Association between serum soluble CD40 ligand levels and mortality in patients with severe sepsis.

INTRODUCTION: CD40 Ligand (CD40L) and its soluble counterpart (sCD40L) are proteins that exhibit prothrombotic and proinflammatory properties on binding to their cell surface receptor CD40. The results of small clinical studies suggest that sCD40L levels could play a role in sepsis; however, there are no data on the association between sCD40L levels and mortality of septic patients. Thus, the aim of this study was to determine whether circulating sCD40L levels could be a marker of adverse outcome in a large cohort of patients with severe sepsis. METHODS: This was a multicenter, observational and prospective study carried out in six Spanish intensive care units. Serum levels of sCD40L, tumour necrosis factor-alpha and interleukin-10, and plasma levels of tissue factor were measured in 186 patients with severe sepsis at the time of diagnosis. Serum sCD40L was also measured in 50 age- and sex-matched controls. Survival at 30 days was used as the endpoint. RESULTS: Circulating sCD40L levels were significantly higher in septic patients than in controls (P = 0.01), and in non-survivors (n = 62) compared to survivors (n = 124) (P = 0.04). However, the levels of CD40L were not different regarding sepsis severity. Logistic regression analysis showed that sCD40L levels >3.5 ng/mL were associated with higher mortality at 30 days (odds ratio = 2.89; 95% confidence interval = 1.37 to 6.07; P = 0.005). The area under the curve of sCD40L levels >3.5 ng/mL as predictor of mortality at 30 days was 0.58 (95% CI = 0.51 to 0.65; P = 0.03). CONCLUSIONS: In conclusion, circulating sCD40L levels are increased in septic patients and are independently associated with mortality in these patients; thus, its modulation could represent an attractive therapeutic target.

Matrix metalloproteinase-9, -10, and tissue inhibitor of matrix metalloproteinases-1 blood levels as biomarkers of severity and mortality in sepsis.

INTRODUCTION: Matrix metalloproteinases (MMPs) play a role in infectious diseases through extracellular matrix (ECM) degradation, which favors the migration of immune cells from the bloodstream to sites of inflammation. Although higher levels of MMP-9 and tissue inhibitor of matrix metalloproteinases-1 (TIMP-1) have been found in small series of patients with sepsis, MMP-10 levels have not been studied in this setting. The objective of this study was to determine the predictive value of MMP-9, MMP-10, and TIMP-1 on clinical severity and mortality in a large series of patients with severe sepsis. METHODS: This was a multicenter, observational, and prospective study carried out in six Spanish Intensive Care Units. We included 192 (125 surviving and 67 nonsurviving) patients with severe sepsis and 50 age- and sex-matched healthy controls in the study. Serum levels of MMP-9, MMP-10, TIMP-1, tumor necrosis factor (TNF)-alpha, and interleukin (IL)-10 were measured in patients with severe sepsis at the time of diagnosis and in healthy controls. RESULTS: Sepsis patients had higher levels of MMP-10 and TIMP-1, higher MMP-10/TIMP-1 ratios, and lower MMP-9/TIMP-1 ratios than did healthy controls (P < 0.001). An association was found between MMP-9, MMP-10, TIMP-1, and MMP-9/TIMP-1 ratios and parameters of sepsis severity, assessed by the SOFA score, the APACHE-II score, lactic acid, platelet count, and markers of coagulopathy. Nonsurviving sepsis patients had lower levels of MMP-9 (P = 0.037), higher levels of TIMP-1 (P < 0.001), lower MMP-9/TIMP-1 ratio (P = 0.003), higher levels of IL-10 (P < 0.001), and lower TNF-alpha/IL-10 ratio than did surviving patients. An association was found between MMP-9, MMP-10, and TIMP-1 levels, and TNF-alpha and IL-10 levels. The risk of death in sepsis patients with TIMP-1 values greater than 531 ng/ml was 80% higher than that in patients with lower values (RR = 1.80; 95% CI = 1.13 to 2.87;P = 0.01; sensitivity = 0.73; specificity = 0.45). CONCLUSIONS: The novel findings of our study on patients with severe sepsis (to our knowledge, the largest series reporting data about MMP levels in sepsis) are that reduced MMP-9/TIMP-1 ratios and increased MMP-10 levels may be of great pathophysiologic significance in terms of severity and mortality, and that TIMP-1 levels may represent a biomarker to predict the clinical outcome of patients with sepsis.

Prognostic value of changes in brain tissue oxygen pressure before and after decompressive craniectomy following severe traumatic brain injury.

OBJECTIVE In severe traumatic brain injury (TBI), the effects of decompressive craniectomy (DC) on brain tissue oxygen pressure (PbtO2) and outcome are unclear. The authors aimed to investigate whether changes in PbtO2 after DC could be used as an independent prognostic factor. METHODS The authors conducted a retrospective, observational study at 2 university hospital ICUs. The study included 42 patients who were admitted with isolated moderate or severe TBI and underwent intracranial pressure (ICP) and PbtO2 monitoring before and after DC. The indication for DC was an ICP higher than 25 mm Hg refractory to first-tier medical treatment. Patients who underwent primary DC for mass lesion evacuation were excluded. However, patients were included who had undergone previous surgery as long as it was not a craniectomy. ICP/PbtO2 monitoring probes were located in an apparently normal area of the most damaged hemisphere based on cranial CT scanning findings. PbtO2 values were routinely recorded hourly before and after DC, but for comparisons the authors used the first PbtO2 value on ICU admission and the number of hours with PbtO2 < 15 mm Hg before DC, as well as the mean PbtO2 every 6 hours during 24 hours pre- and post-DC. The end point of the study was the 6-month Glasgow Outcome Scale; a score of 4 or 5 was considered a favorable outcome, whereas a score of 1-3 was considered an unfavorable outcome. RESULTS Of the 42 patients included, 26 underwent unilateral DC and 16 bilateral DC. The median Glasgow Coma Scale score at the scene of the accident or at the initial hospital before the patient was transferred to one of the 2 ICUs was 7 (interquartile range [IQR] 4-14). The median time from admission to DC was 49 hours (IQR 7-301 hours). Before DC, the median ICP and PbtO2 at 6 hours were 35 mm Hg (IQR 28-51 mm Hg) and 11.4 mm Hg (IQR 3-26 mm Hg), respectively. In patients with favorable outcome, PbtO2 at ICU admission was higher and the percentage of time that pre-DC PbtO2 was < 15 mm Hg was lower (19 ± 4.5 mm Hg and 18.25% ± 21.9%, respectively; n = 28) than in those with unfavorable outcome (12.8 ± 5.2 mm Hg [p < 0.001] and 59.58% ± 38.8% [p < 0.001], respectively; n = 14). There were no significant differences in outcomes according to the mean PbtO2 values only during the last 12 hours before DC, the hours of refractory intracranial hypertension, the timing of DC from admission, or the presence/absence of previous surgery. In contrast, there were significant differences in PbtO2 values during the 12- to 24-hour period before DC. In most patients, PbtO2 increased during the 24 hours after DC but these changes were more pronounced in patients with favorable outcome than in those with unfavorable outcome (28.6 ± 8.5 mm Hg vs 17.2 ± 5.9 mm Hg, p < 0.0001; respectively). The areas under the curve for the mean PbtO2 values at 12 and 24 hours after DC were 0.878 (95% CI 0.75-1, p < 0.0001) and 0.865 (95% CI 0.73-1, p < 0.0001), respectively. CONCLUSIONS The authors' findings suggest that changes in PbtO2 before and after DC, measured with probes in healthy-appearing areas of the most damaged hemisphere, have independent prognostic value for the 6-month outcome in TBI patients.

Acute effects of hamstring stretching on sagittal spinal curvatures and pelvic tilt.

The aim of this study was to determine acute effects of hamstring stretching in thoracic and lumbar spinal curvatures and pelvic tilt. Fifty-five adults (29.24 ± 7.41 years) were recruited for this study. Subjects performed a hamstring stretching protocol consisting of four exercises. The session consisted of 3 sets of each exercise and subjects held the position for 20 seconds with a 30-second rest period between sets and exercises. Thoracic and lumbar spinal angles and pelvic tilt were measured with a SpinalMouse in relaxed standing, sit-and-reach test and Macrae & Wright position. Hamstring extensibility was determined by active straight leg raise test and sit-and-reach score. All measures were performed before and immediately after the hamstring stretching protocol. Active straight leg raise angle and sitand-reach score significantly improved immediately after the stretching protocol (p<0.001). Greater anterior pelvic tilt (p<0.001) and lumbar flexion (p<0.05) and a smaller thoracic kyphosis in the sit-and-reach (p<0.001) were found after the stretching protocol. However, stretching produced no significant change on spinal curvatures or pelvic tilt in standing and maximal trunk flexion with knees flexed. In conclusion, static stretching of the hamstring is associated to an immediate change in the sagittal spinal curvatures and pelvic position when performing trunk flexion with knees extended, so that allowing for greater lumbar flexion and anterior pelvic tilt and lower thoracic kyphosis. Hamstring stretching is recommended prior to sport activities involving trunk flexion with the knees straight.