Search

Background The use of low titer group O whole blood (LTOWB) for resuscitation of patients with traumatic hemorrhage is becoming increasingly common. Practices regarding the administration of RhD-positive LTOWB to childbearing age females (CBAFs) vary between institutions due to concerns about RhD alloimmunization. This study examined practices related to LTOWB transfusion as they pertain to age and sex.Methods This was a secondary analysis of the Shock, Whole blood, and Assessment of TBI (traumatic brain injury) trial, a prospective, multicenter observational cohort study where outcomes following LTOWB transfusion were analyzed at seven level 1 trauma centers between 2018 and 2021, as well as a survey on transfusion practices at these centers conducted in 2023. The proportion of patients who received LTOWB or components was examined over the course of the study and grouped by age and sex, and the RhD group of injured CBAFs was documented.Results A total of 1046 patients were evaluated: 130 females aged

Introduction The utility of pancreaticoduodenectomy (PD) for high-grade traumatic injuries remains unclear and data surrounding its use are limited. We hypothesized that PD does not result in improved outcomes when compared with non-PD surgical management of grade IV–V pancreaticoduodenal injuries.Methods This is a retrospective, multicenter analysis from 35 level 1 trauma centers from January 2010 to December 2020. Included patients were ≥15 years of age with the American Association for the Surgery of Trauma grade IV–V duodenal and/or pancreatic injuries. The study compared operative repair strategy: PD versus non-PD.Results The sample (n=95) was young (26 years), male (82%), with predominantly penetrating injuries (76%). There was no difference in demographics, hemodynamics, or blood product requirement on presentation between PD (n=32) vs non-PD (n=63). Anatomically, PD patients had more grade V duodenal, grade V pancreatic, ampullary, and pancreatic ductal injuries compared with non-PD patients (all p

Purpose Ketamine has historically been contraindicated in traumatic brain injury (TBI) due to concern for raising intracranial pressure. However, it is increasingly being used in TBI due to the favorable respiratory and hemodynamic properties. To date, no studies have evaluated whether ketamine administered in subjects with TBI is associated with patient survival or disability. Methods We performed a retrospective analysis of data from the multicenter Prehospital Tranexamic Acid Use for Traumatic Brain Injury trial, comparing ketamine-exposed and ketamine-unexposed TBI subjects to determine whether an association exists between ketamine administration and mortality, as well as secondary outcome measures. Results We analyzed 841 eligible subjects from the original study, of which 131 (15.5%) received ketamine. Ketamine-exposed subjects were younger (37.3±16.9 years vs. 42.0±18.6 years, P=0.037), had a worse initial Glasgow Coma Scale score (7±3 vs. 8±4, P=0.003), and were more likely to be intubated than ketamine-unexposed subjects (88.5% vs. 44.2%, P

In this focused genetic case–control study, we analyzed two functional single-nucleotide variants (SNVs) associated with breast cancer risk (rs2046210, rs9383590) and one risk SNV for an implantation defect and infertility (rs9340799) for their association with endometriosis susceptibility, progression and ESR1 gene regulation in endometriosis patients. The rs2046210, rs9383590 and rs9340799 SNVs were genotyped in 153 endometriosis patients and 87 control subjects with Caucasian ancestry. We analyzed the association of all SNVs with endometriosis susceptibility in all patients and in subgroups and assessed the concordance between the SNVs. Quantitative reverse transcription PCR was used to determine ESR1 gene expression in the eutopic endometrial tissue of the controls and endometriosis patients. The heterozygous rs2046210 GA genotype was associated with significantly increased endometriosis risk, particularly in younger, leaner and infertile women and with an increased ESR1 gene expression in the eutopic endometrium of these patients, compared to controls. The minor AA genotype of rs2046210 was identified as a potential risk factor for endometriosis progression in women with mild endometriosis. The results from this analysis indicate that rs2046210 may be a functional genetic variant associated with endometriosis development and progression.

Pre-hospital resuscitation of critically injured patients traditionally includes supplemental oxygen therapy to address potential hypoxemia. The objective of this study was to explore the association between pre-hospital hypoxemia, hyperoxemia, and mortality in patients with traumatic brain injury (TBI) and traumatic shock. We hypothesized that both hypoxemia and hyperoxemia would be associated with increased mortality. We used the Resuscitation Outcomes Consortium Prospective Observational Prehospital and Hospital Registry for Trauma (ROC PROPHET) database of critically injured patients to identify a severe TBI cohort (pre-hospital Glasgow Coma Scale [GCS] 3?8) and a traumatic shock cohort (systolic blood pressure ?90?mm Hg and pre-hospital GCS >8). Arterial blood gas (ABG) obtained within 30?min of hospital arrival was required for inclusion. Patients with hypoxemia (PaO2 400?mm Hg) were compared to those with normoxemia (PaO2 80?400?mm Hg) with regard to the primary outcome measure of in-hospital mortality in both the TBI and traumatic shock cohorts. Multiple logistic regression was used to calculate odds ratios (ORs) after adjustment for multiple covariables. In addition, regression spline curves were generated to estimate the risk of death as a continuous function of PaO2 levels. A total of 1248 TBI patients were included, of whom 396 (32%) died before hospital discharge. Associations between hypoxemia and increased mortality (OR, 1.8; 95% confidence interval [CI], 1.2?2.8; p?=?0.008) and between hyperoxemia and decreased mortality (OR, 0.6; 95% CI, 0.4?0.9; p?=?0.018) were observed. A total of 582 traumatic shock patients were included, of whom 52 (9%) died before hospital discharge. No statistically significant associations were observed between in-hospital mortality and either hypoxemia (OR, 1.0; 95% CI, 0.4?2.4; p?=?0.987) or hyperoxemia (OR, 1.9; 95% CI, 0.6?5.7; p?=?0.269). Among patients with severe TBI but not traumatic shock, hypoxemia was associated with an increase of in-hospital mortality and hyperoxemia was associated with a decrease of in-hospital mortality.

COVID-19 diagnosis is commonly performed by PCR testing, however, serologic methods are more accurate and versatile for monitoring disease burden and epidemiology. Here the authors report a protein microarray with antigens from SARS-CoV-2, SARS-CoV, MERS-CoV as well as common human respiratory viruses.

The ABC transporter ABCA7 has been found to be aberrantly expressed in a variety of cancer types, including breast cancer. We searched for specific epigenetic and genetic alterations and alternative splicing variants of ABCA7 in breast cancer and investigated whether these alterations are associated with ABCA7 expression. By analyzing tumor tissues from breast cancer patients, we found CpGs at the exon 5–intron 5 boundary aberrantly methylated in a molecular subtype-specific manner. The detection of altered DNA methylation in tumor-adjacent tissues suggests epigenetic field cancerization. In breast cancer cell lines, DNA methylation levels of CpGs in promoter-exon 1, intron 1, and at the exon 5–intron 5 boundary were not correlated with ABCA7 mRNA levels. By qPCR involving intron-specific and intron-flanking primers, we identified intron-containing ABCA7 mRNA transcripts. The occurrence of intron-containing transcripts was neither molecular subtype-specific nor directly correlated with DNA methylation at the respective exon–intron boundaries. Treatment of breast cancer cell lines MCF-7, BT-474, SK-BR3, and MDA-MB-231 with doxorubicin or paclitaxel for 72 h resulted in altered ABCA7 intron levels. Shotgun proteomics revealed that an increase in intron-containing transcripts was associated with significant dysregulation of splicing factors linked to alternative splicing.

Estrogen receptor α (ERα), encoded by the ESR1 gene, is a key prognostic and predictive biomarker firmly established in routine diagnostics and as a therapeutic target of breast cancer, and it has a central function in breast cancer biology. Genetic variants at 6q25.1, containing the ESR1 gene, were found to be associated with breast cancer susceptibility. The rs2046210 and rs9383590 single nucleotide variants (SNVs) are located in the same putative enhancer region upstream of ESR1 and were separately identified as candidate causal variants responsible for these associations. Here, both SNVs were genotyped in a hospital-based case-control study of 409 female breast cancer patients and 422 female controls of a Central European (Austrian) study population. We analyzed the association of both SNVs with the risk, age at onset, clinically and molecularly relevant characteristics and prognosis of breast cancer. We also assessed the concordances between both SNVs and the associations of each SNV conditional on the other SNV. The minor alleles of both SNVs were found to be non-significantly associated with an increased breast cancer risk. Significant associations were found in specific subpopulations, particularly in patients with an age younger than 55 years. The minor homozygotes of rs2046210 and the minor homozygotes plus heterozygotes of rs9383590 exhibited a several-years-younger age at onset than the common homozygotes, which was more pronounced in ER-positive and luminal patients. Importantly, the observed associations of each SNV were not consistently nullified upon correction for the other SNV nor upon analyses in common homozygotes for the other SNV. We conclude that both SNVs remain independent candidate causal variants.

Traumatic injury is the leading cause of death in young people in the USA. Our knowledge of prehospital resuscitation is constantly evolving and is often informed by research based on military experience. A move toward balanced blood product resuscitation and away from excessive crystalloid use has led to improvements in outcomes for trauma patients. This has been facilitated by new technologies allowing more front-line use of blood products as well as use of tranexamic acid in the prehospital setting. In this article, we review current practices in prehospital resuscitation and the studies that have informed these practices.

Abstract Background Cell based therapies, such as bone marrow derived mesenchymal stem cells (BM-MSCs; also known as mesenchymal stromal cells), are currently under investigation for a number of disease applications. The current challenge facing the field is maintaining the consistency and quality of cells especially for cell dose production for pre-clinical testing and clinical trials. Here we determine how BM-donor variability and thus the derived MSCs factor into selection of the optimal primary cell lineage for cell production and testing in a pre-clinical swine model of trauma induced acute respiratory distress syndrome. Methods We harvested bone marrow and generated three different primary BM-MSCs from Yorkshire swine. Cells from these three donors were characterized based on (a) phenotype (morphology, differentiation capacity and flow cytometry), (b) in vitro growth kinetics and metabolic activity, and (c) functional analysis based on inhibition of lung endothelial cell permeability. Results Cells from each swine donor exhibited varied morphology, growth rate, and doubling times. All expressed the same magnitude of standard MSC cell surface markers by flow cytometry and had similar differentiation potential. Metabolic activity and growth potential at each of the passages varied between the three primary cell cultures. More importantly, the functional potency of the MSCs on inhibition of endothelial permeability was also cell donor dependent. Conclusion This study suggests that for production of MSCs for cell-based therapy, it is imperative to examine donor variability and characterize derived MSCs for marker expression, growth and differentiation characteristics and testing potency in application dependent assays prior to selection of the optimal cell lineage for large scale expansion and dose production.

Identifying computational tasks suitable for (future) quantum computers is an active field of research. Here we explore utilizing quantum computers for the purpose of solving differential equations. We consider two approaches: (i) basis encoding and fixed-point arithmetic on a digital quantum computer, and (ii) representing and solving high-order Runge-Kutta methods as optimization problems on quantum annealers. As realizations applied to two-dimensional linear ordinary differential equations, we devise and simulate corresponding digital quantum circuits, and implement and run a 6$^{\mathrm{th}}$ order Gauss-Legendre collocation method on a D-Wave 2000Q system, showing good agreement with the reference solution. We find that the quantum annealing approach exhibits the largest potential for high-order implicit integration methods. As promising future scenario, the digital arithmetic method could be employed as an "oracle" within quantum search algorithms for inverse problems.