Recommended Resting-State fMRI Acquisition and Preprocessing Steps for Preoperative Mapping of Language and Motor and Visual Areas in Adult and Pediatric Patients with Brain Tumors and Epilepsy.

Resting-state (rs) fMRI has been shown to be useful for preoperative mapping of functional areas in patients with brain tumors and epilepsy. However, its lack of standardization limits its widespread use and hinders multicenter collaboration. The American Society of Functional Neuroradiology, American Society of Pediatric Neuroradiology, and the American Society of Neuroradiology Functional and Diffusion MR Imaging Study Group recommend specific rs-fMRI acquisition approaches and preprocessing steps that will further support rs-fMRI for future clinical use. A task force with expertise in fMRI from multiple institutions provided recommendations on the rs-fMRI steps needed for mapping of language, motor, and visual areas in adult and pediatric patients with brain tumor and epilepsy. These were based on an extensive literature review and expert consensus.Following rs-fMRI acquisition parameters are recommended: minimum 6-minute acquisition time; scan with eyes open with fixation; obtain rs-fMRI before both task-based fMRI and contrast administration; temporal resolution of ≤2 seconds; scanner field strength of 3T or higher. The following rs-fMRI preprocessing steps and parameters are recommended: motion correction (seed-based correlation analysis [SBC], independent component analysis [ICA]); despiking (SBC); volume censoring (SBC, ICA); nuisance regression of CSF and white matter signals (SBC); head motion regression (SBC, ICA); bandpass filtering (SBC, ICA); and spatial smoothing with a kernel size that is twice the effective voxel size (SBC, ICA).The consensus recommendations put forth for rs-fMRI acquisition and preprocessing steps will aid in standardization of practice and guide rs-fMRI program development across institutions. Standardized rs-fMRI protocols and processing pipelines are essential for multicenter trials and to implement rs-fMRI as part of standard clinical practice.

Engineered extracellular vesicles antagonize SARS-CoV-2 infection by inhibiting mTOR signaling.

Effective treatment approaches for patients with COVID-19 remain limited and are neither curative nor widely applicable. Activated specialized tissue effector extracellular vesicles (ASTEX) derived from genetically-enhanced skin fibroblasts, exert disease-modifying bioactivity in vivo in models of heart and lung injury. Here we report that ASTEX antagonizes SARS-CoV-2 infection and its pathogenic sequelae. In human lung epithelial cells exposed to SARS-CoV-2, ASTEX is cytoprotective and antiviral. Transcriptomic analysis implicated the mammalian target of rapamycin (mTOR) pathway, as infected cells upregulated mTOR signaling and pre-exposure to ASTEX attenuated it. The implication of mTOR signaling was further confirmed using mTOR inhibition and activation, which increased and decreased viral load, respectively. Dissection of ASTEX cargo identifies miRs including miR-16 as potential inhibitors of mTOR signaling. The findings reveal a novel, dual mechanism of action for ASTEX as a therapeutic candidate for COVID-19, with synergistic antiviral and cytoprotective benefits.

Functional MRI Shows Altered Deactivation and a Corresponding Decrease in Functional Connectivity of the Default Mode Network in Patients with Gliomas.

BACKGROUND AND PURPOSE: The default mode network normally decreases in activity during externally directed tasks. Although default mode network connectivity is disrupted in numerous brain pathologies, default mode network deactivation has not been studied in patients with brain tumors. We investigated default mode network deactivation with language task-based fMRI by measuring the anticorrelation of a critical default mode network node, the posterior cingulate cortex, in patients with gliomas and controls; furthermore, we examined default mode network functional connectivity in these patients with task-based and resting-state fMRI. MATERIALS AND METHODS: In 10 healthy controls and 30 patients with gliomas, the posterior cingulate cortex was identified on task-based fMRI and was used as an ROI to create connectivity maps from task-based and resting-state fMRI data. We compared the average correlation in each default mode network region between patients and controls for each correlation map and stratified patients by tumor location, hemisphere, and grade. RESULTS: Patients with gliomas (P = .001) and, in particular, patients with tumors near the posterior default mode network (P < .001) showed less posterior cingulate cortex anticorrelation in task-based fMRI than controls. Patients with both left- and right-hemisphere tumors, as well as those with grade IV tumors, showed significantly lower posterior cingulate cortex anticorrelation than controls (P = .02, .03, and <.001, respectively). Functional connectivity in each default mode network region was not significantly different between task-based and resting-state maps. CONCLUSIONS: Task-based fMRI showed impaired deactivation of the default mode network in patients with gliomas. The functional connectivity of the default mode network in both task-based and resting-state fMRI in patients with gliomas using the posterior cingulate cortex identified in task-based fMRI as an ROI for seed-based correlation analysis has strong overlap.

Early cidofovir administration might be associated with a lower probability of respiratory failure in treating human adenovirus pneumonia: a retrospective cohort study.

OBJECTIVE: To compare outcomes of early and delayed treatment with cidofovir for human adenovirus (HAdV) pneumonia. METHODS: A retrospective cohort study in Korean military hospitals was conducted between January 2012 and December 2018. Patients with potentially severe HAdV pneumonia with risk factors for respiratory failure were included and divided into early (within 7 days from symptom onset) and delayed (after 7 days from symptom onset) treatment groups. The primary outcome was respiratory failure development within 21 days after symptom onset. RESULTS: A total of 89 patients with potentially severe HAdV pneumonia were enrolled in the cohort; they included 62 early and 27 delayed treatment patients. All patients were males in their early 20s. Significantly fewer patients in the early treatment group progressed to respiratory failure (8/62, 12.9%), compared to the delayed group (18/27, 66.7%, p < 0.001). Early treatment was associated with a lower 21-day probability of respiratory failure by the Kaplan-Meier method (p < 0.001). On multivariate analysis, monocyte count, hypoxaemia, confusion, whole lung involvement, and early cidofovir treatment within 7 days from symptom onset were included, and monocyte count (HR 0.995, 95%CI 0.991-1.000, p 0.042), confusion (HR 4.964, 95%CI 1.189-20.721, p = 0.028), and early cidofovir treatment (HR 0.319, 95%CI 0.115-0.883, p = 0.028) were significantly associated with respiratory failure. CONCLUSIONS: Early administration of cidofovir was associated with a lower hazard for respiratory failure development. It is suggested that cidofovir be administered within 7 days from symptom onset to prevent respiratory failure in patients with potentially severe HAdV pneumonia.

Resting-State Functional Connectivity of the Middle Frontal Gyrus Can Predict Language Lateralization in Patients with Brain Tumors.

BACKGROUND AND PURPOSE: A recent study using task-based fMRI demonstrated that the middle frontal gyrus is comparable with Broca's area in its ability to determine language laterality using a measure of verbal fluency. This study investigated whether the middle frontal gyrus can be used as an indicator for language-hemispheric dominance in patients with brain tumors using task-free resting-state fMRI. We hypothesized that no significant difference in language lateralization would occur between the middle frontal gyrus and Broca area and that the middle frontal gyrus can serve as a simple and reliable means of measuring language laterality. MATERIALS AND METHODS: Using resting-state fMRI, we compared the middle frontal gyrus with the Broca area in 51 patients with glial neoplasms for voxel activation, the language laterality index, and the effect of tumor grade on the laterality index. The laterality index derived by resting-state fMRI and task-based fMRI was compared in a subset of 40 patients. RESULTS: Voxel activations in the left middle frontal gyrus and left Broca area were positively correlated (r = 0.47, P < .001). Positive correlations were seen between the laterality index of the Broca area and middle frontal gyrus regions (r = 0.56, P < .0005). Twenty-seven of 40 patients (67.5%) showed concordance of the laterality index based on the Broca area using resting-state fMRI and the laterality index based on a language task. Thirty of 40 patients (75%) showed concordance of the laterality index based on the middle frontal gyrus using resting-state fMRI and the laterality index based on a language task. CONCLUSIONS: The middle frontal gyrus is comparable with the Broca area in its ability to determine hemispheric dominance for language using resting-state fMRI. Our results suggest the addition of resting-state fMRI of the middle frontal gyrus to the list of noninvasive modalities that could be used in patients with gliomas to evaluate hemispheric dominance of language before tumor resection. In patients who cannot participate in traditional task-based fMRI, resting-state fMRI offers a task-free alternate to presurgically map the eloquent cortex.

Fluoroquinolones versus trimethoprim-sulfamethoxazole for the treatment of Stenotrophomonas maltophilia infections: a systematic review and meta-analysis.

BACKGROUND: Fluoroquinolones are a popular alternative to trimethoprim-sulfamethoxazole for Stenotrophomonas maltophilia infections. OBJECTIVES: To compare the effects of fluoroquinolones and trimethoprim-sulfamethoxazole on mortality of S. maltophilia infections. DATA SOURCES: PubMed and EMBASE. STUDY ELIGIBILITY CRITERIA: Clinical studies reporting mortality outcomes of S. maltophilia infections. PARTICIPANTS: Patients with clinical infections caused by S. maltophilia. INTERVENTIONS: Fluoroquinolone monotherapy in comparison with trimethoprim-sulfamethoxazole monotherapy. METHODS: Systematic review with meta-analysis technique. RESULTS: Seven retrospective cohort and seven case-control studies were included. Three cohort studies were designed to compare the two drugs, whereas others had other purposes. A total of 663 patients were identified, 332 of which were treated with trimethoprim-sulfamethoxazole (50.1%) and 331 with fluoroquinolones (49.9%). Three cohort studies were designed to compare the effect of the two drugs, whereas the others had other purposes. Levofloxacin was most frequently used among fluoroquinolones (187/331, 56.5%), followed by ciprofloxacin (114/331, 34.4%). The overall mortality rate was 29.6%. Using pooled ORs for the mortality of each study, fluoroquinolone treatment (OR 0.62, 95% CI 0.39-0.99) was associated with survival benefit over trimethoprim-sulfamethoxazole treatment, with low heterogeneity (I2 = 18%). Specific fluoroquinolones such as ciprofloxacin (OR 0.44, 95% CI 0.17-1.12) and levofloxacin (OR 0.78, 95% CI 0.48-1.26) did not show a significant difference in comparison with trimethoprim-sulfamethoxazole. In the sub-group analyses of adult and bacteraemic patients, significant differences in mortality were not observed between fluoroquinolones and trimethoprim-sulfamethoxazole. CONCLUSIONS: Based on a meta-analysis of non-randomized studies, fluoroquinolones demonstrated comparable effects on mortality of S. maltophilia infection to trimethoprim-sulfamethoxazole, supporting the use of fluoroquinolones in clinical S. maltophilia infections. Although the pooled analysis of overall studies favoured fluoroquinolones over trimethoprim-sulfamethoxazole, the studies included were observational, and sub-group analyses of certain fluoroquinolone agents did not show statistical differences with trimethoprim-sulfamethoxazole. Randomized clinical studies are needed to address these issues.

Post-exposure prophylaxis for Middle East respiratory syndrome in healthcare workers.

An effective post-exposure prophylaxis (PEP) strategy may limit the spread of infection. However, there is no consensus regarding PEP for Middle East respiratory syndrome coronavirus (MERS-CoV) infection. This study assessed the efficacy of ribavirin and lopinavir/ritonavir as PEP for healthcare workers (HCWs) exposed to patients with severe MERS-CoV pre-isolation pneumonia. The safety of the PEP regimen was assessed. HCWs with high-risk exposure to MERS-CoV pre-isolation pneumonia were retrospectively enrolled. HCWs who received PEP therapy were classified into the PEP group. PEP therapy was associated with a 40% decrease in the risk of infection. There were no severe adverse events during PEP therapy.

[Evaluation of vascular reactivity to overcome limitations of neurovascular uncoupling in BOLD fMRI of malignant brain tumors]. / Otsenka vazoreaktivnosti dlia preodoleniia ogranichenii neirovaskuliarnogo razobshcheniia BOLD fMRT pri zlokachestvennykh opukholiakh golovnogo mozga.

The sensitivity of fMRI in identification of eloquent cortical centers in the case of large infiltrative growing tumors and pronounced peritumoral edema may be reduced or significantly limited in some cases. The main cause is an attenuated Blood-Oxygen-Level-Dependent response (BOLD) caused by pathological vascular reactivity and subsequent neurovascular uncoupling of fMRI. In our study, we attempted to overcome these limitations and increase the sensitivity of this technique in identification of eloquent cortical areas adjacent to brain tumors by using vasoreactivity features of a breath-holding test and including these data in the BOLD analysis. Local vasoreactivity using a breath-holding paradigm with the same block design of both motor and speech tests was determined in 5 healthy volunteers and 3 patients in the preoperative period (two patients with high grade gliomas and one patient with single metastasis). A coherence-based model was developed for analysis of BOLD fMRI, which took into account altered hemodynamics in peritumoral zones. Obtained coherence maps demonstrated clinically more significant activation zones that were not seen with standard methods of fMRI processing. Thus, neurovascular uncoupling that is known to affect the accuracy of the BOLD fMRI response adjacent to brain tumors may be partially overcome by including an independent measurement of vasoreactivity using a breath-holding test in the BOLD analysis.

Clinical predictors of methicillin-resistance and their impact on mortality associated with Staphylococcus aureus bacteraemia.

We investigated the clinical predictors of methicillin-resistance and their impact on mortality in 371 patients with Staphylococcus aureus bacteraemia identified from two prospective multi-centre studies. Methicillin resistant S. aureus (MRSA) accounted for 42.2% of community-onset and 74.5% of hospital-onset cases. No significant clinical difference was found between patients infected with MRSA vs. methicillin-sensitive S. aureus (MSSA), except that the former were more likely to have had hospital-onset bacteraemia and received antibiotics in the preceding 90 days. After stratifying according to the acquisition site, prior antibiotic use was the only independent predictor of having MRSA in both community-onset and hospital-onset cases. The frequency of inappropriate empirical antibiotic therapy was higher in patients with MRSA than in those with MSSA bacteraemia. However, methicillin resistance was not a predictor of mortality in patients and the clinical characteristics and outcomes of both MRSA and MSSA bacteraemia were similar. This study indicates that there are no definitive clinical or epidemiological risk factors which could distinguish MRSA from MSSA cases with the exception of the previous use of antibiotics for having MRSA bacteraemia, which emphasises the prudent use of glycopeptide treatment of patients at risk for invasive MRSA infections.

Differentiating Atypical Hemangiomas and Metastatic Vertebral Lesions: The Role of T1-Weighted Dynamic Contrast-Enhanced MRI.

BACKGROUND AND PURPOSE: Vertebral hemangiomas are benign vascular lesions that are almost always incidentally found in the spine. Their classic typical hyperintense appearance on T1- and T2-weighted MR images is diagnostic. Unfortunately, not all hemangiomas have the typical appearance, and they can mimic metastases on routine MR imaging. These are generally referred to as atypical hemangiomas and can result in misdiagnosis and ultimately additional imaging, biopsy, and unnecessary costs. Our objective was to assess the utility of dynamic contrast-enhanced MR imaging perfusion in distinguishing vertebral atypical hemangiomas and malignant vertebral metastases. We hypothesized that permeability and vascular density will be increased in metastases compared with atypical hemangiomas. MATERIALS AND METHODS: Consecutive patients from 2011 to 2015 with confirmed diagnoses of atypical hemangiomas and spinal metastases from breast and lung carcinomas with available dynamic contrast-enhanced MR imaging were analyzed. Time-intensity curves were qualitatively compared among the groups. Perfusion parameters, plasma volume, and permeability constant were quantified using an extended Tofts 2-compartment pharmacokinetic model. Statistical significance was tested using the Mann-Whitney U test. RESULTS: Qualitative inspection of dynamic contrast-enhanced MR imaging time-intensity curves demonstrated differences in signal intensity and morphology between metastases and atypical hemangiomas. Quantitative analysis of plasma volume and permeability constant perfusion parameters showed significantly higher values in metastatic lesions compared with atypical hemangiomas (P < .001). CONCLUSIONS: Our data demonstrate that plasma volume and permeability constant perfusion parameters and qualitative inspection of contrast-enhancement curves can be used to differentiate atypical hemangiomas from vertebral metastatic lesions. This work highlights the benefits of adding perfusion maps to conventional sequences to improve diagnostic accuracy.

Appropriate non-carbapenems are not inferior to carbapenems as initial empirical therapy for bacteremia caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae: a propensity score weighted multicenter cohort study.

The efficacy of empirical non-carbapenem antibiotics for extended-spectrum beta-lactamase-producing Enterobacteriaceae bacteremia (ESBL-B) is still inconclusive. We conducted a multicenter retrospective cohort study to evaluate the efficacy of empirical non-carbapenem antibiotics for treating ESBL-B. Electronic medical records of individuals who were diagnosed with ESBL-B were reviewed between January 2010 and December 2014 at four university hospitals in Korea. Patients were classified into non-carbapenem and carbapenem groups according to the empirical antibiotic regimen. Patients treated with appropriate empirical antibiotics and who subsequently received carbapenems as definitive therapy were included in the analysis. The inverse probability of treatment weights, a statistical method that adjusts baseline statistics by giving weights based on propensity score, was used. During the study period, 232 adequately treated patients with ESBL-B were included in the analysis: 49 patients in the non-carbapenem group and 183 in the carbapenem group. The baseline characteristics and severity of infection were similar after propensity score weighting. The 30-day mortality rates for the two groups were not statistically significantly different (non-carbapenems 6.3% and carbapenems 11.4%; P = 0.42). In a multivariate analysis, empirical treatment with non-carbapenem antibiotics was not associated with 30-day all-cause mortality (HR 1.02, 95% CI 0.99-1.06, P = 0.14). In a subgroup analysis, empirical treatment with piperacillin-tazobactam was also not associated with 30-day all-cause mortality (HR 1.21, 95% CI 0.37-4.00, P = 0.75). Appropriate non-carbapenems were not inferior to carbapenems as initial empirical therapy for ESBL-B.

T1-Weighted Dynamic Contrast-Enhanced MR Perfusion Imaging Characterizes Tumor Response to Radiation Therapy in Chordoma.

BACKGROUND AND PURPOSE: Chordomas notoriously demonstrate a paucity of changes following radiation therapy on conventional MR imaging. We hypothesized that dynamic contrast-enhanced MR perfusion imaging parameters of chordomas would change significantly following radiation therapy. MATERIALS AND METHODS: Eleven patients with pathology-proved chordoma who completed dynamic contrast-enhanced MR perfusion imaging pre- and postradiation therapy were enrolled. Quantitative tumor measurements were obtained by 2 attending neuroradiologists. ROIs were used to calculate vascular permeability and plasma volume and generate dynamic contrast-enhancement curves. Quantitative analysis was performed to determine mean and maximum plasma volume and vascular permeability values, while semiquantitative analysis on averaged concentration curves was used to determine the area under the curve. A Mann-Whitney U test at a significance level of P < .05 was used to assess differences of the above parameters between pre- and postradiation therapy. RESULTS: Plasma volume mean (pretreatment mean = 0.82; posttreatment mean = 0.42), plasma volume maximum (pretreatment mean = 3.56; posttreatment mean = 2.27), and vascular permeability mean (pretreatment mean = 0.046; posttreatment mean = 0.028) in the ROIs significantly decreased after radiation therapy (P < .05); this change thereby demonstrated the potential for assessing tumor response. Area under the curve values also demonstrated significant differences (P < .05). CONCLUSIONS: Plasma volume and vascular permeability decreased after radiation therapy, suggesting that these dynamic contrast-enhanced MR perfusion parameters may be useful for monitoring chordoma growth and response to radiation therapy. Additionally, the characteristic dynamic MR signal intensity-time curve of chordoma may provide a radiographic means of distinguishing chordoma from other spinal lesions.

Suggested new breakpoints of anti-MERS-CoV antibody ELISA titers: performance analysis of serologic tests.

To provide optimal cut-off values of anti-Middle East respiratory syndrome coronavirus (MERS-CoV) serologic tests, we evaluated performance of ELISA IgG, ELISA IgA, IFA IgM, and IFA IgG using 138 serum samples of 49 MERS-CoV-infected patients and 219 serum samples of 219 rRT-PCR-negative MERS-CoV-exposed healthcare personnel and patients. The performance analysis was conducted for two different purposes: (1) prediction of neutralization activity in MERS-CoV-infected patients, and (2) epidemiologic surveillance of MERS-CoV infections among MERS-CoV-exposed individuals. To evaluate performance according to serum collection time, we used 'days post onset of illness (dpoi)' and 'days post exposure (dpex)' assessing neutralization activity and infection diagnosis, respectively. Performance of serologic tests improved with delayed sampling time, being maximized after a seroconversion period. In predicting neutralization activity, ELISA IgG tests showed optimal performance using sera collected after 21 dpoi at cut-off values of OD ratio 0.4 (sensitivity 100% and specificity 100%), and ELISA IgA showed optimal performance using sera collected after 14 dpoi at cut-off value of OD ratio 0.2 (sensitivity 85.2% and specificity 100%). In diagnosis of MERS-CoV infection, ELISA IgG exhibited optimal performance using sera collected after 28 dpex, at a cut-off value of OD ratio 0.2 (sensitivity 97.3% and specificity 92.9%). These new breakpoints are markedly lower than previously suggested values (ELISA IgG OD ratio 1.1, sensitivity 34.8% and specificity 100% in the present data set), and the performance data help serologic tests to be practically used in the field of MERS management.

Impact of appropriateness of empiric therapy on outcomes in community-onset bacteremia by extended-spectrum-ß-lactamase producing Escherichia coli and Klebisella pneumoniae definitively treated with carbapenems.

Despite a significant increase of bloodstream infection caused by extended-spectrum-ß-lactamase (ESBL)-producing Enterobacteriaceae in the community-setting, information regarding clinical outcomes of inappropriate empiric therapy (IAT) in patients with those infections is limited. A multicenter-retrospective cohort study was conducted in four hospitals. A total of 249 adults were identified to have community-onset bacteremia caused by ESBL-producing Escherichia coli and Klebsiella pneumoniae, and definitively treated with carbapenems. According to the appropriateness of empiric therapy, individuals were divided into an appropriate empiric therapy (AT) group (n = 106) and IAT group (n = 143). Patients who received AT showed more severe underlying conditions including underlying solid cancer, healthcare-association and intensive care unit (ICU) care, compared to the IAT group. Primary bacteremia was more commonly found in the AT group than in the IAT group, while urinary tract infection predominated more frequently in the IAT group than in the AT group. Multivariate analysis using propensity score analysis indicated that inappropriateness of empiric therapy was not an independent risk factor for 30-day death. ICU care, respiratory tract infection and underlying liver, renal and connective tissue diseases were significantly associated with mortality. In patients with bloodstream infections caused by ESBL-producing E. coli and K. pneumoniae in the community-setting, delay in appropriate therapy was not associated with an increased rate of death if the patients were definitively treated with carbapenems.

Serious fungal infections in Korea.

Information on the incidence and prevalence of fungal infections is of critical value in public health policy. However, nationwide epidemiological data on fungal infections are scarce, due to a lack of surveillance and funding. The objective of this study was to estimate the disease burden of fungal infections in the Republic of Korea. An actuarial approach using a deterministic model was used for the estimation. Data on the number of populations at risk and the frequencies of fungal infections in those populations were obtained from national statistics reports and epidemiology papers. Approximately 1 million people were estimated to be affected by fungal infections every year. The burdens of candidemia (4.12 per 100,000), cryptococcal meningitis (0.09 per 100,000), and Pneumocystis pneumonia (0.51 per 100,000) in South Korea were estimated to be comparable to those in other countries. The prevalence of chronic pulmonary aspergillosis (22.4 per 100,000) was markedly high, probably due to the high burden of tuberculosis in Korea. The low burdens of allergic bronchopulmonary aspergillosis (56.9 per 100,000) and severe asthma with fungal sensitization (75.1 per 100,000) warrant further study. Oral candidiasis (539 per 100,000) was estimated to affect a much larger population than noted in previous studies. Our work provides valuable insight on the epidemiology of fungal infections; however, additional studies are needed.

Empirical combination of a ß-lactam to vancomycin may not improve outcomes of methicillin-susceptible Staphylococcus aureus bacteremia, compared to vancomycin monotherapy.

To evaluate effect of empirical combination of a ß-lactam to vancomycin and vancomycin monotherapy in Staphylococcus aureus bacteremia (MSSA-B), we conducted a retrospective cohort study. Electronic medical records of individuals who were diagnosed with MSSA-B between January 2005 and February 2015 at a tertiary care center were reviewed. Patients were classified into three groups according to empirical antibiotic regimen (BL group, ß-lactam; VAN group, vancomycin; BV group, combination of ß-lactam and vancomycin), and 30-day all-cause mortality of each group was compared. During the study period, 561 patients with MSSA-B were identified. After exclusion of 198 patients (36 with poly-microbial infection, 114 expired within 2 days, and 48 already received parenteral antibiotics) and a matching process, 46 patients for each group were included. Baseline characteristics were similar except for severity and comorbidity scores. The 30-day mortality for all three groups were not significantly different (BL 4.3%, VAN 6.5%, BV 8.7%; P = 0.909). In a multivariate analysis, type of empirical antibiotic regimen was not statistically associated with 30-day all-cause mortality. In comparison with the VAN group, the BV group yielded a HR of 0.579 (95% CI = 0.086-3.890, P = 0.574). Pitt bacteremia score was the only significant factor for mortality. The empirical combination of a ß-lactam to vancomycin was not associated with lower mortality in treating MSSA-B, compared to vancomycin monotherapy.

Emergence of an extended-spectrum ß-lactamase-producing serotype K1 Klebsiella pneumoniae ST23 strain from Asian countries.

Extended-spectrum ß-lactamase (ESBL) production has been very rare in serotype K1 Klebsiella pneumoniae ST23 strains, which are well-known invasive community strains. Among 92 ESBL-producing strains identified in 218 isolates from nine Asian countries, serotype K1 K. pneumoniae strains were screened. Two ESBL-producing K. pneumoniae isolates from Singapore and Indonesia were determined to be serotype K1 and ST23. Their plasmids, which contain CTX-M-15 genes, are transferable rendering the effective transfer of ESBL resistance plasmids to other organisms.

Diagnostic Accuracy of T1-Weighted Dynamic Contrast-Enhanced-MRI and DWI-ADC for Differentiation of Glioblastoma and Primary CNS Lymphoma.

BACKGROUND AND PURPOSE: Glioblastoma and primary CNS lymphoma dictate different neurosurgical strategies; it is critical to distinguish them preoperatively. However, current imaging modalities do not effectively differentiate them. We aimed to examine the use of DWI and T1-weighted dynamic contrast-enhanced-MR imaging as potential discriminative tools. MATERIALS AND METHODS: We retrospectively reviewed 18 patients with primary CNS lymphoma and 36 matched patients with glioblastoma with pretreatment DWI and dynamic contrast-enhanced-MR imaging. VOIs were drawn around the tumor on contrast-enhanced T1WI and FLAIR images; these images were transferred onto coregistered ADC maps to obtain the ADC and onto dynamic contrast-enhanced perfusion maps to obtain the plasma volume and permeability transfer constant. Histogram analysis was performed to determine the mean and relative ADCmean and relative 90th percentile values for plasma volume and the permeability transfer constant. Nonparametric tests were used to assess differences, and receiver operating characteristic analysis was performed for optimal threshold calculations. RESULTS: The enhancing component of primary CNS lymphoma was found to have significantly lower ADCmean (1.1 × 10-3 versus 1.4 × 10-3; P < .001) and relative ADCmean (1.5 versus 1.9; P < .001) and relative 90th percentile values for plasma volume (3.7 versus 5.0; P < .05) than the enhancing component of glioblastoma, but not significantly different relative 90th percentile values for the permeability transfer constant (5.4 versus 4.4; P = .83). The nonenhancing portions of glioblastoma and primary CNS lymphoma did not differ in these parameters. On the basis of receiver operating characteristic analysis, mean ADC provided the best threshold (area under the curve = 0.83) to distinguish primary CNS lymphoma from glioblastoma, which was not improved with normalized ADC or the addition of perfusion parameters. CONCLUSIONS: ADC was superior to dynamic contrast-enhanced-MR imaging perfusion, alone or in combination, in differentiating primary CNS lymphoma from glioblastoma.

Migraine.

This chapter presents an overview of migraine epidemiology and mechanisms. Migraine is a common and disabling neurologic disorder characterized by episodic attacks of severe head pain and other symptoms, including interference with activity, nausea, and sensitivity to light and sound. A number of risk factors for migraine onset and progression have been identified, including the presence of comorbid disorders and overuse of acute headache medications. Though the pathophysiology of migraine is complex and incompletely understood, advances in genetics research and clinical trials methodology offer promise for better understanding the underlying pathophysiologic mechanisms. These advances presently center on genomewide studies, development of antibodies targeting calcitonin gene-related peptide, and understanding the psychologic mechanisms that underlie the efficacy of some interventions. Studies of both pharmacologic and behavioral interventions for migraine and its common comorbidities also offer promise for understanding the neuroepidemiologic mechanisms of migraine. Clinical trials relevant to these mechanisms are reviewed, and methodologic considerations for future trials are discussed.