Fixed-dose prothrombin complex concentrate for emergent warfarin reversal among patients with intracranial hemorrhage.

INTRODUCTION: Four-factor prothrombin complex concentrate (4PCC) is the preferred reversal agent for warfarin reversal, although the ideal dose is unknown. Fixed-dose 4PCC offers simplified dosing compared to standard-dosing algorithms with potentially lower risks of thromboembolic complications given lower doses are typically utilized. METHODS: Retrospective, observational, multicentered, pre- post- study of patients who received 4PCC for warfarin reversal among four hospitals within the same regional health system. Standard-dose patients received variable doses ranging from 25 to 50 units/kg based on total body weight and initial INR and fixed-dose patients received 2000 units. The primary outcome was achievement of a target INR ≤ 1.4 on the first post-4PCC INR result. RESULTS: After exclusions, 48 and 42 patients were analyzed in the standard-dose and fixed-dose groups, respectively. There was no difference in the ability to achieve a target INR of ≤1.4 (82.6% vs 81.5%, p = 0.14). Both groups received the same median dose of 2000 units, although fixed-dose patients actually received a higher weight-based dose than standard-dose patients (27 units/kg vs 24.5 units/kg). CONCLUSION: A fixed-dose 4PCC regimen of 2000 units among patients with ICH was as effective as standard-dose 4PCC for INR reversal among patients with ICH. However, fixed-doses of 2000 units at times exceeded standard 4PCC doses which may be contradictory to the goals of fixed-dose 4PCC for warfarin reversal.

A new inflammatory parameter can predict delayed intracranial hemorrhage following ventriculoperitoneal shunt.

Delayed intracerebral hemorrhage (DICH) secondary to ventriculoperitoneal (VP) shunt is considered to be a potentially severe event. This study aimed to investigate the association between a ratio of postoperative neutrophil-to-lymphocyte ratio to preoperative neutrophil-to-lymphocyte ratio (NLRR) and DICH secondary to VP shunt. We performed a retrospective review of patients who underwent VP shunt between January 2016 and June 2020. Multivariable logistic regression analysis was used to assess the association of DICH and NLRR. Then patients were divided into two groups according to the optimal cut-off point of NLRR, propensity score matching (PSM) method was performed to reconfirm the result. A total of 130 patients were enrolled and DICH occurred in 29 patients. Elevated NLRR and history of craniotomy were independent risk factors for DICH secondary to VP shunt. The optimal cut off point of NLRR was 2.05, and the sensitivity was 89.7%, the specificity was 63.4%. Patients with NLRR > 2.05 had much higher incidence of DICH (40.6% vs 4.5%). Our finding suggested that DICH following VP shunt was not a rare complication and elevated NLRR could independently predict DICH. Inflammatory responses might play an important role in the development of DICH following VP shunt.

Callosal Diffusion-Restriction in Patients with Intracranial Hemorrhage.

OBJECTIVE: We aim to report the incidence and clinical characteristics of patients who were found to have diffusion restricting lesions of the corpus callosum (CC) on Diffusion-weighted imaging (DWI) on magnetic resonance imaging (MRI) following intracranial hemorrhage (ICH). DESIGN/METHODS: A retrospective cross-sectional analysis was performed of medical records of all adult patients admitted to a single tertiary center with a primary diagnosis of ICH and received nicardipine infusion over a 2-year period. Patients without MRI brain available or patients who underwent digital subtraction angiography (DSA) prior to MRI were excluded. ICH and intraventricular hemorrhage (IVH) volumes and scores were calculated. MRI brain scans were evaluated for presence and locations of DWI lesions. RESULTS: Among 162 patients who met inclusion criteria, 6 patients (4%, median age 53, range 37-71, 100% male, 33% white) were found to have DWI lesions in the CC with a median ICH volume of 17ml (range 1-105ml). The ICH locations were lobar (n=3), deep (n=2) and cerebellum (n=1). All patients (100%) had intraventricular hemorrhage (IVH) with median IVH volume of 25ml (range 2.7-55ml). Four patients were on levetiracetam. No identifiable infections or metabolic abnormalities were found among these patients. All but one patient had normal DSA. Follow up MRI was only available in one patient and showed no reversibility at 14 days. CONCLUSION: Although rare, diffusion restricting corpus callosum lesions can be seen in patients with ICH, especially in patients with IVH. The etiology and clinical significance of these lesions remains unknown and warrant further research.

Head Computed Tomography Scans in Elderly Patients with Low Velocity Head trauma after a Fall.

BACKGROUND: Recommendations for a head computed tomography (CT) scan in elderly patients without a loss of consciousness after a traumatic brain injury and without neurological findings on admission and who are not taking oral anticoagulant therapy, are discordant. OBJECTIVES: To determine variables associated with intracranial hemorrhage (ICH) and the need for neurosurgery in elderly patients after low velocity head trauma. METHODS: In a regional hospital, we retrospectively selected 206 consecutive patients aged ≥ 65 years with head CT scans ordered in the emergency department because of low velocity head trauma. Outcome variables were an ICH and neurological surgery. Independent variables included age, sex, disability, neurological findings, facial fractures, mental status, headache, head sutures, loss of consciousness, and anticoagulation therapy. RESULTS: Fourteen patients presented with ICH (6.8%, 3.8-11.1%) and three (1.5%, 0.3-4.2%) with a neurosurgical procedure. One patient with a coma (0.5, 0.0-2.7) died 2 hours after presentation. All patients who required surgery or died had neurological findings. Reducing head CT scans by 97.1% (93.8-98.9%) would not have missed any patient with possible surgical utility. Twelve of the 14 patients (85.7%) with an ICH had neurological findings, post-trauma loss of consciousness or a facial fracture were not present in 83.5% (95% confidence interval 77.7-88.3) of the cohort. CONCLUSIONS: None of our patients with neurological findings required neurosurgery. Careful palpation of the facial bones to identify facial fractures might aid in the decision whether to perform a head CT scan.

Consecutive and temporally distant perseverations after right brain damage: A prospective study.

Objective: Right brain-damaged patients may show omissions and/or additional marks in target cancellation. The latter is classified as perseverative behavior and has been attributed to defective response inhibition or attentional disengagement deficit. This study aimed at (a) verifying that consecutive (immediate) and return (temporally distant) motor perseverations could be due to different mechanisms; (b) investigating the relationships among different types of perseveration (e.g., consecutive, return, scribble), spatial neglect and the impairment in specific components of executive functioning. Method: Seventeen right brain-damaged patients underwent letter, star, bell, and apple cancellation tasks. A global index for each type of perseveration found and Mean Position of Hits, as a neglect index, were calculated. The following components of executive functioning were evaluated: motor programming (Frontal Assessment Battery [FAB] subtest), inhibitory control FAB, interference sensitivity (FAB and Stroop color-word interference test), set-shifting (Weigl sorting test, Phonemic/semantic alternate fluencies), and working memory (Backward Digit span). Results: Ten patients out of 17 showed some degree of perseveration. Regularized linear regression analyses demonstrated that interference sensitivity and Stroop test performances were related to return perseverations and backward digit to scribble ones. No significant relationships were found for consecutive perseverations and between neglect and any type of perseverations. Conclusions: The present study showed that return perseverations might have a distinct etiology from consecutive ones, being related to an inability to update and shift between action programs according to the visual stimuli. A finer classification of perseverations could help in unveiling the neuropsychological mechanisms underlying each type of behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Chronic and End-Stage Kidney Disease in the Neurological Intensive Care Unit.

Patients with renal disease have increased rates of admission to the neurological intensive care unit related to overlapping risk factors for renal and cerebrovascular disease as well as unique risks associated with renal dysfunction alone. Management of acute neurological injury in these patients requires individualized attention to diagnostic and management factors as they relate to coagulopathy, disorders of immune function, encephalopathy and renal replacement modalities. Careful consideration of these brain-kidney interactions is necessary to optimize care for this special patient population and improve neurological and renal outcomes.

Symptomatic Intracranial Hemorrhage after Dural Tear in Spinal Surgery-A Series of 10 Cases and Review of the Literature.

OBJECTIVE: Intracranial hemorrhage (IH) after spinal surgery is a rare but potentially life-threatening complication. Knowledge of predisposing factors and typical clinical signs is essential for early recognition, helping to prevent an unfavorable outcome. METHODS: A retrospective analysis was performed of patients with IH after spinal surgery treated in our institution between 2012 and 2018. The literature dealing with IH complicating spinal surgery was reviewed. RESULTS: Our investigation found 10 patients with IH (6 female and 4 male). To the best of our knowledge, this is the largest series reported so far. The assumable incidence of IH after spinal surgery in our population was 0.0657%. Durotomy was noticed in 6 patients, all of whom were treated according to a local standard protocol. In 4 patients, the dural tear was occult. Hemorrhage occurred mostly in the cerebellar compartment. Eight of 10 patients had long-standing arterial hypertension, which seems to be a risk factor (hazard ratio, 1.58). Five patients were treated conservatively, whereas 3 required a cerebrospinal fluid (CSF) diversion procedure. In 2 patients, revision surgery with duraplasty was necessary. Seven patients were discharged with little to no neurologic symptoms, and 3 had significant deterioration. One patient died because of brainstem herniation. Review of the literature identified 54 articles with 72 patients with IH complicating spinal surgery. CONCLUSIONS: Patients with intraoperative CSF loss should be kept under close supervision postoperatively. After opening of the dura, a watertight closure should be attempted. The use of subfascial suction drainage in cases of a dural tear as well as preexistent arterial hypertension seems to be a risk factor for the development of IH. Intracranial bleeding must be considered in every patient with unexplained neurologic deterioration after spinal surgery and should be ruled out by cranial imaging. To ensure early recognition and prevent an unfavorable outcome, a high index of suspicion is required, especially in revision spinal surgery. The treatment is specific to the extent and location of the IH, thus dictating the outcome. In most patients, conservative treatment led to a good outcome. CSF diversion measures may be necessary in patients with compression or obstruction of the fourth ventricle. Large hematomas with mass effect may require decompressive surgery.

Monitoring of patients with brainstem hemorrhage: A simultaneous study of quantitative electroencephalography and transcranial Doppler.

OBJECTIVE: To explore whether quantitative electroencephalography (QEEG) and transcranial Doppler (TCD) can be used to evaluate patients with acute severe brainstem hemorrhage (ASBH). METHODS: We prospectively enrolled patients with ASBH and assessed their mortality at the 90-day follow-up. The patients' demographic data, serological data, and clinical factors were recorded. Quantitative brain function monitoring was performed using a TCD-QEEG recording system attached to the patient's bedside. RESULTS: Thirty-one patients (55.3 ± 10.6 years; 17 men) were studied. Mortality at 90 days was at 61.3%. There was no significant difference in TCD-related parameters between the survival group and the death group (p > 0.05). Among the QEEG-related indexes, only the (delta + theta)/(alpha + beta) ratio (DTABR) (odds ratio 11.555, 95%confidence interval 1.413-94.503, p = 0.022) was an independent predictor of clinical outcome; the area under the ROC curve of DTABR was 0.921, cut-off point was 3.88, sensitivity was 79%, and specificity was 100%. CONCLUSIONS: In patients with ASBH, QEEG can effectively inform the clinical prognosis regarding 90-day mortality, while TCD cannot. SIGNIFICANCE: QEEG shows promise for informing the mortality prognosis of patients with ASBH.

Does Endovascular Treatment with Curative Intention Have Benefits for Treating High-Grade Arteriovenous Malformation versus Radiosurgery? Efficacy, Safety, and Cost-Effectiveness Analysis.

BACKGROUND: The treatment of high-grade arteriovenous malformations (AVMs) remains challenging. Microsurgery provides a rapid and complete occlusion compared with other options but is associated with undesirable morbidity and mortality. The aim of this study was to compare the occlusion rates, incidence of unfavorable outcomes, and cost-effectiveness of embolization and stereotactic radiosurgery (SRS) as a curative treatment for high-grade AVMs. METHODS: A retrospective series of 57 consecutive patients with high-grade AVM treated with embolization or SRS, with the aim of achieving complete occlusion, was analyzed. Demographic, clinical, and angioarchitectonic variables were collected. Both treatments were compared for the occlusion rate and procedure-related complications. In addition, a cost-effectiveness analysis was performed. RESULTS: Thirty patients (52.6%) were men and 27 (47.4%) were women (mean age, 39 years). AVMs were unruptured in 43 patients (75.4%), and ruptured in 14 patients (24.6%). The presence of deep venous drainage, nidus volume, perforated arterial supply, and eloquent localization was more frequent in the SRS group. Complications such as hemorrhage or worsening of previous seizures were more frequent in the embolization group. No significant differences were observed in the occlusion rates or in the time necessary to achieve occlusion between the groups. The incremental cost-effectiveness ratio for endovascular treatment versus SRS was $53.279. CONCLUSIONS: Both techniques achieved similar occlusion rates, but SRS carried a lower risk of complications. Staged embolization may be associated with a greater risk of hemorrhage, whereas SRS was shown to have a better cost-effectiveness ratio. These results support SRS as a better treatment option for high-grade AVMs.

Clinical and radiological outcomes in relation with the anatomical orientation of clipped middle cerebral artery bifurcation aneurysms.

BACKGROUND: The middle cerebral artery (MCA) bifurcation represents the most frequent location for intracranial aneurysms. Often, the aneurysmal dome can hide the origin of perforating arteries from the M1 segment during the surgical clipping causing ischemic lesions and worse clinical outcome. The aim of this paper is to analyze the association between the orientation of the aneurysm sac and the clinical and radiological outcomes after surgical clipping. METHODS: Data from 50 MCA bifurcation clipped aneurysms in 47 patients were collected retrospectively. Three different groups were identified according to the aneurysmal sac orientation: anterior-inferior, posterior and superior. A possible association between the aneurysmal sac projection and the outcome was searched through a univariable logistic regression analysis. RESULTS: Statistical analysis showed significant correlation between the radiologic evidence of post-operative ischemia in the posterior group (p = 0.046, RR = 1.65) and an increased risk in the superior orientation group (p = 0.145, RR = 1.38). The anterior-inferior group was, instead, significantly associated with no evidence of radiologic ischemia (p = 0.0019, RR = 0.58). CONCLUSION: The orientation of the aneurysmal dome and sac represents a fundamental feature to be considered during the surgical clipping of the MCA aneurysms. Indeed, its posterior and superior projection is associated with a higher incidence of radiologic ischemic lesions due to the origin of perforating arteries from M1 segment behind the aneurysmal sac. The anterior-inferior orientation, on the contrary, is associated with a lower risk.

Effect of tranexamic acid on intracranial haemorrhage and infarction in patients with traumatic brain injury: a pre-planned substudy in a sample of CRASH-3 trial patients.

BACKGROUND: Early tranexamic acid (TXA) treatment reduces head injury deaths after traumatic brain injury (TBI). We used brain scans that were acquired as part of the routine clinical practice during the CRASH-3 trial (before unblinding) to examine the mechanism of action of TXA in TBI. Specifically, we explored the potential effects of TXA on intracranial haemorrhage and infarction. METHODS: This is a prospective substudy nested within the CRASH-3 trial, a randomised placebo-controlled trial of TXA (loading dose 1 g over 10 min, then 1 g infusion over 8 hours) in patients with isolated head injury. CRASH-3 trial patients were recruited between July 2012 and January 2019. Participants in the current substudy were a subset of trial patients enrolled at 10 hospitals in the UK and 4 in Malaysia, who had at least one CT head scan performed as part of the routine clinical practice within 28 days of randomisation. The primary outcome was the volume of intraparenchymal haemorrhage (ie, contusion) measured on a CT scan done after randomisation. Secondary outcomes were progressive intracranial haemorrhage (post-randomisation CT shows >25% of volume seen on pre-randomisation CT), new intracranial haemorrhage (any haemorrhage seen on post-randomisation CT but not on pre-randomisation CT), cerebral infarction (any infarction seen on any type of brain scan done post-randomisation, excluding infarction seen pre-randomisation) and intracranial haemorrhage volume (intraparenchymal + intraventricular + subdural + epidural) in those who underwent neurosurgical haemorrhage evacuation. We planned to conduct sensitivity analyses excluding patients who were severely injured at baseline. Dichotomous outcomes were analysed using relative risks (RR) or hazard ratios (HR), and continuous outcomes using a linear mixed model. RESULTS: 1767 patients were included in this substudy. One-third of the patients had a baseline GCS (Glasgow Coma Score) of 3 (n=579) and 24% had unilateral or bilateral unreactive pupils. 46% of patients were scanned pre-randomisation and post-randomisation (n=812/1767), 19% were scanned only pre-randomisation (n=341/1767) and 35% were scanned only post-randomisation (n=614/1767). In all patients, there was no evidence that TXA prevents intraparenchymal haemorrhage expansion (estimate=1.09, 95% CI 0.81 to 1.45) or intracranial haemorrhage expansion in patients who underwent neurosurgical haemorrhage evacuation (n=363) (estimate=0.79, 95% CI 0.57 to 1.11). In patients scanned pre-randomisation and post-randomisation (n=812), there was no evidence that TXA reduces progressive haemorrhage (adjusted RR=0.91, 95% CI 0.74 to 1.13) and new haemorrhage (adjusted RR=0.85, 95% CI 0.72 to 1.01). When patients with unreactive pupils at baseline were excluded, there was evidence that TXA prevents new haemorrhage (adjusted RR=0.80, 95% CI 0.66 to 0.98). In patients scanned post-randomisation (n=1431), there was no evidence of an increase in infarction with TXA (adjusted HR=1.28, 95% CI 0.93 to 1.76). A larger proportion of patients without (vs with) a post-randomisation scan died from head injury (38% vs 19%: RR=1.97, 95% CI 1.66 to 2.34, p<0.0001). CONCLUSION: TXA may prevent new haemorrhage in patients with reactive pupils at baseline. This is consistent with the results of the CRASH-3 trial which found that TXA reduced head injury death in patients with at least one reactive pupil at baseline. However, the large number of patients without post-randomisation scans and the possibility that the availability of scan data depends on whether a patient received TXA, challenges the validity of inferences made using routinely collected scan data. This study highlights the limitations of using routinely collected scan data to examine the effects of TBI treatments. TRIAL REGISTRATION NUMBER: ISRCTN15088122.

Mechanisms of Cerebral Microvascular Disease in Chronic Kidney Disease.

Numerous studies report linkage between chronic kidney disease (CKD) and cerebrovascular disease. This association has been particularly strong for cerebral small vessel disease. Significant findings have emerged from studies ranging from case reports, small case series, and larger cohort investigations. The latter show a relationship between declining renal function, microvascular disease, and cognitive impairment. One troubling aspect has been the relative paucity of mechanistic investigations addressing the CKD-cerebrovascular disease linkage. Nevertheless, mechanistic observations have begun to emerge, showing cerebral microhemorrhage development in animal models of CKD independent of hypertension, an important co-morbidity in clinical studies. Initial cell culture studies show endothelial monolayer disruption by CKD serum, consistent with blood-brain barrier injury. It is noteworthy that CKD serum is known to contain multiple plausible mediators of microvascular injury. Further studies are on the horizon to address the critical question of potential linkage of renal dysfunction with vascular cognitive impairment.

Bilateral Cerebral Hyperperfusion Syndrome Following Carotid Artery Stenting in Stroke - A Case Report.

BACKGROUND: Revascularization of the symptomatic carotid artery is performed with endarterectomy or stenting. Rarely, patients may develop cerebral hyperperfusion syndrome (CHS) following revascularization. This usually occurs in the cerebral hemisphere ipsilateral to revascularized carotid stenosis. CHS rarely involves the contralateral hemisphere. OBJECTIVE: To present a case of CHS involving bilateral cerebral hemispheres following carotid artery stenting in acute ischemic stroke. CASE DESCRIPTION: A 66-year-old woman presented with right side weakness and aphasia. National Institutes of Health stroke scale score was 27. CT angiogram/perfusion showed high grade left internal carotid artery (ICA) stenosis, left middle cerebral artery (MCA) occlusion, and increased time to peak in left MCA territory. She underwent mechanical thrombectomy with complete reperfusion. Left carotid artery stenting was performed for 85% cervical ICA stenosis with thrombus. She neurologically deteriorated and required intubation after the procedure. Follow-up CT perfusion at 18 hours after thrombectomy showed increased cerebral blood flow and early time to peak in bilateral MCA territories. CT head showed parenchymal hematoma in the left subcortical area with extension to the ventricle. Fluid-attenuated inversion recovery MRI on day 4 showed diffuse white matter hyperintensities in the entire right hemisphere, and left temporal and frontal lobes suggestive of vasogenic edema. CONCLUSION: This case highlights bilateral cerebral hyperperfusion syndrome characterized by neurological worsening, imaging findings of parenchymal hemorrhage, vasogenic edema and increased cerebral blood flow without any new ischemic lesions. The involvement of bilateral hemispheres in the absence of significant contralateral carotid stenosis is unique in this case.

Impact of Intracranial Pressure Monitor-Guided Therapy on Neurologic Outcome After Spontaneous Nontraumatic Intracranial Hemorrhage.

OBJECTIVES: Intracranial pressure (ICP) monitors have been used in some patients with spontaneous intracranial hemorrhage (ICH) to provide information to guide treatment without clear evidence for its use in this population. We assessed the impact of ICP monitor placement, including external ventricular drains and intraparenchymal monitors, on neurologic outcome in this population. MATERIALS AND METHODS: In this secondary analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation III trial, the primary outcome was poor outcome (modified Rankin Scale score 4-6) and the secondary outcome was death, at 1 year from onset. We compared outcomes in patients with or without an ICP monitor using unadjusted and adjusted logistic regression models. The analyses were repeated in a balanced cohort created with propensity score matching. RESULTS: Seventy patients underwent ICP monitor placement and 424 did not. Poor outcome was seen in 77.1% of patients in the ICP-monitor subgroup compared with 53.8% in the no-monitor subgroup (p<0.001). Of patients in the ICP-monitor subgroup, 31.4% died, compared with 21.0% in the no-monitor subgroup (p=0.053). In multivariate models, ICP monitor placement was associated with a >2-fold greater risk of poor outcome (odds ratio 2.76, 95% CI 1.30-5.85, p=0.008), but not with death (p=0.652). Our findings remained consistent in the propensity score-matched cohort. CONCLUSION: These results question whether ICP monitor-guided therapy in patients with spontaneous nontraumatic ICH improves outcome. Further work is required to define the causal pathway and improve identification of patients that might benefit from invasive ICP monitoring.

Characteristics and Outcomes of Patients 80 Years and Older Hospitalized With Coronavirus Disease 2019 (COVID-19).

Patients older than 65 years hospitalized with COVID-19 have higher rates of intensive care unit admission and death when compared with younger patients. Cardiovascular conditions associated with COVID-19 include myocardial injury, acute myocarditis, cardiac arrhythmias, cardiomyopathies, cardiogenic shock, thromboembolic disease, and cardiac arrest. Few studies have described the clinical course of those at the upper extreme of age. We characterize the clinical course and outcomes of 73 patients with 80 years of age or older hospitalized at an academic center between March 15 and May 13, 2020. These patients had multiple comorbidities and often presented with atypical clinical findings such as altered sensorium, generalized weakness and falls. Cardiovascular manifestations observed at the time of presentation included new arrhythmia in 7/73 (10%), stroke/intracranial hemorrhage in 5/73 (7%), and elevated troponin in 27/58 (47%). During hospitalization, 38% of all patients required intensive care, 13% developed a need for renal replacement therapy, and 32% required vasopressor support. All-cause mortality was 47% and was highest in patients who were ever in intensive care (71%), required mechanical ventilation (83%), or vasopressors (91%), or developed a need for renal replacement therapy (100%). Patients older than 80 years old with COVID-19 have multiple unique risk factors which can be associated with increased cardiovascular involvement and death.

[Key problems of nutritional support in patients with ischemic stroke and nontraumatic intracranial hemorrhage].

The presented systematic literature review is focused on the main problems of nutritional support as a complex treatment of patients with ischemic stroke and non-traumatic intracranial hemorrhage. Nutritional support is one of the main points of intensive care in patients with stroke with a neurological deficit. Conducting rational nutritional therapy in this category of patients requires taking into account the characteristics of both the main and concomitant pathologies, in particular diabetes mellitus, cardiovascular pathology. Deep analysis of recent data shows that a number of questions for assessing the severity of hypermetabolic syndrome and differentiated correction of protein and energy metabolic disorders in various clinical forms (ischemic, hemorrhagic) of cerebral stroke with or without comorbid pathology has not been studied enough and are waiting to be resolved. The search continues for new techniques and optimal algorithms for nutritional support with the subsequent development of appropriate clinical recommendations for use in this category of patients. Controversial issues remain regarding the timing of the start of nutritional support, protein and energy requirements, ways to control the adequacy and effectiveness of clinical nutrition.

Multi-centered evaluation of a novel fixed-dose four-factor prothrombin complex concentrate protocol for warfarin reversal.

INTRODUCTION: Previous studies have shown fixed-dose 4PCC to be as effective as standard-dose 4PCC for warfarin reversal. However, certain patient populations such as those with high total body weight (TBW) or elevated baseline INR may be at increased risk for treatment failure. The purpose of this study was to validate the efficacy of a novel fixed-dose 4PCC protocol for warfarin reversal. METHODS: This was a multi-centered observational comparison of patients who received 4PCC for warfarin reversal. Fixed-dose patients received 1500 units of 4PCC with the dose increased to 2000 units in patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or for intracranial hemorrhage (ICH). Standard-dosing followed manufacturer recommendations. The primary outcome was achievement of a post-4PCC INR of ≤1.4. Secondary outcomes included target INR achievement among patients with a baseline INR ≥ 7.5, a TBW ≥ 100 kg, or neurologic bleeding indications; hospital length of stay; cost of therapy; and thromboembolic complications. RESULTS: A total of 116 patients were included in the standard-dose group and 75 in the fixed-dose group. There was no difference in the primary outcome (65% vs 57%, p = 0.32). There was no difference in secondary outcomes aside from cost of therapy in which fixed-dose 4PCC was less expensive than standard-dose 4PCC. CONCLUSION: A fixed-dose 4PCC regimen for warfarin reversal of 1500 units, with an increased dose of 2000 units for select patients, is as effective as standard-dose 4PCC for INR reversal.

Admission Blood Pressure in Relation to Clinical Outcomes and Successful Reperfusion After Endovascular Stroke Treatment.

BACKGROUND AND PURPOSE: Optimal blood pressure (BP) targets before endovascular treatment (EVT) for acute ischemic stroke are unknown. We aimed to assess the relation between admission BP and clinical outcomes and successful reperfusion after EVT. METHODS: We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands) Registry, an observational, prospective, nationwide cohort study of patients with ischemic stroke treated with EVT in routine clinical practice in the Netherlands. Baseline systolic BP (SBP) and diastolic BP (DBP) were recorded on admission. The primary outcome was the score on the modified Rankin Scale at 90 days. Secondary outcomes included successful reperfusion (extended Thrombolysis in Cerebral Infarction score 2B-3), symptomatic intracranial hemorrhage, and 90-day mortality. Multivariable logistic and linear regression were used to assess the associations of SBP and DBP with outcomes. The relations between BPs and outcomes were tested for nonlinearity. Parameter estimates were calculated per 10 mm Hg increase or decrease in BP. RESULTS: We included 3180 patients treated with EVT between March 2014 and November 2017. The relations between admission SBP and DBP with 90-day modified Rankin Scale scores and mortality were J-shaped, with inflection points around 150 and 81 mm Hg, respectively. An increase in SBP above 150 mm Hg was associated with poor functional outcome (adjusted common odds ratio, 1.09 [95% CI, 1.04-1.15]) and mortality at 90 days (adjusted odds ratio, 1.09 [95% CI, 1.03-1.16]). Following linear relationships, higher SBP was associated with a lower probability of successful reperfusion (adjusted odds ratio, 0.97 [95% CI, 0.94-0.99]) and with the occurrence of symptomatic intracranial hemorrhage (adjusted odds ratio, 1.06 [95% CI, 0.99-1.13]). Results for DBP were largely similar. CONCLUSIONS: In patients with acute ischemic stroke treated with EVT, higher admission BP is associated with lower probability of successful reperfusion and with poor clinical outcomes. Further research is needed to investigate whether these patients benefit from BP reduction before EVT.

High Admission Glucose Is Associated With Poor Outcome After Endovascular Treatment for Ischemic Stroke.

BACKGROUND AND PURPOSE: High-serum glucose on admission is a predictor of poor outcome after stroke. We assessed the association between glucose concentrations and clinical outcomes in patients who underwent endovascular treatment. METHODS: From the MR CLEAN Registry, we selected consecutive adult patients with a large vessel occlusion of the anterior circulation who underwent endovascular treatment and for whom admission glucose levels were available. We assessed the association between admission glucose and the modified Rankin Scale score at 90 days, symptomatic intracranial hemorrhage and successful reperfusion rates. Hyperglycemia was defined as admission glucose ≥7.8 mmol/L. We evaluated the association between glucose and modified Rankin Scale using multivariable ordinal logistic regression and assessed whether successful reperfusion (extended Thrombolysis in Cerebral Infarction 2b-3) modified this association. RESULTS: Of 3637 patients in the MR CLEAN Registry, 2908 were included. Median admission glucose concentration was 6.8 mmol/L (interquartile range, 5.9-8.1) and 882 patients (30%) had hyperglycemia. Hyperglycemia on admission was associated with a shift toward worse functional outcome (median modified Rankin Scale score 4 versus 3; adjusted common odds ratio, 1.69 [95% CI, 1.44-1.99]), increased mortality (40% versus 23%; adjusted odds ratio, 1.95 [95% CI, 1.60-2.38]), and an increased risk of symptomatic intracranial hemorrhage (9% versus 5%; adjusted odds ratio, 1.94 [95% CI, 1.41-2.66]) compared with nonhyperglycemic patients. The association between admission glucose levels and poor outcome (modified Rankin Scale score 3-6) was J-shaped. Hyperglycemia was not associated with the rate of successful reperfusion nor did successful reperfusion modify the association between glucose and functional outcome. CONCLUSIONS: Increased admission glucose is associated with poor functional outcome and an increased risk of symptomatic intracranial hemorrhage after endovascular treatment.