In multiple sclerosis, successful remyelination within the injured CNS is largely dependent on the survival and differentiation of oligodendrocyte progenitor cells. During inflammatory injury, ...oligodendrocytes and oligodendrocyte progenitor cells within lesion sites are exposed to secreted products derived from both infiltrating immune cell subsets and CNS-resident cells. Such products may be considered either proinflammatory or anti-inflammatory and have the potential to contribute to both injury and repair processes. Within the CNS, astrocytes also contribute significantly to oligodendrocyte biology during development and following inflammatory injury. The overall objective of the current study was to determine how functionally distinct proinflammatory and anti-inflammatory human immune cell subsets, implicated in multiple sclerosis, can directly and/or indirectly (via astrocytes) impact human oligodendrocyte progenitor cell survival and differentiation. Proinflammatory T cell (Th1/Th17) and M1-polarized myeloid cell supernatants had a direct cytotoxic effect on human A2B5(+) neural progenitors, resulting in decreased O4(+) and GalC(+) oligodendrocyte lineage cells. Astrocyte-conditioned media collected from astrocytes pre-exposed to the same proinflammatory supernatants also resulted in decreased oligodendrocyte progenitor cell differentiation without an apparent increase in cell death and was mediated through astrocyte-derived CXCL10, yet this decrease in differentiation was not observed in the more differentiated oligodendrocytes. Th2 and M2 macrophage or microglia supernatants had neither a direct nor an indirect impact on oligodendrocyte progenitor cell differentiation. We conclude that proinflammatory immune cell responses can directly and indirectly (through astrocytes) impact the fate of immature oligodendrocyte-lineage cells, with oligodendrocyte progenitor cells more vulnerable to injury compared with mature oligodendrocytes.
Background
The objective was to examine the association of blood pressure variability (BPV) during the first 24 h after intensive care unit admission with the likelihood of delirium and depressed ...alertness without delirium (“depressed alertness”).
Methods
This retrospective, observational, cohort study included all consecutive adult patients admitted to an intensive care unit at Mayo Clinic, Rochester, Minnesota, from July 1, 2004, through October 31, 2015. The primary outcomes were delirium and delirium-free days, and the secondary outcomes included depressed alertness and depressed alertness-free days. Logistic regression was performed to determine the association of BPV with delirium and depressed alertness. Proportional odds regression was used to assess the association of BPV with delirium-free days and depressed alertness-free days.
Results
Among 66,549 intensive care unit admissions, delirium was documented in 20.2% and depressed alertness was documented in 24.4%. Preserved cognition was documented in 55.4% of intensive care unit admissions. Increased systolic and diastolic BPV was associated with an increased odds of delirium and depressed alertness. The magnitude of the association per 5-mm Hg increase in systolic average real variability (the average of absolute value of changes between consecutive systolic blood pressure readings) was greater for delirium (odds ratio 1.34; 95% confidence interval 1.29–1.40;
P
< 0.001) than for depressed alertness (odds ratio 1.06; 95% confidence interval 1.02–1.10;
P
= 0.004). Increased systolic and diastolic BPV was associated with fewer delirium-free days but not with depressed alertness-free days.
Conclusions
BPV in the first 24 h after intensive care unit admission is associated with an increased likelihood of delirium and fewer delirium-free days.
Objective
Dimethyl fumarate (DMF), a therapy for relapsing‐remitting multiple sclerosis (RRMS), is implicated as acting on inflammatory and antioxidant responses within both systemic immune and/or ...central nervous system (CNS) compartments. Orally administered DMF is rapidly metabolized to monomethyl fumarate (MMF). Our aim was to analyze the impact of fumarates on antiinflammatory and antioxidant profiles of human myeloid cells found in the systemic compartment (monocytes) and in the inflamed CNS (blood‐derived macrophages and brain‐derived microglia).
Methods
We analyzed cytokine and antioxidant expression in monocytes from untreated or DMF‐treated RRMS patients and controls, and in monocyte‐derived macrophages (MDMs) and microglia isolated from adult and fetal human brain tissue.
Results
Monocytes from multiple sclerosis (MS) patients receiving DMF had reduced expression of the proinflammatory micro‐RNA miR‐155 and of antioxidant genes HMOX1 and OSGIN1 compared to untreated MS patients; similar changes were observed in patients receiving FTY720 and/or natalizumab. In vitro addition of DMF but not MMF to MDMs and microglia inhibited lipopolysaccharide‐induced production of inflammatory cytokines and increased expression of the antioxidant gene HMOX1 in the absence of significant cytotoxicity.
Interpretation
Our in vivo‐based observations that effects of DMF therapy on systemic myeloid cell gene expression are also observed with FTY720 and natalizumab therapy suggests that the effect may be indirect, reflecting reduced overall disease activity. Our in vitro results demonstrate significant effects of DMF but not MMF on inflammation and antioxidant responses by MDMs and microglia, questioning the mechanisms whereby DMF therapy would modulate myeloid cell properties within the CNS.
Background
This study aims to assess the association of postoperative stroke with intraoperative hemodynamic variability and transfusion management.
Methods
In this case-control study, adult patients ...(≥ 18 years) who had a stroke within 72 hours of a surgical procedure were matched to 2 control patients according to age, sex, and procedure type. Primary risk factors assessed were intraoperative fluid administration, blood product transfusion, vasopressor use, and measures of variability in systolic and diastolic blood pressure and heart rate: maximum, minimum, range, SD, and average real variability. The variables were analyzed with conditional logistic regression, which accounted for the 1:2 matched case-control study design.
Results
Among 687 581 procedures, we identified 64 postoperative strokes (incidence, 9.3 95% CI, 7.2-11.9 strokes per 100 000 procedures). These cases were matched with 128 controls. Stroke cases had higher Charlson cmorbidity index scores than did controls (P = .046). Blood pressure and heart rate variability measures were not associated with stroke. The risk of stroke was increased with red blood cell (RBC) transfusion (odds ratio OR, 14.82; 95% CI, 3.40-64.66; P < .001), vasopressor use (OR, 3.91; 95% CI, 1.59-9.60; P = .003), and longer procedure duration (OR, 1.23/h; 95% CI, 1.01-1.51; P = .04). Multivariable analysis of procedure duration, RBC transfusion, and vasopressor use showed that only RBC transfusion was independently associated with an increased risk of stroke (OR, 10.10; 95% CI, 2.14-47.72; P = .004).
Conclusions
Blood pressure variability was not associated with an increased risk of postoperative stroke; however, RBC transfusion was an independent risk factor.
Blood pressure variability (BPV), a modifiable risk factor, can compromise cerebral perfusion in critically ill patients. We studied the association between BPV in the intensive care unit (ICU) and ...short- and long-term cognitive outcomes.
All patients were ≥50 years old. The short-term cognitive end points were delirium and depressed alertness without delirium. The long-term outcome was change in the slope of longitudinal cognitive scores. Primary BPV measure was average real variability (ARV) of systolic blood pressure. Associations were assessed with multivariable multinominal logistic regression and linear mixed effects models.
Of 794 patients (1130 admissions) 185 developed delirium and 274 developed depressed alertness. There was a dose-response association of 24-h systolic ARV with delirium (adjusted OR, 95% CI 2.15 per 5 mm Hg increase, 1.31–3.06, P < 0.017) and with depressed alertness (OR 1.89, 95% CI 1.18–3.03, P < 0.008). For 371 patients with available longitudinal cognitive scores, the decline in cognitive trajectory was accelerated after discharge (annual change OR −0.097, 95% CI −0.122 to −0.073). This acceleration increased with delirium (additional decline −0.132 −0.233 to 0.030, P = 0.011). We found no significant association between BPV and post-ICU cognitive trajectory.
BPV was associated with increased likelihood of delirium in the ICU. Delirium, but not BPV, was associated with long-term cognitive decline.
•Blood pressure variability (BPV) may compromise brain perfusion.•Critically ill patients may have increased BPV, which is a modifiable risk factor.•BPV in ICU is associated with an increased risk for delirium and encephalopathy.•BPV is not associated with long-term cognitive impairment.•Delirium is associated with accelerated cognitive decline after ICU discharge.
Multisystem inflammatory syndrome is a life-threatening condition associated with elevated inflammatory markers and multiple organ injury. A diagnosis of exclusion, it has been reported after severe ...acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2) in children and adults; recently it has been described in some post-COVID-19 vaccinated individuals. The prognosis with supportive care and immunomodulatory therapy is good, although some individuals may require treatment in the intensive care unit (ICU). Here we report a case of a 58-year-old man who developed multi-organ failure after receiving the second dose of the Moderna mRNA-1273 COVID-19 vaccine. He required critical organ support in the ICU. An extensive workup was done to rule out alternative infectious and inflammatory processes. Following a period of gradual in-hospital convalescence, our patient made a full recovery. To our knowledge, this is the first comprehensively described case of multisystem inflammatory syndrome associated with Moderna mRNA-1273 COVID-19 vaccine in an adult over 50 years of age.
IMPORTANCE:
Initial Society of Critical Care Medicine Discovery Viral Infection and Respiratory illness Universal Study (VIRUS) Registry analysis suggested that improvements in critical care ...processes offered the greatest modifiable opportunity to improve critically ill COVID-19 patient outcomes.
OBJECTIVES:
The Structured Team-based Optimal Patient-Centered Care for Virus COVID-19 ICU Collaborative was created to identify and speed implementation of best evidence based COVID-19 practices.
DESIGN, SETTING, AND PARTICIPANTS:
This 6-month project included volunteer interprofessional teams from VIRUS Registry sites, who received online training on the Checklist for Early Recognition and Treatment of Acute Illness and iNjury approach, a structured and systematic method for delivering evidence based critical care. Collaborators participated in weekly 1-hour videoconference sessions on high impact topics, monthly quality improvement (QI) coaching sessions, and received extensive additional resources for asynchronous learning.
MAIN OUTCOMES AND MEASURES:
Outcomes included learner engagement, satisfaction, and number of QI projects initiated by participating teams.
RESULTS:
Eleven of 13 initial sites participated in the Collaborative from March 2, 2021, to September 29, 2021. A total of 67 learners participated in the Collaborative, including 23 nurses, 22 physicians, 10 pharmacists, nine respiratory therapists, and three nonclinicians. Site attendance among the 11 sites in the 25 videoconference sessions ranged between 82% and 100%, with three sites providing at least one team member for 100% of sessions. The majority reported that topics matched their scope of practice (69%) and would highly recommend the program to colleagues (77%). A total of nine QI projects were initiated across three clinical domains and focused on improving adherence to established critical care practice bundles, reducing nosocomial complications, and strengthening patient- and family-centered care in the ICU. Major factors impacting successful Collaborative engagement included an engaged interprofessional team; an established culture of engagement; opportunities to benchmark performance and accelerate institutional innovation, networking, and acclaim; and ready access to data that could be leveraged for QI purposes.
CONCLUSIONS AND RELEVANCE:
Use of a virtual platform to establish a learning collaborative to accelerate the identification, dissemination, and implementation of critical care best practices for COVID-19 is feasible. Our experience offers important lessons for future collaborative efforts focused on improving ICU processes of care.
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