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A response by Al Calleja and colleagues to a letter to the editor about their article "Insulin Resistance Is Associated With a Poor Response to Intravenous Thrombolysis in Acute Ischemic Stroke" in a 2011 issue is presented.

Tetracycline resistance (Tet R ) has been evidenced as a good phenotypic marker for detection of livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) isolates of the clonal complex CC398. The aim of this study was to characterise a collection of 95 Tet R -MRSA isolates, not belonging to the lineage CC398, that were obtained in a previous multicentre study, to detect other MRSA clonal complexes that could be associated with this phenotypic Tet R marker. The Tet R -MRSA isolates were recovered from 20 Spanish hospitals during 2016 and they were characterised to determine their antimicrobial resistance and virulence phenotypes/genotypes as well as the presence of the immune evasion cluster (IEC). A high proportion of isolates belonging to the CC1 lineage (46%) were observed, as well as to the CC5, CC8 and CC45 lineages (11% each one). Thirty-two different spa -types were identified, being predominantly CC1-t127 (40%) and CC45-t1081 (11%). The IEC system (with the gene scn as marker) was present in 73% of isolates and 16% produced the Panton Valentine leucocidin (PVL). A high proportion of MRSA-CC1 isolates were scn -negative (38.6%) and 52.9% of them were blaZ -negative. A multidrug resistance (MDR) phenotype was identified in 86% of MRSA isolates. The knowledge of other Tet R -MRSA genetic lineages, in addition to CC398, is highly relevant, since most of them were MDR and some of them presented important virulence factors. Strains potentially associated with livestock (as the subpopulation CC1-t127- scn -negative) or with humans (as the CC45 lineage or the subpopulation CC1- scn -positive) have been found in this study. The use of tetracycline-resistance for detection, not only of CC398 but also of other LA-MRSA lineages should be tracked in the future.

Introduction: We characterized AmpC β-lactamase mutations that resulted in ceftolozane/tazobactam resistance in extensively drug-resistant (XDR) Pseudomonas aeruginosa isolates recovered from patients treated with this agent from June 2016 to December 2018., Methods: Five pairs of ceftolozane/tazobactam susceptible/resistant P. aeruginosa XDR isolates were included among a total of 49 patients treated. Clonal relationship among isolates was first evaluated by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) was further performed. AmpC mutations were investigated by PCR amplification of the blaPDC gene followed by sequencing., Results: The ST175 high-risk clone was detected in four of the pairs of isolates and the ST1182 in the remaining one. All resistant isolates showed a mutation in AmpC: T96I in two of the isolates, and E247K, G183V, and a deletion of 19 amino acids (G229-E247) in the other three. The G183V mutation had not been described before. The five isolates resistant to ceftolozane/tazobactam showed cross-resistance to ceftazidime/avibactam and lower MICs of imipenem and piperacillin/tazobactam than the susceptible isolates., Conclusions: Ceftolozane/tazobactam resistance was associated in all of the cases with AmpC mutations, including a novel mutation (G183V) not previously described. There is a vital need for surveillance and characterization of emerging ceftolozane/tazobactam resistance, in order to preserve this valuable antipseudomonal agent., (Copyright © 2020 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Introduction: Glycemic variability (GV) represents the amplitude of oscillations in glucose levels over time and is associated with higher mortality in critically ill patients. Our aim is to evaluate the impact of GV on acute ischemic stroke (IS) outcomes in humans and explore the impact of two different insulin administration routes on GV in an animal model., Methods: This translational study consists of two studies conducted in parallel: The first study is an observational, multicenter, prospective clinical study in which 340 patients with acute IS will be subcutaneously implanted a sensor to continuously monitor blood glucose levels for 96 h. The second study is a basic experimental study using an animal model (rats) with permanent occlusion of the middle cerebral artery and induced hyperglycemia (through an intraperitoneal injection of nicotinamide and streptozotocin). The animal study will include the following 6 groups (10 animals per group): sham; hyperglycemia without IS; IS without hyperglycemia; IS and hyperglycemia without treatment; IS and hyperglycemia and intravenous insulin; and IS and hyperglycemia and subcutaneous insulin. The endpoint for the first study is mortality at 3 months, while the endpoints for the animal model study are GV, functional recovery and biomarkers., Discussion: The GLIAS-III study will be the first translational approach analyzing the prognostic influence of GV, evaluated by the use of subcutaneous glucose monitors, in acute stroke. Trial registration https://www.clinicaltrials.gov (NCT04001049).

Background and Purpose: Available data on the clinical course of patients with acute ischemic stroke due to medium vessel occlusion (MeVO) are mostly limited to those with M2 segment occlusions. Outcomes are generally better compared with more proximal occlusions, but many patients will still suffer from severe morbidity. We aimed to determine the clinical course of acute ischemic stroke due to MeVO with and without intravenous alteplase treatment., Methods: Patients with MeVO (M2/M3/A2/A3/P2/P3 occlusion) from the INTERRSeCT (The Identifying New Approaches to Optimize Thrombus Characterization for Predicting Early Recanalization and Reperfusion With IV Alteplase and Other Treatments Using Serial CT Angiography) and PRoveIT (Precise and Rapid Assessment of Collaterals Using Multi-Phase CTA in the Triage of Patients With Acute Ischemic Stroke for IA Therapy) studies were included. Baseline characteristics and clinical outcomes were summarized using descriptive statistics. The primary outcome was a modified Rankin Scale score of 0 to 1 at 90 days, describing excellent functional outcome. Secondary outcomes were the common odds ratio for a 1-point shift across the modified Rankin Scale and functional independence, defined as modified Rankin Scale score of 0 to 2. We compared outcomes between patients with versus without intravenous alteplase treatment and between patients who did and did not show recanalization on follow-up computed tomography angiography. Logistic regression was used to provide adjusted effect-size estimates., Results: Among 258 patients with MeVO, the median baseline National Institutes of Health Stroke Scale score was 7 (interquartile range: 5-12). A total of 72.1% (186/258) patients were treated with intravenous alteplase and in 41.8% (84/201), recanalization of the occlusion (revised arterial occlusive lesion score 2b/3) was seen on follow-up computed tomography angiography. Excellent functional outcome was achieved by 50.0% (129/258), and 67.4% (174/258) patients gained functional independence, while 8.9% (23/258) patients died within 90 days. Recanalization was observed in 21.4% (9/42) patients who were not treated with alteplase and 47.2% (75/159) patients treated with alteplase ( P =0.003). Early recanalization (adjusted odds ratio, 2.29 [95% CI, 1.23-4.28]) was significantly associated with excellent functional outcome, while intravenous alteplase was not (adjusted odds ratio, 1.70 [95% CI, 0.88-3.25])., Conclusions: One of every 2 patients with MeVO did not achieve excellent clinical outcome at 90 days with best medical management. Early recanalization was strongly associated with excellent outcome but occurred in <50% of patients despite intravenous alteplase treatment.

We aimed to study the relationship between the ischemic core's (IC) radiological hypodensity and the risk of parenchymal haematoma after endovascular therapy (EVT) in acute ischemic stroke (AIS) presenting > 4.5 h from onset. We studied AIS patients with a proximal anterior circulation occlusion > 4.5 h from symptoms onset treated with primary EVT. The IC regions of interest (ROI) were manually delineated on pretreatment CT within the affected hemisphere and their specular ROIs on the unaffected side. IC hypodensity ratio was calculated by dividing mean Hounsfield Unit (HU) value from all ROIs in affected/unaffected hemisphere. Primary endpoint: parenchymal hematoma (PH) type hemorrhagic transformation. Secondary: poor long-term clinical outcome. From May 2015 to November 2018, 648 consecutive AIS patients received reperfusion therapies and 107 met all inclusion criteria. PH after EVT was diagnosed in 33 (31%) patients. In bivariate analyses, IC hypodensity ratio (p < 0.001) and minimum HU value (p = 0.008) were associated with PH. A lower IC hypodensity ratio [OR < 0.001 (< 0.001-0.116) p 0.016] predicted PH but not poor clinical outcome in multivariable logistic regression models. A lower IC radiological density predicted a higher risk of PH in > 4.5 h-window AIS patients treated with primary EVT, although it was not independently associated with a worse clinical outcome.

Background and Purpose- We aimed to evaluate the impact of brain atrophy on long-term clinical outcome in patients with acute ischemic stroke treated with endovascular therapy, and more specifically, to test whether there are interactions between the degree of atrophy and infarct volume, and between atrophy and age, in determining the risk of futile reperfusion. Methods- We studied consecutive patients with acute ischemic stroke with proximal anterior circulation intracranial arterial occlusions treated with endovascular therapy achieving successful arterial recanalization. Brain atrophy was evaluated on baseline computed tomography with the global cortical atrophy scale, and Evans index was calculated to assess subcortical atrophy. Infarct volume was assessed on control computed tomography at 24 hours using the formula for irregular volumes (A×B×C/2). Main outcome variable was futile recanalization, defined by functional dependence (modified Rankin Scale score >2) at 3 months. The predefined interactions of atrophy with age and infarct volume were studied in regression models. Results- From 361 consecutive patients with anterior circulation acute ischemic stroke treated with endovascular therapy, 295 met all inclusion criteria. Futile reperfusion was observed in 144 out of 295 (48.8%) patients. Cortical atrophy affecting parieto-occipital and temporal regions was associated with futile recanalization. Total global cortical atrophy score and Evans index were independently associated with futile recanalization in an adjusted logistic regression. Multivariable adjusted regression models disclosed significant interactions between global cortical atrophy score and infarct volume (odds ratio, 1.003 [95%CI, 1.002-1.004], P <0.001) and between global cortical atrophy score and age (odds ratio, 1.001 [95% CI, 1.001-1.002], P <0.001) in determining the risk of futile reperfusion. Conclusions- A higher degree of cortical and subcortical brain atrophy is associated with futile endovascular reperfusion in anterior circulation acute ischemic stroke. The impact of brain atrophy on insufficient clinical recovery after endovascular reperfusion appears to be independently amplified by age and by infarct volume.

Purpose: To compare the association of different measures of intracranial thrombus permeability on non-contrast computerized tomography (NCCT) and computed tomography angiography (CTA) with recanalization with or without intravenous alteplase., Methods: Patients with anterior circulation occlusion from the INTERRSeCT study were included. Thrombus permeability was measured on non-contrast CT and CTA using the following methods: [1] automated method, mean attenuation increase on co-registered thin (< 2.5 mm) CTA/NCCT; [2] semi-automated method, maximum attenuation increase on non-registered CTA/NCCT (ΔHUmax); [3] manual method, maximum attenuation on CTA (HUmax); and [4] visual method, residual flow grade. Primary outcome was recanalization with intravenous alteplase on the revised AOL scale (2b/3). Regression models were compared using C-statistic, Akaike (AIC), and Bayesian information criterion (BIC)., Results: Four hundred eighty patients were included in this analysis. Statistical models using methods 2, 3, and 4 were similar in their ability to discriminate recanalizers from non-recanalizers (C-statistic 0.667, 0.683, and 0.634, respectively); method 3 had the least information loss (AIC = 483.8; BIC = 492.2). A HU max ≥ 89 measured with method 3 provided optimal sensitivity and specificity in discriminating recanalizers from non-recanalizers [recanalization 55.4% (95%CI 46.2-64.6) when HU max > 89 vs. 16.8% (95%CI 13.0-20.6) when HU max ≤ 89]. In sensitivity analyses restricted to patients with co-registered CTA/NCCT (n = 88), methods 1-4 predicted recanalization similarly (C-statistic 0.641, 0.688, 0.640, 0.648, respectively) with Method 2 having the least information loss (AIC 104.8, BIC 109.8)., Conclusion: Simple methods that measure thrombus permeability are as reliable as complex image processing methods in discriminating recanalizers from non-recanalizers.

Objective: We tested the hypothesis that the risk of intracranial hemorrhage (ICH) in patients with cardioembolic ischemic stroke who are treated with oral anticoagulants (OAs) can be predicted by evaluating surrogate markers of hemorrhagic-prone cerebral angiopathies using a baseline MRI., Methods: Patients were participants in a multicenter and prospective observational study. They were older than 64 years, had a recent cardioembolic ischemic stroke, and were new users of OAs. They underwent a baseline MRI analysis to evaluate microbleeds, white matter hyperintensities, and cortical superficial siderosis. We collected demographic variables, clinical characteristics, risk scores, and therapeutic data. The primary endpoint was ICH that occurred during follow-up. We performed bivariate and multivariate Cox regression analyses., Results: We recruited 937 patients (aged 77.6 ± 6.5 years; 47.9% were men). Microbleeds were detected in 207 patients (22.5%), moderate/severe white matter hyperintensities in 419 (45.1%), and superficial siderosis in 28 patients (3%). After a mean follow-up of 23.1 ± 6.8 months, 18 patients (1.9%) experienced an ICH. In multivariable analysis, microbleeds (hazard ratio 2.7, 95% confidence interval [CI] 1.1-7, p = 0.034) and moderate/severe white matter hyperintensities (hazard ratio 5.7, 95% CI 1.6-20, p = 0.006) were associated with ICH (C index 0.76, 95% CI 0.66-0.85). Rate of ICH was highest in patients with both microbleed and moderate/severe WMH (3.76 per 100 patient-years, 95% CI 1.62-7.4)., Conclusion: Patients taking OAs who have advanced cerebral small vessel disease, evidenced by microbleeds and moderate to severe white matter hyperintensities, had an increased risk of ICH. Our results should help to determine the risk of prescribing OA for a patient with cardioembolic stroke., Clinicaltrialsgov Identifier: NCT02238470., (© 2019 American Academy of Neurology.)

Background: We describe the feasibility of monitoring with a Textile Wearable Holter (TWH) in patients included in Crypto AF registry., Methods: We monitored cryptogenic stroke patients from stroke onset (<3days) continuously during 28days. We employed a TWH composed by a garment and a recorder. We compared two garments (Lead and Vest) to assess rate of undiagnosed Atrial Fibrillation (AF) detection, monitoring compliance, comfortability (1 to 5 points), skin lesions, and time analyzed. We describe the timing of AF detection in three periods (0-3, 4-15 and 16-28days)., Results: The rate of undiagnosed AF detection with TWH was 21.9% (32 out of 146 patients who completed the monitoring). Global time compliance was 90% of the time expected (583/644h). The level of comfortability was 4 points (IQR 3-5). We detected reversible skin lesions in 5.47% (8/146). The comfortability was similar but time compliance (in hours) was longer in Vest group 591 (IQR [521-639]) vs. Lead 566 (IQR [397-620]) (p=0.025). Also, time analyzed was more prolonged in Vest group 497 (IQR [419-557]) vs. Lead (336h (IQR [140-520]) (p=0.001)). The incidence of AF increases from 5.6% (at 3days) to 17.5% (at 15th day) and up to 20.9% (at 28th day). The percentage of AF episodes detected only in each period was 12.5% (0-3days); 21.7% (4-15days) and 19% (16-28days)., Conclusions: 28days Holter monitoring from the acute phase of the stroke was feasible with TWH. Following our protocol, only five patients were needed to screen to detected one case of AF., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Miniscrews are used as orthodontic anchorage devices in the dentistry clinical practice but the in vivo metallic release from these structures has been not previously investigated. The aim of this study was to determine the content of Al, Co, Cr, Cu, Ni, Ti and V in oral mucosa cells of control subjects, patients under orthodontic treatment and with both, orthodontic treatment and miniscrew, in order to know the contribution of these mini-implants to the total metallic content. ICP-MS measurements revealed the following ascending order: Cr

The release of metal ions from fixed orthodontic appliances is a source of major concern. Various studies have evaluated the discharge of metals from these appliances in biological fluids, such as saliva or blood, overlooking the cells with prolonged contact with fixed appliances. The aim of this work is to develop and optimize an analytical procedure to determine Ti, V and Zr in oral mucosa cells in patients with and without orthodontic appliances by Inductively Coupled Plasma Mass Spectrometry (ICP-MS). The analytical procedure is based on an extraction and digestion of the samples and quantification of the elements. A suitable and practical procedure for assessing the trueness and precision of the proposed method has been applied by using validation standards. The method has been suitably validated: the regression equation was calculated from standards prepared in the same matrix without oral mucosa cells and the linear range was 0.5-50.0 ng/mL for Zr and 5.0-50.0 ng/mL for Ti and V. Limits of detection were 0.9, 2.8 and 0.4 ng/mL and limits of quantification 1.8, 3.4 and 0.7 ng/mL for Ti, V and Zr, respectively. The recovery percentages (%) obtained oscillated between 101 and 108 for Ti, 98 and 111 for V, and 92 and 104 for Zr. Intermediate precision (RSD%) data obtained were also adequate. The present method showed to be robust for the three factors considered: heating time, volume of the deionized water, and volume of PlasmaPure 65% HNO₃ used to dilute the samples, which permits its validation and application to oral mucosa cells from orthodontic patients., (© 2013 Published by Elsevier B.V.)

The Mycobacterium tuberculosis insertion sequence IS6110, besides being a very useful tool in molecular epidemiology, seems to have an impact on the biology of bacilli. In the present work, we mapped the 12 points of insertion of IS6110 in the genome of a successful strain named M. tuberculosis Zaragoza (which has been referred to as the MTZ strain). This strain, belonging to principal genetic group 3, caused a large unsuspected tuberculosis outbreak involving 85 patients in Zaragoza, Spain, in 2001 to 2004. The mapping of the points of insertion of IS6110 in the genome of the Zaragoza strain offers clues for a better understanding of the adaptability and virulence of M. tuberculosis. Surprisingly, the presence of one copy of IS6110 was found in Rv2286c, as was recently described for a successful Beijing sublineage. As a result of this analysis, a rapid method for detecting this particular M. tuberculosis strain has been designed.

Overweight derived from the intake of new antipsychotic medication in order to treat schizophrenia is a growing problem. The main purpose of this study is to launch a cognitive behavioural program in outpatients. It is focused on the weight control of patients with chronic mental diseases, especially those diagnosed as psychotic, and who are under treatment in a Psychosocial Rehabilitation Centre. In this study, the results of an experimental group and a control group were compared. The experimental group was made up of 7 individuals, 3 males and 4 females, and the control group comprised 4 males and 4 females. The program had a duration of twelve sessions administered over a period of three months. Three months after concluding the program, both groups were followed up. The data obtained indicate the efficiency of the cognitive-behavioural treatment in the patients. The achievements of this project were, on the one hand, to significantly reduce the patients' weight and, on the other, to modify their nutritional and physical exercise habits.