient on days 1 and 3 of admission. The primary endpoint was predicted vs actual in-hospital mortality. Secondary endpoints included the association of SCORTEN, as well as individual components of SCORTEN, with hospital length of stay, length of stay in the intensive care unit, and in-hospital complications.Of 128 patients included, the mean age was 44.5 years, 40.6% (n = 52) were males, and 50.0% (n = 64) were Caucasians. The median TBSA was 12.25% on day 1 and 25% on day 3. The median SCORTEN at admission was 2 (interquartile range: 1-3.5). There were a total of 20 deaths (17.2%). SCORTEN exhibited good discrimination (c-statistic = 0.83, 95% CI: 0.75-0.91) and performed directionally as expected, but a low but nonsignificant standardized mortality ratio (75.3%, P = .164) and a Hosmer-Lemeshow test of borderline significance (P = .088) make the model's fit unclear.The accuracy of the SCORTEN model in predicting mortality for SJS/TEN patients treated in a burn center remains unclear. This study may encourage future multicenter studies to further clarify its predictive ability and may also enhance future investigation into the use of a reformulated or reweighted SCORTEN.

Seeing the forest beyond the trees: Predicting survival in burn patients with machine learning.

BACKGROUND: This study aims to identify predictors of survival for burn patients at the patient and hospital level using machine learning techniques. METHODS: The HCUP SID for California, Florida and New York were used to identify patients admitted with a burn diagnosis and merged with hospital data from the AHA Annual Survey. Random forest and stochastic gradient boosting (SGB) were used to identify predictors of survival at the patient and hospital level from the top performing model. RESULTS: We analyzed 31,350 patients from 670 hospitals. SGB (AUC 0.93) and random forest (AUC 0.82) best identified patient factors such as age and absence of renal failure (p < 0.001) and hospital factors such as full time residents (p < 0.001) and nurses (p = 0.004) to be associated with increased survival. CONCLUSIONS: Patient and hospital factors are predictive of survival in burn patients. It is difficult to control patient factors, but hospital factors can inform decisions about where burn patients should be treated.

Cervical spine clearance when unable to be cleared clinically: a pooled analysis of combined computed tomography and magnetic resonance imaging.

BACKGROUND: The role of cervical spine magnetic resonance imaging (MRI) in the evaluation of clinically unevaluable blunt trauma patients has been called into question by several recent studies. METHODS: A PubMed search was performed for all studies comparing computed tomography and MRI in the assessment of the cervical spine in patients who cannot be evaluated clinically. The radiologic findings and clinical outcomes from each study were collated for analysis. RESULTS: Data for 1,714 patients were available. All patients had a negative computed tomography scan and then underwent an MRI. There were 271 (15.8%) patients who had a previously undocumented finding on MRI with the majority (98.2%) being a ligamentous injury. Only 5 injuries (1.8%) resulted in surgical intervention. CONCLUSIONS: MRI identifies additional injuries; however, the vast majority are of minor clinical significance. Routine MRI after a negative computed tomography of the cervical spine is not supported by the current literature.

Effect of aging on renal function plus monitoring and support.

Several anatomic changes and physiologic alterations occur in the aging kidney, awareness of which is essential for the early recognition of acute kidney injury (AKI) to improve outcomes in hospitalized geriatric patients. There are no unique diagnostic methods or treatment modalities in the care of the geriatric patient with AKI. Therapy is mainly supportive, and the full spectrum of treatment options, including renal replacement therapy (RRT), should not be withheld from a patient based on age. More studies need to be performed to determine the optimal timing, intensity, and modality of RRT in the geriatric population.