Elevated Baseline C-Reactive Protein as a Predictor of Outcome After Aneurysmal Subarachnoid Hemorrhage: Data From the Simvastatin in Aneurysmal Subarachnoid Hemorrhage (STASH) Trial.

BACKGROUND: There remains a proportion of patients with unfavorable outcomes after aneurysmal subarachnoid hemorrhage, of particular relevance in those who present with a good clinical grade. A forewarning of those at risk provides an opportunity towards more intensive monitoring, investigation, and prophylactic treatment prior to the clinical manifestation of advancing cerebral injury. OBJECTIVE: To assess whether biochemical markers sampled in the first days after the initial hemorrhage can predict poor outcome. METHODS: All patients recruited to the multicenter Simvastatin in Aneurysmal Hemorrhage Trial (STASH) were included. Baseline biochemical profiles were taken between time of ictus and day 4 post ictus. The t-test compared outcomes, and a backwards stepwise binary logistic regression was used to determine the factors providing independent prediction of an unfavorable outcome. RESULTS: Baseline biochemical data were obtained in approximately 91% of cases from 803 patients. On admission, 73% of patients were good grade (World Federation of Neurological Surgeons grades 1 or 2); however, 84% had a Fisher grade 3 or 4 on computed tomographic scan. For patients presenting with good grade on admission, higher levels of C-reactive protein, glucose, and white blood cells and lower levels of hematocrit, albumin, and hemoglobin were associated with poor outcome at discharge. C-reactive protein was found to be an independent predictor of outcome for patients presenting in good grade. CONCLUSION: Early recording of C-reactive protein may prove useful in detecting those good grade patients who are at greater risk of clinical deterioration and poor outcome.

Simvastatin in aneurysmal subarachnoid haemorrhage (STASH): a multicentre randomised phase 3 trial.

BACKGROUND: The benefit of statins in patients with acute aneurysmal subarachnoid haemorrhage is unclear. We aimed to determine whether simvastatin 40 mg could improve the long-term outcome in patients with this disorder. METHODS: In this international, multicentre, randomised, double-blind trial, we enrolled patients aged 18-65 years with confirmatory evidence of an aneurysmal subarachnoid haemorrhage and presenting less than 96 h from ictus from 35 acute neurosurgical centres in nine countries. Patients were randomly allocated (1:1) to receive either simvastatin 40 mg or placebo once a day for up to 21 days. We used a computer-generated randomisation code to randomise patients in every centre by blocks of ten (five simvastatin, five placebo). Participants and investigators were masked to treatment assignment. The primary outcome was the distribution of modified Rankin Scale (mRS) score obtained by questionnaire at 6 months. Analyses were done on the intention-to-treat population. This trial has been completed and is registered with Current Controlled Trials, number ISRCTN75948817. FINDINGS: Between Jan 6, 2007, and Feb 1, 2013, apart from the period between May 15, 2009, and Feb 8, 2011, when recruitment was on hold, 803 patients were randomly assigned to receive either simvastatin 40 mg (n=391) or placebo (n=412). All patients were included in the intention-to-treat population. 782 (97%) patients had outcome data recorded at 6 months, of whom 560 (72%) were classed as having a favourable outcome, mRS 0-2 (271 patients in the simvastatin group vs 289 in the placebo group). The primary ordinal analysis of the mRS, adjusted for age and World Federation of Neurological Surgeons grade on admission, gave a common odds ratio (OR) of 0·97, 95% CI 0·75-1·25; p=0·803. At 6 months, we recorded 37 (10%) deaths in the simvastatin group compared with 35 (9%) in the placebo group (log-rank p=0·592). 70 (18%) serious adverse events were reported in the simvastatin group compared with 74 (18%) in the placebo group. No suspected unexpected serious adverse reactions were reported. INTERPRETATION: The STASH trial did not detect any benefit in the use of simvastatin for long-term or short-term outcome in patients with aneurysmal subarachnoid haemorrhage. Despite demonstrating no safety concerns, we conclude that patients with subarachnoid haemorrhage should not be treated routinely with simvastatin during the acute stages. FUNDING: British Heart Foundation.

Biological effects of acute pravastatin treatment in patients after aneurysmal subarachnoid hemorrhage: a double-blind, placebo-controlled trial.

OBJECT: The authors previously demonstrated that acute pravastatin therapy in patients after aneurysmal subarachnoid hemorrhage (SAH) ameliorates vasospasm-related delayed ischemic neurological deficits. The object of this study was to continue to examine potential mechanisms of these beneficial effects. METHODS: Eighty patients with aneurysmal SAH (age range 18-84 years; time to onset 1.8 +/- 1.3 days) were enrolled in a double-blind study and randomized to receive 40 mg of oral pravastatin or placebo daily for as long as 14 days. Daily transcranial Doppler ultrasonography and blood tests every 3 days (including full blood cell counts, coagulation profiles, fasting glucose and lipid profiles, and serum biochemistry) were performed during the trial period. RESULTS: No significant differences were found in baseline laboratory data between the trial groups. Subsequent measurements during the 14-day trial showed reduced low-density lipoprotein (LDL) cholesterol levels and total/high-density lipoprotein cholesterol ratios between Days 3 and 15 (p < 0.05), and increased D-dimer levels (p < 0.05) on Day 6, in the pravastatin group. Patients who received pravastatin but developed vasospasm had significantly lower baseline LDL cholesterol levels or a less extensive reduction in LDL cholesterol levels (p < 0.05), and greater increases in plasma fibrinogen (p = 0.009) and serum C-reactive protein on Day 3 (p = 0.007), compared with those patients without vasospasm. The reduction in LDL cholesterol levels on Day 3 in the placebo group correlated with the duration of normal cerebral autoregulation on the ipsilateral side of the ruptured aneurysm (p = 0.002). CONCLUSIONS: In addition to functioning through a cholesterol-independent pathway, cerebrovascular protection from acute statin therapy following aneurysmal SAH may also function through cholesterol-dependent mechanisms.

A randomized trial of synthetic patch versus direct primary closure in carotid endarterectomy.

OBJECTIVE: To define whether or not direct microscopic closure with or without the use of a vascular patch is advantageous in terms of clinical outcome and late vessel occlusion rates after microsurgical carotid endarterectomy. METHODS: Three hundred thirty-eight elective carotid endarterectomies in 315 patients were randomized to direct arteriotomy or closure with a polyester collagen-coated vascular patch. Ten procedures did not follow the randomization process because of technical difficulties and were excluded. Vessel patency (duplex ultrasound) and outcome were assessed during and immediately after surgery and at 4 and 12 months after surgery. RESULTS: Four-month ultrasound assessment (n = 321) identified five occluded vessels: two in the patch group (n = 149) and three in the direct closure group (n = 172). Six patients in the patch group had died or were significantly disabled at 4 months, compared with five in the direct closure group. At the 12-month assessment (n = 313), eight vessels had occluded: five from the patched group (n = 146) and three from the direct closure group (n = 167). Eight patients in the patch group had died or were significantly disabled, compared with four in the direct closure group. No statistically significant difference between the two groups in terms of vessel occlusion, morbidity, or mortality was seen (P > 0.1). CONCLUSION: No difference in vessel patency and clinical outcome has been identified after microscopic patch angioplasty and direct arteriotomy repair. The authors conclude that there is no benefit from the routine use of patch angioplasty in microscopic carotid endarterectomy.

Use of antihypertension agents for the suppression of arterial pulse pressure waveforms in patients with intracranial aneurysms.

OBJECT: Patients with intracranial aneurysms tend toward raised blood pressure and abnormal pulse pressure profiles. The authors have investigated the influence of three antihypertension agents on blood pressure and pulse pressure waveforms in patients with known intracranial aneurysms, with a view to assessing the potential benefits of longterm antihypertension therapy on the progression of unruptured intracranial aneurysms. METHODS: Nineteen patients with a mean age of 56 years (range 38-76 years) were recruited for this study. All patients had confirmed intracranial aneurysms. A double-blind, randomized, crossover study was performed using perindopril, irbesartan, isosorbide mononitrate, and a placebo. Blood pressure and pulse pressure waveforms were assessed at the end of each 4-week treatment period. Perindopril and irbesartan were well tolerated. For all measured parameters except heart rate (p = 0.03), no significant difference between baseline and placebo was identified. Each drug when compared with placebo reduced peripheral arterial blood pressure. Perindopril significantly decreased mean blood pressure by 10 mm Hg (p = 0.004), irbesartan by 9 mm Hg (p = 0.004), and isosorbide mononitrate by 13 mm Hg (p = 0.005). The administration of each drug effected a significant reduction in the carotid artery augmentation index (AIX) compared with baseline values (perindopril p = 0.01, irbesartan p = 0.0002, and isosorbide mononitrate p = 0.03). There was also a significant difference in the AIX between irbesartan and the placebo (p = 0.05). Compared with the placebo, there was a significant difference in AIX (adjusted for heart rate) following the administration of irbesartan (p = 0.003) and isosorbide mononitrate (p = 0.01), but not with perindopril (p = 0.17). CONCLUSIONS: Irbesartan appears to be the most effective treatment for the combined suppression of blood pressure and AIX in patients with intracranial aneurysms and has a high degree of patient tolerance.

Women and war. What physicians should know.

Most of today's 1.7 million women veterans obtain all or most of their medical care outside the VA health care system, where their veteran status is rarely recognized or acknowledged. Several aspects of women's military service have been associated with adverse psychologic and physical outcomes, and failure to assess women's veteran status, their deployment status, and military trauma history could delay identifying or treating such conditions. Yet few clinicians know of women's military history--or of military service's impact on women's subsequent health and well being. Because an individual's military service may be best understood within the historical context in which it occurred, we provide a focused historical overview of women's military contributions and their steady integration into the Armed Forces since the War for Independence. We then describe some of the medical and psychiatric conditions associated with military service.

Intracranial aneurysms treated with endovascular coils: detection of recurrences using unenhanced and contrast-enhanced transcranial color-coded duplex sonography.

BACKGROUND AND PURPOSE: Because neck recurrence after endovascular treatment of intracranial aneurysms (IAs) is not uncommon, surveillance to assess long-term stability of occlusion is clearly important. This study evaluated unenhanced and contrast-enhanced transcranial color-coded duplex sonography (TCCS) in detecting refilling of IAs treated with detachable coils. METHODS: Patients with coiled IAs were imaged before and after contrast enhancement. The results were compared with those of a surveillance digital subtraction angiogram (DSA). The operator was blinded to the results of the DSA. Aneurysms were classed as either occluded or with residual flow and quantified as minor, moderate, or extensive. There were 208 studies performed in 4 neurosurgical centers. Of those, 141 studies received ultrasonic contrast enhancement with Levovist, and 68 had an additional enhanced study with SonoVue. RESULTS: We excluded 44 studies. Of the 164 unenhanced studies, TCCS correctly identified 52 of 67 cases defined as completely occluded by DSA (sensitivity 78%; specificity 77%), 13 of 50 aneurysms with minor refilling (sensitivity 26%; specificity 88%), 15 of 27 aneurysms with moderate refilling (sensitivity 56%; specificity 95%), and 9 of 20 aneurysms with extensive refilling (sensitivity 45%; specificity 100%). TCCS correctly identified an additional 10 aneurysms with minor refilling after Levovist enhancement and 3 with SonoVue. Both SonoVue and Levovist enhancement identified an additional 1 aneurysm with moderate refilling and 3 with extensive refilling. CONCLUSIONS: TCCS could be used to selectively monitor IAs, which would reduce the requirement for long-term invasive monitoring. The detection of neck refilling is improved with contrast enhancement.

Assessment of transcranial color-coded duplex sonography for the surveillance of intracranial aneurysms treated with Guglielmi detachable coils.

OBJECTIVE: We sought to evaluate the sensitivity and specificity of transcranial color-coded duplex sonography (TCCS) and the effect of an ultrasonographic contrast agent in the long-term surveillance of intracranial aneurysms treated with Guglielmi detachable coils. METHODS: Forty-six studies were obtained in patients with intracranial aneurysms treated with coils. All studies were obtained within 2 months of surveillance digital subtraction angiograms, which was adopted as the standard for observing aneurysm refilling. For 34 of the studies, imaging was performed both before and after infusing an ultrasonographic contrast agent (Levovist). The remaining 12 studies were unenhanced. Aneurysms were described either as being fully occluded or as having residual flow. The degree of residual flow was quantified as minor, moderate, or extensive. The operator was blinded to the results of digital subtraction angiography during TCCS assessment. RESULTS: TCCS correctly identified 19 of 20 aneurysms with complete occlusion (sensitivity, 95%; specificity, 84%). TCCS also identified all 16 of the clinically relevant aneurysms with either moderate or extensive residual flow visualized on digital subtraction angiograms and 5 aneurysms only after contrast enhancement (sensitivity, 100%; specificity, 97%). The overall accuracy of TCCS in identifying clinically relevant aneurysms was 85% without contrast enhancement and 96% with contrast enhancement. CONCLUSION: Contrast-enhanced TCCS shows promise as a noninvasive imaging method for the surveillance of coiled intracranial aneurysms.