Management of pediatric blunt abdominal trauma in a Dutch level one trauma center

Purpose: Most children with intra-abdominal injuries can be managed non-operatively. However, in Europe, there are many different healthcare systems for the treatment of pediatric trauma patients. Therefore, the aim of this study was to describe the management strategies and outcomes of all pediatric patients with blunt intra-abdominal injuries in our unique dedicated pediatric trauma center with a pediatric trauma surgeon. Methods: We performed a retrospective, single-center, cohort study to investigate the management of pediatric patients with blunt abdominal trauma. From the National Trauma Registration database, we retrospectively identified pediatric (≤ 18 years) patients with blunt abdominal injuries admitted to the UMCU from January 2012 till January 2018. Results: A total of 121 pediatric patients were included in the study. The median [interquartile range (IQR)] age of patients was 12 (8–16) years, and the median ISS was 16 (9–25). High-grade liver injuries were found in 12 patients. Three patients had a pancreas injury grade V. Furthermore, 2 (1.6%) patients had urethra injuries and 10 (8.2%) hollow viscus injuries were found. Eighteen (14.9%) patients required a laparotomy and 4 (3.3%) patients underwent angiographic embolization. In 6 (5.0%) patients, complications were found and in 4 (3.3%) children intervention was needed for their complication. No mortality was seen in patients treated non-operatively. One patient died in the operative management group. Conclusions: In conclusion, it is safe to treat most children with blunt abdominal injuries non-operatively if monitoring is adequate. These decisions should be made by the clinicians operating on these children, who should be an integral part of the entire group of treating physicians. Surgical interventions are only needed in case of hemodynamic instability or specific injuries such as bowel perforation

New automated analysis to monitor neutrophil function point-of-care in the intensive care unit after trauma

BACKGROUND: Patients often develop infectious complications after severe trauma. No biomarkers exist that enable early identification of patients who are at risk. Neutrophils are important immune cells that combat these infections by phagocytosis and killing of pathogens. Analysis of neutrophil function used to be laborious and was therefore not applicable in routine diagnostics. Hence, we developed a quick and point-of-care method to assess a critical part of neutrophil function, neutrophil phagosomal acidification. The aim of this study was to investigate whether this method was able to analyze neutrophil functionality in severely injured patients and whether a relation with the development of infectious complications was present. RESULTS: Fifteen severely injured patients (median ISS of 33) were included, of whom 6 developed an infection between day 4 and day 9 after trauma. The injury severity score did not significantly differ between patients who developed an infection and patients who did not (p = 0.529). Patients who developed an infection showed increased acidification immediately after trauma (p = 0.006) and after 3 days (p = 0.026) and a decrease in the days thereafter to levels in the lower normal range. In contrast, patients who did not develop infectious complications showed high-normal acidification within the first days and increased tasset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. CONCLUSION: Neutrophil function can be measured in the ICU setting by rapid point-of-care analysis of phagosomal acidification. This analysis differed between trauma patients who developed infectious complications and trauma patients who did not. Therefore, this assay might prove a valuable asset to identify patients at risk for infections after trauma and to monitor the inflammatory state of these trauma patients. TRIAL REGISTRATION: Central Committee on Research Involving Human Subjects, NL43279.041.13. Registered 14 February 2014. https://www.toetsingonline.nl/to/ccmo_search.nsf/Searchform?OpenForm

Comprehensive multivariate evaluation of the effects on cell phenotypes in multicolor flow cytometry data using ANOVA simultaneous component analysis

This work proposes an approach to assess the effects observed in multicolor flow cytometry (MFC) experiments, for all markers and experimental factors simultaneously. It achieves this end by extending ANOVA simultaneous component analysis (ASCA), a multivariate version of ANOVA, to flow cytometry data. It is based on an initial multiset PCA model to describe the main variation patterns of cell marker expression, followed by an ASCA model on the histograms built from these PCA scores. This approach allows for determining the variations in cell phenotype distribution that are related to the experimental design. On a data set from a study of the immune response to prolonged physical exercise, the proposed method computed the effect size and statistical significance of all the experimental factors and their interactions. Most notably, it provided easily interpretable submodels for the overall effect of the walking exercise and for the interaction between exercise and the responsiveness to a bacterial stimulus. The application of a time-guided sequential clustering algorithm to the ASCA scores revealed a stratification of the studied individuals based on their neutrophil activation dynamics. These effects were not clearly detectable using PCA alone. In comparison with pairwise classification models by DAMACY (a discriminant analysis method for MFC data), ASCA results were less detailed in describing differences between specific samples, but had the advantage of modeling several factors and levels simultaneously. Such characteristics make the proposed implementation of ASCA an effective and complementary addition to the chemometric methodologies for the analysis of MFC data

The Systemic Immune Response in COVID-19 Is Associated with a Shift to Formyl-Peptide Unresponsive Eosinophils

A malfunction of the innate immune response in COVID-19 is associated with eosinopenia, particularly in more severe cases. This study tested the hypothesis that this eosinopenia is COVID-19 specific and is associated with systemic activation of eosinophils. Blood of 15 healthy controls and 75 adult patients with suspected COVID-19 at the ER were included before PCR testing and analyzed by point-of-care automated flow cytometry (CD10, CD11b, CD16, and CD62L) in the absence or presence of a formyl peptide (fNLF). Forty-five SARS-CoV-2 PCR positive patients were grouped based on disease severity. PCR negative patients with proven bacterial (n = 20) or other viral (n = 10) infections were used as disease controls. Eosinophils were identified with the use of the FlowSOM algorithm. Low blood eosinophil numbers (<100 cells/µL; p < 0.005) were found both in patients with COVID-19 and with other infectious diseases, albeit less pronounced. Two discrete eosinophil populations were identified in healthy controls both before and after activation with fNLF based on the expression of CD11b. Before activation, the CD11b bright population consisted of 5.4% (CI 95% = 3.8, 13.4) of total eosinophils. After activation, this population of CD11b bright cells comprised nearly half the population (42.21%, CI 95% = 35.9, 54.1). Eosinophils in COVID-19 had a similar percentage of CD11b bright cells before activation (7.6%, CI 95% = 4.5, 13.6), but were clearly refractory to activation with fNLF as a much lower percentage of cells end up in the CD11b bright fraction after activation (23.7%, CI 95% = 18.5, 27.6; p < 0.001). Low eosinophil numbers in COVID-19 are associated with refractoriness in responsiveness to fNLF. This might be caused by migration of fully functional cells to the tissue

Quantitative EMG Changes During 12-Week DeLorme's Axiom Strength Training

Strength training is one of the most common exercises practiced in the field of physical therapy or sports training. However, limited methodology is available to evaluate its effect on the target muscle. This study aimed to test the hypothesis that surface electromyographic (EMG) data from both isometric and isotonic exercise can express changes within the muscle during a 12-week strength training program. Ten healthy male volunteer students (5 for training, 5 for controls) from Yonsei University were recruited for evaluation in this study. DeLorme's axiom was practiced for 12 weeks in the dominant elbow flexors and knee extensors of the training group. Tension for 1 repetition maximum and maximal voluntary isometric contraction, and surface EMG information such as the integrated EMG and three variables from the regression line of median frequency (MDF) data were measured at weeks 0, 3, 6, 9, and 12. The limb circumference was measured at weeks 0 and 12. During the strength training, which was enough for the increment of muscle strength and limb circumference, the rectified-integrated EMG and initial MDF increased with a significant linear pattern in both types of contraction. The two surface EMG variables were able to monitor the physiologic muscle changes during the training. Based on these results, we propose that these two surface EMG variables can be used for monitoring electrophysiological changes in the specific muscle that is undergoing the training program, under conditions where the contraction mode for EMG data collection is either static or dynamic

An increase in CD62Ldim neutrophils precedes the development of pulmonary embolisms in COVID-19 patients

OBJECTIVES: A high incidence of pulmonary embolism (PE) is reported in patients with critical Corona Virus Disease 2019 (COVID-19). Neutrophils may contribute to this through a process referred to as immunothrombosis. The aim of this study was to investigate the occurrence of neutrophil subpopulations in blood preceding the development of COVID-19 associated PE. METHODS: We studied COVID-19 patients admitted to the ICU of our tertiary hospital between 19-03-2020 and 17-05-2020. Point-of-care fully automated flow cytometry was performed prior to ICU admission, measuring the neutrophil activation/maturation markers CD10, CD11b, CD16 and CD62L. Neutrophil receptor expression was compared between patients who did or did not develop PE (as diagnosed on CT angiography) during or after their ICU stay. RESULTS: Among 25 eligible ICU patients, 22 subjects were included for analysis, of whom nine developed PE. The median (IQR) time between neutrophil phenotyping and PE occurrence was 9 (7-12) days. A significant increase in the immune-suppressive neutrophil phenotype CD16bright /CD62Ldim was observed on the day of ICU admission (p=0.014) in patients developing PE compared to patients who did not. CONCLUSION: The increase in this neutrophil phenotype indicates that the increased number of CD16bright /CD62Ldim neutrophils might be used as prognostic marker to predict those patients that will develop PE in critical COVID19 patients

Identification of neutrophil phenotype categories in geriatric hip fracture patients aids in personalized medicine

OBJECTIVES: The number of geriatric hip fracture patients is high and expected to rise in the coming years, and many are frail and at risk for adverse outcomes. Early identification of high-risk patients is crucial to balance treatment and optimize outcome, but remains challenging. Previous research in patients with multitrauma suggested that neutrophil phenotype analysis could aid in early identification of high-risk patients. This pilot study investigated the feasibility and clinical value of neutrophil phenotype analysis in geriatric patients with a hip fracture. METHODS: A prospective study was conducted in a regional teaching hospital in the Netherlands. At the emergency department, blood samples were collected from geriatric patients with a hip fracture and analyzed using automated flow cytometry. Flow cytometry data were processed using an automated clustering algorithm. Neutrophil activation data were compared with a healthy control cohort. Neutrophil phenotype categories were assessed based on two-dimensional visual assessment of CD16/CD62L expression. RESULTS: Blood samples from 45 geriatric patients with a hip fracture were included. Neutrophils showed an increased activation profile and decreased responsiveness to formyl peptides when compared to healthy controls. The neutrophil phenotype of all patients was categorized. The incidence of severe adverse outcome was significantly different between the different categories ( P = 0.0331). Moreover, patients with neutrophil phenotype category 0 developed no severe adverse outcomes. CONCLUSIONS: Using point-of-care fully automated flow cytometry to analyze the neutrophil compartment in geriatric hip fracture patients is feasible and holds clinical value in determining patients at risk for adverse outcome. This study is a first step toward immuno-based precision medicine for identifying geriatric hip fracture patients that are deemed fit for surgery

Kinetics of Neutrophil Subsets in Acute, Subacute, and Chronic Inflammation

At homeostasis the vast majority of neutrophils in the circulation expresses CD16 and CD62L within a narrow expression range, but this quickly changes in disease. Little is known regarding the changes in kinetics of neutrophils phenotypes in inflammatory conditions. During acute inflammation more heterogeneity was found, characterized by an increase in CD16dim banded neutrophils. These cells were probably released from the bone marrow (left shift). Acute inflammation induced by human experimental endotoxemia (LPS model) was additionally accompanied by an immediate increase in a CD62Llow neutrophil population, which was not as explicit after injury/trauma induced acute inflammation. The situation in sub-acute inflammation was more complex. CD62Llow neutrophils appeared in the peripheral blood several days (>3 days) after trauma with a peak after 10 days. A similar situation was found in the blood of COVID-19 patients returning from the ICU. Sorted CD16low and CD62Llow subsets from trauma and COVID-19 patients displayed the same nuclear characteristics as found after experimental endotoxemia. In diseases associated with chronic inflammation (stable COPD and treatment naive HIV) no increases in CD16low or CD62Llow neutrophils were found in the peripheral blood. All neutrophil subsets were present in the bone marrow during homeostasis. After LPS rechallenge, these subsets failed to appear in the circulation, but continued to be present in the bone marrow, suggesting the absence of recruitment signals. Because the subsets were reported to have different functionalities, these results on the kinetics of neutrophil subsets in a range of inflammatory conditions contribute to our understanding on the role of neutrophils in health and disease

Flow cytometric evaluation of the neutrophil compartment in COVID-19 at hospital presentation: A normal response to an abnormal situation

Coronavirus disease 2019 (COVID-19) is a rapidly emerging pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Critical COVID-19 is thought to be associated with a hyper-inflammatory process that can develop into acute respiratory distress syndrome, a critical disease normally mediated by dysfunctional neutrophils. This study tested the hypothesis whether the neutrophil compartment displays characteristics of hyperinflammation in COVID-19 patients. Therefore, a prospective study was performed on all patients with suspected COVID-19 presenting at the emergency room of a large academic hospital. Blood drawn within 2 d after hospital presentation was analyzed by point-of-care automated flow cytometry and compared with blood samples collected at later time points. COVID-19 patients did not exhibit neutrophilia or eosinopenia. Unexpectedly neutrophil activation markers (CD11b, CD16, CD10, and CD62L) did not differ between COVID-19-positive patients and COVID-19-negative patients diagnosed with other bacterial/viral infections, or between COVID-19 severity groups. In all patients, a decrease was found in the neutrophil maturation markers indicating an inflammation-induced left shift of the neutrophil compartment. In COVID-19 this was associated with disease severity