First Case of 2019 Novel Coronavirus in the United States Holshue, Michelle L; DeBolt, Chas; Lindquist, Scott ...
New England journal of medicine/The New England journal of medicine,
03/2020, Volume:
382, Issue:
10
Journal Article
Peer reviewed
Open access
A healthy 35 year-old man who had visited Wuhan, China, presented with cough and fever that progressed to pneumonia. This report describes the diagnosis, clinical course, and management of the ...condition. The case highlights the importance of close coordination between clinicians and public health authorities at the local, state, and federal levels.
Implementation studies are often poorly reported and indexed, reducing their potential to inform initiatives to improve healthcare services. The Standards for Reporting Implementation Studies (StaRI) ...initiative aimed to develop guidelines for transparent and accurate reporting of implementation studies. Informed by the findings of a systematic review and a consensus-building e-Delphi exercise, an international working group of implementation science experts discussed and agreed the StaRI Checklist comprising 27 items. It prompts researchers to describe both the implementation strategy (techniques used to promote implementation of an underused evidence-based intervention) and the effectiveness of the intervention that was being implemented. An accompanying Explanation and Elaboration document (published in BMJ Open, doi:10.1136/bmjopen-2016-013318) details each of the items, explains the rationale, and provides examples of good reporting practice. Adoption of StaRI will improve the reporting of implementation studies, potentially facilitating translation of research into practice and improving the health of individuals and populations.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
The brain's initial innate response to stroke is primarily mediated by microglia, the resident macrophage of the CNS. However, as early as 4 h after stroke, the blood-brain barrier is compromised and ...monocyte infiltration occurs. The lack of discriminating markers between these two myeloid populations has led many studies to generate conclusions based on the grouping of these two populations. A growing body of evidence now supports the distinct roles played by microglia and monocytes in many disease models.
Using a flow cytometry approach, combined with ex-vivo functional assays, we were able to distinguish microglia from monocytes using the relative expression of CD45 and assess the function of each cell type following stroke over the course of 7 days.
We found that at 72 h after a 90-min middle cerebral artery occlusion (MCAO), microglia populations decrease whereas monocytes significantly increase in the stroke brain compared to sham. After stroke, BRDU incorporation into monocytes in the bone marrow increased. After recruitment to the ischemic brain, these monocytes accounted for nearly all BRDU-positive macrophages. Inflammatory activity peaked at 72 h. Microglia produced relatively higher reactive oxygen species and TNF, whereas monocytes were the predominant IL-1β producer. Although microglia showed enhanced phagocytic activity after stroke, monocytes had significantly higher phagocytic capacity at 72 h. Interestingly, we found a positive correlation between TNF expression levels and phagocytic activity of microglia after stroke.
In summary, the resident microglia population is vulnerable to the effects of severe ischemia, show compromised cell cycle progression, and adopt a largely pro-inflammatory phenotype after stroke. Infiltrating monocytes are primarily involved with early debris clearance of dying cells. These findings suggest that the early wave of infiltrating monocytes may be beneficial to stroke repair and future therapies aimed at mitigating microglia cell death may prove more effective than attempting to elicit targeted anti-inflammatory responses from damaged cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Microglia and ischemic stroke: a double-edged sword Patel, Anita R; Ritzel, Rodney; McCullough, Louise D ...
International journal of physiology, pathophysiology and pharmacology,
2013, Volume:
5, Issue:
2
Journal Article
Inflammatory processes have a fundamental role in the pathophysiology of stroke. A key initial event is the rapid activation of resident immune cells, primarily microglia. This cell population is an ...important target for new therapeutic approaches to limit stroke damage. Activation of microglia is normally held in check by strictly controlled mechanisms involving neuronal-glial communication. Ischemic stroke is a powerful stimulus that disables the endogenous inhibitory signaling and triggers microglial activation. Once activated, microglia exhibit a spectrum of phenotypes, release both pro- and anti-inflammatory mediators, and function to either exacerbate ischemic injury or help repair depending on different molecular signals the microglial receptors receive. Various ligands and receptors have been identified for microglial activation. Experimental tools to detect these inflammatory signals are being increasingly developed in an effort to define the functional roles of microglia. Fine-tuning immunomodulatory interventions based on the heterogeneous profiles of microglia are urgently needed for ischemic stroke.
Delirium in Pediatric Critical Care Patel, Anita K; Bell, Michael J; Traube, Chani
The Pediatric clinics of North America,
10/2017, Volume:
64, Issue:
5
Journal Article
Peer reviewed
Delirium occurs frequently in the critically ill child. It is a syndrome characterized by an acute onset and fluctuating course, with behaviors that reflect a disturbance in awareness and cognition. ...Delirium represents global cerebral dysfunction due to the direct physiologic effects of an underlying medical illness or its treatment. Pediatric delirium is strongly associated with poor outcomes, including increased mortality, prolonged intensive care unit length of stay, longer time on mechanical ventilation, and increased cost of care. With heightened awareness, the pediatric intensivist can detect, treat, and prevent delirium in at-risk children.
To assess the single site performance of the Dynamic Criticality Index (CI-D) models developed from a multi-institutional database to predict future care. Secondarily, to assess future care-location ...predictions in a single institution when CI-D models are re-developed using single-site data with identical variables and modeling methods. Four CI-D models were assessed for predicting care locations >6-12 hours, >12-18 hours, >18-24 hours, and >24-30 hours in the future.
Prognostic study comparing multi-institutional CI-D models' performance in a single-site electronic health record dataset to an institution-specific CI-D model developed using identical variables and modelling methods. The institution did not participate in the multi-institutional dataset.
All pediatric inpatients admitted from January 1st 2018 -February 29th 2020 through the emergency department.
The main outcome was inpatient care in routine or ICU care locations.
A total of 29,037 pediatric hospital admissions were included, with 5,563 (19.2%) admitted directly to the ICU, 869 (3.0%) transferred from routine to ICU care, and 5,023 (17.3%) transferred from ICU to routine care. Patients had a median IQR age 68 months (15-157), 47.5% were female and 43.4% were black. The area under the receiver operating characteristic curve (AUROC) for the multi-institutional CI-D models applied to a single-site test dataset was 0.493-0.545 and area under the precision-recall curve (AUPRC) was 0.262-0.299. The single-site CI-D models applied to an independent single-site test dataset had an AUROC 0.906-0.944 and AUPRC range from 0.754-0.824. Accuracy at 0.95 sensitivity for those transferred from routine to ICU care was 72.6%-81.0%. Accuracy at 0.95 specificity was 58.2%-76.4% for patients who transferred from ICU to routine care.
Models developed from multi-institutional datasets and intended for application to individual institutions should be assessed locally and may benefit from re-development with site-specific data prior to deployment.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aging is associated with an increase in basal inflammation in the CNS and an overall decline in cognitive function and poorer recovery following injury. Growing evidence suggests that leukocyte ...recruitment to the CNS is also increased with normal aging, but, to date, no systematic evaluation of these age-associated leukocytes has been performed. In this work, the effect of aging on CNS leukocyte recruitment was examined. Aging was associated with more CD45(high) leukocytes, primarily composed of conventional CD8(+) T cells. These results were strain independent and seen in both sexes. Intravascular labeling and immunohistology revealed the presence of parenchymal CD8(+) T cells in several regions of the brain, including the choroid plexus and meninges. These cells had effector memory (CD44(+)CD62L(-)) and tissue-resident phenotypes and expressed markers associated with TCR activation. Analysis of TCRvβ repertoire usage suggested that entry into the CNS is most likely stochastic rather than Ag driven. Correlational analyses revealed a positive association between CD8 T cell numbers and decreased proinflammatory function of microglia. However, the effects of cerebral ischemia and ex vivo stimulation of these cells dramatically increased production of TNF, IFN-γ, and MCP-1/CCL2. Taken together, we identified a novel population of resident memory, immunosurveillant CD8 T cells that represent a hallmark of CNS aging and appear to modify microglia homeostasis under normal conditions, but are primed to potentiate inflammation and leukocyte recruitment following ischemic injury.
Abstract Inflammation in the central nervous system (CNS) is primarily regulated by microglia. No longer considered a homogenous population, microglia display a high degree of heterogeneity, ...immunological diversity and regional variability in function. Given their low rate of self-renewal, the microenvironment in which microglia reside may play an important role in microglial senescence. This study examines age-related changes in microglia in the brain and spinal cord. Using ex-vivo flow cytometry analyses, functional assays were performed to assess changes in microglial morphology, oxidative stress, cytokine production, and phagocytic activity with age in both the brain and spinal cord. The regional CNS environment had a significant effect on microglial activity with age. Blood-CNS barrier permeability was greater in the aging spinal cord compared with aging brain; this was associated with increased tissue cytokine levels. Aged microglia had deficits in phagocytosis at baseline and after stimulus-induced activation. The identification of age-specific, high scatter microglia together with the use of ex-vivo functional analyses provides the first functional characterization of senescent microglia. Age and regional-specificity of CNS disease should be taken into consideration when developing immune-modulatory treatments.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Summary Background Post-stroke pneumonia is associated with increased mortality and poor functional outcomes. This study assessed the effectiveness of antibiotic prophylaxis for reducing pneumonia in ...patients with dysphagia after acute stroke. Methods We did a prospective, multicentre, cluster-randomised, open-label controlled trial with masked endpoint assessment of patients older than 18 years with dysphagia after new stroke recruited from 48 stroke units in the UK, accredited and included in the UK National Stroke Audit. We excluded patients with contraindications to antibiotics, pre-existing dysphagia, or known infections, or who were not expected to survive beyond 14 days. We randomly assigned the units (1:1) by computer to give either prophylactic antibiotics for 7 days plus standard stroke unit care or standard stroke unit care only to patients clustered in the units within 48 h of stroke onset. We did the randomisation with minimisation to stratify for number of admissions and access to specialist care. Patient and staff who did the assessments and analyses were masked to stroke unit allocation. The primary outcome was post-stroke pneumonia in the first 14 days, assessed with both a criteria-based, hierarchical algorithm and by physician diagnosis in the intention-to-treat population. Safety was also analysed by intention to treat. This trial is closed to new participants and is registered with isrctn.com , number ISRCTN37118456. Findings Between April 21, 2008, and May 17, 2014, we randomly assigned 48 stroke units (and 1224 patients clustered within the units) to the two treatment groups: 24 to antibiotics and 24 to standard care alone (control). 11 units and seven patients withdrew after randomisation before 14 days, leaving 1217 patients in 37 units for the intention-to-treat analysis (615 patients in the antibiotics group, 602 in control). Prophylactic antibiotics did not affect the incidence of algorithm-defined post-stroke pneumonia (71 13% of 564 patients in antibiotics group vs 52 10% of 524 in control group; marginal adjusted odds ratio OR 1·21 95% CI 0·71–2·08, p=0·489, intraclass correlation coefficient ICC 0·06 95% CI 0·02–0·17. Algorithm-defined post-stroke pneumonia could not be established in 129 (10%) patients because of missing data. Additionally, we noted no differences in physician-diagnosed post-stroke pneumonia between groups (101 16% of 615 patients vs 91 15% of 602, adjusted OR 1·01 95% CI 0·61–1·68, p=0·957, ICC 0·08 95% CI 0·03–0·21). The most common adverse events were infections unrelated to post-stroke pneumonia (mainly urinary tract infections), which were less frequent in the antibiotics group (22 4% of 615 vs 45 7% of 602; OR 0·55 0·32–0·92, p=0·02). Diarrhoea positive for Clostridium difficile occurred in two patients (<1%) in the antibiotics group and four (<1%) in the control group, and meticillin-resistant Staphylococcus aureus colonisation occurred in 11 patients (2%) in the antibiotics group and 14 (2%) in the control group. Interpretation Antibiotic prophylaxis cannot be recommended for prevention of post-stroke pneumonia in patients with dysphagia after stroke managed in stroke units. Funding UK National Institute for Health Research.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
To describe the incidence of delirium in pediatric patients after cardiac bypass surgery and explore associated risk factors and effect of delirium on in-hospital outcomes.
Prospective observational ...single-center study.
Fourteen-bed pediatric cardiothoracic ICU.
One hundred ninety-four consecutive admissions following cardiac bypass surgery, 1 day to 21 years old.
Subjects were screened for delirium daily using the Cornell Assessment of Pediatric Delirium.
Incidence of delirium in this sample was 49%. Delirium most often lasted 1-2 days and developed within the first 1-3 days after surgery. Age less than 2 years, developmental delay, higher Risk Adjustment for Congenital Heart Surgery 1 score, cyanotic disease, and albumin less than three were all independently associated with development of delirium in a multivariable model (all p < 0.03). Delirium was an independent predictor of prolonged ICU length of stay, with patients who were ever delirious having a 60% increase in ICU days compared with patients who were never delirious (p < 0.01).
In our institution, delirium is a frequent problem in children after cardiac bypass surgery, with identifiable risk factors. Our study suggests that cardiac bypass surgery significantly increases children's susceptibility to delirium. This highlights the need for heightened, targeted delirium screening in all pediatric cardiothoracic ICUs to potentially improve outcomes in this vulnerable patient population.
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