Reduced circulating endothelial progenitor cells in reversible cerebral vasoconstriction syndrome

Background

The pathophysiology of reversible cerebral vasoconstriction syndrome (RCVS) remains elusive. Endothelial dysfunction might play a role, but direct evidence is lacking. This study aimed to explore whether patients with RCVS have a reduced level of circulating circulating endothelial progenitor cells (EPCs) to repair the dysfunctional endothelial vasomotor control.

Methods

We prospectively recruited 24 patients with RCVS within one month of disease onset and 24 healthy age- and sex-matched controls. Flow cytometry was used to quantify the numbers of circulating EPCs, defined as KDR⁺CD133⁺, CD34⁺CD133⁺, and CD34⁺KDR⁺ double-positive mononuclear cells. The Lindegaard index, an index of vasoconstriction, was calculated by measuring the mean flow velocity of middle cerebral arteries and distal extracranial internal carotid arteries via color-coded sonography on the same day as blood drawing. A Lindegaard index of 2 was chosen as the cutoff value for significant vasoconstriction of middle cerebral arteries based on our previous study.

Results

Patients with RCVS had a reduced number of CD34⁺KDR⁺ cells (0.009 ± 0.006% vs. 0.014 ± 0.010%, p = 0.031) but not KDR⁺CD133⁺ cells or CD34⁺CD133⁺ EPCs, in comparison with controls. The number of CD34⁺KDR⁺ cells was inversely correlated with the Lindegaard index (rs = -0.418, p = 0.047). Of note, compared to controls, patients with a Lindegaard index > 2 (n = 13) had a reduced number of CD34⁺KDR⁺ cells (0.007 ± 0.005% vs. 0.014 ± 0.010%, p = 0.010), but those with a Lindegaard index ≤ 2 did not.

Conclusions

Patients with RCVS had reduced circulating CD34⁺KDR⁺ EPCs, which were correlated with the severity of vasoconstriction. Endothelial dysfunction might contribute to the pathogenesis of RCVS.     

Use of a fixed combination of acetylsalicylic acid,acetaminophen and caffeine compared with acetaminophen alone in episodic tension-type headache: meta-analysis of four randomized,double-blind,placebo-controlled,crossover studies

Background

Most patients with episodic tension-type headache treat headache episodes with over-the-counter medication. Combination analgesics containing caffeine may be more effective and as well tolerated as monotherapy. The aim of this study was to evaluate the efficacy of the combination of acetylsalicylic acid, acetaminophen (paracetamol) and caffeine in episodic tension-type headache using recently recommended endpoints.

Methods

Four randomized, controlled trials of identical design in 1,900 patients with episodic tension-type headache comparing acetylsalicylic acid, acetaminophen and caffeine vs. acetaminophen or placebo were pooled. Analysis populations were ‘all headache episodes’ and those with ‘severe pain at baseline’. Post-hoc defined primary endpoint: headache episodes pain-free at 2 h. Secondary endpoints: headache episodes pain-free at 1 h, headache response at 2 h (mild or no pain), degree of interference with daily activities.

Results

6,861 headache episodes were treated, including 2,215 severe headache episodes. The proportion of headache episodes pain-free at 2 h was significantly higher with the triple combination (28.5%) vs. acetaminophen (21.0%) and placebo (18.0%) (p < 0.0001), and similarly for those severe at baseline (20.2% vs. 12.1% and 10.8%; p ≤ 0.0003). A similar pattern of superiority was observed for secondary endpoints. The triple combination was generally well tolerated.

Conclusions

The combination of acetylsalicylic acid, acetaminophen and caffeine is effective and well tolerated in episodic tension-type headache, and significantly superior to acetaminophen with regard to being pain-free at 2 h, headache response at 2 h and ability to return to daily activities, even in those with pain rated severe at baseline.     

Post-reversible cerebral vasoconstriction syndrome headache

BackgroundChronic headache may persist after the remission of reversible cerebral vasoconstriction syndrome (RCVS) in some patients. We aimed to investigate the prevalence, characteristics, risk factors, and the impact of post-RCVS headache.MethodsWe prospectively recruited patients with RCVS and collected their baseline demographics, including psychological distress measured by Hospital Anxiety and Depression scale. We evaluated whether the patients developed post-RCVS headache 3 months after RCVS onset. The manifestations of post-RCVS headache and headache-related disability measured by Migraine Disability Assessment (MIDAS) scores were recorded.ResultsFrom 2017 to 2019, 134 patients with RCVS were recruited, of whom, 123 finished follow-up interviews (response rate 91.8%). Sixty (48.8%) patients had post-RCVS headache. Migrainous features were common in post-RCVS headache. Post-RCVS headache caused moderate-to-severe headache-related disability (MIDAS score > 10) in seven (11.7%) patients. Higher anxiety level (odds ratio 1.21, p = 0.009) and a history of migraine (odds ratio 2.59, p = 0.049) are associated with post-RCVS headache. Survival analysis estimated that 50% post-RCVS headache would recover in 389 days (95% confidence interval: 198.5–579) after disease onset.ConclusionsPost-RCVS headache is common, affecting half of patients and being disabling in one-tenth. Higher anxiety level and migraine history are risk factors. Half of the patients with post-RCVS headache would recover in about a year.     

Cognitive processing of cluster headache patients: evidence from event-related potentials

Background

The peripheral and central origins of pain in cluster headache (CH) have been a matter of much debate. The development and application of functional imaging techniques have provided more evidence supporting the hypothesis that CH is not a disorder exclusively peripheral in origin, and in fact central regions might be more important. Event-related potentials confer advantages in the functional evaluation of the cortex, but few studies thus far have employed this method in cluster headache.

Methods

Seventeen cluster patients (15 males; mean age = 35.4 years) and 15 age-matched healthy participants (13 males; mean age = 34.6 years) were recruited. A visual oddball paradigm was employed to analyze target processing using event-related potentials. We investigated the P3/P3d components in the experiment.

Results

P3/P3d amplitudes were decreased in CH patients (P3, 3.82 μV; P3d, 5.8 μV) compared with controls (P3, 7.28 μV; P3d, 8.95 μV), F(1,30) = 4.919, p < 0.05, η2 = 0.141 for P3 and F(1,30) = 8.514, p < 0.05, η2 = 0.221 for P3d, respectively). Moreover, the amplitudes of P3/P3d were no significantl difference in the side of pain as compared to contralateral one (p > 0.05).

Conclusions

These results provide evidence of dysfunction in the cognitive processing of CH patients, which may also contribute to the pathophysiology of CH.     

Anxiety,depression and behavioral problems among adolescents with recurrent headache: the Young-HUNT study

Background

It is well documented that both anxiety and depression are associated with headache, but there is limited knowledge regarding the relation between recurrent primary headaches and symptoms of anxiety and depression as well as behavioral problems among adolescents. Assessment of co-morbid disorders is important in order to improve the management of adolescents with recurrent headaches. Thus the main purpose of the present study was to assess the relationship of recurrent headache with anxiety and depressive symptoms and behavioral problems in a large population based cross-sectional survey among adolescents in Norway.

Methods

A cross-sectional, population-based study was conducted in Norway from 1995 to 1997 (Young-HUNT1). In Young-HUNT1, 4872 adolescents aged 12 to 17 years were interviewed about their headache complaints and completed a comprehensive questionnaire that included assessment of symptoms of anxiety and depression and behavioral problems, i.e. conduct and attention difficulties.

Results

In adjusted multivariate analyses among adolescents aged 12–14 years, recurrent headache was associated with symptoms of anxiety and depression (OR: 2.05, 95% CI: 1.61-2.61, p < 0.001), but not with behavioral problems. A significant association with anxiety and depressive symptoms was evident for all headache categories; i.e. migraine, tension-type headache and non-classifiable headache. Among adolescents aged 15–17 years there was a significant association between recurrent headache and symptoms of anxiety and depression (OR: 1.64, 95% CI: 1.39-1.93, p < 0,001) and attention difficulties (OR: 1.25, 95% CI: 1.09-1.44, p =0.001). For migraine there was a significant association with both anxiety and depressive symptoms and attention difficulties, while tension-type headache was significantly associated only with symptoms of anxiety and depression. Non-classifiable headache was associated with attention difficulties and conduct difficulties, but not with anxiety and depressive symptoms. Headache frequency was significantly associated with increasing symptoms scores for anxiety and depressive symptoms as well as attention difficulties, evident for both age groups.

Conclusions

The results from the present study indicate that both anxiety and depressive symptoms and behavioral problems are associated with recurrent headache, and should accordingly be considered a part of the clinical assessment of children and adolescents with headache. Identification of these associated factors and addressing them in interventions may improve headache management.     

Assessment of cardiovascular physiology using dobutamine stress cardiovascular magnetic resonance reveals impaired contractile reserve in patients with cirrhotic cardiomyopathy

Background

Liver cirrhosis has been shown to affect cardiac performance. However cardiac dysfunction may only be revealed under stress conditions. The value of non-invasive stress tests in diagnosing cirrhotic cardiomyopathy is unclear. We sought to investigate the response to pharmacological stimulation with dobutamine in patients with cirrhosis using cardiovascular magnetic resonance.

Methods

Thirty-six patients and eight controls were scanned using a 1.5 T scanner (Siemens Symphony TIM; Siemens, Erlangen, Germany). Conventional volumetric and feature tracking analysis using dedicated software (CMR42; Circle Cardiovascular Imaging Inc, Calgary, Canada and Diogenes MRI; Tomtec; Germany, respectively) were performed at rest and during low to intermediate dose dobutamine stress.

Results

Whilst volumetry based parameters were similar between patients and controls at rest, patients had a smaller increase in cardiac output during stress (p = 0.015). Ejection fraction increase was impaired in patients during 10 μg/kg/min dobutamine as compared to controls (6.9 % vs. 16.5 %, p = 0.007), but not with 20 μg/kg/min (12.1 % vs. 17.6 %, p = 0.12). This was paralleled by an impaired improvement in circumferential strain with low dose (median increase of 14.4 % vs. 30.9 %, p = 0.03), but not with intermediate dose dobutamine (median increase of 29.4 % vs. 33.9 %, p = 0.54). There was an impaired longitudinal strain increase in patients as compared to controls during low (median increase of 6.6 % vs 28.6 %, p < 0.001) and intermediate dose dobutamine (median increase of 2.6%vs, 12.6 % p = 0.016). Radial strain response to dobutamine was similar in patients and controls (p > 0.05).

Conclusion

Cirrhotic cardiomyopathy is characterized by an impaired cardiac pharmacological response that can be detected with magnetic resonance myocardial stress testing. Deformation analysis parameters may be more sensitive in identifying abnormalities in inotropic response to stress than conventional methods.     

The global burden of headache in children and adolescents – developing a questionnaire and methodology for a global study

Background

Burden of headache has been assessed in adults in countries worldwide, and is high, but data for children and adolescents are sparse. The objectives of this study were o develop a questionnaire and methodology for the global estimation of burden of headache in children and adolescents, to test these in use and to present preliminary data.

Methods

We designed structured questionnaires for mediated-group self-administration in schools by children aged 6-11 years and adolescents aged 12-17 years. In two pilot studies, we offered the questionnaires to pupils in Vienna and Istanbul. We performed face-to-face interviews in a randomly selected subsample of 199 pupils to validate the headache diagnostic questions.

Results

Data were collected from 1,202 pupils (mean 13.9 ± 2.4 years; 621 female, 581 male). The participation rate was 81.1% in Istanbul, 67.2% in Vienna. The questionnaire proved acceptable: ≤5% of participants disagreed partially or totally with its length, comprehensibility or simplicity. The sensitivity, specificity, positive and negative predictive values ranged between 0.71 and 0.76 for migraine and between 0.61 and 0.85 for tension-type headache (TTH). Cronbach’s alpha was 0.83. The 1-year prevalence of headache was 89.3%, of migraine 39.3% and of TTH 37.9%. The prevalence of headache on ≥15 days/month was 4.5%. One fifth (20.7%) of pupils with headache lost ≥1 day of school during the preceding 4 weeks and nearly half (48.8%) reported ≥1 day when they could not do activities they had wanted to. The vast majority of pupils with headache experienced difficulties in coping with headache and in concentrating during headache. Quality of life was poorer in pupils with headache than in those without.

Conclusion

These pilot studies demonstrate the usefulness of the questionnaires and feasibility of the methodology for assessing the global burden of headache in children and adolescents, and predict substantial impact of headache in these age groups.     

Clinical guidelines in pediatric headache: evaluation of quality using the AGREE II instrument

Background

The Appraisal of Guidelines for Research and Evaluation (AGREE II) tool is a validated questionnaire used to assess the methodological quality of clinical guidelines (CGs). We used the AGREE II tool to assess the development process, the methodological quality, and the quality of reporting of available pediatric CGs for the management of headache in children. We also studied the variability in responses related to the characteristics of eleven Italian neuropediatric centers, showing similarities and differences in the main recommendations reported in CGs.

Methods

A systematic literature search was conducted from January 2002 to June 2013 on Mediline, the Cochrane database, the National Guideline Clearinghouse website and the NHS evidence search tool, using the following terms: headache, cephalalgia, guidelines and children (MESH or text words). Six CGs providing information on the diagnosis and management of headache and specific recommendations for children were selected. Eleven neuropediatric centers assessed the overall quality and the appropriateness of all available CGs using of the AGREE II instrument.

Results

Six CGs meeting the inclusion and exclusion criteria were identified and assessed by 11 reviewers. Our study showed that the NICE CGs was “strongly recommended” while the French and Danish CGs were mainly “not recommended”. The comparison between the overall quality score of the French CGs and the NICE CGs was statistically significant (6.54 ± 0.69 vs 4.18 ± 1.08; p =0.001). The correlation analysis between quality domain score and guideline publication date showed a statistically significant association only for the “editorial independence” domain (r = 0.842 p = 0.035). The intra-class coefficients showed that the 11 reviewers had the highest agreement for the Lewis CGs (r = 0.857), and the lowest one for the NICE CGs (r = 0.656). Statistical analyses showed that professionals from outpatient services dedicated pediatric headache assigned a higher overall quality score to the NICE CGs as compared to professionals from non-outpatient services (6.86 ± 0.38 vs 6.0 ± 0.82; p = 0.038).

Conclusions

CGs resulted definitely of low-moderate quality and non “homogeneous”. Further major efforts are needed to update the existing CGs according to the principles of evidence based medicine.     

Incremental value of cardiovascular magnetic resonance over echocardiography in the detection of acute and chronic myocardial infarction

Background

Although echocardiography is used as a first line imaging modality, its accuracy to detect acute and chronic myocardial infarction (MI) in relation to infarct characteristics as assessed with late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) is not well described.

Methods

One-hundred-forty-one echocardiograms performed in 88 first acute ST-elevation MI (STEMI) patients, 2 (IQR1-4) days (n = 61) and 102 (IQR92-112) days post-MI (n = 80), were pooled with echocardiograms of 36 healthy controls. 61 acute and 80 chronic echocardiograms were available for analysis (53 patients had both acute and chronic echocardiograms). Two experienced echocardiographers, blinded to clinical and CMR data, randomly evaluated all 177 echocardiograms for segmental wall motion abnormalities (SWMA). This was compared with LGE-CMR determined infarct characteristics, performed 104 ± 11 days post-MI. Enhancement on LGE-CMR matched the infarct-related artery territory in all patients (LAD 31%, LCx 12% and RCA 57%).

Results

The sensitivity of echocardiography to detect acute MI was 78.7% and 61.3% for chronic MI; specificity was 80.6%. Undetected MI were smaller, less transmural, and less extensive (6% [IQR3-12] vs. 15% [IQR9-24], 50 ± 14% vs. 61 ± 15%, 7 ± 3 vs. 9 ± 3 segments, p < 0.001 for all) and associated with higher left ventricular ejection fraction (LVEF) and non-anterior location as compared to detected MI (58 ± 5% vs. 46 ± 7%, p < 0.001 and 82% vs. 63%, p = 0.03). After multivariate analysis, LVEF and infarct size were the strongest independent predictors of detecting chronic MI (OR 0.78 [95%CI 0.68-0.88], p < 0.001 and OR 1.22 [95%CI0.99-1.51], p = 0.06, respectively). Increasing infarct transmurality was associated with increasing SWMA (p < 0.001).

Conclusions

In patients presenting with STEMI, and thus a high likelihood of SWMA, the sensitivity of echocardiography to detect SWMA was higher in the acute than the chronic phase. Undetected MI were smaller, less extensive and less transmural, and associated with non-anterior localization and higher LVEF. Further work is needed to assess the diagnostic accuracy in patients with non-STEMI.     

Interest of low-dose hydrocortisone therapy during brain-dead organ donor resuscitation: the CORTICOME study

Introduction

Circulatory failure during brain death organ donor resuscitation is a problem that compromises recovery of organs. Combined administration of steroid, thyroxine and vasopressin has been proposed to optimize the management of brain deceased donors before recovery of organs. However the single administration of hydrocortisone has not been rigorously evaluated in any trial.

Methods

In this prospective multicenter cluster study, 259 subjects were included. Administration of low-dose steroids composed the steroid group (n = 102).

Results

Although there were more patients in the steroid group who received norepinephrine before brain death (80% vs. 66%: P = 0.03), mean dose of vasopressor administered after brain death was significantly lower than in the control group (1.18 ± 0.92 mg/H vs. 1.49 ± 1.29 mg/H: P = 0.03), duration of vasopressor support use was shorter (874 min vs. 1160 min: P < 0.0001) and norepinephrine weaning before aortic clamping was more frequent (33.8% vs. 9.5%: P < 0.0001). Using a survival approach, probability of norepinephrine weaning was significantly different between the two groups (P < 0.0001) with a probability of weaning 4.67 times higher in the steroid group than in the control group (95% CI: 2.30 – 9.49).

Conclusions

Despite no observed benefits of the steroid administration on primary function recovery of transplanted grafts, administration of glucocorticoids should be a part of the resuscitation management of deceased donors with hemodynamic instability.     

Decision support tool for differential diagnosis of Acute Respiratory Distress Syndrome (ARDS) vs Cardiogenic Pulmonary Edema (CPE): a prospective validation and meta-analysis

Introduction

We recently presented a prediction score providing decision support with the often-challenging early differential diagnosis of acute lung injury (ALI) vs cardiogenic pulmonary edema (CPE). To facilitate clinical adoption, our objective was to prospectively validate its performance in an independent cohort.

Methods

Over 9 months, adult patients consecutively admitted to any intensive care unit of a tertiary-care center developing acute pulmonary edema were identified in real-time using validated electronic surveillance. For eligible patients, predictors were abstracted from medical records within 48 hours of the alert. Post-hoc expert review blinded to the prediction score established gold standard diagnosis.

Results

Of 1,516 patients identified by electronic surveillance, data were abstracted for 249 patients (93% within 48 hours of disease onset), of which expert review (kappa 0.93) classified 72 as ALI, 73 as CPE and excluded 104 as “other”. With an area under the curve (AUC) of 0.81 (95% confidence interval =0.73 to 0.88) the prediction score showed similar discrimination as in prior cohorts (development AUC = 0.81, P = 0.91; retrospective validation AUC = 0.80, P = 0.92). Hosmer-Lemeshow test was significant (P = 0.01), but across eight previously defined score ranges probabilities of ALI vs CPE were the same as in the development cohort (P = 0.60). Results were the same when comparing acute respiratory distress syndrome (ARDS, Berlin definition) vs CPE.

Conclusion

The clinical prediction score reliably differentiates ARDS/ALI vs CPE. Pooled results provide precise estimates of the score’s performance which can be used to screen patient populations or to assess the probability of ALI/ARDS vs CPE in specific patients. The score may thus facilitate early inclusion into research studies and expedite prompt treatment.

Electronic supplementary material

The online version of this article (doi:10.1186/s13054-014-0659-x) contains supplementary material, which is available to authorized users.     

Continuous regional arterial infusion for acute pancreatitis: a propensity score analysis using a nationwide administrative database

Introduction

Although continuous regional arterial infusion (CRAI) of a protease inhibitor and an antibiotic may be effective in patients with severe acute pancreatitis, CRAI has not yet been validated in large patient populations. We therefore evaluated the effectiveness of CRAI based on data from a national administrative database covering 1,032 Japanese hospitals.

Methods

In-hospital mortality, length of stay and costs were compared in the CRAI and non-CRAI groups, using propensity score analysis to adjust for treatment selection bias.

Results

A total of 17,415 eligible patients with acute pancreatitis were identified between 1 July and 30 September 2011, including 287 (1.6%) patients who underwent CRAI. One-to-one propensity-score matching generated 207 pairs with well-balanced baseline characteristics. In-hospital mortality rates were similar in the CRAI and non-CRAI groups (7.7% vs. 8.7%; odds ratio, 0.88; 95% confidence interval, 0.44–1.78, P = 0.720). CRAI was associated with significantly longer median hospital stay (29 vs. 18 days, P < 0.001), significantly higher median total cost (21,800 vs. 12,600 United States dollars, P < 0.001), and a higher rate of interventions for infectious complications, such as endoscopic/surgical necrosectomy or percutaneous drainage (2.9% vs. 0.5%, P = 0.061).

Conclusions

CRAI was not effective in reducing in-hospital mortality rate in patients with acute pancreatitis, but was associated with longer hospital stay and higher costs. Randomized controlled trials in large numbers of patients are required to further evaluate CRAI for this indication.     

T1 mapping and T2 mapping at 3T for quantifying the area-at-risk in reperfused STEMI patients

Background

Whether T1-mapping cardiovascular magnetic resonance (CMR) can accurately quantify the area-at-risk (AAR) as delineated by T2 mapping and assess myocardial salvage at 3T in reperfused ST-segment elevation myocardial infarction (STEMI) patients is not known and was investigated in this study.

Methods

18 STEMI patients underwent CMR at 3T (Siemens Bio-graph mMR) at a median of 5 (4–6) days post primary percutaneous coronary intervention using native T1 (MOLLI) and T2 mapping (WIP #699; Siemens Healthcare, UK). Matching short-axis T1 and T2 maps covering the entire left ventricle (LV) were assessed by two independent observers using manual, Otsu and 2 standard deviation thresholds. Inter- and intra-observer variability, correlation and agreement between the T1 and T2 mapping techniques on a per-slice and per patient basis were assessed.

Results

A total of 125 matching T1 and T2 mapping short-axis slices were available for analysis from 18 patients. The acquisition times were identical for the T1 maps and T2 maps. 18 slices were excluded due to suboptimal image quality. Both mapping sequences were equally prone to susceptibility artifacts in the lateral wall and were equally likely to be affected by microvascular obstruction requiring manual correction. The Otsu thresholding technique performed best in terms of inter- and intra-observer variability for both T1 and T2 mapping CMR. The mean myocardial infarct size was 18.8 ± 9.4 % of the LV. There was no difference in either the mean AAR (32.3 ± 11.5 % of the LV versus 31.6 ± 11.2 % of the LV, P = 0.25) or myocardial salvage index (0.40 ± 0.26 versus 0.39 ± 0.27, P = 0.20) between the T1 and T2 mapping techniques. On a per-slice analysis, there was an excellent correlation between T1 mapping and T2 mapping in the quantification of the AAR with an R² of 0.95 (P < 0.001), with no bias (mean ± 2SD: bias 0.0 ± 9.6 %). On a per-patient analysis, the correlation and agreement remained excellent with no bias (R² 0.95, P < 0.0001, bias 0.7 ± 5.1 %).

Conclusions

T1 mapping CMR at 3T performed as well as T2 mapping in quantifying the AAR and assessing myocardial salvage in reperfused STEMI patients, thereby providing an alternative CMR measure of the the AAR.     

Headache prevalence and characteristics among adolescents in the general population: a comparison between retrospect questionnaire and prospective paper diary data

Background

In the present school-based study, a convenience sample of 237 adolescents in grade 6-9 and second year in high school (age 12-18 years) was recruited from a city and a smaller town. The aim of the study was to compare information on the prevalence and various characteristics of headaches not related to disease in a retrospect questionnaire and prospective daily recordings of headaches in a standard paper diary during a 3-week period.

Methods

Besides headache severity, number of headache days, intensity levels and duration of headache episodes were estimated with both assessment methods. Most of the school children suffered from tension-type headaches and a smaller portion of migraine attacks.

Results

The overall results showed that school children significantly (p < 0.001) overestimated headache intensity in questionnaires as compared to diary recordings, whereas they underestimated frequency (p < 0.001) and duration (p < 0.001) of headaches. While the correlations on headache severity, frequency and duration between retrospect information in questionnaires and prospective diary recordings were low, the agreement varied with levels of headache characteristics.

Conclusions

Our findings concur well with results from a few similar community studies on headache complaints in school-aged children. We recommend that prospective recordings in diaries should be systematically used in clinical practice but also in epidemiological surveys to increase the validity and reliability in estimates of point prevalence of headache complaints in children and adolescents.     

Better lactate clearance associated with good neurologic outcome in survivors who treated with therapeutic hypothermia after out-of-hospital cardiac arrest

Introduction

Several methods have been proposed to evaluate neurological outcome in out-of-hospital cardiac arrest (OHCA) patients. Blood lactate has been recognized as a reliable prognostic marker for trauma, sepsis, or cardiac arrest. The objective of this study was to examine the association between initial lactate level or lactate clearance and neurologic outcome in OHCA survivors who were treated with therapeutic hypothermia.

Methods

This retrospective cohort study included patients who underwent protocol-based 24-hour therapeutic hypothermia after OHCA between January 2010 and March 2012. Serum lactate levels were measured at the start of therapy (0 hours), and after 6 hours, 12 hours, 24 hours, 48 hours and 72 hours. The 6 hour and 12 hour lactate clearance were calculated afterwards. Patients’ neurologic outcome was assessed at one month after cardiac arrest; good neurological outcome was defined as Cerebral Performance Category one or two. The primary outcome was an association between initial lactate level and good neurologic outcome. The secondary outcome was an association between lactate clearance and good neurologic outcome in patients with initial lactate level >2.5 mmol/l.

Results

Out of the 76 patients enrolled, 34 (44.7%) had a good neurologic outcome. The initial lactate level showed no significant difference between good and poor neurologic outcome groups (6.07 ±4 .09 mmol/L vs 7.13 ± 3.99 mmol/L, P = 0.42), However, lactate levels at 6 hours, 12 hours, 24 hours, and 48 hours in the good neurologic outcome group were lower than in the poor neurologic outcome group (3.81 ± 2.81 vs 6.00 ± 3.22 P <0.01, 2.95 ± 2.07 vs 5.00 ± 3.49 P <0.01, 2.17 ± 1.24 vs 3.86 ± 3.92 P <0.01, 1.57 ± 1.02 vs 2.21 ± 1.35 P = 0.03, respectively). The secondary analysis showed that the 6-hour and 12-hour lactate clearance was higher for good neurologic outcome patients (35.3 ± 34.6% vs 6.89 ± 47.4% P = 0.01, 54.5 ± 23.7% vs 25.6 ± 43.7% P <0.01, respectively). After adjusting for potential confounding variables, the 12-hour lactate clearance still showed a statistically significant difference (P = 0.02).

Conclusion

The lactate clearance rate, and not the initial lactate level, was associated with neurological outcome in OHCA patients after therapeutic hypothermia.     

Fluid balance and cardiac function in septic shock as predictors of hospital mortality

Introduction

Septic shock is a major cause of morbidity and mortality throughout the world. Unfortunately, the optimal fluid management of septic shock is unknown and currently is empirical.

Methods

A retrospective analysis was performed at Barnes-Jewish Hospital (St. Louis, Missouri). Consecutive patients (n = 325) hospitalized with septic shock who had echocardiographic examinations performed within 24 hours of shock onset were enrolled.

Results

A total of 163 (50.2%) patients with septic shock died during hospitalization. Non-survivors had a significantly larger positive net fluid balance within the 24 hour window of septic shock onset (median (IQR): 4,374 ml (1,637 ml, 7,260 ml) vs. 2,959 ml (1,639.5 ml, 4,769.5 ml), P = 0.004). The greatest quartile of positive net fluid balance at 24 hours and eight days post-shock onset respectively were found to predict hospital mortality, and the greatest quartile of positive net fluid balance at eight days post-shock onset was an independent predictor of hospital mortality (adjusted odds ratio (AOR), 1.66; 95% CI, 1.39 to 1.98; P = 0.004). Survivors were significantly more likely to have mild left ventricular dysfunction as evaluated by bedside echocardiography and non-survivors had slightly elevated left ventricular ejection fraction, which was also found to be an independent predictor of outcome.

Conclusions

Our data confirms the importance of fluid balance and cardiac function as outcome predictors in patients with septic shock. A clinical trial to determine the optimal administration of intravenous fluids to patients with septic shock is needed.     

Susceptibility-weighted cardiovascular magnetic resonance in comparison to T2 and T2 star imaging for detection of intramyocardial hemorrhage following acute myocardial infarction at 3 Tesla

Background

Intramyocardial hemorrhage (IMH) identified by cardiovascular magnetic resonance (CMR) is an established prognostic marker following acute myocardial infarction (AMI). Detection of IMH by T2-weighted or T2 star CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3T. We compared the image quality and diagnostic ability of susceptibility-weighted magnetic resonance imaging (SW MRI) with T2-weighted and T2 star CMR to detect IMH at 3T.

Methods

Forty-nine patients (42 males; mean age 58 years, range 35–76) underwent 3T cardiovascular magnetic resonance (CMR) 2 days following re-perfused AMI. T2-weighted, T2 star and SW MRI images were obtained. Signal and contrast measurements were compared between the three methods and diagnostic accuracy of SW MRI was assessed against T2w images by 2 independent, blinded observers. Image quality was rated on a 4-point scale from 1 (unusable) to 4 (excellent).

Results

Of 49 patients, IMH was detected in 20 (41%) by SW MRI, 21 (43%) by T2-weighted and 17 (34%) by T2 star imaging (p = ns). Compared to T2-weighted imaging, SW MRI had sensitivity of 93% and specificity of 86%. SW MRI had similar inter-observer reliability to T2-weighted imaging (κ = 0.90 and κ = 0.88 respectively); both had higher reliability than T2 star (κ = 0.53). Breath hold times were shorter for SW MRI (4 seconds vs. 16 seconds) with improved image quality rating (3.8 ± 0.4, 3.3 ± 1.0, 2.8 ± 1.1 respectively; p < 0.01).

Conclusions

SW MRI is an accurate and reproducible way to detect IMH at 3T. The technique offers considerably shorter breath hold times than T2-weighted and T2 star imaging, and higher image quality scores.     

Comparison of cardiovascular magnetic resonance characteristics and clinical consequences in children and adolescents with isolated left ventricular non-compaction with and without late gadolinium enhancement

Background

Although cardiovascular magnetic resonance (CMR) is showing increasingly diagnostic potential in left ventricular non-compaction (LVNC), relatively little research relevant to CMR is conducted in children with LVNC. This study was performed to characterize and compare CMR features and clinical outcomes in children with LVNC with and without late gadolinium enhancement (LGE).

Methods

A cohort of 40 consecutive children (age, 13.7 ± 3.3 years; 29 boys and 11 girls) with isolated LVNC underwent a baseline CMR scan with subsequent clinical follow-up. Short-axis cine images were used to calculate left ventricular (LV) ejection fraction (EF), end-diastolic volume (EDV), end-systolic volume (ESV), myocardial mass, ratio of non-compacted-to-compacted myocardial thickness (NC/C ratio), and number of non-compacted segments. The LGE images were analyzed to assess visually presence and patterns of LGE. The primary end point was a composite of cardiac death and heart transplantation.

Results

The LGE was present in 10 (25 %) children, and 46 (27 %) segments were involved, including 23 non-compacted segments and 23 normal segments. Compared with LGE- cohort, LGE+ cohort had significantly lower LVEF (23.8 ± 10.7 % vs. 42.9 ± 16.7 %, p < 0.001) and greater LVEDV (169.2 ± 65.1 vs. 118.2 ± 48.9 mL/m², p = 0.010), LVESV (131.3 ± 55.5 vs. 73.3 ± 46.7 mL/m², p = 0.002), and sphericity indices (0.75 ± 0.19 vs. 0.60 ± 0.20, p = 0.045). There were no differences in terms of number and distribution of non-compacted segments, NC/C ratio, and myocardial mass index between LGE+ and LGE- cohort. In the LGE+ cohort, adverse events occurred in 6 patients compared to 2 events in the LGE- cohort. Kaplan-Meier analysis showed a significant difference in outcome between LGE+ and LGE- cohort for cardiac death and heart transplantation (p = 0.011).

Conclusions

The LGE was present in up to one-fourth of children with LVNC, and the LGE+ children exhibited a more maladaptive LV remodeling and a higher incidence of cardiovascular death and heart transplantation.     

Individual component analysis of the multi-parametric cardiovascular magnetic resonance protocol in the CE-MARC trial

Background

The CE-MARC study assessed the diagnostic performance investigated the use of cardiovascular magnetic resonance (CMR) in patients with suspected coronary artery disease (CAD). The study used a multi-parametric CMR protocol assessing 4 components: i) left ventricular function; ii) myocardial perfusion; iii) viability (late gadolinium enhancement (LGE)) and iv) coronary magnetic resonance angiography (MRA). In this pre-specified CE-MARC sub-study we assessed the diagnostic accuracy of the individual CMR components and their combinations.

Methods

All patients from the CE-MARC population (n = 752) were included using data from the original blinded-read. The four individual core components of the CMR protocol was determined separately and then in paired and triplet combinations. Results were then compared to the full multi-parametric protocol.

Results

CMR and X-ray angiography results were available in 676 patients. The maximum sensitivity for the detection of significant CAD by CMR was achieved when all four components were used (86.5 %). Specificity of perfusion (91.8 %), function (93.7 %) and LGE (95.8 %) on its own was significantly better than specificity of the multi-parametric protocol (83.4 %) (all P < 0.0001) but with the penalty of decreased sensitivity (86.5 % vs. 76.9 %, 47.4 % and 40.8 % respectively). The full multi-parametric protocol was the optimum to rule-out significant CAD (Likelihood Ratio negative (LR-) 0.16) and the LGE component alone was the best to rue-in CAD (LR+ 9.81). Overall diagnostic accuracy was similar with the full multi-parametric protocol (85.9 %) compared to paired and triplet combinations. The use of coronary MRA within the full multi-parametric protocol had no additional diagnostic benefit compared to the perfusion/function/LGE combination (overall accuracy 84.6 % vs. 84.2 % (P = 0.5316); LR- 0.16 vs. 0.21; LR+ 5.21 vs. 5.77).

Conclusions

From this pre-specified sub-analysis of the CE-MARC study, the full multi-parametric protocol had the highest sensitivity and was the optimal approach to rule-out significant CAD. The LGE component alone was the optimal rule-in strategy. Finally the inclusion of coronary MRA provided no additional benefit when compared to the combination of perfusion/function/LGE.

Trial registration

Current Controlled Trials ISRCTN77246133