Should Inflammatory Bowel Disease Clinicians Provide Their Patients with e-Health Resources? Patients' and Professionals' Perspectives.

Introduction: The internet is emerging as a source of information for patients with inflammatory bowel disease (IBD). However, it is not always reliable and may cause anxiety. We aim to assess patients' information habits and patients' and professionals' perceptions of a national website integrated as an educational resource for the IBD unit. Methods: Patients aged 18-65 years, comfortable with the internet, and attending follow-ups at participating IBD units (March-June 2019) and their professionals were invited to evaluate a recommended website through an online survey. Results: Three hundred eighty-nine patients and 95 professionals completed the survey. The internet (n = 109; 27.4%) was the second preferred source of information after the health care team (n = 229; 57.5%). Eighty percent of patients searched the internet for information on their disease and 28.6% did so at least once a week (n = 114), especially newly diagnosed ones (<2 years). Patients valued a website recommended by their professional (n = 379; 95.2%) and endorsed by the National Working Group (n = 377; 94.7%). They would attend online educational initiatives on the website (n = 279; 70.1%) and complete periodical surveys to improve its usefulness (n = 338; 84.9%). According to IBD professionals, this type of website is the best patient source of supplementary information (n = 76; 80%) and they "prescribe" it to most patients (67.0 ± 25.2%), especially the newly diagnosed patients (52.7 ± 26.5%). It effectively integrates routine face-to-face education (n = 95; 100%). Conclusions: Patients of IBD units, especially newly diagnosed ones, appreciate a trusted e-Health resource to back up professional information. The favorable opinion of patients and professionals will allow its use in training interventions.

Clinical Course of Acute Ischemic Stroke Due to Medium Vessel Occlusion With and Without Intravenous Alteplase Treatment.

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.

Brain Atrophy and the Risk of Futile Endovascular Reperfusion in Acute Ischemic Stroke.

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.

Glycemic variability: prognostic impact on acute ischemic stroke and the impact of corrective treatment for hyperglycemia. The GLIAS-III translational study.

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).

Comparison of different methods of thrombus permeability measurement and impact on recanalization in the INTERRSeCT multinational multicenter prospective cohort study.

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 HUmax ≥ 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 HUmax > 89 vs. 16.8% (95%CI 13.0-20.6) when HUmax ≤ 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.

Association of Clinical, Imaging, and Thrombus Characteristics With Recanalization of Visible Intracranial Occlusion in Patients With Acute Ischemic Stroke.

Importance: Recanalization of intracranial thrombus is associated with improved clinical outcome in patients with acute ischemic stroke. The association of intravenous alteplase treatment and thrombus characteristics with recanalization over time is important for stroke triage and future trial design. Objective: To examine recanalization over time across a range of intracranial thrombus occlusion sites and clinical and imaging characteristics in patients with ischemic stroke treated with intravenous alteplase or not treated with alteplase. Design, Setting, and Participants: Multicenter prospective cohort study of 575 patients from 12 centers (in Canada, Spain, South Korea, the Czech Republic, and Turkey) with acute ischemic stroke and intracranial arterial occlusion demonstrated on computed tomographic angiography (CTA). Exposures: Demographics, clinical characteristics, time from alteplase to recanalization, and intracranial thrombus characteristics (location and permeability) defined on CTA. Main Outcomes and Measures: Recanalization on repeat CTA or on first angiographic acquisition of affected intracranial circulation obtained within 6 hours of baseline CTA, defined using the revised arterial occlusion scale (rAOL) (scores from 0 [primary occlusive lesion remains the same] to 3 [complete revascularization of primary occlusion]). Results: Among 575 patients (median age, 72 years [IQR, 63-80]; 51.5% men; median time from patient last known well to baseline CTA of 114 minutes [IQR, 74-180]), 275 patients (47.8%) received intravenous alteplase only, 195 (33.9%) received intravenous alteplase plus endovascular thrombectomy, 48 (8.3%) received endovascular thrombectomy alone, and 57 (9.9%) received conservative treatment. Median time from baseline CTA to recanalization assessment was 158 minutes (IQR, 79-268); median time from intravenous alteplase start to recanalization assessment was 132.5 minutes (IQR, 62-238). Successful recanalization occurred at an unadjusted rate of 27.3% (157/575) overall, including in 30.4% (143/470) of patients who received intravenous alteplase and 13.3% (14/105) who did not (difference, 17.1% [95% CI, 10.2%-25.8%]). Among patients receiving alteplase, the following factors were associated with recanalization: time from treatment start to recanalization assessment (OR, 1.28 for every 30-minute increase in time [95% CI, 1.18-1.38]), more distal thrombus location, eg, distal M1 middle cerebral artery (39/84 [46.4%]) vs internal carotid artery (10/92 [10.9%]) (OR, 5.61 [95% CI, 2.38-13.26]), and higher residual flow (thrombus permeability) grade, eg, hairline streak (30/45 [66.7%]) vs none (91/377 [24.1%]) (OR, 7.03 [95% CI, 3.32-14.87]). Conclusions and Relevance: In patients with acute ischemic stroke, more distal thrombus location, greater thrombus permeability, and longer time to recanalization assessment were associated with recanalization of arterial occlusion after administration of intravenous alteplase; among patients who did not receive alteplase, rates of arterial recanalization were low. These findings may help inform treatment and triage decisions in patients with acute ischemic stroke.

Evaluation of incubation time for dermatophytes cultures.

In general, it is recommended to incubate dermatophytes cultures for a minimum of 4 weeks. Several aspects of routine fungal cultures should be evaluated in order to implement appropriate and necessary changes. The aim of this study was to determine the optimum incubation time for routine dermatophytes cultures, analysing the time to find first fungal growth by visual observation. We recorded the time when the initial growth was detected for all dermatophyte isolates during a 4-year period. A total of 5459 dermatophyte cultures were submitted to our laboratory. From the total cultures, only 16 (1.42%) isolates were recovered over/after 17 days of incubation and only three dermatophyte species were recovered over 17 days. Fourteen isolates belong to Trichophyton rubrum, one isolate to Trichophyton mentagrophytes complex and one isolate to Epidermophyton floccosum. We concluded that an incubation period of 17 days is enough to establish a microbiological diagnosis of dermatophytosis.

Relative cerebral blood volume as a marker of durable tissue-at-risk viability in hyperacute ischemic stroke.

BACKGROUND AND PURPOSE: Selection of best responders to reperfusion therapies could be aided by predicting the duration of tissue-at-risk viability, which may be dependant on collateral circulation status. We aimed to identify the best predictor of good collateral circulation among perfusion computed tomography (PCT) parameters in middle cerebral artery (MCA) ischemic stroke and to analyze how early MCA response to intravenous thrombolysis and PCT-derived markers of good collaterals interact to determine stroke outcome. METHODS: We prospectively studied patients with acute MCA ischemic stroke treated with intravenous thrombolysis who underwent PCT before treatment showing a target mismatch profile. Collateral status was assessed using a PCT source image-based score. PCT maps were quantitatively analyzed. Cerebral blood volume (CBV), cerebral blood flow, and Tmax were calculated within the hypoperfused volume and in the equivalent region of unaffected hemisphere. Occluded MCAs were monitored by transcranial Duplex to assess early recanalization. Main outcome variables were brain hypodensity volume and modified Rankin scale score at day 90. RESULTS: One hundred patients with MCA ischemic stroke imaged by PCT received intravenous thrombolysis, and 68 met all inclusion criteria. A relative CBV (rCBV) >0.93 emerged as the only predictor of good collaterals (odds ratio, 12.6; 95% confidence interval, 2.9-55.9; P=0.001). Early MCA recanalization was associated with better long-term outcome and lower infarct volume in patients with rCBV<0.93, but not in patients with high rCBV. None of the patients with rCBV<0.93 achieved good outcome in absence of early recanalization. CONCLUSIONS: High rCBV was the strongest marker of good collaterals and may characterize durable tissue-at-risk viability in hyperacute MCA ischemic stroke.

Characterization of wound infections among patients injured during the Ruso-Ukrainian war in a Role 4 hospital.

INTRODUCTION: The management of infections in war wounds is a problem aggravated by the presence of multiresistant bacteria and requires a combined approach with surgery. Literature has identified the risks and patterns of antibiotic resistance in previous armed conflicts, but the Russian-Ukrainian conflict has required the study of specific bacterial resistance patterns. METHODS: We included war-injured patients from the Russian-Ukrainian conflict transferred for treatment to the General Defense Hospital of Zaragoza from May 2022 to October 2023. Epidemiological data, factors related to the injury, presence of infection and microbiological results were collected; These data were subsequently analyzed statistically. RESULTS: Fifty-three patients were included in the study, with a mean age of 35.6 years; 83% were injured by an explosive mechanism and all received antibiotic therapy prior to transfer. Seventeen patients had skin, soft tissue or joint infection. Correlation was demonstrated with the presence of bone lesion (p 0.03), skin coverage defect (p 0.000) and presence of foreign bodies (p 0.006). Nine patients had monomicrobial cultures, and the most frequently isolated microorganisms were Gram negative bacilli (GNB) and Staphylococcus aureus. Virtually all GNB presented some resistance mechanism. CONCLUSION: Our work shows the correlation of war wound infection with the presence of foreign bodies and affected tissues. Likewise, the presence of polymicrobial wounds is emphasized, with a predominance of GNB and multidrug-resistant S. aureus.

Global study of IS6110 in a successful Mycobacterium tuberculosis strain: clues for deciphering its behavior and for its rapid detection.

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.

In vitro synergy screens of FDA-approved drugs reveal novel zidovudine- and azithromycin-based combinations with last-line antibiotics against Klebsiella pneumoniae.

Treatment of infections caused by multi-drug resistant (MDR) enterobacteria remains challenging due to the limited therapeutic options available. Drug repurposing could accelerate the development of new urgently needed successful interventions. This work aimed to identify and characterise novel drug combinations against Klebsiella pneumoniae based on the concepts of synergy and drug repurposing. We first performed a semi-qualitative high-throughput synergy screen (sHTSS) with tigecycline, colistin and fosfomycin (last-line antibiotics against MDR Enterobacteriaceae) against a FDA-library containing 1430 clinically approved drugs; a total of 109 compounds potentiated any of the last-line antibiotics. Selected hits were further validated by secondary checkerboard (CBA) and time-kill (TKA) assays, obtaining 15.09% and 65.85% confirmation rates, respectively. Accordingly, TKA were used for synergy classification based on determination of bactericidal activities at 8, 24 and 48 h, selecting 27 combinations against K. pneumoniae. Among them, zidovudine or azithromycin combinations with last-line antibiotics were further evaluated by TKA against a panel of 12 MDR/XDR K. pneumoniae strains, and their activities confronted with those clinical combinations currently used for MDR enterobacteria treatment; these combinations showed better bactericidal activities than usual treatments without added cytotoxicity. Our studies show that sHTSS paired to TKA are powerful tools for the identification and characterisation of novel synergistic drug combinations against K. pneumoniae. Further pre-clinical studies might support the translational potential of zidovudine- and azithromycin-based combinations for the treatment of these infections.

Intracranial atherosclerotic plaque enhancement and long-term risk of future strokes: A prospective, longitudinal study.

BACKGROUND AND PURPOSE: The prognostic significance of postcontrast enhancement of intracranial atheromatous plaque is uncertain. Prospective, long-term follow-up studies in Caucasians, using a multicenter design, are lacking. We aimed to evaluate whether this radiological sign predicts long-term new stroke in symptomatic and asymptomatic intracranial atherosclerotic disease (ICAD) patients. METHODS: This was a prospective, observational, longitudinal, multicenter study. We included a symptomatic and an asymptomatic cohort of ICAD patients that underwent 3T MRI including high-resolution sequences focused on the atheromatous plaque. We evaluated grade of stenosis, plaque characteristics, and gadolinium enhancement ratio (postcontrast plaque signal/postcontrast corpus callosum signal). The occurrence of new events was evaluated at 3, 6, 9, and 12 months and annually thereafter. The association between plaque characteristics and new stroke was studied using Cox multiple regression survival analysis and Kaplan-Meier curves. RESULTS: Forty-eight symptomatic and 13 asymptomatic patients were included. During 56.3 ± 16.9 months, 11 patients (18%) suffered a new event (seven ischemic, two hemorrhagic, and two transient ischemic attacks). A receiver operating characteristic curve identified an enhancement ratio of >1.77 to predict a new event. In a multivariable Cox regression, postcontrast enhancement ratio >1.77 (hazard ratio [HR]= 3.632; 95% confidence interval [CI], 1.082-12.101) and cerebral microbleeds (HR = 5.244; 95% CI, 1.476-18.629) were independent predictors of future strokes. Patients with a plaque enhancement ratio >1.77 had a lower survival free of events (p < .05). CONCLUSIONS: High intracranial postcontrast enhancement is a long-term predictor of new stroke in ICAD patients. Further studies are needed to elucidate whether postcontrast enhancement reflects inflammatory activity of intracranial atheromatous plaque.

Comparison of the first and sixth waves of the SARS-COV-2 coronavirus pandemic in patients with immune-mediated disease.

INTRODUCTION: Recent evidence shows that COVID-19 infection does not have a worse prognosis in patients with immune-mediated inflammatory diseases (IMID), although they develop a worse response to vaccination. OBJECTIVE: To compare the incidence of COVID-19 and clinical features in patients with IMID between the first and sixth waves. METHOD: Prospective observational study of two cohorts of IMID patients diagnosed with COVID-19. First cohort March to May 2020, and second cohort December/2021 to February/2022. Sociodemographic and clinical variables were collected and, in the second cohort, COVID-19 vaccination status. Statistical analysis established differences in characteristics and clinical course between the two cohorts. RESULTS: In total, 1627 patients were followed up, of whom 77 (4.60%) contracted COVID-19 during the first wave and 184 in the sixth wave (11.3%). In the sixth wave, there were fewer hospitalisations, intensive care unit admissions, and deaths than in the first wave (p=.000) and 180 patients (97.8%) had at least one dose of vaccine. CONCLUSION: Early detection and vaccination have prevented the occurrence of serious complications.

Perfusion computed tomography-guided intravenous thrombolysis for acute ischemic stroke beyond 4.5 hours: a case-control study.

BACKGROUND: Extending the therapeutic window of intravenous thrombolysis for acute ischemic stroke beyond the established 4.5-hour limit is of critical importance in order to increase the proportion of thrombolysed stroke patients. In this setting, the capacity of MRI to select acute stroke patients for reperfusion therapies in delayed time windows has been and is being tested in clinical trials. However, whether the more available and cost-effective perfusion computed tomography (PCT) may be useful to select candidates for delayed intravenous thrombolysis remains largely unexplored. We aimed to evaluate the safety and efficacy of PCT-guided intravenous thrombolysis beyond 4.5 h after stroke onset. METHODS: We prospectively studied all consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA) in our stroke unit between January 2008 and December 2010. Patients treated within 0- 4.5 h were treated according to non-contrast CT (NCCT) criteria. Beyond 4.5 h, patients received intravenous tPA according to PCT criteria, i.e. an infarct core on cerebral blood volume (CBV) maps not exceeding one third of the middle cerebral artery (MCA) territory and tissue at risk as defined by mean transit time-CBV mismatch greater than 20%. Predetermined primary endpoints were symptomatic hemorrhagic transformation and favorable long-term outcome, while early neurological improvement and MCA recanalization were considered secondary endpoints. Statistical analysis included bivariate comparisons between the two groups for each endpoint and logistic regression models when significance was found in bivariate analyses. This study was approved by our local ethics committee. RESULTS: A total of 245 patients received intravenous thrombolysis. After the groups were matched by baseline National Institutes of Health Stroke Scale score, 172 patients treated at <4.5 h and 43 patients treated at >4.5 h were finally included. Early and late groups were comparable regarding baseline variables; only cardioembolic etiology was more frequent in the >4.5 h group. Rates of symptomatic hemorrhagic transformation (2.9% in the <4.5 h group vs. 2.3% in the >4.5 h group; p = 1.0) and good long-term outcome (64.5 vs. 60.5%, respectively; p = 0.620) were similar between the groups. However, delayed intravenous thrombolysis was independently associated with a worse early clinical course [odds ratio (OR) 2.07, 95% confidence interval (CI) 1.04-4.1; p = 0.038] and lower 2-hour MCA recanalization rates (OR 0.4, 95% CI 0.17-0.92; p = 0.03). CONCLUSION: Primary safety and efficacy endpoints were comparable between the early and delayed thrombolysis groups. The results of our exploratory study may justify a randomized clinical trial to test the safety and efficacy of PCT-guided intravenous thrombolysis in acute ischemic stroke patients presenting beyond 4.5 h from symptom onset.

Beyond CC398: Characterisation of Other Tetracycline and Methicillin-Resistant Staphylococcus aureus Genetic Lineages Circulating in Spanish Hospitals.

Tetracycline resistance (TetR) 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 TetR-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 TetR marker. The TetR-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 TetR-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.

Use of MALDI-TOF MS (Bruker Daltonics) for identification of Mycobacterium species isolated directly from liquid medium.

OBJECTIVES: The aim of this study was to describe the evaluation of the use of MALDI-TOF MS for the identification of non-tuberculous mycobacteria (NTM) and Mycobacterium tuberculosis directly from liquid MGIT cultures from January 2017 to December 2017. MATERIAL/METHODS: A total of 155 isolates (mainly respiratory) were analyzed by MALDI-TOF MS (Bruker Daltonics) directly from MGIT liquid medium with a previous extraction procedure. RESULTS: MALDI-TOF MS generated acceptable scores for 152 isolates (98.06%). Fifty isolates were identified as M. tuberculosis complex and the remaining 105 as NTM (M. abscessus subsp. abscessus, M. avium, M. celatum, M chelonae, M. chimaera, M. fortuitum, M. gordonae, M. intracellulare, M. kansasii, M. lentiflavum, M. mageritense, M. mucogenicum and M. xenopi). CONCLUSIONS: These results indicate that MALDI-TOF MS can be useful to identify mycobacteria directly from MGIT cultures and is an accurate, rapid and cost-effective system to be used as a routine method.

Prevalence and Genetic Characteristics of Staphylococcus aureus CC398 Isolates From Invasive Infections in Spanish Hospitals, Focusing on the Livestock-Independent CC398-MSSA Clade.

BACKGROUND: Livestock-associated (LA)-CC398-MRSA is closely related to pigs, being unfrequently detected in human invasive infections. CC398-MSSA is emerging in human invasive infections in some countries, but genetic and epidemiological characteristics are still scarcely reported. OBJECTIVES: To determine the prevalence of Staphylococcus aureus (SA) CC398, both MRSA and MSSA, among blood cultures SA isolates recovered in Spanish hospitals located in regions with different pig-farming densities (PD) and characterize the recovered isolates. METHODS: One thousand twenty-two SA isolates (761 MSSA, 261 MRSA) recovered from blood cultures during 6-12 months in 17 Spanish hospitals (2018-2019) were studied. CC398 lineage identification, detection of spa-types, and antibiotic resistance, virulence and human immune evasion cluster (IEC) genes were analyzed by PCR/sequencing. RESULTS: Forty-four CC398-MSSA isolates (4.3% of SA; 5.8% of MSSA) and 10 CC398-MRSA isolates (1% of SA; 3.8% of MRSA) were detected. Eleven spa-types were found among the CC398-MSSA isolates with t571 and t1451 the most frequent spa-types detected (75%). Most of CC398-MSSA isolates were Immune-Evasion-Cluster (IEC)-positive (88.6%), tetracycline-susceptible (95.5%) and erythromycin/clindamycin-inducible-resistant/erm(T)-positive (75%). No statistical significance was detected when the CC398-MSSA/MSSA rate was correlated to PD (pigs/km2) (p = 0.108). On the contrary, CC398-MRSA isolates were all IEC-negative, predominately spa-t011 (70%), and the CC398-MRSA/MRSA rate was significantly associated to PD (p < 0.005). CONCLUSION: CC398-MSSA is an emerging clade in invasive infections in Spanish hospitals. CC398-MRSA (mostly t011) and CC398-MSSA (mostly t571 and t1451) show important differences, possibly suggesting divergent steps in host-adaptation evolutionary processes. While CC398-MRSA is livestock-associated (lacking IEC-system), CC398-MSSA seems to be mostly livestock-independent, carrying human-adaptation markers.

Characterization of AmpC ß-lactamase mutations of extensively drug-resistant Pseudomonas aeruginosa isolates that develop resistance to ceftolozane/tazobactam during therapy.

INTRODUCTION: We characterized AmpC ß-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.

Quantified ischemic core's radiological hypodensity and risk of parenchymal hematoma in > 4.5 h-window stroke thrombectomy.

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.