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.     

Non-invasive assessment of vasospasm following aneurysmal SAH using C-arm FDCT parenchymal blood volume measurement in the neuro-interventional suite: Technical feasibility

Introduction

Cerebral vasospasm is the leading cause of morbidity and mortality in patients with aneurysmal subarachnoid haemorrhage (SAH) surviving the initial ictus. Commonly used techniques for vasospasm assessment are digital subtraction angiography and transcranial Doppler sonography. These techniques can reliably identify only the major vessel spasm and fail to estimate its haemodynamic significance. To overcome these issues and to enable comprehensive non-invasive assessment of vasospasm inside the interventional suite, a novel protocol involving measurement of parenchymal blood volume (PBV) using C-arm flat detector computed tomography (FDCT) was implemented.

Materials and methods

Patients from the neuro-intensive treatment unit (ITU) with suspected vasospasm following aneurysmal SAH were scanned with a biplane C-arm angiography system using an intravenous contrast injection protocol. The PBV maps were generated using prototype software. Contemporaneous clinically indicated MR scan including the diffusion- and perfusion-weighted sequences was performed. C-arm PBV maps were compared against the MR perfusion maps.

Results

Distribution of haemodynamic impairment on C-arm PBV maps closely matched the pattern of abnormality on MR perfusion maps. On visual comparison between the two techniques, the extent of abnormality indicated PBV to be both cerebral blood flow and cerebral blood volume weighted.

Conclusion

C-arm FDCT PBV measurements allow an objective assessment of the severity and localisation of cerebral hypoperfusion resulting from vasospasm. The technique has proved feasible and useful in very sick patients after aneurysmal SAH. The promise shown in this early study indicates that it deserves further evaluation both for post-SAH vasospasm and in other relevant clinical settings.     

Endothelin-receptor antagonists for aneurysmal subarachnoid hemorrhage: an updated meta-analysis of randomized controlled trials

Introduction

The previous meta-analysis on the use of endothelin-receptor antagonists (ETRAs) to treat aneurysmal subarachnoid hemorrhage (SAH) has become outdated due to recently published phase 3 clinical trials. An up-to-date meta-analysis is needed to provide the best available evidence for the efficacy of ETRAs for aneurysmal SAH.

Methods

We performed a systematic review and meta-analysis of published randomized controlled trials that investigate efficacy of ETRAs in patients with aneurysmal SAH. Mortality, unfavorable outcome, delayed ischemic neurological deficit (DIND), delayed cerebral infarction (DCI), angiographic vasospasm and adverse events were analyzed. Meta-analysis was performed in terms of the risk ratio (RR) and 95% confidence interval (CI).

Results

Five eligible studies were reviewed and analyzed, involving 2,595 patients. The pooled RRs of mortality and unfavorable outcome after SAH were 1.03 (95% CI = 0.77 to 1.36) and 1.07 (95% CI = 0.93 to 1.22), respectively. The pooled RRs were 0.87 (95% CI = 0.74 to 1.03) for DCI, 0.77 (95% CI = 0.66 to 0.90) for DIND, and 0.66 (95% CI = 0.57 to 0.77) for angiographic vasospasm. There were significant increases in lung complications (RR = 1.80, 95% CI = 1.55 to 2.09), hypotension (RR = 2.42, 95% CI = 1.78 to 3.29) and anemia (RR = 1.47, 95% CI = 1.19 to 1.83) in patients administered ETRAs.

Conclusion

There is no evidence that ETRAs could benefit clinical outcome in patients with SAH. Owing to the increased adverse events, further clinical trials of ETRAs in SAH patients should be more carefully formulated and designed. The present results also suggest that DCI may be a better outcome measure than vasospasm and DIND in SAH clinical trials and observational studies.     

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.     

Multivariate analysis of risk factors for QT prolongation following subarachnoid hemorrhage

Background

Subarachnoid hemorrhage (SAH) often causes a prolongation of the corrected QT (QTc) interval during the acute phase. The aim of the present study was to examine independent risk factors for QTc prolongation in patients with SAH by means of multivariate analysis.

Method

We studied 100 patients who were admitted within 24 hours after onset of SAH. Standard 12-lead electrocardiography (ECG) was performed immediately after admission. QT intervals were measured from the ECG and were corrected for heart rate using the Bazett formula. We measured serum levels of sodium, potassium, calcium, adrenaline (epinephrine), noradrenaline (norepinephrine), dopamine, antidiuretic hormone, and glucose.

Results

The average QTc interval was 466 ± 46 ms. Patients were categorized into two groups based on the QTc interval, with a cutoff line of 470 ms. Univariate analyses showed significant relations between categories of QTc interval, and sex and serum concentrations of potassium, calcium, or glucose. Multivariate analyses showed that female sex and hypokalemia were independent risk factors for severe QTc prolongation. Hypokalemia (<3.5 mmol/l) was associated with a relative risk of 4.53 for severe QTc prolongation as compared with normokalemia, while the relative risk associated with female sex was 4.45 as compared with male sex. There was a significant inverse correlation between serum potassium levels and QTc intervals among female patients.

Conclusion

These findings suggest that female sex and hypokalemia are independent risk factors for severe QTc prolongation in patients with SAH.     

Endothelin antagonists in subarachnoid hemorrhage: what next?

In the previous issue of Critical Care, Ma and colleagues perform a meta-analysis of five randomized, clinical trials of endothelin antagonists in patients with aneurysmal subarachnoid hemorrhage. There are four trials using clazosentan and one trial with TAK-044. These studies show that endothelin plays an important role in the genesis of angiographic vasospasm. The benefit of these drugs is less on delayed cerebral ischemia and nonexistent on overall clinical outcome. Why the drugs reduce vasospasm but do not improve outcome could be because of side effects such as hypotension and pulmonary complications that are more common in patients treated with endothelin antagonists or because rescue therapy, which is used more in the placebo groups, improves outcome in these patients to the same extent as the endothelin antagonists. As the authors conclude, future studies of these drugs will need to consider these and other factors in their design.In the previous issue of Critical Care, Ma and colleagues report a meta-analysis of the randomized, clinical trials of clazosentan and TAK-044 in patients with aneurysmal subarachnoid hemorrhage (SAH) [1]. The endothelins (ETs) are a family of three (ET-1, ET-2 and ET-3) 21-amino-acid peptides that act on several receptors, principally ET_A and ET_B receptors in the vasculature. The main effect is to cause vasoconstriction. Experimental data as well as the results of this meta-analysis show that this system is important in the pathogenesis of angiographic vasospasm after SAH [2]. A variety of ET receptor antagonists have been developed. Clazosentan is a heteroarylsulfonamido pyrimidine that was specifically developed to be a relatively water-soluble, small-molecule, highly-selective ET_A receptor antagonist for prevention of angiographic vasospasm [3]. TAK-044 is a relatively nonselective antagonist of ET_A and ET_B receptors [4].Ma and colleagues identified five randomized clinical trials of ET antagonists for SAH. Their meta-analysis gives the same results as the trials, which at least for the four largest studies all had basically the same results. The pooled relative risk (RR) of angiographic vasospasm with ET antagonist treatment was 0.66 (95% confidence interval (CI) = 0.57 to 0.77), so these drugs effectively reduce vasospasm. The main consequence of vasospasm, delayed cerebral ischemia (DCI), was defined in the last three clazosentan studies as delayed ischemic neurological deficit. The current meta-analysis reports delayed ischemic neurological deficit and DCI, but DCI is defined as infarction on computed tomography ''only attributable to cerebral vasospasm and DCI'' [1], which is a partly circular definition. These varied definitions lead to confusion since the definitions vary in the studies and the terminology of Ma and colleagues does not match that recommended by Vergouwen and colleagues [5]. Interestingly, and not unexpectedly, there was a significant reduction in delayed ischemic neurological deficit (RR = 0.77, 95% CI = 0.66 to 0.90) and a trend towards reduction in DCI (RR = 0.87, 95% CI = 0.74 to 1.03). Despite these improvements, there was no effect on mortality and unfavorable outcome. Thus, considering the pathway from angiographic vasospasm to ischemia (DCI by most definitions), to infarction, and to poor outcome, the benefits of ET antagonists diminish at each step.The findings of Ma and colleagues are virtually identical to a meta-analysis conducted by Vergouwen and colleagues [6]. Vergouwen and colleagues, however, also reported data from a subset of the studies showing that there was no significant reduction in vasospasm-related cerebral infarction (RR = 0.76, 95% CI = 0.53 to 1.11) although the RR is reduced, in keeping with the analysis of Ma and colleagues. ET antagonists did not seem to have any effect on all new cerebral infarction (RR = 1.04; 95% CI = 0.91 to 1.19). This is an important finding since cerebral infarction is one of the most important prognostic factors for outcome after SAH. The odds ratios show the same pattern as mentioned above.Why is there a substantial effect on angiographic vasospasm, less effect on infarction judged to be due to vasospasm and no effect on all delayed infarcts and clinical outcome? One theory is that the delayed infarctions are not due solely to angiographic vasospasm. This theory predicts that reducing angiographic vasospasm may not be adequate to reduce infarction and improve outcome. Under this theory, the vasospasm-related and any new infarction incidences should be the same. Strictly speaking, they are the same - although, as noted above, the trends in the odds ratios seem different. One alternative theory is that side effects of the drugs, such as hypotension and pulmonary complications, counteract the beneficial effects of reducing vasospasm so that there is no overall beneficial effect on outcome. Indeed, both meta-analyses report virtually identical and significant increases in lung complications, hypotension and anemia in the patients treated with ET antagonists. To fit the data, this theory would require those side effects being sufficient to cause infarctions so that the overall infarction rate is about the same. One could argue that the data, while not conclusive, favor the second theory. Another fundamental issue is that patients in the placebo groups of these studies are administered rescue therapies for DCI in a higher percentage of cases than in the drug-treated groups. If rescue therapy is efficacious, then this also could reduce the difference between the groups in cerebral infarction and overall clinical outcome.What are some of the limitations of Ma and colleagues'' meta-analysis? The strengths of the current analysis are that it is rigorous and follows preferred reporting items for systematic review and meta-analysis (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines [7]. The results of this meta-analysis are not surprising, given that the results for all of the individual studies are the same - which is not a weakness but a comment. Another issue is the inclusion of drugs of different chemical classes and with different known pharmacologic actions in these sorts of meta-analyses. Multiple doses and methods and timing of administration of different drugs are combined into single treatment groups, which makes no sense biologically.What does the future hold for ET antagonists in SAH? Since all of the studies are only recently completed, obtaining the individual patient data from the sponsors may allow further analysis to guide further studies. This collation is obviously being done, since Actelion (Allschwill, Switzerland) sponsored all of the clazosentan studies, have the data and have invested heavily in clazosentan. According to Vergouwen and colleagues, Actelion did not provide individual patient data or data that would enable an intention-to-treat analysis [6]. The former omission is an issue. The latter missing data, however, given the small number of patients involved, are not going to change the overall findings. Actelion, however, must be complimented for supporting development of clazosentan and for conducting these studies that would not have occurred if we waited for funding from peer-reviewed granting agencies. The studies they have conducted have been fundamentally directed at improving the outcome of patients with SAH and there cannot be any question about their motivation to develop a drug that will address this.In summary, the authors'' conclusion is that future studies of ET antagonists should be ''more carefully formulated and designed''. Input into the design of these studies would be welcome, given that all of these studies were already very carefully formulated and designed. My opinion is that some method of reducing the side effects of ET antagonists, primarily hypotension and pulmonary complications, is the key to the future of these drugs.     

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.     

Ethyl pyruvate attenuates delayed experimental cerebral vasospasm following subarachnoid haemorrhage in rats: possible role of JNK pathway

The pathophysiology of delayed cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is multifaceted and involves endothelial apoptosis and inflammation. Ethyl pyruvate (EP) could attenuate early brain injury following SAH via anti-inflammation and inhibition of the c-Jun N-terminal kinase (JNK) signalling pathway. However, the role of EP in the delayed CVS has yet to be determined. In this study, we examined the effect of EP on endothelial apoptosis and inflammation and explore possible signalling pathways. We found that EP could significantly attenuate the delayed CVS. Possible mechanisms include a decrease in the endothelial cell apoptosis of the basilar artery and alleviation of endothelial inflammation. The JNK signalling pathway may play an important role in the neuroprotective effects of EP on delayed CVS. The results suggest that EP may be a possible therapy for delayed CVS, and the JNK signalling pathway should be targeted for therapeutic purposes in the future.

The pathophysiology of delayed cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is multifaceted and involves endothelial apoptosis and inflammation.     

Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study

Introduction

We sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH).

Methods

We used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE).

Results

Daily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels.

Conclusions

In the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage.     

Cleavage of plasma high molecular weight kininogen in surgical ICU patients

Objective

To characterize kininogens in plasma from surgical patients in the intensive care unit (ICU).

Design

Prospective study.

Setting

Surgical ICU.

Patients

35 patients aged 19–79 years, divided into two groups: sepsis (defined by standard criteria) and nonsepsis.

Measurements and results

Studies of proteolytic degradation of H-kininogen showed degradation in both patient groups compared to healthy controls. Functional quantification of prekallikrein showed a reduction of prekallikrein in plasma from both patients groups. Functional quantification of kininogens by a cysteine proteinase inhibitor assay showed no significant differences between the patients and the controls. Immunological levels of H-kininogen and total kininogen were not significantly different from normal plasma. No differences could be detected between the two patient groups in any of the parameters studied.

Conclusions

This study showed that contact activation took place in surgical ICU patients: partial kinin release and consumption of prekallikrein took place in vivo.     

Cerebrolysin for the Treatment of Aneurysmal Subarachnoid Hemorrhage in Adults: A Retrospective Chart Review

Introduction

Cerebrolysin is a neuroprotective drug used in the treatment of acute ischemic stroke. To our knowledge, this drug has never been evaluated in patients with aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of Cerebrolysin in patients with aneurysmal SAH.

Methods

Aneurysmal SAH patients who had their aneurysm obliterated at our institution from 2007 to 2016 were retrospectively studied. Patients received Cerebrolysin treatment or standard care only (control group). Subgroup analyses were performed according to Hunt and Hess grade (good grade?≤?2, N?=?216; poor grade?≥?3, N?=?246) and treatment procedure (clip or coil).

Results

In good-grade patients (N?=?216), clinical outcomes and mortality did not differ significantly between the control and Cerebrolysin groups. In poor-grade patients (N?=?246), the mortality rate was significantly lower in the Cerebrolysin group (8.7%) than in the control group (25.4%, p?=?0.006). In patients who received microsurgical clipping (N?=?328), the mortality rate was significantly lower in the Cerebrolysin group (7.3%) than in the control group (18.5%, p?=?0.016).

Conclusion

Cerebrolysin injection during the acute period of SAH appeared to reduce the mortality rate, especially in poor-grade patients. This study suggests the potential of Cerebrolysin for treating aneurysmal SAH. Further studies are needed to confirm our results.

     

Bath-Related Headache

Purpose of Review

The purpose of this review is to summarize the most up-to-date literature on bath-related headache, a rare disorder.

Recent Findings

Initially described in middle-aged Asian women, it is now reported in a wider demographic. More information is available about the pathophysiology of bath-related headache, including its classification as a subtype of reversible cerebral vasoconstriction syndrome (RCVS). Nimodipine can be effective in patients both with and without vasospasm.

Summary

Bath-related headache is a rare form of thunderclap headache. Although its mechanism is still unclear, it is associated with vasospasm and RCVS. Controlled trials investigating the use of nimodipine and other agents may be useful in furthering our understanding of and treatment of this phenomenon.

     

Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts

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.     

Pseudoaneurysm of the superficial femoral artery detected by emergency medicine bedside ultrasound

Background

Femoral artery pseudoaneurysm following by cardiac catheterization is a serious groin complication requiring careful assessment and prompt intervention.

Aims

Risk of femoral artery pseudoaneurysm is estimated at 0.6 to 17 following diagnostic and interventional procedures.

Methods

The clinical usage of bedside ultrasonography as part of the physical examination by attending emergency physicians has increased significantly over recent years.

Results

Bedside Emergency Department ultrasonography provides the clinician with critical information noninvasively, rapidly determining various anatomical structures.

Conclusions

We presented the case of a femoral artery pseudoaneurysm detected by the bedside emergency department ultrasonography secondary to angiographic catheterization.     

Intermittent pneumatic compression for prevention of pulmonary thromboembolism after gynecologic surgery

Background

Dengue virus infected patients have high plasminogen activator inhibitor type I (PAI-1) plasma concentrations. Whether the insertion/deletion (4G/5G) polymorphism in the promotor region of the PAI-1 gene is associated with increased PAI-1 plasma concentrations and with death from dengue is unknown. We, therefore, investigated the relationship between the 4G/5G polymorphism and PAI-1 plasma concentrations in dengue patients and risk of death from dengue.

Methods

A total of 194 patients admitted to the Dr. Kariadi Hospital in Semarang, Indonesia, with clinical suspected severe dengue virus infection were enrolled. Blood samples were obtained on day of admission, days 1, 2 and 7 after admission and at a 1-month follow-up visit. Plasma concentrations of PAI-1 were measured using a sandwich ELISA kit. The PAI-1 4G/5G polymorphism was typed by allele-specific PCR analysis.

Results

Concentrations of PAI-1 on admission and peak values of PAI-1 during admission were higher than the values measured in healthy controls. Survival was significantly worse in patients with PAI-1 concentrations in the highest tertile (at admission: OR 4.7 [95% CI 0.9–23.8], peak value during admission: OR 6.3 [95%CI 1.3–30.8]). No association was found between the PAI-1 4G/5G polymorphism, and PAI-1 plasma concentrations, dengue disease severity and mortality from dengue.

Conclusion

These data suggest that the 4G/5G polymorphism has no significant influence on PAI-1 concentrations in dengue virus infected patients and is not associated with the risk of death from dengue. Other factors contributing to the variability of PAI-1 plasma concentrations in patients with dengue need to be explored.     

Mortality and morbidity in children caused by falling televisions: a retrospective analysis of 71 cases

Background

Femoral artery pseudoaneurysm following cardiac catheterization is a serious groin complication requiring careful assessment and prompt intervention.

Aims

The risk of femoral artery pseudoaneurysm is estimated at 0.6 to 17% following diagnostic and interventional procedures.

Methods

The clinical use of bedside ultrasonography as part of the physical examination by attending emergency physicians has increased significantly over recent years.

Results

Bedside emergency department ultrasonography provides the clinician with critical information noninvasively, rapidly determining various anatomical structures.

Conclusions

We present the case of a patient with femoral artery pseudoaneurysm detected by bedside emergency department ultrasonography secondary to angiographic catheterization.     

Procarboxypeptidase U (proCPU,TAFI, proCPB2) in cerebrospinal fluid during ischemic stroke is associated with stroke progression,outcome and blood–brain barrier dysfunction

Essentials

• Little is known of procarboxypeptidase U (proCPU) in cerebrospinal fluid (CSF) of stroke patients.
• ProCPU levels were studied in CSF of controls and non‐thrombolyzed acute ischemic stroke patients.
• ProCPU is elevated in CSF of stroke patients compared with controls.
• ProCPU in CSF correlates with stroke progression, outcome, and blood‐brain barrier dysfunction.

Summary

Background

Procarboxypeptidase U (proCPU, TAFI, proCPB2), the zymogen of CPU, which is a potent antifibrinolytic enzyme and a modulator of inflammation, has previously been investigated in plasma of stroke patients, but so far, no information on the proCPU levels in cerebrospinal fluid (CSF) during acute ischemic stroke (AIS) is available.

Objectives

This case–control observational study investigates proCPU in CSF of AIS patients compared with controls with an intact blood–brain barrier (BBB) and evaluates the relationship of CSF/plasma proCPU ratios with stroke parameters.

Methods

A sensitive HPLC‐based enzymatic assay was used to determine proCPU levels in CSF of non‐thrombolyzed patients in the hyperacute phase (< 24 h after onset) of AIS (n = 72). Individuals (n = 32) without stroke, an intact BBB and no apparent abnormalities in biochemical and microbiological tests, served as controls. Relations between the CSF/plasma proCPU ratio and (i) stroke severity, (ii) stroke progression/recurrence, (iii) stroke outcome and (iv) BBB dysfunction (CSF/serum albumin ratio) were assessed.

Results

Mean (SEM) proCPU levels were elevated in the CSF of stroke patients compared with controls (4.36 (0.23) U L^?1 vs. 3.50 (0.23) U L^?1). Higher median [IQR] CSF/plasma proCPU ratios were found in patients with stroke progression ((6.0 [4.2–6.9]) × 10^?3) and poor outcome ((6.4 [3.9–7.0]) × 10^?3) after 3 months (modified Rankin Scale; mRS > 3) compared with patients without progression ((3.9 [2.7–5.4]) × 10^?3) or better outcome ((4.0 [2.8–5.0]) × 10^?3). In stroke patients with a disrupted BBB, proCPU ratios were higher compared with stroke patients with an intact BBB ((6.4 [5.8–9.0]) × 10^?3 vs. (3.7 [2.8–5.0]) × 10^?3).

Conclusions

ProCPU is increased in CSF during hyperacute ischemic stroke and is associated with stroke progression and outcome after 3 months, most likely due to BBB dysfunction in the hyperacute phase of ischemic stroke.

     

Accuracy of plasma neutrophil gelatinase-associated lipocalin in the early diagnosis of contrast-induced acute kidney injury in critical illness

Purpose

Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury (AKI). We evaluated the diagnostic and prognostic accuracies of plasma NGAL (pNGAL) for contrast-induced AKI (CI-AKI) in critically ill patients.

Methods

In a prospective observational study in two adult intensive care units in a university hospital, 100 consecutive critically ill patients with stable serum creatinine concentrations up to 48 h before contrast medium (CM) injection were enrolled. Serial blood sampling for pNGAL analysis was performed at enrolment, 2, 6, and 24 h after CM injection. The primary outcome was CI-AKI, defined by AKIN criteria, within the first 72 h following CM injection. Secondary outcomes were the need for renal replacement therapy (RRT) and mortality.

Results

Of the 98 patients analyzed, 30 developed CI-AKI. The pNGAL levels did not differ in patients with or without CI-AKI, and were higher in septic patients compared to nonseptic patients, and in patients with AKI preceding CM injection. The discriminative value of pNGAL to predict CI-AKI and mortality was poor; although, it did predict the need for RRT requirement after CM injection (area under receiver-operating characteristic curve, 0.85, 0.80, 0.83 and 0.86 at H0, H2, H6 and H24, respectively).

Conclusion

CI-AKI was common in critically ill patients. pNGAL levels were higher in patients with sepsis or previous AKI, but did not help to diagnose CI-AKI any earlier than serum creatinine after CM injection. However, pNGAL could be of interest to detect patients at risk of subsequent RRT requirement.