Non-septic Intensive Care Unit Patients Research Articles

Presepsin: gelsolin ratio, as a promising marker of sepsis-related organ dysfunction: a prospective observational study.

We aimed to facilitate the diagnosis and prognosis of sepsis-related organ dysfunction through analyzing presepsin (PSEP) and gelsolin (GSN) levels along with a novel marker, the presepsin:gelsolin (PSEP:GSN) ratio. Blood samples were collected from septic patients at the intensive care unit (ICU) at three time points (T1-3): T1: within 12 h after admission; T2: second day morning; T3: third day morning. Sampling points for non-septic ICU patients were T1 and T3. PSEP was measured by a chemiluminescence-based POCT method while GSN was determined by an automated immune turbidimetric assay. Data were compared with routine lab and clinical parameters. Patients were categorized by the Sepsis-3 definitions. PSEP:GSN ratio was evaluated in major sepsis-related organ dysfunctions including hemodynamic instability, respiratory insufficiency and acute kidney injury (AKI). In our single center prospective observational study, 126 patients were enrolled (23 control, 38 non-septic and 65 septic patients). In contrast to controls, significantly elevated (p < 0.001) admission PSEP:GSN ratios were found in non-septic and septic patients. Regarding 10-day mortality prediction, PSEP:GSN ratios were lower (p < 0.05) in survivors than in non-survivors during follow-up, while the prognostic performance of PSEP:GSN ratio was similar to widely used clinical scores (APACHE II, SAPS II, SOFA). PSEP:GSN ratios were also higher (p < 0.001) in patients with sepsis-related AKI than septic non-AKI patients during follow-up, especially in sepsis-related AKI patients needing renal replacement therapy. Furthermore, increasing PSEP:GSN ratios were in good agreement (p < 0.001) with the dosage and the duration of vasopressor requirement in septic patients. Moreover, PSEP:GSN ratios were markedly greater (p < 0.001) in patients with septic shock than in septic patients without shock. Compared to septic patients requiring oxygen supplementation, substantially elevated (p < 0.001) PSEP:GSN ratios were observed in septic patients with demand for mechanical ventilation, while higher PSEP:GSN ratios (p < 0.001) were also associated with extended periods of mechanical ventilation requirement in septic patients. PSEP:GSN ratio could be a useful complementary marker besides the routinely used SOFA score regarding the diagnosis and short term mortality prediction of sepsis. Furthermore, the significant increase of this biomarker may also indicate the need for prolonged vasopressor or mechanical ventilation requirement of septic patients. PSEP:GSN ratio could yield valuable information regarding the extent of inflammation and the simultaneous depletion of the patient's scavenger capacity during sepsis. NIH U.S. National Library of Medicine, ClinicalTrails.gov. Trial identifier: NCT05060679, (https://clinicaltrials.gov/ct2/show/NCT05060679) 23.03.2022, Retrospectively registered.

GLOBAL SIGNATURES OF THE MICROBIOME AND METABOLOME DURING HOSPITALIZATION OF SEPTIC PATIENTS.

Background: The gut plays an important role in the development of sepsis and acts as one of the possible drivers of multiple-organ dysfunction syndrome. This study aimed to explore the dynamic alterations in the gut microbiota and its metabolites in septic patients at different stages of intensive care unit (ICU) admission. Methods: In this prospective observational study, a total of 109 fecal samples from 23 septic patients, 16 nonseptic ICU patients and 10 healthy controls were analyzed. 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry targeted metabolomics were used for microbiota and metabolome analysis. A prediction model combining the Sequential Organ Failure Assessment score, Klebsiella , taurocholic acid, and butyric acid was used to predict the prognosis of sepsis. Results: The diversity and dominant species of the gut microbiota of septic patients were significantly disturbed. The proportions of normal gut microbiota, such as Firmicutes on the phylum level, as well as Faecalibacterium, Subdoligranulum , Ruminococcus , Agathobacter , and Blautia on the genus level, were decreased at different stages of ICU admission, while the proportions of potential pathogenic bacteria, such as Proteobacteria on the phylum level, and Enterococcus and Stenotrophomonas on the genus level were significantly increased. In addition, the amount of short-chain fatty acids and secondary bile acids decreased in septic patients, while that of the primary bile acids increased markedly. Bacterial richness and diversity were lower in the nonsurviving patients than those in the surviving patients in the later stage of ICU admission. In the nomogram model, the higher abundance of Klebsiella , concentration of taurocholic acid, and Sequential Organ Failure Assessment score, combined with a lower butyric acid concentration, could predict a higher probability of death from sepsis. Conclusions: Our study indicated that the dynamical alterations of gut microbiota and its metabolites were associated with the prognosis of the sepsis. Based on these alterations and clinical indicators, a nomogram model to predict the prognosis of septic patients was performed.

Clusterin Plasma Concentrations Are Decreased in Sepsis and Inversely Correlated with Established Markers of Inflammation.

Clusterin is a multifunctional protein that is recognized to mediate cellular stress response associated with organ failure, systemic inflammation, and metabolic alterations. The aim of this study was to determine the value of clusterin as a clinical biomarker in critical ill patients with or without sepsis. We analyzed clusterin plasma concentrations in 200 critically ill patients (133 with sepsis, 67 without sepsis) on admission to the medical intensive care unit (ICU). The results were compared with 66 healthy controls. Clusterin plasma concentration was significantly elevated in critically ill patients compared to healthy subjects. Clusterin levels were significantly higher in non-septic ICU patients than in patients with sepsis. Clusterin correlated inversely with routinely used biomarkers of inflammatory response. Furthermore, clusterin levels were higher in ICU patients with pre-existing obesity and type 2 diabetes. Clusterin was not associated with disease severity, organ failure, or mortality in the ICU. This study highlights significantly elevated clusterin levels in critically ill patients, predominantly in non-sepsis conditions, and associates circulating clusterin to inflammatory and metabolic dysfunctions.

Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis

ABSTRACTBackgroundDiagnosing sepsis early is important for its successful management. Various biomarkers are being used currently, but mostly they are either expensive or not readily available. This study aims to evaluate usefulness of automated immature granulocyte count (IG#) and immature granulocyte percentage (IG%) as early diagnostic markers of sepsis and compares it to other established predictive markers.Patients and methodsIn this prospective observational study, 137 eligible, critically ill, nonseptic intensive care unit patients were analyzed for automated IG#, IG%, serum procalcitonin (PCT), and blood lactate (Lac), daily for 7 days after recruitment. Patients were followed for the development of sepsis, defined by the new Sepsis-3 criteria. The study was divided into four time periods of 24 hours each with respect to the day of developing organ dysfunction. Using area under receiver operator characteristic and diagnostic odds ratio (DOR) methods, the best biomarker for the prediction of sepsis in each time period was calculated.ResultsIG# and IG% were the earliest biomarkers to have a significant discriminating value with area under the curve of 0.81 and 0.82, respectively, as early as 24 hours before clinical sepsis is diagnosed by Sepsis-3 criteria. Both IG# and IG% have a high DOR of 34.91 and 18.11, respectively, when compared to others like PCT and Lac having a DOR of 27.06 and 4.78, respectively.ConclusionIG# and IG% are easily available, rapid, and inexpensive tools to differentiate between septic and nonseptic patients with high specificity and sensitivity. It is the earliest biomarker to show a significant rise in patients developing sepsis.How to cite this articleBhansaly P, Mehta S, Sharma N, Gupta E, Mehta S, Gupta S. Evaluation of Immature Granulocyte Count as the Earliest Biomarker for Sepsis. Indian J Crit Care Med 2022;26(2):216–223.

Diagnostic and prognostic value of new bioscore in critically ill septic patients

Objective To evaluate the diagnostic and prognostic value of biomarkers and new bioscore in septic patients in intensive care unit (ICU). Materials and methods A study was conducted on septic and non-septic patients in ICU. Diagnostic and prognostic values of C-reactive protein (CRP), procalcitonin (PCT), Sequential Organ Failure Assessments (SOFA) score and new bioscore were analysed statistically. Results A total of 226 patients were enrolled in the study. In septic patients, PCT, SOFA and bioscore were found significantly increased (p = .007, p = .001 and p = .001, respectively). The AUC value of bioscore was higher than PCT and SOFA in septic patients. SOFA was found to be more significant prognostic marker than bioscore in predicting 28-day mortality. The prognostic value of bioscore and SOFA was similar for predicting 90-day mortality. Conclusions The new bioscore formed by combination of CRP, PCT and SOFA score may be useful in early diagnosis of sepsis.

A worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from The Intensive Care Over Nations audit

BackgroundAcute kidney injury (AKI) is a common complication of critical illness and is associated with worse outcomes. However, the influence of deterioration or improvement in renal function on clinical outcomes is unclear. Using a large international database, we evaluated the prevalence and evolution of AKI over a 7-day period and its effects on clinical outcomes in septic and non-septic critically ill patients worldwide.MethodsFrom the 10,069 adult intensive care unit (ICU) patients in the Intensive Care Over Nations database, all those with creatinine and urine output data were included in this substudy. Patients who developed sepsis during the ICU stay (≥ 2 days after admission) were excluded. AKI was evaluated within 72 hours after admission and before discharge/death up to day 7 according to the Acute Kidney Injury Network (AKIN) criteria.ResultsA total of 7970 patients were included, 59% of whom met AKIN criteria for AKI within the first 72 hours of the ICU stay. Twenty-four per cent of patients had sepsis on admission, of whom 68% had AKI, compared to 57% of those without sepsis on admission (p < 0.001). AKIN stage 3 (40% vs 24%, p < 0.001) and use of renal replacement therapy (20% vs 5%, p < 0.0001) were more prevalent in patients with sepsis. Patients with sepsis and AKIN stage 3 were less likely to improve to a lower stage during the 7-day follow-up period than non-septic patients with AKIN stage 3 (21% vs 32%, p < 0.0001). In-hospital mortality was related to severity of AKI and was reduced in patients in whom AKI improved compared to those who remained stable or deteriorated, but remained higher than in patients without AKI, even if there was apparent full recovery at day 7.ConclusionThese findings illustrate the different kinetics of AKI in septic and non-septic ICU patients and emphasize the important impact of AKI on mortality rates even when there is apparent full renal recovery at day 7.

Neutrophil CD64, C-reactive protein, and procalcitonin in the identification of sepsis in the ICU — Post-test probabilities

PurposeWe were interested in whether C-reactive protein (CRP) and procalcitonin (PCT) distinguish sepsis from non-septic controls and whether a combination of CRP, PCT, and neutrophil CD64 improves identification of sepsis in the intensive care unit (ICU). Materials and methodsWe analyzed the CRP and PCT concentrations from 27 patients with sepsis and 15 ICU controls. In addition, CD64 on neutrophils was measured using quantitative flow cytometry. We present a multiple marker analysis for sepsis diagnostics combining neutrophil CD64, CRP, and PCT using post-test analysis. ResultsThe CRP and PCT values separated sepsis and non-septic ICU patients. In post-test analysis, CRP provided a positive probability of 0.48 and a negative probability of 0.053 for sepsis in the ICU; while, the corresponding values were 0.35 and 0.0059, respectively, for PCT and 0.62 and 0.0013, respectively, for neutrophil CD64. When neutrophil CD64 was analyzed with PCT and CRP, the probabilities were 0.98 and <0.001, respectively. ConclusionsNeutrophil CD64 expression was superior to PCT and CRP for the identification of sepsis in ICU. Positive post-test probability for any combinations of simultaneously analyzed CRP, PCT and CD64 showed improved diagnostic accuracy for sepsis. This approach may be useful for guiding antibiotic treatment in ICU.

Differentiating sepsis from non-infectious systemic inflammation based on microvesicle-bacteria aggregation.

Sepsis is a severe medical condition and a leading cause of hospital mortality. Prompt diagnosis and early treatment has a significant, positive impact on patient outcome. However, sepsis is not always easy to diagnose, especially in critically ill patients. Here, we present a conceptionally new approach for the rapid diagnostic differentiation of sepsis from non-septic intensive care unit patients. Using advanced microscopy and spectroscopy techniques, we measure infection-specific changes in the activity of nano-sized cell-derived microvesicles to bind bacteria. We report on the use of a point-of-care-compatible microfluidic chip to measure microvesicle-bacteria aggregation and demonstrate rapid (≤1.5 hour) and reliable diagnostic differentiation of bacterial infection from non-infectious inflammation in a double-blind pilot study. Our study demonstrates the potential of microvesicle activities for sepsis diagnosis and introduces microvesicle-bacteria aggregation as a potentially useful parameter for making early clinical management decisions.

Pancreatic stone protein as a postmortem biochemical marker for the diagnosis of sepsis.

Pancreatic stone protein/regenerating protein has recently emerged as an interesting diagnostic and prognostic marker of inflammation and sepsis in the clinical field. Increased blood concentrations have been described in patients with sepsis. Moreover, a high accuracy in predicting fatal outcomes in septic patients admitted to intensive care units has been reported. In this study, we investigated pancreatic stone protein/regenerating protein in postmortem serum in a series of sepsis-related fatalities, local infections and non-infectious cases that underwent medico-legal investigations. Procalcitonin, C-reactive protein, interleukin 6, soluble triggering receptor expressed on myeloid cells-1 and pancreatic stone protein/regenerating protein were measured in the postmortem serum collected during autopsy in a group of sepsis-related deaths, local infections and non-septic intensive care unit patients. Statistically significant differences in pancreatic stone protein/regenerating protein concentrations were observed between sepsis and control patients. A significant positive correlation was found between procalcitonin and pancreatic stone protein/regenerating protein values in septic cases. Pancreatic stone protein/regenerating protein is measurable in postmortem serum from femoral blood collected during autopsy. Additionally, as in the clinical field, pancreatic stone protein/regenerating protein can be used as a postmortem biochemical marker for the diagnosis of sepsis.

Altered melatonin secretion and circadian gene expression with increased proinflammatory cytokine expression in early-stage sepsis patients

Inflammatory and immune responses, as well as melatonin secretion, are affected by circadian regulation. Abnormal circadian rhythm of melatonin release has been reported to be associated with the later stages of sepsis; however, its role in the early stages of sepsis is unclear. We studied 11 septic and 11 non-septic patients in our intensive care unit (ICU). Peripheral blood was drawn at 4-h intervals on the first day, beginning at 2:00 p.m., over a total period of 24 h. Plasma levels of melatonin, tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were measured by radioimmunoassay or enzyme-linked immunosorbent assay (ELISA). Messenger RNA levels of circadian genes Cry-1 and Per-2 were analyzed using quantitative real-time PCR. Results show the circadian rhythm of melatonin secretion was altered in the early stages of sepsis. The melatonin secretion acrophase occurred earlier in septic patients at 6:00 p.m., compared with at 2:00 a.m. in non-septic ICU patients. Compared with the non-septic group, both Cry-1 and Per-2 expression were significantly decreased while TNF-α and IL-6 expression were significantly increased in septic patients [TNF-α, 64.1 (43.6-89.1) vs. 11.4 (10.4-12.5) ng/ml; IL-6, 41.2 (35.7-50.8) vs. 19.1 (16-136.7) ng/ml; median (range), both P=0.04]. The peak concentrations of TNF-α and IL-6 were shown to be in concordance with the rhythm of melatonin secretion. The circadian rhythm of melatonin secretion and circadian gene expression were altered in the early stages of sepsis, which likely led to the changes in pro-inflammatory cytokine release. These findings shed light on the potential link between circadian rhythm and the progression of early-stage sepsis.

Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors

ObjectivesThe objective of this preliminary study was to explore long-term changes in neurobehavioral parameters, brain morphology and electroencephalography of sepsis patients who received intensive care compared to non-septic intensive care...

Diurnal variation of melatonin and cortisol is maintained in non-septic intensive care patients

To study the diurnal variation of melatonin and cortisol in critically ill patients and to assess whether the severity of organ dysfunction, sedation and sympathetic activity correlate with the production of these hormones. Prospective clinical study. Surgical intensive care unit in a university hospital. Forty non-septic patients without brain injury and treatment with adrenergic agonists or corticosteroids. Twenty-five of the patients were sedated with benzodiazepines. None. The pattern of melatonin production was monitored by the determination of 6-sulphatoxymelatonin (aMT6s) in urine. The 12-h aMT6s excretions at nights (11.8 +/- 8.9 microg, mean +/- SD) were higher than in the daytime (6.8 +/- 7.5 microg; P < 0.0001), and benzodiazepine treatment did not abolish the diurnal periodicity of aMT6s excretion during the entire 3-day study period. Serum cortisol concentrations at noon (524 +/- 276 nmol/l, mean +/- SD) were higher than at midnight (415 +/- 172 nmol/l; P < 0.0001), and the decrease at midnight was significant also in the patients treated with benzodiazepines. Sympathetic activity was monitored with urine vanillylmandelic acid (VMA). The 12-h VMA excretions did not show a diurnal variation, but a significant positive relationship between the 12-h VMA and aMT6s excretions was observed. The severity of organ dysfunction did not correlate either with the aMT6s and VMA excretion or with serum cortisol concentration. The diurnal variation of melatonin and cortisol is maintained in non-septic intensive care unit patients. Benzodiazepines do not impair the diurnal variation of melatonin and cortisol.

Increased circulating endothelial progenitor cells in septic patients: Correlation with survival

Endothelial damage and detachment of endothelial cells are known to occur in septic patients. Thus, recruitment of circulating endothelial progenitor cells (cEPCs) to these lesions might have a beneficial effect on the clinical course in septic patients. Therefore, we were interested in whether EPCs, detected by flow cytometry, are increasingly mobilized during sepsis and if this mobilization is associated with clinical outcome. Prospective, nonrandomized study. Intensive care unit of a university hospital. Patients with (n = 32) and without (n = 15) sepsis and healthy volunteers (n = 15). Peripheral blood mononuclear cells were isolated by Ficoll density gradient centrifugation, and cEPCs were characterized by three-color fluorescence flow cytometry using antibodies against CD133, CD34, and vascular endothelial growth factor receptor-2. Serum concentrations of vascular endothelial growth factor, granulocyte macrophage-colony stimulating factor, and erythropoietin were determined by enzyme-linked immunosorbent assay. Severity of sepsis was assessed according to Acute Physiology and Chronic Health Evaluation II scoring. In septic patients, the number of cEPCs was significantly higher than in nonseptic intensive care unit patients (p < .05) and healthy controls (p < .02). Nonsurvivors (n = 8), defined as death within 28 days after onset of sepsis, had significantly lower numbers of cEPCs than survivors (n = 24) (p < .0001). The number of cEPCs was correlated with survival in septic patients. Serum vascular endothelial growth factor concentrations were significantly higher in septic patients compared with nonseptic intensive care unit patients and healthy controls (p < .01) and correlated with the cEPC numbers (p < .0001). Similar findings were observed for granulocyte macrophage-colony stimulating factor and erythropoietin. Our data suggest that cEPC enumeration in peripheral blood of septic patients might be a valuable marker to assess the clinical outcome in these patients.

Relative adrenal insufficiency: an identifiable entity in nonseptic critically ill patients?

To determine whether relative adrenal insufficiency (RAI) can be identified in nonseptic hypotensive patients in the intensive care unit (ICU). Retrospective study in a medical-surgical ICU of a university hospital. One hundred and seventy-two nonseptic ICU patients (51% after trauma or surgery), who underwent a short 250 microg ACTH test because of > 6 h hypotension or vasopressor/inotropic therapy. On the test day, the Simplified Acute Physiology Score II (SAPS II) and Sequential Organ Failure Assessment (SOFA) score were calculated to estimate disease severity. The ICU mortality until day 28 was recorded. Best discriminative levels of baseline cortisol, increases and peaks were established using receiver operating characteristic curves. These and corticosteroid treatment (in n = 112, 65%), among other variables, were examined by multiple logistic regression and Cox proportional hazard regression analyses to find independent predictors of ICU mortality until day 28. ICU mortality until day 28 was 23%. Nonsurvivors had higher SAPS II and SOFA scores. Baseline cortisol levels correlated directly with albumin levels and SAPS II. In the multivariate analyses, a cortisol baseline > 475 nmol/l and cortisol increase < 200 nmol/l predicted mortality, largely dependent on disease severity but independent of albumin levels. Corticosteroid (hydrocortisone) treatment was not associated with an improved outcome, regardless of the ACTH test results. In nonseptic hypotensive ICU patients, a low cortisol/ACTH response and treatment with corticosteroids do not contribute to mortality prediction by severity of disease. The data thus argue against RAI identifiable by cortisol/ACTH testing and necessitating corticosteroid substitution treatment in these patients.

Procalcitonin for early prediction of survival outcome in postoperative critically ill patients with severe sepsis

Identification of postoperative patients at high risk of dying early after intensive care unit (ICU) admission through a fast and readily available parameter may help in determining therapeutic interventions or further diagnostic procedures that could have an impact on patients' outcome. The aim of our study was to assess the utility of procalcitonin (PCT) and other readily available parameters, as useful early (days 1-3) predictors of mortality in postoperative patients diagnosed with severe sepsis within 24 h preceding their operation. More than a period of 2 yr, subsets of 69 postoperative patients admitted with severe sepsis and 890 non-septic ICU patients were investigated. PCT, C-reactive protein (CRP) and sequential organ failure assessment (SOFA) score were recorded over the duration of ICU stay. PCT area under receiver operating characteristic (ROC) curve was 0.78 on day 3 and was highly predictive of fatal outcome (0.90) at day 6. Area under ROC curve of SOFA score was 0.85 on day 3 and remained in this range until day 6. Area under ROC curves on day 3 of CRP (0.61) was non-predictive and remained non-predictive over the duration of ICU stay. PCT exhibited no discriminative power early after ICU admission for prediction of mortality in critically ill patients with severe sepsis, compared with a high predictive power of SOFA score on day 3. However, using PCT could still serve as a useful complementary comparator for prediction of survival outcome using the SOFA score.

Sepsis and SOFA score: related outcome for critically ill renal patients

To evaluate the influence of sepsis in critically ill patients with acute renal failure (ARF), and to analyze the value of the sequential organ failure assessment (SOFA) score for assessing the morbidity and related mortality of these patients. A prospective observational study developed in a medical intensive care unit (ICU) of a tertiary care university hospital. Data were collected from January 1, 2001 - July 31, 2002. The inclusion criterion was either a creatinine plasma level > or = 2 mg/dl on ICU admission or increases > or = 30% from its initial value. Sepsis was evaluated at the time of study inclusion, and patients were distributed into 2 groups (septic and nonseptic patients). Two hundred patients with ARF were prospectively enrolled in the study (91 (45.5%) septic and 109 (54.5%) nonseptic patients). Median age was 68 years in septic patients and 72 in nonseptic ones while the percentage of males in both groups was 66% vs 69%, respectively. Septic patients showed more organ failures and more respiratory, cardiovascular and coagulation failures at the time of study admission as well as a worse mean SOFA score during the first 4 days after inclusion (p < 0.01). Mortality rate at the ICU was significantly higher in the septic group when compared to the nonseptic one (55% vs 19.3%, OR = 2.21 (1.65 - 2.97)). Using stepwise logistic regression, acute tubular necrosis and oliguria in septic patients as well as cardiovascular failure (evaluated by SOFA score) in nonseptic patients were identified as independent risk factors for mortality. Septic and nonseptic ICU patients with ARF have an increased risk of ICU mortality depending on the type of organ failure. Although SOFA score does not predict outcome, it is a useful tool to categorize these patients and to describe a sequence of complications in critically ill patients.

Impaired circadian rhythm of melatonin secretion in sedated critically ill patients with severe sepsis.

Melatonin is involved in the regulation of the sleep-wake cycle and exhibits multiple interactions with the neuroendocrine and the immune system. Melatonin secretion in healthy individuals follows a stable circadian rhythm. Critical illness, continuous administration of drugs, and loss of external zeitgeber might impair the circadian rhythm of melatonin secretion in the intensive care unit (ICU), thereby compromising the physiologic stress-induced immune response. Prospective, controlled clinical study. Medical intensive care unit in a university hospital. Seventeen septic, sedated ICU patients (group A); 7 nonseptic ICU patients (group B); and 21 control patients (group C) were studied. 6-Sulfatoxymelatonin (aMT6s) was determined from urine samples taken at 4-hr intervals over a total period of 24 hrs. aMT6s was measured by enzyme-linked immunosorbent assay. Circadian mesors, phase amplitudes, and timing of the acrophase were assessed by cosinor analysis. Differences between groups were calculated by contingency data analysis and by analysis of variance. Circadian mesors of urinary aMT6s were 3904 +/- 1597, 2622 +/- 927, and 3183 +/- 1514 ng/4 hrs in groups A, B, and C, respectively (p = NS). aMT6s exhibited significant circadian periodicity in only 1/17 (6%) patients of group A but in 6/7 (86%) patients of group B and in 18/23 (78%) patients of group C (group A vs. groups B and C: p = .0001) Phase amplitudes were markedly lower in group A (1071 +/- 1005 ng/4 hrs) compared with group B (2284 +/- 581 ng/4 hrs, p = .009) and C (2838 +/- 2255 ng/4 hrs, p = .006). The acrophase was significantly delayed in patients of group A (10:35 am +/- 255 mins) compared with group B (05:43 am +/- 114 mins, p = .01) and group C (4:20 am +/- 107 mins, p < .0001). In sepsis survivors, aMT6s excretion profiles tended to normalize, but still lacked a significant circadian rhythm at ICU discharge. The present study revealed striking abnormalities in urinary aMT6s excretion in septic ICU patients. In contrast, circadian rhythm was preserved in nonseptic ICU patients, indicating that impaired circadian melatonin secretion in septic patients is mainly related to the presence of severe sepsis and/or concomitant medication. Further investigations are required to examine the underlying pathophysiologic mechanism and the clinical implications of this finding.

Increased Serum Concentration of Soluble CD14 Is a Prognostic Marker in Gram-Positive Sepsis

Increased serum sCD14 concentrations are associated with poor outcome in Gram-negative sepsis and trauma patients. In the present study serum sCD14 concentrations were measured in patients with Gram-positive sepsis and compared with Gram-negative septic and nonseptic intensive care unit patients. Furthermore, serum sCD14 concentration was correlated with patient's outcome. Serum samples of 28 Gram-positive (8 nonsurvivors/20 survivors) and 10 Gram-negative bacteriemic patients (3 nonsurvivors/7 survivors) were obtained at the day they met the sepsis criteria defined by Boneet al.(Day 0) and at Days 4 and 7 and compared with 10 nonseptic ICU patients and 10 healthy volunteers. Serum concentrations of sCD14 were measured by ELISA. Significantly higher sCD14 serum concentrations were found on Days 4 and 7 in Gram-positive nonsurvivors than in Gram-positive survivors (Day 4: 5.85 ± 0.48 vs 4.07 ± 0.43 μg/ml,P< 0.05; Day 7: 6.12 ± 0.46 vs 3.53 ± 0.33 μg/ml,P< 0.01). In addition, sCD14 concentrations of Gram-positive nonsurvivors were significantly higher than those of nonseptic ICU patients and healthy volunteers at any time of observation. However, no significant difference was calculated between Gram-positive and Gram-negative patients. Summarizing our results, the serum level of sCD14 could be proven to be a good prognostic marker in the course of Gram-positive sepsis. Increased levels are associated with a high mortality.