Αρχειοθήκη ιστολογίου

Δευτέρα 2 Μαΐου 2022

Unsuspected clonal spread of Methicillin-resistant Staphylococcus aureus causing bloodstream infections in hospitalized adults detected using whole genome sequencing

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Abstract
Background
Though detection of transmission clusters of methicillin-resistant Staphylococcus aureus (MRSA) infections is a priority for infection control personnel in hospitals, the transmission dynamics of MRSA among hospitalized patients with bloodstream infections (BSIs) has not been thoroughly studied. Whole genome sequencing (WGS) of MRSA isolates for surveillance is valuable for detecting outbreaks in hospitals, but the bioinformatic approaches used are diverse and difficult to compare.
Methods
We combined short-read WGS with genotypic, phenotypic, and epidemiological characteristics of 106 MRSA BSI isolates collected for routine microbiological diagnosis from inpatients in two hospitals over 12 months. Clinical data and hospitalization history were abstracted from electronic medical records. We compared three genome sequence alignment strategies to assess similarity in cluster asce rtainment. We conducted logistic regression to measure the probability of predicting prior hospital overlap between clustered patient isolates by the genetic distance of their isolates.
Results
While the three alignment approaches detected similar results, they showed some variation. A Gene-family-based alignment pipeline was most consistent across MRSA clonal complexes. We identified nine unique clusters of closely related BSI isolates. Most BSI were healthcare-associated and community-onset. Our logistic model showed that with 13 single nucleotide polymorphisms the likelihood that any two patients in a cluster had overlapped in a hospital was 50 percent.
Conclusions
Multiple clusters of closely related MRSA isolates can be identified using WGS among strains cultured from BSI in two hospitals. Genomic clustering of these infections suggest that transmission resulted from a mix of community spread and healthcare exposures long before BSI diagnosis.
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Investigating aluminum cookpots as a source of lead exposure

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Journal of Exposure Science & Environmental Epidemiology, Published online: 02 May 2022; doi:10.1038/s41370-022-00431-y

Investigating aluminum cookpots as a source of lead exposure in Afghan refugee children resettled in the United States
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The tight rope act: A multicenter regional experience of tourniquets in acute trauma resuscitation

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imageBACKGROUND As tourniquets have become more prevalent, device use has been questioned. This study sought to characterize the incidence, indication, and efficacy of tourniquet placement in acute trauma resuscitation. METHODS Nine regional level 1 trauma centers prospectively enrolled for 12 months adult patients (18 years or older) who had a tourniquet placed. Age, sex, mechanism, tourniquet type, indication, applying personnel, location placed, level of occlusion, and degree of hemostasis were collected. Major vascular injury, imaging and operations performed, and outcomes were assessed. Analyses were performed with significance at p
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Extravasation and outcomes in computed tomography and angiography in patients with pelvic fractures requiring transcatheter arterial embolization: A single-center observational study

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imageBACKGROUND Extravasation on contrast-enhanced computed tomography (CECT) is a helpful indicator of the need for transcatheter arterial embolization (TAE) for pelvic fractures. However, previous reports were inconsistent on cases in which angiography is necessary, even though there is no extravasation on computed tomography. This study aimed to describe and analyze the contradictory findings in cases where extravasation is observed on angiography but not on CECT, to contribute to improved management of patients with pelvic fractures. METHODS This was a retrospective single-center study. Patients with pelvic fractures who underwent CECT and TAE between 2014 and 2020 were included. We classified the patients into three groups: CECT and angiography with extravasation (CT+Angio+), CECT with no extravasation and angiography with extravasation (CT−Angio+), and CECT with extravasation and angiography without extravasation (CT+Angio−). RESULTS A total of 113 patients were included in the study: the CT+Angio+ group had 54 patients, CT−Angio+ group, 47; and CT+Angio− group, 12. The CT−Angio+ group had a significantly longer time from arrival to CECT than the CT+Angio+ group (27 minutes vs. 23 minutes, p
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Life threat during assaultive trauma: Critical posttraumatic stress disorder risk factors for injured patients

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imageBACKGROUND Rates of posttraumatic stress disorder (PTSD) among injury survivors are higher relative to the general population, supporting the need to identify those most at risk for PTSD following injury given negative impact of PTSD on recovery. Perceived life threat and assaultive trauma are consistent risk factors for subsequent PTSD development, although less work has explored them in combination. The current study evaluated whether trauma type (assaultive vs. nonassaultive) and perceived life threat, together, led to greater PTSD symptoms 1 month and 6 months postinjury. METHODS Participants included adult injured trauma survivors admitted to a level 1 trauma center. While hospitalized, perceived life threat during trauma was assessed and mechanism of injury was collected via record review and was collapsed into two categories: assaultive and nonassaultive. The Clinician-Administered PTSD Scale (Diagnostic and Statistical Manual of Mental Disorders [Fifth Edition]) was administered at 1 month (N = 137) and 6 months (N = 220) after injury. RESULTS The four symptoms clusters of PTSD (intrusions, avoidance, hyperarousal, and negative mood/cognitions) were examined using four 2 (time) × 2 (life threat) × 2 (trauma type) mixed methods analyses of variance to assess differences based on risk factors and time. Results showed significant interaction effects of life threat, trauma type, and time for intrusive symptoms and avoidance symptoms. Individuals with life threat during assaultive traumas maintained heightened intrusive symptoms across time and increased avoidance at 6 months. On the other hand, participants with either life threat or assaultive traumas had decreased symptoms at 6 months. CONCLUSION Experiencing assaultive trauma and life threat led to greater symptoms of PTSD. Individuals with assaultive traumas who experienced life threat may represent a specific at-risk group following injury. Avoidance can protract functional impairment and impede access to care, negatively impacting recovery. This study highlights a need to assess for these peritrauma factors during hospitalization and supports early intervention targeting avoidance and intrusive symptoms in this group. LEVEL OF EVIDENCE Prognostic/Epidemiologic, Level IV.
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Evaluating the complex association between Social Vulnerability Index and trauma mortality

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imageINTRODUCTION Social determinants of health are known to impact patient-level outcomes, but they are often difficult to measure. The Social Vulnerability Index was created by the Centers for Disease Control to identify vulnerable communities using population-based measures. However, the relationship between SVI and trauma outcomes is poorly understood. METHODS In this retrospective study, we merged SVI data with a statewide trauma registry and used three analytic models to evaluate the association between SVI quartile and inpatient trauma mortality: (1) an unadjusted model, (2) a claims-based model using only covariates available to claims datasets, and (3) a registry-based model incorporating robust clinical variables collected in accordance with the National Trauma Data Standard. RESULTS We identified 83,607 adult trauma admissions from January 1, 2017, to September 30, 2020. Higher SVI was associated with worse mortality in the unadjusted model (odds ratio, 1.72 [95% confidence interval, 1.30–2.29] for highest vs. lowest SVI quintile). A weaker association between SVI and mortality was identified after adjusting for covariates common to claims data. Finally, there was no significant association between SVI and inpatient mortality after adjusting for covariates common to robust trauma registries (adjusted odds ratio, 1.10 [95% confidence interval, 0.80–1.53] for highest vs. lowest SVI quintile). Higher SVI was also associated with a higher likelihood of presenting with penetrating injuries, a shock index of >0.9, any Abbreviated Injury Scale score of >5, or in need of a blood transfusion (p
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Prehospital low titer group O whole blood is feasible and safe: Results of a prospective randomized pilot trial

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imageINTRODUCTION Low titer group O whole blood (LTOWB) resuscitation is increasingly common in both military and civilian settings. Data regarding the safety and efficacy of prehospital LTOWB remain limited. METHODS We performed a single-center, prospective, cluster randomized, prehospital through in-hospital whole blood pilot trial for injured air medical patients. We compared standard prehospital air medical care including red cell transfusion and crystalloids followed by in-hospital component transfusion to prehospital and in-hospital LTOWB resuscitation. Prehospital vital signs were used as inclusion criteria (systolic blood pressure ≤90 mm Hg and heart rate ≥108 beats per minute or systolic blood pressure ≤70 mm Hg for patients at risk of hemorrhage). Primary outcome was feasibility. Secondary outcomes included 28-day and 24-hour mortality, multiple organ failure, nosocomial infection, 24-hour transfusion requirements, and arrival coagulation parameters. RESULTS Between November 2018 and October 2020, 86 injured patients were cluster randomized by helicopter base. The trial has halted early at 77% enrollment. Overall, 28-day mortality for the cohort was 26%. Injured patients randomized to prehospital LTOWB (n = 40) relative to standard care (n = 46) were similar in demographics and injury characteristics. Intent-to-treat Kaplan-Meier survival analysis demonstrated no statistical mortality benefit at 28 days (25.0% vs. 26.1%, p = 0.85). Patients randomized to prehospital LTOWB relative to standard care had lower red cell transfusion requirements at 24 hours (p
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The effect of tranexamic acid dosing regimen on trauma/hemorrhagic shock-related glycocalyx degradation and endothelial barrier permeability: An in vitro model

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imageBACKGROUND Improved outcomes with early tranexamic acid (TXA) following trauma hemorrhagic shock (T/HS) may be related to its antifibrinolytic, as well as anti-inflammatory properties. Previous in vitro studies have shown that early TXA administration protects against T/HS endothelial barrier dysfunction and associated glycocalyx degradation. An intact endothelial glycocalyx may protect against subsequent neutrophil mediated tissue injury. We postulated that early TXA administration would mitigate against glycocalyx damage and resultant neutrophil adherence and transmigration through the endothelial barrier. This was studied in vitro using a microfluidic flow platform. METHODS Human umbilical vein endothelial cell monolayers were subjected to control or shock conditions (hypoxia + epinephrine) followed by administration of TXA 90 minutes or 180 minutes later. RESULTS "Early" TXA administration protected against glycocalyx degradation, biomarkers of increased permeability and the development of a fibrinolytic phenotype. This was associated with decreased neutrophil endothelial adherence and transmigration. There were no differences in low versus high TXA concentrations. The protective effects were only significant with "early" TXA administration. CONCLUSION There was a concentration and temporal effect of TXA administration on endothelial glycocalyx degradation. This was associated with "vascular leakiness" as indexed by the relative ratio of Ang-2/1 and polymorphonuclear neutrophil transmigration. Tranexamic acid if administered in patients with T/HS should be administered "early"; this includes in the prehospital setting.
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Direct to OR resuscitation of abdominal trauma: An NTDB propensity matched outcomes study

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imageBACKGROUND Direct to operating room resuscitation (DOR) is used by some trauma centers for severely injured trauma patients as an approach to minimize time to hemorrhage control. It is unknown whether this strategy results in favorable outcomes. We hypothesized that utilization of an emergency department operating room (EDOR) for resuscitation of patients with abdominal trauma at an urban Level I trauma center would be associated with decreased time to laparotomy and improved outcomes. METHODS We included patients 15 years or older with abdominal trauma who underwent emergent laparotomy within 120 minutes of arrival both at our institution and within a National Trauma Data Bank sample between 2007 to 2019 and 2013 to 2016, respectively. Our institutional sample was matched 1:1 to an American College of Surgeons National Trauma Databank sample using propensity score matching based on age, sex, mechanism of injury, and abdominal Abbreviated Injury Scale score. The primary outcome was time to laparotomy incision. Secondary outcomes included blood transfusion requirement, intensive care unit (ICU) length of stay (LOS), ventilator days, hospital LOS, and in-hospital mortality. RESULTS Two hundred forty patients were included (120 institutional, 120 national). Both samples were well balanced, and 83.3% sustained penetrating trauma. There were 84.2% young adults between the ages of 15 and 47, 91.7% were male, 47.5% Black/African American, with a median Injury Severity Score of 14 (interquartile range [IQR], 8–29), Glasgow Coma Scale score of 15 (IQR, 13–15), 71.7% had an systolic blood pressure of >90 mm Hg, and had a shock index of 0.9 (IQR, 0.7–1.1) which did not differ between groups (p > 0.05). Treatment in the EDOR was associated with decreased time to incision (25.5 minutes vs. 40 minutes; p ≤ 0.001), ICU LOS (1 vs. 3.1 days; p
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Beta blockade in TBI: Dose-dependent reductions in BBB leukocyte mobilization and permeability in vivo

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imageBACKGROUND Traumatic brain injury (TBI) is accompanied by a hyperadrenergic catecholamine state that can cause penumbral neuroinflammation. Prospective human studies demonstrate improved TBI survival with beta blockade (bb), although mechanisms remain unclear. We hypothesized that deranged post-TBI penumbral blood brain barrier (BBB) leukocyte mobilization and permeability are improved by bb. METHODS CD1 male mice (n = 64) were randomly assigned to severe TBI—controlled cortical impact: 6 m/s velocity, 1 mm depth, 3 mm diameter—or sham craniotomy, and IP injection of either saline or propranolol (1, 2, or 4 mg/kg) every 12 hours for 2 days. At 48 hours, in vivo pial intravital microscopy visualized live endothelial-leukocyte (LEU) interactions and BBB microvascular leakage. Twice daily clinical recovery was assessed by regaining of lost body weight and the Garcia Neurological Test (motor, sensory, reflex, balance assessments). Brain edema was determined by hemispheric wet-to-dry ratios. RESULTS Propranolol after TBI reduced both in vivo LEU rolling and BBB permeability in a dose-dependent fashion compared with no treatment (p
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DNA Methylation subclass Receptor Tyrosine Kinase II (RTK II) is predictive for seizure development in glioblastoma patients

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Abstract
Background
Seizures can present at any time before or after the diagnosis of a glioma. Roughly, 25-30 % of glioblastoma (GBM) patients initially present with seizures, and an additional 30 % develop seizures during the course of the disease. Early studies failed to show an effect of general administration of anti-epileptic drugs for glioblastoma patients, since they were unable to stratify patients into high- or low-risk seizure groups.
Methods
111 patients, who underwent surgery for a GBM, were included. Genome-wide DNA methylation profiling was performed, before methylation subclasses and copy number changes inferred from methylation data were correlated with clinical characteristics. Independently, global gene expression was analyzed in GBM methylation subclasses from TCGA datasets (n=68).
Results
Receptor tyrosine Kinase (RTK) II GBM showed a significantly higher incidence of seizures than RTK I and mesenchymal (ME S) GBM (p<0.01). Accordingly, RNA expression datasets revealed an upregulation of genes involved in neurotransmitter synapses and vesicle transport in RTK II glioblastomas. In a multivariate analysis, temporal location (p=0.02, OR 5.69) and RTK II (p=0.03, OR 5.01) were most predictive for preoperative seizures. During postoperative follow-up, only RTK II remained significantly associated with the development of seizures (p<0.01, OR 8.23). Consequently, the need for antiepileptic medication and its increase due to treatment failure was highly associated with the RTK II methylation subclass (p<0.01).
Conclusion
Our study shows a strong correlation of RTK II glioblastomas with preoperative and long-term seizures. These results underline the benefit of molecular glioblastoma profiling with important implications for postoperative seizure control.
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