WoundClot® Hemostatic Gauze Reduces Bleeding Time after Arterial Venous Fistula Decannulation.

INTRODUCTION: Decannulation of the arteriovenous fistula (AVF) after each hemodialysis session requires a precise compression on the needle puncture site. The objective of our study was to evaluate the bleeding time (BT) needed to achieve hemostasis using WoundClot, an innovative hemostatic gauze, and to assess whether its long-term use can improve AVF preservation. METHODS: This is a prospective single center study. Initially, the time to hemostasis after AVF decannulation was compared between WoundClot and cotton gauze in 24 prevalent hemodialysis patients. Thereafter, the patients continued to use WoundClot for 12 months and were compared to a control group consisting of 25 patients using regular cotton gauze. Follow-up data included parameters of dialysis adequacy, AVF interventions, and thrombotic events. RESULTS: WoundClot use shortened significantly the time needed for hemostasis. Mean venous BT decreased by 3.99 (±4.6) min and mean arterial BT by 6.38 (±4.8) min when using WoundClot compared to cotton gauze (p < 0.001). At the end of the study, dialysis adequacy expressed by spKt/V was higher in the WoundClot group compared to control (1.73 vs. 1.53, respectively, p = 0.047). Although patients in WoundClot group had a higher baseline BT, arterial and venous pressures did not differ between the groups after a median follow up of 10.8 months. AVF thrombosis rate was similar between the groups. CONCLUSIONS: WoundClot hemostatic gauze significantly reduced the time required for hemostasis after AVF decannulation and may be associated with better AVF preservation. We suggest using WoundClot for arterial BT longer than 15 min and for venous BT longer than 12.5 min.

Brain lesions in cerebral venous sinus thrombosis.

BACKGROUND AND PURPOSE: Analyze the relationship between the location and extent of sinus thrombosis and presence and severity of brain lesions. METHODS: Retrospective chart and neuroimaging review of patients with documented CVST. A CVST score was devised to quantify the extent of cerebral venous sinus thrombosis. RESULTS: Nineteen of 56 (34%) patients had brain lesions. The extent of sinus thrombus was associated with increased risk of brain lesions (CVST score 1.9 among patients without brain lesions versus 3.1 in those with lesions; P=0.006). Age, sex, and acquired or hereditary thrombophilias were not associated with the risk of parenchymal lesions. Functional outcomes were favorable even in patients with extensive CVST and parenchymal lesions at presentation. CONCLUSIONS: The extent of the sinus involvement correlates with the risk of brain lesions in patients with CVST, but additional factors might also contribute to their occurrence.

Medical management of cerebral vasospasm: present and future.

Cerebral vasospasm is one of the major complications of subarachnoid hemorrhage. The delayed occurrence of this complication allows for preventive management and early therapeutic interventions. Yet, accurate and timely diagnosis remains challenging and therapeutic options are rather limited. This review discusses new developments in the diagnosis and medical management of cerebral vasospasm made possible by technological advances and growing understanding of the complex pathophysiology of this disorder. CT protocols including CT perfusion and MRI with diffusion and perfusion sequences are increasingly employed in the evaluation of patients with suspected vasospasm. These radiological studies can add important information to that provided by transcranial Doppler and conventional angiography. Nimodipine for the prevention of delayed functional sequelae and hemodynamic augmentation therapy for the treatment of symptomatic vasospasm remains the mainstay of medical management. Novel strategies under investigation include the use of endothelin receptor antagonists, magnesium sulphate and statins. The value of albumin is being formally studied in an ongoing trial. Interventions to enhance nitric oxide may prove viable in the near future.

Deep venous thrombosis prophylaxis in cerebral hemorrhage.

Deep vein thrombosis (DVT) is a risk factor for patients with acute stroke. Subclinical DVT is more common than clinically apparent DVT. DVT manifests with lower extremity swelling that might be associated with pain. Venous duplex ultrasound is a simple diagnostic procedure for detection of a DVT. However, as many as 30% of patients with acute pulmonary embolism show no evidence of lower extremity DVT, and thus a negative venous duplex ultrasound does not exclude the diagnosis of acute pulmonary embolism. Data suggest that heparin, of any type, may reduce the risk of venous thromboembolism in neurosurgical patients. One trial has shown that mechanical devices, such as intermittent pneumatic compression, significantly decrease the occurrence of asymptomatic DVT for patients with intracerebral hemorrhage as compared with elastic stockings alone, although this advantage was not found in a meta-analysis of prospective studies. Limitations in DVT prophylaxis raise a question about the need for more aggressive DVT surveillance.

Rate of arterial occlusion in patients with acute ischemic stroke.

OBJECTIVE: Computed tomographic angiography (CTA) was invented more than 20 years ago, but only gained acceptance recently, thanks to advancements in the computer technology. It can demonstrate areas of arterial stenosis or occlusion with accuracy nearly that of digital subtraction angiography (DSA). It is also able to clearly illustrate calcification, which is more difficult to define on magnetic resonance angiography and is not clearly depicted on DSA. METHODS: Our retrospective study attempted to clarify the rate of occlusion or stenosis in the patients with acute ischemic stroke. RESULTS: Over the period of 7 months, 93 consecutive patients were admitted with acute ischemic stroke. Fifty-six patients underwent CTA and were included in this study. Most of the patients were admitted after 6 hours following onset of symptoms. There were 28 men and 28 women, and 80.4% of the cohort was of African-American origin. The majority of strokes were attributed to small-vessel disease (25/56). The rest of the cases were deemed secondary to atheroembolism (15/56), cardioembolism (9/56) or of unclear etiology (7/56). In 24 (42.9%) patients, CTA failed to reveal any abnormalities of the cerebrovascular tree. CTA demonstrated arterial occlusion in ten (17.9%) patients and stenosis of extracranial or intracranial arteries on the symptomatic side in 22 (39.2%) patients. There was very good correlation between CTA and ultrasound techniques (carotid duplex and transcranial Doppler). CTA was superior in demonstrating distal intracranial stenosis. CONCLUSION: Overall, CTA is an extremely valuable and fast way to emergently evaluate the cerebrovascular anatomy, making it very useful for pre-thrombolysis evaluation of patients with ischemic stroke.

Antiepileptic drugs in aneurysmal subarachnoid hemorrhage.

Seizures may occur during or soon after rupture of an intracranial aneurysm. The use of antiepileptic drugs (AEDs) is a controversial issue. The overall conclusions from 2 recent studies in aneurysmal subarachnoid hemorrhage are that 1) many patients receive AEDs but should not; 2) long-term use is associated with worse outcome; and 3) short-term use is safer. Phenytoin may not be the first choice for seizure prophylaxis; newer AEDs such as levetiracetam might be more helpful in prevention and treatment of seizures.

Following the clot in spectacular shrinking deficit.

A subset of patients with major cerebral hemispheric ischemia due to distal internal carotid artery or proximal middle cerebral artery occlusion has rapid spontaneous improvement of neurologic deficits. This phenomenon has been designated the "spectacular shrinking deficit." A 79-year-old woman had the sudden onset of neurologic deficits consistent with a large right middle cerebral artery territory infarct. Serial multimodality imaging studies documented distal propagation and fragmentation of a proximal middle cerebral artery thrombus coinciding with rapid clinical improvement. Spectacular shrinking deficit provides a unique insight into the underlying characteristics of a patient population not treated with thrombolytics with impressive recovery from major hemispheric ischemia.

Warfarin-associated intraventricular hemorrhage.

OBJECTIVE: In this study, we have reviewed our experience with anticoagulation-associated intraventricular hemorrhage (IVH). Our goal was to determine if IVH is also an independent prognosticator of fatal outcome in patients with anticoagulation-associated intracerebral hemorrhage (ICH). METHODS: This study is a retrospective analysis of medical records and computed tomographic imaging. Eighty-eight patients with warfarin-associated ICH were analysed, including eight patients with predominant IVH. RESULTS: There was a very low rate of hemorrhage extension in patients with predominant IVH. Despite that, those patients had 50% 30 day mortality. Overall patients with ICH had 45% 30 day mortality. Ventricular extension raised mortality in ICH patients to 75%, while the absence of ventricular extension carried only 23% 30 day mortality. IVH was significantly associated with 30 day mortality (p<0.001). Panventricular extension was uniformly fatal in patients with ICH and carried 75% 30 day mortality in patients with predominant IVH. On a multivariate logistic regression model including age, ICH volume and IVH, ICH volume (p<0.001) and IVH (p = 0.003) remained independently associated with early mortality. CONCLUSION: Extension of anticoagulation-associated ICH into ventricular system caused a high mortality, especially in patients with panventricular involvement. IVH is an independent predictor of early death in these patients. In our experience, the majority of IVH do not expand over time and poor outcome appears to be related to the magnitude of the initial insult.

Effects of hyperbaric oxygen on skin blood flow and tissue morphology following sciatic nerve constriction.

BACKGROUND: Constriction of the sciatic nerve by loose ligation produces an inflammatory neuropathic injury. This represents an animal model for peripheral mononeuropathy. Oxygen-derived free radicals are suspected to play an important role in the pathogenesis of ischemia/reperfusion injury, leading to neurogenic inflammation. Hyperbaric oxygen (HBO) has been used anecdotally to treat clinically similar conditions in humans, but specific effects on the animal model have not been well studied. OBJECTIVE: This study in a rat model examined the effects of hyperbaric oxygen on skin blood flow and tissue morphology by light and electron microscopy following sciatic nerve constriction. DESIGN: A scientific investigation in a rat model. METHODS: In this study, the neuropathic injury was established by loose ligation of the rat sciatic nerve. The animals were divided into three groups, sham (S, n=8), ligation but no treatment (LN, n=8) and ligation and treatment with hyperbaric oxygen (LT, n=8). The treatment group (n=8) received hyperbaric oxygen treatment immediately following the injury and daily for four additional days at the same time interval. One hundred percent O2 at 3 atmospheres absolute pressure (66 feet sea water) was administered for two hours. The hindpaws of the rats were observed by light microscopy, electron microscopy, laser Doppler flowmetry (LDF), and clinically for the presence of edema. RESULTS: Untreated animals demonstrated marked tissue edema following sciatic constriction, whereas animals that received hyperbaric oxygen had minimal to no edema. The sham group demonstrated normal histology. The group not treated with hyperbaric oxygen demonstrated swollen mitochondria (2-3 times), with loss of cellular integrity, multiple vacuole formation in both nerve and muscle tissue, widened sarcomeres in muscle, and degenerative changes in the nerve myelin sheaths. The group treated with hyperbaric oxygen demonstrated preservation of cellular structure including mitochondrial integrity, no vacuole formation, and maintenance of normal, easily identifiable nerve structure. The sham group had no change of skin blood flow. Skin blood flow of LT group was decreased immediately after ligation (p<0.05) and recovered to baseline level before ligation on Day 5 after four hyperbaric oxygen treatments. Skin blood flow of LN group was decreased immediately after ligation (p <0.01) and did not recover (p <0.01). CONCLUSION: This study evaluated tissue changes after nerve injury caused by loose ligation of the sciatic nerve in rats. Hyperbaric oxygen treatment following sciatic nerve injury reduced tissue edema, improved skin blood flow, and preserved muscle and neuronal ultrastructural integrity.

Morphological changes of cerebral arteries in a canine double hemorrhage model.

Cerebral vasospasm is a major cause of morbidity and mortality in patients suffering from subarachnoid hemorrhage (SAH). Despite numerous studies, the pathogenesis of this deadly disorder is not clearly understood. Alterations in endothelial cells are a distinct morphological feature of cerebral vasospasm and some recent studies suggest that apoptosis might play a role in the cells' death. The goal of the present study is to examine the time course of apoptosis in endothelial cells of spastic cerebral arteries following experimental subarachnoid hemorrhage. Fifteen dogs were used in the present study. Twelve of them were divided into three groups (four per group) and subjected to a double-hemorrhage method of SAH. Following SAH, groups were sacrificed respectively on days 3, 5, and 7. Three dogs served as controls without blood injection. The basilar arteries were studied with the transmission electron microscopy and with angiography. Angiographic vasospasm began on day 3 and peaked on day 7. In morphologic studies, control dogs did not demonstrate apoptotic-like changes in endothelial cells of the basilar arteries. Beginning with day 3, apoptotic-like changes were noted in endothelial cells and consisted of condensation of peripheral nuclear chromatin, blebbing of the cell membrane, and condensation of the cytoplasm. Such changes progressed with time and were maximally developed by day 7. This is the first study that demonstrates the time course of apoptotic-like changes in the endothelial cells in the vasospastic basilar artery. Apoptosis might play an important role in the pathogenesis of vasospasm.

Signal transduction of ET-1 in contraction of cerebral arteries.

The signaling pathways of endothelin-1-induced contraction, including the role of protein tyrosine kinase (PTK), mitogen-activated protein kinase (MAPK), protein kinase C (PKC) and RhoA/Rho-kinase were studied using rabbit basilar arteries by isometric tension and Western blot. The following results were observed: (1) endothelin-1 produced phosphorylation of MAPK and RhoA and contraction by activation of endothelin-A but not endothelin-B receptors; (2) MAPK inhibitors, PD 98059 and U0126, PTK inhibitor, genistein, Src kinase inhibitor, damnacanthal, and Janus tyrosine kinase (JAK2) inhibitor, AG-490, abolished endothelin-1-induced contraction and MAPK immunoreactivity; (3) PTK inhibitor, staurosporine, and phosphatidylinositol 3-kinase (PI- 3K) inhibitor wortmannin abolished endothelin-1 induced contraction but not MAPK immunoreactivity; (4) Rho-kinase inhibitor, Y-27632, reduced endothelin-1-induced contraction; (5) PI-3K inhibitor, wortmannin, but not PKC and PTK inhibitors, reduced endothelin-1-induced RhoA activation; (6) endothelin-1 increased the level of myosin light chain (MLC) phosphorylation, and Rho-kinase inhibitor, Y-27632, reduced the effect of endothelin- 1 on MLC phosphorylation. This study demonstrated that three signaling pathways Src-JAK2-PTK-MAPK, PI-3K-RhoA-Rhokinase- MLC and PKC all contribute to endothelin-1-induced contraction in the rabbit basilar artery. MAPK is downstream of PTK, Src and JAK pathways. PI-3 kinase and MLC might be the upstream and downstream factors of RhoA activation.

Preliminary study of the effects of caspase inhibitors on vasospasm in dog penetrating arteries.

This preliminary study was undertaken to explore the possible protective effect of caspase inhibitors Z-VDVAD-FMK and Z-DEVD-FMK in apoptosis and vasospasm in penetrating arteries during cerebral vasospasm. Experimental subarachnoid hemorrhage (SAH) was induced in 16 dogs by an intracisternal injection of autologous arterial blood (0.4 ml/kg) on Day 0 and Day 2. The dogs were then randomly divided into four groups: control-SAH, vehicle-control, and two treatment groups. In the treatment groups, caspase inhibitors (10 microM) were intracisternally injected each day beginning on Day 2 until Day 6. Effects of the inhibitors were analyzed utilizing angiography, the clinical status of the dogs (activity, appetite, and neurological deficits), and transmission electron microscopy of the penetrating arteries. All the dogs were sacrificed on Day 7. In control-SAH and vehicle-control groups, severe angiographic vasospasm, poor clinical status, and penetrating vasospasm were registered in all the dogs. In the treatment groups, all the dogs developed angiographic vasospasm and vasospasm in penetrating arteries, however, with benign clinical statues. The occurrence of apoptosis in endothelial cells was reduced by caspase-2 but not by caspase-3 inhibitor. Caspase inhibitors failed to prevent vasospasm either in major or in penetrating arteries. The improvement of clinical scores by the caspase inhibitors may be related to their protection of the endothelial cells. Further investigations using more rigorous clinical scoring system and quantitative information on the degree of apoptosis in the vessels, as well as in the brain parenchyma are recommended.

Signal transduction pathways in cerebral vasospasm.

Cerebral vasospasm is a deadly complication following the rupture of intracranial aneurysms. The time course of cerebral vasospasm is unique in that it is slow developing, usually takes 4-7 days to peak, but lasts up to 2-3 weeks, and is resistant to most known vasodilators. These special features make cerebral vasospasm the most important determinant in the outcome of patients suffering subarachnoid hemorrhage. The available treatment strategies include mechanical dilation of spastic cerebral arteries (angioplasty) and non-selective vasodilatation such as by Ca(2+) channel blockers. One new development in the experimental treatment of cerebral vasospasm is the looming target of signaling pathways. Understanding vasospastic signals in cerebral arteries might offer a new avenue for selective treatment of cerebral vasospasm in the future.

Therapeutic effect of caspase inhibitors in the prevention of apoptosis and reversal of chronic cerebral vasospasm.

One of the important histological changes in cerebral vasospasm after subarachnoid hemorrhage (SAH) is endothelial cell damage, which involves apoptosis. The current study was undertaken to determine whether anti-apoptosis therapy prevents apoptosis and reverses vasospasm in a dog SAH model. Twenty-three mongrel dogs of either sex, weighing 17-25 kg, were subjected to autologous arterial blood injection into the cisterna magna on day 0 and day 2, and sacrificed on day 7. Angiography was performed on day 0 before blood injection and on day 7 before sacrifice. Caspase-2 (Z-VDVAD-FMK, 10 microM) inhibitor, caspase-3 (Z-DEVD-FMK, 10 microM) inhibitor, or vehicle (DMSO) were injected intrathecally from day 2 to day 6. The effects of caspase inhibitors on apoptosis and vasospasm were evaluated by angiography and transmission electron microscopy. The residual diameter of the basilar artery on day 7 in SAH dogs without treatment was 53.4+/-5.5% of the day 0 diameter. Marked damage to the endothelial cells, including apoptotic like changes, was observed in these arteries. Both caspase inhibitors prevented apoptosis in the endothelial cells. Only caspase-3 inhibitor, however, had a near-significant effect on reducing 13.3% of angiographic vasospasm. Higher doses and early treatment, as well as other more potent apoptosis inhibitors, are recommended for future studies.

Development of ultra-sensitive soybean peroxidase-based CL-ELISA for the determination of human thyroglobulin.

Serum thyroglobulin (Tg) is a main marker of thyroid cancer relapses after total or near-total thyroidectomy of patients with differentiated thyroid carcinoma. In this study, we developed a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) for detecting Tg in human serum. Soybean peroxidase (SbP) in combination with 3-(10'-phenothiazinyl)propane-1-sulfonate (SPTZ) and 4-morpholinopyridine (MORPH) and horseradish peroxidase (HRP) with p-iodophenol (PIP) were used as detection systems in the sandwich CL-ELISA. Comparison of these two systems showed that a lower detection limit (LOD) of CL-ELISA with SbP/SPTZ/MORPH was 10 times lower than for the immunoassay with HRP/PIP. The LOD value for SbP-based CL-ELISA of 0.2 ng/mL was identical to LOD value typical of CL-ELISA Immulite kit produced with alkaline phosphatase. The sensitivity of Tg CL-ELISA using SbP/SPTZ/MORPH completely satisfies the requirements of modern endocrinology. Comparative study of clinical serum specimens assayed by the SbP-based CL-ELISA (x) and Immulite kit (y) for detecting Tg showed a good correlation between these two immunoassays (y=1.15 x -0.14, R=0.99). The obtained results open good perspectives for use of SbP/SPTZ/MORPH system in the development of ultra-sensitive immunoassays.

Successful recovery from carotid terminus occlusion after mechanical embolectomy in a fully anticoagulated patient.

CASE DESCRIPTION: We describe a case of the patient with multiple contraindications for thrombolysis who underwent successful mechanical embolectomy for occlusion of the right carotid terminus. Her pre-procedural NIHSS was 16. DISCUSSION: The patient demonstrated remarkable recovery within an hour of the procedure, and this clinical improvement was sustained at followup. RESULTS: This case illustrates that mechanical embolectomy is a safe and potentially very effective intervention to treat major intracranial vessel occlusions in patients with multiple contraindications for thrombolysis.

Massive tongue swelling in refractory status epilepticus treated with high-dose pentobarbital.

INTRODUCTION: The potential causes of acquired macroglossia are extensive. The authors report two cases of subacute marked tongue swelling resulting in airway compromise in patients with refractory status epilepticus requiring prolonged pentobarbital coma. METHOD: The hospitalization histories of the reported patients were retrospectively reviewed. RESULT: The tongue swelling completely resolved in one case and significantly improved in the other after discontinuation of pentobarbital infusion or switching to phenobarbital. The authors speculate that the causes were multifarious, likely a combination of localized angioedema due to barbiturate vehicle and triggered by an initial tongue bite. CONCLUSION: Progressive tongue swelling causing airway obstruction can occur well beyond the acute phase of status epilepticus and may potentially cause problems with extubation in nontracheotomized patients.

Validity of the FOUR score coma scale in the medical intensive care unit.

OBJECTIVE: To evaluate the validity of the FOUR (Full Outline of UnResponsiveness) score (ranging from 0 to 16), a new coma scale consisting of 4 components (eye response, motor response, brainstem reflexes, and respiration pattern), when used by the staff members of a medical intensive care unit (ICU). PATIENTS AND METHODS: This interobserver agreement study prospectively evaluated the use of the FOUR score to describe the condition of 100 critically ill patients from May 1, 2007, to April 30, 2008. We compared the FOUR score to the Glasgow Coma Scale (GCS) score. For each patient, the FOUR score and the GCS score were determined by a randomly selected staff pair (nurse/fellow, nurse/consultant, fellow/fellow, or fellow/consultant). Pair wise weighted kappa values were calculated for both scores for each observer pair. RESULTS: The interrater agreement with the FOUR score was excellent (weighted kappa: eye response, 0.96; motor response, 0.97; brainstem reflex, 0.98; respiration pattern, 1.00) and similar to that obtained with the GCS (weighted kappa: eye response, 0.96; motor response, 0.97; verbal response, 0.98). In terms of the predictive power for poor neurologic outcome (Modified Rankin Scale score, 3-6), the area under the receiver operating characteristic curve was 0.75 for the FOUR score and 0.76 for the GCS score. The mortality rate for patients with the lowest FOUR score of 0 (89%) was higher than that for patients with the lowest GCS score of 3 (71%). CONCLUSION: The interrater agreement of FOUR score results was excellent among medical intensivists. In contrast to the GCS, all components of the FOUR score can be rated even when patients have undergone intubation. The FOUR score is a good predictor of the prognosis of critically ill patients and has important advantages over the GCS in the ICU setting.

Restarting anticoagulation therapy after warfarin-associated intracerebral hemorrhage.

BACKGROUND: Reinitiating warfarin sodium therapy in a patient with a recent warfarin-related intracerebral hemorrhage (WAICH) is a difficult clinical decision. Therefore, it is important to assess the outcome of resumption or discontinuation of warfarin therapy after WAICH. OBJECTIVE: To compare patients who survived an episode of WAICH and restarted warfarin therapy with a group of WAICH patients who did not resume warfarin therapy. Design, Setting, and Patients We conducted a follow-up study from November 1, 2001, through December 31, 2005, in a cohort from a single center. Long-term outcome was assessed at last clinical follow-up or via questionnaire. MAIN OUTCOME MEASURES: Recurrent WAICH and thromboembolic events. RESULTS: Fifty-two patients were discharged from the hospital after a diagnosis of WAICH. Four patients were lost to follow-up. Mean follow-up among all patients was 43 (range, 1-108) months. Of the 23 patients who restarted warfarin therapy, 1 had a recurrent nontraumatic WAICH, 2 had traumatic intracerebral hemorrhages, and 2 had major extracranial hemorrhages. Of the 25 patients who did not restart warfarin therapy, 3 had a thromboembolic stroke, 1 had a pulmonary embolus, and 1 had a distal arterial embolus. CONCLUSIONS: Restarting warfarin therapy in patients with a recent WAICH is associated with a low risk of recurrence, but patients are subjected to known, substantial risks of warfarin use. Withholding warfarin therapy is associated with a risk of thromboembolization.