Is Impaired Autoregulation Associated with Mortality in Patients with Severe Cerebral Diseases?

BACKGROUND: Cerebral autoregulation (CA) is a mechanism that compensates for variations in cerebral perfusion pressure (CPP) by changes in cerebral blood flow resistance to keep the cerebral blood flow constant. In this study, the relationship between lethal outcome during hospitalisation and the autoregulation-related indices PRx and Mx was investigated. MATERIALS AND METHODS: Thirty patients (aged 18-77 years, mean 53 ± 16 years) with severe cerebral diseases were studied. Cerebral blood flow velocity (CBFV), arterial blood pressure (ABP) and intracranial pressure (ICP) were repeatedly recorded. CA indices were calculated as the averaged correlation between CBFV and CPP (Mx) and between ABP and ICP (PRx). Positive index values indicated impairment of CA. RESULTS: Six patients died in hospital. In this group both PRx and Mx were significantly higher than in the group of survivors (PRx: 0.41 ± 0.33 vs 0.09 ± 0.25; Mx: 0.28 ± 0.40 vs 0.03 ± 0.21; p = 0.01 and 0.04, respectively). PRx and Mx correlated significantly with Glasgow Outcome Scale (GOS) score (PRx: R = -0.40, p < 0.05; Mx: R = -0.54, p < 0.005). PRx was the only significant risk factor for mortality (p < 0.05, logistic regression). CONCLUSION: Increased PRx and Mx were associated with risk of death in patients with severe cerebral diseases. The relationship with mortality was more pronounced in PRx, whereas Mx showed a better correlation with GOS score.

Autoregulation monitoring and outcome prediction in neurocritical care patients: Does one index fit all?

Indexes PRx and Mx have been formerly introduced to assess cerebral autoregulation and have been shown to be associated with 3-month clinical outcome. In a mixed cohort of neurocritical care patients, we retrospectively investigated the impact of selected clinical characteristics on this association. Forty-one patients (18-77 years) with severe traumatic (TBI, N = 20) and non-traumatic (N = 21) brain injuries were studied. Cerebral blood flow velocity, arterial blood pressure and intracranial pressure were repeatedly recorded during 1-h periods. Calculated PRx and Mx were correlated with 3-month clinical outcome score of modified Rankin Scale (mRS) in different subgroups with specific clinical characteristics. Both PRx and Mx correlated significantly with outcome (PRx: r = 0.38, p < 0.05; AUC = 0.64, n.s./Mx: r = 0.48, p < 0.005; AUC = 0.80, p < 0.005) in the overall group, and in patients with hemicraniectomy (N = 17; PRx: r = 0.73, p < 0.001; AUC = 0.89, p < 0.01/Mx: r = 0.69, p < 0.005; AUC = 0.87, p < 0.05). Mx, not PRx, correlated significantly with mRS in patients with heart failure (N = 17; r = 0.69, p < 0.005; AUC = 0.92, p < 0.005), and in non-traumatic patients (r = 0.49, p < 0.05; AUC = 0.79, p < 0.05). PRx, not Mx, correlated significantly with mRS in TBI patients (r = 0.63, p < 0.01; AUC = 0.89, p < 0.01). Both indexes did not correlate with mRS in diabetes patients (N = 15), PRx failed in hypocapnic patients (N = 26). Both PRx and Mx were significantly associated with 3-month clinical outcome, even in patients with hemicraniectomy. PRx was more appropriate for TBI patients, while Mx was better suited for non-traumatic patients and patients with heart failure. Prognostic values of indexes were affected by diabetes (both Mx and PRx) and hypocapnia (PRx only).

Effect of different biomaterials on the expression pattern of the transcription factor Ets2 in bone-like constructs.

Tissue engineering offers an exciting prospect for reconstructive surgery by replacing missing natural scaffolds with artificial ones. For optimal success the artificial scaffold should provide an environment closely resembling the natural tissue. Little is known about the direct influence of the scaffold on the expression of regulators of bone development, such as transcription factors. The aim of this study was to investigate the influence of the scaffold material on the expression of V-ets erythroblastosis virus E26 oncogene homolog 2 (avian) (Ets2), a key transcription factor in bone biology. Human primary bone precursor cells were seeded in three-dimensional constructs consisting of hydroxyapatite (HA) or poly (lactic-co-glycolic acid) (PLGA). Cells grown on tissue culture polystyrene dishes served as controls. After cultivation for up to 21 days the expression of Ets2 and other important bone-specific genes was assessed by reverse transcription polymerase chain reaction (RT-PCR) and Western Blotting. Ets2 mRNA showed significantly higher expression in controls than in bone-like constructs, and more Ets2 mRNA was expressed in cells grown in HA than in PLGA constructs. At protein level however, Ets2 expression was higher in constructs than in controls after prolonged culture. Our study showed for the first time a differential expression of Ets2 in tissue engineered bone constructs in vitro, demonstrating that scaffold chemistry has an influence on the expression of genes regulating osteogenesis.

Phenothiazine chloride and soft laser light have a biostimulatory effect on human osteoblastic cells.

OBJECTIVE: Low-level laser therapy (LLLT) is a well accepted tool to accelerate wound healing and to reduce inflammation after oral implant insertion. Since there are no in vitro data on a combination of LLLT with prior photosensitization, it was the aim of this study to investigate if photosensitization with phenothiazine chloride results in an alteration of the biostimulatory effect of low-level laser irradiation. BACKGROUND DATA: LLLT and antimicrobial photodynamic therapy are well established for the treatment of peri-implantitis. In vitro studies have shown a biostimulatory effect of LLLT on various cell types, including osteogenic cells. MATERIALS AND METHODS: SaOS-2 cells were treated with the photosensitizer phenothiazine chloride before irradiation with matched laser light. At 24-h intervals the viability and differentiation were analyzed in treated and untreated cells. RESULTS: While the biostimulatory effect of the LLLT could be observed for the lower irradiation dose, the pretreatment with phenothiazine chloride did not significantly affect the growth and differentiation of the SaOS-2 cells. CONCLUSION: It can thus be concluded that combined treatment with phenothiazine chloride and LLLT does not result in a synergistic enhancement of the biostimulatory effect of LLLT, but there was also no evidence for antagonizing effects on growth and differentiation of human osteoblasts.