Rehabilitation interventions for postintensive care syndrome: a systematic review

Item does not contain fulltextOBJECTIVE: An increasing number of ICU patients survive and develop mental, cognitive, or physical impairments. Various interventions support recovery from this postintensive care syndrome. Physicians in charge of post-ICU patients need to know which interventions are effective. DATA SOURCES: Systematic literature search in databases (MEDLINE, EMBASE, Cochrane CENTRAL, PsycInfo, CINAHL; 1991-2012), reference lists, and hand search. STUDY SELECTION: We included comparative studies of rehabilitation interventions in adult post-ICU patients if they considered health-related quality of life, frequency/severity of postintensive care syndrome symptoms, functional recovery, need for care, autonomy in activities of daily living, mortality, or hospital readmissions. DATA EXTRACTION: Two reviewers extracted data and assessed risk of bias independently. DATA SYNTHESIS: From 4,761 publications, 18 studies with 2,510 patients were included. Studies addressed 20 outcomes, using 45 measures, covering inpatient (n = 4 trials), outpatient (n = 9), and mixed (n = 5) healthcare settings. Eight controlled trials with moderate to high quality were considered for evaluation of effectiveness. They investigated inpatient geriatric rehabilitation, ICU follow-up clinic, outpatient rehabilitation, disease management, and ICU diaries. Five of these trials assessed posttraumatic stress disorder, with four trials showing positive effects: first, ICU diaries reduced new-onset posttraumatic stress disorder (5% vs 13%, p = 0.02) after 3 months and second showed a lower mean Impact of Event Scale-Revised score (21.0 vs 32.1, p = 0.03) after 12 months. Third, aftercare by ICU follow-up clinic reduced Impact of Event Scale for women (20 vs 31; p < 0.01). Fourth, a self-help manual led to fewer patients scoring high in the Impact of Event Scale after 8 weeks (p = 0.026) but not after 6 months. For none of the other outcomes did more than one study report positive impacts. CONCLUSION: Interventions which have substantial effects in post-ICU patients are rare. Positive effects were seen for ICU-diary interventions for posttraumatic stress disorder. More interventions for the growing number of ICU survivors are needed

The relevance of ceramides and their synthesizing enzymes for multiple sclerosis

Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that the genetic deletion of CerS2 suppresses EAE pathology by interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil migration. In the present study, we investigated the importance of Cers and their synthesizing/metabolizing enzymes in MS. For this purpose, a longitudinal study with 72 MS patients and 25 healthy volunteers was performed. Blood samples were collected from healthy controls and MS patients over 1- or 3-year periods, respectively. Immune cells were counted using flow cytometry, ceramide levels were determined using liquid chromatography-tandem mass spectrometry, and mRNA expression was analyzed using quantitative PCR. In white blood cells, C16-LacCer and C24-Cer were down-regulated in MS patients in comparison with healthy controls. In plasma, C16-Cer, C24:1-Cer, C16-GluCer, and C24:1-GluCer were up-regulated and C16-LacCer was down-regulated in MS patients in comparison with healthy controls. Blood samples from MS patients were characterized by an increased B-cell number. However, there was no correlation between B-cell number and Cer levels. mRNA expression of Cer metabolizing enzymes and G-CSF signaling enzymes was significantly increased in MS patients. Interestingly, G-CSF receptor (G-CSFR) and CXCR2 mRNA expression correlated with CerS2 and UDP-glucose Cer glucosyltransferase (UGCG) mRNA expression. In conclusion, our results indicate that Cer metabolism is linked to G-CSF signaling in MS

Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis

Bioactive lipids contribute to the pathophysiology of multiple sclerosis. Here, we show that lysophosphatidic acids (LPAs) are dysregulated in multiple sclerosis (MS) and are functionally relevant in this disease. LPAs and autotaxin, the major enzyme producing extracellular LPAs, were analyzed in serum and cerebrospinal fluid in a cross-sectional population of MS patients and were compared with respective data from mice in the experimental autoimmune encephalomyelitis (EAE) model, spontaneous EAE in TCR1640 mice, and EAE in Lpar2(-/-) mice. Serum LPAs were reduced in MS and EAE whereas spinal cord LPAs in TCR1640 mice increased during the 'symptom-free' intervals, i.e. on resolution of inflammation during recovery hence possibly pointing to positive effects of brain LPAs during remyelination as suggested in previous studies. Peripheral LPAs mildly re-raised during relapses but further dropped in refractory relapses. The peripheral loss led to a redistribution of immune cells from the spleen to the spinal cord, suggesting defects of lymphocyte homing. In support, LPAR2 positive T-cells were reduced in EAE and the disease was intensified in Lpar2 deficient mice. Further, treatment with an LPAR2 agonist reduced clinical signs of relapsing-remitting EAE suggesting that the LPAR2 agonist partially compensated the endogenous loss of LPAs and implicating LPA signaling as a novel treatment approach