ABSTRACT
Injury to endothelial cells (ECs) often results in cell retraction and gap formation. When caused by antigen aggregation or complement, this injury can be prevented by pretreatment of the ECs with IL-4, suggesting that IL-4 modifies the intercellular junction. Therefore, we investigated the effects of IL-4 on expression of intercellular junction proteins and whether such effects are required for IL-4-induced resistance of ECs against complement-mediated injury. We found that IL-4 induces upregulation of the junction protein claudin-5 in porcine ECs through activation of Jak/STAT6 and phosphorylation and translocation of FoxO1 from the nucleus to the cytoplasm. Increased claudin-5 expression resulted in increased transmembrane electrical resistance of the endothelial monolayer and participated in IL-4-induced protection of the ECs from complement injury. Down-regulation of FoxO1 using siRNA by itself caused up-regulation of claudin-5 expression and partial protection from cytotoxicity. This protection was enhanced by stimulation with IL-4. We previously reported that increased phospholipid synthesis and mitochondrial protection were required for IL-4-induced resistance of ECs against complement injury and now we demonstrate a contribution of claudin-5 expression in IL-4-induced protection.
Subject(s)
Claudin-5/metabolism , Endothelial Cells/drug effects , Forkhead Transcription Factors/metabolism , Interleukin-4/pharmacology , Up-Regulation/drug effects , Animals , Cell Nucleus/metabolism , Cell Survival/drug effects , Cells, Cultured , Complement System Proteins/toxicity , Cytoplasm/metabolism , Endothelial Cells/metabolism , Forkhead Transcription Factors/genetics , Humans , Immunoblotting , Janus Kinase 3/antagonists & inhibitors , Janus Kinase 3/metabolism , Microscopy, Confocal , Microscopy, Fluorescence , Phosphorylation/drug effects , Protein Transport/drug effects , Pyrimidines/pharmacology , Pyrroles/pharmacology , RNA Interference , STAT6 Transcription Factor/genetics , STAT6 Transcription Factor/metabolism , SwineABSTRACT
OBJECTIVE: To determine the positive predictive value (PPV) of a sepsis-screening protocol in patients with cervical spinal cord injury (SCI). DESIGN/METHOD: Retrospective review of all patients with cervical SCI who screened positive for two or more systemic inflammatory response syndrome (SIRS) criteria while hospitalized in acute care or inpatient rehabilitation units over a 3.5-year period. Sepsis was defined by the occurrence of (1) any culture order followed by an intravenous (IV) antibiotic within 72 hours or (2) an IV antimicrobial followed by a culture order within 24 hours. RESULTS: A total of 134 patients screened positive for two or more SIRS criteria. Of these, 36 patients (26.9%) were diagnosed with sepsis. Factors associated with a true-positive SIRS screen on multivariable analysis included American Spinal Injury Association Impairment Scale (AIS) grade A-C (vs. D; p < .001). The PPV of the screen was 38% in patients with AIS A-C and 9% in patients with AIS D. Altered mental status (AMS) was strongly associated with a diagnosis of sepsis; 16 of 18 (88.9%) of those with AMS had sepsis (p < .001). Age, sex, and neurologic level of injury were not associated with true-positive screening. For patients with new SCI, the first true-positive screen occurred a median of 31 days post-injury. The most common SIRS criteria combinations in patients with true-positive screens were elevated heart rate and either abnormal white blood cell count (43% of true positives) or abnormal temperature (26% of true positives). Abnormally low body temperature (<36°C) contributed to false-positive screening for 10 of 38 (26%) AIS D patients who screened positive. CONCLUSION: Sepsis screening using SIRS criteria in hospitalized patients with tetraplegia has a PPV of 26.9%; it is significantly higher in patients with AIS A-C versus D injuries. AMS, when combined with a positive SIRS screening, is strongly associated with sepsis.
Subject(s)
Sepsis , Spinal Cord Injuries , Humans , Predictive Value of Tests , Sepsis/diagnosis , Systemic Inflammatory Response Syndrome/diagnosis , Systemic Inflammatory Response Syndrome/etiology , Systemic Inflammatory Response Syndrome/epidemiology , Retrospective Studies , Quadriplegia/complications , Quadriplegia/diagnosis , Spinal Cord Injuries/complications , Spinal Cord Injuries/diagnosisABSTRACT
Both quaternary ammonium and bleach-based cleaning products are effective in reducing the transmission of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus in hospitals, but bleach-based compounds demonstrate better control of Clostridium difficile infections. Our pilot study demonstrates the potential to reduce C. difficile transmission in an acute care hospital by eliminating the need for providers to choose the appropriate cleaning product from isolation precaution carts.
Subject(s)
Clostridioides difficile/drug effects , Disinfectants , Housekeeping, Hospital , Patient Isolation , Humans , Pilot Projects , Quality ImprovementABSTRACT
Evolving subacute myelopathies have many possible etiologies. This is a report of a patient who presented with progressive paresthesias, proprioceptive loss, and gait disturbance with acute myelitis seen on magnetic resonance imaging initially concerning for transverse myelitis. However, she also had vitamin B12 deficiency, and her clinical course ultimately suggested a diagnosis more compatible with subacute combined degeneration. The clinical features, laboratory, and imaging findings and prognosis of the 2 disorders are compared. LEVEL OF EVIDENCE: V.