Patients In Poor Clinical Condition Research Articles

Cardiac decompensation of patients before transcatheter aortic valve implantation-clinical presentation, responsiveness to associated medication, and prognosis.

Cardiac decompensation (CD) in patients with aortic stenosis is a "red flag" for future adverse events. We classified patients undergoing transcatheter aortic valve implantation (TAVI) into those with acute, prior, or no prior CD at the timepoint of TAVI and compared their clinical presentation, prognosis, and effects of the prescribed medication during follow-up. Retrospective analysis of patients of one center fulfilling the criteria of 30-day device success after transfemoral TAVI. From those patients with no CD (n = 1,985) ranging to those with prior CD (n = 497) and to those with acute CD (n = 87), we observed a stepwise increase in the proportion of patients in poor clinical condition, NYHA class III/IV, low psoas muscle area, fluid overload (rales, oedema, pleural effusion), reduced ejection fraction, renal insufficiency, and anemia. More diuretics but less renin-angiotensin system inhibitors (ACEI/ARB) were prescribed for patients with acute CD compared to other groups. Prior CD (hazard ratio and 95% CI 1.40; 1.02-1.91) and acute CD (1.72; 1.01-2.91), a reduced general condition (1.53; 1.06-2.20), fluid overload (1.54;1.14-2.08), atrial fibrillation (1.76; 1.32-2.33), and anemia (1.43;1.08-1.89) emerged as strong independent predictors of one-year mortality. In all three classes of CD, prescribing of ACEI/ARB was associated with a substantial improvement of survival. The clinical presentation of (acute or prior) cardiac decompensation in patients with AS overlapped substantially with that of patients with classical signs of heart failure. Our results may support an early treatment strategy in patients with left ventricular dysfuntion before clinical signs of congestion are manifest. Moreover, these patients require intensive medical attention after TAVI.

OS05.6.A TELEMEDICINE IN NEURO-ONCOLOGY - AN EVALUATION OF REMOTE CONSULTATIONS DURING THE COVID-19 PANDEMIC

Abstract BACKGROUND To minimize the risk of infections during the Covid-19 pandemic, remote video consultations (VC) experienced an upswing in most medical fields. However, despite its multiple benefits, telemedicine in neuro-oncology comprises unique challenges and opportunities: Comprehensive neurological examinations that might not translate sufficiently to VC are very relevant for neuro-oncological patients. Also, communication in neuro-oncology can be highly emotional and challenging on a personal level, and VC have been accused of creating emotional distance between the patients and doctors. So far, evidence-based insights to evaluate and potentially customize current concepts of VC in neuro-oncology are scarce. MATERIAL AND METHODS We analyzed >3.700 neuro-oncological consultations conducted at our institution between the 1st of April 2020 and the 30th of June 2021, of which >300 were conducted as VC by patients' preference. Then we collected patients' basic demographic and clinical data and compared how the collective of patients that chose to participate in VC distinguished from those who did not. Also, we examined the reasons, suitable/less suitable encounters, VC's benefits and disadvantages and future opportunities by conducting an anonymized survey in the VC collective. RESULTS The ratio of VC participation correlated with the incidence of SARS-CoV-2 infections (r=0.5, p=0.03). Patients that participated in VC had worse clinical conditions and higher grades of malignancy, were more often diagnosed with glioblastoma, and had a longer travel distance (all p<0.01). VC were considered a fully adequate alternative to face-to-face consultations for almost all encounters that patients chose to participate in (>70%), except initial consultations. Most participants preferred to alternate between both modalities rather than participate in one alone but preferred VC over telephone consultation. Patients stated that VC made them feel safer. Participants also expressed interest in implementing other telemedicine modalities (e.g. apps) into neuro-oncology. CONCLUSION VC are a promising addition to patient care in neuro-oncology. However, patients and encounters should be selected individually. Patient subgroups that might be especially suitable for VC are patients with long travel distances seeking an expert opinion, patients in poor clinical condition, glioblastoma patients and patients requiring frequent consultations in person. A strength of face-to-face consultations is the more intense personal contact, whereas VC convince with a lower expense. VC made patients feel safer, and participants expressed their interest in expanding the offer of telemedicine in neuro-oncology further.

Development of 'Core Outcome Sets' for Meningioma in Clinical Studies (The COSMIC Project): protocol for two systematic literature reviews, eDelphi surveys and online consensus meetings.

IntroductionMeningioma is the most common primary intracranial tumour in adults. The majority are non-malignant, but a proportion behave more aggressively. Incidental/minimally symptomatic meningioma are often managed by serial imaging. Symptomatic meningioma, those that threaten neurovascular structures, or demonstrate radiological growth, are usually resected as first-line management strategy. For patients in poor clinical condition, or with inoperable, residual or recurrent disease, radiotherapy is often used as primary or adjuvant treatment. Effective pharmacotherapy treatments do not currently exist. There is heterogeneity in the outcomes measured and reported in meningioma clinical studies. Two ‘Core Outcome Sets’ (COS) will be developed: (COSMIC: Intervention) for use in meningioma clinical effectiveness trials and (COSMIC: Observation) for use in clinical studies of incidental/untreated meningioma.Methods and analysisTwo systematic literature reviews and trial registry searches will identify outcomes measured and reported in published and ongoing (1) meningioma clinical effectiveness trials, and (2) clinical studies of incidental/untreated meningioma. Outcomes include those that are clinician reported, patient reported, caregiver reported and based on objective tests (eg, neurocognitive tests), as well as measures of progression and survival. Outcomes will be deduplicated and categorised to generate two long lists. The two long lists will be prioritised through two, two-round, international, modified eDelphi surveys including patients with meningioma, healthcare professionals, researchers and those in caring/supporting roles. The two final COS will be ratified through two 1-day online consensus meetings, with representation from all stakeholder groups.Ethics and disseminationInstitutional review board (University of Liverpool) approval was obtained for the conduct of this study. Participant eConsent will be obtained prior to participation in the eDelphi surveys and consensus meetings. The two systematic literature reviews and two final COS will be published and freely available.Trial registration numberCOMET study ID 1508

Guiding Interventions for Secondary Tricuspid Regurgitation: Follow the Intricate Interplay Between Form and Function.

Secondary tricuspid regurgitation (TR) has long been considered a benign and well-tolerated valvular lesion that resolves after treatment of the underlying disease. This view has been challenged by data indicating that long-standing TR can be a progressive disorder, contributing to right ventricular failure and end-organ damage, despite adequate treatment of the underlying disease. Surgical correction is curative, but infrequently performed and historically associated with poor outcomes. This may be due to delayed diagnosis, lack of well-defined surgical indications, and, consequently, late intervention in patients in poor clinical condition with failing right ventricles. Because of limited evidence about timing and corresponding outcome of tricuspid valve surgery, current guideline recommendations are rather conservative and show several inconsistencies. Nevertheless, there has been a trend toward a more aggressive approach in the surgical treatment of TR with improved outcomes. Moreover, emerging transcatheter options claim to provide a lower-risk alternative for selected patients. This may facilitate earlier treatment and improve the attitude toward an early treatment strategy of secondary TR, yet is not reflected in the guidelines. Future research is needed for risk stratification to determine inclusion criteria and optimal timing for intervention.

Combined surgery and embolization to treat ruptured cerebral aneurysms with cerebral hematoma and intracranial hypertension: A retrospective analysis and review of the literature

ObjectiveTo determine whether the urgent embolization of a cerebral aneurysms and posterior surgery on cerebral hematomas is safe and efficacious in patients with hematomas and signs of intracranial hypertension due to the rupture of cerebral aneurysms. MethodsWe included 23 consecutive patients in poor clinical condition due to an intracranial hematoma caused by a ruptured cerebral aneurysm who were treated with both embolization and surgery within 4h of the onset of symptoms. All patients had clinical signs of intracranial hypertension and/or altered levels of consciousness, including coma due to rostrocaudal deterioration. We evaluated the efficacy of the combined technique by determining the degree of closure of the aneurysms and the patients’ prognosis one month after the procedures; we evaluated safety by analyzing the complications of the treatments. ResultsAll but two of the patients (21/23; 91.3%) had an aneurysm of the middle cerebral artery. All patients scored 4 on the Fisher scale and were classified as Hunt and Hess IV or V. The mean time from the identification of the aneurysm on computed tomography to embolization was 115min. A balloon remodelling technique was used in 18 (78%) patients; embolization achieved adequate closure in 19 (82.6%) patients. During surgery, a ventricular drain was placed in 9 (39.1%) patients. One month after treatment, 13 (56.5%) patients were functionally independent and 3 (13%) had died. No episodes of rebleeding were observed. ConclusionIn our experience, combined treatment including embolization of the aneurysm and surgical decompression with evacuation of the hematoma is a safe and effective alternative to surgical treatment alone.

Tratamiento combinado, mediante embolización y cirugía, de los aneurismas cerebrales rotos con hematoma cerebral e hipertensión intracraneal: Análisis retrospectivo y revisión de la bibliografía

ObjectiveTo determine whether the urgent embolization of a cerebral aneurysms and posterior surgery on cerebral hematomas is safe and efficacious in patients with hematomas and signs of intracranial hypertension due to the rupture of cerebral aneurysms. MethodsWe included 23 consecutive patients in poor clinical condition due to an intracranial hematoma caused by a ruptured cerebral aneurysm who were treated with both embolization and surgery within 4hours of the onset of symptoms. All patients had clinical signs of intracranial hypertension and / or altered levels of consciousness, including coma due to rostrocaudal deterioration. We evaluated the efficacy of the combined technique by determining the degree of closure of the aneurysms and the patients’ prognosis one month after the procedures; we evaluated safety by analyzing the complications of the treatments. ResultsAll but two of the patients (21/23; 91.3%) had an aneurysm of the middle cerebral artery. All patients scored 4 on the Fisher scale and were classified as Hunt and Hess IV or V. The mean time from the identification of the aneurysm on computed tomography to embolization was 115minutes. A balloon remodeling technique was used in 18 (78%) patients; embolization achieved adequate closure in 19 (82.6%) patients. During surgery, a ventricular drain was placed in 9 (39.1%) patients. One month after treatment, 13 (56.5%) patients were functionally independent and 3 (13%) had died. No episodes of rebleeding were observed. ConclusionIn our experience, combined treatment including embolization of the aneurysm and surgical decompression with evacuation of the hematoma is a safe and effective alternative to surgical treatment alone.

Nimodipine Dose Reductions in the Treatment of Patients with Aneurysmal Subarachnoid Hemorrhage.

The incidence of cerebral infarction and poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH) is reduced by oral nimodipine but acute effects of the drug may include a significant decrease in mean arterial blood pressure (MAP). A dose reduction or discontinuation of the drug is recommended if recurrent MAP drops occur. The aim of our study was to evaluate the frequency and clinical significance of nimodipine dose modifications in patients suffering from aSAH. 270 patients were included in our retrospective analysis of consecutively collected data of patients suffering from aSAH. The local treatment protocol was in accordance to national and international guidelines. Nimodipine was intended to be applied orally with a dosage of 60mg every 4h. Only 43.6% of patients eligible for vasospasm prophylaxis with nimodipine received the full daily dose of 60mg every 4h. In 28.6%, the dose had to be reduced by 50% due to a significant reduction in blood pressure after administration and/or high dose of catecholamines. In 27.7% of patients, oral administration of the drug was discontinued for the same reason. Dose reduction and discontinuation occurred with a significantly higher frequency in patients in poor clinical condition. Application of the full nimodipine dosage decreased the risk of unfavorable clinical outcome in multivariate analysis (OR 0.895, p=0.029). Our results show that dose reduction or discontinuation of nimodipine due to changes in MAP occur frequently in clinical routine and may be associated with unfavorable clinical outcome.

Endovascular Interventions in Ruptured Intracranial Aneurysms and Arteriovenous Malformations - Initial Experience

Introduction: Endovascular treatment of ruptured aneurysms and arterio-venous malformations (AVMs) is often challenging because of there locations and structure. Emergency action in first hours to days after haemorrage is crucial for saving the patient's life. Aim: To present the first emergency steps and strategy in diagnosis and treatment of intracranial vascular malformations and aneurysms after acute bleeding. Material and Methods: For period of one year seventeen patients with acute subarachnoid hemorrhage underwent CT, CT angiography with multiplanar and 3D reconstructions, MRI and DSA. Fourteen patients presented with ruptured aneurysms and 3 with AVMs. All the AVMs were classified according to Spetzler-Martin scale as Grade III or higher. Results: All patients underwent endovascular treatment. In two patients with aneurysms, the embolization was unsuccessful due to some anatomical peculiarities. In the patient's group with AVMs was used the embolic agent ONYX, as one patient underwent repeated embolization. In the group with ruptured aneurysms were used 3D and helical mechanically detachable coils. Endovascular complications were associated with permanent neurological defficite in 2 patients (11.7%) and one death (5.9%) on the third day after the intervention. Conclusion: Endovascular treatment in patients with acute intracranial hemorrhage after rupturing of brain aneurysms or AVMs is fast end safe. This is the method of choice in patients in poor clinical condition and represents an attractive alternative of open surgery.

Tracheo-innominate artery fistula successfully treated by endovascular stent-graft repair

We report two patients who developed a tracheo-innominate artery fistula (TIF) after tracheostomy. Contrast-enhanced computed tomography revealed a pseudoaneurysm of the innominate artery protruding into the trachea. Stent grafts were deployed for the innominate artery via two different access routes: the transfemoral approach and the right carotid artery approach. Endovascular stent-graft repair resulted in complete exclusion of the TIF and control of the bleeding from the tracheal stoma. At 12- and 16-month follow-ups, neither patient had clinical signs of graft infection, recurrent fistulization, or ischemic complications. It is feasible and useful to employ the carotid artery approach for stent-graft implantation in patients who have vascular anatomical limitations for the transfemoral approach. Endovascular repair of TIF by stent grafting is a minimally invasive treatment that can be tolerated by patients in poor clinical condition, and is a feasible alternative to surgical treatment.

Evaluation of collaborative tuberculosis and human immunodeficiency virus activities in Phnom Penh, Cambodia

Phnom Penh, Cambodia. 1) To monitor the number of tuberculosis (TB) patients undergoing human immunodeficiency (HIV) testing during TB treatment and trends of referral of TB-HIV patients to HIV services following the appointment of TB-HIV coordinators in TB wards, and 2) to investigate factors that influence undesirable TB treatment outcomes. Retrospective descriptive study based on a review of patient records and interviews with programme staff. Eighty-six per cent of newly registered TB patients underwent HIV testing. Most of the TB-HIV patients were referred to HIV services. Using logistic regression analysis, the risk of an undesirable treatment outcome in extra-pulmonary TB was significantly lower than in smear-positive pulmonary TB. Interviews revealed that patients in poor clinical condition at the start of TB treatment or who faced social problems, such as homelessness or foreign nationality, were at considerable risk for undesirable TB treatment outcomes. The appointment of TB-HIV coordinators to TB wards resulted in better HIV testing uptake and referral to HIV care and treatment services. To save TB-HIV patients' lives, it is important to continue this kind of study over a longer term to monitor these activities and to identify high-risk patients.

Does High-Dose Metformin Cause Lactic Acidosis in Type 2 Diabetic Patients after CABG Surgery? A Double Blind Randomized Clinical Trial

Metformin is a dimethyl biguanide oral anti-hyperglycemic agent. Lactic acidosis due to metformin is a fatal metabolic condition that limits its use in patients in poor clinical condition, consequently reducing the number of patients who benefit from this medication. In a double blind randomized clinical trial, we investigated 200 type 2 diabetic patients after coronary artery bypass surgery in the open heart ICU of the Mazandaran Heart Center, and randomly assigned them to equal intervention and control groups. The intervention group received regular insulin infusion along with 2 metformin 500 mg tablets every twelve hours, while the control group received only intravenous insulin with 2 placebo tablets every twelve hours. Lactate level, pH, base excess, blood glucose and serum creatinine were measured over five 12 h periods, with data averaged for each period. The primary outcome in this study was high lactate levels. Comparison between the 2 groups was made by independent Student’s t-test. To compare changes in multiple measures in each group and analysis of group interaction, a repeated measurement ANOVA test was used.There was no significant difference between the 2 groups regarding pH, base excess, or bicarbonate intake (P>0.05). No patient showed lactic acidosis in either group. Lactate levels were 23.0 vs 23.4 in the insulin-metformin and insulin only groups when the study was started, respectively. At the end of the study, those levels were 18.7 vs 18.9, respectively. In addition, the ANOVA repeated measurement test did not show a significant difference in terms of changes in the amount of lactate level between the 2 groups during the five measurement tests of the study period (P>0.05).High-dose metformin (1,000 mg twice daily with insulin) does not cause lactic acidosis in type 2 diabetic patients after coronary artery bypass surgery.

Interdisciplinary treatment selection in admitted patients with acute subarachnoid hemorrhage

Objective: To review the angiographic and clinical outcomes from acute (first 6 hours after bleeding) interdisciplinary treated patients with ruptured intracranial aneurysm.Method: An interventional neuroradiologist and a neurosurgeon set the emergent treatment of 100 consecutive patients with subarachnoid hemorrhage (SAH) harboring 111 cerebral aneurysms. Decisions were based on the patient's clinical condition, aneurysm's morphology and location, presence of intracranial mass-occupying process (IMOP), angiographic flow distribution patterns and treatment-related risk profit. The benefits of a joined case assessment were retrospectively analyzed, comparing our clinical and radiological results with those of the averaged literature series.Results: Initially, 39 aneurysms in 34 patients were endovascularly (EV) treated and 68 aneurysms in 66 patients were surgically (S) treated. Four nonruptured aneurysms remain under control. Complete radiological aneurysm occlusion was initially achieved in 35 (89.7%) EV and 62 (95.4%) S treated aneurysms. Twenty-six patients in poor clinical condition with IMOP as well as ten patients with distally located, 18 with EV unfavorable and 12 with highly expected recanalization rate aneurysms required S treatment. Four aneurysm remnants (two EV and two S) remain unchanged. Two EV treated aneurysms grew and were surgically occluded, and another three patients required an additional coiling procedure after recanalization. Favorable evolution was observed in 27 (79.4%) EV and 55 (83.3%) S treated patients. Computed tomography-documented rebleedings (7:1), angiographic vasospasm (3:5) and occlusion of main vessels (2:2) were the method-related complications in the EV and S groups, respectively.Conclusion: After comparing the literature data, acute interdisciplinary treatment of patients with SAH increases the rate of aneurysm occlusion, improves patient's evolution and reduces the number of complications.

Predictors of 1-year outcome after coiling for poor-grade subarachnoid aneurysmal hemorrhage

To describe features in patients admitted to the intensive care unit (ICU) for poor-grade aneurysmal subarachnoid hemorrhage (SAH) and to identify predictors of 12-month outcome. We conducted a controlled observational study of 51 consecutive patients treated with endovascular coiling within 96 h of rupture for poor-grade aneurysmal SAH (20 men and 31 women, age 54 +/- 12 years). We recorded co-morbidities; initial severity; aneurysm location; occurrence of acute hydrocephalus, initial seizures, and/or neurogenic lung edema; troponin values, Fisher grade; computed tomography (CT) findings; treatment intensity; and occurrence of vasospasm. The brain injury marker S100B was assayed daily over the first 8 days. Glasgow Outcome Scores (GOS) were recorded at ICU discharge, at 6 and 12 months. The main outcome criterion was the 1-year GOS score, which we used to classify patients as having a poor outcome (GOS 1-3) or a good outcome (GOS 4-5). Overall, clinical status after 1 year was very good (GOS 5) in 41% of patients and good (GOS 4) in 16%. Neither baseline characteristics nor interventions differed significantly between patients with good outcome (GOS 4-5) and those with poor outcome (GOS 1-3). Persistent intracranial pressure elevation and higher mean 8-day S100B value significantly and independently predicted the 1-year GOS outcome (P = 0.008 and P = 0.001, respectively). Patients in poor clinical condition after SAH have more than a 50:50 chance of a favorable outcome after 1 year. High mean 8-day S100B value and persistent intracranial hypertension predict a poor outcome (GOS 1-3) after 1 year.

Timing of aneurysm surgery in subarachnoid haemorrhage – an observational study in The Netherlands

There is still lack of evidence on the optimal timing of surgery in patients with aneurysmal subarachnoid haemorrhage. Only one randomised clinical trial has been done, which showed no difference between early and late surgery. Other studies were observational in nature and most had methodological drawbacks that preclude clinically meaningful conclusions. We performed a retrospective observational study on the timing of aneurysm surgery in The Netherlands over a two-year period. In eight hospitals we identified 1,500 patients with an aneurysmal subarachnoid haemorrhage. They were subjected to predefined inclusion criteria. We included all patients who were admitted and were conscious at any one time between admission and the end of the third day after the haemorrhage. We categorised the clinical condition on admission according the World Federation of Neurological Surgeons (WFNS) grading scale. Early aneurysm surgery was defined as operation performed within three days after onset of subarachnoid haemorrhage; intermediate surgery as performed on days four to seven, and late surgery as performed after day seven. Outcome was classified as the proportion of patients with poor outcome (death or dependent) two to four months after onset of subarachnoid haemorrhage. We calculated crude odds ratios with late surgery as reference. We distinguished between management results (reconstructed intention to treat analysis) and surgical results (on treatment analysis). The results were adjusted for the major prognosticators for outcome after subarachnoid haemorrhage. We included 411 patients. There were 276 patients in the early surgery group, 36 in the intermediate surgery group and 99 in the late surgery group. On admission 78% were in good neurological condition (WFNS I-III). MANAGEMENT RESULTS: Overall, 93 patients (34%) operated on early had a poor outcome, 13 (36%) of those with intermediate surgery and 37 (37%) in the late surgery group had a poor outcome. For patients in good clinical condition on admission and planned for early surgery the adjusted odds ratio (OR) was 1.3 (95% CI 0.5 to 3.0). The adjusted OR for patients admitted in poor neurologicalcondition (WFNS IV-V) and planned for early surgery was 0.1 (95% CI 0.0 to 0.6). SURGICAL RESULTS: For patients in good clinical condition on admission who underwent early operation the adjusted OR was 1.1 (95% CI 0.4 to 3.2); it was 0.2 (95% CI 0.0 to 0.9) for patients admitted in poor clinical condition. In this observational study we found no significant difference in outcome between early and late operation for patients in good clinical condition on admission. For patients in poor clinical condition on admission outcome was significantly better after early surgery. The optimal timing of surgery is not yet settled. Ideally, evidence on this issue should come from a randomised clinical trial. However, such a trial or even a prospective study are unlikely to be ever performed because of the rapid development of endovascular coiling.

くも膜下出血の急性期治療 くも膜下出血重症例に対する急性期治療−ＧＤＣ塞栓術導入による変化−

Indication of early treatment remains controversial for patients in poor clinical condition (Hunt & Kosnik Grade 4 or 5) after subarachnoid hemorrhage (SAH). Since 1997, we have adopted endovascular treatment using Guglielmi detachable coil (GDC) as a treatment option for these patients. In this study, we compared clinical courses of the cases treated in 1990-1996 to those treated in 1997-2002 to evaluate the efficacy of changes in treatment strategy. Between 1990 and 2002, 130 cases with SAH in Grade 4 and 5 underwent angiography as candidates of early aggressive treatment in our hospital. For the 63 cases in 1990-96 (Group 1), treatment options were early and intensively delayed craniotomy surgery and conservative management, while for the 67 cases in 1997-2002 (Group 2), GDC embolization at acute stage was added to these 3 treatment options. We compared the 2 groups of patients in terms of clinical courses and outcomes, assessed with Glasgow Outcome Scale Score (GOS) at discharge. The percentage of the patients in which aneurysm was occluded at acute stage increased from 67% in Group 1 to 87% in Group 2 for Grade 4 and from 33% to 52% for Grade 5. In Group 2, 44% of Grade 4 and 83% of Grade 5 patients were treated by GDC embolization. The outcomes of the cases in both Grade 4 and 5 were better in Group 2 than in Group 1. That is, for Grade 4 cases, the percentage of Good Recovery (GR) significantly increased from 7% in Group 1 to 27% in Group 2. And for Grade 5 cases, good outcome (GR or MD) increased from 5% in Group 1 to 18% in Group 2. Two patients recovered completely from Grade 5 in Group 2, both of which were treated with GDC while none in Group 1 recovered completely from Grade 5. The incidence of symptomatic vasospasm was not changed between Group 1 (20%) and Group 2 (16%). The introduction of GDC embolization extended the indication of early treatment for severe SAH patients because it was less invasive and, as a consequence, improved the outcome of those patients.

Endothelial cell activation after subarachnoid hemorrhage.

Evidence from animal experiments suggests that endothelial cell activation plays a pathogenetic role in the development of cerebral ischemia after subarachnoid hemorrhage (SAH). We measured plasma concentrations of two markers of endothelial cell activation, i.e., ED1-fibronectin (ED1-fn) and von Willebrand factor (vWf), among patients with aneurysmal SAH. We analyzed the relationships of concentrations to initial clinical conditions, treatment modalities, and the occurrence of delayed cerebral ischemia. We collected 123 blood samples from 27 patients with aneurysmal SAH. Aneurysms were treated surgically in 19 cases, were treated endovascularly in 7 cases, and remained untreated in 1 case. Twelve patients developed symptomatic delayed cerebral ischemia. Initial concentrations of ED1-fn (4.3 +/- 3.7 microg/ml) and vWf (17.8 +/- 8.2 microg/ml) were higher than the reference values (ED1-fn, 1.7 +/- 0.9 microg/ml, P < 0.001; vWf, 11.5 +/- 5.2 microg/ml, P = 0.003). Concentrations were higher among patients in poor clinical condition at admission, compared with patients in good clinical condition (mean difference, ED1-fn, 5.7 microg/ml, P = 0.04; vWf, 10.4 microg/ml, P = 0.02). Levels of both markers increased significantly after surgery (mean increase, ED1-fn, 7.5 microg/ml, P = 0.01; vWf, 13.2 microg/ml, P = 0.05) and after ischemic episodes (mean increase, ED1-fn, 8.3 microg/ml, P = 0.02; vWf, 5.0 microg/ml, P = 0.04). Plasma concentrations of markers of endothelial cell activation were increased early after SAH and were significantly associated with the clinical condition at admission. We also observed a significant increase in concentrations after surgery and after ischemic episodes. Whether endothelial cell activation is a causal or indirectly related factor in the pathogenesis of delayed cerebral ischemia after SAH is still uncertain.

Calcium antagonists for aneurysmal subarachnoid haemorrhage.

Secondary ischaemia is a frequent cause of poor outcome in patients with subarachnoid haemorrhage. Its pathogenesis has not been elucidated yet, but may be related to vasospasm. Experimental studies have indicated that calcium antagonists can prevent or reverse vasospasm. Calcium antagonists have been studied in several trials, but data are conflicting. There is no overview concerning all available calcium antagonists. To determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). We searched the Cochrane Stroke Group Trials Register (last searched November 2001). In addition, we handsearched two Russian journals (1990-1995) and contacted trialists and pharmaceutical companies to identify further studies All completed, unconfounded, truly randomised controlled trials comparing any calcium antagonist with control, within ten days of SAH onset. Eleven trials that met the inclusion criteria were included in the overview. Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information We analysed 11 trials totaling 2804 randomised patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analysed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877 (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by angiography or autopsy. Overall, calcium antagonists significantly reduced the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0.72 to 0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event is 20. For oral nimodipine alone the RR was 0.69 (0.58 to 0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80 to 1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59 to 0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71 to 0.89). Calcium antagonists reduce the proportion of patients with poor outcome and ischaemic neurological deficits after aneurysmal SAH. The results for 'poor outcome' are statistically robust, but depend largely on one large trial with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The evidence for nimodipine is not beyond every doubt, but given the potential benefits and modest risks associated with this treatment, against the background of a devastating natural history, oral nimodipine (60 mg every 4 hours) is indicated in patients with aneurysmal SAH. Intravenous administration of calcium antagonists cannot be recommended on the basis of the present evidence. For oral nimodipine uncertainty remains regarding the (dis)advantages in patients in poor clinical condition on admission or in patients with established cerebral ischaemia, the optimal dose and time window, the question whether other types of calcium antagonists offer better protection and the intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH.

Postoperative anticonvulsant prophylaxis for patients treated for cerebral aneurysms.

The incidences of postoperative seizures and side effects were evaluated in 193 patients with cerebral aneurysm who received anticonvulsant prophylaxis and underwent 224 craniotomies for cerebral aneurysms between 1993 and 1995. The patients were 73 males and 120 females aged between 31 and 80 years. One hundred and sixteen patients had ruptured cerebral aneurysms and 108 had unruptured aneurysms. Phenytoin followed by valproic acid were administered. Early postoperative seizures occurred in five patients (4 with ruptured and 1 with unruptured aneurysms) within 14 days after surgery. Late postoperative seizures occurred in four different patients with ruptured aneurysms more than 14 days after surgery. The presence of cortical lesions detected by cerebral computed tomography and occurrence of symptomatic vasospasm were correlated with the occurrence of early postoperative seizure (p < 0.05). Three of the four patients with late postoperative seizure had cortical lesions and two were receiving continued medication. Side effects that warranted discontinuation of therapy were seen in the follow-up period in 12.9% of patients. Anticonvulsant prophylaxis is not recommended due to the higher incidence of side effects than seizure, except in patients in poor clinical condition for the purpose of brain protection. Otherwise, anticonvulsant medication should be initiated at the time of the initial seizure attack.

Hemostasis and fibrinolysis activation after subarachnoid hemorrhage.

The authors assessed hemostasis and fibrinolysis serially: on admission and on the 1st and 7th days after surgery for subarachnoid hemorrhage (SAH), examining the complications of aneurysm rupture and its surgical repair. Of 32 patients, 25 with SAH were compared with seven control patients who underwent surgery for an unruptured intracranial aneurysm. On admission, patients with SAH had higher thrombin-antithrombin III complex (TAT) levels (13.3 +/- 3.8 vs. 3.8 +/- 0.6 ng/ml, p = 0.01), fibrin degradation product, D-dimer levels (1310 +/- 220 vs. 556 +/- 89 ng/ml, p = 0.0001), and leukocyte counts (14.6 +/- 0.7 vs. 10.6 +/- 1.8 x 10(9) cells/L, p < 0.05) than did control patients. Postoperative D-dimer values (p = 0.007) remained higher in the SAH group. Furthermore, admission D-dimer levels were higher in the patients in poor clinical condition than in those in good condition (2017 +/- 377 vs. 934 +/- 208 ng/ml, p = 0.007), and D-dimer levels were associated with the outcome at 3 months after admission. Additionally, thrombin generation and fibrinolytic markers measured on admission were related to clinical grade, amount of subarachnoid blood seen on computerized tomography (CT) scanning, and patient fatality. Patients with hypodense lesions verified on follow-up CT scanning or with persistent neurological deficits at 3 months had higher prothrombin fragments 1 and 2, TAT, D-dimer, and plasminogen activator inhibitor-1 values on the 1st day postoperatively than did patients without such lesions. In short, in patients with SAH, activation of coagulation and fibrinolysis was strongly associated with clinical state, patient fatality, and outcome at 3 months, and postoperatively this activation correlated with the development of brain infarction.

Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-alpha following subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) causes an inflammatory reaction and may lead to ischemic brain damage. Experimental ischemia has been shown to be connected with the alarm-reaction cytokines interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor-alpha (TNF alpha). Increased levels of these cytokines, however, have not been detected thus far in patients following an SAH event. For this reason daily cerebrospinal fluid (CSF) samples were collected from 22 consecutively enrolled patients with SAH and from 10 non-SAH patients (controls). The CSF samples were studied using immunoassays for IL-1Ra and TNF alpha to investigate whether an SAH caused increased cytokine levels. The mean IL-1Ra levels were significantly higher in patients with SAH who were in poor clinical condition on admission than in those who were in good condition (318 pg/ml vs. 82 pg/ml, p < 0.02). The IL-1Ra levels increased during delayed ischemic episodes and after surgery in patients who were in poor clinical condition. Significant increases in IL-1Ra and TNF alpha were detected during Days 4 through 10 in patients suffering from SAH who eventually had a poor outcome (p < 0.05). Patients with good outcomes and control patients had low levels of these cytokines. The levels of IL-1Ra increased after surgery in patients with Hunt and Hess Grades III through V, but not in those with Grade I or II. This finding indicates that patients in poor clinical condition have a labile biochemical state in the brain that is reflected in increased cytokine levels following the surgical trauma. Both IL-1Ra and TNF alpha are known to induce fever, malaise, leukocytosis, and nitric oxide synthesis and to mediate ischemic and traumatic brain injuries. The present study shows that levels of these cytokines increase after SAH occurs and that high cytokine levels correlate with brain damage. It is therefore likely that fever, leukocytosis, and nitric oxide synthesis are also mediated by IL-1 in patients suffering from SAH and it is probable that the inflammatory mediators contribute to brain damage.