The role of angiogenic factors in predicting clinical outcome in severe bacterial infection in Malawian children

Introduction

Severe sepsis is a disease of the microcirculation, with endothelial dysfunction playing a key role in its pathogenesis and subsequent associated mortality. Angiogenesis in damaged small vessels may ameliorate this dysfunction. The aim of the study was to determine whether the angiogenic factors (vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), and angiopoietin-1 (Ang-1) and -2 (Ang-2)) are mortality indicators in Malawian children with severe bacterial infection.

Methods

In 293 children with severe bacterial infection, plasma VEGF, PDGF, FGF, and Ang-1 and Ang-2 were measured on admission; in 50 of the children with meningitis, VEGF, PDGF, and FGF were also measured in the CSF. Healthy controls comprised children from some of the villages of the index cases. Univariable and multivariable logistic regression analyses were performed to develop a prognostic model.

Results

The median age was 2.4 years, and the IQR, 0.7 to 6.0 years. There were 211 children with bacterial meningitis (72%) and 82 (28%) with pneumonia, and 154 (53%) children were HIV infected. Mean VEGF, PDGF, and FGF concentrations were higher in survivors than in nonsurvivors, but only PDGF remained significantly increased in multivariate analysis (P = 0.007). Mean Ang-1 was significantly increased, and Ang-2 was significantly decreased in survivors compared with nonsurvivors (6,000 versus 3,900 pg/ml, P = 0.03; and 7,700 versus 11,900 pg/ml, P = 0.02, respectively). With a logistic regression model and controlling for confounding factors, only female sex (OR, 3.95; 95% CI, 1.33 to 11.76) and low Ang-1 (OR, 0.23; 95% CI, 0.08 to 0.69) were significantly associated with mortality. In children with bacterial meningitis, mean CSF VEGF, PDGF, and FGF concentrations were higher than paired plasma concentrations, and mean CSF, VEGF, and FGF concentrations were higher in nonsurvivors than in survivors (P = 0.02 and 0.001, respectively).

Conclusions

Lower plasma VEGF, PDGF, FGF, and Ang-1 concentrations and higher Ang-2 concentrations are associated with an unfavorable outcome in children with severe bacterial infection. These angiogenic factors may be important in the endothelial dysregulation seen in severe bacterial infection, and they could be used as biomarkers for the early identification of patients at risk of a poor outcome.     

Delayed cerebral thrombosis in bacterial meningitis: a prospective cohort study

Purpose

To study the incidence and clinical characteristics of delayed cerebral thrombosis in bacterial meningitis patients.

Methods

We assessed the incidence and clinical characteristics of delayed cerebral thrombosis in adults with cerebrospinal fluid (CSF) culture-proven community-acquired bacterial meningitis included in a prospective nationwide study in The Netherlands performed from 2006 to 2012.

Results

Delayed cerebral thrombosis occurred in 11 of 1,032 episodes (1.1 %). CSF culture yielded Streptococcus pneumoniae in ten patients and Listeria monocytogenes in one. Adjunctive dexamethasone therapy was administered before or with the first dose of antibiotics in 9 of 11 patients; two patients were initially not treated with dexamethasone. All patients made good initial recovery, followed by sudden deterioration after 7–42 days. Cranial imaging studies showed multiple cerebral infarctions in all patients. The outcome was unfavorable in all but one patient. In an explorative analysis, patients with delayed cerebral thrombosis had eightfold higher complement C5a CSF concentrations on the diagnostic lumbar puncture as compared in those without delayed cerebral thrombosis (p = 0.04).

Conclusion

Delayed cerebral thrombosis is a rare but devastating complication of bacterial meningitis. Adjunctive dexamethasone therapy seems to predispose patients with bacterial meningitis to this complication. We found some evidence that this thrombotic complication is associated with activation of the complement system.     

High mobility group box 1 and angiogenetic growth factor levels in children with central nerve system infections

IntroductionTo clarify the pathology of children with acute encephalopathy and other neurological disorders, the involvement of high-mobility group box 1 (HMGB1), which is a representative of danger-associated molecular patterns, and angiogenesis-related growth factors were investigated.Patients and methodsParticipants were 12 children with acute encephalopathy (influenza, rotavirus, and others), 7 with bacterial meningitis, and 6 with epilepsy disease (West syndrome). Twenty-four patients with non-central nervous system (CNS) infections as a control group were admitted to our hospital. We examined the levels of HMGB1, platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), and other cytokines in the serum and cerebrospinal fluid (CSF) of the subjects.ResultsSerum and CSF HMGB1 levels were significantly higher in the encephalopathy and meningitis groups than in the West syndrome and control groups. CSF HMGB1 levels correlated with those of interleukin-6 and -8. CSF HMGB1 and VEGF levels were correlated, and PDGF showed a positive relationship.ConclusionHMGB1 and angiogenesis-related growth factors appear to play pivotal roles in the pathophysiology of CNS infections.     

Occult hypoperfusion is associated with increased mortality in hemodynamically stable, high-risk, surgical patients

Background

Our aim was to examine whether serial blood lactate levels could be used as predictors of outcome.

Methods

We prospectively studied 44 high-risk, hemodynamically stable, surgical patients. Blood lactate values, mean arterial pressure, heart rate and urine output were obtained at patient admission to the study, at 12, 24 and 48 hours.

Results

The nonsurvivors (n = 7) had similar blood lactate levels initially (3.1 ± 2.3 mmol/l versus 2.2 ± 1.0 mmol/l, P = not significant [NS]), but had higher levels after 12 hours (2.9 ± 1.7 mmol/l versus 1.6 ± 0.9 mmol/l, P = 0.012), after 24 hours (2.1 ± 0.6 mmol/l versus 1.5 ± 0.7 mmol/l, P = NS) and after 48 hours (2.7 ± 1.8 mmol/l versus 1.9 ± 1.4 mmol/l, P = NS) as compared with the survivors (n = 37). Arterial bicarbonate concentrations increased significantly in survivors and were higher than in nonsurvivors after 24 hours (22.9 ± 5.2 mEq/l versus 16.7 ± 3.9 mEq/l, P = 0.01) and after 48 hours (23.1 ± 4.1 mEq/l versus 17.6 ± 7.1 mEq/l, P = NS). The PaO₂/FiO₂ ratio was higher in survivors initially (334 ± 121 mmHg versus 241 ± 133 mmHg, P = 0.03) and remained elevated for 48 hours. There were no significant differences in mean arterial pressure, heart rate, and arterial blood oxygenation at any time between survivors and nonsurvivors. The intensive care unit stay (40 ± 42 hours versus 142 ± 143 hours, P < 0.001) and the hospital stay (12 ± 11 days versus 24 ± 17 days, P = 0.022) were longer for nonsurvivors than for survivors. The Simplified Acute Physiology Score II score was higher for nonsurvivors than for survivors (34 ± 9 versus 25 ± 14, P = NS). The urine output was slightly lower in the nonsurvivor group (P = NS). The areas under the receiving operating characteristic curves were larger for initial values of Simplified Acute Physiology Score II and blood lactate for predicting death.

Conclusion

Elevated blood lactate levels are associated with a higher mortality rate and postoperative complications in hemodynamically stable surgical patients.     

Usefulness of interleukin 6 levels in the cerebrospinal fluid for the diagnosis of bacterial meningitis

Purpose

Interleukin 6 (IL-6) is a proinflammatory cytokine produced during infections. We hypothesized that IL-6 levels in the cerebrospinal fluid (CSF) would be elevated in bacterial meningitis and useful for diagnosing and predicting neurologic outcomes.

Materials and methods

For the differentiation of bacterial meningitis, serum and CSF samples were obtained from patients with an altered level of consciousness. Patients were classified into 3 groups: bacterial meningitis, nonbacterial central nervous system disease, and other site sepsis.

Results

Of the 70 patients included in this study, there were 13 in the bacterial meningitis group, 21 in the nonbacterial central nervous system disease group, and 36 in the other site sepsis group. The CSF IL-6 level was significantly higher in the bacterial meningitis group than in the other 2 groups (P < .0001). Of the 5 CSF parameters assessed, CSF IL-6 level exhibited the largest area under the receiver operating characteristic curve (0.962), with a cut-off value of 644 pg/mL (sensitivity, 92.3%; specificity, 89.5%). To examine a potential association between a high CSF level and neurologic outcome, CSF IL-6 levels were divided into 4 quartiles, and each level was compared with the frequency of a good neurologic outcome. The frequency of a good neurologic outcome was significantly lower in the highest CSF IL-6 quartile than in the other 3 quartiles (odds ratio, 0.18; 95% confidence interval, 0.05-0.69; P = .013).

Conclusions

Measurement of the CSF IL-6 level is useful for diagnosing bacterial meningitis.     

Cerebrospinal creatinine kinase level in children with meningitis

Background

The aim of this study is to evaluate the diagnostic value of the enzyme creatine kinase (CK) in the cerebrospinal fluid (CSF) of children with meningitis.

Method

CSF samples were collected from seventy one children suspected of having meningitis. The levels of total CK, CK-BB, Glucose, total protein, WBC counts, and culture were determined in the CSF. The cutoff value for total CK in the CSF was defined as 18 U/L.

Results

Three cases (4%) of bacterial meningitis and 11 cases (15%) of aseptic meningitis were confirmed by culture. The sensitivity and specificity of total CK CSF level alone to diagnose bacterial meningitis were found to be 33% and 91% respectively. The positive and negative predictive values were found to be 14% and 98% respectively. On the other hand, the sensitivity and specificity of total CK level in aseptic meningitis were found to be 40% and 98% respectively and the positive and negative predictive values were 86% and 94% respectively. The sensitivity and specificity of total protein and glucose in CSF were also calculated. Streptococcus pneumonia and homophiles influenza were the main types identified in our cases.

Discussion and conclusion

Measuring the total CK level in the CSF may be very useful in diagnosis of meningitis if only combined with other CSF markers. It is not of any much benefit if it is used solely.     

Cerebrospinal fluid/blood glucose ratio as an indicator for bacterial meningitis

Background

Bacterial meningitis is an emergent disease requiring prompt diagnosis and treatment with appropriate antimicrobials. Although the lumbar puncture is widely used as a diagnostic tool for bacterial meningitis, it remains unclear which value in cerebrospinal fluid (CSF) analysis in emergency laboratory tests precisely predicts the presence of bacterial meningitis.

Methods

This is a single-center, retrospective review of medical records to determine which emergency laboratory CSF test results are useful for predicting bacterial meningitis. The diagnosis of meningitis is made when the white blood cell count in CSF exceeds 5 cells/μL, while the diagnosis of bacterial meningitis additionally requires the growth of a pathogen from a CSF culture or the identification of a pathogen in Gram staining of CSF specimen.

Results

We identified 15 patients with bacterial meningitis and 129 patients with aseptic meningitis. While neutrophil-predominant pleocytosis and a decreased glucose level in CSF can predict the presence of bacterial meningitis, the CSF/blood glucose ratio is more precise (optimal cut-off = 0.36, sensitivity = 92.9%, specificity = 92.9%, area under the curve = .97) even after administration of antimicrobials prior to examination in the emergency department.

Conclusion

This study suggests that the CSF/blood glucose ratio may be a better single indicator for bacterial meningitis. Since the CSF glucose and blood glucose values are promptly and easily obtained from a lumbar puncture, the CSF/blood glucose ratio should be considered as a timely diagnostic indicator of bacterial meningitis. It may also help exclude the diagnosis of bacterial meningitis especially in cases in which no microorganisms can be cultured.     

Acute meningitis prognosis using cerebrospinal fluid interleukin-6 levels

Background

Improved diagnostic tests would aid in diagnosing and treating community-acquired meningitis.

Objective

To analyze the diagnostic value of interleukin-6 (IL-6) in the cerebrospinal fluid (CSF) of patients presenting with symptoms of acute meningitis.

Material and Methods

In a 6-month prospective, observational, cross-sectional emergency department (ED) study, serum and CSF samples were obtained from all patients with a headache and fever in whom the physician suspected meningitis. Patients were excluded if computed tomography findings contraindicated a lumbar puncture, if they had bleeding disorders, or if their serum indicated bleeding. IL-6 levels were measured and compared in patients with (Group A) and without (Group B) bacterial meningitis.

Results

Samples were obtained from 53 patients, of whom 40 were ultimately found to have meningitis. These 40 patients averaged 49.6 ± 21.9 years, with number of men 18 (45%), hospitalizations 21 (52%), mortality 3 (.07%), and IL-6 average rating 491 (median: 14.5; range 0000–6000). Findings in the two groups were: Group A (with meningitis): n = 13, average IL-6 level: 1495 (median: 604; 25/75 percentiles: 232.5–2030; 95% confidence interval [CI] 371.7–2618.6; range 64–6000). Group B (with aseptic meningitis): n = 27, average IL-6 level: 7.34 (median: 5; 25/75 percentiles: 0.0/15.1; 95% CI 3.94–10.73; range 0–23.6). Mann-Whitney rank sum test: p < 0.0001.

Conclusions

In patients with acute bacterial meningitis, CSF cytokine concentrations are elevated. Measuring CSF inflammatory cytokine levels in patients with acute meningitis could be a valuable ED diagnostic tool. Using this tool could improve the prognosis of patients with bacterial meningitis by allowing more rapid initiation of antibiotic treatment.     

A Review of the Impact of Pneumococcal Polysaccharide Conjugate Vaccine (7-valent) on Pneumococcal Meningitis

Introduction

Streptococcus pneumoniae is the leading cause of bacterial meningitis. Young children, the elderly and those who are immunocompromised or who suffer from chronic diseases have the highest risk of developing pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed in 2000 in the US and in 2001 in Europe.

Methods

A literature search was performed in PubMed to identify studies assessing the impact of routine childhood PCV7 vaccination on pneumococcal diseases. Here, we report the impact on pneumococcal meningitis.

Results

A total of 17 articles reporting impact data on pneumococcal meningitis were included in this review: 11 from Western Europe and 6 from North America. In the post-vaccination period, compared with the pre-vaccination period, a reduction ranging from 59.2% in the US, 1 year after vaccine introduction, to 100% in Belgium, 4 years after vaccine introduction in vaccine-type (VT) pneumococcal meningitis incidence was reported in vaccine-eligible children in seven studies. In addition, the majority of studies reported reductions in VT and all-type pneumococcal meningitis incidence in age groups that were not vaccine-eligible.

Conclusions

The results from this review demonstrate that PCV7 has had a significant impact on pneumococcal meningitis across all ages through its use in pediatric immunization programs. With the introduction of 13-valent PCV (PCV13) we can expect to see a reduction in the incidence of pneumococcal meningitis due to the six additional serotypes included, as well as continued protection against pneumococcal meningitis due to PCV7 serotypes. Robust surveillance systems are essential for the evaluation of the impact of PCV13 on all-type pneumococcal meningitis and for monitoring the evolution of non-vaccine serotype pneumococcal meningitis.     

Biomarkers of inflammation, coagulation and fibrinolysis predict mortality in acute lung injury

Background

Acute lung injury (ALI) is a major cause of acute respiratory failure with high mortality despite lung-protective ventilation. Prior work has shown disordered inflammation and coagulation in ALI, with strong correlations between biomarker abnormalities and worse clinical outcomes. We measured plasma markers of inflammation, coagulation and fibrinolysis simultaneously to assess whether these markers remain predictive in the era of lung-protective ventilation.

Methods

Plasma samples and ventilator data were prospectively collected from 50 patients with early ALI. Plasma biomarkers of inflammation (IL-6, IL-8, intercellular adhesion molecule 1), of coagulation (thrombomodulin, protein C) and of fibrinolysis (plasminogen activator inhibitor 1) were measured by ELISA. Biomarker levels were compared between survivors (n = 29) and non-survivors (n = 21) using Mann–Whitney analysis.

Results

The tidal volume for the study group was 6.6 ± 1.1 ml/kg predicted body weight and the plateau pressure was 25 ± 7 cmH₂O (mean ± standard deviation), consistent with lung-protective ventilation. All markers except IL-6 were significantly different between survivors and nonsurvivors. Nonsurvivors had more abnormal values. Three biomarkers – IL-8, intercellular adhesion molecule 1 and protein C – remained significantly different by multivariate analysis that included age, gender, Simplified Acute Physiology Score II and all biomarkers that were significant on bivariate analysis. Higher levels of IL-8 and intercellular adhesion molecule 1 were independently predictive of worse outcomes (odds ratio = 2.0 and 5.8, respectively; P = 0.04 for both). Lower levels of protein C were independently associated with an increased risk of death (odds ratio = 0.5), a result that nearly reached statistical significance (P = 0.06).

Conclusion

Despite lung-protective ventilation, abnormalities in plasma levels of markers of inflammation, coagulation and fibrinolysis predict mortality in ALI patients, indicating more severe activation of these biologic pathways in nonsurvivors.     

A multicenter study of septic shock due to candidemia: outcomes and predictors of mortality

Purpose

Candida is the most common cause of severe yeast infections worldwide, especially in critically ill patients. In this setting, septic shock attributable to Candida is characterized by high mortality rates. The aim of this multicenter study was to investigate the determinants of outcome in critically ill patients with septic shock due to candidemia.

Methods

This was a retrospective study in which patients with septic shock attributable to Candida who were treated during the 3-year study period at one or more of the five participating teaching hospitals in Italy and Spain were eligible for enrolment. Patient characteristics, infection-related variables, and therapy-related features were reviewed. Multiple logistic regression analysis was performed to identify the risk factors significantly associated with 30-day mortality.

Results

A total of 216 patients (mean age 63.4 ± 18.5 years; 58.3 % males) were included in the study. Of these, 163 (75 %) were admitted to the intensive care unit. Overall 30-day mortality was 54 %. Significantly higher Acute Physiology and Chronic Health Evaluation (APACHE) II scores, dysfunctional organs, and inadequate antifungal therapy were compared in nonsurvivors and survivors. No differences in survivors versus nonsurvivors were found in terms of the time from positive blood culture to initiation of adequate antifungal therapy. Multivariate logistic regression identified inadequate source control, inadequate antifungal therapy, and 1-point increments in the APACHE II score as independent variables associated with a higher 30-day mortality rate.     

Luminal concentrations of L- and D-lactate in the rectum may relate to severity of disease and outcome in septic patients

Introduction

Little is known about the condition of the large bowel in patients with sepsis. We have previously demonstrated increased concentrations of L-lactate in the rectal lumen in patients with abdominal septic shock. The present study was undertaken to assess the concentrations of L- and D-lactate in rectal lumen and plasma in septic patients including the possible relation to site of infection, severity of disease, and outcome.

Methods

An intensive care unit observational study was conducted at two university hospitals, and 23 septic patients and 11 healthy subjects were enrolled. Participants were subjected to rectal equilibrium dialysis, and concentrations of L- and D-lactate in dialysates and plasma were analysed by spectrophotometry.

Results

Luminal concentrations of L-lactate in rectum were related to the sequential organ failure assessment scores (R ² = 0.27, P = 0.01) and were higher in non-survivors compared to survivors and healthy subjects (mean [range] 5.0 [0.9 to 11.8] versus 2.2 [0.4 to 4.9] and 0.5 [0 to 1.6] mmol/l, respectively, P < 0.0001), with a positive linear trend (R ² = 0.53, P < 0.0001). Also, luminal concentrations of D-lactate were increased in non-survivors compared to survivors and healthy subjects (1.1 [0.3 to 2.5] versus 0.3 [0 to 1.2] and 0.1 [0 to 0.8] mmol/l, respectively, P = 0.01), with a positive linear trend (R ² = 0.14, P = 0.04). Luminal concentrations of L- and D-lactate were unaffected by the site of infection. Plasma concentrations of L-lactate were also increased in non-survivors compared to survivors (3.8 [1.7 to 7.0] versus 1.5 [0 to 3.6] mmol/l, P < 0.01). In contrast, plasma concentrations of D-lactate were equally raised in non-survivors (0.4 [0.1 to 0.7] mmol/l) and survivors (0.3 [0.1 to 0.6] mmol/l) compared with healthy subjects (0.03 [0 to 0.13] mmol/l).

Conclusion

In patients with severe sepsis and septic shock, luminal concentrations of L- and D-lactate in the rectum were related to severity of disease and outcome.     

Does This Child Have Bacterial Meningitis? A Systematic Review of Clinical Prediction Rules for Children with Suspected Bacterial Meningitis

Background

Acute meningitis is a relatively common phenomenon in children. Identifying which children are most likely to have bacterial meningitis vs. self-limiting aseptic meningitis is important, as these children require investigation and antibiotic treatment.

Objective

Our aim was to systematically identify and review the quality and performance of published clinical prediction rules (CPRs) for children with suspected bacterial meningitis.

Methods

Medline and Embase were searched for CPRs involving children 0–18 years of age with suspected bacterial meningitis, with cerebral spinal fluid (CSF) culture used as the reference diagnostic standard. CPR quality was assessed using 17 previously published items. CPR performance was evaluated using sensitivity, negative likelihood ratio, and the treatment frequency that would result if the rule was used.

Results

Eleven studies involving 6675 children with acute meningitis fulfilled all inclusion criteria and were entered in the study. They all describe the derivation or validation of six unique CPRs. A rigorously developed, high-performing, and well-validated CPR ready for clinical use to guide which children with suspected bacterial meningitis should be hospitalized and treated with intravenous antibiotics and which can be safely discharged home was not identified. Areas for quality improvement for future CPR studies include prospective validation using standardized inclusion criteria, adequate blinding, predictor reproducibility assessment, and meticulous follow-up of outcomes. The Bacterial Meningitis Score had the highest quality and performance and is the best candidate for prospective validation.

Conclusions

Until consistently high methodological quality and diagnostic performance are demonstrated through prospective validation, caution is warranted in the routine clinical use of existing CPRs for children with suspected bacterial meningitis.     

Cerebrospinal fluid pentraxin 3 early after subarachnoid hemorrhage is associated with vasospasm

Purpose

To investigate plasma and cerebrospinal fluid (CSF) concentrations of pentraxin 3 (PTX3), a prototypic long pentraxin protein induced by proinflammatory signals, in subarachnoid hemorrhage (SAH), and its relation with SAH-associated vasospasm.

Methods

Serial plasma and CSF samples were collected from 38 consecutive SAH patients admitted to the Neurosurgical Intensive Care. PTX3 concentrations were analyzed in relation to clinical status and clinical vasospasm (defined as neuro-worsening and angiographic confirmation of vessel narrowing). Since neutrophils are an important source of preformed PTX3, myeloperoxidase (MPO) in CSF was measured to assess the correlation with CSF PTX3 and establish whether blood contamination was the determinant of PTX3 increase.

Results

PTX3 was elevated in all SAH patients both in plasma and CSF. Acute peak (first 48?h after SAH) CSF PTX3 was significantly higher in patients who later developed vasospasm [median 13.6 (range 2.3?C51.9)?ng/ml] compared to those who did not [3.2 (0.1?C50.5)?ng/ml, p?=?0.03]. The temporal pattern of CSF PTX3 in patients with vasospasm was triphasic with a peak during the first 48?h after SAH, a subsequent decrease in the following 48?C96?h and a secondary significant increase with the occurrence of vasospasm. A loose correlation between CSF PTX3 and MPO was observed (r ²?=?0.13), indicating that following SAH there is a brain production of PTX3.

Conclusions

Acute increased concentrations of PTX3 in CSF but not in plasma are related to the occurrence of vasospasm, indicating that measurement of CSF PTX3 associated with the clinical evaluation can improve early diagnosis of this complication.     

Correlation between vancomycin penetration into cerebrospinal fluid and protein concentration in cerebrospinal fluid/serum albumin ratio

Bacterial meningitis is a life-threatening condition. Vancomycin (VCM) is one of the antibiotics used as empirical therapy for bacterial meningitis. It is essential to maintain an adequate concentration of VCM in cerebrospinal fluid (CSF) to treat bacterial meningitis effectively. VCM administered intravenously must pass the blood-brain barrier (BBB) to enter the CSF and the extent of VCM penetration into CSF varies widely among patients. Previous report indicated that CSF albumin level is useful for estimation of VCM CSF penetration. However, CSF albumin level is not measured in routine practice. We focused on CSF protein concentration that is generally examined at the beginning of diagnosis and treatment of bacterial meningitis. We examined the relationship between CSF protein concentration/serum albumin ratio and the extent of VCM penetration into CSF.This retrospective study involved 7 patients admitted to our hospital who were treated with VCM for suspected bacterial meningitis. The VCM concentrations in serum and CSF were 17.6 ± 7.2 μg/mL and 3.31 ± 3.14 μg/mL, respectively. The serum VCM concentrations showed no significant correlation with CSF VCM concentrations. On the other hand, the protein concentration in CSF/serum albumin ratio showed a strong positive correlation with the VCM CSF/serum ratio (r = 0.877, p < 0.005). Our study indicates that the ratio of CSF protein concentration/serum albumin is likely useful for estimating the approximate VCM CSF/serum ratio. This could contribute to an improvement in the treatment of bacterial meningitis.     

Early hyperlactataemia in critically ill children

Objective: To examine the relationships between early hyperlactataemia, acidosis, organ failure, and mortality in children admitted to intensive care.¶Design: Prospective observational study. Children with lactate levels > 2 mmol/l were eligible for enrolment. Post-operative patients and those with inherited metabolic disease were excluded. Seven hundred and five children admitted to intensive care were screened, and 50 children with hyperlactataemia (incidence 7 %), aged 20.3 months (0.1–191) were enrolled and followed up. The Paediatric Risk of Mortality (PRISM) score, Multiorgan System Failure (MOSF) score, length of ICU stay, and outcome were recorded. Data were collected for lactate (mmol/l), pH, and base excess (BE) until 24 h after admission. Data are reported as median (range) and were analysed by the Mann-Whitney, Fisher's Exact, and Kruskal-Wallis tests, and chi-squared test for trend.¶Results: Overall mortality in the screening group was 70/705 (10 %). In the study group (n = 50) median PRISM score was 19 (4–49), median MOSF score 2 (1–4), and observed mortality 32/50 (64 %). Median duration of ICU stay was 6 days (2–32) in survivors, and median time until death 3 days (0–13) in nonsurvivors. Eleven nonsurvivors (34 %) died within 24 h. In the screening group, hyperlactataemia on admission identified mortality with likelihood ratio = 15. In the study group, neither the admission lactate (3.8 vs 4.6 mmol/l, P = 0.27), pH (7.32 vs 7.30, P = 0.6), nor BE (–7.5 vs –8, P = 0.45) differed significantly between survivors and nonsurvivors. Neither the admission nor peak lactate increased with increasing MOSF score (P = 0.5 and 0.54). The median peak lactate level was 5 mmol/l (2–9.3) in survivors compared to 6.8 mmol/l (2.3–22) in nonsurvivors (P = 0.02), and the cumulative average lactate level was 2.4 mmol/l (1–4.9) in survivors, compared to 4.5 mmol/l (1.6–21) in nonsurvivors (P = 0.0003). Persistent hyperlactataemia 24 h after admission identified mortality with likelihood ratio = 7.¶Conclusion: Hyperlactataemia on admission to intensive care is associated with a high mortality in children. Nonsurvivors within this group may be distinguished by the peak lactate level, or by persistent hyperlactataemia after 24 h of treatment.     

Viral Meningitis: Which Patients Can Be Discharged from the Emergency Department?

Background

Even in an era when cases of viral meningitis outnumber bacterial meningitis by at least 25:1, most patients with clinical meningitis are hospitalized.

Objective

We describe the clinical characteristics of an unusual outbreak of viral meningitis that featured markedly elevated cerebrospinal fluid white blood cell counts (CSF WBC). A validated prediction model for viral meningitis was applied to determine which hospital admissions could have been avoided.

Methods

Data were collected retrospectively from patients presenting to our tertiary care center. Charts were reviewed in patients with CSF pleocytosis (CSF WBC > 7 cells/mm³) and a clinical diagnosis of meningitis between March 1, 2003 and July 1, 2003. Cases were identified through hospital infection control and by surveying all CSF specimens submitted to the microbiology laboratory during the outbreak.

Results

There were 78 cases of viral meningitis and 1 case of bacterial meningitis identified. Fifty-eight percent of the viral meningitis cases were confirmed by culture or polymerase chain reaction to be due to Enterovirus. Mean CSF WBC count was 571 cells/mm³, including 20 patients with a CSF WBC count > 750 cells/mm³ (25%) and 11 patients with values > 1000 cells/mm³ (14%). Sixty-four of 78 patients (82%) were hospitalized. Rates of headache, photophobia, nuchal rigidity, vomiting, and administration of intravenous fluids in the Emergency Department were no different between admitted and discharged patients. Only 26/78 (33%) patients with viral meningitis would have been admitted if the prediction model had been used.

Conclusions

Although not all cases of viral meningitis are necessarily suitable for outpatient management, use of a prediction model for viral meningitis may have helped decrease hospitalization by nearly 60%, even though this outbreak was characterized by unusually high levels of CSF pleocytosis.     

Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis

Introduction  

Making a differential diagnosis between bacterial meningitis and aseptic meningitis is a critical clinical problem. The utility of a cerebrospinal fluid (CSF) lactate assay for this purpose has been debated and is not yet routinely clinically performed. To adequately evaluate this assay, a systematic review and meta-analysis of studies of the CSF lactate concentration as a marker for both bacterial meningitis and aseptic meningitis was performed.     

Desire for children,difficulties achieving a pregnancy,and infertility distress 3 to 7 years after cancer diagnosis

Purpose

The aim was to investigate desire for children, difficulties achieving a pregnancy, and infertility distress among survivors 3 to 7 years after cancer treatment in reproductive age.

Methods

Cancer survivors were identified in national population-based cancer registries. Eligible subjects presented with selected cancer diagnoses between 2003 and 2007 between the ages of 18 to 45. A postal questionnaire including study-specific questions, the Short-Form 36 Health Survey and the Fertility Problem Inventory, was sent to 810 survivors, and 484 participated (60 % response).

Results

Most survivors who had a pretreatment desire for children still wanted children 3–7 years after treatment, and this group was characterized by young age and being childless at diagnosis. In addition, a substantial group of survivors (n?=?55, 17 %) that did not have a pretreatment desire for children had changed their mind about wanting children after treatment. About a third of the survivors with a desire to have children had experienced difficulties achieving a pregnancy after the cancer treatment, and an unfulfilled desire to have children was associated with worse mental health. Survivors presently facing difficulties achieving a pregnancy reported moderate levels of infertility distress and expressed low interest in using gamete donation.

Conclusions

Health professionals in cancer care need to be aware that patients’ plans for future children may change, particularly if they are young and childless. All patients of reproductive age should be provided with adequate information about the impact of cancer treatment on future fertility and fertility preservation.     

Soluble triggering receptor expressed on myeloid cells 1: a biomarker for bacterial meningitis

OBJECTIVE: To evaluate whether soluble triggering receptor expressed on myeloid cells 1 (sTREM-1) in CSF can serve as a biomarker for the presence of bacterial meningitis and outcome in patients with this disease. DESIGN: Retrospective study of diagnostic accuracy. SETTING AND PATIENTS: CSF was collected from 92 adults with community-acquired bacterial meningitis who participated in the prospective Dutch Meningitis Cohort Study; 8 patients with viral meningitis and 9 healthy control subjects. RESULTS: CSF sTREM-1 levels were higher in patients with bacterial meningitis (median 82 pg/ml, range 0-988) than in those with viral meningitis (0 pg/ml, 0-48) and controls (0 pg/ml, 0-36). The diagnostic accuracy of sTREM-1 in discriminating between patients with and without bacterial meningitis, expressed as the area under the receiver operating characteristic curve, was 0.82. At a cutoff level of 20 pg/ml the sensitivity was 0.73 and specificity 0.77. In patients with bacterial meningitis CSF sTREM-1 levels were associated with mortality (survivors, median 73 pg/ml, range 0-449 pg/ml; nonsurvivors, 15 pg/ml, 0-988). CONCLUSIONS: Measuring sTREM-1 in CSF may be a valuable new additional approach to accurately diagnose bacterial meningitis and identify patients at high risk for adverse outcome. Therefore a prospective study of sTREM-1 as a biomarker in bacterial meningitis is needed.