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BACKGROUND AND PURPOSE: Contrast-enhanced MRI (CEMRI) is a commonly used imaging modality for craniopharyngioma surveillance; however, it carries risks such as allergic reaction and gadolinium deposition. This study evaluates the efficacy of non-contrast enhanced MRI (NCMRI) with a balanced steady state free precession (bSSFP) sequence compared with CEMRI T1-weighted imaging for craniopharyngioma surveillance. MATERIALS AND METHODS: 29 craniopharyngioma patients (16 female/13 male, mean age=21.5± 4.3 years) with CEMRIs including a bSSFP sequence were evaluated. For each patient, 2 blinded neuroradiologists compared the dimensions of residual craniopharyngioma on noncontrast and contrast-enhanced sequences. Tumor volume and solid/cystic component measurements were evaluated using paired t-tests. Diagnostic confidence levels for NC-and CE evaluations were measured using a 3-point scale (2=confident,1=adequate,0=unsure). Analyses of tumor involvement of cranial nerves and adjacent vasculature and diagnostic confidence were performed using Fisher's exact and chi-square tests. RESULTS: No significant difference was observed between residual tumor volumes in both studies (18.86±21.67 cm3 vs 17.64±23.85 cm3, p=0.55) and measurements of dominant solid component volume, number of cystic components, and largest cystic component volume (2.71±3.47 cm3 vs 3.95±5.51 cm3, p=0.10; 2.5±1.5 vs 2.9±1.5, p=0.10; 7.61±13.41 vs 6.84±13.37 cm3, p=0.22, respectively). Tumoral involvement of cranial nerves II (p=0.64), III (p=0.42), and adjacent vasculature (p=0.05) showed no significant differences in detection. Diagnostic confidence was comparable evaluating cranial nerve II, vascular structures, and third ventricle (p>0.05) involvement. Higher levels of confidence were observed with bSSFP sequences for detection of cranial nerve III involvement (p=0.0001) and with ce-T1W for cavernous sinus involvement (p=0.02). CONCLUSIONS: NCMRI techniques using a bSSFP sequence provides similar characterization of craniopharyngiomas as contrast enhanced techniques. ABBREVIATIONS: 3D DRIVE, 3-dimensional driven equilibrium; ACA, anterior cerebral artery; bSSFP, balanced steady-state free precession; ce-T1W, contrast-enhanced T1-weighted imaging; CN, cranial nerve; GTR, gross total resection; STR, subtotal resection.
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The cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with MSSA infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess for S. aureus colonization on admission to the ICU and some individuals had follow-up swabs. We performed cefazolin MIC by broth-microdilution using standard and high-inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics and Agr-typing. All swabs were subjected to 16S-rRNA metabarcoding sequencing to evaluate microbiome characteristics associated with the CzIE. A total of 352 patients were included; 46/352 (13%) patients were colonized with S. aureus; 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients that contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE and SNP analyses supported transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4% and 97.7% sensitivity, specificity and accuracy, respectively. We found a high prevalence point prevalence of the CzIE in MSSA colonizing the nares of critically-ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.
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BACKGROUND AND PURPOSE: Mass effect and vasogenic edema are critical findings on CT of the head. This study compared the accuracy of an artificial intelligence model (Annalise Enterprise CTB) with consensus neuroradiologists' interpretations in detecting mass effect and vasogenic edema. MATERIALS AND METHODS: A retrospective stand-alone performance assessment was conducted on data sets of noncontrast CT head cases acquired between 2016 and 2022 for each finding. The cases were obtained from patients 18 years of age or older from 5 hospitals in the United States. The positive cases were selected consecutively on the basis of the original clinical reports using natural language processing and manual confirmation. The negative cases were selected by taking the next negative case acquired from the same CT scanner after positive cases. Each case was interpreted independently by up-to-three neuroradiologists to establish consensus interpretations. Each case was then interpreted by the artificial intelligence model for the presence of the relevant finding. The neuroradiologists were provided with the entire CT study. The artificial intelligence model separately received thin (≤1.5 mm) and/or thick (>1.5 and ≤5 mm) axial series. RESULTS: The 2 cohorts included 818 cases for mass effect and 310 cases for vasogenic edema. The artificial intelligence model identified mass effect with a sensitivity of 96.6% (95% CI, 94.9%-98.2%) and a specificity of 89.8% (95% CI, 84.7%-94.2%) for the thin series, and 95.3% (95% CI, 93.5%-96.8%) and 93.1% (95% CI, 89.1%-96.6%) for the thick series. It identified vasogenic edema with a sensitivity of 90.2% (95% CI, 82.0%-96.7%) and a specificity of 93.5% (95% CI, 88.9%-97.2%) for the thin series, and 90.0% (95% CI, 84.0%-96.0%) and 95.5% (95% CI, 92.5%-98.0%) for the thick series. The corresponding areas under the curve were at least 0.980. CONCLUSIONS: The assessed artificial intelligence model accurately identified mass effect and vasogenic edema in this CT data set. It could assist the clinical workflow by prioritizing interpretation of cases with abnormal findings, possibly benefiting patients through earlier identification and subsequent treatment.
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Glycerol is a carbon source that produces good biomass under mixotrophic conditions. Enhancing the composition of culture media in algae biomass production improves growth rates, biomass yield, nutrient utilization efficiency, and overall cost-effectiveness. Among the key nutrients in the medium, nitrogen plays a pivotal role. Urea can be effectively used as a nitrogen source and is considered a low-cost form of nitrogen compared to other sources. Urea metabolism releases some CO2 in photosynthesis, and magnesium plays a major role in urea uptake. Magnesium is another key nutrient that is key in photosynthesis and other metabolic reactions. To maximize glycerol consumption in the mixotrophic system and to obtain high biomass and lipid productions, the variations in MgSO4·7H2O and urea concentrations were evaluated in the growth medium of the microalgae. A response surface methodology (RSM) using a central composite design (CCD) was designed to maximize glycerol consumption at the initial cellular growth rates (up to four days). The magnesium and urea supply varied from 0.3 to 1.7 g L-1. Response surface methodology was utilized to analyze the results, and the highest glycerol consumption rate, 770.2 mg L-1 d-1, was observed when C. vulgaris was grown at 1.7 g L-1 urea, 1.0 g L-1 MgSO4·7H2O. Using the optimal urea and magnesium concentrations with acetate, glucose, and glycerol as carbon sources, the same lipid content (10% average) was achieved on day 4 of mixotrophic C. vulgaris culture. Overall, the results show that mixotrophic growth of C. vulgaris using urea with an optimum magnesium concentration yields large amounts of fatty acids and that the carbon source greatly influences the profile of the fatty acids.
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Daptomycin (DAP) is often used as a first-line therapy to treat vancomycin-resistant Enterococcus faecium infections, but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system, and deletion of liaR encoding the response regulator results in hypersusceptibility to DAP and antimicrobial peptides. The main genes regulated by LiaR are a cluster of three genes, designated liaXYZ. In Enterococcus faecalis, LiaX is surface-exposed with a C-terminus that functions as a negative regulator of cell membrane remodeling and an N-terminal domain that is released to the extracellular medium where it binds DAP. Thus, in E. faecalis, LiaX functions as a sentinel molecule recognizing DAP and controlling the cell membrane response, but less is known about LiaX in E. faecium. Here, we found that liaX is essential in E. faecium with an activated LiaFSR system. Unlike E. faecalis, E. faecium LiaX is not detected in the extracellular milieu and does not appear to alter phospholipid architecture. We further postulated that LiaX could be used as a surrogate marker for cell envelope activation and non-susceptibility to DAP. For this purpose, we developed and optimized a LiaX enzyme-linked immunosorbent assay (ELISA). We then assessed 86 clinical E. faecium bloodstream isolates for DAP MICs and used whole genome sequencing to assess for substitutions in LiaX. All DAP-resistant clinical strains of E. faecium exhibited elevated LiaX levels. Strikingly, 73% of DAP-susceptible isolates by standard MIC determination also had elevated LiaX ELISAs compared to a well-characterized DAP-susceptible strain. Phylogenetic analyses of predicted amino acid substitutions showed 12 different variants of LiaX without a specific association with DAP MIC or LiaX ELISA values. Our findings also suggest that many E. faecium isolates that test DAP susceptible by standard MIC determination are likely to have an activated cell stress response that may predispose to DAP failure. As LiaX appears to be essential for the cell envelope response to DAP, its detection could prove useful to improve the accuracy of susceptibility testing by anticipating therapeutic failure.
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Membrana Celular , Daptomicina , Enterococcus faecium , Infecções por Bactérias Gram-Positivas , Humanos , Antibacterianos/uso terapêutico , Biomarcadores/metabolismo , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Farmacorresistência Bacteriana/genética , Enterococcus faecalis , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/metabolismo , Testes de Sensibilidade Microbiana , Filogenia , Reprodutibilidade dos TestesRESUMO
The hippocampus is a complex structure located in the mesial temporal lobe that plays a critical role in cognitive and memory-related processes. The hippocampal formation consists of the dentate gyrus, hippocampus proper, and subiculum, and its importance in the neural circuitry makes it a key anatomic structure to evaluate in neuroimaging studies. Advancements in imaging techniques now allow detailed assessment of hippocampus internal architecture and signal features that has improved identification and characterization of hippocampal abnormalities. This review aims to summarize the neuroimaging features of the hippocampus and its common pathologies. It provides an overview of the hippocampal anatomy on magnetic resonance imaging and discusses how various imaging techniques can be used to assess the hippocampus. The review explores neuroimaging findings related to hippocampal variants (incomplete hippocampal inversion, sulcal remnant and choroidal fissure cysts), and pathologies of neoplastic (astrocytoma and glioma, ganglioglioma, dysembryoplastic neuroepithelial tumor, multinodular and vacuolating neuronal tumor, and metastasis), epileptic (mesial temporal sclerosis and focal cortical dysplasia), neurodegenerative (Alzheimer's disease, progressive primary aphasia, and frontotemporal dementia), infectious (Herpes simplex virus and limbic encephalitis), vascular (ischemic stroke, arteriovenous malformation, and cerebral cavernous malformations), and toxic-metabolic (transient global amnesia and opioid-associated amnestic syndrome) etiologies.
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Doença de Alzheimer , Epilepsia do Lobo Temporal , Epilepsia , Glioma , Humanos , Criança , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Epilepsia/patologia , Lobo Temporal/patologia , Imageamento por Ressonância Magnética , Doença de Alzheimer/patologia , Glioma/patologiaRESUMO
Introduction Most medical students are not familiar with Anesthesiology, as it is infrequently addressed properly in medical school curricula. However, anesthesiology skills are widely practiced across specialties and commonly performed by general practitioners. Currently, anesthesia curricula are often based on shadowing and lectures without emphasizing relevant skills, behaviors, and attitudes, whereas simulation-based curricula enable a holistic evaluation of the trainee. Objective To implement and assess the perceptions of students and professors of a novel simulation-based anesthesiology curriculum. Methods A descriptive study was planned for evaluating the new proposal. A simulation-based 3-week curriculum was organized using a blended course with skill laboratories. We designed flipped classroom-based lectures (2 weeks) combined with activities using standardized patients, manikins, and hybrid scenarios (1 week). After each activity, feedback was given by an anesthesiologist, as well as individual grading and a survey based on the Kirkpatrick levels. Results From June to November 2020, 53 students were enrolled in the clerkship. Each week, every group of 6-8 students was assigned to the same specialist to perform the activities and track individual progress. The response rate of the survey was 83%. Across the levels of Kirkpatrick, there was an excellent opinion of the activities, as well as a high similarity between the perception of both students and professors. Conclusion Our simulation-based curriculum, which was highly appraised by students and professors, was found to be feasible, appealing, and offered a good introduction to the principles and practices of anesthesiology to medical students.
Introducción: La mayoría de los estudiantes de medicina no están familiarizados con la Anestesiología, ya que la materia pocas veces se aborda adecuadamente en el programa académico de la facultad de medicina. Sin embargo, las habilidades en anestesiología son ampliamente utilizadas por los médicos generales. En la actualidad los currículos de anestesiología suelen basarse en prácticas y conferencias donde no se enfatizan las destrezas pertinentes, las conductas y las actitudes, mientras que los currículos basados en simulación permiten una evaluación integral del aprendiz. Objetivo: Implementar y evaluar las percepciones de estudiantes y de los profesores de un novedoso plan de estudios de anestesiología basado en la simulación. Métodos: Se diseñó un estudio descriptivo para valorar la nueva propuesta. Se organizó un plan de estudios de 3 semanas, basado en simulación, utilizando un curso mixto con habilidades de laboratorio. Diseñamos conferencias basadas en el modelo de aula invertida (2 semanas), combinadas con actividades basadas en pacientes estandarizados, maniquíes y escenarios híbridos (1 semana). Luego de cada actividad, un anestesiólogo ofrecía su retroalimentación, así como calificaciones individuales y una encuesta basada en los niveles de Kirkpatrick. Resultados: Se inscribieron 53 estudiantes en la pasantía de junio a noviembre de 2020. Cada semana se asignaba un grupo de 6-8 estudiantes a un mismo especialista para llevar a cabo las actividades y hacer un seguimiento al progreso alcanzado de manera individual. La tasa de respuesta de la encuesta fue de 83%. En todos los niveles de Kirkpatrick, hubo una excelente opinión sobre las actividades y una elevada similitud en la percepción, tanto de los estudiantes como de los profesores. Conclusión: Nuestro currículo basado en simulación fue muy bien valorado por estudiantes y profesores y se consideró factible, atractivo y que ofrecía a los estudiantes una buena introducción a los principios y prácticas de la anestesiología.
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Daptomycin (DAP) is often used as a first line therapy to treat vancomycin-resistant Enterococcus faecium (VR Efm ) infections but emergence of DAP non-susceptibility threatens the effectiveness of this antibiotic. Moreover, current methods to determine DAP MICs have poor reproducibility and accuracy. In enterococci, DAP resistance is mediated by the LiaFSR cell membrane stress response system and deletion of liaR encoding the response regulator results in hypersusceptibility to DAP and antimicrobial peptides. The main genes regulated by LiaR are a cluster of three genes, designated liaXYZ . In Enterococcus faecalis , LiaX is surface exposed with a C-terminus that functions as a negative regulator of cell membrane remodeling and an N-terminal domain that is released to the extracellular medium where it binds DAP. Thus, in E. faecalis , LiaX functions as a sentinel molecule recognizing DAP and controlling the cell membrane response, but less is known about LiaX in E. faecium . Here, we found that liaX is essential in E. faecium ( Efm ) with an activated LiaFSR system. Unlike E. faecalis , Efm LiaX is not detected in the extracellular milieu and does not appear to alter phospholipid architecture. We further postulated that LiaX could be used as a surrogate marker for cell envelope activation and non-susceptibility to DAP. For this purpose, we developed and optimized a LiaX ELISA. We then assessed 86 clinical E. faecium BSI isolates for DAP MICs and used whole genome sequencing to assess for substitutions in LiaX. All DAP-R clinical strains of E. faecium exhibited elevated LiaX levels. Strikingly, 73% of DAP-S isolates by standard MIC determination had elevated LiaX ELISAs above the established cut-off. Phylogenetic analyses of predicted amino acid substitutions showed 12 different variants of LiaX without a specific association with DAP MIC or LiaX ELISA values. Our findings also suggest that many Efm isolates that test DAP susceptible by standard MIC determination are likely to have an activated cell stress response that may predispose to DAP failure. As LiaX appears to be essential for the cell envelope response to DAP, its detection could prove useful to improve the accuracy of susceptibility testing by anticipating therapeutic failure.
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The global dissemination of methicillin-resistant Staphylococcus aureus (MRSA) is associated with the emergence and establishment of clones in specific geographic areas. The Chilean-Cordobes clone (ChC) (ST5-SCCmecI) has been the predominant MRSA clone in Chile since its first description in 1998, despite the report of other emerging MRSA clones in recent years. Here, we characterize the evolutionary history of MRSA from 2000 to 2016 in a Chilean tertiary health care center using phylogenomic analyses. We sequenced 469 MRSA isolates collected between 2000 and 2016. We evaluated the temporal trends of the circulating clones and performed a phylogenomic reconstruction to characterize the clonal dynamics. We found a significant increase in the diversity and richness of sequence types (STs; Spearman r = 0.8748, P < 0.0001) with a Shannon diversity index increasing from 0.221 in the year 2000 to 1.33 in 2016, and an effective diversity (Hill number; q = 2) increasing from 1.12 to 2.71. The temporal trend analysis revealed that in the period 2000 to 2003 most of the isolates (94.2%; n = 98) belonged to the ChC clone. However, since then, the frequency of the ChC clone has decreased over time, accounting for 52% of the collection in the 2013 to 2016 period. This decline was accompanied by the rise of two emerging MRSA lineages, ST105-SCCmecII and ST72-SCCmecVI. In conclusion, the ChC clone remains the most frequent MRSA lineage, but this lineage is gradually being replaced by several emerging clones, the most important of which is clone ST105-SCCmecII. To the best of our knowledge, this is the largest study of MRSA clonal dynamics performed in South America. IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) is a major public health pathogen that disseminates through the emergence of successful dominant clones in specific geographic regions. Knowledge of the dissemination and molecular epidemiology of MRSA in Latin America is scarce and is largely based on small studies or more limited typing techniques that lack the resolution to represent an accurate description of the genomic landscape. We used whole-genome sequencing to study 469 MRSA isolates collected between 2000 and 2016 in Chile providing the largest and most detailed study of clonal dynamics of MRSA in South America to date. We found a significant increase in the diversity of MRSA clones circulating over the 17-year study period. Additionally, we describe the emergence of two novel clones (ST105-SCCmecII and ST72-SCCmecVI), which have been gradually increasing in frequency over time. Our results drastically improve our understanding of the dissemination and update our knowledge about MRSA in Latin America.
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Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/epidemiologia , Chile/epidemiologia , Filogenia , Centros de Atenção Terciária , AntibacterianosRESUMO
Methicillin-resistant Staphylococcus aureus (MRSA) is a priority pathogen listed by the World Health Organization. The global spread of MRSA is characterized by successive waves of epidemic clones that predominate in specific geographical regions. The acquisition of genes encoding resistance to heavy-metals is thought to be a key feature in the divergence and geographical spread of MRSA. Increasing evidence suggests that extreme natural events, such as earthquakes and tsunamis, could release heavy-metals into the environment. However, the impact of environmental exposition to heavy-metals on the divergence and spread of MRSA clones has been insufficiently explored. We assess the association between a major earthquake and tsunami in an industrialized port in southern Chile and MRSA clone divergence in Latin America. We performed a phylogenomic reconstruction of 113 MRSA clinical isolates from seven Latin American healthcare centers, including 25 isolates collected in a geographic area affected by an earthquake and tsunami that led to high levels of heavy-metal environmental contamination. We found a divergence event strongly associated with the presence of a plasmid harboring heavy-metal resistance genes in the isolates obtained in the area where the earthquake and tsunami occurred. Moreover, clinical isolates carrying this plasmid showed increased tolerance to mercury, arsenic, and cadmium. We also observed a physiological burden in the plasmid-carrying isolates in absence of heavy-metals. Our results are the first evidence that suggests that heavy-metal contamination, in the aftermath of an environmental disaster, appears to be a key evolutionary event for the spread and dissemination of MRSA in Latin America.
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BACKGROUND: Data on clinical outcomes for base of skull (BOS) chordomas in the pediatric population is limited. We report patient outcomes after surgery and proton radiotherapy (PRT). METHODS: Pediatric patients with BOS chordomas were treated with PRT or combined proton/photon approach (proton-based; for most, 80% proton/20% photon) at the Massachusetts General Hospital from 1981 to 2021. Endpoints of interest were overall survival (OS), disease-specific survival, progression-free survival (PFS), freedom from local recurrence (LC), and freedom from distant failure (DC). RESULTS: Of 204 patients, median age at diagnosis was 11.1 years (range, 1-21). Chordoma location included 59% upper and/or middle clivus, 36% lower clivus, 4% craniocervical junction, and 1% nasal cavity. Fifteen (7%) received pre-RT chemotherapy. Forty-seven (23%) received PRT, and 157 (77%) received comboRT. Median total dose was 76.7 Gy (RBE) (range, 59.3-83.3). At a median follow-up of 10 years (interquartile range, 5-16 years), 56 recurred. Median OS and PFS were 26 and 25 years, with 5-, 10-, and 20-year OS and PFS rates of 84% and 74%, 78% and 69%, and 64% and 64%, respectively. Multivariable actuarial analyses showed poorly differentiated subtype, radiographical progression prior to RT, larger treatment volume, and lower clivus location to be prognostic factors for worse OS, PFS, and LC. RT was well tolerated at a median follow-up of 9 years (interquartile range, 4-16 years). Side effects included 166 patients (80%) with mild/moderate acute toxicities, 24 (12%) patients with late toxicities, and 4 (2%) who developed secondary radiation-related malignancies. CONCLUSION: This is the largest cohort of BOS chordomas in the literature, pediatric and/or adult. High-dose PRT following surgical resection is effective with low rates of late toxicity.
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Condrossarcoma , Cordoma , Terapia com Prótons , Neoplasias da Base do Crânio , Adulto , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Adulto Jovem , Prótons , Cordoma/radioterapia , Cordoma/cirurgia , Cordoma/patologia , Neoplasias da Base do Crânio/radioterapia , Neoplasias da Base do Crânio/cirurgia , Condrossarcoma/radioterapia , Condrossarcoma/cirurgia , Base do Crânio/patologia , Resultado do Tratamento , SeguimentosRESUMO
Machine learning (ML) algorithms to detect critical findings on head CTs may expedite patient management. Most ML algorithms for diagnostic imaging analysis utilize dichotomous classifications to determine whether a specific abnormality is present. However, imaging findings may be indeterminate, and algorithmic inferences may have substantial uncertainty. We incorporated awareness of uncertainty into an ML algorithm that detects intracranial hemorrhage or other urgent intracranial abnormalities and evaluated prospectively identified, 1000 consecutive noncontrast head CTs assigned to Emergency Department Neuroradiology for interpretation. The algorithm classified the scans into high (IC+) and low (IC-) probabilities for intracranial hemorrhage or other urgent abnormalities. All other cases were designated as No Prediction (NP) by the algorithm. The positive predictive value for IC+ cases (N = 103) was 0.91 (CI: 0.84-0.96), and the negative predictive value for IC- cases (N = 729) was 0.94 (0.91-0.96). Admission, neurosurgical intervention, and 30-day mortality rates for IC+ was 75% (63-84), 35% (24-47), and 10% (4-20), compared to 43% (40-47), 4% (3-6), and 3% (2-5) for IC-. There were 168 NP cases, of which 32% had intracranial hemorrhage or other urgent abnormalities, 31% had artifacts and postoperative changes, and 29% had no abnormalities. An ML algorithm incorporating uncertainty classified most head CTs into clinically relevant groups with high predictive values and may help accelerate the management of patients with intracranial hemorrhage or other urgent intracranial abnormalities.
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Aprendizado Profundo , Humanos , Incerteza , Tomografia Computadorizada por Raios X/métodos , Hemorragias Intracranianas/diagnóstico por imagem , Algoritmos , Estudos RetrospectivosRESUMO
BACKGROUND: Heterogeneous vancomycin-intermediate Staphylococcus aureus (hVISA) compromise the clinical efficacy of vancomycin. The hVISA isolates spontaneously produce vancomycin-intermediate Staphylococcus aureus (VISA) cells generated by diverse and intriguing mechanisms. OBJECTIVE: To characterize the biomolecular profile of clinical hVISA applying genomic, transcriptomic and metabolomic approaches. METHODS: 39 hVISA and 305 VSSA and their genomes were included. Core genome-based Bayesian phylogenetic reconstructions were built and alterations in predicted proteins in VISA/hVISA were interrogated. Linear discriminant analysis and a Genome-Wide Association Study were performed. Differentially expressed genes were identified in hVISA-VSSA by RNA-sequencing. The undirected profiles of metabolites were determined by liquid chromatography and hydrophilic interaction in six CC5-MRSA. RESULTS: Genomic relatedness of MRSA associated to hVISA phenotype was not detected. The change Try38âââHis in Atl (autolysin) was identified in 92% of the hVISA. We identified SNPs and k-mers associated to hVISA in 11 coding regions with predicted functions in virulence, transport systems, carbohydrate metabolism and tRNA synthesis. Further, capABCDE, sdrD, esaA, esaD, essA and ssaA genes were overexpressed in hVISA, while lacABCDEFG genes were downregulated. Additionally, valine, threonine, leucine tyrosine, FAD and NADH were more abundant in VSSA, while arginine, glycine and betaine were more abundant in hVISA. Finally, we observed altered metabolic pathways in hVISA, including purine and pyrimidine pathway, CoA biosynthesis, amino acid metabolism and aminoacyl tRNA biosynthesis. CONCLUSIONS: Our results show that the mechanism of hVISA involves major changes in regulatory systems, expression of virulence factors and reduction in glycolysis via TCA cycle. This work contributes to the understanding of the development of this complex resistance mechanism in regional strains.
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Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Vancomicina/farmacologia , Staphylococcus aureus/genética , Staphylococcus aureus Resistente à Vancomicina/genética , Estudo de Associação Genômica Ampla , América Latina , Teorema de Bayes , Multiômica , Filogenia , Resistência a Vancomicina/genética , RNA de Transferência , Testes de Sensibilidade Microbiana , Antibacterianos/farmacologiaAssuntos
Neoplasias Cardíacas , Doenças das Valvas Cardíacas , Ataque Isquêmico Transitório , Adulto , Feminino , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico por imagem , Doenças das Valvas Cardíacas/complicações , Doenças das Valvas Cardíacas/diagnóstico por imagem , Humanos , Ataque Isquêmico Transitório/etiologia , Valva Mitral/diagnóstico por imagemRESUMO
En este artículo se conceptualiza la inmigración como un fenómeno social mundial y un problema insostenible para el sector económico, educativo e inclusivo, seguridad social y jurídica, salud y cultura. Seguidamente, se propone el objetivo específico: analizar la violencia de género padecida por las mujeres inmigrantes venezolanas radicadas en la invasión Caraquitas, en el barrio El Bosque, Barranquilla (Colombia). Luego se contextualiza el tema en el marco constitucional colombiano característico del Estado social de derecho. Más adelante, se explica la metodología mixta integrada por el enfoque, paradigma cualitativo y cuantitativo, cuyo propósito es la articulación del ejercicio teórico y el práctico. Se describen los resultados relevantes, encontrando en ellos la normalización cultural de los tipos de violencia ocasionados a la mujer inmigrante venezolana por su compañero permanente y/o familiar, el bajo nivel de escolaridad, la sujeción económica a su cónyuge o expareja, la indocumentación, los riesgos de deportación latentes y la remuneración inequitativa de su labor (mano de obra barata). Asimismo, se profundiza en la discusión hasta enunciar los productos provenientes de la aplicación de las técnicas e instrumentos de recolección de información. Y como conclusión, las mujeres inmigrantes venezolanas son víctimas de varias formas de violencia y discriminación por su género.
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Vítimas de Crime , Violência contra a Mulher , Emigrantes e ImigrantesRESUMO
More than a year after the start of the COVID-19 pandemic, long-term neurological manifestations of COVID-19 are increasingly being reported. The long-term sequelae of COVID-19-related leukoencephalopathy, however, remain unclear. Here, we present long-term neuroimaging follow-up in two cases of COVID-19-related leukoencephalopathy. The two cases demonstrate the utility of brain MRI for evaluating neurologic symptoms in critically ill patients with COVID-19, for diagnosis of underlying neural injury and prognostication of future recovery. The presence of leukoencephalopathy may result in chronic neurologic manifestations and may represent a poor prognosticator of neurologic recovery. The presence of leukoencephalomalacia on follow-up neuroimaging is potentially an indicator of irreversible white matter damage, which may be associated with more severe chronic deficits.
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COVID-19 , Leucoencefalopatias , Seguimentos , Humanos , Leucoencefalopatias/induzido quimicamente , Leucoencefalopatias/diagnóstico por imagem , Neuroimagem , Pandemias , SARS-CoV-2RESUMO
The National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH-NINDS) Traumatic Brain Injury (TBI) Imaging Common Data Elements (CDEs) are standardized definitions for pathological intracranial lesions based on their appearance on neuroimaging studies. The NIH-NINDS TBI Imaging CDEs were designed to be as consistent as possible with the U.S. Food and Drug Administration (FDA) definition of biomarkers as "an indicator of normal biological processes, pathogenic processes, or biological responses to an exposure or intervention." However, the FDA qualification process for biomarkers requires proof of reliable biomarker test measurements. We determined the interrater reliability of TBI Imaging CDEs on subacute brain magnetic resonance imaging (MRI) performed on 517 mild TBI patients presenting to 11 U.S. level 1 trauma centers. Three U.S. board-certified neuroradiologists independently evaluated brain MRI performed 2 weeks post-injury for the following CDEs: traumatic axonal injury (TAI), diffuse axonal injury (DAI), and brain contusion. We found very high interrater agreement for brain contusion, with prevalence- and bias-adjusted kappa (PABAK) values for pairs of readers from 0.92 [95% confidence interval, 0.88-0.95] to 0.94 [0.90-0.96]. We found intermediate agreement for TAI and DAI, with PABAK values of 0.74-0.78 [0.70-0.82]. The near-perfect agreement for subacute brain contusion is likely attributable to the high conspicuity and distinctive appearance of these lesions on T1-weighted images. Interrater agreement for TAI and DAI was lower, because signal void in small vascular structures, and artifactual foci of signal void, can be difficult to distinguish from the punctate round or linear areas of slight hemorrhage that are a common hallmark of TAI/DAI on MRI.
Assuntos
Concussão Encefálica/diagnóstico por imagem , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adolescente , Adulto , Idoso , Artefatos , Biomarcadores , Contusão Encefálica/diagnóstico por imagem , Elementos de Dados Comuns , Lesão Axonal Difusa/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estados Unidos , Adulto JovemRESUMO
Hirayama disease is a cervical flexion myelopathy that typically causes upper extremity weakness in young male patients. We present two male patients (age 15 and 29) with MRI findings of thoracic ligamentous laxity similar in appearance to Hirayama disease. However, patients presented with atypical symptoms, specifically back pain and paresthesia of the upper and/or lower extremities, likely correlating to the abnormal thoracic spinal levels involved. Flexion/extension MRI sequences demonstrated the forward displacement of the dorsal dura and compression the thoracic cord with prominence of the posterior epidural space and venous plexus. Follow-up MRAs were negative for a spinal vascular malformation. Patients were managed conservatively with no surgical intervention. Clinical history, thoracic MRI, and follow-up flexion and angiographic imaging sequences may help confirm a diagnosis of Hirayama-like thoracic ligamentous laxity.
RESUMO
The cefazolin inoculum effect (CzIE) has been associated with therapeutic failures and mortality in invasive methicillin-susceptible Staphylococcus aureus (MSSA) infections. A diagnostic test to detect the CzIE is not currently available. We developed a rapid (â¼3 h) CzIE colorimetric test to detect staphylococcal-ß-lactamase (BlaZ) activity in supernatants after ampicillin induction. The test was validated using 689 bloodstream MSSA isolates recovered from Latin America and the United States. The cefazolin MIC determination at a high inoculum (107 CFU/ml) was used as a reference standard (cutoff ≥16 µg/ml). All isolates underwent genome sequencing. A total of 257 (37.3%) of MSSA isolates exhibited the CzIE by the reference standard method. The overall sensitivity and specificity of the colorimetric test was 82.5% and 88.9%, respectively. Sensitivity in MSSA isolates harboring type A BlaZ (the most efficient enzyme against cefazolin) was 92.7% with a specificity of 87.8%. The performance of the test was lower against type B and C enzymes (sensitivities of 53.3% and 72.3%, respectively). When the reference value was set to ≥32 µg/ml, the sensitivity for isolates carrying type A enzymes was 98.2%. Specificity was 100% for MSSA lacking blaZ The overall negative predictive value ranged from 81.4% to 95.6% in Latin American countries using published prevalence rates of the CzIE. MSSA isolates from the United States were genetically diverse, with no distinguishing genomic differences from Latin American MSSA, distributed among 18 sequence types. A novel test can readily identify most MSSA isolates exhibiting the CzIE, particularly those carrying type A BlaZ. In contrast to the MIC determination using high inoculum, the rapid test is inexpensive, feasible, and easy to perform. After minor validation steps, it could be incorporated into the routine clinical laboratory workflow.