Exploring a general multi-pronged activation strategy for natural product discovery in Actinomycetes.

Natural products possess significant therapeutic potential but remain underutilized despite advances in genomics and bioinformatics. While there are approaches to activate and upregulate natural product biosynthesis in both native and heterologous microbial strains, a comprehensive strategy to elicit production of natural products as well as a generalizable and efficient method to interrogate diverse native strains collection, remains lacking. Here, we explore a flexible and robust integrase-mediated multi-pronged activation approach to reliably perturb and globally trigger antibiotics production in actinobacteria. Across 54 actinobacterial strains, our approach yielded 124 distinct activator-strain combinations which consistently outperform wild type. Our approach expands accessible metabolite space by nearly two-fold and increases selected metabolite yields by up to >200-fold, enabling discovery of Gram-negative bioactivity in tetramic acid analogs. We envision these findings as a gateway towards a more streamlined, accelerated, and scalable strategy to unlock the full potential of Nature's chemical repertoire.

67 million natural product-like compound database generated via molecular language processing.

Natural products are a rich resource of bioactive compounds for valuable applications across multiple fields such as food, agriculture, and medicine. For natural product discovery, high throughput in silico screening offers a cost-effective alternative to traditional resource-heavy assay-guided exploration of structurally novel chemical space. In this data descriptor, we report a characterized database of 67,064,204 natural product-like molecules generated using a recurrent neural network trained on known natural products, demonstrating a significant 165-fold expansion in library size over the approximately 400,000 known natural products. This study highlights the potential of using deep generative models to explore novel natural product chemical space for high throughput in silico discovery.

Cost-effective hybrid long-short read assembly delineates alternative GC-rich Streptomyces hosts for natural product discovery.

With the advent of rapid automated in silico identification of biosynthetic gene clusters (BGCs), genomics presents vast opportunities to accelerate natural product (NP) discovery. However, prolific NP producers, Streptomyces, are exceptionally GC-rich (>80%) and highly repetitive within BGCs. These pose challenges in sequencing and high-quality genome assembly which are currently circumvented via intensive sequencing. Here, we outline a more cost-effective workflow using multiplex Illumina and Oxford Nanopore sequencing with hybrid long-short read assembly algorithms to generate high quality genomes. Our protocol involves subjecting long read-derived assemblies to up to 4 rounds of polishing with short reads to yield accurate BGC predictions. We successfully sequenced and assembled 8 GC-rich Streptomyces genomes whose lengths range from 7.1 to 12.1 Mb with a median N50 of 8.2 Mb. Taxonomic analysis revealed previous misrepresentation among these strains and allowed us to propose a potentially new species, Streptomyces sydneybrenneri. Further comprehensive characterization of their biosynthetic, pan-genomic and antibiotic resistance features especially for molecules derived from type I polyketide synthase (PKS) BGCs reflected their potential as alternative NP hosts. Thus, the genome assemblies and insights presented here are envisioned to serve as gateway for the scientific community to expand their avenues in NP discovery.

Resisted Inspiration: A New Technique to Aid in the Detection of CSF-Venous Fistulas.

We describe a technique termed "resisted inspiration" that could be used during myelography to decrease superior vena cava venous pressure and increase lumbar CSF pressure, potentially aiding in the detection of CSF-venous fistulas.

MRI Findings after Recent Image-Guided Lumbar Puncture: The Rate of Dural Enhancement and Subdural Collections.

BACKGROUND AND PURPOSE: The rate of abnormal intracranial MR imaging findings including subdural collections and dural enhancement after recent lumbar puncture is not known. The purpose of our study was to examine the intracranial MR imaging findings after recent image-guided lumbar puncture. MATERIALS AND METHODS: Patients who underwent contrast-enhanced MR imaging of the brain within 7 days of a CT-guided lumbar puncture between January 2014 and April 2021 were included. Contrast-enhanced MR images were reviewed for diffuse dural enhancement, morphologic findings of brain sag, dural venous sinus distension, and subdural collections. RESULTS: Of the 160 patients who met the inclusion criteria, only 6 patients (3.9%) had new diffuse dural enhancement, though none had dural enhancement when the MR imaging was within 2 days of lumbar puncture. All 6 patients with dural enhancement had small, concurrent subdural collections. Two additional patients had subdural collections, for a total of 5.2% of our population. CONCLUSIONS: Our study is the first to examine intracranial MR imaging after recent lumbar puncture and has 2 key findings: First, 5.2% of patients had small, bilateral subdural collections after recent lumbar puncture, suggesting that asymptomatic subdural collections after recent lumbar puncture are not atypical and do not require further work-up. Additionally, when MR imaging was performed within 2 days of lumbar puncture, none of our patients had diffuse dural enhancement. This argues against the commonly held practice of performing MR imaging before lumbar puncture to avoid findings of dural enhancement, and should not delay diagnostic work-up.

Spinal Compliance Curves: Preliminary Experience with a New Tool for Evaluating Suspected CSF Venous Fistulas on CT Myelography in Patients with Spontaneous Intracranial Hypotension.

BACKGROUND AND PURPOSE: Craniospinal space compliance reflects the distensibility of the spinal and intracranial CSF spaces as a system. Craniospinal space compliance has been studied in intracranial pathologies, but data are limited in assessing it in spinal CSF leak. This study describes a method to estimate craniospinal space compliance using saline infusion during CT myelography and explores the use of craniospinal space compliance and pressure-volume curves in patients with suspected cerebrospinal-venous fistula. MATERIALS AND METHODS: Patients with suspected cerebrospinal-venous fistula underwent dynamic CT myelography. During the procedure, 1- to 5-mL boluses of saline were infused, and incremental changes in CSF pressure were recorded. These data were used to plot craniospinal space compliance curves. We calculated 3 quantitative craniospinal space compliance parameters: overall compliance, compliance at opening pressure, and the pressure volume index. These variables were compared between patients with confirmed cerebrospinal-venous fistula and those with no confirmed source of CSF leak. RESULTS: Thirty-four CT myelograms in 22 patients were analyzed. Eight of 22 (36.4%) patients had confirmed cerebrospinal-venous fistulas. Bolus infusion was well-tolerated with no complications and transient headache in 2/34 (5.8%). Patients with confirmed cerebrospinal-venous fistulas had higher compliance at opening pressure and overall compliance (2.6 versus 1.8 mL/cm H20, P < .01). There was no difference in the pressure volume index (77.5 versus 54.3 mL, P = .13) between groups. CONCLUSIONS: A method of deriving craniospinal space compliance curves using saline intrathecal infusion is described. Preliminary analysis of craniospinal space compliance curves provides qualitative and quantitative information about pressure-volume dynamics and may serve as a diagnostic tool in patients with known or suspected cerebrospinal-venous fistulas.

Recent Administration of Iodinated Contrast Renders Core Infarct Estimation Inaccurate Using RAPID Software.

BACKGROUND AND PURPOSE: Automated CTP software is increasingly used for extended window emergent large-vessel occlusion to quantify core infarct. We aimed to assess whether RAPID software underestimates core infarct in patients with an extended window recently receiving IV iodinated contrast. MATERIALS AND METHODS: We reviewed a prospective, single-center data base of 271 consecutive patients who underwent CTA ± CTP for acute ischemic stroke from May 2018 through January 2019. Patients with emergent large-vessel occlusion confirmed by CTA in the extended window (>6 hours since last known well) and CTP with RAPID postprocessing were included. Two blinded raters independently assessed CT ASPECTS on NCCT performed at the time of CTP. RAPID software used relative cerebral blood flow of <30% as a surrogate for irreversible core infarct. Patients were dichotomized on the basis of receiving recent IV iodinated contrast (<8 hours before CTP) for a separate imaging study. RESULTS: The recent IV contrast and contrast-naïve cohorts comprised 23 and 15 patients, respectively. Multivariate linear regression analysis demonstrated that recent IV contrast administration was independently associated with a decrease in the RAPID core infarct estimate (proportional increase = 0.34; 95% CI, 0.12-0.96; P = .04). CONCLUSIONS: Patients who received IV iodinated contrast in proximity (<8 hours) to CTA/CTP as part of a separate imaging study had a much higher likelihood of core infarct underestimation with RAPID compared with contrast-naïve patients. Over-reliance on RAPID postprocessing for treatment disposition of patients with extended window emergent large-vessel occlusion should be avoided, particularly with recent IV contrast administration.

Long-Term Effectiveness of Direct CT-Guided Aspiration and Fenestration of Symptomatic Lumbar Facet Synovial Cysts.

BACKGROUND AND PURPOSE: Lumbar facet synovial cysts are commonly seen in facet degenerative arthropathy and may be symptomatic when narrowing the spinal canal or compressing nerve roots. The purpose of this study was to analyze the safety, effectiveness, and long-term outcomes of direct CT-guided lumbar facet synovial cyst aspiration and fenestration for symptom relief and for obviating an operation. MATERIALS AND METHODS: We retrospectively reviewed the medical records and imaging studies of 64 consecutive patients between 2006 and 2016 who underwent 85 CT-guided lumbar facet synovial cyst fenestration procedures in our department. We recorded patient demographics, lumbar facet synovial cyst imaging characteristics, presenting symptoms, change in symptoms after the procedure, and whether they underwent a subsequent operation. We also assessed long-term outcomes from the medical records and via follow-up telephone surveys with patients. RESULTS: Direct CT-guided lumbar facet synovial cyst puncture was technically successful in 98% of procedures. At first postprocedural follow-up, 86% of patients had a complete or partial symptomatic response. During a mean follow-up of 49 months, 56% of patients had partial or complete long-term relief without the need for an operation; 44% of patients underwent an operation. Patients with calcified, thick-rimmed, or low T2 signal intensity cysts were less likely to respond to the procedure and more likely to need an operation. CONCLUSIONS: CT-guided direct lumbar facet synovial cyst aspiration and fenestration procedures are safe, effective, and minimally invasive for symptomatic treatment of lumbar synovial facet cysts. This procedure obviates an operation in a substantial number of patients, even at long-term follow-up, and should be considered before surgical intervention.

[18F]-Sodium Fluoride PET MR-Based Localization and Quantification of Bone Turnover as a Biomarker for Facet Joint-Induced Disability.

Our aim was to prospectively evaluate the relationship between low back pain-related disability and quantitative measures from [18F]-sodium fluoride ([18F]-NaF) MR imaging. Six patients with facetogenic low back pain underwent dynamic [18F]-NaF PET/MR imaging. PET metrics were correlated with clinical measures and MR imaging grading of lumbar facet arthropathy. A significant positive correlation was observed between maximum facet joint uptake rate and clinical disability (P < .05). These data suggest that dynamic [18F]-NaF PET may serve as a useful biomarker for facetogenic disability.

Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology.

BACKGROUND AND PURPOSE: The entorhinal cortex, a critical gateway between the neocortex and hippocampus, is one of the earliest regions affected by Alzheimer disease-associated neurofibrillary tangle pathology. Although our prior work has automatically delineated an MR imaging-based measure of the entorhinal cortex, whether antemortem entorhinal cortex thickness is associated with postmortem tangle burden within the entorhinal cortex is still unknown. Our objective was to evaluate the relationship between antemortem MRI measures of entorhinal cortex thickness and postmortem neuropathological measures. MATERIALS AND METHODS: We evaluated 50 participants from the Rush Memory and Aging Project with antemortem structural T1-weighted MR imaging and postmortem neuropathologic assessments. Here, we focused on thickness within the entorhinal cortex as anatomically defined by our previously developed MR imaging parcellation system (Desikan-Killiany Atlas in FreeSurfer). Using linear regression, we evaluated the association between entorhinal cortex thickness and tangles and amyloid-ß load within the entorhinal cortex and medial temporal and neocortical regions. RESULTS: We found a significant relationship between antemortem entorhinal cortex thickness and entorhinal cortex (P = .006) and medial temporal lobe tangles (P = .002); we found no relationship between entorhinal cortex thickness and entorhinal cortex (P = .09) and medial temporal lobe amyloid-ß (P = .09). We also found a significant association between entorhinal cortex thickness and cortical tangles (P = .003) and amyloid-ß (P = .01). We found no relationship between parahippocampal gyrus thickness and entorhinal cortex (P = .31) and medial temporal lobe tangles (P = .051). CONCLUSIONS: Our findings indicate that entorhinal cortex-associated in vivo cortical thinning may represent a marker of postmortem medial temporal and neocortical Alzheimer disease pathology.

Multiple Procedure Payment Reduction: Health Policy Update.

Multiple Procedure Payment Reduction currently applies to multiple diagnostic imaging services administered to the same patient during the same day and entails a 50% decrease in the technical component and a 25% decrease in the professional component reimbursement. This might change with time due to further legislation, so it is important to be up-to-date on these health policy developments.

Pro-angiogenic cellular and genomic expression patterns within glioblastoma influences dynamic susceptibility weighted perfusion MRI.

AIM: To investigate whether quantitative dynamic susceptibility-weighted contrast-enhanced (DSC) perfusion magnetic resonance imaging (MRI) metrics are influenced by cellular and genomic expression patterns of glioblastoma angiogenesis. MATERIALS AND METHODS: Twenty-five stereotactic neurosurgical tissue samples were prospectively obtained from enhancing and non-enhancing tumour regions from 10 patients with treatment-naïve glioblastoma. Using monoclonal antibodies, histopathological features of angiogenesis were examined: total microvascular density, vascular morphology, and hypoxia. Angiogenic expression patterns of tissue samples were investigated using RNA microarrays. DSC perfusion MRI metrics were measured from the tissue sampling sites. MRI and histopathological variables were compared using Pearson's correlations. Microarray analysis was performed using false discovery rate (FDR) statistics. RESULTS: Thirteen enhancing and 12 non-enhancing MR image-guided tissue specimens were prospectively obtained. Enhancing tumour regions demonstrated a significant difference in DSC perfusion and histopathological metrics of angiogenesis when compared to non-enhancing regions. Four angiogenic pathways (vascular endothelial growth factor [VEGF], hypoxia inducible factor [HIF], platelet-derived growth factor [PDGF], fibroblast growth factor [FGF]; 25 individual genes) were significantly up-regulated within enhancing regions when compared to non-enhancing regions (adjusted p<0.05, FDR <0.05). A statistically significant correlation was observed between VEGF-A expression, microvascular density, microvascular morphology, and DSC perfusion MRI metrics (p<0.05). CONCLUSION: Pro-angiogenic genomic and cellular expression patterns of treatment-naïve primary glioblastoma significantly influences morphological and physiological DSC perfusion metrics suggesting that expression levels of therapeutically relevant genetic signatures can be quantified using MRI.

MR myelography for identification of spinal CSF leak in spontaneous intracranial hypotension.

BACKGROUND AND PURPOSE: CT myelography has historically been the test of choice for localization of CSF fistula in patients with spontaneous intracranial hypotension. This study evaluates the additional benefits of intrathecal gadolinium MR myelography in the detection of CSF leak. MATERIALS AND METHODS: We performed a retrospective review of patients with spontaneous intracranial hypotension who underwent CT myelography followed by intrathecal gadolinium MR myelography. All patients received intrathecal iodine and off-label gadolinium-based contrast followed by immediate CT myelography and subsequent intrathecal gadolinium MR myelography with multiplanar T1 fat-suppressed sequences. CT myelography and intrathecal gadolinium MR myelography images were reviewed by an experienced neuroradiologist to determine the presence of CSF leak. Patient records were reviewed for demographic data and adverse events following the procedure. RESULTS: Twenty-four patients met both imaging and clinical criteria for spontaneous intracranial hypotension and underwent CT myelography followed by intrathecal gadolinium MR myelography. In 3/24 patients (13%), a CSF leak was demonstrated on both CT myelography and intrathecal gadolinium MR myelography, and in 9/24 patients (38%), a CSF leak was seen on intrathecal gadolinium MR myelography (P = .011). Four of 6 leaks identified independently by intrathecal gadolinium MR myelography related to meningeal diverticula. CT myelography did not identify any leaks independently. There were no reported adverse events. CONCLUSIONS: Present data demonstrate a higher rate of leak detection with intrathecal gadolinium MR myelography when investigating CSF leaks in our cohort of patients with spontaneous intracranial hypotension. Although intrathecal gadolinium is an FDA off-label use, all patients tolerated the medication without evidence of complications. Our data suggest that intrathecal gadolinium MR myelography is a well-tolerated examination with significant benefit in the evaluation of CSF leak, particularly for patients with leak related to meningeal diverticula.

Changes in the thalamus in atypical parkinsonism detected using shape analysis and diffusion tensor imaging.

BACKGROUND AND PURPOSE: The thalamus is interconnected with the nigrostriatal system and cerebral cortex and has a major role in cognitive function and sensorimotor integration. The purpose of this study was to determine how regional involvement of the thalamus differs among Parkinson disease, progressive supranuclear palsy, and corticobasal syndrome. MATERIALS AND METHODS: Nine patients with Parkinson disease, 5 with progressive supranuclear palsy, and 6 with corticobasal syndrome underwent 3T MR imaging along with 12 matched, asymptomatic volunteers by using a protocol that included volumetric T1 and diffusion tensor imaging. Acquired data were automatically processed to delineate the margins of the motor and nonmotor thalamic nuclear groups, and measurements of ADC were calculated from the DTI data within these regions. Thalamic volume, shape, and ADC were compared across groups. RESULTS: Thalamic volume was smaller in the progressive supranuclear palsy and corticobasal syndrome groups compared with the Parkinson disease and control groups. Shape analysis revealed that this was mainly due to the diminished size of the lateral thalamus. Overall, ADC measurements were higher in the progressive supranuclear palsy group compared with both the Parkinson disease and control groups, and anatomic subgroup analysis demonstrated that these changes were greater within the motor regions of the thalamus in progressive supranuclear palsy and corticobasal degeneration. CONCLUSIONS: Reduced size and increased ADC disproportionately involve the lateral thalamus in progressive supranuclear palsy and corticobasal syndrome, consistent with selective neurodegeneration and atrophy in this region. Because these findings were not observed in Parkinson disease, they may be more specific markers of tau-related neurodegeneration.

Idiopathic thoracic spinal cord herniation: retrospective analysis supporting a mechanism of diskogenic dural injury and subsequent tamponade.

BACKGROUND AND PURPOSE: tSCH in the absence of spinal trauma or surgery is a rare disorder for which numerous mechanisms have been proposed. Here, we have conducted an analysis of images in all published reports of idiopathic tSCH and identified evidence supporting a pathogenesis in which anterior dural erosion at thoracic levels generates a CSF leak that pushes adjacent spinal tissue to tamponade the dural defect, causing progressive myelopathy. Additionally, we describe a case of tSCH in which postural headache was a significant symptom before myelopathy. This finding suggests that tSCH pathogenesis may be related to spontaneous intracranial hypotension. MATERIALS AND METHODS: Published imaging from all available prior case reports in the scientific literature was reviewed to determine whether tSCH occurred at the disk or bone level. The presence of EDF, HNP, or an osteophyte in the spinal canal was determined from review of published images. Additionally, 3 previously unreported cases from the teaching files of our department were assessed by using these criteria. RESULTS: In greater than two-thirds (47 of 67) of identified cases with published images, tSCH occurred at a disk level. When assessment was possible, EDF, HNP, and osteophytes were present in 26.8%, 30.7%, and 26.2% of cases, respectively. Overall, 52.3% of cases with published images demonstrated evidence of these abnormalities. CONCLUSIONS: Our analysis of published imaging indicates that tSCH occurs preferentially at spinal levels and with imaging findings consistent with dural injury that support the proposed etiology of this disorder.

Reducing patient radiation dose during CT-guided procedures: demonstration in spinal injections for pain.

BACKGROUND AND PURPOSE: CT guidance may improve precision for diagnostic and therapeutic spinal injections, but it can increase patient radiation dose. This study examined the impact of reducing tube current on patient radiation exposure and the technical success for these procedures, by using axial acquisitions for short scan lengths and eliminating nonessential imaging. MATERIALS AND METHODS: Our institutional review board approved retrospective analysis of records from 100 consecutive outpatients undergoing spinal injections for pain before and after the CT protocol modification to reduce radiation dose. Data collected included patient age and sex, response to injection, number of sites and spinal levels treated, injection type, performing physician, CT acquisition method, number of imaging series, tube current, scan length, and DLP. RESULTS: Image contrast was reduced with the low-dose protocol, but this did not affect technical success or immediate pain relief. Mean DLP for all procedures decreased from 1458 ± 1022 to 199 ± 101 mGy · cm (P < .001). The range of radiologist-dependent DLP per procedure also was reduced significantly with the modified protocol. Selective nerve root blocks, lumbar injections, multiple injection sites, and the lack of prior imaging were each associated with a slightly higher DLP (<50 mGy · cm). CONCLUSIONS: Radiation to patients undergoing CT-guided spinal injections can be decreased significantly without affecting outcome by reducing tube current, using axial acquisitions for short scan lengths, and eliminating nonessential imaging guidance. These measures also decrease variability in radiation doses between different practitioners and should be useful for other CT-guided procedures in radiology.

Intraosseous CSF fistula in a patient with Gorham disease resulting in intracranial hypotension.

A 7-year-old girl with a history of headaches and Gorham disease was surgically treated in infancy for Chiari I malformation. Subsequent investigation revealed that her cerebellar tonsillar ectopia was due to a long-standing spinal CSF-lymphatic fistula causing intracranial hypotension. Percutaneous fistula closure was performed several times, resulting in transient symptomatic improvement.

MR imaging of partially thrombosed cerebral aneurysms: characteristics and evolution.

BACKGROUND AND PURPOSE: A comprehensive evaluation of aneurysmal morphometry requires appreciation of both the vascular lumen and the intraluminal thrombus. MR imaging methods can both evaluate the lumen and directly image the vessel wall. We investigated the ability of T1-weighted, T2-weighted, and steady-state MR imaging techniques to delineate thrombus morphology and reveal changes with time. MATERIALS AND METHODS: Nine patients with fusiform basilar or intracranial vertebral artery aneurysms that contained intraluminal thrombus were studied with MR imaging. All patients underwent at least 2 imaging sessions, which were separated by 4-22 months. Analysis of signal intensity to determine the mean signal intensity from thrombus, blood, CSF, and brain in matched regions was performed. Aneurysm maximal diameter and cross-sectional area were determined with and without thrombus. RESULTS: Thrombus was identified on all image sequences, and its general appearance was consistent between imaging sessions. Thrombus produced the highest and most consistent signal intensities with T1-weighted and steady-state techniques, though the latter showed superior contrast between luminal blood and thrombus. Heterogeneity within clot was evident in 4/9 of patients, with peripheral hyperintensity being a common feature. CONCLUSIONS: Steady-state imaging was found to be superior to T1- and T2-weighted imaging for delineating and characterizing intraluminal thrombus within aneurysms. The imaging characteristics of intraluminal thrombus proved to be very consistent for long periods. Assessment of overall aneurysm size, including thrombosed portions, permits more accurate evaluation of aneurysm growth and concomitantly may permit more informed clinical decision-making with regard to the timing and need for aneurysm treatment.

Blood-brain barrier permeability assessed by perfusion CT predicts symptomatic hemorrhagic transformation and malignant edema in acute ischemic stroke.

BACKGROUND AND PURPOSE: SHT and ME are feared complications in patients with acute ischemic stroke. They occur >10 times more frequently in tPA-treated versus placebo-treated patients. Our goal was to evaluate the sensitivity and specificity of admission BBBP measurements derived from PCT in predicting the development of SHT and ME in patients with acute ischemic stroke. MATERIALS AND METHODS: We retrospectively analyzed a dataset consisting of 32 consecutive patients with acute ischemic stroke with appropriate admission and follow-up imaging. We calculated admission BBBP by using delayed-acquisition PCT data and the Patlak model. Collateral flow was assessed on the admission CTA, while recanalization and reperfusion were assessed on the follow-up CTA and PCT, respectively. SHT and ME were defined according to ECASS III criteria. Clinical data were obtained from chart review. In our univariate and forward selection-based multivariate analysis for predictors of SHT and ME, we incorporated both clinical and imaging variables, including age, admission NIHSS score, admission blood glucose level, admission blood pressure, time from symptom onset to scanning, treatment type, admission PCT-defined infarct volume, admission BBBP, collateral flow, recanalization, and reperfusion. Optimal sensitivity and specificity for SHT and ME prediction were calculated by using ROC analysis. RESULTS: In our sample of 32 patients, 3 developed SHT and 3 developed ME. Of the 3 patients with SHT, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device; of the 3 patients with ME, 2 received IV tPA, while 1 received IA tPA and treatment with the Merci device. Admission BBBP measurements above the threshold were 100% sensitive and 79% specific in predicting SHT and ME. Furthermore, all patients with SHT and ME--and only those with SHT and ME--had admission BBBP measurements above the threshold, were older than 65 years of age, and received tPA. Admission BBBP, age, and tPA were the independent predictors of SHT and ME in our forward selection-based multivariate analysis. Of these 3 variables, only BBBP measurements and age were known before making the decision of administering tPA and thus are clinically meaningful. CONCLUSIONS: Admission BBBP, a pretreatment measurement, was 100% sensitive and 79% specific in predicting SHT and ME.